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FUNDAMENTAL

ORGANIC CHEMISTRY I
Chem 236: Fundamental Organic Chemistry I
(Chan)
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This text was compiled on 01/13/2024
TABLE OF CONTENTS
Licensing

1: Intro to Chemical Structure and Resonance

1.1: Drawing Chemical Structures
1.2: Electron-Dot Model of Bonding - Lewis Structures
1.3: VSPER Theory- The Effect of Lone Pairs
1.4: Electronegativity and Bond Polarity (Review)
1.5: Resonance
1.6: Molecular Orbitals and Covalent Bonding
1.7: Hybrid Orbitals- Bonding in Complex Molecules and Practice Problems

2: Alkanes
2.1: Chemical Properties of Alkanes
2.2: Physical Properties of Alkanes
2.3: Nomenclature of Alkanes
2.4: Nomenclature of Cycloalkanes
2.5: Practice - Alkane Nomenclature
2.6: Ethane Conformers
2.7: Gibbs Free Energy (review)
2.8: Enthalpy Changes in Reactions
2.9: Entropy Changes in Chemical Reactions
2.10: Activation Energy and Rate

3: Acids, Bases, and Arrow Pushing

3.1: Acids and Bases - The Brønsted-Lowry Definition
3.2: Acids and Bases - The Lewis Definition
3.3: Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases
3.4: Using Curved Arrows in Polar Reaction Mechanisms
3.5: Acid Strength and $pK_{a}$
3.6: A Summary of the Factors that Determine Acid Strength
3.7: Organic Acids and Bases

4: Introduction to Alkenes
4.1: The $\pi$ Bond
4.2: Nomenclature of Alkenes
4.3: Degree of Unsaturation
4.4: Electrophilic Addition Reactions of Alkenes
4.5: Carbocation Structure and Stability
4.6: Carbocation Rearrangements
4.7: Markovnikov Addition

5: Addition Reactions of Alkenes

5.1: Electrophilic Addition of Hydrogen Halides
5.2: Addition of Strong Brønsted Acids
5.3: Electrophilic Addition of Halogens to Alkenes
5.4: Hydration of Alkenes

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5.5: Formation of alcohols from alkenes
5.6: Catalytic Hydrogenation
5.7: Hydration- Oxymercuration-Demercuration
5.8: Hydration- Hydroboration-Oxidation
5.9: Oxidative Cleavage of Alkenes
5.10: Free Radicals
5.11: Addition of Radicals to Alkenes
5.12: Anti-Markovnikov Product Formation
5.13: Homolytic Cleavage and Bond Dissociation Energies
5.14: Polymerization of Alkenes

6: Principles of Stereochemistry
6.1: Chirality and Stereoisomers
6.2: R-S Sequence Rules
6.3: Optical Activity
6.4: Optical Activity - more detail
6.5: Racemic Mixtures and the Resolution of Enantiomers
6.6: Diastereomers
6.7: Diastereomers - more detail
6.8: Meso Compounds

7: Cyclic Compounds - Stereochemistry of Reactions

7.1: Ring Strain and the Structure of Cycloalkanes
7.2: Cycloalkanes and Ring Strain
7.3: Cyclohexane Conformations
7.4: Conformations of Monosubstituted Cyclohexanes
7.5: Conformations of Disubstituted Cyclohexanes
7.6: Polycyclic Alkanes
7.7: Carbocyclic Products in Nature
7.8: Steroids

8: Introduction to Alkyl Halides, Alcohols, Ethers, Thiols, and Sulfides

8.1: Alkyl Halides
8.2: Haloalkanes
8.2.1: Alkyl Halide Occurrence
8.3: Nomenclature of Alcohols
8.3.1: Nomenclature of Alcohols
8.4: Thiols (Mercaptans)
8.5: Nomenclature of Ethers
8.6: Solvents
8.6.1: Boiling Points
8.6.2: Solvent-Solutes
8.7: Acidity of Alcohols and Phenols
8.8: Grignard and Organolithium Reagents
8.9: Grignard Reagents

9: The Chemistry of Alkyl Halides

9.1: An Overview of Nucleophilic Substitution
9.2: Elimination Reactions

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9.3: Rate Laws in Nucleophilic Substitution
9.4: Reaction Rates and Rate Laws
9.5: The SN2 Reaction
9.6: E2 Elimination
9.7: SN1 Reaction
9.7.1: 6.06.1 Kinetics, Stereochemistry and Energy Diagram
9.8: E1 Eliminations
9.9: Comparison of SN2 and SN1
9.10: Comparing E1 and E2
9.11: Determining SN2, SN¬1, E2 or E1
9.12: Carbenes
9.13: Cyclopropane Synthesis

10: The Chemistry of Alcohols and Thiols

10.1: Dehydration Reactions of Alcohols
10.2: Reactions of Alcohols with Hydrohalic Acids
10.3: Converting an Alcohol to a Sulfonate Ester
10.4: Oxidation and Reduction in Organic Chemistry
10.5: Oxidation of Alcohols
10.6: The Formation of Carboxylic Acids
10.7: Nicotinamide Adenine Dinucleotide (NAD)
10.8: Dehydrogenases
10.9: Prochirality
10.10: Thiols and Sulfides
10.11: Nucleophilicity of Sulfur Compounds
10.12: Redox Reactions of Thiols and Disulfides
10.13: An Introduction to Organic Synthesis

11: The Chemistry of Ethers, Epoxides, Glycols, and Sulfides

11.1: Williamson Ether Synthesis
11.2: Synthesis of Epoxides
11.3: Acidic Cleavage of Ethers
11.4: Opening of Epoxides
11.5: Dihydroxylation of Alkenes
11.6: Periodate cleavage of 1,2-diols (glycols)
11.7: Epoxidation
11.8: Sharpless Epoxidation

Index
Glossary
Detailed Licensing

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Licensing
A detailed breakdown of this resource's licensing can be found in Back Matter/Detailed Licensing.

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CHAPTER OVERVIEW

1: Intro to Chemical Structure and Resonance

1: Intro to Chemical Structure and Resonance is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
1.1: Drawing Chemical Structures
Objectives
After completing this section, you should be able to
1. propose one or more acceptable Kekulé structures (structural formulas) for any given molecular formula
2. write the molecular formula of a compound, given its Kekulé structure.
3. draw the shorthand structure of a compound, given its Kekulé structure.
4. interpret shorthand structures and convert them to Kekulé structures.
5. write the molecular formula of a compound, given its shorthand structure.

Study Notes
When drawing the structure of a neutral organic compound, you will find it helpful to remember that
each carbon atom has four bonds.
each nitrogen atom has three bonds.
each oxygen atom has two bonds.
each hydrogen atom has one bond.

It is necessary to draw structural formulas for organic compounds because in most cases a molecular formula does not uniquely
represent a single compound. Different compounds having the same molecular formula are called isomers, and the prevalence of
organic isomers reflects the extraordinary versatility of carbon in forming strong bonds to itself and to other elements. When the
group of atoms that make up the molecules of different isomers are bonded together in fundamentally different ways, we refer to
such compounds as constitutional isomers. There are seven constitutional isomers of C4H10O, and structural formulas for these
are drawn in the following table. These formulas represent all known and possible C4H10O compounds, and display a common
structural feature. There are no double or triple bonds and no rings in any of these structures.
Table 1.1.1: Structural Formulas for C4H10O isomers
Kekulé Formula Condensed Formula Shorthand Formula

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Kekulé Formula Condensed Formula Shorthand Formula

Simplification of structural formulas may be achieved without any loss of the information they convey. In condensed structural
formulas the bonds to each carbon are omitted, but each distinct structural unit (group) is written with subscript numbers
designating multiple substituents, including the hydrogens. Shorthand (line) formulas omit the symbols for carbon and hydrogen
entirely (unless the hydrogen is bonded to an atom other than carbon). Each straight line segment represents a bond, the ends and
intersections of the lines are carbon atoms, and the correct number of hydrogens is calculated from the tetravalency of carbon. Non-
bonding valence shell electrons are omitted in these formulas.
Developing the ability to visualize a three-dimensional structure from two-dimensional formulas requires practice, and in most
cases the aid of molecular models. As noted earlier, many kinds of model kits are available to students and professional chemists,
and the beginning student is encouraged to obtain one.

Kekulé Formula
A Kekulé Formula or structural formula displays the atoms of the molecule in the order they are bonded. It also depicts how the
atoms are bonded to one another, for example single, double, and triple covalent bond. Covalent bonds are shown using lines. The

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number of dashes indicate whether the bond is a single, double, or triple covalent bond. Structural formulas are helpful because
they explain the properties and structure of the compound which empirical and molecular formulas cannot always represent.

Figure 1.1.1 : Kekulé Formula for Ethanol

Condensed Formula
Condensed structural formulas show the order of atoms like a structural formula but are written in a single line to save space and
make it more convenient and faster to write out. Condensed structural formulas are also helpful when showing that a group of
atoms is connected to a single atom in a compound. When this happens, parenthesis are used around the group of atoms to show
they are together.
Ex. Condensed Structural Formula for Ethanol: CH3CH2OH (Molecular Formula for Ethanol C2H6O).

Shorthand Formula
Because organic compounds can be complex at times, line-angle formulas are used to write carbon and hydrogen atoms more
efficiently by replacing the letters with lines. A carbon atom is present wherever a line intersects another line. Hydrogen atoms are
then assumed to complete each of carbon's four bonds. All other atoms that are connected to carbon atoms are written out. Line
angle formulas help show structure and order of the atoms in a compound making the advantages and disadvantages similar to
structural formulas.

Figure 1.1.2 : Shorthand Formula for Ethanol

Exercises
Write down the molecular formula for each of the compounds shown here.
compounds A through D for naming

Answers:
A. C7H7N
B. C5H10
C. C5H4O
D. C5H6Br2
Questions
Q1.12.1
Below is the molecule for caffeine. Give the molecular formula for it.

Solutions
S1.12.1
C8H10O2N4

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Contributors
Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

1.1: Drawing Chemical Structures is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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1.2: Electron-Dot Model of Bonding - Lewis Structures
Using Lewis Dot Symbols to Describe Covalent Bonding
This sharing of electrons allowing atoms to "stick" together is the basis of covalent bonding. There is some intermediate distant,
generally a bit longer than 0.1 nm, or if you prefer 100 pm, at which the attractive forces significantly outweigh the repulsive forces
and a bond will be formed if both atoms can achieve a completen s2np6 configuration. It is this behavior that Lewis captured in his
octet rule. The valence electron configurations of the constituent atoms of a covalent compound are important factors in
determining its structure, stoichiometry, and properties. For example, chlorine, with seven valence electrons, is one electron short
of an octet. If two chlorine atoms share their unpaired electrons by making a covalent bond and forming Cl2, they can each
complete their valence shell:

1. Arrange the atoms to show specific connections. When there is a central atom, it is usually the least electronegative element
in the compound. Chemists usually list this central atom first in the chemical formula (as in CCl4 and CO32−, which both have C
as the central atom), which is another clue to the compound’s structure. Hydrogen and the halogens are almost always
connected to only one other atom, so they are usually terminal rather than central.
Note
The central atom is usually the least electronegative element in the molecule or ion; hydrogen and the halogens are usually
terminal.

Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.
1. Determine the total number of valence electrons in the molecule or ion. Add together the valence electrons from each atom.
(Recall from Chapter 2 that the number of valence electrons is indicated by the position of the element in the periodic table.) If
the species is a polyatomic ion, remember to add or subtract the number of electrons necessary to give the total charge on the
ion. For CO32−, for example, we add two electrons to the total because of the −2 charge.
2. Place a bonding pair of electrons between each pair of adjacent atoms to give a single bond. In H O, for example, there is
2

a bonding pair of electrons between oxygen and each hydrogen.

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3. Beginning with the terminal atoms, add enough electrons to each atom to give each atom an octet (two for hydrogen).
These electrons will usually be lone pairs.
4. If any electrons are left over, place them on the central atom. Some atoms are able to accommodate more than eight
electrons.
5. If the central atom has fewer electrons than an octet, use lone pairs from terminal atoms to form multiple (double or
triple) bonds to the central atom to achieve an octet. This will not change the number of electrons on the terminal atoms.

H2O
1. Because H atoms are almost always terminal, the arrangement within the molecule must be HOH.
2. Each H atom (group 1) has 1 valence electron, and the O atom (group 16) has 6 valence electrons, for a total of 8 valence
electrons.
3. Placing one bonding pair of electrons between the O atom and each H atom gives H:O:H, with 4 electrons left over.
4. Each H atom has a full valence shell of 2 electrons.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.

OCl−
1. With only two atoms in the molecule, there is no central atom.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a

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covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.

CH2O
1. Because carbon is less electronegative than oxygen and hydrogen is normally terminal, C must be the central atom. One possible
arrangement is as follows:

Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.

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covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Each chlorine atom now has an octet. The electron pair being shared by the atoms is called a bonding pair ; the other three pairs of
electrons on each chlorine atom are called lone pairs. Lone pairs are not involved in covalent bonding. If both electrons in a
covalent bond come from the same atom, the bond is called a coordinate covalent bond.
Example
Write the Lewis electron structure for each species.
1. NCl3
2. S22−
3. NOCl
Given: chemical species
Asked for: Lewis electron structures
Strategy:
Use the six-step procedure to write the Lewis electron structure for each species.
Solution:
Nitrogen is less electronegative than chlorine, and halogen atoms are usually terminal, so nitrogen is the central atom. The
nitrogen atom (group 15) has 5 valence electrons and each chlorine atom (group 17) has 7 valence electrons, for a total of 26
valence electrons. Using 2 electrons for each N–Cl bond and adding three lone pairs to each Cl account for (3 × 2) + (3 × 2 × 3)
= 24 electrons. Rule 5 leads us to place the remaining 2 electrons on the central N:

Nitrogen trichloride is an unstable oily liquid once used to bleach flour; this use is now prohibited in the United States.

1.
2. In a diatomic molecule or ion, we do not need to worry about a central atom. Each sulfur atom (group 16) contains 6 valence
electrons, and we need to add 2 electrons for the −2 charge, giving a total of 14 valence electrons. Using 2 electrons for the
S–S bond, we arrange the remaining 12 electrons as three lone pairs on each sulfur, giving each S atom an octet of electrons:

3. Because nitrogen is less electronegative than oxygen or chlorine, it is the central atom. The N atom (group 15) has 5 valence
electrons, the O atom (group 16) has 6 valence electrons, and the Cl atom (group 17) has 7 valence electrons, giving a total
of 18 valence electrons. Placing one bonding pair of electrons between each pair of bonded atoms uses 4 electrons and gives
the following:

Adding three lone pairs each to oxygen and to chlorine uses 12 more electrons, leaving 2 electrons to place as a lone pair on
nitrogen:

4. Because this Lewis structure has only 6 electrons around the central nitrogen, a lone pair of electrons on a terminal atom
must be used to form a bonding pair. We could use a lone pair on either O or Cl. Because we have seen many structures in
which O forms a double bond but none with a double bond to Cl, it is reasonable to select a lone pair from O to give the
following:

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All atoms now have octet configurations. This is the Lewis electron structure of nitrosyl chloride, a highly corrosive,
reddish-orange gas.

Exercise
Write Lewis electron structures for CO2 and SCl2, a vile-smelling, unstable red liquid that is used in the manufacture of rubber.
Answer:

Formal Charges
It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis structure
by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the free atom
and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge distribution
within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the overall charge on
the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is simply used to predict
the most likely structure when a compound has more than one valid Lewis structure.
It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis structure
by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the free atom
and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge distribution
within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the overall charge on
the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is simply used to predict
the most likely structure when a compound has more than one valid Lewis structure.
It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis
structure by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the
free atom and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge
distribution within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the
overall charge on the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is
simply used to predict the most likely structure when a compound has more than one valid Lewis structure.
For each atom, we then compute a formal charge:

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It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis structure
by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the free atom
and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge distribution
within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the overall charge on
the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is simply used to predict
the most likely structure when a compound has more than one valid Lewis structure.

A neutral nitrogen atom has five valence electrons (it is in group 15). From its Lewis electron structure, the nitrogen atom in
ammonia has one lone pair and shares three bonding pairs with hydrogen atoms, so nitrogen itself is assigned a total of five
electrons [2 nonbonding e− + (6 bonding e−/2)]. Substituting into Equation 5.3.1, we obtain

It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis structure
by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the free atom
and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge distribution
within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the overall charge on
the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is simply used to predict
the most likely structure when a compound has more than one valid Lewis structure.
It is sometimes possible to write more than one Lewis structure for a substance that does not violate the octet rule, as we saw for
CH2O, but not every Lewis structure may be equally reasonable. In these situations, we can choose the most stable Lewis structure
by considering the formal charge on the atoms, which is the difference between the number of valence electrons in the free atom
and the number assigned to it in the Lewis electron structure. The formal charge is a way of computing the charge distribution
within a Lewis structure; the sum of the formal charges on the atoms within a molecule or an ion must equal the overall charge on
the molecule or ion. A formal charge does not represent a true charge on an atom in a covalent bond but is simply used to predict
the most likely structure when a compound has more than one valid Lewis structure.
Example
Calculate the formal charges on each atom in the NH4+ ion.
Given: chemical species
Asked for: formal charges
Strategy:
Identify the number of valence electrons in each atom in the NH4+ ion. Use the Lewis electron structure of NH4+ to identify the
number of bonding and nonbonding electrons associated with each atom and then use Equation 4.4.1 to calculate the formal
charge on each atom.

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Solution:
The Lewis electron structure for the NH4+ ion is as follows:

The nitrogen atom shares four bonding pairs of electrons, and a neutral nitrogen atom has five valence electrons. Using Equation
4.4.1, the formal charge on the nitrogen atom is therefore

Each hydrogen atom in has one bonding pair. The formal charge on each hydrogen atom is therefore

The formal charges on the atoms in the NH4+ ion are thus

Adding together the formal charges on the atoms should give us the total charge on the molecule or ion. In this case, the sum of
the formal charges is 0 + 1 + 0 + 0 + 0 = +1.

Exercise
Write the formal charges on all atoms in BH4−.
Answer:

If an atom in a molecule or ion has the number of bonds that is typical for that atom (e.g., four bonds for carbon), its formal
charge is zero.

Using Formal Charges to Distinguish between Lewis Structures

CO2
1. C is less electronegative than O, so it is the central atom.

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As an example of how formal charges can be used to determine the most stable Lewis structure for a substance, we can compare
two possible structures for CO2. Both structures conform to the rules for Lewis electron structures.

As an example of how formal charges can be used to determine the most stable Lewis structure for a substance, we can compare
two possible structures for CO2. Both structures conform to the rules for Lewis electron structures.
As an example of how formal charges can be used to determine the most stable Lewis structure for a substance, we can compare
two possible structures for CO2. Both structures conform to the rules for Lewis electron structures.
Example
The thiocyanate ion (SCN−), which is used in printing and as a corrosion inhibitor against acidic gases, has at least two possible
Lewis electron structures. Draw two possible structures, assign formal charges on all atoms in both, and decide which is the
preferred arrangement of electrons.
Given: chemical species
Asked for: Lewis electron structures, formal charges, and preferred arrangement
Strategy:
A Use the step-by-step procedure to write two plausible Lewis electron structures for SCN−.
B Calculate the formal charge on each atom using Equation 4.4.1.
C Predict which structure is preferred based on the formal charge on each atom and its electronegativity relative to the other
atoms present.
Solution:
A Possible Lewis structures for the SCN− ion are as follows:

B We must calculate the formal charges on each atom to identify the more stable structure. If we begin with carbon, we notice
that the carbon atom in each of these structures shares four bonding pairs, the number of bonds typical for carbon, so it has a
formal charge of zero. Continuing with sulfur, we observe that in (a) the sulfur atom shares one bonding pair and has three lone
pairs and has a total of six valence electrons. The formal charge on the sulfur atom is therefore
In (c), nitrogen has a formal charge of −2.
C Which structure is preferred? Structure (b) is preferred because the negative charge is on the more electronegative atom (N),
and it has lower formal charges on each atom as compared to structure (c): 0, −1 versus +1, −2.

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Exercise
Salts containing the fulminate ion (CNO−) are used in explosive detonators. Draw three Lewis electron structures for CNO− and
use formal charges to predict which is more stable. (Note: N is the central atom.)
Answer:

The second structure is predicted to be more stable.

Drawing isomers of Lewis Structures

Contributors
Anonymous
Layne Morsch (University of Illinois Springfield)
Three cases can be constructed that do not follow the octet rule, and as such, they are known as the exceptions to the octet rule.
Following the Octet Rule for Lewis Dot Structures leads to the most accurate depictions of stable molecular and atomic structures
and because of this we always want to use the octet rule when drawing Lewis Dot Structures. However, it is hard to imagine that
one rule could be followed by all molecules. There is always an exception, and in this case, three exceptions. The octet rule is
violated in these three scenarios:
1. When there are an odd number of valence electrons
2. When there are too few valence electrons
3. When there are too many valence electrons

Exception 1: Species with Odd Numbers of Electrons

The first exception to the Octet Rule is when there are an odd number of valence electrons. An example of this would be Nitrogen
(II) Oxide (NO ,refer to figure one). Nitrogen has 5 valence electrons while Oxygen has 6. The total would be 11 valence electrons
to be used. The Octet Rule for this molecule is fulfilled in the above example, however that is with 10 valence electrons. The last

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one does not know where to go. The lone electron is called an unpaired electron. But where should the unpaired electron go? The
unpaired electron is usually placed in the Lewis Dot Structure so that each element in the structure will have the lowest formal
charge possible. The formal charge is the perceived charge on an individual atom in a molecule when atoms do not contribute
equal numbers of electrons to the bonds they participate in. The formula to find a formal charge is:
Formal Charge= [# of valence e- the atom would have on its own] - [# of lone pair electrons on that atom]
- [# of bonds that atom participates in]
No formal charge at all is the most ideal situation. An example of a stable molecule with an odd number of valence electrons would
be nitrogen monoxide. Nitrogen monoxide has 11 valence electrons. If you need more information about formal charges, see Lewis
Structures. If we were to imagine nitrogen monoxide had ten valence electrons we would come up with the Lewis Structure (Figure
8.7.1):

Figure 8.7.1. This is if Nitrogen monoxide has only ten valence electrons, which it does not.
Let's look at the formal charges of Figure 8.7.2 based on this Lewis structure. Nitrogen normally has five valence electrons. In
Figure 8.7.1, it has two lone pair electrons and it participates in two bonds (a double bond) with oxygen. This results in nitrogen
having a formal charge of +1. Oxygen normally has six valence electrons. In Figure 8.7.1, oxygen has four lone pair electrons and
it participates in two bonds with nitrogen. Oxygen therefore has a formal charge of 0. The overall molecule here has a formal
charge of +1 (+1 for nitrogen, 0 for oxygen. +1 + 0 = +1). However, if we add the eleventh electron to nitrogen (because we want
the molecule to have the lowest total formal charge), it will bring both the nitrogen and the molecule's overall charges to zero, the
most ideal formal charge situation. That is exactly what is done to get the correct Lewis structure for nitrogen monoxide (Figure
8.7.2):

Figure 8.7.2. The proper Lewis structure for NO molecule

Free Radicals

There are actually very few stable molecules with odd numbers of electrons that exist, since that unpaired electron is willing to
react with other unpaired electrons. Most odd electron species are highly reactive, which we call Free Radicals. Because of their
instability, free radicals bond to atoms in which they can take an electron from in order to become stable, making them very
chemically reactive. Radicals are found as both reactants and products, but generally react to form more stable molecules as soon as
they can. In order to emphasize the existence of the unpaired electron, radicals are denoted with a dot in front of their chemical
symbol as with , the hydroxyl radical. An example of a radical you may by familiar with already is the gaseous chlorine atom,
denoted . Interestingly, odd Number of Valence Electrons will result in the molecule being paramagnetic.

Exception 2: Incomplete Octets

The second exception to the Octet Rule is when there are too few valence electrons that results in an incomplete Octet. There are
even more occasions where the octet rule does not give the most correct depiction of a molecule or ion. This is also the case with
incomplete octets. Species with incomplete octets are pretty rare and generally are only found in some beryllium, aluminum, and
boron compounds including the boron hydrides. Let's take a look at one such hydride, BH3 (Borane).
If one was to make a Lewis structure for BH3 following the basic strategies for drawing Lewis structures, one would probably come
up with this structure (Figure 8.7.3):

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Figure 8.7.3
The problem with this structure is that boron has an incomplete octet; it only has six electrons around it. Hydrogen atoms can
naturally only have only 2 electrons in their outermost shell (their version of an octet), and as such there are no spare electrons to
form a double bond with boron. One might surmise that the failure of this structure to form complete octets must mean that this
bond should be ionic instead of covalent. However, boron has an electronegativity that is very similar to hydrogen, meaning there is
likely very little ionic character in the hydrogen to boron bonds, and as such this Lewis structure, though it does not fulfill the octet
rule, is likely the best structure possible for depicting BH3 with Lewis theory. One of the things that may account for BH3's
incomplete octet is that it is commonly a transitory species, formed temporarily in reactions that involve multiple steps.
Let's take a look at another incomplete octet situation dealing with boron, BF3 (Boron trifluorine). Like with BH3, the initial
drawing of a Lewis structure of BF3 will form a structure where boron has only six electrons around it (Figure 8.7.4).

Figure 8.7.4
If you look Figure 8.7.4, you can see that the fluorine atoms possess extra lone pairs that they can use to make additional bonds
with boron, and you might think that all you have to do is make one lone pair into a bond and the structure will be correct. If we
add one double bond between boron and one of the fluorines we get the following Lewis Structure (Figure 8.7.5):

Figure 8.7.5
Each fluorine has eight electrons, and the boron atom has eight as well! Each atom has a perfect octet, right? Not so fast. We must
examine the formal charges of this structure. The fluorine that shares a double bond with boron has six electrons around it (four
from its two lone pairs of electrons and one each from its two bonds with boron). This is one less electron than the number of
valence electrons it would have naturally (Group Seven elements have seven valence electrons), so it has a formal charge of +1.
The two flourines that share single bonds with boron have seven electrons around them (six from their three lone pairs and one
from their single bonds with boron). This is the same amount as the number of valence electrons they would have on their own, so
they both have a formal charge of zero. Finally, boron has four electrons around it (one from each of its four bonds shared with
fluorine). This is one more electron than the number of valence electrons that boron would have on its own, and as such boron has a
formal charge of -1.
This structure is supported by the fact that the experimentally determined bond length of the boron to fluorine bonds in BF3 is less
than what would be typical for a single bond (see Bond Order and Lengths). However, this structure contradicts one of the major
rules of formal charges: Negative formal charges are supposed to be found on the more electronegative atom(s) in a bond, but in the
structure depicted in Figure 8.7.5, a positive formal charge is found on fluorine, which not only is the most electronegative element
in the structure, but the most electronegative element in the entire periodic table ( ). Boron on the other hand, with the
much lower electronegativity of 2.0, has the negative formal charge in this structure. This formal charge-electronegativity
disagreement makes this double-bonded structure impossible.
However the large electronegativity difference here, as opposed to in BH3, signifies significant polar bonds between boron and
fluorine, which means there is a high ionic character to this molecule. This suggests the possibility of a semi-ionic structure such as
seen in Figure 8.7.6:

Figure 8.7.6

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None of these three structures is the "correct" structure in this instance. The most "correct" structure is most likely a resonance of
all three structures: the one with the incomplete octet (Figure 8.7.4), the one with the double bond (Figure 8.7.5), and the one with
the ionic bond (Figure 8.7.6). The most contributing structure is probably the incomplete octet structure (due to Figure 8.7.5 being
basically impossible and Figure 8.7.6 not matching up with the behavior and properties of BF3). As you can see even when other
possibilities exist, incomplete octets may best portray a molecular structure.
As a side note, it is important to note that BF3 frequently bonds with a F- ion in order to form BF4- rather than staying as BF3. This
structure completes boron's octet and it is more common in nature. This exemplifies the fact that incomplete octets are rare, and
other configurations are typically more favorable, including bonding with additional ions as in the case of BF3 .

Example 8.7.1:

Draw the Lewis structure for boron trifluoride (BF3).

SOLUTION
1. Add electrons (3*7) + 3 = 24
2. Draw connectivities:

3. Add octets to outer atoms:

4. Add extra electrons (24-24=0) to central atom:

5. Does central electron have octet?

NO. It has 6 electrons
Add a multiple bond (double bond) to see if central atom can achieve an octet:

6. The central Boron now has an octet (there would be three resonance Lewis structures)
However...
In this structure with a double bond the fluorine atom is sharing extra electrons with the boron.
The fluorine would have a '+' partial charge, and the boron a '-' partial charge, this is inconsistent with the electronegativities of fluorine and
boron.
Thus, the structure of BF3, with single bonds, and 6 valence electrons around the central boron is the most likely structure
BF3 reacts strongly with compounds which have an unshared pair of electrons which can be used to form a bond with the boron:

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Exception 3: Expanded Valence Shells

More common than incomplete octets are expanded octets where the central atom in a Lewis structure has more than eight
electrons in its valence shell. In expanded octets, the central atom can have ten electrons, or even twelve. Molecules with expanded
octets involve highly electronegative terminal atoms, and a nonmetal central atom found in the third period or below, which those
terminal atoms bond to. For example, is a legitimate compound (whereas ) is not:

Note

Expanded valence shells are observed only for elements in period 3 (i.e. n=3) and beyond

The 'octet' rule is based upon available ns and np orbitals for valence electrons (2 electrons in the s orbitals, and 6 in the p orbitals).
Beginning with the n=3 principle quantum number, the d orbitals become available (l=2). The orbital diagram for the valence shell
of phosphorous is:

Hence, the third period elements occasionally exceed the octet rule by using their empty d orbitals to accommodate additional
electrons. Size is also an important consideration:
The larger the central atom, the larger the number of electrons which can surround it
Expanded valence shells occur most often when the central atom is bonded to small electronegative atoms, such as F, Cl and O.
There is currently much scientific exploration and inquiry into the reason why expanded valence shells are found. The top area of
interest is figuring out where the extra pair(s) of electrons are found. Many chemists think that there is not a very large energy
difference between the 3p and 3d orbitals, and as such it is plausible for extra electrons to easily fill the 3d orbital when an
expanded octet is more favorable than having a complete octet. This matter is still under hot debate, however and there is even
debate as to what makes an expanded octet more favorable than a configuration that follows the octet rule.
One of the situations where expanded octet structures are treated as more favorable than Lewis structures that follow the octet rule
is when the formal charges in the expanded octet structure are smaller than in a structure that adheres to the octet rule, or when
there are less formal charges in the expanded octet than in the structure a structure that adheres to the octet rule.

Example 8.7.2: The ion

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Such is the case for the sulfate ion, SO4-2. A strict adherence to the octet rule forms the following Lewis structure:

Figure 8.7.12
If we look at the formal charges on this molecule, we can see that all of the oxygen atoms have seven electrons around them (six from the three
lone pairs and one from the bond with sulfur). This is one more electron than the number of valence electrons then they would have normally, and
as such each of the oxygens in this structure has a formal charge of -1. Sulfur has four electrons around it in this structure (one from each of its
four bonds) which is two electrons more than the number of valence electrons it would have normally, and as such it carries a formal charge of +2.
If instead we made a structure for the sulfate ion with an expanded octet, it would look like this:

Figure 8.7.13
Looking at the formal charges for this structure, the sulfur ion has six electrons around it (one from each of its bonds). This is the same amount as
the number of valence electrons it would have naturally. This leaves sulfur with a formal charge of zero. The two oxygens that have double bonds
to sulfur have six electrons each around them (four from the two lone pairs and one each from the two bonds with sulfur). This is the same amount
of electrons as the number of valence electrons that oxygen atoms have on their own, and as such both of these oxygen atoms have a formal
charge of zero. The two oxygens with the single bonds to sulfur have seven electrons around them in this structure (six from the three lone pairs
and one from the bond to sulfur). That is one electron more than the number of valence electrons that oxygen would have on its own, and as such
those two oxygens carry a formal charge of -1. Remember that with formal charges, the goal is to keep the formal charges (or the difference
between the formal charges of each atom) as small as possible. The number of and values of the formal charges on this structure (-1 and 0
(difference of 1) in Figure 8.7.12, as opposed to +2 and -1 (difference of 3) in Figure 8.7.12) is significantly lower than on the structure that
follows the octet rule, and as such an expanded octet is plausible, and even preferred to a normal octet, in this case.

Example 8.7.3: The Ion

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Draw the Lewis structure for ion.
SOLUTION
1. Count up the valence electrons: 7+(4*7)+1 = 36 electrons
2. Draw the connectivities:

3. Add octet of electrons to outer atoms:

4. Add extra electrons (36-32=4) to central atom:

5. The ICl4- ion thus has 12 valence electrons around the central Iodine (in the 5d orbitals)

Expanded Lewis structures are also plausible depictions of molecules when experimentally determined bond lengths suggest partial
double bond characters even when single bonds would already fully fill the octet of the central atom. Despite the cases for
expanded octets, as mentioned for incomplete octets, it is important to keep in mind that, in general, the octet rule applies.

Contributors
Mike Blaber (Florida State University)

1.2: Electron-Dot Model of Bonding - Lewis Structures is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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1.3: VSPER Theory- The Effect of Lone Pairs
 Learning Objectives
To use the VSEPR model to predict molecular geometries.
To predict whether a molecule has a dipole moment.

The Lewis electron-pair approach can be used to predict the number and types of bonds between the atoms in a substance, and it
indicates which atoms have lone pairs of electrons. This approach gives no information about the actual arrangement of atoms in
space, however. We continue our discussion of structure and bonding by introducing the valence-shell electron-pair repulsion
(VSEPR) model (pronounced “vesper”), which can be used to predict the shapes of many molecules and polyatomic ions. Keep in
mind, however, that the VSEPR model, like any model, is a limited representation of reality; the model provides no information
about bond lengths or the presence of multiple bonds.

The VSEPR Model

The VSEPR model can predict the structure of nearly any molecule or polyatomic ion in which the central atom is a nonmetal, as
well as the structures of many molecules and polyatomic ions with a central metal atom. The premise of the VSEPR theory is that
electron pairs located in bonds and lone pairs repel each other and will therefore adopt the geometry that places electron pairs as far
apart from each other as possible. This theory is very simplistic and does not account for the subtleties of orbital interactions that
influence molecular shapes; however, the simple VSEPR counting procedure accurately predicts the three-dimensional structures of
a large number of compounds, which cannot be predicted using the Lewis electron-pair approach.

Figure 1.3.1 : Common Structures for Molecules and Polyatomic Ions That Consist of a Central Atom Bonded to Two or Three
Other Atoms. (CC BY-NC-SA; anonymous)
We can use the VSEPR model to predict the geometry of most polyatomic molecules and ions by focusing only on the number of
electron pairs around the central atom, ignoring all other valence electrons present. According to this model, valence electrons in
the Lewis structure form groups, which may consist of a single bond, a double bond, a triple bond, a lone pair of electrons, or even
a single unpaired electron, which in the VSEPR model is counted as a lone pair. Because electrons repel each other
electrostatically, the most stable arrangement of electron groups (i.e., the one with the lowest energy) is the one that minimizes
repulsions. Groups are positioned around the central atom in a way that produces the molecular structure with the lowest energy, as
illustrated in Figures 1.3.1 and 1.3.2.

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Figure 1.3.2 : Electron Geometries for Species with Two to Six Electron Groups. Groups are placed around the central atom in a
way that produces a molecular structure with the lowest energy, that is, the one that minimizes repulsions. (CC BY-NC-SA;
anonymous)
In the VSEPR model, the molecule or polyatomic ion is given an AXmEn designation, where A is the central atom, X is a bonded
atom, E is a nonbonding valence electron group (usually a lone pair of electrons), and m and n are integers. Each group around the
central atom is designated as a bonding pair (BP) or lone (nonbonding) pair (LP). From the BP and LP interactions we can predict
both the relative positions of the atoms and the angles between the bonds, called the bond angles. Using this information, we can
describe the molecular geometry, the arrangement of the bonded atoms in a molecule or polyatomic ion.

 VESPR Produce to predict Molecular geometry

This VESPR procedure is summarized as follows:

1. Draw the Lewis electron structure of the molecule or polyatomic ion.
2. Determine the electron group arrangement around the central atom that minimizes repulsions.
3. Assign an AXmEn designation; then identify the LP–LP, LP–BP, or BP–BP interactions and predict deviations from ideal
bond angles.
4. Describe the molecular geometry.

We will illustrate the use of this procedure with several examples, beginning with atoms with two electron groups. In our
discussion we will refer to Figure 1.3.2 and Figure 1.3.3, which summarize the common molecular geometries and idealized bond
angles of molecules and ions with two to six electron groups.

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Figure 1.3.3 : Common Molecular Geometries for Species with Two to Six Electron Groups. Lone pairs are shown using a dashed
line. (CC BY-NC-SA; anonymous)
Linear, bent, trigonal planar, trigonal pyramidal, square planar, tetrahedral, trigonal bipyramidal, octahedral.

Two Electron Groups

Our first example is a molecule with two bonded atoms and no lone pairs of electrons, BeH . 2

 AX2 Molecules: BeH2

1. The central atom, beryllium, contributes two valence electrons, and each hydrogen atom contributes one. The Lewis electron
structure is

Figure 1.3.2 that the arrangement that minimizes repulsions places the groups 180° apart. (CC BY-NC-SA; anonymous)
3. Both groups around the central atom are bonding pairs (BP). Thus BeH2 is designated as AX2.
4. From Figure 1.3.3 we see that with two bonding pairs, the molecular geometry that minimizes repulsions in BeH2 is linear.

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 AX2 Molecules: CO2
1. The central atom, carbon, contributes four valence electrons, and each oxygen atom contributes six. The Lewis electron
structure is

2. The carbon atom forms two double bonds. Each double bond is a group, so there are two electron groups around the central
atom. Like BeH2, the arrangement that minimizes repulsions places the groups 180° apart.
3. Once again, both groups around the central atom are bonding pairs (BP), so CO2 is designated as AX2.
4. VSEPR only recognizes groups around the central atom. Thus the lone pairs on the oxygen atoms do not influence the
molecular geometry. With two bonding pairs on the central atom and no lone pairs, the molecular geometry of CO2 is linear
(Figure 1.3.3). The structure of CO is shown in Figure 1.3.1.
2

Three Electron Groups

 AX3 Molecules: BCl3

1. The central atom, boron, contributes three valence electrons, and each chlorine atom contributes seven valence electrons.
The Lewis electron structure is

Figure 1.3.2 ): (CC BY-NC-SA; anonymous)

3. All electron groups are bonding pairs (BP), so the structure is designated as AX3.
4. From Figure 1.3.3 we see that with three bonding pairs around the central atom, the molecular geometry of BCl3 is trigonal
planar, as shown in Figure 1.3.2.

 AX3 Molecules: CO32−

1. The central atom, carbon, has four valence electrons, and each oxygen atom has six valence electrons. As you learned
previously, the Lewis electron structure of one of three resonance forms is represented as

Figure 1.3.2 ).
The three oxygens are arranged in a triangular shape with carbon at the center. Two of the oxygens have three lone pairs. One
ocht oxygens has 2 lone pairs and is double bonded to the carbon. The molecule has a minus 2 charge.
3. All electron groups are bonding pairs (BP). With three bonding groups around the central atom, the structure is designated as
AX3.
4. We see from Figure 1.3.3 that the molecular geometry of CO32− is trigonal planar with bond angles of 120°.

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In our next example we encounter the effects of lone pairs and multiple bonds on molecular geometry for the first time.

 AX2E Molecules: SO2

1. The central atom, sulfur, has 6 valence electrons, as does each oxygen atom. With 18 valence electrons, the Lewis electron
structure is shown below.

Figure 1.3.2 ): (CC BY-NC-SA; anonymous)

The two oxygens are double bonded to the sulfur. The oxygens have 2 lone pairs while sulfur had one lone pair.
3. There are two bonding pairs and one lone pair, so the structure is designated as AX2E. This designation has a total of three
electron pairs, two X and one E. Because a lone pair is not shared by two nuclei, it occupies more space near the central atom
than a bonding pair (Figure 1.3.4). Thus bonding pairs and lone pairs repel each other electrostatically in the order BP–BP <
LP–BP < LP–LP. In SO2, we have one BP–BP interaction and two LP–BP interactions.
4. The molecular geometry is described only by the positions of the nuclei, not by the positions of the lone pairs. Thus with
two nuclei and one lone pair the shape is bent, or V shaped, which can be viewed as a trigonal planar arrangement with a
missing vertex (Figures 1.3.2 and 1.3.3). The O-S-O bond angle is expected to be less than 120° because of the extra space
taken up by the lone pair.

Figure 1.3.4 : The Difference in the Space Occupied by a Lone Pair of Electrons and by a Bonding Pair. (CC BY-NC-SA;
anonymous)
As with SO2, this composite model of electron distribution and negative electrostatic potential in ammonia shows that a lone
pair of electrons occupies a larger region of space around the nitrogen atom than does a bonding pair of electrons that is shared
with a hydrogen atom.

Like lone pairs of electrons, multiple bonds occupy more space around the central atom than a single bond, which can cause other
bond angles to be somewhat smaller than expected. This is because a multiple bond has a higher electron density than a single
bond, so its electrons occupy more space than those of a single bond. For example, in a molecule such as CH2O (AX3), whose

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structure is shown below, the double bond repels the single bonds more strongly than the single bonds repel each other. This causes
a deviation from ideal geometry (an H–C–H bond angle of 116.5° rather than 120°).

Four Electron Groups

One of the limitations of Lewis structures is that they depict molecules and ions in only two dimensions. With four electron groups,
we must learn to show molecules and ions in three dimensions.

 AX4 Molecules: CH4

1. The central atom, carbon, contributes four valence electrons, and each hydrogen atom has one valence electron, so the full
Lewis electron structure is

2. There are four electron groups around the central atom. As shown in Figure 1.3.2, repulsions are minimized by placing the
groups in the corners of a tetrahedron with bond angles of 109.5°.
3. All electron groups are bonding pairs, so the structure is designated as AX4.
4. With four bonding pairs, the molecular geometry of methane is tetrahedral (Figure 1.3.3).

 AX3E Molecules: NH3

1. In ammonia, the central atom, nitrogen, has five valence electrons and each hydrogen donates one valence electron,
producing the Lewis electron structure

2. There are four electron groups around nitrogen, three bonding pairs and one lone pair. Repulsions are minimized by
directing each hydrogen atom and the lone pair to the corners of a tetrahedron.
3. With three bonding pairs and one lone pair, the structure is designated as AX3E. This designation has a total of four electron
pairs, three X and one E. We expect the LP–BP interactions to cause the bonding pair angles to deviate significantly from the

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angles of a perfect tetrahedron.
4. There are three nuclei and one lone pair, so the molecular geometry is trigonal pyramidal. In essence, this is a tetrahedron
with a vertex missing (Figure 1.3.3). However, the H–N–H bond angles are less than the ideal angle of 109.5° because of LP–
BP repulsions (Figure 1.3.3 and Figure 1.3.4).

 AX2E2 Molecules: H2O

1. Oxygen has six valence electrons and each hydrogen has one valence electron, producing the Lewis electron structure

Figure 1.3.2 : (CC BY-NC-SA; anonymous)

3. With two bonding pairs and two lone pairs, the structure is designated as AX2E2 with a total of four electron pairs. Due to
LP–LP, LP–BP, and BP–BP interactions, we expect a significant deviation from idealized tetrahedral angles.
4. With two hydrogen atoms and two lone pairs of electrons, the structure has significant lone pair interactions. There are two
nuclei about the central atom, so the molecular shape is bent, or V shaped, with an H–O–H angle that is even less than the H–
N–H angles in NH3, as we would expect because of the presence of two lone pairs of electrons on the central atom rather than
one. This molecular shape is essentially a tetrahedron with two missing vertices.

Five Electron Groups

In previous examples it did not matter where we placed the electron groups because all positions were equivalent. In some cases,
however, the positions are not equivalent. We encounter this situation for the first time with five electron groups.

 AX5 Molecules: PCl5

1. Phosphorus has five valence electrons and each chlorine has seven valence electrons, so the Lewis electron structure of PCl5
is

Figure 1.3.2 ): (CC BY-NC-SA; anonymous)

3. All electron groups are bonding pairs, so the structure is designated as AX5. There are no lone pair interactions.
4. The molecular geometry of PCl5 is trigonal bipyramidal, as shown in Figure 1.3.3. The molecule has three atoms in a plane
in equatorial positions and two atoms above and below the plane in axial positions. The three equatorial positions are
separated by 120° from one another, and the two axial positions are at 90° to the equatorial plane. The axial and equatorial
positions are not chemically equivalent, as we will see in our next example.

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 AX4E Molecules: SF4
1. The sulfur atom has six valence electrons and each fluorine has seven valence electrons, so the Lewis electron structure is

Four fluorenes are bonded to a central sulfur. Each fluorine has three lone pairs. Sulfur has one lone pair.
With an expanded valence, this species is an exception to the octet rule.
2. There are five groups around sulfur, four bonding pairs and one lone pair. With five electron groups, the lowest energy
arrangement is a trigonal bipyramid, as shown in Figure 1.3.2.
3. We designate SF4 as AX4E; it has a total of five electron pairs. However, because the axial and equatorial positions are not
chemically equivalent, where do we place the lone pair? If we place the lone pair in the axial position, we have three LP–BP
repulsions at 90°. If we place it in the equatorial position, we have two 90° LP–BP repulsions at 90°. With fewer 90° LP–BP
repulsions, we can predict that the structure with the lone pair of electrons in the equatorial position is more stable than the one
with the lone pair in the axial position. We also expect a deviation from ideal geometry because a lone pair of electrons
occupies more space than a bonding pair.

Figure 1.3.5 : Illustration of the Area Shared by Two Electron Pairs versus the Angle between Them
180 degree angle has no shared space between teo electron pair, 120 degree angle has some shared area between two electron
pairs. 90 degree angle has more shared space than 120.
At 90°, the two electron pairs share a relatively large region of space, which leads to strong repulsive electron–electron
interactions.
4. With four nuclei and one lone pair of electrons, the molecular structure is based on a trigonal bipyramid with a missing
equatorial vertex; it is described as a seesaw. The Faxial–S–Faxial angle is 173° rather than 180° because of the lone pair of
electrons in the equatorial plane.

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 AX3E2 Molecules: BrF3

1. The bromine atom has seven valence electrons, and each fluorine has seven valence electrons, so the Lewis electron
structure is

Three fluorines are bonded to a central bromine. Each fluorine has three lone pairs, Bromine has two lone pairs.
Once again, we have a compound that is an exception to the octet rule.
2. There are five groups around the central atom, three bonding pairs and two lone pairs. We again direct the groups toward the
vertices of a trigonal bipyramid.
3. With three bonding pairs and two lone pairs, the structural designation is AX3E2 with a total of five electron pairs. Because
the axial and equatorial positions are not equivalent, we must decide how to arrange the groups to minimize repulsions. If we
place both lone pairs in the axial positions, we have six LP–BP repulsions at 90°. If both are in the equatorial positions, we
have four LP–BP repulsions at 90°. If one lone pair is axial and the other equatorial, we have one LP–LP repulsion at 90° and
three LP–BP repulsions at 90°:

If the lone pairs are axiam, the 90 degree LP-LP interactions are o and the 90 degree LP-BP interaction is zero. If the Lone
pares are equatorial there are zero 90 degree LP-LP interactions and four 90 degree LP-BP intereactions. If the lone pairs are
axial and equatorial there is one 90 degree LP-LP interaction and three 90 degree LP-BP interaction.
Structure (c) can be eliminated because it has a LP–LP interaction at 90°. Structure (b), with fewer LP–BP repulsions at 90°
than (a), is lower in energy. However, we predict a deviation in bond angles because of the presence of the two lone pairs of
electrons.
4. The three nuclei in BrF3 determine its molecular structure, which is described as T shaped. This is essentially a trigonal
bipyramid that is missing two equatorial vertices. The Faxial–Br–Faxial angle is 172°, less than 180° because of LP–BP
repulsions (Figure 1.3.2.1).

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Because lone pairs occupy more space around the central atom than bonding pairs, electrostatic repulsions are more
important for lone pairs than for bonding pairs.

 AX2E3 Molecules: I3−

1. Each iodine atom contributes seven electrons and the negative charge one, so the Lewis electron structure is

2. There are five electron groups about the central atom in I3−, two bonding pairs and three lone pairs. To minimize repulsions,
the groups are directed to the corners of a trigonal bipyramid.
3. With two bonding pairs and three lone pairs, I3− has a total of five electron pairs and is designated as AX2E3. We must now
decide how to arrange the lone pairs of electrons in a trigonal bipyramid in a way that minimizes repulsions. Placing them in
the axial positions eliminates 90° LP–LP repulsions and minimizes the number of 90° LP–BP repulsions.

The three lone pairs of electrons have equivalent interactions with the three iodine atoms, so we do not expect any deviations in
bonding angles.
4. With three nuclei and three lone pairs of electrons, the molecular geometry of I3− is linear. This can be described as a
trigonal bipyramid with three equatorial vertices missing. The ion has an I–I–I angle of 180°, as expected.

Six Electron Groups

Six electron groups form an octahedron, a polyhedron made of identical equilateral triangles and six identical vertices (Figure
1.3.2.)

 AX6 Molecules: SF6

1. The central atom, sulfur, contributes six valence electrons, and each fluorine atom has seven valence electrons, so the Lewis
electron structure is

With an expanded valence, this species is an exception to the octet rule.

2. There are six electron groups around the central atom, each a bonding pair. We see from Figure 1.3.2 that the geometry that
minimizes repulsions is octahedral.
3. With only bonding pairs, SF6 is designated as AX6. All positions are chemically equivalent, so all electronic interactions are
equivalent.

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4. There are six nuclei, so the molecular geometry of SF6 is octahedral.

 AX5E Molecules: BrF5

1. The central atom, bromine, has seven valence electrons, as does each fluorine, so the Lewis electron structure is

Five fluorines are bonded to a central bromine. Each fluorine has three lone pairs, Bromine has one lone pair.
With its expanded valence, this species is an exception to the octet rule.
2. There are six electron groups around the Br, five bonding pairs and one lone pair. Placing five F atoms around Br while
minimizing BP–BP and LP–BP repulsions gives the following structure:

3. With five bonding pairs and one lone pair, BrF5 is designated as AX5E; it has a total of six electron pairs. The BrF5 structure
has four fluorine atoms in a plane in an equatorial position and one fluorine atom and the lone pair of electrons in the axial
positions. We expect all Faxial–Br–Fequatorial angles to be less than 90° because of the lone pair of electrons, which occupies
more space than the bonding electron pairs.
4. With five nuclei surrounding the central atom, the molecular structure is based on an octahedron with a vertex missing. This
molecular structure is square pyramidal. The Faxial–B–Fequatorial angles are 85.1°, less than 90° because of LP–BP repulsions.

 AX4E2 Molecules: ICl4−

1. The central atom, iodine, contributes seven electrons. Each chlorine contributes seven, and there is a single negative charge.
The Lewis electron structure is

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Four chlorines are bonded to a central iodine. Each chlorine has three electron pairs. The iodine has two electron pairs. The
molecule is negatively charged.
2. There are six electron groups around the central atom, four bonding pairs and two lone pairs. The structure that minimizes
LP–LP, LP–BP, and BP–BP repulsions is

3. ICl4− is designated as AX4E2 and has a total of six electron pairs. Although there are lone pairs of electrons, with four
bonding electron pairs in the equatorial plane and the lone pairs of electrons in the axial positions, all LP–BP repulsions are the
same. Therefore, we do not expect any deviation in the Cl–I–Cl bond angles.
4. With five nuclei, the ICl4− ion forms a molecular structure that is square planar, an octahedron with two opposite vertices
missing.

The relationship between the number of electron groups around a central atom, the number of lone pairs of electrons, and the
molecular geometry is summarized in Figure 1.3.6.

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Figure 1.3.6 : Overview of Molecular Geometries

Shapes of Molecules

 Example 1.3.1

Using the VSEPR model, predict the molecular geometry of each molecule or ion.
1. PF5 (phosphorus pentafluoride, a catalyst used in certain organic reactions)
2. H3O+ (hydronium ion)

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Given: two chemical species
Asked for: molecular geometry

Strategy:
A. Draw the Lewis electron structure of the molecule or polyatomic ion.
B. Determine the electron group arrangement around the central atom that minimizes repulsions.
C. Assign an AXmEn designation; then identify the LP–LP, LP–BP, or BP–BP interactions and predict deviations in bond
angles.
D. Describe the molecular geometry.

Solution:
1. A The central atom, P, has five valence electrons and each fluorine has seven valence electrons, so the Lewis structure of
PF5 is

Figure 1.3.6 ): (CC BY-NC-SA; anonymous)

C All electron groups are bonding pairs, so PF5 is designated as AX5. Notice that this gives a total of five electron pairs.
With no lone pair repulsions, we do not expect any bond angles to deviate from the ideal.
D The PF5 molecule has five nuclei and no lone pairs of electrons, so its molecular geometry is trigonal bipyramidal.

2. A The central atom, O, has six valence electrons, and each H atom contributes one valence electron. Subtracting one
electron for the positive charge gives a total of eight valence electrons, so the Lewis electron structure is

Three hydrogens are bonded to a central oxygen. The oxygen has two lone pairs. The molecule has a charge of plus one.

B There are four electron groups around oxygen, three bonding pairs and one lone pair. Like NH3, repulsions are minimized
by directing each hydrogen atom and the lone pair to the corners of a tetrahedron.
C With three bonding pairs and one lone pair, the structure is designated as AX3E and has a total of four electron pairs
(three X and one E). We expect the LP–BP interactions to cause the bonding pair angles to deviate significantly from the
angles of a perfect tetrahedron.
D There are three nuclei and one lone pair, so the molecular geometry is trigonal pyramidal, in essence a tetrahedron
missing a vertex. However, the H–O–H bond angles are less than the ideal angle of 109.5° because of LP–BP repulsions:

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 Exercise 1.3.1

Using the VSEPR model, predict the molecular geometry of each molecule or ion.
a. XeO3
b. PF6−
c. NO2+

Answer a
trigonal pyramidal
Answer b
octahedral
Answer c
linear

 Example 1.3.2

Predict the molecular geometry of each molecule.

1. XeF2
2. SnCl2
Given: two chemical compounds
Asked for: molecular geometry

Strategy:
Use the strategy given in Example1.3.1.

Solution:
1. A Xenon contributes eight electrons and each fluorine seven valence electrons, so the Lewis electron structure is

B There are five electron groups around the central atom, two bonding pairs and three lone pairs. Repulsions are minimized
by placing the groups in the corners of a trigonal bipyramid.
C From B, XeF2 is designated as AX2E3 and has a total of five electron pairs (two X and three E). With three lone pairs
about the central atom, we can arrange the two F atoms in three possible ways: both F atoms can be axial, one can be axial
and one equatorial, or both can be equatorial:

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If the two F atoms are axial ther are zero 90 LP-LP interactions. If the two F atoms are axial and equatorial or just
equatorial, there are 2 90 LP-LP interactions.
The structure with the lowest energy is the one that minimizes LP–LP repulsions. Both (b) and (c) have two 90° LP–LP
interactions, whereas structure (a) has none. Thus both F atoms are in the axial positions, like the two iodine atoms around
the central iodine in I3−. All LP–BP interactions are equivalent, so we do not expect a deviation from an ideal 180° in the
F–Xe–F bond angle.
D With two nuclei about the central atom, the molecular geometry of XeF2 is linear. It is a trigonal bipyramid with three
missing equatorial vertices.
2. A The tin atom donates 4 valence electrons and each chlorine atom donates 7 valence electrons. With 18 valence electrons,
the Lewis electron structure is

Two chlorines are bonded to a central tin. Each chlorine has three lone pairs. Tin has one lone pair.
B There are three electron groups around the central atom, two bonding groups and one lone pair of electrons. To minimize
repulsions the three groups are initially placed at 120° angles from each other.
C From B we designate SnCl2 as AX2E. It has a total of three electron pairs, two X and one E. Because the lone pair of
electrons occupies more space than the bonding pairs, we expect a decrease in the Cl–Sn–Cl bond angle due to increased
LP–BP repulsions.
D With two nuclei around the central atom and one lone pair of electrons, the molecular geometry of SnCl2 is bent, like
SO2, but with a Cl–Sn–Cl bond angle of 95°. The molecular geometry can be described as a trigonal planar arrangement
with one vertex missing.

 Exercise 1.3.2
Predict the molecular geometry of each molecule.
a. SO3
b. XeF4

Answer a
trigonal planar
Answer b
square planar

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Sample Molecular Shape Problems

Molecules with No Single Central Atom

The VSEPR model can be used to predict the structure of somewhat more complex molecules with no single central atom by
treating them as linked AXmEn fragments. We will demonstrate with methyl isocyanate (CH3–N=C=O), a volatile and highly toxic
molecule that is used to produce the pesticide Sevin. In 1984, large quantities of Sevin were accidentally released in Bhopal, India,
when water leaked into storage tanks. The resulting highly exothermic reaction caused a rapid increase in pressure that ruptured the
tanks, releasing large amounts of methyl isocyanate that killed approximately 3800 people and wholly or partially disabled about
50,000 others. In addition, there was significant damage to livestock and crops.
We can treat methyl isocyanate as linked AXmEn fragments beginning with the carbon atom at the left, which is connected to three
H atoms and one N atom by single bonds. The four bonds around carbon mean that it must be surrounded by four bonding electron
pairs in a configuration similar to AX4. We can therefore predict the CH3–N portion of the molecule to be roughly tetrahedral,
similar to methane:

The nitrogen atom is connected to one carbon by a single bond and to the other carbon by a double bond, producing a total of three
bonds, C–N=C. For nitrogen to have an octet of electrons, it must also have a lone pair:

One carbon bonded to nitrogen and another carbon double bonded to the nitrogen. The nitrogen has one lone pair.
Because multiple bonds are not shown in the VSEPR model, the nitrogen is effectively surrounded by three electron pairs. Thus
according to the VSEPR model, the C–N=C fragment should be bent with an angle less than 120°.
The carbon in the –N=C=O fragment is doubly bonded to both nitrogen and oxygen, which in the VSEPR model gives carbon a
total of two electron pairs. The N=C=O angle should therefore be 180°, or linear. The three fragments combine to give the
following structure:

Figure 1.3.7 ).
Three hydrogens are bonded to a carbon. The carbon is also bonded to a nitrogen. The nitrogen is double bonded to another carbon.
The second carbon is double bonded to an oxygen. The nitrogen has one lone pair. The oxygen has two lone pairs.

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Figure 1.3.7 : The Experimentally Determined Structure of Methyl Isocyanate
Certain patterns are seen in the structures of moderately complex molecules. For example, carbon atoms with four bonds (such as
the carbon on the left in methyl isocyanate) are generally tetrahedral. Similarly, the carbon atom on the right has two double bonds
that are similar to those in CO2, so its geometry, like that of CO2, is linear. Recognizing similarities to simpler molecules will help
you predict the molecular geometries of more complex molecules.

 Example 1.3.3
Use the VSEPR model to predict the molecular geometry of propyne (H3C–C≡CH), a gas with some anesthetic properties.
Given: chemical compound
Asked for: molecular geometry

Strategy:
Count the number of electron groups around each carbon, recognizing that in the VSEPR model, a multiple bond counts as a
single group. Use Figure 1.3.3 to determine the molecular geometry around each carbon atom and then deduce the structure of
the molecule as a whole.

Solution:
Because the carbon atom on the left is bonded to four other atoms, we know that it is approximately tetrahedral. The next two
carbon atoms share a triple bond, and each has an additional single bond. Because a multiple bond is counted as a single bond
in the VSEPR model, each carbon atom behaves as if it had two electron groups. This means that both of these carbons are
linear, with C–C≡C and C≡C–H angles of 180°.

 Exercise 1.3.3

Predict the geometry of allene (H2C=C=CH2), a compound with narcotic properties that is used to make more complex organic
molecules.

Answer
The terminal carbon atoms are trigonal planar, the central carbon is linear, and the C–C–C angle is 180°.

Molecular Dipole Moments

You previously learned how to calculate the dipole moments of simple diatomic molecules. In more complex molecules with polar
covalent bonds, the three-dimensional geometry and the compound’s symmetry determine whether there is a net dipole moment.
Mathematically, dipole moments are vectors; they possess both a magnitude and a direction. The dipole moment of a molecule is
therefore the vector sum of the dipole moments of the individual bonds in the molecule. If the individual bond dipole moments
cancel one another, there is no net dipole moment. Such is the case for CO2, a linear molecule (Figure 1.3.8a). Each C–O bond in
CO2 is polar, yet experiments show that the CO2 molecule has no dipole moment. Because the two C–O bond dipoles in CO2 are
equal in magnitude and oriented at 180° to each other, they cancel. As a result, the CO2 molecule has no net dipole moment even
though it has a substantial separation of charge. In contrast, the H2O molecule is not linear (Figure 1.3.8b); it is bent in three-
dimensional space, so the dipole moments do not cancel each other. Thus a molecule such as H2O has a net dipole moment. We
expect the concentration of negative charge to be on the oxygen, the more electronegative atom, and positive charge on the two

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hydrogens. This charge polarization allows H2O to hydrogen-bond to other polarized or charged species, including other water
molecules.

Figure 1.3.8 : How Individual Bond Dipole Moments Are Added Together to Give an Overall Molecular Dipole Moment for Two
Triatomic Molecules with Different Structures. (a) In CO2, the C–O bond dipoles are equal in magnitude but oriented in opposite
directions (at 180°). Their vector sum is zero, so CO2 therefore has no net dipole. (b) In H2O, the O–H bond dipoles are also equal
in magnitude, but they are oriented at 104.5° to each other. Hence the vector sum is not zero, and H2O has a net dipole moment.
Other examples of molecules with polar bonds are shown in Figure 1.3.9. In molecular geometries that are highly symmetrical
(most notably tetrahedral and square planar, trigonal bipyramidal, and octahedral), individual bond dipole moments completely
cancel, and there is no net dipole moment. Although a molecule like CHCl3 is best described as tetrahedral, the atoms bonded to
carbon are not identical. Consequently, the bond dipole moments cannot cancel one another, and the molecule has a dipole moment.
Due to the arrangement of the bonds in molecules that have V-shaped, trigonal pyramidal, seesaw, T-shaped, and square pyramidal
geometries, the bond dipole moments cannot cancel one another. Consequently, molecules with these geometries always have a
nonzero dipole moment. Molecules with asymmetrical charge distributions have a net dipole moment.

Figure 1.3.9 : Molecules with Polar Bonds. Individual bond dipole moments are indicated in red. Due to their different three-
dimensional structures, some molecules with polar bonds have a net dipole moment (HCl, CH2O, NH3, and CHCl3), indicated in
blue, whereas others do not because the bond dipole moments cancel (BCl3, CCl4, PF5, and SF6).

Dipole Intermolecular Force

 Example 1.3.4

Which molecule(s) has a net dipole moment?

a. H S
2

b. NHF 2

c. BF 3

Given: three chemical compounds

Asked for: net dipole moment

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Strategy:
For each three-dimensional molecular geometry, predict whether the bond dipoles cancel. If they do not, then the molecule has
a net dipole moment.

Solution:
1. The total number of electrons around the central atom, S, is eight, which gives four electron pairs. Two of these electron
pairs are bonding pairs and two are lone pairs, so the molecular geometry of H S is bent (Figure 1.3.6). The bond dipoles
2

cannot cancel one another, so the molecule has a net dipole moment.

2. Difluoroamine has a trigonal pyramidal molecular geometry. Because there is one hydrogen and two fluorines, and because
of the lone pair of electrons on nitrogen, the molecule is not symmetrical, and the bond dipoles of NHF2 cannot cancel one
another. This means that NHF2 has a net dipole moment. We expect polarization from the two fluorine atoms, the most
electronegative atoms in the periodic table, to have a greater affect on the net dipole moment than polarization from the
lone pair of electrons on nitrogen.

3. The molecular geometry of BF3 is trigonal planar. Because all the B–F bonds are equal and the molecule is highly
symmetrical, the dipoles cancel one another in three-dimensional space. Thus BF3 has a net dipole moment of zero:

 Exercise 1.3.4

Which molecule(s) has a net dipole moment?

CH Cl
3

SO
3

XeO
3

Answer
CH Cl
3
and XeO
3

Summary
Lewis electron structures give no information about molecular geometry, the arrangement of bonded atoms in a molecule or
polyatomic ion, which is crucial to understanding the chemistry of a molecule. The valence-shell electron-pair repulsion
(VSEPR) model allows us to predict which of the possible structures is actually observed in most cases. It is based on the
assumption that pairs of electrons occupy space, and the lowest-energy structure is the one that minimizes electron pair–electron
pair repulsions. In the VSEPR model, the molecule or polyatomic ion is given an AXmEn designation, where A is the central atom,
X is a bonded atom, E is a nonbonding valence electron group (usually a lone pair of electrons), and m and n are integers. Each

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group around the central atom is designated as a bonding pair (BP) or lone (nonbonding) pair (LP). From the BP and LP
interactions we can predict both the relative positions of the atoms and the angles between the bonds, called the bond angles. From
this we can describe the molecular geometry. The VSEPR model can be used to predict the shapes of many molecules and
polyatomic ions, but it gives no information about bond lengths and the presence of multiple bonds. A combination of VSEPR and
a bonding model, such as Lewis electron structures, is necessary to understand the presence of multiple bonds.
Molecules with polar covalent bonds can have a dipole moment, an asymmetrical distribution of charge that results in a tendency
for molecules to align themselves in an applied electric field. Any diatomic molecule with a polar covalent bond has a dipole
moment, but in polyatomic molecules, the presence or absence of a net dipole moment depends on the structure. For some highly
symmetrical structures, the individual bond dipole moments cancel one another, giving a dipole moment of zero.

1.3: VSPER Theory- The Effect of Lone Pairs is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by
LibreTexts.
9.2: The VSEPR Model is licensed CC BY-NC-SA 3.0.

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1.4: Electronegativity and Bond Polarity (Review)
Learning Objective
Identify polar bonds and compounds

Electronegativity is a measure of the tendency of an atom to attract a bonding pair of electrons. The Pauling scale is the most
commonly used. Fluorine (the most electronegative element) is assigned a value of 4.0, and values range down to cesium and
francium which are the least electronegative at 0.7.

Patterns of electronegativity in the Periodic Table

Electronegativity is defined as the ability of an atom in a

particular molecule to attract electrons to itself. The greater
the value, the greater the attractiveness for electrons.

Trends in electronegativity across a period

The positively charged protons in the nucleus attract the negatively charged electrons. As the number of
protons in the nucleus increases, the electronegativity or attraction will increase. Therefore
electronegativity increases from left to right in a row in the periodic table. This effect only holds true
for a row in the periodic table because the attraction between charges falls off rapidly with distance. The
chart shows electronegativities from sodium to chlorine (ignoring argon since it does not does not form
bonds).

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Trends in electronegativity down a group

As you go down a group, electronegativity decreases. (If it increases up to fluorine, it must decrease as
you go down.) The chart shows the patterns of electronegativity in Groups 1 and 7.

Explaining the patterns in electronegativity

The attraction that a bonding pair of electrons feels for a particular nucleus depends on:
the number of protons in the nucleus;
the distance from the nucleus;
the amount of screening by inner electrons.

Why does electronegativity increase across a period?

Consider sodium at the beginning of period 3 and chlorine at the end (ignoring the noble gas, argon).
Think of sodium chloride as if it were covalently bonded.

Both sodium and chlorine have their bonding electrons in the 3-level. The electron pair is screened from
both nuclei by the 1s, 2s and 2p electrons, but the chlorine nucleus has 6 more protons in it. It is no
wonder the electron pair gets dragged so far towards the chlorine that ions are formed. Electronegativity
increases across a period because the number of charges on the nucleus increases. That attracts the
bonding pair of electrons more strongly.

Why does electronegativity fall as you go down a group?

As you go down a group, electronegativity decreases because the bonding pair of electrons is
increasingly distant from the attraction of the nucleus. Consider the hydrogen fluoride and hydrogen
chloride molecules:

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The bonding pair is shielded from the fluorine's nucleus only by the 1s2 electrons. In the chlorine case it
is shielded by all the 1s22s22p6 electrons. In each case there is a net pull from the center of the fluorine or
chlorine of +7. But fluorine has the bonding pair in the 2-level rather than the 3-level as it is in chlorine.
If it is closer to the nucleus, the attraction is greater.
Dipole moments occur when there is a separation of charge. They can occur between two ions in an ionic bond or between atoms in
a covalent bond; dipole moments arise from differences in electronegativity. The larger the difference in electronegativity, the
larger the dipole moment. The distance between the charge separation is also a deciding factor into the size of the dipole moment.
The dipole moment is a measure of the polarity of the molecule.

Bond Polarity & Dipole Moment

Atoms with differences in electronegativity will share electrons unequally. The shared electrons of the covalent bond are held more
tightly at the more electronegative element creating a partial negative charge, while the less electronegative element has a partial
The larger the difference in electronegativity between the two atoms, the more polar
positive charge, .
the bond. To be considered a polar bond, the difference in electronegativity must >0.4 on the Pauling
scale. Since the two electrical partial charges have opposite sign and equal magnitude and are separated by a distance, a dipole is
established. Dipole moment is measured in debye units, which is equal to the distance between the charges multiplied by the charge
(1 debye equals 3.34 x 10-30 coulomb-meters).

Figure 1.4.4 : The Electron Distribution in a Nonpolar Covalent Bond, a Polar Covalent Bond, and an
Ionic Bond Using Lewis Electron Structures. In a purely covalent bond (a), the bonding electrons are
shared equally between the atoms. In a purely ionic bond (c), an electron has been transferred
completely from one atom to the other. A polar covalent bond (b) is intermediate between the two
extremes: the bonding electrons are shared unequally between the two atoms, and the electron
distribution is asymmetrical with the electron density being greater around the more electronegative
atom. Electron-rich (negatively charged) regions are shown in blue; electron-poor (positively charged)
regions are shown in red.

Polarity and Structure of Molecules

The OVERALL POLARITY of a molecule is determined by the shape of a molecule AND the
polarity of its bonds. A molecule that contains polar bonds, might not have any overall polarity,

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depending upon its shape. The simple definition of whether a complex molecule is polar or not depends
upon whether its overall centers of positive and negative charges overlap. If these centers lie at the same
point in space, then the molecule has no overall polarity (and is non polar).

Figure 3: Charge distrubtions

If a molecule is completely symmetric, then the dipole moment vectors on each molecule will cancel each other out, making the
molecule nonpolar. A molecule can only be polar if the structure of that molecule is not symmetric.
A good example of a nonpolar molecule that contains polar bonds is carbon dioxide. This is a linear molecule and the C=O bonds
are, in fact, polar. The central carbon will have a net positive charge, and the two outer oxygens a net negative charge. However,
since the molecule is linear, these two bond dipoles cancel each other out (i.e. vector addition of the dipoles equals zero). And the
overall molecule has no dipole ( .
μ=0
Although a polar bond is a prerequisite for a molecule to have a dipole, not all molecules with polar bonds exhibit dipoles

Geometric Considerations

EXAMPLE 1: POLAR BONDS VS. POLAR MOLECULES

In a simple diatomic molecule like HCl, if the bond is polar, then the whole molecule is polar. What
about more complicated molecules?

Figure: (left) CCl4 (right) CHCl3

Consider CCl4, (left panel in figure above), which as a molecule is not polar - in the sense that it
doesn't have an end (or a side) which is slightly negative and one which is slightly positive. The
whole of the outside of the molecule is somewhat negative, but there is no overall separation of
charge from top to bottom, or from left to right.
In contrast, CHCl3 is a polar molecule (right panel in figure above). The hydrogen at the top of the
molecule is less electronegative than carbon and so is slightly positive. This means that the molecule
now has a slightly positive "top" and a slightly negative "bottom", and so is overall a polar molecule.
A polar molecule will need to be "lop-sided" in some way.

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Example 2:
C
Although the
2 C–Cl
C l4 bonds are rather polar, the individual bond dipoles cancel one another in this symmetrical structure, and
Cl2C=CCl2 does not have a net dipole moment.

Example 3:
C Cl
C-Cl, the key H
polar bond, is 178 pm. Measurement reveals 1.87 D. From this data, % ionic character can be computed. If this bond were 100%
3
ionic (based on proton & electron),

μ= (4.80 D) = 8.54D
100
178

Example 4:
HCl
Since measurement 1.87 D,
% ionic = (1.7/8.54)x100 = 22%
HCl
u = 1.03 D (measured) H-Cl bond length 127 pm
If 100% ionic,

μ= (4.80 D) = 6.09D
ionic = (1.03/6.09)x100 = 17%
100
127

A "spectrum" of bonds
The implication of all this is that there is no clear-cut division between covalent and ionic bonds. In a pure covalent bond, the
electrons are held on average exactly half way between the atoms. In a polar bond, the electrons have been dragged slightly
towards one end. How far does this dragging have to go before the bond counts as ionic? There is no real answer to that. Sodium
chloride is typically considered an ionic solid, but even here the sodium has not completely lost control of its electron. Because of
the properties of sodium chloride, however, we tend to count it as if it were purely ionic. Lithium iodide, on the other hand, would
be described as being "ionic with some covalent character". In this case, the pair of electrons has not moved entirely over to the
iodine end of the bond. Lithium iodide, for example, dissolves in organic solvents like ethanol - not something which ionic
substances normally do.
Summary
No electronegativity difference between two atoms leads to a pure non-polar covalent bond.
A small electronegativity difference leads to a polar covalent bond.
A large electronegativity difference leads to an ionic bond.

Example 1: Polar Bonds vs. Polar Molecules

In a simple diatomic molecule like HCl, if the bond is polar, then the whole molecule is polar. What about more complicated
molecules?

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Figure: (left) CCl4 (right) CHCl3
Consider CCl4, (left panel in figure above), which as a molecule is not polar - in the sense that it doesn't have an end (or a side)
which is slightly negative and one which is slightly positive. The whole of the outside of the molecule is somewhat negative, but
there is no overall separation of charge from top to bottom, or from left to right.
In contrast, CHCl3 is a polar molecule (right panel in figure above). The hydrogen at the top of the molecule is less
electronegative than carbon and so is slightly positive. This means that the molecule now has a slightly positive "top" and a
slightly negative "bottom", and so is overall a polar molecule.
A polar molecule will need to be "lop-sided" in some way.

Exercises

For the following compounds,

a) add lone pairs of electrons to complete octets
b) add dipole moment arrows or partial +/- signs to indicate polar bonds
c) predict the molecular polarity (Remember to visualize each compound in three dimensions.)

Solutions

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Contributors
Mike Blaber (Florida State University)
Jim Clark (Chemguide.co.uk)
Prof. Richard Bank, Boise State University, Emeritus,

1.4: Electronegativity and Bond Polarity (Review) is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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1.5: Resonance
Learning Objective
Draw resonance forms and predict the relative contribution of each resonance form to the overall
structure of the compound or ion

Recognizing resonance
Resonance contributors involve the ‘imaginary movement’ of pi-bonded electrons or of lone-pair electrons that are adjacent to (i.e.
conjugated to) pi bonds. You can never shift the location of electrons in sigma bonds – if you show a sigma bond forming or
breaking, you are showing a chemical reaction taking place. Likewise, the positions of atoms in the molecule cannot change
between two resonance contributors.
Because benzene will appear throughout this course, it is important to recognize the stability gained through the resonance
delocalization of the six pi electrons throughout the six carbon atoms. Benzene also illustrates one way to recognize resonance -
when it is possible to draw two or more equivalent Lewis strucutres. If we were to draw the structure of an aromatic molecule such
as 1,2-dimethylbenzene, there are two ways that we could draw the double bonds:

Which way is correct? There are two simple answers to this question: 'both' and 'neither one'. Both ways of drawing the molecule
are equally acceptable approximations of the bonding picture for the molecule, but neither one, by itself, is an accurate picture of
the delocalized pi bonds. The two alternative drawings, however, when considered together, give a much more accurate picture
than either one on its own. This is because they imply, together, that the carbon-carbon bonds are not double bonds, not single
bonds, but about halfway in between.
When it is possible to draw more than one valid structure for a compound or ion, we have identified resonance contributors: two
or more different Lewis structures depicting the same molecule or ion that, when considered together, do a better job of
approximating delocalized pi-bonding than any single structure. By convention, resonance contributors are linked by a double-
headed arrow, and are sometimes enclosed by brackets:

In order to make it easier to visualize the difference between two resonance contributors, small, curved arrows are often used. Each
of these arrows depicts the ‘movement’ of two pi electrons. A few chapters from now when we begin to study organic reactions - a
process in which electron density shifts and covalent bonds between atoms break and form - this ‘curved arrow notation’ will
become extremely important in depicting electron movement. In the drawing of resonance contributors, however, this electron
‘movement’ occurs only in our minds, as we try to visualize delocalized pi bonds. Nevertheless, use of the curved arrow notation is
an essential skill that you will need to develop in drawing resonance contributors.
The depiction of benzene using the two resonance contributors A and B in the figure above does not imply that the molecule at one
moment looks like structure A, then at the next moment shifts to look like structure B. Rather, at all moments, the molecule is a
combination, or resonance hybrid of both A and B.

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Caution! It is very important to be clear that in drawing two (or more) resonance contributors, we are not drawing two different
molecules: they are simply different depictions of the exact same molecule. Furthermore, the double-headed resonance arrow
does NOT mean that a chemical reaction has taken place.
Usually, derivatives of benzene (and phenyl groups, when the benzene ring is incorporated into a larger organic structure) are
depicted with only one resonance contributor, and it is assumed that the reader understands that resonance hybridization is implied.
This is the convention that will be used for the most part in this book. In other books or articles, you may sometimes see benzene or
a phenyl group drawn with a circle inside the hexagon, either solid or dashed, as a way of drawing a resonance hybrid.

Curved arrows communicate electron flow (movement)

Curved arrows indicate electron flow. The base of the curved arrow is placed at the source of
the electrons that are moving. The head of the arrow is placed at the destination of the
electrons. A single barbed arrow represents one electron and a double barb represents two
electrons. Electrons move from regions of relative high density to regions of low density or
toward electronegative elements. It is important to use accuracy and precision when drawing
curved arrows.

It is also important to consciously use the correct type of arrow. There are four primary types of arrows
used by chemists to communicate one of the following: completion reaction, equilibrium reaction,
electron movement, resonance forms. The three other types of arrows are shown below to build
discernment between them.

Resonance Delocalizes Charge to Increase Stability

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Resonance is most useful wen it delocalizes charge to stabilize reactive intermediates and products.
Recognizing, drawing, and evaluating the relative stability of resonance contributors is essential to
understanding organic reaction mechanisms.
Guidelines for drawing and working with resonance contributors
Learning to draw and interpret resonance structures, there are a few basic guidelines to help avoid drawing nonsensical structures.
All of these guidellines make perfect sense as long as we remember that resonance contributors are merely a human-invented
convention for depicting the delocalization of pi electrons in conjugated systems. When we see two different resonance
contributors, we are not seeing a chemical reaction! We are seeing the exact same molecule or ion depicted in two different ways.
All resonance contributors must be drawn as proper Lewis structures, with correct formal charges. Never show curved 'electron
movement' arrows that would lead to a situation where a second-row element (ie. carbon, nitrogen, or oxygen) has more than eight
electrons: this would break the 'octet rule'. Sometimes, however, we will draw resonance contributors in which a carbon atom has
only six electrons (ie. a carbocation). In general, all oxygen and nitrogen atoms should have a complete octet of valence electrons.
1. There is ONLY ONE STRUCTURE for each compound or ion. This structure takes its character from the sum of all the
contributors, not all resonance structures contribute equally to the sum.
2. Atoms must maintain their same position.
3. Only e- move !
4. All resonance contributors for a molecule or ion must have the same net charge.
5. Recognize which electrons can participate in resonance
a) unshared e- pairs or radicals
b) pi bond electrons
6. Recognize electron receptors
a) atoms with a positive (+) charge
b) electronegative atoms that can tolerate a negative charge
c) atoms which possess delocalizable electrons - see #4 above
7. Common electron flow patterns
a) move pi e- toward positive (+) charge or other pi bonds
b) move non-bonding e- pairs toward pi bonds
c) move single non-bonding e- toward pi bonds

Evaluating Resonance Contributors

1. Identical structures are equally important.
2. Structures will a greater number of bonds are more important.
3. Structures with charge separation are less important.
4. Pay attention to electronegativities.
5. Neutral atoms need to have complete octets.
Resonance Contributors for the Carboxylate Group
The convention of drawing two or more resonance contributors to approximate a single structure may seem a bit clumsy to you at
this point, but as you gain experience you will see that the practice is actually very useful when discussing the manner in which
many functional groups react. Let’s next consider the carboxylate ion (the conjugate base of a carboxylic acid). As our example, we

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will use formate, the simplest possible carboxylate-containing molecule. The conjugate acid of formate is formic acid, which
causes the painful sting you felt if you have ever been bitten by an ant.

Usually, you will see carboxylate groups drawn with one carbon-oxygen double bond and one carbon-oxygen single bond, with a
negative formal charge located on the single-bonded oxygen. In actuality, however, the two carbon-oxygen bonds are the same
length, and although there is indeed an overall negative formal charge on the group, it is shared equally between the two oxygens.
Therefore, the carboxylate can be more accurately depicted by a pair of resonance contributors. Alternatively, a single structure can
be used, with a dashed line depicting the resonance-delocalized pi bond and the negative charge located in between the two
oxygens.

Let’s see if we can correlate these drawing conventions to a valence bond theory picture of the bonding in a carboxylate group. We
know that the carbon must be sp2-hybridized, (the bond angles are close to 120˚, and the molecule is planar), and we will treat both
oxygens as being sp2-hybridized as well. Both carbon-oxygen sigma bonds, then, are formed from the overlap of carbon sp2
orbitals and oxygen sp2 orbitals.

In addition, the carbon and both oxygens each have an unhybridized 2pz orbital situated perpendicular to the plane of the sigma
bonds. These three 2pz orbitals are parallel to each other, and can overlap in a side-by-side fashion to form a delocalized pi bond.

Resonance contributor A shows oxygen #1 sharing a pair of electrons with carbon in a pi bond, and oxygen #2 holding a lone pair
of electrons in its 2pz orbital. Resonance contributor B, on the other hand, shows oxygen #2 participating in the pi bond with
carbon, and oxygen #1 holding a lone pair in its 2pz orbital. Overall, the situation is one of three parallel, overlapping 2pz orbitals
sharing four delocalized pi electrons. Because there is one more electron than there are 2pz orbitals, the system has an overall
charge of –1. This is the kind of 3D picture that resonance contributors are used to approximate, and once you get some practice
you should be able to quickly visualize overlapping 2pz orbitals and delocalized pi electrons whenever you see resonance structures

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being used. In this text, carboxylate groups will usually be drawn showing only one resonance contributor for the sake of
simplicity, but you should always keep in mind that the two C-O bonds are equal, and that the negative charge is delocalized to
both oxygens.

Exercise 2.13: There is a third resonance contributor for formate (which we will soon learn is considered a 'minor' contributor).
Draw this resonance contributor.

Here's another example, this time with a carbocation. Recall from section 2.1 that carbocations are sp2-hybridized, with an empty
2p orbital oriented perpendicular to the plane formed by three sigma bonds. If a carbocation is adjacent to a double bond, then three
2p orbitals can overlap and share the two pi electrons - another kind of conjugated pi system in which the positive charge is shared
over two carbons.

Exercise 2.14: Draw the resonance contributors that correspond to the curved, two-electron movement arrows in the resonance
expressions below.

Exercise 2.15: In each resonance expression, draw curved two-electron movement arrows on the left-side contributor that
shows how we get to the right-side contributor. Be sure to include formal charges.

Solutions to exercises

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Guided Resonance Practice
Below are a few more examples of 'legal' resonance expressions. Confirm for yourself that the octet rule is not exceeded for any
atoms, and that formal charges are correct.

Exercise 2.16: Each of the 'illegal' resonance expressions below contains one or more mistakes. Explain what is incorrect in
each.

Solutions to exercises

Major vs minor resonance contributors

Different resonance contributors do not always make the same contribution to the overall structure of the
hybrid - rather, in many cases one contributor comes closer to depicting the actual bonding picture than
another. In the case of carboxylates, contributors A and B below are equivalent in terms of their relative
contribution to the hybrid structure. However, there is also a third resonance contributor ‘C, in which the
carbon bears a positive formal charge and both oxygens are single-bonded and bear negative charges.

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Structure C makes a less important contribution to the overall bonding picture of the group relative to A
and B. How do we know that structure C is the ‘minor’ contributor? There are four basic rules which you
need to learn in order to evaluate the relative importance of different resonance contributors. We will
number them 5-8 so that they may be added to in the 'rules for resonance' list earlier on this page.
Rules for determining major and minor resonance contributors:
5. The carbon in contributor C does not have an octet – in general, resonance contributors in which a carbon does not fulfill the
octet rule are relatively less important.
6. In structure C, a separation of charge has been introduced that is not present in A or B. In general, resonance contributors in
which there is a greater separation of charge are relatively less important.
7. In structure C, there are only three bonds, compared to four in A and B. In general, a resonance structure with a lower
number of total bonds is relatively less important.
8. The resonance contributor in which a negative formal charge is located on a more electronegative atom, usually oxygen or
nitrogen, is more stable than one in which the negative charge is located on a less electronegative atom such as carbon. An
example is in the upper left expression in the next figure.

Below are some additional examples of major and minor resonance contributors:

Why do we worry about a resonance contributor if it is the minor one? We will see later that very often a minor contributor can still
be extremely important to our understanding of how a molecule reacts.

Exercise 2.17:
a. Draw a minor resonance structure for acetone (IUPAC name 2-propanone). Explain why it is a minor contributor.
b. Are acetone and 2-propanol resonance contributors of each other? Explain.
Exercise 2.18: Draw four additional resonance contributors for the molecule below. Label each one as major or minor (the
structure below is of a major contributor).

Exercise 2.19: Draw three resonance contributors of methyl acetate (IUPAC name methyl methanoate), and order them
according to their relative importance to the bonding picture of the molecule. Explain your reasoning.

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Solutions to exercises

Resonance and peptide bonds

What is the hybridization state of the nitrogen atom in an amide? At first glance, it would seem logical to say that it is sp3-
hybridized, because, like the nitrogen in an amine, the Lewis structure shows three single bonds and a lone pair. The picture looks
quite different, though, if we consider another resonance contributor in which the nitrogen has a double bond to the carbonyl
carbon: in this case, we would have to say that applicable hybridization is sp2, and the bonding geometry trigonal planar rather than
tetrahedral.

In fact, the latter picture is more accurate: the lone pair of electrons on an amide nitrogen are not
localized in an sp3 orbital, rather, they are delocalized as part of a conjugated pi system, and the bonding
geometry around the nitrogen is trigonal planar as expected for sp2 hybridization. This is a good
illustration of an important point: conjugation and the corresponding delocalization of electron density is
stabilizing, thus if conjugation can occur, it probably will.
One of the most important examples of amide groups in nature is the ‘peptide bond’ that links amino
acids to form polypeptides and proteins.

Critical to the structure of proteins is the fact that, although it is conventionally drawn as a single bond, the C-N bond in a peptide
linkage has a significant barrier to rotation, indicating that to some degree, C-N pi overlap is present - in other words, there is
some double bond character, and the nitrogen is sp2 hybridized with trigonal planar geometry.

The barrier to rotation in peptide bonds is an integral part of protein structure, introducing more rigidity to the protein's backbone.
If there were no barrier to rotation in a peptide bond, proteins would be much more 'floppy' and three dimensional folding would be
very different.

Exercise 2.20: Draw two pictures showing the unhybridized 2p orbitals and the location of pi electrons in methyl amide. One
picture should represent the major resonance contributor, the other the minor contributor. How many overlapping 2p orbitals are
sharing how many pi-bonded electrons?
Exercise 2.21: Draw two pictures showing the unhybridized 2p orbitals and the location of pi electrons in the 'enolate' anion
shown below. One picture should represent the major resonance contributor, the other the minor contributor. How many

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overlapping 2p orbitals are sharing how many pi-bonded electrons?

Exercise 2.22: Below is a minor resonance contributor of a species known as an 'enamine', which we will study more in chapter
12. Draw the major resonance contributor for the enamine, and explain why your contributor is the major one (refer to
resonance rules #5-8 from this section).

Solutions to exercises

Solved example: Draw the major resonance contributor of the structure below. Include in your figure the appropriate
curved arrows showing how you got from the given structure to your structure. Explain why your contributor is the major one.
In what kind of orbitals are the two lone pairs on the oxygen?

Solution: In the structure above, the carbon with the positive formal charge does not have a complete octet of valence electrons.
Using the curved arrow convention, a lone pair on the oxygen can be moved to the adjacent bond to the left, and the electrons in
the double bond shifted over to the left (see the rules for drawing resonance contributors to convince yourself that these are
'legal' moves).

The resulting resonance contributor, in which the oxygen bears the formal charge, is the major one because all atoms have a
complete octet, and there is one additional bond drawn (resonance rules #5 and #7 both apply). This system can be thought of as
four parallel 2p orbitals (one each on C2, C3, and C4, plus one on oxygen) sharing four pi electrons. One lone pair on the oxygen
is in an unhybridized 2p orbital and is part of the conjugated pi system, and the other is located in an sp2 orbital.
Also note that one additional contributor can be drawn, but it is also minor because it has a carbon with an incomplete octet:

Exercise 2.23:
a) Draw three additional resonance contributors for the carbocation below. Include in your figure the appropriate curved arrows
showing how one contributor is converted to the next.

b) Fill in the blanks: the conjugated pi system in this carbocation is composed of ______ 2p orbitals sharing ________
delocalized pi electrons.

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Exercise 2.24: Draw the major resonance contributor for each of the anions below.

c) Fill in the blanks: the conjugated pi system in part (a) is composed of ______ 2p orbitals containing ________ delocalized pi
electrons.
Exercise 2.25: The figure below shows how the negative formal charge on the oxygen can be delocalized to the carbon
indicated by an arrow. More resonance contributors can be drawn in which negative charge is delocalized to three other atoms
on the molecule.
a) Circle these atoms.
b) Draw the two most important resonance contributors for the molecule.

Solutions to exercises

A word of advice
Becoming adept at drawing resonance contributors, using the curved arrow notation to show how one contributor can be
converted to another, and understanding the concepts of conjugation and resonance delocalization are some of the most
challenging but also most important jobs that you will have as a beginning student of organic chemistry. If you work hard now
to gain a firm grasp of these ideas, you will have come a long way toward understanding much of what follows in your organic
chemistry course. Conversely, if you fail to come to grips with these concepts now, a lot of what you see later in the course will
seem like a bunch of mysterious and incomprehensible lines, dots, and arrows, and you will be in for a rough ride, to say the
least. More so than many other topics in organic chemistry, understanding bonding, conjugation, and resonance is something
that most students really need to work on 'in person' with an instructor or tutor, preferably using a molecular modeling kit.
Keep working problems, keep asking questions, and keep at it until it all makes sense!

Kahn Academy video tutorials

Drawing resonance structures
More on resonance
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

1.5: Resonance is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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1.6: Molecular Orbitals and Covalent Bonding
 Learning Objectives
To use molecular orbital theory to predict bond order

None of the approaches we have described so far can adequately explain why some compounds are colored and others are not, why
some substances with unpaired electrons are stable, and why others are effective semiconductors. These approaches also cannot
describe the nature of resonance. Such limitations led to the development of a new approach to bonding in which electrons are not
viewed as being localized between the nuclei of bonded atoms but are instead delocalized throughout the entire molecule. Just as
with the valence bond theory, the approach we are about to discuss is based on a quantum mechanical model.
Previously, we described the electrons in isolated atoms as having certain spatial distributions, called orbitals, each with a
particular orbital energy. Just as the positions and energies of electrons in atoms can be described in terms of atomic orbitals
(AOs), the positions and energies of electrons in molecules can be described in terms of molecular orbitals (MOs) A particular
spatial distribution of electrons in a molecule that is associated with a particular orbital energy.—a spatial distribution of electrons
in a molecule that is associated with a particular orbital energy. As the name suggests, molecular orbitals are not localized on a
single atom but extend over the entire molecule. Consequently, the molecular orbital approach, called molecular orbital theory is a
delocalized approach to bonding.

Molecular Orbital Theory: A Delocalized Bonding Approach

Although the molecular orbital theory is computationally demanding, the principles on which it is based are similar to those we
used to determine electron configurations for atoms. The key difference is that in molecular orbitals, the electrons are allowed to
interact with more than one atomic nucleus at a time. Just as with atomic orbitals, we create an energy-level diagram by listing the
molecular orbitals in order of increasing energy. We then fill the orbitals with the required number of valence electrons according to
the Pauli principle. This means that each molecular orbital can accommodate a maximum of two electrons with opposite spins.

Molecular Orbitals Involving Only ns Atomic Orbitals

We begin our discussion of molecular orbitals with the simplest molecule, H2, formed from two isolated hydrogen atoms, each with
a 1s1 electron configuration. As we explained in Chapter 9, electrons can behave like waves. In the molecular orbital approach, the
overlapping atomic orbitals are described by mathematical equations called wave functions. The 1s atomic orbitals on the two
hydrogen atoms interact to form two new molecular orbitals, one produced by taking the sum of the two H 1s wave functions, and
the other produced by taking their difference:

M O(1) = AO(atom A) + AO(atomB)

(1.6.1)
M O(1) = AO(atom A) − AO(atomB)

The molecular orbitals created from Equation 1.6.1 are called linear combinations of atomic orbitals (LCAOs) Molecular orbitals
created from the sum and the difference of two wave functions (atomic orbitals). A molecule must have as many molecular orbitals
as there are atomic orbitals.

A molecule must have as many molecular orbitals as there are atomic orbitals.

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Figure 1.6.1 : Molecular Orbitals for the H2 Molecule. (a) This diagram shows the formation of a bonding σ1s molecular orbital for
H2 as the sum of the wave functions (Ψ) of two H 1s atomic orbitals. (b) This plot of the square of the wave function (Ψ2) for the
bonding σ1s molecular orbital illustrates the increased electron probability density between the two hydrogen nuclei. (Recall that
the probability density is proportional to the square of the wave function.) (c) This diagram shows the formation of an antibonding
σ
∗
1s
molecular orbital for H2 as the difference of the wave functions (Ψ) of two H 1s atomic orbitals. (d) This plot of the square of
the wave function (Ψ2) for the σ antibonding molecular orbital illustrates the node corresponding to zero electron probability
∗
1s

density between the two hydrogen nuclei.

Adding two atomic orbitals corresponds to constructive interference between two waves, thus reinforcing their intensity; the
internuclear electron probability density is increased. The molecular orbital corresponding to the sum of the two H 1s orbitals is
called a σ1s combination (pronounced “sigma one ess”) (part (a) and part (b) in Figure 1.6.1). In a sigma (σ) orbital, (i.e., a bonding
molecular orbital in which the electron density along the internuclear axis and between the nuclei has cylindrical symmetry), the
electron density along the internuclear axis and between the nuclei has cylindrical symmetry; that is, all cross-sections
perpendicular to the internuclear axis are circles. The subscript 1s denotes the atomic orbitals from which the molecular orbital was
derived: The ≈ sign is used rather than an = sign because we are ignoring certain constants that are not important to our argument.
σ1s ≈ 1s (A) + 1s (B) (1.6.2)

Conversely, subtracting one atomic orbital from another corresponds to destructive interference between two waves, which reduces
their intensity and causes a decrease in the internuclear electron probability density (part (c) and part (d) in Figure 1.6.1). The
resulting pattern contains a node where the electron density is zero. The molecular orbital corresponding to the difference is called
σ
∗
1s
(“sigma one ess star”). In a sigma star (σ*) orbital An antibonding molecular orbital in which there is a region of zero electron
probability (a nodal plane) perpendicular to the internuclear axis., there is a region of zero electron probability, a nodal plane,
perpendicular to the internuclear axis:
⋆
σ ≈ 1s (A) − 1s (B) (1.6.3)
1s

The electron density in the σ1s molecular orbital is greatest between the two positively charged nuclei, and the resulting electron–
nucleus electrostatic attractions reduce repulsions between the nuclei. Thus the σ1s orbital represents a bonding molecular orbital. A
molecular orbital that forms when atomic orbitals or orbital lobes with the same sign interact to give increased electron probability
between the nuclei due to constructive reinforcement of the wave functions. In contrast, electrons in the σ orbital are generally
⋆
1s

found in the space outside the internuclear region. Because this allows the positively charged nuclei to repel one another, the σ ⋆
1s

orbital is an antibonding molecular orbital (a molecular orbital that forms when atomic orbitals or orbital lobes of opposite sign
interact to give decreased electron probability between the nuclei due to destructive reinforcement of the wave functions).

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Antibonding orbitals contain a node perpendicular to the internuclear axis; bonding
orbitals do not.
Energy-Level Diagrams
Because electrons in the σ1s orbital interact simultaneously with both nuclei, they have a lower energy than electrons that interact
with only one nucleus. This means that the σ1s molecular orbital has a lower energy than either of the hydrogen 1s atomic orbitals.
Conversely, electrons in the σ orbital interact with only one hydrogen nucleus at a time. In addition, they are farther away from
⋆
1s

the nucleus than they were in the parent hydrogen 1s atomic orbitals. Consequently, the σ molecular orbital has a higher energy
⋆
1s

than either of the hydrogen 1s atomic orbitals. The σ1s (bonding) molecular orbital is stabilized relative to the 1s atomic orbitals,
and the σ (antibonding) molecular orbital is destabilized. The relative energy levels of these orbitals are shown in the energy-
⋆
1s

level diagram (a schematic drawing that compares the energies of the molecular orbitals (bonding, antibonding, and nonbonding)
with the energies of the parent atomic orbitals) in Figure 1.6.2

Figure 1.6.2 : Molecular Orbital Energy-Level Diagram for H2. The two available electrons (one from each H atom) in this diagram
fill the bonding σ1s molecular orbital. Because the energy of the σ1s molecular orbital is lower than that of the two H 1s atomic
orbitals, the H2 molecule is more stable (at a lower energy) than the two isolated H atoms.

A bonding molecular orbital is always lower in energy (more stable) than the component
atomic orbitals, whereas an antibonding molecular orbital is always higher in energy
(less stable).
To describe the bonding in a homonuclear diatomic molecule (a molecule that consists of two atoms of the same element) such as
H2, we use molecular orbitals; that is, for a molecule in which two identical atoms interact, we insert the total number of valence
electrons into the energy-level diagram (Figure 1.6.2). We fill the orbitals according to the Pauli principle and Hund’s rule: each
orbital can accommodate a maximum of two electrons with opposite spins, and the orbitals are filled in order of increasing energy.
Because each H atom contributes one valence electron, the resulting two electrons are exactly enough to fill the σ1s bonding
molecular orbital. The two electrons enter an orbital whose energy is lower than that of the parent atomic orbitals, so the H2
molecule is more stable than the two isolated hydrogen atoms. Thus molecular orbital theory correctly predicts that H2 is a stable
molecule. Because bonds form when electrons are concentrated in the space between nuclei, this approach is also consistent with
our earlier discussion of electron-pair bonds.

Bond Order in Molecular Orbital Theory

In the Lewis electron structures, the number of electron pairs holding two atoms together was called the bond order. In the
molecular orbital approach, bond order One-half the net number of bonding electrons in a molecule. is defined as one-half the net
number of bonding electrons:
number of bonding electrons − number of antibonding electrons
bond order = (1.6.4)
2

To calculate the bond order of H2, we see from Figure 1.6.2 that the σ1s (bonding) molecular orbital contains two electrons, while
the σ (antibonding) molecular orbital is empty. The bond order of H2 is therefore
⋆
1s

2 −0
=1 (1.6.5)
2

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This result corresponds to the single covalent bond predicted by Lewis dot symbols. Thus molecular orbital theory and the Lewis
electron-pair approach agree that a single bond containing two electrons has a bond order of 1. Double and triple bonds contain
four or six electrons, respectively, and correspond to bond orders of 2 and 3. We can use energy-level diagrams such as the one in
Figure 1.6.2 to describe the bonding in other pairs of atoms and ions where n = 1, such as the H2+ ion, the He2+ ion, and the He2
molecule. Again, we fill the lowest-energy molecular orbitals first while being sure not to violate the Pauli principle or Hund’s rule.

Figure 1.6.3 : Molecular Orbital Energy-Level Diagrams for Diatomic Molecules with Only 1s Atomic Orbitals. (a) The H2+ ion,
(b) the He2+ ion, and (c) the He2 molecule are shown here.
for the H2+ ion the H has one unpaired electron in the 1s orbital so the H2+ has one unpaired electron in the sigmas 1 s orbital. for
He2+ ion, He has a full 1 s orbital and He+ has one upaired electron in the 1 s orbital. This means that the sigmal 1s orbital is full
and the sigmal*1s orbital has one upaired electron. For the He2 molecule, each He has a full 1 s orbital. This means that sigma 1s
and sigma * 1s orbital are full.
Figure 1.6.3a shows the energy-level diagram for the H2+ ion, which contains two protons and only one electron. The single
electron occupies the σ1s bonding molecular orbital, giving a (σ1s)1 electron configuration. The number of electrons in an orbital is
indicated by a superscript. In this case, the bond order is
1 −0
= 1/2
2

Because the bond order is greater than zero, the H2+ ion should be more stable than an isolated H atom and a proton. We can
therefore use a molecular orbital energy-level diagram and the calculated bond order to predict the relative stability of species such
as H2+. With a bond order of only 1/2 the bond in H2+ should be weaker than in the H2 molecule, and the H–H bond should be
longer. As shown in Table 1.6.1, these predictions agree with the experimental data.
Figure 1.6.3b is the molecular orbital energy-level diagram for He2+. This ion has a total of three valence electrons. Because the
first two electrons completely fill the σ1s molecular orbital, the Pauli principle states that the third electron must be in the σ ⋆
1s
1
antibonding orbital, giving a (σ ) (σ ) electron configuration. This electron configuration gives a bond order of
1s
2 ⋆
1s

2 −1
= 1/2
2

As with H2+, the He2+ ion should be stable, but the He–He bond should be weaker and longer than in H2. In fact, the He2+ ion can
be prepared, and its properties are consistent with our predictions (Table 1.6.1).
Table 1.6.1 : Molecular Orbital Electron Configurations, Bond Orders, Bond Lengths, and Bond Energies for some Simple Homonuclear
Diatomic Molecules and Ions
Molecule or Ion Electron Configuration Bond Order Bond Length (pm) Bond Energy (kJ/mol)

H2+ (σ1s)1 1/2 106 269

H2 (σ1s)2 1 74 436

He2+ 2
(σ1s ) (σ
1s
⋆
)
1
1/2 108 251

He2 2
(σ1s ) (σ
1s
⋆
)
2
0 not observed not observed

Finally, we examine the He2 molecule, formed from two He atoms with 1s2 electron configurations. Figure 1.6.3c is the molecular
orbital energy-level diagram for He2. With a total of four valence electrons, both the σ1s bonding and σ antibonding orbitals must
⋆
1s
2 2
contain two electrons. This gives a (σ ) (σ ) electron configuration, with a predicted bond order of (2 − 2) ÷ 2 = 0, which
1s
⋆
1s

indicates that the He2 molecule has no net bond and is not a stable species. Experiments show that the He2 molecule is actually less
stable than two isolated He atoms due to unfavorable electron–electron and nucleus–nucleus interactions.

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In molecular orbital theory, electrons in antibonding orbitals effectively cancel the stabilization resulting from electrons in bonding
orbitals. Consequently, any system that has equal numbers of bonding and antibonding electrons will have a bond order of 0, and it
is predicted to be unstable and therefore not to exist in nature. In contrast to Lewis electron structures and the valence bond
approach, molecular orbital theory is able to accommodate systems with an odd number of electrons, such as the H2+ ion.

In contrast to Lewis electron structures and the valence bond approach, molecular orbital
theory can accommodate systems with an odd number of electrons.

Molecular Orbital Theory

 Example 1.6.1

Use a molecular orbital energy-level diagram, such as those in Figure 1.6.2, to predict the bond order in the He22+ ion. Is this a
stable species?
Given: chemical species
Asked for: molecular orbital energy-level diagram, bond order, and stability

Strategy:
A. Combine the two He valence atomic orbitals to produce bonding and antibonding molecular orbital
B. s. Draw the molecular orbital energy-level diagram for the system.
C. Determine the total number of valence electrons in the He22+ ion. Fill the molecular orbitals in the energy-level diagram
beginning with the orbital with the lowest energy. Be sure to obey the Pauli principle and Hund’s rule while doing so.
D. Calculate the bond order and predict whether the species is stable.

Solution:
A Two He 1s atomic orbitals combine to give two molecular orbitals: a σ1s bonding orbital at lower energy than the atomic
orbitals and a σ antibonding orbital at higher energy. The bonding in any diatomic molecule with two He atoms can be
⋆
1s

described using the following molecular orbital diagram:

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B The He22+ ion has only two valence electrons (two from each He atom minus two for the +2 charge). We can also view
He22+ as being formed from two He+ ions, each of which has a single valence electron in the 1s atomic orbital. We can now fill
the molecular orbital diagram:

Each He+ has one unpaired electron in the 1 s orbital. This means that He2 2+ has a full sigma 1 s orbital.
The two electrons occupy the lowest-energy molecular orbital, which is the bonding (σ1s) orbital, giving a (σ1s)2 electron
configuration. To avoid violating the Pauli principle, the electron spins must be paired. C So the bond order is
2 −0
=1
2

He22+ is therefore predicted to contain a single He–He bond. Thus it should be a stable species.

 Exercise 1.6.1

Use a molecular orbital energy-level diagram to predict the valence-electron configuration and bond order of the H22− ion. Is
this a stable species?

Answer
H22− has a valence electron configuration of (σ
2
1s )
2
(σ
1s
⋆
) with a bond order of 0. It is therefore predicted to be unstable.

So far, our discussion of molecular orbitals has been confined to the interaction of valence orbitals, which tend to lie farthest from
the nucleus. When two atoms are close enough for their valence orbitals to overlap significantly, the filled inner electron shells are
largely unperturbed; hence they do not need to be considered in a molecular orbital scheme. Also, when the inner orbitals are
completely filled, they contain exactly enough electrons to completely fill both the bonding and antibonding molecular orbitals that
arise from their interaction. Thus the interaction of filled shells always gives a bond order of 0, so filled shells are not a factor when
predicting the stability of a species. This means that we can focus our attention on the molecular orbitals derived from valence
atomic orbitals.
A molecular orbital diagram that can be applied to any homonuclear diatomic molecule with two identical alkali metal atoms (Li2
and Cs2, for example) is shown in part (a) in Figure 1.6.4, where M represents the metal atom. Only two energy levels are
important for describing the valence electron molecular orbitals of these species: a σns bonding molecular orbital and a σ*ns
antibonding molecular orbital. Because each alkali metal (M) has an ns1 valence electron configuration, the M2 molecule has two
valence electrons that fill the σns bonding orbital. As a result, a bond order of 1 is predicted for all homonuclear diatomic species
formed from the alkali metals (Li2, Na2, K2, Rb2, and Cs2). The general features of these M2 diagrams are identical to the diagram
for the H2 molecule in Figure 1.6.4. Experimentally, all are found to be stable in the gas phase, and some are even stable in
solution.

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Figure 1.6.4 : Molecular Orbital Energy-Level Diagrams for Alkali Metal and Alkaline Earth Metal Diatomic (M2) Molecules. (a)
For alkali metal diatomic molecules, the two valence electrons are enough to fill the σns (bonding) level, giving a bond order of 1.
(b) For alkaline earth metal diatomic molecules, the four valence electrons fill both the σns (bonding) and the σns* (nonbonding)
levels, leading to a predicted bond order of 0.
Similarly, the molecular orbital diagrams for homonuclear diatomic compounds of the alkaline earth metals (such as Be2), in which
each metal atom has an ns2 valence electron configuration, resemble the diagram for the He2 molecule in part (c) in Figure 1.6.2.
As shown in part (b) in Figure 1.6.4, this is indeed the case. All the homonuclear alkaline earth diatomic molecules have four
valence electrons, which fill both the σns bonding orbital and the σns* antibonding orbital and give a bond order of 0. Thus Be2,
Mg2, Ca2, Sr2, and Ba2 are all expected to be unstable, in agreement with experimental data.In the solid state, however, all the
alkali metals and the alkaline earth metals exist as extended lattices held together by metallic bonding. At low temperatures, Be is 2

stable.

 Example 1.6.2
Use a qualitative molecular orbital energy-level diagram to predict the valence electron configuration, bond order, and likely
existence of the Na2− ion.
Given: chemical species
Asked for: molecular orbital energy-level diagram, valence electron configuration, bond order, and stability

Strategy:
A. Combine the two sodium valence atomic orbitals to produce bonding and antibonding molecular orbitals. Draw the
molecular orbital energy-level diagram for this system.
B. Determine the total number of valence electrons in the Na2− ion. Fill the molecular orbitals in the energy-level diagram
beginning with the orbital with the lowest energy. Be sure to obey the Pauli principle and Hund’s rule while doing so.
C. Calculate the bond order and predict whether the species is stable.

Solution:
A Because sodium has a [Ne]3s1 electron configuration, the molecular orbital energy-level diagram is qualitatively identical to
the diagram for the interaction of two 1s atomic orbitals. B The Na2− ion has a total of three valence electrons (one from each
2 1
Na atom and one for the negative charge), resulting in a filled σ3s molecular orbital, a half-filled σ3s* and a (σ3s ) (σ
⋆
3s
)

electron configuration.

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C The bond order is (2-1)÷2=1/2 With a fractional bond order, we predict that the Na2− ion exists but is highly reactive.

 Exercise 1.6.2
Use a qualitative molecular orbital energy-level diagram to predict the valence electron configuration, bond order, and likely
existence of the Ca2+ ion.

Answer
Ca2+ has a (σ
1

4s )
2
(σ
4s
⋆
) electron configurations and a bond order of 1/2 and should exist.

Molecular Orbitals Formed from ns and np Atomic Orbitals

Atomic orbitals other than ns orbitals can also interact to form molecular orbitals. Because individual p, d, and f orbitals are not
spherically symmetrical, however, we need to define a coordinate system so we know which lobes are interacting in three-
dimensional space. Recall that for each np subshell, for example, there are npx, npy, and npz orbitals. All have the same energy and
are therefore degenerate, but they have different spatial orientations.
σnp = npz (A) − npz (B) (1.6.6)
z

Just as with ns orbitals, we can form molecular orbitals from np orbitals by taking their mathematical sum and difference. When
two positive lobes with the appropriate spatial orientation overlap, as illustrated for two npz atomic orbitals in part (a) in Figure
1.6.5, it is the mathematical difference of their wave functions that results in constructive interference, which in turn increases the

electron probability density between the two atoms. The difference therefore corresponds to a molecular orbital called a σ npz

bonding molecular orbital because, just as with the σ orbitals discussed previously, it is symmetrical about the internuclear axis (in
this case, the z-axis):
σnp = npz (A) − npz (B) (1.6.7)
z

The other possible combination of the two npz orbitals is the mathematical sum:
σnp = npz (A) + npz (B) (1.6.8)
z

In this combination, shown in part (b) in Figure 1.6.5, the positive lobe of one npz atomic orbital overlaps the negative lobe of the
other, leading to destructive interference of the two waves and creating a node between the two atoms. Hence this is an antibonding
molecular orbital. Because it, too, is symmetrical about the internuclear axis, this molecular orbital is called a
σnp = np (A) − np (B) antibonding molecular orbital. Whenever orbitals combine, the bonding combination is always lower
z z
z

in energy (more stable) than the atomic orbitals from which it was derived, and the antibonding combination is higher in energy
(less stable).

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Figure 1.6.5 Formation of Molecular Orbitals from npz Atomic Orbitals on Adjacent Atoms.(a) By convention, in a linear molecule
or ion, the z-axis always corresponds to the internuclear axis, with +z to the right. As a result, the signs of the lobes of the npz
atomic orbitals on the two atoms alternate − + − +, from left to right. In this case, the σ (bonding) molecular orbital corresponds to
the mathematical difference, in which the overlap of lobes with the same sign results in increased probability density between the
nuclei. (b) In contrast, the σ* (antibonding) molecular orbital corresponds to the mathematical sum, in which the overlap of lobes
with opposite signs results in a nodal plane of zero probability density perpendicular to the internuclear axis.

Overlap of atomic orbital lobes with the same sign produces a bonding molecular orbital, regardless of whether it corresponds
to the sum or the difference of the atomic orbitals.

The remaining p orbitals on each of the two atoms, npx and npy, do not point directly toward each other. Instead, they are
perpendicular to the internuclear axis. If we arbitrarily label the axes as shown in Figure 1.6.6, we see that we have two pairs of np
orbitals: the two npx orbitals lying in the plane of the page, and two npy orbitals perpendicular to the plane. Although these two
pairs are equivalent in energy, the npx orbital on one atom can interact with only the npx orbital on the other, and the npy orbital on
one atom can interact with only the npy on the other. These interactions are side-to-side rather than the head-to-head interactions
characteristic of σ orbitals. Each pair of overlapping atomic orbitals again forms two molecular orbitals: one corresponds to the
arithmetic sum of the two atomic orbitals and one to the difference. The sum of these side-to-side interactions increases the electron
probability in the region above and below a line connecting the nuclei, so it is a bonding molecular orbital that is called a pi (π)
orbital (a bonding molecular orbital formed from the side-to-side interactions of two or more parallel np atomic orbitals). The
difference results in the overlap of orbital lobes with opposite signs, which produces a nodal plane perpendicular to the internuclear
axis; hence it is an antibonding molecular orbital, called a pi star (π*) orbital An antibonding molecular orbital formed from the
difference of the side-to-side interactions of two or more parallel np atomic orbitals, creating a nodal plane perpendicular to the
internuclear axis..
πnp = npx (A) + npx (B) (1.6.9)
x

⋆
πnp = npx (A) − npx (B) (1.6.10)
x

The two npy orbitals can also combine using side-to-side interactions to produce a bonding π molecular orbital and an
npy

antibonding π ⋆
npy molecular orbital. Because the npx and npy atomic orbitals interact in the same way (side-to-side) and have the
same energy, the π and π molecular orbitals are a degenerate pair, as are the π
npx npy and π⋆
npx molecular orbitals.
⋆
npy

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Figure 1.6.6 : Formation of π Molecular Orbitals from npx and npy Atomic Orbitals on Adjacent Atoms.(a) Because the signs of the
lobes of both the npx and the npy atomic orbitals on adjacent atoms are the same, in both cases the mathematical sum corresponds to
a π (bonding) molecular orbital. (b) In contrast, in both cases, the mathematical difference corresponds to a π* (antibonding)
molecular orbital, with a nodal plane of zero probability density perpendicular to the internuclear axis.
Figure 1.6.7 is an energy-level diagram that can be applied to two identical interacting atoms that have three np atomic orbitals
each. There are six degenerate p atomic orbitals (three from each atom) that combine to form six molecular orbitals, three bonding
and three antibonding. The bonding molecular orbitals are lower in energy than the atomic orbitals because of the increased
stability associated with the formation of a bond. Conversely, the antibonding molecular orbitals are higher in energy, as shown.
The energy difference between the σ and σ* molecular orbitals is significantly greater than the difference between the two π and π*
sets. The reason for this is that the atomic orbital overlap and thus the strength of the interaction are greater for a σ bond than a π
bond, which means that the σ molecular orbital is more stable (lower in energy) than the π molecular orbitals.

Figure 1.6.7 : The Relative Energies of the σ and π Molecular Orbitals Derived from npx, npy, and npz Orbitals on Identical
Adjacent Atoms. Because the two npz orbitals point directly at each other, their orbital overlap is greater, so the difference in energy
between the σ and σ* molecular orbitals is greater than the energy difference between the π and π* orbitals.
Although many combinations of atomic orbitals form molecular orbitals, we will discuss only one other interaction: an ns atomic
orbital on one atom with an npz atomic orbital on another. As shown in Figure 1.6.8, the sum of the two atomic wave functions (ns
+ npz) produces a σ bonding molecular orbital. Their difference (ns − npz) produces a σ* antibonding molecular orbital, which has a
nodal plane of zero probability density perpendicular to the internuclear axis.

Figure 1.6.8 : Formation of Molecular Orbitals from an ns Atomic Orbital on One Atom and an npz Atomic Orbital on an Adjacent
Atom.(a) The mathematical sum results in a σ (bonding) molecular orbital, with increased probability density between the nuclei.
(b) The mathematical difference results in a σ* (antibonding) molecular orbital, with a nodal plane of zero probability density
perpendicular to the internuclear axis.

Summary
Molecular orbital theory, a delocalized approach to bonding, can often explain a compound’s color, why a compound with unpaired
electrons is stable, semiconductor behavior, and resonance, none of which can be explained using a localized approach. A

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molecular orbital (MO) is an allowed spatial distribution of electrons in a molecule that is associated with a particular orbital
energy. Unlike an atomic orbital (AO), which is centered on a single atom, a molecular orbital extends over all the atoms in a
molecule or ion. Hence the molecular orbital theory of bonding is a delocalized approach. Molecular orbitals are constructed
using linear combinations of atomic orbitals (LCAOs), which are usually the mathematical sums and differences of wave
functions that describe overlapping atomic orbitals. Atomic orbitals interact to form three types of molecular orbitals.
A completely bonding molecular orbital contains no nodes (regions of zero electron probability) perpendicular to the internuclear
axis, whereas a completely antibonding molecular orbital contains at least one node perpendicular to the internuclear axis. A
sigma (σ) orbital (bonding) or a sigma star (σ*) orbital (antibonding) is symmetrical about the internuclear axis. Hence all cross-
sections perpendicular to that axis are circular. Both a pi (π) orbital (bonding) and a pi star (π*) orbital (antibonding) possess a
nodal plane that contains the nuclei, with electron density localized on both sides of the plane.
The energies of the molecular orbitals versus those of the parent atomic orbitals can be shown schematically in an energy-level
diagram. The electron configuration of a molecule is shown by placing the correct number of electrons in the appropriate energy-
level diagram, starting with the lowest-energy orbital and obeying the Pauli principle; that is, placing only two electrons with
opposite spin in each orbital. From the completed energy-level diagram, we can calculate the bond order, defined as one-half the
net number of bonding electrons. In bond orders, electrons in antibonding molecular orbitals cancel electrons in bonding molecular
orbitals, while electrons in nonbonding orbitals have no effect and are not counted. Bond orders of 1, 2, and 3 correspond to single,
double, and triple bonds, respectively. Molecules with predicted bond orders of 0 are generally less stable than the isolated atoms
and do not normally exist.

Contributors and Attributions

Modified by Joshua Halpern (Howard University)
1. Orbitals or orbital lobes with the same sign interact to give increased electron probability along the plane of the internuclear
axis because of constructive reinforcement of the wave functions. Consequently, electrons in such molecular orbitals help to
hold the positively charged nuclei together. Such orbitals are bonding molecular orbitals, and they are always lower in energy
than the parent atomic orbitals.
2. Orbitals or orbital lobes with opposite signs interact to give decreased electron probability density between the nuclei because
of destructive interference of the wave functions. Consequently, electrons in such molecular orbitals are primarily located
outside the internuclear region, leading to increased repulsions between the positively charged nuclei. These orbitals are called
antibonding molecular orbitals, and they are always higher in energy than the parent atomic orbitals.
3. Some atomic orbitals interact only very weakly, and the resulting molecular orbitals give essentially no change in the electron
probability density between the nuclei. Hence electrons in such orbitals have no effect on the bonding in a molecule or ion.
These orbitals are nonbonding molecular orbitals, and they have approximately the same energy as the parent atomic orbitals.

1.6: Molecular Orbitals and Covalent Bonding is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
9.7: Molecular Orbitals is licensed CC BY-NC-SA 3.0.

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1.7: Hybrid Orbitals- Bonding in Complex Molecules and Practice Problems
Formation of sigma bonds: the H2 molecule
The simplest case to consider is the hydrogen molecule, H2. When we say that the two electrons from each of the hydrogen atoms
are shared to form a covalent bond between the two atoms, what we mean in valence bond theory terms is that the two spherical 1s
orbitals overlap, allowing the two electrons to form a pair within the two overlapping orbitals.

These two electrons are now attracted to the positive charge of both of the hydrogen nuclei, with the result that they serve as a sort
of ‘chemical glue’ holding the two nuclei together.

Bonding in Methane

Now let’s turn to methane, the simplest organic molecule. Recall the valence electron configuration of the central carbon:

This picture, however, is problematic. How does the carbon form four bonds if it has only two half-filled p orbitals available for
bonding? A hint comes from the experimental observation that the four C-H bonds in methane are arranged with tetrahedral
geometry about the central carbon, and that each bond has the same length and strength. In order to explain this observation,
valence bond theory relies on a concept called orbital hybridization. In this picture, the four valence orbitals of the carbon (one 2s
and three 2p orbitals) combine mathematically (remember: orbitals are described by equations) to form four equivalent hybrid
orbitals, which are named sp3 orbitals because they are formed from mixing one s and three p orbitals. In the new electron
configuration, each of the four valence electrons on the carbon occupies a single sp3 orbital.

The sp3 hybrid orbitals, like the p orbitals of which they are partially composed, are oblong in shape, and have two lobes of
opposite sign. Unlike the p orbitals, however, the two lobes are of very different size. The larger lobes of the sp3 hybrids are
directed towards the four corners of a tetrahedron, meaning that the angle between any two orbitals is 109.5o.

This geometric arrangement makes perfect sense if you consider that it is precisely this angle that allows the four orbitals (and the
electrons in them) to be as far apart from each other as possible.This is simply a restatement of the Valence Shell Electron Pair
Repulsion (VSEPR) theory that you learned in General Chemistry: electron pairs (in orbitals) will arrange themselves in such a
way as to remain as far apart as possible, due to negative-negative electrostatic repulsion.
Each C-H bond in methane, then, can be described as an overlap between a half-filled 1s orbital in a hydrogen atom and the larger
lobe of one of the four half-filled sp3 hybrid orbitals in the central carbon. The length of the carbon-hydrogen bonds in methane is
1.09 Å (1.09 x 10-10 m).

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While previously we drew a Lewis structure of methane in two dimensions using lines to denote each covalent bond, we can now
draw a more accurate structure in three dimensions, showing the tetrahedral bonding geometry. To do this on a two-dimensional
page, though, we need to introduce a new drawing convention: the solid / dashed wedge system. In this convention, a solid wedge
simply represents a bond that is meant to be pictured emerging from the plane of the page. A dashed wedge represents a bond that
is meant to be pictured pointing into, or behind, the plane of the page. Normal lines imply bonds that lie in the plane of the page.

This system takes a little bit of getting used to, but with practice your eye will learn to immediately ‘see’ the third dimension being
depicted.

Example

Imagine that you could distinguish between the four hydrogens in a methane molecule, and labeled them Ha through Hd. In the images below, the
exact same methane molecule is rotated and flipped in various positions. Draw the missing hydrogen atom labels. (It will be much easier to do this
if you make a model.)

Example

Describe, with a picture and with words, the bonding in chloroform, CHCl3.
Solutions

The bonding arrangement here is also tetrahedral: the three N-H bonds of ammonia can be pictured as forming the base of a
trigonal pyramid, with the fourth orbital, containing the lone pair, forming the top of the pyramid.

Recall from your study of VSEPR theory in General Chemistry that the lone pair, with its slightly greater repulsive effect, ‘pushes’
the three N-H sbonds away from the top of the pyramid, meaning that the H-N-H bond angles are slightly less than tetrahedral, at
107.3˚ rather than 109.5˚.

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VSEPR theory also predicts, accurately, that a water molecule is ‘bent’ at an angle of approximately 104.5˚. It would seem logical,
then, to describe the bonding in water as occurring through the overlap of sp3-hybrid orbitals on oxygen with 1sorbitals on the two
hydrogen atoms. In this model, the two nonbonding lone pairs on oxygen would be located in sp3 orbitals.

Some experimental evidence, however, suggests that the bonding orbitals on the oxygen are actually unhybridized 2p orbitals rather
than sp3 hybrids. Although this would seem to imply that the H-O-H bond angle should be 90˚ (remember that p orbitals are
oriented perpendicular to one another), it appears that electrostatic repulsion has the effect of distorting this p-orbital angle to
104.5˚. Both the hybrid orbital and the nonhybrid orbital models present reasonable explanations for the observed bonding
arrangement in water, so we will not concern ourselves any further with the distinction.

Example

Draw, in the same style as the figures above, an orbital picture for the bonding in methylamine.
Solution

Formation of π bonds - sp and sp hybridization

The valence bond theory, along with the hybrid orbital concept, does a very good job of describing double-bonded compounds such
as ethene. Three experimentally observable characteristics of the ethene molecule need to be accounted for by a bonding model:
1. Ethene is a planar (flat) molecule.
2. Bond angles in ethene are approximately 120o, and the carbon-carbon bond length is 1.34 Å, significantly shorter than the 1.54
Å single carbon-carbon bond in ethane.
3. There is a significant barrier to rotation about the carbon-carbon double bond.

Clearly, these characteristics are not consistent with an sp3 hybrid bonding picture for the two carbon atoms. Instead, the bonding in
ethene is described by a model involving the participation of a different kind of hybrid orbital. Three atomic orbitals on each
carbon – the 2s, 2px and 2py orbitals – combine to form three sp2 hybrids, leaving the 2pz orbital unhybridized.

The three sp2 hybrids are arranged with trigonal planar geometry, pointing to the three corners of an equilateral triangle, with
angles of 120°between them. The unhybridized 2pz orbital is perpendicular to this plane (in the next several figures, sp2 orbitals
and the sigma bonds to which they contribute are represented by lines and wedges; only the 2pz orbitals are shown in the 'space-
filling' mode).

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The carbon-carbon double bond in ethene consists of one sbond, formed by the overlap of two sp2 orbitals, and a second bond,
calleda π (pi) bond, which is formed by the side-by-side overlap of the two unhybridized 2pz orbitals from each carbon.

spacefilling image of bonding in ethene

The pi bond does not have symmetrical symmetry. Because they are the result of side-by-side overlap (rather then end-to-end
overlap like a sigma bond), pi bonds are not free to rotate. If rotation about this bond were to occur, it would involve disrupting the
side-by-side overlap between the two 2pz orbitals that make up the pi bond. The presence of the pi bond thus ‘locks’ the six atoms
of ethene into the same plane. This argument extends to larger alkene groups: in each case, the six atoms of the group form a single
plane.

Conversely, sbonds such as the carbon-carbon single bond in ethane (CH3CH3) exhibit free rotation, and can assume many different
conformations, or shapes - this is one of the main subjects of Chapter 3.

Example 1.20

Circle the six atoms in the molecule below that are ‘locked’ into the same plane.

Example

What kinds of orbitals are overlapping in bonds a-d indicated below?

Example

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What is wrong with the way the following structure is drawn?

Solutions

A similar picture can be drawn for the bonding in carbonyl groups, such as formaldehyde. In this molecule, the carbon is sp2-
hybridized, and we will assume that the oxygen atom is also sp2 hybridized. The carbon has three sigma bonds: two are formed by
overlap between two of its sp2 orbitals with the 1sorbital from each of the hydrogens, and the third sigma bond is formed by
overlap between the remaining carbon sp2 orbital and an sp2 orbital on the oxygen. The two lone pairs on oxygen occupy its other
two sp2 orbitals.

The pi bond is formed by side-by-side overlap of the unhybridized 2pz orbitals on the carbon and the oxygen. Just like in alkenes,
the 2pz orbitals that form the pi bond are perpendicular to the plane formed by the sigma bonds.

Example

Describe and draw the bonding picture for the imine group shown below. Use the drawing of formaldehyde above as your guide.

Solution

Contributors
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

1.7: Hybrid Orbitals- Bonding in Complex Molecules and Practice Problems is shared under a not declared license and was authored, remixed,
and/or curated by LibreTexts.

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CHAPTER OVERVIEW

2: Alkanes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
2.1: Chemical Properties of Alkanes
Alkanes are not very reactive when compared with other chemical species. This is because the backbone carbon atoms in alkanes
have attained their octet of electrons through forming four covalent bonds (the maximum allowed number of bonds under the octet
rule; which is why carbon's valence number is 4). These four bonds formed by carbon in alkanes are sigma bonds, which are more
stable than other types of bond because of the greater overlap of carbon's atomic orbitals with neighboring atoms' atomic orbitals.
To make alkanes react, the input of additional energy is needed; either through heat or radiation.
Gasoline is a mixture of the alkanes and unlike many chemicals, can be stored for long periods and transported without problem. It
is only when ignited that it has enough energy to continue reacting. This property makes it difficult for alkanes to be converted into
other types of organic molecules. (There are only a few ways to do this). Alkanes are also less dense than water, as one can
observe, oil, an alkane, floats on water.
Alkanes are non-polar solvents. Since only C and H atoms are present, alkanes are nonpolar. Alkanes are immiscible in water but
freely miscible in other non-polar solvents. Alkanes consisting of weak dipole dipole bonds can not break the strong hydrogen bond
between water molecules hence it is not miscible in water. The same character is also shown by alkenes. Because alkanes contain
only carbon and hydrogen, combustion produces compounds that contain only carbon, hydrogen, and/or oxygen. Like other
hydrocarbons, combustion under most circumstances produces mainly carbon dioxide and water. However, alkanes require more
heat to combust and do not release as much heat when they combust as other classes of hydrocarbons. Therefore, combustion of
alkanes produces higher concentrations of organic compounds containing oxygen, such as aldehydes and ketones, when
combusting at the same temperature as other hydrocarbons.
The general formula for alkanes is CNH2N+2; the simplest possible alkane is therefore methane, CH4. The next simplest is ethane,
C2H6; the series continues indefinitely. Each carbon atom in an alkane has sp³ hybridization.
Alkanes are also known as paraffins, or collectively as the paraffin series. These terms are also used for alkanes whose carbon
atoms form a single, unbranched chain. Branched-chain alkanes are called isoparaffins.
Methane through Butane are very flammable gases at standard temperature and pressure (STP). Pentane is an extremely
flammable liquid boiling at 36 °C and boiling points and melting points steadily increase from there; octadecane is the first alkane
which is solid at room temperature. Longer alkanes are waxy solids; candle wax generally has between C20 and C25 chains. As
chain length increases ultimately we reach polyethylene, which consists of carbon chains of indefinite length, which is generally a
hard white solid.

Reactions
Alkanes react only very poorly with ionic or other polar substances. The pKa values of all alkanes are above 50, and so they are
practically inert to acids and bases. This inertness is the source of the term paraffins (Latin para + affinis, with the meaning here of
"lacking affinity"). In crude oil the alkane molecules have remained chemically unchanged for millions of years.
However redox reactions of alkanes, in particular with oxygen and the halogens, are possible as the carbon atoms are in a strongly
reduced condition; in the case of methane, the lowest possible oxidation state for carbon (−4) is reached. Reaction with oxygen
leads to combustion without any smoke; with halogens, substitution. In addition, alkanes have been shown to interact with, and
bind to, certain transition metal complexes.
Free radicals, molecules with unpaired electrons, play a large role in most reactions of alkanes, such as cracking and reformation
where long-chain alkanes are converted into shorter-chain alkanes and straight-chain alkanes into branched-chain isomers.
In highly branched alkanes and cycloalkanes, the bond angles may differ significantly from the optimal value (109.5°) in order to
allow the different groups sufficient space. This causes a tension in the molecule, known as steric hinderance, and can substantially
increase the reactivity. The same is preferred for alkenes too.

Contributors
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2.2: Physical Properties of Alkanes
Alkanes are not very reactive and have little biological activity; all alkanes are colorless and odorless.

Boiling Points
The boiling points shown are for the "straight chain" isomers of which there is more than one. The first four alkanes are gases at
room temperature, and solids do not begin to appear until about C H , but this is imprecise because different isomers typically
17 36

have different melting and boiling points. By the time you get 17 carbons into an alkane, there are unbelievable numbers of
isomers!

Cycloalkanes have boiling points that are approximately 20 K higher than the corresponding straight chain alkane.

There is not a significant electronegativity difference between carbon and hydrogen, thus, there is not any significant bond polarity.
The molecules themselves also have very little polarity. A totally symmetrical molecule like methane is completely non-polar,
meaning that the only attractions between one molecule and its neighbors will be Van der Waals dispersion forces. These forces
will be very small for a molecule like methane but will increase as the molecules get bigger. Therefore, the boiling points of the
alkanes increase with molecular size.
Where you have isomers, the more branched the chain, the lower the boiling point tends to be. Van der Waals dispersion forces are
smaller for shorter molecules and only operate over very short distances between one molecule and its neighbors. It is more
difficult for short, fat molecules (with lots of branching) to lie as close together as long, thin molecules.

 Example 2.2.1: Structure dependent Boiling Points

For example, the boiling points of the three isomers of C 5 H12 are:
pentane: 309.2 K
2-methylbutane: 301.0 K
2,2-dimethylpropane: 282.6 K
The slightly higher boiling points for the cycloalkanes are presumably because the molecules can get closer together because
the ring structure makes them tidier and less "wriggly"!

Solubility
Alkanes (both alkanes and cycloalkanes) are virtually insoluble in water, but dissolve in organic solvents. However, liquid alkanes
are good solvents for many other non-ionic organic compounds.

Solubility in Water
When a molecular substance dissolves in water, the following must occur:
break the intermolecular forces within the substance. In the case of the alkanes, these are the Van der Waals dispersion forces.
break the intermolecular forces in the water so that the substance can fit between the water molecules. In water, the primary
intermolecular attractions are hydrogen bonds.

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Breaking either of these attractions requires energy, although the amount of energy to break the Van der Waals dispersion forces in
something like methane is relatively negligible; this is not true of the hydrogen bonds in water.
As something of a simplification, a substance will dissolve if there is enough energy released when new bonds are made between
the substance and the water to compensate for what is used in breaking the original attractions. The only new attractions between
the alkane and the water molecules are Van der Waals forces. These forces do not release a sufficient amount of energy to
compensate for the energy required to break the hydrogen bonds in water.; the alkane does not dissolve.

The energy only description of solvation is an oversimplification because entropic effects are also important when things
dissolve.

Solubility in organic solvents

In most organic solvents, the primary forces of attraction between the solvent molecules are Van der Waals - either dispersion
forces or dipole-dipole attractions. Therefore, when an alkane dissolves in an organic solvent, the Van der Waals forces are broken
and are replaced by new Van der Waals forces. The two processes more or less cancel each other out energetically; thus, there is no
barrier to solubility.

Contributors
Jim Clark (Chemguide.co.uk)

This page titled 2.2: Physical Properties of Alkanes is shared under a CC BY-NC 4.0 license and was authored, remixed, and/or curated by Jim
Clark.
Physical Properties of Alkanes by Jim Clark is licensed CC BY-NC 4.0.

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2.3: Nomenclature of Alkanes
The names of all alkanes end with -ane. Whether or not the carbons are linked together end-to-end in a ring (called cyclic alkanes
or cycloalkanes) or whether they contain side chains and branches, the name of every carbon-hydrogen chain that lacks any double
bonds or functional groups will end with the suffix -ane.
Alkanes with unbranched carbon chains are simply named by the number of carbons in the chain. The first four members of the
series (in terms of number of carbon atoms) are named as follows:
1. CH4 = methane = one hydrogen-saturated carbon
2. C2H6 = ethane = two hydrogen-saturated carbons
3. C3H8 = propane = three hydrogen-saturated carbons
4. C4H10 = butane = four hydrogen-saturated carbons
Alkanes with five or more carbon atoms are named by adding the suffix -ane to the appropriate numerical multiplier, except the
terminal -a is removed from the basic numerical term. Hence, C5H12 is called pentane, C6H14 is called hexane, C7H16 is called
heptane and so forth.
Straight-chain alkanes are sometimes indicated by the prefix n- (for normal) to distinguish them from branched-chain alkanes
having the same number of carbon atoms. Although this is not strictly necessary, the usage is still common in cases where there is
an important difference in properties between the straight-chain and branched-chain isomers: e.g. n-hexane is a neurotoxin while its
branched-chain isomers are not.
IUPAC nomenclature
The IUPAC nomenclature is a system on which most organic chemists have agreed to provide guidelines to allow them to learn
from each others' works. Nomenclature, in other words, provides a foundation of language for organic chemistry.

Number of Hydrogen to Carbons

This equation describes the relationship between the number of hydrogen and carbon atoms in alkanes:

H = 2C + 2

where "C" and "H" are used to represent the number of carbon and hydrogen atoms present in one molecule. If C = 2, then H = 6.
Many textbooks put this in the following format:

CnH2n+2

where "Cn" and "H2n+2" represent the number of carbon and hydrogen atoms present in one molecule. If Cn = 3, then H2n+2 = 2(3)
+ 2 = 8. (For this formula look to the "n" for the number, the "C" and the "H" letters themselves do not change.)
Progressively longer hydrocarbon chains can be made and are named systematically, depending on the number of carbons in the
longest chain.
The following table contains the systematic names for the first twenty straight chain alkanes. It will be important to familiarize
yourself with these names because they will be the basis for naming many other organic molecules throughout your course of study.

Drawing Hydrocarbons
Recall that when carbon makes four bonds, it adopts the tetrahedral geometry. In the tetrahedral geometry, only two bonds can
occupy a plane simultaneously. The other two bonds point in back or in front of this plane. In order to represent the tetrahedral
geometry in two dimensions, solid wedges are used to represent bonds pointing out of the plane of the drawing toward the viewer,
and dashed wedges are used to represent bonds pointing out of the plane of the drawing away from the viewer. Consider the
following representation of the molecule methane:

Figure 1: Two dimensional representation of methane

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In the above drawing, the two hydrogens connected by solid lines, as well as the carbon in the center of the molecule, exist in a
plane (specifically, the plane of the computer monitor / piece of paper, etc.). The hydrogen connected by a solid wedge points out of
this plane toward the viewer, and the hydrogen connected by the dashed wedge points behind this plane and away from the viewer.
In drawing hydrocarbons, it can be time-consuming to write out each atom and bond individually. In organic chemistry,
hydrocarbons can be represented in a shorthand notation called a skeletal structure. In a skeletal structure, only the bonds between
carbon atoms are represented. Individual carbon and hydrogen atoms are not drawn, and bonds to hydrogen are not drawn. In the
case that the molecule contains just single bonds (sp3 bonds), these bonds are drawn in a "zig-zag" fashion. This is because in the
tetrahedral geometry all bonds point as far away from each other as possible, and the structure is not linear. Consider the following
representations of the molecule propane:

Figure 2: Full structure of propane and skeletal structure of propane

Only the bonds between carbons have been drawn, and these have been drawn in a "zig-zag" manner. Note that there is no
representation of hydrogens in a skeletal structure. Since, in the absence of double or triple bonds, carbon makes four bonds total,
the presence of hydrogens is implicit. Whenever an insufficient number of bonds to a carbon atom are specified in the structure, it
is assumed that the rest of the bonds are made to hydrogens. For example, if the carbon atom makes only one explicit bond, there
are three hydrogens implicitly attached to it. If it makes two explicit bonds, there are two hydrogens implicitly attached, etc. Note
also that two lines are sufficient to represent three carbon atoms. It is the bonds only that are being drawn out, and it is understood
that there are carbon atoms (with three hydrogens attached!) at the terminal ends of the structure.

Alkyl Groups
Alkanes can be described by the general formula CnH2n+2. An alkyl group is formed by removing one hydrogen from the alkane
chain and is described by the formula CnH2n+1. The removal of this hydrogen results in a stem change from -ane to -yl. Take a look
at the following examples.

The same concept can be applied to any of the straight chain alkane names provided in the table above.

Name Molecular Formula Condensed Structural Formula

Methane CH4 CH4

Ethane C2H6 CH3CH3

Propane C3H8 CH3CH2CH3

Butane C4H10 CH3(CH2)2CH3

Pentane C5H12 CH3(CH2)3CH3

Hexane C6H14 CH3(CH2)4CH3

Heptane C7H16 CH3(CH2)5CH3

Octane C8H18 CH3(CH2)6CH3

Nonane C9H20 CH3(CH2)7CH3

Decane C10H22 CH3(CH2)8CH3

Undecane C11H24 CH3(CH2)9CH3

Dodecane C12H26 CH3(CH2)10CH3

Tridecane C13H28 CH3(CH2)11CH3

Tetradecane C14H30 CH3(CH2)12CH3

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Name Molecular Formula Condensed Structural Formula

Pentadecane C15H32 CH3(CH2)13CH3

Hexadecane C16H34 CH3(CH2)14CH3

Heptadecane C17H36 CH3(CH2)15CH3

Octadecane C18H38 CH3(CH2)16CH3

Nonadecane C19H40 CH3(CH2)17CH3

Eicosane C20H42 CH3(CH2)18CH3

Using Common Names with Branched Alkanes

Certain branched alkanes have common names that are still widely used today. These common names make use of prefixes, such as
iso-, sec-, tert-, and neo-. The prefix iso-, which stands for isomer, is commonly given to 2-methyl alkanes. In other words, if there
is methyl group located on the second carbon of a carbon chain, we can use the prefix iso-. The prefix will be placed in front of the
alkane name that indicates the total number of carbons. Examples:
isopentane which is the same as 2-methylbutane
isobutane which is the same as 2-methylpropane
To assign the prefixes sec-, which stands for secondary, and tert-, for tertiary, it is important that we first learn how to classify
carbon molecules. If a carbon is attached to only one other carbon, it is called a primary carbon. If a carbon is attached to two
other carbons, it is called a seconday carbon. A tertiary carbon is attached to three other carbons and last, a quaternary carbon is
attached to four other carbons. Examples:
4-sec-butylheptane (30g)
4-tert-butyl-5-isopropylhexane (30d); if using this example, may want to move sec/tert after iso disc
The prefix neo- refers to a substituent whose second-to-last carbon of the chain is trisubstituted (has three methyl groups attached
to it). A neo-pentyl has five carbons total. Examples:
neopentane
neoheptane

Alkoxy Groups
Alkoxides consist of an organic group bonded to a negatively charged oxygen atom. In the general form, alkoxides are written as
RO-, where R represents the organic substituent. Similar to the alkyl groups above, the concept of naming alkoxides can be applied
to any of the straight chain alkanes provided in the table above.

Three Principles of Naming

1. Choose the longest, most substituted carbon chain containing a functional group.
2. A carbon bonded to a functional group must have the lowest possible carbon number. If there are no functional groups, then any
substitute present must have the lowest possible number.
3. Take the alphabetical order into consideration; that is, after applying the first two rules given above, make sure that your
substitutes and/or functional groups are written in alphabetical order.
Example 1
What is the name of the following molecule?

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SOLUTION
Rule #1: Choose the longest, most substituted carbon chain containing a functional group. This example does not contain any
functional groups, so we only need to be concerned with choosing the longest, most substituted carbon chain. The longest
carbon chain has been highlighted in red and consists of eight carbons.

Rule #2: Carbons bonded to a functional group must have the lowest possible carbon number. If there are no functional groups,
then any substitute present must have the lowest possible number. Because this example does not contain any functional groups,
we only need to be concerned with the two substitutes present, that is, the two methyl groups. If we begin numbering the chain
from the left, the methyls would be assigned the numbers 4 and 7, respectively. If we begin numbering the chain from the right,
the methyls would be assigned the numbers 2 and 5. Therefore, to satisfy the second rule, numbering begins on the right side of
the carbon chain as shown below. This gives the methyl groups the lowest possible numbering.

Rule 3: In this example, there is no need to utilize the third rule. Because the two substitutes are identical, neither takes
alphabetical precedence with respect to numbering the carbons. This concept will become clearer in the following examples.

Example 2
What is the name of the following molecule?

SOLUTION
Rule #1: Choose the longest, most substituted carbon chain containing a functional group. This example contains two functional
groups, bromine and chlorine. The longest carbon chain has been highlighted in red and consists of seven carbons.

Rule #2: Carbons bonded to a functional group must have the lowest possible carbon number. If there are no functional groups,
then any substitute present must have the lowest possible number. In this example, numbering the chain from the left or the right
would satisfy this rule. If we number the chain from the left, bromine and chlorine would be assigned the second and sixth
carbon positions, respectively. If we number the chain from the right, chlorine would be assigned the second position and
bromine would be assigned the sixth position. In other words, whether we choose to number from the left or right, the functional
groups occupy the second and sixth positions in the chain. To select the correct numbering scheme, we need to utilize the third
rule.

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Rule #3: After applying the first two rules, take the alphabetical order into consideration. Alphabetically, bromine comes before
chlorine. Therefore, bromine is assigned the second carbon position, and chlorine is assigned the sixth carbon position.

Example 3
What is the name of the follow molecule?

SOLUTION
Rule #1: Choose the longest, most substituted carbon chain containing a functional group. This example contains two functional
groups, bromine and chlorine, and one substitute, the methyl group. The longest carbon chain has been highlighted in red and
consists of seven carbons.

Rule #2: Carbons bonded to a functional group must have the lowest possible carbon number. After taking functional groups
into consideration, any substitutes present must have the lowest possible carbon number. This particular example illustrates the
point of difference principle. If we number the chain from the left, bromine, the methyl group and chlorine would occupy the
second, fifth and sixth positions, respectively. This concept is illustrated in the second drawing below. If we number the chain
from the right, chlorine, the methyl group and bromine would occupy the second, third and sixth positions, respectively, which
is illustrated in the first drawing below. The position of the methyl, therefore, becomes a point of difference. In the first
drawing, the methyl occupies the third position. In the second drawing, the methyl occupies the fifth position. To satisfy the
second rule, we want to choose the numbering scheme that provides the lowest possible numbering of this substitute. Therefore,
the first of the two carbon chains shown below is correct.

Therefore, the first numbering scheme is the appropriate one to use.

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Once you have determined the correct numbering of the carbons, it is often useful to make a list, including the functional
groups, substitutes, and the name of the parent chain.
Rule #3: After applying the first two rules, take the alphabetical order into consideration. Alphabetically, bromine comes before
chlorine. Therefore, bromine is assigned the second carbon position, and chlorine is assigned the sixth carbon position.
Parent chain: heptane 2-Chloro 3-Methyl 6-Bromo
6-bromo-2-chloro-3-methylheptane

Problems
What is the name of the follow molecules?

Contributors
Jonathan Mooney (McGill University)
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2.4: Nomenclature of Cycloalkanes
Cycloalkanes are cyclic hydrocarbons, meaning that the carbons of the molecule are arranged in the form of a ring. Cycloalkanes
are also saturated, meaning that all of the carbons atoms that make up the ring are single bonded to other atoms (no double or triple
bonds). There are also polycyclic alkanes, which are molecules that contain two or more cycloalkanes that are joined, forming
multiple rings.

Introduction
Many organic compounds found in nature or created in a laboratory contain rings of carbon atoms with distinguishing chemical
properties; these compounds are known as cycloalkanes. Cycloalkanes only contain carbon-hydrogen bonds and carbon-carbon
single bonds, but in cycloalkanes, the carbon atoms are joined in a ring. The smallest cycloalkane is cyclopropane.

Figure 1: The first four cycloalkanes

If you count the carbons and hydrogens, you will see that they no longer fit the general formula C H . By joining the carbon
n 2n+2

atoms in a ring,two hydrogen atoms have been lost. The general formula for a cycloalkane is C H . Cyclic compounds are not all
n 2n

flat molecules. All of the cycloalkanes, from cyclopentane upwards, exist as "puckered rings". Cyclohexane, for example, has a
ring structure that looks like this:

Figure 2: This is known as the "chair" form of cyclohexane from its shape, which vaguely resembles a chair. Note: The
cyclohexane molecule is constantly changing, with the atom on the left, which is currently pointing down, flipping up, and the atom
on the right flipping down. During this process, another (slightly less stable) form of cyclohexane is formed known as the "boat"
form. In this arrangement, both of these atoms are either pointing up or down at the same time
In addition to being saturated cyclic hydrocarbons, cycloalkanes may have multiple substituents or functional groups that further
determine their unique chemical properties. The most common and useful cycloalkanes in organic chemistry are cyclopentane and
cyclohexane, although other cycloalkanes varying in the number of carbons can be synthesized. Understanding cycloalkanes and
their properties are crucial in that many of the biological processes that occur in most living things have cycloalkane-like structures.

Glucose (6 carbon sugar) Ribose (5 carbon sugar) Cholesterol (polycyclic)

Although polycyclic compounds are important, they are highly complex and typically have common names accepted by IUPAC.
However, the common names do not generally follow the basic IUPAC nomenclature rules. The general formula of the
cycloalkanes is C H where n is the number of carbons. The naming of cycloalkanes follows a simple set of rules that are built
n 2n

upon the same basic steps in naming alkanes. Cyclic hydrocarbons have the prefix "cyclo-".

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Parent Chains
For simplicity, cycloalkane molecules can be drawn in the form of skeletal structures in which each intersection between two lines
is assumed to have a carbon atom with its corresponding number of hydrogens.

same as same as
Cycloalkane Molecular Formula Basic Structure

Cyclopropane \(C_3H_6\0

Cyclobutane C4 H8

Cyclopentane C5 H10

Cyclohexane C6 H12

Cycloheptane C7 H14

Cyclooctane C8 H16

Cyclononane C9 H18

Cyclodecane C10 H20

IUPAC Rules for Nomenclature

1. Determine the cycloalkane to use as the parent chain. The parent chain is the one with the highest number of carbon atoms. If
there are two cycloalkanes, use the cycloalkane with the higher number of carbons as the parent chain.
2. If there is an alkyl straight chain that has a greater number of carbons than the cycloalkane, then the alkyl chain must be used as
the primary parent chain. Cycloalkane acting as a substituent to an alkyl chain has an ending "-yl" and, therefore, must be
named as a cycloalkyl.

Cycloalkane Cycloalkyl

cyclopropane cyclopropyl
cyclobutane cyclobutyl

cyclopentane cyclopentyl
cyclohexane cyclohexyl
cycloheptane cycloheptyl
cyclooctane cyclooctyl

cyclononane cyclononanyl
cyclodecane cyclodecanyl

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 Example 1

The longest straight chain contains 10 carbons, compared with cyclopropane, which only contains 3 carbons. Because
cyclopropane is a substituent, it would be named a cyclopropyl-substituted alkane.

3. Determine any functional groups or other alkyl groups.

4. Number the carbons of the cycloalkane so that the carbons with functional groups or alkyl groups have the lowest possible
number. A carbon with multiple substituents should have a lower number than a carbon with only one substituent or functional
group. One way to make sure that the lowest number possible is assigned is to number the carbons so that when the numbers
corresponding to the substituents are added, their sum is the lowest possible.

(1+3=4) NOT (1+5=6)

3. When naming the cycloalkane, the substituents and functional groups must be placed in alphabetical order.

(ex: 2-bromo-1-chloro-3-methylcyclopentane)
4. Indicate the carbon number with the functional group with the highest priority according to alphabetical order. A dash"-" must
be placed between the numbers and the name of the substituent. After the carbon number and the dash, the name of the
substituent can follow. When there is only one substituent on the parent chain, indicating the number of the carbon atoms with
the substituent is not necessary.

(ex: 1-chlorocyclohexane or cholorocyclohexane is acceptable)

7. If there is more than one of the same functional group on one carbon, write the number of the carbon two, three, or four times,
depending on how many of the same functional group is present on that carbon. The numbers must be separated by commas,
and the name of the functional group that follows must be separated by a dash. When there are two of the same functional
group, the name must have the prefix "di". When there are three of the same functional group, the name must have the prefix
"tri". When there are four of the same functional group, the name must have the prefix "tetra". However, these prefixes cannot
be used when determining the alphabetical priorities. There must always be commas between the numbers and the dashes that
are between the numbers and the names.

 Example 2

(2-bromo-1,1-dimethylcyclohexane)

Notice that "f" of fluoro alphabetically precedes the "m" of methyl. Although "di" alphabetically precedes "f", it is not used in
determining the alphabetical order.

2.4.3 https://chem.libretexts.org/@go/page/205215
 Example 3

(2-fluoro-1,1,-dimethylcyclohexane NOT 1,1-dimethyl-2-fluorocyclohexane)

8) If the substituents of the cycloalkane are related by the cis or trans configuration, then indicate the configuration by placing "cis-
" or "trans-" in front of the name of the structure.

Blue=Carbon Yellow=Hydrogen Green=Chlorine

Notice that chlorine and the methyl group are both pointed in the same direction on the axis of the molecule; therefore, they are cis.

cis-1-chloro-2-methylcyclopentane
9) After all the functional groups and substituents have been mentioned with their corresponding numbers, the name of the
cycloalkane can follow.

Reactivity
Cycloalkanes are very similar to the alkanes in reactivity, except for the very small ones, especially cyclopropane. Cyclopropane is
significantly more reactive than what is expected because of the bond angles in the ring. Normally, when carbon forms four single
bonds, the bond angles are approximately 109.5°. In cyclopropane, the bond angles are 60°.

With the electron pairs this close together, there is a significant amount of repulsion between the bonding pairs joining the carbon
atoms, making the bonds easier to break.

Alcohol Substituents on Cycloalkanes

Alcohol (-OH) substituents take the highest priority for carbon atom numbering in IUPAC nomenclature. The carbon atom with the
alcohol substituent must be labeled as 1. Molecules containing an alcohol group have an ending "-ol", indicating the presence of an
alcohol group. If there are two alcohol groups, the molecule will have a "di-" prefix before "-ol" (diol). If there are three alcohol
groups, the molecule will have a "tri-" prefix before "-ol" (triol), etc.

 Example 4

The alcohol substituent is given the lowest number even though the two methyl groups are on the same carbon atom and
labeling 1 on that carbon atom would give the lowest possible numbers. Numbering the location of the alcohol substituent is
unnecessary because the ending "-ol" indicates the presence of one alcohol group on carbon atom number 1.

2.4.4 https://chem.libretexts.org/@go/page/205215
2,2-dimethylcyclohexanol NOT 1,1-dimethyl-cyclohexane-2-ol

 Example 5

3-bromo-2-methylcyclopentanol NOT 1-bromo-2-methyl-cyclopentane-2-ol

 Example 6

Blue=Carbon Yellow=Hydrogen Red=Oxygen

trans-cyclohexane-1,2-diol

Other Substituents on Cycloalkanes

There are many other functional groups like alcohol, which are later covered in an organic chemistry course, and they determine
the ending name of a molecule. The naming of these functional groups will be explained in depth later as their chemical properties
are explained.

Name Name ending

alkene -ene

alkyne -yne
alcohol -ol

ether -ether
nitrile -nitrile

amine -amine

aldehyde -al
ketone -one

carboxylic acid -oic acid

ester -oate

amide -amide

Although alkynes determine the name ending of a molecule, alkyne as a substituent on a cycloalkane is not possible because
alkynes are planar and would require that the carbon that is part of the ring form 5 bonds, giving the carbon atom a negative charge.

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However, a cycloalkane with a triple bond-containing substituent is possible if the triple bond is not directly attached to the ring.

 Example 7

ethynylcyclooctane

 Example 8

1-propylcyclohexane

Summary
1. Determine the parent chain: the parent chain contains the most carbon atoms.
2. Number the substituents of the chain so that the sum of the numbers is the lowest possible.
3. Name the substituents and place them in alphabetical order.
4. If stereochemistry of the compound is shown, indicate the orientation as part of the nomenclature.
5. Cyclic hydrocarbons have the prefix "cyclo-" and have an "-alkane" ending unless there is an alcohol substituent present. When
an alcohol substituent is present, the molecule has an "-ol" ending.

Glossary
alcohol: An oxygen and hydrogenOH hydroxyl group that is bonded to a substituted alkyl group.
alkyl: A structure that is formed when a hydrogen atom is removed from an alkane.
cyclic: Chemical compounds arranged in the form of a ring or a closed chain form.
cycloalkanes: Cyclic saturated hydrocarbons with a general formula of CnH(2n). Cycloalkanes are alkanes with carbon atoms
attached in the form of a closed ring.
functional groups: An atom or groups of atoms that substitute for a hydrogen atom in an organic compound, giving the
compound unique chemical properties and determining its reactivity.
hydrocarbon: A chemical compound containing only carbon and hydrogen atoms.
saturated: All of the atoms that make up a compound are single bonded to the other atoms, with no double or triple bonds.
skeletal structure: A simplified structure in which each intersection between two lines is assumed to have a carbon atom with
its corresponding number of hydrogens.

Problems
Name the following structures. (Note: The structures are complex for practice purposes and may not be found in nature.)

1) 2) 3) 4) 5) 6)

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7)
Draw the following structures.
8) 1,1-dibromo-5-fluoro-3-butyl-7-methylcyclooctane 9) trans-1-bromo-2-chlorocyclopentane
10) 1,1-dibromo-2,3-dichloro-4-propylcyclobutane 11) 2-methyl-1-ethyl-1,3-dipropylcyclopentane 12) cycloheptane-1,3,5-triol
Name the following structures.
Blue=Carbon Yellow=Hydrogen Red=Oxygen Green=Chlorine

13) 14) 15) 16) 17)

18) 19)

Answers to Practice Problems

1) cyclodecane 2) chlorocyclopentane or 1-chlorocyclopentane 3) trans-1-chloro-2-methylcycloheptane
4) 3-cyclopropyl-6-methyldecane 5) cyclopentylcyclodecane or 1-cyclopentylcyclodecane 6) 1,3-dibromo-1-chloro-2-
fluorocycloheptane
7) 1-cyclobutyl-4-isopropylcyclohexane

8) 9) 10) 11) 12)

13) cyclohexane 14) cyclohexanol 15) chlorocyclohexane 16) cyclopentylcyclohexane 17) 1-chloro-3-methylcyclobutane
18) 2,3-dimethylcyclohexanol 19) cis-1-propyl-2-methylcyclopentane

References
1. ACD/ChemSketch Freeware, version 11.0, Advanced Chemistry Development, Inc., Toronto, ON, Canada, www.acdlabs.com,
2008.
2. Bruice, Paula Yurkanis. Oragnic Chemistry. 5th. CA. Prentice Hall, 2006.
3. Fryhle, C.B. and G. Solomons. Organic Chemistry. 9th ed. Danvers, MA: Wiley, 2008.
4. McMurry, John. Organic Chemistry. 7th ed. Belmont, California: Thomson Higher Education, 2008.
5. Sadava, Heller, Orians, Purves, Hillis. Life The Science of Biology. 8th ed. Sunderland, MA: W.H. Freeman, 2008.
6. Vollhardt, K. Peter C., and Neil E. Schore. Organic Chemistry. 5th ed. New York: W.H. Freeman, 2007.

Contributors
Pwint Zin
Jim Clark (ChemGuide)

This page titled 2.4: Nomenclature of Cycloalkanes is shared under a CC BY-NC 4.0 license and was authored, remixed, and/or curated by Jim
Clark.

2.4.7 https://chem.libretexts.org/@go/page/205215
Nomenclature of Cycloalkanes by Jim Clark is licensed CC BY-NC 4.0.

2.4.8 https://chem.libretexts.org/@go/page/205215
2.5: Practice - Alkane Nomenclature
I. The parent compound must have the longest chain of carbon atoms
Learn: methane (1 carbon atom), ethane (2 carbon atoms), propane (3 carbon atoms), butane (4 carbon atoms), pentane (5 carbon
atoms), hexane (6 carbon atoms), heptane (7 carbon atoms), octane (8 carbon atoms), nonane (9 carbon atoms) and decane (10
carbon atoms).
Try to name the following compounds:
1. CH3-CH2-CH2-CH3
2. CH3-CH2-CH2-CH2-CH2-CH3
3. CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH3
Try to draw structures for the following compounds:
4. propane
5. pentane
6. octane

II. The parent chain is numbered to give substituents the lowest possible numbers
Substituent names are methyl, ethyl, propyl, butyl, etc. The number showing the point of attachment to the parent chain precedes
the substituent name. If you have more than one substituent with the same name, a number of attachment must be given for each
substituent and the number of the substituents must be designated with di-, tri-, etc.
Try to name the following compounds...

9.
Try to draw structures for the following compounds...
10. 2,2-dimethylpropane
11. 3-methylheptane
12. 4,5-diethylnonane

III. Substituents are named in alphabetical order

Remember that the numbering of the parent chain must give all substituents the lowest possible numbers regardless of their names.
Try to name the following compound...

13.

IV. A large substituent is numbered to give its point of attachment

The point of attachment is number one and any other smaller groups are named as substituent groups on the larger group. This
numbering is independent of the numbering of the parent chain. Try to name the following compounds...
14.

2.5.1 https://chem.libretexts.org/@go/page/205216
15.
Try to draw structures for the following compounds...
16. 4-(1-methylethyl)heptane
17. 5-(1,1-dimethylethyl)nonane

V. Ring compounds are designated with a cyclo- prefix and are numbered to give multiple
substituents the lowest possible numbers
A single substituent does not need to be numbered. A ring can also be named as a substituent. Try to name the following
compounds:

18.

19.

20.
Try to draw structures for the following compounds...
21. ethylcyclobutane
22. 1-ethyl-4-methylcyclohexane
23. cyclobutylcyclooctane

VI. Common Names

isopropyl = 1-methylethyl
isobutyl = 2-methylpropyl
sec-butyl = 1-methylpropyl
tert-butyl = 1,1-dimethylethyl
neo-pentyl = 2,2-dimethylpropyl
iso-pentyl = 3-methylbutyl
Try to name the following compounds using common names...

24.

25.

Try to draw structures for the following compounds...

2.5.2 https://chem.libretexts.org/@go/page/205216
26. 4-isopropyloctane
27. isopentylcyclohexane

Answers
1. butane
2. hexane
3. nonane
4. CH3-CH2-CH3
5. CH3-CH2-CH2-CH2-CH3
6. CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH3
7. 2-methylbutane
8. 3-ethylhexane
9. 3-methyloctane (Remember that you must number the parent chain to give the substituent the lowest possible number.)

10.

11.

12.
13. 4-ethyl-3-methylheptane
14. 4-(1-methylethyl)octane
15. 5-(1-methylpropyl)decane

16.

17.
18. 1-ethyl-2-methylcyclohexane
19. methylcyclopentane (You do not need a number since there is only one substituent and it is assumed to be on the first carbon
regardless of how the ring compound is drawn.)
20. cyclopropylcyclopentane

21.

22.

2.5.3 https://chem.libretexts.org/@go/page/205216
23.
24. neo-pentylcycloheptane (1-(2,2-dimethyl-1-propyl)cycloheptane is the proper name.)
25. isopropylcyclohexane

26.

27.

Contributors
Richard Banks (Boise State University)

2.5: Practice - Alkane Nomenclature is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

2.5.4 https://chem.libretexts.org/@go/page/205216
2.6: Ethane Conformers
The simple alkane ethane provides a good introduction to conformational analysis. Here there is only one carbon-carbon bond, and
the rotational structures (rotamers) that it may assume fall between two extremes, staggered and eclipsed. In the following
description of these conformers, several structural notations are used. The first views the ethane molecule from the side, with the
carbon-carbon bond being horizontal to the viewer. The hydrogens are then located in the surrounding space by wedge (in front of
the plane) and hatched (behind the plane) bonds. If this structure is rotated so that carbon #1 is canted down and brought closer to
the viewer, the "sawhorse" projection is presented. Finally, if the viewer looks down the carbon-carbon bond with carbon #1 in
front of #2, the Newman projection is seen.
Name of Conformer Wedge-Hatched Bond Structure Sawhorse Structure Newman Projection

Figure 1: Extreme Conformations of Ethane

As a result of bond-electron repulsions, illustrated in Figure 2, the eclipsed conformation is less stable than the staggered
conformation by roughly 3 kcal / mol (eclipsing strain). The most severe repulsions in the eclipsed conformation are depicted by
the red arrows. There are six other less strong repulsions that are not shown. In the staggered conformation there are six equal bond
repulsions, four of which are shown by the blue arrows, and these are all substantially less severe than the three strongest eclipsed
repulsions.

Figure 2: Bond Repulsions in Ethane

Consequently, the potential energy associated with the various conformations of ethane varies with the dihedral angle of the
bonds, as shown below. Although the conformers of ethane are in rapid equilibrium with each other, the 3 kcal/mol energy
difference leads to a substantial preponderance of staggered conformers (> 99.9%) at any given time.

2.6.1 https://chem.libretexts.org/@go/page/204775
Dihedral Angle

Potential Energy Profile for Ethane Conformers: The above animation illustrates the relationship between ethane's potential
energy and its dihedral angle

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

This page titled 2.6: Ethane Conformers is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by William
Reusch.

2.6.2 https://chem.libretexts.org/@go/page/204775
2.7: Gibbs Free Energy (review)
Learning Objectives
To understand the relationship between Gibbs free energy and work.

One of the major goals of chemical thermodynamics is to establish criteria for predicting whether a particular reaction or process will
occur spontaneously. We have developed one such criterion, the change in entropy of the universe: if ΔSuniv > 0 for a process or a
reaction, then the process will occur spontaneously as written. Conversely, if ΔSuniv < 0, a process cannot occur spontaneously; if ΔSuniv =
0, the system is at equilibrium. The sign of ΔSuniv is a universally applicable and infallible indicator of the spontaneity of a reaction.
Unfortunately, using ΔSuniv requires that we calculate ΔS for both a system and its surroundings. This is not particularly useful for two
reasons: we are normally much more interested in the system than in the surroundings, and it is difficult to make quantitative
measurements of the surroundings (i.e., the rest of the universe). A criterion of spontaneity that is based solely on the state functions of a
system would be much more convenient and is provided by a new state function: the Gibbs free energy.

Gibbs Free Energy and the Direction of Spontaneous Reactions

The Gibbs free energy (G), often called simply free energy, was named in honor of J. Willard Gibbs (1838–1903), an American physicist
who first developed the concept. It is defined in terms of three other state functions with which you are already familiar: enthalpy,
temperature, and entropy:
G = H −TS (2.7.1)

Because it is a combination of state functions, G is also a state function.

J. Willard Gibbs (1839–1903)
Born in Connecticut, Josiah Willard Gibbs attended Yale, as did his father, a professor of sacred literature at Yale, who was involved in
the Amistad trial. In 1863, Gibbs was awarded the first engineering doctorate granted in the United States. He was appointed professor
of mathematical physics at Yale in 1871, the first such professorship in the United States. His series of papers entitled “On the
Equilibrium of Heterogeneous Substances” was the foundation of the field of physical chemistry and is considered one of the great
achievements of the 19th century. Gibbs, whose work was translated into French by Le Chatelier, lived with his sister and brother-in-
law until his death in 1903, shortly before the inauguration of the Nobel Prizes.

The criterion for predicting spontaneity is based on (ΔG), the change in G, at constant temperature and pressure. Although very few
chemical reactions actually occur under conditions of constant temperature and pressure, most systems can be brought back to the initial
temperature and pressure without significantly affecting the value of thermodynamic state functions such as G. At constant temperature
and pressure,

ΔG = ΔH − T ΔS (2.7.2)

where all thermodynamic quantities are those of the system. Recall that at constant pressure, ΔH = q , whether a process is reversible or
irreversible, and TΔS = qrev. Using these expressions, we can reduce Equation 2.7.2 to ΔG = q − q . Thus ΔG is the difference
rev

between the heat released during a process (via a reversible or an irreversible path) and the heat released for the same process occurring in
a reversible manner. Under the special condition in which a process occurs reversibly, q = qrev and ΔG = 0. As we shall soon see, if ΔG is
zero, the system is at equilibrium, and there will be no net change.
What about processes for which ΔG ≠ 0? To understand how the sign of ΔG for a system determines the direction in which change is
spontaneous, we can rewrite the relationship between ΔS and q , discussed earlier.
rev

qrev
ΔS = (2.7.3)
T

with the definition of ΔH in terms of q rev

qrev = ΔH (2.7.4)

to obtain
ΔHsys
ΔSsurr = − (2.7.5)
T

Thus the entropy change of the surroundings is related to the enthalpy change of the system. We have stated that for a spontaneous
reaction, ΔS > 0 , so substituting we obtain
univ

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ΔSuniv = ΔSsys + ΔSsurr > 0 (2.7.6)

ΔHsys
= ΔSsys − >0 (2.7.7)
T

Multiplying both sides of the inequality by −T reverses the sign of the inequality; rearranging,

ΔHsys − T ΔSsys < 0 (2.7.8)

which is equal to ΔG (Equation 2.7.2). We can therefore see that for a spontaneous process, ΔG < 0 .
The relationship between the entropy change of the surroundings and the heat gained or lost by the system provides the key connection
between the thermodynamic properties of the system and the change in entropy of the universe. The relationship shown in Equation 2.7.2
allows us to predict spontaneity by focusing exclusively on the thermodynamic properties and temperature of the system. We predict that
highly exothermic processes (ΔH ≪ 0 ) that increase the disorder of a system (ΔS ≫ 0 ) would therefore occur spontaneously. An
sys

example of such a process is the decomposition of ammonium nitrate fertilizer. Ammonium nitrate was also used to destroy the Murrah
Federal Building in Oklahoma City, Oklahoma, in 1995. For a system at constant temperature and pressure, we can summarize the
following results:
If ΔG < 0 , the process occurs spontaneously.
If ΔG = 0 , the system is at equilibrium.
If ΔG > 0 , the process is not spontaneous as written but occurs spontaneously in the reverse direction.
To further understand how the various components of ΔG dictate whether a process occurs spontaneously, we now look at a simple and
familiar physical change: the conversion of liquid water to water vapor. If this process is carried out at 1 atm and the normal boiling point
of 100.00°C (373.15 K), we can calculate ΔG from the experimentally measured value of ΔHvap (40.657 kJ/mol). For vaporizing 1 mol of
water, ΔH = 40, 657; J, so the process is highly endothermic. From the definition of ΔS (Equation 2.7.5), we know that for 1 mol of
water,
ΔHvap
ΔSvap =
Tb

40,657 J
=
373.15 K

= 108.96 J/K

Hence there is an increase in the disorder of the system. At the normal boiling point of water,
ΔG100∘ C = ΔH100∘ C − T ΔS100∘ C

= 40,657 J − [(373.15 K)(108.96 J/K)]

=0 J

The energy required for vaporization offsets the increase in disorder of the system. Thus ΔG = 0, and the liquid and vapor are in
equilibrium, as is true of any liquid at its boiling point under standard conditions.
Now suppose we were to superheat 1 mol of liquid water to 110°C. The value of ΔG for the vaporization of 1 mol of water at 110°C,
assuming that ΔH and ΔS do not change significantly with temperature, becomes
ΔG110∘ C = ΔH − T ΔS

= 40,657 J − [(383.15 K)(108.96 J/K)]

= −1091 J

At 110°C, ΔG < 0 , and vaporization is predicted to occur spontaneously and irreversibly.

We can also calculate ΔG for the vaporization of 1 mol of water at a temperature below its normal boiling point—for example, 90°C—
making the same assumptions:
ΔG90∘ C = ΔH − T ΔS

= 40,657 J − [(363.15 K)(108.96 J/K)]

= 1088 J

At 90°C, ΔG > 0, and water does not spontaneously convert to water vapor. When using all the digits in the calculator display in carrying
out our calculations, ΔG110°C = 1090 J = −ΔG90°C, as we would predict.

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Relating Enthalpy and Entropy changes under Equilibrium Conditions
ΔG = 0 only if ΔH = T ΔS .

We can also calculate the temperature at which liquid water is in equilibrium with water vapor. Inserting the values of ΔH and ΔS into the
definition of ΔG (Equation 2.7.2), setting ΔG = 0 , and solving for T ,
0 J=40,657 J−T(108.96 J/K)
T=373.15 K
Thus ΔG = 0 at T = 373.15 K and 1 atm, which indicates that liquid water and water vapor are in equilibrium; this temperature is called
the normal boiling point of water. At temperatures greater than 373.15 K, ΔG is negative, and water evaporates spontaneously and
irreversibly. Below 373.15 K, ΔG is positive, and water does not evaporate spontaneously. Instead, water vapor at a temperature less than
373.15 K and 1 atm will spontaneously and irreversibly condense to liquid water. Figure 2.7.1 shows how the ΔH and T ΔS terms vary
with temperature for the vaporization of water. When the two lines cross, ΔG = 0 , and ΔH = T ΔS .

Figure 2.7.1 : Temperature Dependence of ΔH and TΔS for the Vaporization of Water. Both ΔH and TΔS are temperature dependent, but
the lines have opposite slopes and cross at 373.15 K at 1 atm, where ΔH = TΔS. Because ΔG = ΔH − TΔS, at this temperature ΔG = 0,
indicating that the liquid and vapor phases are in equilibrium. The normal boiling point of water is therefore 373.15 K. Above the normal
boiling point, the TΔS term is greater than ΔH, making ΔG < 0; hence, liquid water evaporates spontaneously. Below the normal boiling
point, the ΔH term is greater than TΔS, making ΔG > 0. Thus liquid water does not evaporate spontaneously, but water vapor
spontaneously condenses to liquid.
A similar situation arises in the conversion of liquid egg white to a solid when an egg is boiled. The major component of egg white is a
protein called albumin, which is held in a compact, ordered structure by a large number of hydrogen bonds. Breaking them requires an
input of energy (ΔH > 0), which converts the albumin to a highly disordered structure in which the molecules aggregate as a disorganized
solid (ΔS > 0). At temperatures greater than 373 K, the TΔS term dominates, and ΔG < 0, so the conversion of a raw egg to a hard-boiled
egg is an irreversible and spontaneous process above 373 K.

The Relationship between ΔG and Work

In the previous subsection, we learned that the value of ΔG allows us to predict the spontaneity of a physical or a chemical change. In
addition, the magnitude of ΔG for a process provides other important information. The change in free energy (ΔG) is equal to the
maximum amount of work that a system can perform on the surroundings while undergoing a spontaneous change (at constant
temperature and pressure): ΔG = wmax. To see why this is true, let’s look again at the relationships among free energy, enthalpy, and
entropy expressed in Equation 2.7.2. We can rearrange this equation as follows:
ΔH = ΔG + T ΔS (2.7.9)

This equation tells us that when energy is released during an exothermic process (ΔH < 0), such as during the combustion of a fuel, some
of that energy can be used to do work (ΔG < 0), while some is used to increase the entropy of the universe (TΔS > 0). Only if the process
occurs infinitely slowly in a perfectly reversible manner will the entropy of the universe be unchanged. (For more information on entropy
and reversibility, see the previous section). Because no real system is perfectly reversible, the entropy of the universe increases during all
processes that produce energy. As a result, no process that uses stored energy can ever be 100% efficient; that is, ΔH will never equal ΔG
because ΔS has a positive value.

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One of the major challenges facing engineers is to maximize the efficiency of converting stored energy to useful work or converting one
form of energy to another. As indicated in Table 2.7.1, the efficiencies of various energy-converting devices vary widely. For example, an
internal combustion engine typically uses only 25%–30% of the energy stored in the hydrocarbon fuel to perform work; the rest of the
stored energy is released in an unusable form as heat. In contrast, gas–electric hybrid engines, now used in several models of automobiles,
deliver approximately 50% greater fuel efficiency. A large electrical generator is highly efficient (approximately 99%) in converting
mechanical to electrical energy, but a typical incandescent light bulb is one of the least efficient devices known (only approximately 5%
of the electrical energy is converted to light). In contrast, a mammalian liver cell is a relatively efficient machine and can use fuels such as
glucose with an efficiency of 30%–50%.
Table 2.7.1 : Approximate Thermodynamic Efficiencies of Various Devices
Device Energy Conversion Approximate Efficiency (%)

large electrical generator mechanical → electrical 99

chemical battery chemical → electrical 90

home furnace chemical → heat 65

small electric tool electrical → mechanical 60

space shuttle engine chemical → mechanical 50

mammalian liver cell chemical → chemical 30–50

spinach leaf cell light → chemical 30

internal combustion engine chemical → mechanical 25–30

fluorescent light electrical → light 20

solar cell light → electricity 10-20

incandescent light bulb electricity → light 5

yeast cell chemical → chemical 2–4

Standard Free-Energy Change

We have seen that there is no way to measure absolute enthalpies, although we can measure changes in enthalpy (ΔH) during a chemical
reaction. Because enthalpy is one of the components of Gibbs free energy, we are consequently unable to measure absolute free energies;
we can measure only changes in free energy. The standard free-energy change (ΔG°) is the change in free energy when one substance or a
set of substances in their standard states is converted to one or more other substances, also in their standard states. The standard free-
energy change can be calculated from the definition of free energy, if the standard enthalpy and entropy changes are known, using
Equation 2.7.10:
ΔG° = ΔH ° − T ΔS° (2.7.10)

If ΔS° and ΔH° for a reaction have the same sign, then the sign of ΔG° depends on the relative magnitudes of the ΔH° and TΔS° terms. It
is important to recognize that a positive value of ΔG° for a reaction does not mean that no products will form if the reactants in their
standard states are mixed; it means only that at equilibrium the concentrations of the products will be less than the concentrations of the
reactants.

A positive ΔG° means that the equilibrium constant is less than 1.

Example 2.7.1
Calculate the standard free-energy change (ΔG ) at 25°C for the reaction
o

H (g) + O (g) ⇌ H O (l)onumber (2.7.11)

2 2 2 2

At 25°C, the standard enthalpy change (ΔH°) is −187.78 kJ/mol, and the absolute entropies of the products and reactants are:
S°(H2O2) = 109.6 J/(mol•K),
S°(O2) = 205.2 J/(mol•K), and
S°(H2) = 130.7 J/(mol•K).
Is the reaction spontaneous as written?
Given: balanced chemical equation, ΔH° and S° for reactants and products

2.7.4 https://chem.libretexts.org/@go/page/204776
Asked for: spontaneity of reaction as written
Strategy:
A. Calculate ΔS° from the absolute molar entropy values given.
B. Use Equation 2.7.10, the calculated value of ΔS°, and other data given to calculate ΔG° for the reaction. Use the value of ΔG° to
determine whether the reaction is spontaneous as written.
SOLUTION
A To calculate ΔG° for the reaction, we need to know ΔH , ΔS , and T . We are given ΔH , and we know that T = 298.15 K. We
o o o

can calculate ΔS° from the absolute molar entropy values provided using the “products minus reactants” rule:
∘ ∘ ∘ ∘
ΔS =S (H2 O2 ) − [ S (O2 ) + S (H2 )]onumber

= [1 mol H2 O2 × 109.6 J/(mol ⋅ K)]onumber

− {[ 1 mol H2 × 130.7 J/(mol ⋅ K)] + [ 1 mol O2 × 205.2 J/(mol ⋅ K)]} onumber

= −226.3 J/K (per mole of H2 O2 )

As we might expect for a reaction in which 2 mol of gas is converted to 1 mol of a much more ordered liquid, ΔS is very negative o

for this reaction.

B Substituting the appropriate quantities into Equation 2.7.10,
∘ ∘ ∘
ΔG = ΔH − T ΔS

= −187.78 kJ/mol − (298.15 K)[−226.3 J/(mol ⋅ K) × 1 kJ/1000 J]onumber

= −187.78 kJ/mol + 67.47 kJ/mol

= −120.31 kJ/molonumber

The negative value of ΔG indicates that the reaction is spontaneous as written. Because ΔS and ΔH for this reaction have the
o o o

same sign, the sign of ΔG depends on the relative magnitudes of the ΔH and T ΔS terms. In this particular case, the enthalpy
o o o

term dominates, indicating that the strength of the bonds formed in the product more than compensates for the unfavorable ΔS term o

and for the energy needed to break bonds in the reactants.

Exercise 2.7.1
Calculate the standard free-energy change (ΔG ) at 25°C for the reaction
o

2 H2 (g) + N2 (g) ⇌ N2 H4 (l)onumber. (2.7.12)

Is the reaction spontaneous as written at 25°C?

Hint
At 25°C, the standard enthalpy change (ΔH ) is 50.6 kJ/mol, and the absolute entropies of the products and reactants are
o

S°(N2H4) = 121.2 J/(mol•K),

S°(N2) = 191.6 J/(mol•K), and
S°(H2) = 130.7 J/(mol•K).

Answer
149.5 kJ/mol
no, not spontaneous
Video Solution

Tabulated values of standard free energies of formation allow chemists to calculate the values of ΔG° for a wide variety of chemical
reactions rather than having to measure them in the laboratory. The standard free energy of formation (ΔG )of a compound is the change
∘
f

in free energy that occurs when 1 mol of a substance in its standard state is formed from the component elements in their standard states.
By definition, the standard free energy of formation of an element in its standard state is zero at 298.15 K. One mole of Cl2 gas at 298.15
K, for example, has ΔG = 0 . The standard free energy of formation of a compound can be calculated from the standard enthalpy of
∘
f

formation (ΔH∘f) and the standard entropy of formation (ΔS∘f) using the definition of free energy:

2.7.5 https://chem.libretexts.org/@go/page/204776
o o o
ΔG = ΔH − T ΔS (2.7.13)
f f f

Using standard free energies of formation to calculate the standard free energy of a reaction is analogous to calculating standard enthalpy
changes from standard enthalpies of formation using the familiar “products minus reactants” rule:
o o o
ΔGrxn = ∑ mΔG (products) − ∑ nΔf (reactants) (2.7.14)
f

where m and n are the stoichiometric coefficients of each product and reactant in the balanced chemical equation. A very large negative
ΔG° indicates a strong tendency for products to form spontaneously from reactants; it does not, however, necessarily indicate that the
reaction will occur rapidly. To make this determination, we need to evaluate the kinetics of the reaction.
The "Products minus Reactants" Rule
The ΔG of a reaction can be calculated from tabulated ΔG∘f values (Table T1) using the “products minus reactants” rule.
o

Example 2.7.2
Calculate ΔG° for the reaction of isooctane with oxygen gas to give carbon dioxide and water (described in Example 7). Use the
following data:
ΔG°f(isooctane) = −353.2 kJ/mol,
ΔG°f(CO2) = −394.4 kJ/mol, and
ΔG°f(H2O) = −237.1 kJ/mol. Is the reaction spontaneous as written?
Given: balanced chemical equation and values of ΔG°f for isooctane, CO2, and H2O
Asked for: spontaneity of reaction as written
Strategy:
Use the “products minus reactants” rule to obtain ΔG∘rxn, remembering that ΔG°f for an element in its standard state is zero. From the
calculated value, determine whether the reaction is spontaneous as written.
SOLUTION
The balanced chemical equation for the reaction is as follows:
25
C H (l) + O (g) → 8 CO (g) + 9 H O(l)onumber (2.7.15)
8 18 2 2 2 2

We are given ΔG∘f values for all the products and reactants except O2(g). Because oxygen gas is an element in its standard state, ΔG∘f
(O2) is zero. Using the “products minus reactants” rule,

∘
25
∘ ∘ ∘ ∘
ΔG = [8ΔG (C O2 ) + 9ΔG (H2 O)] − [1ΔG (C8 H18 ) + ΔG (O2 )] onumber
f f f f
2

= [(8 mol)(−394.4 kJ/mol) + (9 mol)(−237.1 kJ/mol)]onumber

25
− [(1 mol)(−353.2 kJ/mol) + ( mol) (0 kJ/mol)] onumber
2

= −4935.9 kJ (per mol of C8 H18 )onumber

Because ΔG° is a large negative number, there is a strong tendency for the spontaneous formation of products from reactants (though
not necessarily at a rapid rate). Also notice that the magnitude of ΔG° is largely determined by the ΔG∘f of the stable products: water
and carbon dioxide.

Exercise 2.7.2
Calculate ΔG° for the reaction of benzene with hydrogen gas to give cyclohexane using the following data
ΔG∘f(benzene) = 124.5 kJ/mol
ΔG∘f (cyclohexane) = 217.3 kJ/mol.
Is the reaction spontaneous as written?

Answer
92.8 kJ; no
Video Solution

2.7.6 https://chem.libretexts.org/@go/page/204776
Calculated values of ΔG° are extremely useful in predicting whether a reaction will occur spontaneously if the reactants and products are
mixed under standard conditions. We should note, however, that very few reactions are actually carried out under standard conditions, and
calculated values of ΔG° may not tell us whether a given reaction will occur spontaneously under nonstandard conditions. What
determines whether a reaction will occur spontaneously is the free-energy change (ΔG) under the actual experimental conditions, which
are usually different from ΔG°. If the ΔH and TΔS terms for a reaction have the same sign, for example, then it may be possible to reverse
the sign of ΔG by changing the temperature, thereby converting a reaction that is not thermodynamically spontaneous, having Keq < 1, to
one that is, having a Keq > 1, or vice versa. Because ΔH and ΔS usually do not vary greatly with temperature in the absence of a phase
change, we can use tabulated values of ΔH° and ΔS° to calculate ΔG° at various temperatures, as long as no phase change occurs over the
temperature range being considered.

In the absence of a phase change, neither ΔH nor ΔS vary greatly with temperature.

Example 2.7.3
Calculate (a) ΔG° and (b) ΔG300°C for the reaction N2(g)+3H2(g)⇌2NH3(g), assuming that ΔH and ΔS do not change between 25°C
and 300°C. Use these data:
S°(N2) = 191.6 J/(mol•K),
S°(H2) = 130.7 J/(mol•K),
S°(NH3) = 192.8 J/(mol•K), and
ΔH∘f (NH3) = −45.9 kJ/mol.
Given: balanced chemical equation, temperatures, S° values, and ΔH∘f for NH3
Asked for: ΔG° and ΔG at 300°C
Strategy:
A. Convert each temperature to kelvins. Then calculate ΔS° for the reaction. Calculate ΔH° for the reaction, recalling that ΔH∘f for
any element in its standard state is zero.
B. Substitute the appropriate values into Equation 2.7.10 to obtain ΔG° for the reaction.
C. Assuming that ΔH and ΔS are independent of temperature, substitute values into Equation 2.7.2 to obtain ΔG for the reaction at
300°C.
SOLUTION
A To calculate ΔG° for the reaction using Equation 2.7.10, we must know the temperature as well as the values of ΔS° and ΔH°. At
standard conditions, the temperature is 25°C, or 298 K. We can calculate ΔS° for the reaction from the absolute molar entropy values
given for the reactants and the products using the “products minus reactants” rule:
∘ ∘ ∘ ∘
ΔSrxn = 2 S (NH3 ) − [ S (N2 ) + 3 S (H2 )]onumber (2.7.16)

= [ 2 mol NH3 × 192.8 J/(mol ⋅ K)]onumber (2.7.17)

onu
− {[ 1 mol N2 × 191.6 J/(mol ⋅ K)] + [ 3 mol H2 × 130.7 J/(mol ⋅ K)]} onumber (2.7.18)

= −198.1 J/K (per mole of N ) (2.7.19)

We can also calculate ΔH° for the reaction using the “products minus reactants” rule. The value of ΔH∘f (NH3) is given, and ΔH∘f is
zero for both N2 and H2:
∘ ∘ ∘ ∘
ΔHrxn = 2ΔH (NH3 ) − [ΔH (N2 ) + 3ΔH (H2 )]onumber (2.7.20)
f f f

= [2 × (−45.9 kJ/mol)] − [(1 × 0 kJ/mol) + (3 × 0 kJ/mol)]onumber (2.7.21)onu

= −91.8 kJ(per mole of N )onumber (2.7.22)

B Inserting the appropriate values into Equation 2.7.10

∘ ∘ ∘
ΔGrxn = ΔH − T ΔS = (−91.8 kJ) − (298 K)(−198.1 J/K)(1 kJ/1000 J) = (2.7.23)

−32.7 kJ (per mole of N2 )onumber

C To calculate ΔG for this reaction at 300°C, we assume that ΔH and ΔS are independent of temperature (i.e., ΔH300°C = H° and
ΔS300°C = ΔS°) and insert the appropriate temperature (573 K) into Equation 2.7.2:

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ΔG300∘ C = ΔH300∘ C − (573 K)(ΔS300∘ C )

∘ ∘
= ΔH − (573 K)ΔS onumber

= (−91.8 kJ) − (573 K)(−198.1 J/K)(1 kJ/1000 J)

= 21.7 kJ (per mole of N )

In this example, changing the temperature has a major effect on the thermodynamic spontaneity of the reaction. Under standard
conditions, the reaction of nitrogen and hydrogen gas to produce ammonia is thermodynamically spontaneous, but in practice, it is too
slow to be useful industrially. Increasing the temperature in an attempt to make this reaction occur more rapidly also changes the
thermodynamics by causing the −TΔS° term to dominate, and the reaction is no longer spontaneous at high temperatures; that is, its
Keq is less than one. This is a classic example of the conflict encountered in real systems between thermodynamics and kinetics, which
is often unavoidable.

Exercise 2.7.3
Calculate
a. ΔG° and
b. ΔG 750°C

for the following reaction

2 NO(g) + O (g) ⇌ 2 NO (g)onumber (2.7.24)

2 2

which is important in the formation of urban smog. Assume that ΔH and ΔS do not change between 25.0°C and 750°C and use these
data:
S°(NO) = 210.8 J/(mol•K),
S°(O2) = 205.2 J/(mol•K),
S°(NO2) = 240.1 J/(mol•K),
ΔH∘f(NO2) = 33.2 kJ/mol, and
ΔH∘f (NO) = 91.3 kJ/mol.

Answer a
−72.5 kJ/mol of O 2

Answer b
33.8 kJ/mol of O 2

The effect of temperature on the spontaneity of a reaction, which is an important factor in the design of an experiment or an industrial
process, depends on the sign and magnitude of both ΔH° and ΔS°. The temperature at which a given reaction is at equilibrium can be
calculated by setting ΔG° = 0 in Equation 2.7.10, as illustrated in Example 2.7.4.

Example 2.7.4
As you saw in Example 2.7.3, the reaction of nitrogen and hydrogen gas to produce ammonia is one in which ΔH° and ΔS° are both
negative. Such reactions are predicted to be thermodynamically spontaneous at low temperatures but nonspontaneous at high
temperatures. Use the data in Example 9.5.3 to calculate the temperature at which this reaction changes from spontaneous to
nonspontaneous, assuming that ΔH° and ΔS° are independent of temperature.
Given: ΔH° and ΔS°
Asked for: temperature at which reaction changes from spontaneous to nonspontaneous
Strategy:
Set ΔG° equal to zero in Equation 2.7.10 and solve for T, the temperature at which the reaction becomes nonspontaneous.
SOLUTION
In Example 2.7.3, we calculated that ΔH° is −91.8 kJ/mol of N2 and ΔS° is −198.1 J/K per mole of N2, corresponding to ΔG° = −32.7
kJ/mol of N2 at 25°C. Thus the reaction is indeed spontaneous at low temperatures, as expected based on the signs of ΔH° and ΔS°.
The temperature at which the reaction becomes nonspontaneous is found by setting ΔG° equal to zero and rearranging Equation 2.7.10
to solve for T:

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∘ ∘ ∘
ΔG = ΔH − T ΔS =0

∘ ∘
ΔH = T ΔS

∘
ΔH (−91.8 kJ)(1000 J/kJ)
T = = = 463 K
∘
ΔS −198.1 J/K

This is a case in which a chemical engineer is severely limited by thermodynamics. Any attempt to increase the rate of reaction of
nitrogen with hydrogen by increasing the temperature will cause reactants to be favored over products above 463 K.

Exercise 2.7.4
As you found in the exercise in Example 2.7.3, ΔH° and ΔS° are both negative for the reaction of nitric oxide and oxygen to form
nitrogen dioxide. Use those data to calculate the temperature at which this reaction changes from spontaneous to nonspontaneous.

Answer
792.6 K
Video Solution

Summary
The change in Gibbs free energy, which is based solely on changes in state functions, is the criterion for predicting the spontaneity of a
reaction.
Free-energy change:
ΔG = ΔH − T ΔSonumber (2.7.25)

Standard free-energy change:

ΔG° = ΔH ° − T ΔS°onumber (2.7.26)

We can predict whether a reaction will occur spontaneously by combining the entropy, enthalpy, and temperature of a system in a new
state function called Gibbs free energy (G). The change in free energy (ΔG) is the difference between the heat released during a process
and the heat released for the same process occurring in a reversible manner. If a system is at equilibrium, ΔG = 0. If the process is
spontaneous, ΔG < 0. If the process is not spontaneous as written but is spontaneous in the reverse direction, ΔG > 0. At constant
temperature and pressure, ΔG is equal to the maximum amount of work a system can perform on its surroundings while undergoing a
spontaneous change. The standard free-energy change (ΔG°) is the change in free energy when one substance or a set of substances in
their standard states is converted to one or more other substances, also in their standard states. The standard free energy of formation
(ΔG∘f), is the change in free energy that occurs when 1 mol of a substance in its standard state is formed from the component elements in
their standard states. Tabulated values of standard free energies of formation are used to calculate ΔG° for a reaction.

2.7: Gibbs Free Energy (review) is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.

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2.8: Enthalpy Changes in Reactions
Thermodynamics is the study of the relationship between heat (or energy) and work. Enthalpy is a central factor in
thermodynamics. It is the heat content of a system. The heat that passes into or out of the system during a reaction is the enthalpy
change. Whether the enthalpy of the system increases (i.e. when energy is added) or decreases (because energy is given off) is a
crucial factor that determines whether a reaction can happen.

Sometimes, we call the energy of the molecules undergoing change the "internal enthalpy". Sometimes, we call it the "enthalpy of
the system." These two phrases refer to the same thing. Similarly, the energy of the molecules that do not take part in the reaction is
called the "external enthalpy" or the "enthalpy of the surroundings".
Roughly speaking, the energy changes that we looked at in the introduction to thermodynamics were changes in enthalpy. We will
see in the next section that there is another energetic factor, entropy, that we also need to consider in reactions. For now, we will
just look at enthalpy.
Enthalpy is the heat content of a system.
The enthalpy change of a reaction is roughly equivalent to the amount of energy lost or gained during the reaction.
A reaction is favored if the enthalpy of the system decreases over the reaction.
That last statement is a lot like the description of energetics on the previous page. If a system undergoes a reaction and gives off
energy, its own energy content decreases. It has less energy left over if it gave some away. Why does the energy of a set of
molecules change when a reaction occurs? To answer that, we need to think about what happens in a chemical reaction.
In a reaction, there is a change in chemical bonding. Some of the bonds in the reactants are broken, and new bonds are made to
form the products. It costs energy to break bonds, but energy is released when new bonds are made.

Whether a reaction is able to go forward may depend on the balance between these bond-making and bond-breaking steps.

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A reaction is exothermic if more energy is released by formation of new bonds than is consumed by breaking old bonds.
A reaction is exothermic if weaker bonds are traded for stronger ones.
A reaction is endothermic if bond-breaking costs more energy than what is provided in bond-making.

Bond energies (the amount of energy that must be added in order to break a bond) are an important factor in determining whether a
reaction will occur. Bond strengths are not always easy to predict, because the strength of a bond depends on a number of factors.
However, lots of people have done lots of work measuring bond strengths, and they have collected the information in tables, so if
you need to know how strong a bond is, you can just look up the information you need.

Bond Bond Energy (kcal/mol) Bond Bond Energy (kcal/mol)

H-H 104 O-H 111

C-C 83 C-H 99

O=O 119 N-H 93

N=N 226 C=O 180

For example, suppose you wanted to know whether the combustion of methane were an exothermic or endothermic reaction. I am
going to guess that it's exothermic, because this reaction (and others like it) is used to provide heat for lots of homes by burning
natural gas in furnaces.
The "combustion" of methane means that it is burned in air, so that it reacts with oxygen. The products of burning hydrocarbons are
mostly carbon dioxide and water. The carbon atom in methane (CH4) gets incorporated into a carbon dioxide molecule. The
hydrogen atoms get incorporated into water molecules. There are four hydrogen atoms in methane, so that's enough to make two
molecules of H2O.
Four C-H bonds must be broken in the combustion of methane.
Four new O-H bonds are made when the hydrogens from methane are added into new water molecules.
Two new C=O bonds are made when the carbon from methane is added into a CO2 molecule.

2.8.2 https://chem.libretexts.org/@go/page/204777
The other piece of the puzzle is the oxygen source for the reaction. Oxygen is present in the atmosphere mostly as O2. Because we
need two oxygen atoms in the CO2 molecule and two more oxygen atoms for the two water molecules, we need a total of four
oxygen atoms for the reaction, which could be provided by two O2 molecules.
Two O=O bonds must be broken to provide the oxygen atoms for the products.
Altogether, that's four C-H and two O=O bonds broken, plus two C=O and four O-H bonds made. That's 4 x 99 kcal/mol for the C-
H bonds and 2 x 119 kcal/mol for the O=O bonds, a total of 634 kJ/mol added. The reaction releases 2 x 180 kcal/mol for the C=O
bonds and 4 x 111 kcla/mol for the OH bonds, totaling 804 kcal/mol. Overall, there is 170 kcal/mol more released than is
consumed.
That means the reaction is exothermic, so it produces heat. It's probably a good way to heat your home.

Problem TD2.1.
Compare the combustion of ethane to the combustion of methane.
1. Write a reaction for the combustion of ethane, CH3CH3, to carbon dioxide and water.
2. How many carbon dioxide molecules would be produced from one molecule of ethane?
3. How many water molecules would be produced from one molecule of ethane?
4. How many oxygen molecules would be needed to provide oxygen atoms to accomplish the steps in questions (b) and (c)?
5. How much energy is consumed / produced by the reaction? Compare this result to the one for methane.

Problem TD2.2.
The Haber-Bosch process is used to make ammonia for fertilizer. It employs the reaction of hydrogen gas (H2) with atmospheric
nitrogen (N2) in a 3:1 ratio to produce ammonia (NH3).
1. Write a reaction for the Haber-Bosch process.
2. How many ammonia molecules would be produced from one molecule of nitrogen?
3. How much energy is consumed / produced by the reaction?

Contributors
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)

2.8: Enthalpy Changes in Reactions is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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2.9: Entropy Changes in Chemical Reactions
Learning Objectives
To calculate entropy changes for a chemical reaction

We have seen that the energy given off (or absorbed) by a reaction, and monitored by noting the change in temperature of the
surroundings, can be used to determine the enthalpy of a reaction (e.g. by using a calorimeter). Tragically, there is no comparable
easy way to experimentally measure the change in entropy for a reaction. Suppose we know that energy is going into a system (or
coming out of it), and yet we do not observe any change in temperature. What is going on in such a situation? Changes in internal
energy, that are not accompanied by a temperature change, might reflect changes in the entropy of the system.
For example, consider water at °0C at 1 atm pressure
This is the temperature and pressure condition where liquid and solid phases of water are in equilibrium (also known as the
melting point of ice)
H O(s) → H O(l) (2.9.1)
2 2

At such a temperature and pressure we have a situation (by definition) where we have some ice and some liquid water
If a small amount of energy is input into the system the equilibrium will shift slightly to the right (i.e. in favor of the liquid
state)
Likewise if a small amount of energy is withdrawn from the system, the equilibrium will shift to the left (more ice)

However, in both of the above situations, the energy change is not accompanied by a
change in temperature (the temperature will not change until we no longer have an
equilibrium condition; i.e. all the ice has melted or all the liquid has frozen)
Since the quantitative term that relates the amount of heat energy input vs. the rise in temperature is the heat capacity, it would
seem that in some way, information about the heat capacity (and how it changes with temperature) would allow us to determine the
entropy change in a system. In fact, values for the "standard molar entropy" of a substance have units of J/mol K, the same units as
for molar heat capacity.

Standard Molar Entropy, S0

The entropy of a substance has an absolute value of 0 entropy at 0 K.
Standard molar entropies are listed for a reference temperature (like 298 K) and 1 atm pressure (i.e. the entropy of a pure
substance at 298 K and 1 atm pressure). A table of standard molar entropies at 0K would be pretty useless because it would be 0
for every substance (duh!) Standard molar entropy values are listed for a variety of substances in Table T2.
When comparing standard molar entropies for a substance that is either a solid, liquid or gas at 298 K and 1 atm pressure, the
gas will have more entropy than the liquid, and the liquid will have more entropy than the solid
Unlike enthalpies of formation, standard molar entropies of elements are not 0.
The entropy change in a chemical reaction is given by the sum of the entropies of the products minus the sum of the entropies of
the reactants. As with other calculations related to balanced equations, the coefficients of each component must be taken into
account in the entropy calculation (the n, and m, terms below are there to indicate that the coefficients must be accounted for):
0 0 0
ΔS = ∑ nS (products) − ∑ m S (reactants) (2.9.2)

n m

Example 2.9.1 : Haber Process

Calculate the change in entropy associated with the Haber process for the production of ammonia from nitrogen and hydrogen
gas.

N (g) + 3 H (g) ⇌ 2 NH (g)

2 2 3

At 298K as a standard temperature:

S0(NH3) = 192.5 J/mol K

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S0(H2) = 130.6 J/mol K
S0(N2) = 191.5 J/mol K
Solution
From the balanced equation we can write the equation for ΔS0 (the change in the standard molar entropy for the reaction):
ΔS0 = 2*S0(NH3) - [S0(N2) + (3*S0(H2))]
ΔS0 = 2*192.5 - [191.5 + (3*130.6)]
ΔS0 = -198.3 J/mol K
It would appear that the process results in a decrease in entropy - i.e. a decrease in disorder. This is expected because we are
decreasing the number of gas molecules. In other words the N2(g) used to float around independently of the H2 gas molecules.
After the reaction, the two are bonded together and can't float around freely from one another. (I guess you can consider
marriage as a negative entropy process!)

To calculate ΔS° for a chemical reaction from standard molar entropies, we use the familiar “products minus reactants” rule, in
which the absolute entropy of each reactant and product is multiplied by its stoichiometric coefficient in the balanced chemical
equation. Example 2.9.2 illustrates this procedure for the combustion of the liquid hydrocarbon isooctane (C8H18; 2,2,4-
trimethylpentane).

ΔS° for a reaction can be calculated from absolute entropy values using the same “products minus reactants” rule used to
calculate ΔH°.

Example 2.9.2 : Combustion of Octane

Use the data in Table T2 to calculate ΔS° for the combustion reaction of liquid isooctane with O2(g) to give CO2(g) and H2O(g)
at 298 K.
Given: standard molar entropies, reactants, and products
Asked for: ΔS°
Strategy:
Write the balanced chemical equation for the reaction and identify the appropriate quantities in Table T2. Subtract the sum of the
absolute entropies of the reactants from the sum of the absolute entropies of the products, each multiplied by their appropriate
stoichiometric coefficients, to obtain ΔS° for the reaction.
Solution:
The balanced chemical equation for the complete combustion of isooctane (C8H18) is as follows:
25
C H (l) + O (g) → 8 CO (g) + 9 H O(g)
8 18 2 2 2 2

We calculate ΔS° for the reaction using the “products minus reactants” rule, where m and n are the stoichiometric coefficients of
each product and each reactant:
∘ ∘ ∘
ΔSrxn = ∑ m S (products) − ∑ nS (reactants)

∘ ∘ ∘
25 ∘
= [8 S (C O2 ) + 9 S (H2 O)] − [ S (C8 H18 ) + S (O2 )]
2

= {[8 mol C O2 × 213.8 J/(mol ⋅ K)] + [9 mol H2 O × 188.8 J/(mol ⋅ K)]}

25
− {[1 mol C8 H18 × 329.3 J/(mol ⋅ K)] + [ mol O2 × 205.2 J/(mol ⋅ K)]}
2

= 515.3 J/K

ΔS° is positive, as expected for a combustion reaction in which one large hydrocarbon molecule is converted to many molecules
of gaseous products.

Exercise 2.9.2

2.9.2 https://chem.libretexts.org/@go/page/204778
Use the data in Table T2 to calculate ΔS° for the reaction of H2(g) with liquid benzene (C6H6) to give cyclohexane (C6H12).

Answer
−361.1 J/K

2.9: Entropy Changes in Chemical Reactions is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by
LibreTexts.

2.9.3 https://chem.libretexts.org/@go/page/204778
2.10: Activation Energy and Rate
 Learning Objectives
To understand why and how chemical reactions occur.

It is possible to use kinetics studies of a chemical system, such as the effect of changes in reactant concentrations, to deduce events
that occur on a microscopic scale, such as collisions between individual particles. Such studies have led to the collision model of
chemical kinetics, which is a useful tool for understanding the behavior of reacting chemical species. The collision model explains
why chemical reactions often occur more rapidly at higher temperatures. For example, the reaction rates of many reactions that
occur at room temperature approximately double with a temperature increase of only 10°C. In this section, we will use the collision
model to analyze this relationship between temperature and reaction rates. Before delving into the relationship between temperature
and reaction rate, we must discuss three microscopic factors that influence the observed macroscopic reaction rates.

Microscopic Factor 1: Collisional Frequency

Central to collision model is that a chemical reaction can occur only when the reactant molecules, atoms, or ions collide. Hence, the
observed rate is influence by the frequency of collisions between the reactants. The collisional frequency is the average rate in
which two reactants collide for a given system and is used to express the average number of collisions per unit of time in a defined
system. While deriving the collisional frequency (Z ) between two species in a gas is straightforward, it is beyond the scope of
AB

this text and the equation for collisional frequency of A and B is the following:
−−−−−−
2
8π kB T
ZAB = NA NB (rA + rB ) √ (2.10.1)
μAB

with
NA and N are the numbers of A and B molecules in the system, respectively
B

ra and r are the radii of molecule A and B , respectively

kB is the Boltzmann constant k = 1.380 x 10-23 Joules Kelvin

T is the temperature in Kelvin

mA mB
μAB is calculated via μ =
AB mA +mB

The specifics of Equation 2.10.1 are not important for this conversation, but it is important to identify that Z increases with
AB

increasing density (i.e., increasing N and N ), with increasing reactant size (r and r ), with increasing velocities (predicted via
A B a b

Kinetic Molecular Theory), and with increasing temperature (although weakly because of the square root function).

Collision Theory of Kinetics

A Video Discussing Collision Theory of Kinetics: Collusion Theory of Kinetics (opens in new window) [youtu.be]

2.10.1 https://chem.libretexts.org/@go/page/204779
Microscopic Factor 2: Activation Energy
Previously, we discussed the kinetic molecular theory of gases, which showed that the average kinetic energy of the particles of a
gas increases with increasing temperature. Because the speed of a particle is proportional to the square root of its kinetic energy,
increasing the temperature will also increase the number of collisions between molecules per unit time. What the kinetic molecular
theory of gases does not explain is why the reaction rate of most reactions approximately doubles with a 10°C temperature
increase. This result is surprisingly large considering that a 10°C increase in the temperature of a gas from 300 K to 310 K
increases the kinetic energy of the particles by only about 4%, leading to an increase in molecular speed of only about 2% and a
correspondingly small increase in the number of bimolecular collisions per unit time.
The collision model of chemical kinetics explains this behavior by introducing the concept of activation energy (E ). We will a

define this concept using the reaction of NO with ozone, which plays an important role in the depletion of ozone in the ozone
layer:

NO(g) + O (g) → NO (g) + O (g)

3 2 2

Increasing the temperature from 200 K to 350 K causes the rate constant for this particular reaction to increase by a factor of more
than 10, whereas the increase in the frequency of bimolecular collisions over this temperature range is only 30%. Thus something
other than an increase in the collision rate must be affecting the reaction rate.
Experimental rate law for this reaction is

rate = k[NO][ O ]
3

and is used to identify how the reaction rate (not the rate constant) vares with concentration. The rate constant, however, does vary
with temperature. Figure 2.10.1 shows a plot of the rate constant of the reaction of NO with O at various temperatures. The
3

relationship is not linear but instead resembles the relationships seen in graphs of vapor pressure versus temperature (e.g, the
Clausius-Claperyon equation). In all three cases, the shape of the plots results from a distribution of kinetic energy over a
population of particles (electrons in the case of conductivity; molecules in the case of vapor pressure; and molecules, atoms, or ions
in the case of reaction rates). Only a fraction of the particles have sufficient energy to overcome an energy barrier.

Figure 2.10.1 : Rate Constant versus Temperature for the Reaction of NO with O The nonlinear shape of the curve is caused by a
3

distribution of kinetic energy over a population of molecules. Only a fraction of the particles have enough energy to overcome an
energy barrier, but as the temperature is increased, the size of that fraction increases. (CC BY-SA-NC; anonymous)
In the case of vapor pressure, particles must overcome an energy barrier to escape from the liquid phase to the gas phase. This
barrier corresponds to the energy of the intermolecular forces that hold the molecules together in the liquid. In conductivity, the
barrier is the energy gap between the filled and empty bands. In chemical reactions, the energy barrier corresponds to the amount of
energy the particles must have to react when they collide. This energy threshold, called the activation energy, was first postulated
in 1888 by the Swedish chemist Svante Arrhenius (1859–1927; Nobel Prize in Chemistry 1903). It is the minimum amount of
energy needed for a reaction to occur. Reacting molecules must have enough energy to overcome electrostatic repulsion, and a
minimum amount of energy is required to break chemical bonds so that new ones may be formed. Molecules that collide with less
than the threshold energy bounce off one another chemically unchanged, with only their direction of travel and their speed altered
by the collision. Molecules that are able to overcome the energy barrier are able to react and form an arrangement of atoms called
the activated complex or the transition state of the reaction. The activated complex is not a reaction intermediate; it does not last
long enough to be detected readily.

2.10.2 https://chem.libretexts.org/@go/page/204779
Any phenomenon that depends on the distribution of thermal energy in a population of
particles has a nonlinear temperature dependence.
We can graph the energy of a reaction by plotting the potential energy of the system as the reaction progresses. Figure 2.10.2 shows
a plot for the NO–O3 system, in which the vertical axis is potential energy and the horizontal axis is the reaction coordinate, which
indicates the progress of the reaction with time. The activated complex is shown in brackets with an asterisk. The overall change in
potential energy for the reaction (ΔE) is negative, which means that the reaction releases energy. (In this case, ΔE is −200.8
kJ/mol.) To react, however, the molecules must overcome the energy barrier to reaction (E is 9.6 kJ/mol). That is, 9.6 kJ/mol must
a

be put into the system as the activation energy. Below this threshold, the particles do not have enough energy for the reaction to
occur.

Figure 2.10.2 : Energy of the Activated Complex for the NO–O3 System. The diagram shows how the energy of this system varies
as the reaction proceeds from reactants to products. Note the initial increase in energy required to form the activated complex. (CC
BY-SA-NC; anonymous)
Figure 2.10.3a illustrates the general situation in which the products have a lower potential energy than the reactants. In contrast,
Figure 2.10.3b illustrates the case in which the products have a higher potential energy than the reactants, so the overall reaction
requires an input of energy; that is, it is energetically uphill, and $ΔE > 0$. Although the energy changes that result from a reaction
can be positive, negative, or even zero, in most cases an energy barrier must be overcome before a reaction can occur. This means
that the activation energy is almost always positive; there is a class of reactions called barrierless reactions, but those are discussed
elsewhere.

Figure 2.10.3 : Differentiating between E and ΔE. The potential energy diagrams for a reaction with (a) ΔE < 0 and (b) ΔE > 0
a

illustrate the change in the potential energy of the system as reactants are converted to products. In both cases, E is positive. For a
a

reaction such as the one shown in (b), Ea must be greater than ΔE. (CC BY-SA-NC; anonymous)

For similar reactions under comparable conditions, the one with the smallest Ea will
occur most rapidly.
Whereas ΔE is related to the tendency of a reaction to occur spontaneously, E gives us information about the reaction rate and
a

how rapidly the reaction rate changes with temperature. For two similar reactions under comparable conditions, the reaction with

2.10.3 https://chem.libretexts.org/@go/page/204779
the smallest E will occur more rapidly.
a

Figure 2.10.4 shows both the kinetic energy distributions and a potential energy diagram for a reaction. The shaded areas show that
at the lower temperature (300 K), only a small fraction of molecules collide with kinetic energy greater than Ea; however, at the
higher temperature (500 K) a much larger fraction of molecules collide with kinetic energy greater than Ea. Consequently, the
reaction rate is much slower at the lower temperature because only a relatively few molecules collide with enough energy to
overcome the potential energy barrier.

Figure 2.10.4 : Surmounting the Energy Barrier to a Reaction. This chart juxtaposes the energy distributions of lower-temperature
(300 K) and higher-temperature (500 K) samples of a gas against the potential energy diagram for a reaction. Only those molecules
in the shaded region of the energy distribution curve have E > E and are therefore able to cross the energy barrier separating
a

reactants and products. The fraction of molecules with E > E is much greater at 500 K than at 300 K, so the reaction will occur
a

much more rapidly at 500 K. (CC BY-SA-NC; anonymous)

Energy is on the y axis while reaction coordinate and fraction of molecules with a particular kinetic energy E are on the x axis.

Transition State Theory

Video Discussing Transition State Theory: Transition State Theory(opens in new window) [youtu.be]

Microscopic Factor 3: Sterics

Even when the energy of collisions between two reactant species is greater than E , most collisions do not produce a reaction. The
a

probability of a reaction occurring depends not only on the collision energy but also on the spatial orientation of the molecules
when they collide. For NO and O to produce NO and O , a terminal oxygen atom of O must collide with the nitrogen atom of
3 2 2 3

NO at an angle that allows O to transfer an oxygen atom to NO to produce NO (Figure 2.10.4). All other collisions produce no
3 2

reaction. Because fewer than 1% of all possible orientations of NO and O result in a reaction at kinetic energies greater than E ,
3 a

most collisions of NO and O are unproductive. The fraction of orientations that result in a reaction is called the steric factor (ρ)
3

and its value can range from ρ = 0 (no orientations of molecules result in reaction) to ρ = 1 (all orientations result in reaction).

2.10.4 https://chem.libretexts.org/@go/page/204779
Figure 2.10.4 : The Effect of Molecular Orientation on the Reaction of NO and O . Most collisions of NO and O molecules occur
3 3

with an incorrect orientation for a reaction to occur. Only those collisions in which the N atom of NO collides with one of the
terminal O atoms of O are likely to produce NO and O , even if the molecules collide with E > E . (CC BY-SA-NC;
3 2 2 a

anonymous)

Macroscopic Behavior: The Arrhenius Equation

The collision model explains why most collisions between molecules do not result in a chemical reaction. For example, nitrogen
and oxygen molecules in a single liter of air at room temperature and 1 atm of pressure collide about 1030 times per second. If
every collision produced two molecules of NO, the atmosphere would have been converted to NO and then NO a long time ago. 2

Instead, in most collisions, the molecules simply bounce off one another without reacting, much as marbles bounce off each other
when they collide.
For an A + B elementary reaction, all three microscopic factors discussed above that affect the reaction rate can be summarized in
a single relationship:

rate = (collision frequency) × (steric factor) × (fraction of collisions with E > Ea )

where
rate = k[A][B] (2.10.2)

Arrhenius used these relationships to arrive at an equation that relates the magnitude of the rate constant for a reaction to the
temperature, the activation energy, and the constant, A , called the frequency factor:
−Ea /RT
k = Ae (2.10.3)

The frequency factor is used to convert concentrations to collisions per second (scaled by the steric factor). Because the frequency
of collisions depends on the temperature, A is actually not constant (Equation 2.10.1). Instead, A increases slightly with
temperature as the increased kinetic energy of molecules at higher temperatures causes them to move slightly faster and thus
undergo more collisions per unit time.
Equation 2.10.3 is known as the Arrhenius equation and summarizes the collision model of chemical kinetics, where T is the
absolute temperature (in K) and R is the ideal gas constant [8.314 J/(K·mol)]. E indicates the sensitivity of the reaction to changes
a

in temperature. The reaction rate with a large E increases rapidly with increasing temperature, whereas the reaction rate with a
a

smaller E increases much more slowly with increasing temperature.

If we know the reaction rate at various temperatures, we can use the Arrhenius equation to calculate the activation energy. Taking
the natural logarithm of both sides of Equation 2.10.3,
Ea
ln k = ln A + (− ) (2.10.4)
RT

Ea 1
= ln A + [(− )( )] (2.10.5)
R T

Equation 2.10.5 is the equation of a straight line,

y = mx + b

2.10.5 https://chem.libretexts.org/@go/page/204779
where y = ln k and x = 1/T . This means that a plot of ln k versus 1/T is a straight line with a slope of −E a /R and an intercept
of ln A . In fact, we need to measure the reaction rate at only two temperatures to estimate E .
a

Knowing the E at one temperature allows us to predict the reaction rate at other temperatures. This is important in cooking and
a

food preservation, for example, as well as in controlling industrial reactions to prevent potential disasters. The procedure for
determining E from reaction rates measured at several temperatures is illustrated in Example 2.10.1.
a

The Arrhenius Equation

A Video Discussing The Arrhenius Equation: The Arrhenius Equation(opens in new window) [youtu.be]

 Example 2.10.1: Chirping Tree Crickets

Many people believe that the rate of a tree cricket’s chirping is related to temperature. To see whether this is true, biologists
have carried out accurate measurements of the rate of tree cricket chirping (f ) as a function of temperature (T ). Use the data in
the following table, along with the graph of ln[chirping rate] versus 1/T to calculate E for the biochemical reaction that
a

controls cricket chirping. Then predict the chirping rate on a very hot evening, when the temperature is 308 K (35°C, or 95°F).
Chirping Tree Crickets Frequency Table
Frequency (f; chirps/min) ln f T (K) 1/T (K)

200 5.30 299 3.34 × 10−3

179 5.19 298 3.36 × 10−3

158 5.06 296 3.38 × 10−3

141 4.95 294 3.40 × 10−3

126 4.84 293 3.41 × 10−3

112 4.72 292 3.42 × 10−3

100 4.61 290 3.45 × 10−3

89 4.49 289 3.46 × 10−3

79 4.37 287 3.48 × 10−3

Given: chirping rate at various temperatures

Asked for: activation energy and chirping rate at specified temperature

Strategy:
A. From the plot of ln f versus 1/T , calculate the slope of the line (−Ea/R) and then solve for the activation energy.
B. Express Equation 2.10.5 in terms of k1 and T1 and then in terms of k2 and T2.
C. Subtract the two equations; rearrange the result to describe k2/k1 in terms of T2 and T1.

2.10.6 https://chem.libretexts.org/@go/page/204779
D. Using measured data from the table, solve the equation to obtain the ratio k2/k1. Using the value listed in the table for k1,
solve for k2.

Solution
A If cricket chirping is controlled by a reaction that obeys the Arrhenius equation, then a plot of ln f versus 1/T should give a
straight line (Figure 2.10.6).

Figure 2.10.6 : Graphical Determination of E for Tree Cricket Chirping. When the natural logarithm of the rate of tree cricket
a

chirping is plotted versus 1/T, a straight line results. The slope of the line suggests that the chirping rate is controlled by a
single reaction with an E of 55 kJ/mol. (CC BY-SA-NC; anonymous)
a

Also, the slope of the plot of ln f versus 1/T should be equal to −Ea /R . We can use the two endpoints in Figure 2.10.6 to
estimate the slope:
Δ ln f
slope =
Δ(1/T )

5.30 − 4.37
=
−3 −1 −3 −1
3.34 × 10 K − 3.48 × 10 K

0.93
=
−3 −1
−0.14 × 10 K

3
= −6.6 × 10 K

A computer best-fit line through all the points has a slope of −6.67 × 103 K, so our estimate is very close. We now use it to
solve for the activation energy:
Ea = −(slope)(R)

8.314 J 1 KJ
3
= −(−6.6 × 10 K) ( )( )
K ⋅ mol 1000 J

55 kJ
=
mol

B If the activation energy of a reaction and the rate constant at one temperature are known, then we can calculate the reaction
rate at any other temperature. We can use Equation 2.10.5 to express the known rate constant (k ) at the first temperature (T )
1 1

as follows:
Ea
ln k1 = ln A −
RT1

Similarly, we can express the unknown rate constant (k ) at the second temperature (T ) as follows:
2 2

Ea
ln k2 = ln A −
RT2

2.10.7 https://chem.libretexts.org/@go/page/204779
C These two equations contain four known quantities (Ea, T1, T2, and k1) and two unknowns (A and k2). We can eliminate A by
subtracting the first equation from the second:
Ea Ea
ln k2 − ln k1 = (ln A − ) − (ln A − )
RT2 RT1

Ea Ea
=− +
RT2 RT1

Then
k2 Ea 1 1
ln = ( − )
k1 R T1 T2

D To obtain the best prediction of chirping rate at 308 K (T2), we try to choose for T1 and k1 the measured rate constant and
corresponding temperature in the data table that is closest to the best-fit line in the graph. Choosing data for T1 = 296 K, where
f = 158, and using the E calculated previously,
a

kT Ea 1 1
2
ln = ( − )
kT R T1 T2
1

55 kJ/mol 1000 J 1 1
= ( )( − )
8.314 J/(K ⋅ mol) 1 kJ 296 K 308 K

= 0.87

Thus k308/k296 = 2.4 and k308 = (2.4)(158) = 380, and the chirping rate on a night when the temperature is 308 K is predicted to
be 380 chirps per minute.

 Exercise 2.10.1A

The equation for the decomposition of NO to NO and O is second order in NO :

2 2 2

2 NO (g) → 2 NO(g) + O (g)

2 2

Data for the reaction rate as a function of temperature are listed in the following table. Calculate Ea for the reaction and the
rate constant at 700 K.
Data for the reaction rate as a function of temperature
T (K) k (M−1·s−1)

592 522

603 755

627 1700

652 4020

656 5030

Answer
Ea = 114 kJ/mol; k700= 18,600 M−1·s−1 = 1.86 × 104 M−1·s−1.

 Exercise 2.10.1B
What E results in a doubling of the reaction rate with a 10°C increase in temperature from 20° to 30°C?
a

Answer
about 51 kJ/mol

2.10.8 https://chem.libretexts.org/@go/page/204779
Graphing Using the Arrhenius Equation

A Video Discussing Graphing Using the Arrhenius Equation: Graphing Using the Arrhenius Equation (opens in new window)
[youtu.be] (opens in new window)

Summary
For a chemical reaction to occur, an energy threshold must be overcome, and the reacting species must also have the correct spatial
orientation. The Arrhenius equation is k = Ae −Ea /RT
. A minimum energy (activation energy,vE ) is required for a collision
a

between molecules to result in a chemical reaction. Plots of potential energy for a system versus the reaction coordinate show an
energy barrier that must be overcome for the reaction to occur. The arrangement of atoms at the highest point of this barrier is the
activated complex, or transition state, of the reaction. At a given temperature, the higher the Ea, the slower the reaction. The
fraction of orientations that result in a reaction is the steric factor. The frequency factor, steric factor, and activation energy are
related to the rate constant in the Arrhenius equation: k = Ae −Ea /RT
. A plot of the natural logarithm of k versus 1/T is a straight
line with a slope of −Ea/R.

2.10: Activation Energy and Rate is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.
14.5: Temperature and Rate is licensed CC BY-NC-SA 3.0.

2.10.9 https://chem.libretexts.org/@go/page/204779
CHAPTER OVERVIEW

3: Acids, Bases, and Arrow Pushing

3: Acids, Bases, and Arrow Pushing is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
3.1: Acids and Bases - The Brønsted-Lowry Definition
 Objectives

After completing this section, you should be able to

1. state the Brønsted-Lowry definition of an acid and a base.
2. identify the Brønsted-Lowry acid and base in a given acid-base reaction.
3. identify the conjugate base of an acid and identify the conjugate acid of a base.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
Brønsted-Lowry acid
Brønsted-Lowry base
conjugate acid
conjugate base

 Study Notes

You should already be familiar with the Brønsted-Lowry concept of acidity and the differences between strong and weak acids.
You may wish to review this topic before proceeding.

In 1923, chemists Johannes Brønsted and Martin Lowry independently developed definitions of acids and bases based on
compounds abilities to either donate or accept protons (H+ ions). Here, acids are defined as being able to donate protons in the form
of hydrogen ions; whereas bases are defined as being able to accept protons. This took the Arrhenius definition one step further as
water is no longer required to be present in the solution for acid and base reactions to occur.

Brønsted-Lowry Definition
J.N. Brønsted and T.M. Lowry independently developed the theory of proton donors and proton acceptors in acid-base reactions,
coincidentally in the same region and during the same year. The Arrhenius theory where acids and bases are defined by whether the
molecule produces hydrogen ion or hydroxide ion when dissolved in water was too limiting, because not all chemical reactions,
especially organic reactions, occur in water. The Brønsted-Lowry Theory defines an acid a proton donor, while a base is a proton
acceptor. This is illustrated in the following reactions:
+ −
H C l + H OH → H3 O + Cl

+ −
H OH + N H3 → N H + OH
4

Acid Base

Donates hydrogen ions Accepts hydrogen ions.

HCl HOH → H3O+ + Cl−

HOH NH3→ NH4+ + −OH

The determination of a substance as a Brønsted-Lowry acid or base can only be done by examining the reaction, since many
chemicals can be either an acid or a base. For example, HOH is a base in the first reaction and an acid in the second reaction.
Bronsted-Lowry Acids and Bases

3.1.1 https://chem.libretexts.org/@go/page/205312
HCO3 + HOH H2CO3 + OH

base acid

HCO3 + HOH H2CO3 + OH

conjugate conjugate
acid base

To determine whether a substance is an acid or a base, count the hydrogens on each substance before and after the reaction. If the
number of hydrogens has decreased, then that substance is the acid (donates hydrogen ions). If the number of hydrogens has
increased, then that substance is the base (accepts hydrogen ions). These definitions are normally applied to the reactants on the
left. If the reaction is viewed in reverse a new acid and base can be identified. The substances on the right side of the equation are
called the conjugate acid and conjugate base compared to those on the left. Also note that an acid turns into a conjugate base, and
the base turns into the conjugate acid after the reaction is over.

Conjugate Acid–Base Pairs

In aqueous solutions, acids and bases can be defined in terms of the transfer of a proton from an acid to a base. Thus for every
acidic species in an aqueous solution, there exists a species derived from the acid by the loss of a proton. These two species that
differ by only a proton constitute a conjugate acid–base pair. For example, in the reaction of HCl with water shown below, HCl ,
the parent acid, donates a proton to a water molecule, the parent base, thereby forming Cl-. Thus HCl and Cl- constitute a conjugate
acid–base pair. By convention, we always write a conjugate acid–base pair as the acid followed by its conjugate base. In the reverse
reaction, the Cl- ion in solution acts as a base to accept a proton from H3O+, forming H2O and HCl. Thus H3O+ and H2O constitute
a second conjugate acid–base pair. In general, any acid–base reaction must contain two conjugate acid–base pairs, which in this
case are HCl/Cl- and H3O+/H2O.

proton gained proton lost

H
H Cl + O H O H + Cl
H H

HCl(aq) H2O(l) H3O (aq) Cl (aq)

parent acid parent base conjugate acid conjugate base

All acid–base reactions contain two conjugate acid–base pairs.

Similarly, in the reaction of acetic acid with water, acetic acid donates a proton to water, which acts as the base. In the reverse
reaction, H3O+ is the acid that donates a proton to the acetate ion, which acts as the base. Once again, we have two conjugate acid–
base pairs: the parent acid and its conjugate base (CH3CO2H/CH3CO2-) and the parent base and its conjugate acid (H3O+/H2O).

proton gained proton lost

O H O
C H+ O H O H + C
H3C O H H H3C O

CH3CO2H(aq) H2O(l) H3O (aq) CH3CO2 (aq)

parent acid parent base conjugate acid conjugate base

In the reaction of ammonia with water to give ammonium ions and hydroxide ions, ammonia acts as a base by accepting a proton
from a water molecule, which in this case means that water is acting as an acid. In the reverse reaction, an ammonium ion acts as an
acid by donating a proton to a hydroxide ion, and the hydroxide ion acts as a base. The conjugate acid–base pairs for this reaction
are NH4+/NH3 and H2O/OH-.

3.1.2 https://chem.libretexts.org/@go/page/205312
proton gained proton lost

H
+ O H N H + O
N H
H H H H H
H
NH3(aq) H2O(l) NH4 (aq) OH(aq)
parent base parent acid conjugate acid conjugate base

 Example 3.1.1

Aniline (C6H5NH2) is slightly soluble in water. It has a nitrogen atom that can accept a hydrogen ion from a water molecule
just like the nitrogen atom in ammonia does. Write the chemical equation for this reaction and identify the Brønsted-Lowry
acid and base.

Solution
C6H5NH2 and H2O are the reactants. When C6H5NH2 accepts a proton from H2O, it gains an extra H and a positive charge and
leaves an OH− ion behind. The reaction is as follows:
+ −
C H NH (aq) + H O(ℓ) −
↽⇀
− C H NH (aq) + OH (aq)
6 5 2 2 6 5 3

Because C6H5NH2 accepts a proton, it is the Brønsted-Lowry base. The H2O molecule, because it donates a proton, is the
Brønsted-Lowry acid.

 Example 3.1.1

Identify the conjugate acid-base pairs in this equilibrium.

+ −
(C H3 )3 N + H2 O ⇌ (C H3 )3 N H + OH

Solution
One pair is H2O and OH−, where H2O has one more H+ and is the conjugate acid, while OH− has one less H+ and is the
conjugate base.
The other pair consists of (CH3)3N and (CH3)3NH+, where (CH3)3NH+ is the conjugate acid (it has an additional proton) and
(CH3)3N is the conjugate base.

Some common conjugate acid–base pairs are shown in Figure 2.7.1. The strongest acids are at the bottom left, and the strongest
bases are at the top right. The conjugate base of a strong acid is a very weak base, and, conversely, the conjugate acid of a strong
base is a very weak acid.
Figure 2.7.1 The Relative Strengths of Some Common Conjugate Acid–Base Pairs

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Exercises
1. Identify the Brønsted-Lowry acids and bases in the reactions given below.
a. C H 3C H 2 O
−
+ H 2O <=> C H 3C H 2OH + OH
−

b. C H 3C H 2OH + H 2SO4 <=> C H 3C H 2OH 2 + +H SO4−

2. Show the structures of species X and Y in the following acid-base reactions:

Answer:
1. a.

2. a)

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Questions
Q2.7.1
Is the following molecule a Brønsted acid or base?
HSO4−
Solutions
S2.7.1
It can be both, consider the following schemes:

3.1: Acids and Bases - The Brønsted-Lowry Definition is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.
2.7: Acids and Bases - The Brønsted-Lowry Definition by Dietmar Kennepohl, Krista Cunningham, Steven Farmer, Tim Soderberg is
licensed CC BY-SA 4.0.

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3.2: Acids and Bases - The Lewis Definition
 Objectives

After completing this section, you should be able to

1. state the Lewis definition of an acid and a base.
2. identify a given compound as being a Lewis acid or Lewis base, given its Lewis structure or its Kekulé structure.
3. identify an organic molecule or ion in a reaction as either an electrophile or nucleophile.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
Lewis acid
Lewis base
Electrophile
Nucleophile

 Study Notes

The Lewis concept of acidity and basicity will be of great use to you when you study reaction mechanisms. The realization that
an ion such as
H
C
H H

is electron deficient, and is therefore a Lewis acid, should help you understand why this ion reacts with substances which are
Lewis bases (e.g., H2O).

Introduction to Lewis Acid-Base Theory

The Brønsted acid-base theory has been used throughout the history of acid and base chemistry. However, this theory is very
restrictive and focuses primarily on acids and bases acting as proton donors and acceptors. Sometimes conditions arise where the
theory doesn't necessarily fit, such as in solids and gases. In 1923, G.N. Lewis from UC Berkeley proposed an alternate theory to
describe acids and bases. His theory gave a generalized explanation of acids and bases based on structure and bonding. Through the
use of the Lewis definition of acids and bases, chemists are now able to predict a wider variety of acid-base reactions. Lewis'
theory used electrons instead of proton transfer and specifically stated that an acid is a species that accepts an electron pair while a
base donates an electron pair.
2+
Mg
O Mg
O
C C
R R R R

Example of Lewis base (oxygen atom from carbonyl) reacting with Lewis Acid (Mg2+ ion).
The reaction of a Lewis acid and a Lewis base will produce a coordinate covalent bond. A coordinate covalent bond is just a type
of covalent bond in which one reactant donates both electrons to form the bond. In this case the Lewis base donates its electrons to
form a bond to the Lewis acid. The resulting product is called an addition compound, or more commonly a complex. The electron-
pair flow from Lewis base to Lewis acid is shown using curved arrows much like those used for resonance structures in Section
2.5. Curved arrows always mean that an electron pair moves from the atom at the tail of the arrow to the atom at the head of the
arrow. In this case the lone pair on the Lewis base attacks the Lewis acid forming a bond. This new type of electron pair movement,
along with those described in Section 2.5 will be used throughout this text to describe electron flow during reactions.
Lewis Acid: a species that accepts an electron pair and will typically either have vacant orbitals or a polar bond involving
hydrogen such that it can donate H+ (which has an empty 1s orbital)
Lewis Base: a species that donates an electron pair and will have lone-pair electrons of pi bonding electrons.

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Lewis Acids
Neutral compounds of boron, aluminum, and the other Group 13 elements, (BF3, AlCl3), which possess only six valence electrons,
have a very strong tendency to gain an additional electron pair. Because these compounds are only surrounded by three electron
groups, they are sp2 hybridized, contained a vacant p orbital, and are potent Lewis acids. Trimethylamine's lone pair elections are
contained in an sp3 hybrid orbital making it a Lewis base. These two orbitals overlap, creating a covalent bond in a boron
trifluoride-trimethylamine complex. The movement of electrons during this interaction is show by by an arrow.

H 3C F F H3C F
+ B H3C N B F
N
H 3C CH3 F H3C F

Positive ions are often Lewis acids because they have an electrostatic attraction for electron donors. Examples include alkali and
alkaline earth metals in the group IA and IIA columns. K+, Mg2+ and Ca2+ are sometimes seen as Lewis acidic sites in biology, for
example. These ions are very stable forms of these elements because of their low electron ionization potentials. However, their
positive charges do attract electron donors.The interaction between a magnesium cation (Mg+2) and a carbonyl oxygen is a
common example of a Lewis acid-base reaction. The carbonyl oxygen (the Lewis base) donates a pair of electrons to the
magnesium cation (the Lewis acid). As we will see in Chapter 19 when we begin the study of reactions involving carbonyl groups,
this interaction has the very important effect of increasing the polarity of the carbon-oxygen double bond.
2+
Mg
O Mg
O
C C
R R R R

The eight-electron rule does not hold throughout the periodic table. In order to obtain noble gas configurations, some atoms may
need eighteen electrons in their valence shell. Transition metals such as titanium, iron and nickel may have up to eighteen electrons
and can frequently accept electron pairs from Lewis bases. Transition metals are often Lewis acids. For example, titanium has four
valence electrons and can form four bonds in compounds such as titanium tetrakis (isopropoxide), below, or titanium tetrachloride,
TiCl4. However, the titanium atom in that compound has only eight valence electrons, not eighteen. It can easily accept electrons
from donors.

O
Ti O
O
O

CH3 CH3
N N
H 3C Ce CH3
N
H 3C CH3

Figure 3.2.1 : Although titanium has eight electrons in this molecule, titanium tetrakis(isopropoxide), it can accommodate up to
eighteen. It is a Lewis acid. The cerium atom in cerium tris(dimethylamide) comes from a similar part of the periodic table and is
also a Lewis acid.
For example, when THF and TiCl4 are combined, a Lewis acid-base complex is formed, TiCl4(THF)2. TiCl4(THF)2 is a yellow
solid at room temperature.
Cl
O
Ti TiCl4(THF) THF TiCl4(THF)2
+ Cl Cl
Cl
THF TiCl4

Figure 3.2.2 : A Lewis acid-base complex between tetrahydrofuran (THF) and titanium tetrachloride.

The Proton as a Common Lewis Acid

Perhaps the most common example of a Lewis acid is also the simplest. It is the hydrogen cation (H+) or proton. It is called a
proton because, in most hydrogen atoms, the only particle in the nucleus is a proton. If an electron is removed to make a cation, a
proton is all that is left. A proton is a Lewis acid for a number of reasons. It has a positive charge, and so it will attract electrons,
which are negative. Also, it lacks the electron configuration of its noble gas neighbor, helium. Helium has two electrons. If a Lewis
base or nucleophile donates a pair of electrons to a proton, the proton will obtain a helium noble gas configuration.

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B + H B H

B = base
Figure 3.2.3 : Proton reacting as a Lewis acid.
There is something about hydrogen cations that is not so simple, however. They are actually not so common. Instead, protons are
generally always bound to a Lewis base. Hydrogen is almost always covalently (or coordinately) bonded to another atom. Many of
the other elements commonly found in compounds with hydrogen are more electronegative than hydrogen. As a result, hydrogen
often has a partial positive charge making is still act as a Lewis Acid.
A acid-base reaction involving protons might better be expressed as:

H
O + H Cl + Cl
H H O
H H
Figure 3.2.4 : Proton transfer from one site to another.
The Lewis acid-base interactions we have looked at so far are slightly different here. Instead of two compounds coming together
and forming a bond, we have one Lewis base replacing another at a proton. Two specific movements of electrons are shown in the
reaction both of which are show by arrows. Lone pair electrons on oxygen attack the hydrogen to form an O-H bond in the product.
Also, the electrons of the H-Cl bond move to become a lone pair on chlorine as the H-Cl bond breaks. These two arrows together
are said to represent the mechanism of this acid-base reaction.

Lewis Bases
What makes a molecule (or an atom or ion) a Lewis base? It must have a pair of electrons available to share with another atom to
form a bond. The most readily available electrons are those that are not already in bonds. Bonding electrons are low in energy.
Non-bonding electrons are higher in energy and may be stabilized when they are delocalized in a new bond. Lewis bases usually
have non-bonding electrons or lone pairs this makes oxygen and nitrogen compounds common Lewis bases. Lewis bases may be
anionic or neutral. The basic requirement is that they have a pair of electrons to donate.
NH2 OH O S

O O O O

H O NH2

Figure 3.2.5 : Some common organic examples of Lewis bases. Most oxygen, nitrogen and sulfur containing compounds can act as
Lewis Bases.

 Note 1: Ammonia

Ammonia, NH3, has a lone pair and is a Lewis base. It can donate to compounds that will accept electrons.

NH3 + A H3 N A

Ammonia donating to an electron acceptor or Lewis acid.

Not all compounds can act as a Lewis base. For example, methane, CH4, has all of its valence electrons in bonding pairs. These
bonding pairs are too stable to donate under normal conditions therefore methane is not a Lewis base. Neutral boron compounds
also have all electrons in bonding pairs. For example, borane, BH3 has no lone pairs; all its valence electrons are in bonds. Boron
compounds are not typically Lewis bases.
H H
B
H H H C H
H

no lone pairs to donate

Figure 3.2.6 : Carbon and boron compounds with all sigma bonds do not have lone pairs, and do not act as Lewis bases.

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 Exercise 3.2.1
Which of the following compounds would you expect to be Lewis bases?
a) SiH4 b) AlH3 c) PH3 d) SH2 e) -SH

Answer
a) No, silicon has 4 valence electrons (like carbon) and all 4 are involved in sigma bonds
b) No, aluminum has 3 valence electrons and all 3 are involved in sigma bonds
c) Yes, phosphorus has 5 valence electrons, so there is one lone pair available
d) Yes, sulfur has 6 valence electrons, so there are two lone pairs available
e) Yes, this ion has 3 lone pairs available

Lewis Acid-Base Complexes

What happens when a Lewis base donates a pair of electrons to a Lewis acid? The electron pushing formalism (arrows) we have
been using to illustrate the behavior of Lewis acids and Lewis bases is meant to show the direction of electron movement from the
donor to the acceptor. However, given that a bond can be thought of as a pair of electrons that are shared between two atoms (in
this case, between the donor and the acceptor), these arrows also show where bonds are forming.

B + A B A
electron electron
donor acceptor
(Lewis base) (Lewis acid)
Figure 3.2.7 : Donation of electrons from a Lewis base to a Lewis acid.
The electrons donated from a Lewis base to a Lewis acid form a new bond. A new, larger compound is formed from the smaller
Lewis acid and Lewis base. This compound is called a Lewis acid-base complex. A simple example of Lewis acid-base
complexation involves ammonia and boron trifluoride. The nitrogen atom has a lone pair and is an electron donor. The boron has
no octet and is an electron acceptor. The two compounds can form a Lewis acid-base complex or a coordination complex together.

F H F
F
H N H +
B N B
H F F HH F

Figure 3.2.8 : Formation of a Lewis acid-base complex from ammonia and boron trifluoride.
When the nitrogen donates a pair of electrons to share with the boron, the bond that forms is sometimes called a coordinate bond. A
coordinate bond is any covalent bond that arose because one atom brought a pair of its electrons and donated them to another.
In organic chemistry terminology, the electron donor is called a nucleophile and the electron acceptor is called an electrophile.
Ammonia is a nucleophile and boron trifluoride is an electrophile.
Because Lewis bases are attracted to electron-deficient atoms, and because positive charge is generally associated with the
nucleus of an atom, Lewis bases are sometimes refered to as "nucleophiles". Nucleophile means nucleus-loving.
Because Lewis acids attract electron pairs, Lewis acids are sometimes called "electrophiles". Electrophile means electron-
loving.

 Exercise 3.2.2
For the following reaction, add curved arrows (electron pushing formalism) to indicate the electron flow.

Answer

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 Exercise 3.2.3

A Lewis acid-base complex is formed between THF (tetrahyrofuran) and borane, BH3.
a) Which compound is the Lewis acid? Which one is the Lewis base?
b) Which atom in the Lewis acid is the acidic site? Why?
c) Which atom in the Lewis base is the basic site? Why?
d) How many donors would be needed to satisfy the acidic site?
e) Show, using arrow notation, the reaction to form a Lewis acid-base complex.
f) Borane is highly pyrophoric; it reacts violently with air, bursting into flames. Show, using arrow notation, what might be
happening when borane contacts the air.
g) Borane-THF complex is much less pyrophoric than borane. Why do you suppose that is so?
Add exercises text here.

Answer
a) Borane is the Lewis acid. THF has lone pair electrons so it is the Lewis base.
b) The Boron atom has an unfilled octet so it has an empty p orbital that can accept electrons.
c) The oxygen atom in THF has lone pair electrons contained in a sp3 hybridized orbital.
d) The boron in borane has six electrons around it so it would only need one lone pair donor to reach an octet.
e) Show, using arrow notation, the reaction to form a Lewis acid-base complex.

f) The Borane initially reacts with water in air.

g) After the Borane-THF complex is formed, the boron atom has a complete octet making it less reactive.

Exercises
Questions
Q2.11.1
For the following molecules state wither they are Lewis acid or base and wither or not they are a Brønsted acid or base.

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Solutions
S2.11.1
Acetone is a Lewis base and a Brønsted base. Ammonium cation is both a Lewis acid and a weak Brønsted acid.

3.2: Acids and Bases - The Lewis Definition is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
2.11: Acids and Bases - The Lewis Definition by Chris Schaller, Dietmar Kennepohl, Layne Morsch, Steven Farmer, Tim Soderberg is
licensed CC BY-SA 4.0.

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3.3: Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases
To understand ionic reactions, we need to be able to recognize whether a particular reagent will act to acquire an electron pair or to
donate an electron pair. Reagents that acquire an electron pair in chemical reactions are said to be electrophilic ("electron-
loving"). We can picture this in a general way as a heterolytic bond breaking of compound X : Y by an electrophile E such that E
becomes bonded to Y by the electron pair of the XY bond. Thus

Reagents that donate an electron pair in chemical reactions are said to be nucleophilic ("nucleus loving"). Thus the X : Y bond
also can be considered to be broken by the nucleophile N u : , which donates its electron pair to X while Y leaves as Y : with the
⊖

electrons of the X : Y bond:

Thus, by definition, electrophiles are electron-pair acceptors and nucleophiles are electron-pair donors. These definitions
correspond closely to definitions used in the generalized theory of acids and bases proposed by G. N. Lewis (1923). According to
Lewis, an acid is any substance that can accept an electron pair, and a base is any substance that can donated an electron pair to
form a covalent bond. Therefore acids must be electrophiles and bases must be nucleophiles. For example, the methyl cation may
be regarded as a Lewis acid, or an electrophile, because it accepts electrons from reagents such as chloride ion or methanol. In
turn, because chloride ion and methanol donate electrons to the methyl cation they are classified as Lewis bases, or nucleophiles:

The generalized Lewis concept of acids and bases also includes common proton-transfer reactions. Thus water acts as a base
1

because one of the electron pairs on oxygen can abstract a proton from a reagent such as hydrogen fluoride:

Alternatively, the hydronium ion (H 3O

⊕
) is an acid because it can accept electrons from another reagent (e.g., fluoride ion) by
donating a proton.
A proton donor can be classified as an electrophile and a proton acceptor as a nucleophile. For example, hydrogen chloride can
transfer a proton to ethene to form the ethyl cation. Therefore hydrogen chloride functions as the electrophile, or acid, and ethene
functions as the nucleophile, or base:

What then is the difference between an acid and an electrophile, or between a base and nucleophile? No great difference until we
try to use the terms in a quantitative sense. For example, if we refer to acid strength, or acidity, this means the position of
equilibrium in an acid-base reaction. The equilibrium constant K for the dissociation of an acid H A, or the pK , is a quantitative
a a

measure of acid strength. The larger the value of K or the smaller the pK , the stronger the acid.
a a

A summary of the relationships between K and pK follow, where the quantities in brackets are concentrations:
a a

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By definition, −log K a = p Ka and −log [ H3 O
⊕
] = pH ; hence

However, in referring to the strength of reagents as electrophiles or nucleophiles we usually are not referring to chemical equilibria
but to reaction rates. A good nucleophile is a reagent that reacts rapidly with a particular electrophile. In contrast, a poor
nucleophile reacts only slowly with the same electrophile. Consequently, it should not then be taken for granted that there is a
parallel between the acidity or basicity of a reagent and its reactivity as an electrophile or nucleophile. For instance, it is incorrect
to assume that the strengths of a series of bases, B : , in aqueous solution will necessarily parallel their nucleophilicities toward a
carbon electrophile, such as methyl chloride:

Figure 4-4). Even so, it turns out that most strong bases are good nucleophiles and that most strong proton acids are good
electrophiles. We will see that the converse may not be true. Good nucleophiles are not always strong bases [examples are C l ,
⊖

Br , I , and (C H ) S ] and good electrophiles are not always strong acids by either the Bronsted-Lowry or Lewis definitions
⊖ ⊖
3 2

(examples are H OBr , Br , C l , I ).

2 2 2

In what follows we will be concerned with the rates of ionic reactions under nonequilibrium conditions. We shall use the term
nucleophilic repeatedly and we want you to understand that a nucleophile is any neutral or charged reagent that supplies a pair of
electrons, either bonding or nonbonding, to form a new covalent bond. In substitution reactions the nucleophile usually is an anion,
Y : , or a neutral molecule, Y : or H Y : . The operation of each of these is illustrated in the following equations for reactions of
⊖

the general compound RX and some specific examples:

An electrophile is any neutral or charged reagent that accepts an electron pair (from a nucleophile) to form a new bond. In the
preceding substitution reactions, the electrophile is RX. The electrophile in other reactions may be a carbon cation or a proton
donor, as in the following examples:

1
The concept of an acid as a proton donor and a base as a proton acceptor is due to Bronsted and Lowry (1923). Previous to this
time, acids and bases generally were defined as substances that functioned by forming H or OH in water solutions. The
⊕ ⊖

Bronsted-Lowry concept was important because it liberated acid-base phenomena from the confines of water-containing solvents

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by focusing attention on proton transfers rather than the formation of H or OH . The Lewis concept of generalized acids and
⊕ ⊖

bases further broadened the picture by showing the relationship between proton transfers and reactions where an electron-pair
acceptor is transferred from one electron-pair donor to another.

Contributors and Attributions

John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. ,
Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission
for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any
format."

3.3: Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases is shared under a not declared license and was authored,
remixed, and/or curated by LibreTexts.
8.2: Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases by John D. Roberts and Marjorie C. Caserio is
licensed CC BY-NC-SA 4.0.

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3.4: Using Curved Arrows in Polar Reaction Mechanisms
 Objective

After completing this section, you should be able to use curved (curly) arrows, in conjunction with a chemical equation, to
show the movement of electron pairs in a simple polar reaction, such as electrophilic addition.

 Key Terms

Make certain that you can define, and use in context, the key terms below.
electrophlic
nucleophlic

Pushing Electrons and Curved Arrows

Understanding the location of electrons and being able to draw the curved arrows that depict the mechanisms by which
the reactions occur is one of the most critical tools for learning organic chemistry since they allow you to understand
what controls reactions, and how reactions proceed.
Before you can do this you need to understand that a bond is due to a pair of electrons shared between atoms.
When asked to draw a mechanism, curved arrows should be used to show all the bonding changes that occur.
A few simple lessons that illustrate these concepts can be found below.

Lesson 1
If we remove the pair of electrons in a bond, then we BREAK that bond. This is true for single and multiple bonds as shown below:
CH3 CH3
H 3C arrow illustrating electron
C C + Br
H 3C Br flow in a reaction
H 3C CH3

O O arrow illustrating electron

C C flow in resonance
H H H H

arrow illustrating electron

H C N H C N
flow in resonance

Notice that since the starting materials were neutral, the products are also neutral. In general terms, the sum of the charges on the
starting materials MUST equal the sum of the charges on the products since we have the same number of electrons.
The first example is a REACTION since we broke a sigma bond. In the second two examples, we moved pi electrons into long
pairs. This is RESONANCE.
If we move electrons between two atoms, then we MAKE a new bond:
CH3 CH3
H3C arrow illustrating electron
C C + Br
H3C Br flow in a reaction
H3C CH3

O O arrow illustrating electron

C C flow in resonance
H H H H

arrow illustrating electron

H C N H C N
flow in resonance

We always show electrons moving from electron rich to electron poor.

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Lesson 2
H
O + H Cl + Cl
H H O
H H

This is a simple acid/base reaction, showing the formation of the hydronium ion produced when hydrochloric acid is dissolved in
water. It is useful to analyze the bond changes that are occurring. Water is functioning as a base and hydrochloric acid as an acid.
Consider the differences in bonding between the starting materials and the products:
electrons are used to
form a new bond to H
new bond
H
O + H Cl + Cl
H H O
H H

bond is broken; lone pair gained from

electrons become a lone breaking H-Cl bond
pair on Cl

One of the lone pairs on the oxygen atom of water was used to form a bond to a hydrogen atom, creating the hydronium ion (H3O+)
seen in the products. The hydrogen-chlorine bond of HCl was broken, and the electrons in this bond became a lone pair on the
chlorine atom, thus generating a chloride ion. We can illustrate these changes in bonding using the curved arrows shown below.

H
O + H Cl + Cl
H H O
H H

Note that in this diagram, the overall charge of the reactants is the same as the overall charge of the products. We can also show the
curved arrows for the reverse reaction:

H
Cl + H Cl + O
O H H
H H

This shows the formation of the new H-Cl bond by using a lone pair of electrons from the electron-rich chloride ion to form a bond
to an electron poor hydrogen atom of the hydronium ion. Because hydrogen can only form one bond, the oxygen-hydrogen bond is
broken and its electrons become a lone pair on the electron-poor oxygen atom. Notice that the charges balance!

Lesson 3
In this section, we will look at the curved arrows for some nucleophilic substitution reactions. Overall, the processes involved are
similar to those for the acid/base reactions described above. In a nucleophilic substitution reaction, an electron-rich nucleophile
(Nu) becomes bonded to an electron-poor carbon atom, and a leaving group (LG) is displaced. In bonding terms, we must make a
Nu-C bond and break a C-LG bond.
R R
Nu + R R +
C C LG
R LG R Nu

Let's consider the stepwise SN1 reaction between (1-chloroethyl)benzene and sodium cyanide. The first step of this process is
breaking the C-Cl bond, where the electrons in that bond become a lone pair on the chlorine atom. The carbon atom has lost
electrons and therefore becomes positive, generating a secondary carbocation. Because the chlorine atom gained an additional lone
pair of electrons, it becomes a negatively charged chloride ion.

Cl + Cl

(1-chloroethyl)benzene

In the second step, the electron-rich nucleophile donates electrons to form a new C-C bond with the electron-poor secondary
carbocation.

+ C +
Na C N N Na

In an SN2 reaction, the bond forming and breaking processes occur simultaneously. The scheme below shows the Nu donating
electrons to form a new C-C bond at the same time that the C-Cl bond is breaking. The electrons in the C-Cl bond become a long

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pair on the chlorine atom, generating a chloride ion. Forming and breaking the bonds simultaneously allows carbon to obey the
octet rule throughout this process.

Cl + C + Na Cl
Na C N N

Notice that in all steps for the processes above, the overall charges of the starting materials match those of the products.

Lesson 4
This section will dissect another substitution reaction, although it is more involved. Let's consider the SN1 reaction of tert-butyl
bromide with water.

+ O + H Br
Br H H OH

It can be helpful to take inventory of which bonds have been formed, and which bonds have been broken.
FORMED: C-O, H-Br
+ O + H Br
Br H H OH BROKEN: C-Br, O-H

The curved arrows we draw must account for ALL of these bonding changes. Since we are dealing with an SN1 reaction process,
the first step will be cleavage of the C-Br bond to give a carbocation and and a bromide anion.

+ Br
Br

Water then acts as a nucleophile, using one of its lone pairs to form a bond to the electron-poor t-butyl cation. This generates an
oxonium ion, where oxygen has three bonds and a positive formal charge.

O H
+ O
H H
H

The final step is an acid/base reaction between the bromide anion generated in step 1 and the oxonium product of step 2. The
bromide anion acts as a base, using a lone pair to form a bond to one of the hydrogen atoms. The O-H bond then breaks, and its
electrons become a lone pair on oxygen. This gives the final products of HBr and t-butyl alcohol.

H
O + Br + H Br
OH
H

Notice that in each of the mechanistic steps above, the overall charge of the reactant side balances with the overall charge of the
product side.
While the above process was broken down into distinct steps, however it is important to note that mechanisms are almost always
shown as a continuous process. The overall mechanism for this processes can be found below:

+ O
Br H H

+ H Br
OH H
O + Br
H

Now consider the reverse reaction, i.e. the reaction of t-butyl alcohol with hydrobromic acid to generate t-butyl bromide and water.
The scheme is shown below, along with an analysis of the bonds formed and broken in this process:
FORMED: C-Br, O-H
+ H Br + O
OH Br H H BROKEN: C-O, H-Br

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The mechanism must occur via the same pathway as shown above (Law of Macroscopic Reversibility), however this mechanism
can still be deduced without knowing that. First, it is known that HBr is a strong acid and can donate a proton to a base. The most
basic sites in the whole system are the lone pairs on the oxygen atom of t-butanol. Since the lone pairs are the electron-rich area of
the molecule, the arrow starts at a lone pair and ends at the proton of HBr. The H-Br bond breaks, pushing its electrons onto the
bromine atom and generating a bromide ion.

H
+ H Br O + Br
OH
H

H O
O +
H H
H

The bromide ion generated in the first step can then react with the t-butyl cation to generate t-butyl bromide.

+ Br
Br

Once again, the above the overall process is broken down into individual steps, however it is more common to illustrate this as one
overall process:

+ H Br H + Br
OH O
H

+ Br
Br

+ O
H H

Curved Arrow Summary

Curved arrows flow from electron rich to electron poor.
Therefore they start from lone pairs or bonds.
The charges in any particular step should always be balanced.
Remember to obey the rules of valence (eg. octet rule for C,N,O,F etc.)
If electrons are taken out of a bond, then that bond is broken.
If electrons are placed between two atoms then it implies a bond is being made.

Exercises
Draw curved arrows to indicate mechanisms for the following reactions:

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Solutions

3.4: Using Curved Arrows in Polar Reaction Mechanisms is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.
6.6: Using Curved Arrows in Polar Reaction Mechanisms by Dietmar Kennepohl, Krista Cunningham, Layne Morsch, Steven Farmer is
licensed CC BY-SA 4.0.

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3.5: Acid Strength and p K a pKa
You are no doubt aware that some acids are stronger than others. Sulfuric acid is strong enough to be used as a drain cleaner, as it
will rapidly dissolve clogs of hair and other organic material.

Not surprisingly, concentrated sulfuric acid will also cause painful burns if it touches your skin, and permanent damage if it gets in
your eyes (there’s a good reason for those safety goggles you wear in chemistry lab!). Acetic acid (vinegar), will also burn your
skin and eyes, but is not nearly strong enough to make an effective drain cleaner. Water, which we know can act as a proton donor,
is obviously not a very strong acid. Even hydroxide ion could theoretically act as an acid – it has, after all, a proton to donate – but
this is not a reaction that we would normally consider to be relevant in anything but the most extreme conditions.
The relative acidity of different compounds or functional groups – in other words, their relative capacity to donate a proton to a
common base under identical conditions – is quantified by a number called the dissociation constant, abbreviated Ka. The
common base chosen for comparison is water.
We will consider acetic acid as our first example. When a small amount of acetic acid is added to water, a proton-transfer event
(acid-base reaction) occurs to some extent.

Notice the phrase ‘to some extent’ – this reaction does not run to completion, with all of the acetic acid converted to acetate, its
conjugate base. Rather, a dynamic equilibrium is reached, with proton transfer going in both directions (thus the two-way arrows)
and finite concentrations of all four species in play. The nature of this equilibrium situation, as you recall from General Chemistry,
is expressed by an equilibrium constant, Keq. The equilibrium constant is actually a ratio of activities (represented by the symbol
a ), but activities are rarely used in courses other than analytical or physical chemistry. To simplify the discussion for general

chemistry and organic chemistry courses, the activities of all of the solutes are replaced with molarities, and the activity of the
solvent (usually water) is defined as having the value of 1.
In our example, we added a small amount of acetic acid to a large amount of water: water is the solvent for this reaction. Therefore,
in the course of the reaction, the concentration of water changes very little, and the water can be treated as a pure solvent, which is
always assigned an activity of 1. The acetic acid, acetate ion and hydronium ion are all solutes, and so their activities are
approximated with molarities. The acid dissociation constant, or Ka, for acetic acid is therefore defined as:
− +
a − ⋅a +
[C H3 C OO ][ H3 O ]
C H3 C OO H3 O
Keq = ≈ (3.5.1)
aC H3 C OOH ⋅ aH2 O [C H3 C OOH ][1]

Because dividing by 1 does not change the value of the constant, the "1" is usually not written, and Ka is written as:
− +
[C H3 C OO ][ H3 O ]
−5
Keq = Ka = = 1.75 × 10 (3.5.2)
[C H3 C OOH ]

In more general terms, the dissociation constant for a given acid is expressed as:
− +
[A ][ H3 O ]
Ka = (3.5.3)
[H A]

3.5.1 https://chem.libretexts.org/@go/page/205316
+
[A][ H3 O ]
Ka = (3.5.4)
+
[H A ]

The first expression applies to a neutral acid such as like HCl or acetic acid, while the second applies to a cationic acid like
ammonium (NH4+).
The value of Ka = 1.75 x 10-5 for acetic acid is very small - this means that very little dissociation actually takes place, and there is
much more acetic acid in solution at equilibrium than there is acetate ion. Acetic acid is a relatively weak acid, at least when
compared to sulfuric acid (Ka = 109) or hydrochloric acid (Ka = 107), both of which undergo essentially complete dissociation in
water.
A number like 1.75 x 10- 5 is not very easy either to say or to remember. Chemists have therefore come up with a more convenient
term to express relative acidity: the pKa value.
pKa = -log Ka
Doing the math, we find that the pKa of acetic acid is 4.8. The use of pKa values allows us to express the acidity of common
compounds and functional groups on a numerical scale of about –10 (very strong acid) to 50 (not acidic at all). Table 7 at the end of
the text lists exact or approximate pKa values for different types of protons that you are likely to encounter in your study of organic
and biological chemistry. Looking at Table 7, you see that the pKa of carboxylic acids are in the 4-5 range, the pKa of sulfuric acid
is –10, and the pKa of water is 14. Alkenes and alkanes, which are not acidic at all, have pKa values above 30. The lower the pKa
value, the stronger the acid.
It is important to realize that pKa is not at all the same thing as pH: the former is an inherent property of a compound or functional
group, while the latter is the measure of the hydronium ion concentration in a particular aqueous solution:
pH = -log [H3O+]
Any particular acid will always have the same pKa (assuming that we are talking about an aqueous solution at room temperature)
but different aqueous solutions of the acid could have different pH values, depending on how much acid is added to how much
water.
Our table of pKa values will also allow us to compare the strengths of different bases by comparing the pKavalues of their
conjugate acids. The key idea to remember is this: the stronger the conjugate acid, the weaker the conjugate base. Sulfuric acid is
the strongest acid on our list with a pKa value of –10, so HSO4- is the weakest conjugate base. You can see that hydroxide ion is a
stronger base than ammonia (NH3), because ammonium (NH4+, pKa = 9.2) is a stronger acid than water (pKa = 14.0).
While Table 7 provides the pKa values of only a limited number of compounds, it can be very useful as a starting point for
estimating the acidity or basicity of just about any organic molecule. Here is where your familiarity with organic functional groups
will come in very handy. What, for example, is the pKaof cyclohexanol? It is not on the table, but as it is an alcohol it is probably
somewhere near that of ethanol (pKa = 16). Likewise, we can use Table 7 to predict that para-hydroxyphenyl acetaldehyde, an
intermediate compound in the biosynthesis of morphine, has a pKa in the neighborhood of 10, close to that of our reference
compound, phenol.

Notice in this example that we need to evaluate the potential acidity at four different locations on the molecule.

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Aldehyde and aromatic protons are not at all acidic (pKavalues are above 40 – not on our table). The two protons on the carbon
next to the carbonyl are slightly acidic, with pKa values around 19-20 according to the table. The most acidic proton is on the
phenol group, so if the compound were to be subjected to a single molar equivalent of strong base, this is the proton that would be
donated.
As you continue your study of organic chemistry, it will be a very good idea to commit to memory the approximate pKa ranges of
some important functional groups, including water, alcohols, phenols, ammonium, thiols, phosphates, carboxylic acids and carbons
next to carbonyl groups (so-called a-carbons). These are the groups that you are most likely to see acting as acids or bases in
biological organic reactions.
A word of caution: when using the pKa table, be absolutely sure that you are considering the correct conjugate acid/base pair. If you
are asked to say something about the basicity of ammonia (NH3) compared to that of ethoxide ion (CH3CH2O-), for example, the
relevant pKa values to consider are 9.2 (the pKa of ammonium ion) and 16 (the pKa of ethanol). From these numbers, you know
that ethoxide is the stronger base. Do not make the mistake of using the pKa value of 38: this is the pKa of ammonia acting as an
acid, and tells you how basic the NH2- ion is (very basic!)

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Example

Exercise 7.2: Using the pKa table, estimate pKa values for the most acidic group on the compounds below, and draw the structure of the conjugate
base that results when this group donates a proton.
a) H c)
O OH
O e)
O OH
NH3 SH

N
CH3
H
O
b) O d)

NH2 NH2 N
OH H
H 3N
OH
O

Solution

Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

3.5: Acid Strength and pK is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
a

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3.6: A Summary of the Factors that Determine Acid Strength
Now that we know how to quantify the strength of an acid or base, our next job is to gain an understanding of the fundamental
reasons behind why one compound is more acidic or more basic than another. This is a big step: we are, for the first time, taking our
knowledge of organic structure and applying it to a question of organic reactivity. Many of the ideas that we’ll see for the first here
will continue to apply throughout the book as we tackle many other organic reaction types.

A: Periodic trends
First, we will focus on individual atoms, and think about trends associated with the position of an element on the periodic table.
We’ll use as our first models the simple organic compounds ethane, methylamine, and ethanol, but the concepts apply equally to
more complex biomolecules with the same functionalities, for example the side chains of the amino acids alanine (alkane), lysine
(amine), and serine (alcohol).

Horizontal periodic trend in acidity and basicity

We can see a clear trend in acidity as we move from left to right along the second row of the periodic table from carbon to nitrogen
to oxygen. The key to understanding this trend is to consider the hypothetical conjugate base in each case: the more stable (weaker)
the conjugate base, the stronger the acid. Look at where the negative charge ends up in each conjugate base. In the conjugate base
of ethane, the negative charge is borne by a carbon atom, while on the conjugate base of methylamine and ethanol the negative
charge is located on a nitrogen and an oxygen, respectively. Remember that electronegativity also increases as we move from left to
right along a row of the periodic table, meaning that oxygen is the most electronegative of the three atoms, and carbon the least.

The more electronegative an atom, the better able it is to bear a negative charge. Weaker bases have negative charges on
more electronegative atoms; stronger bases have negative charges on less electronegative atoms.

Thus, the methoxide anion is the most stable (lowest energy, least basic) of the three conjugate bases, and the ethyl carbanion anion
is the least stable (highest energy, most basic). Conversely, ethanol is the strongest acid, and ethane the weakest acid.
When moving vertically within a given column of the periodic table, we again observe a clear periodic trend in acidity. This is best
illustrated with the haloacids and halides: basicity, like electronegativity, increases as we move up the column.

Vertical periodic trend in acidity and basicity

Conversely, acidity in the haloacids increases as we move down the column.

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In order to make sense of this trend, we will once again consider the stability of the conjugate bases. Because fluorine is the most
electronegative halogen element, we might expect fluoride to also be the least basic halogen ion. But in fact, it is the least stable,
and the most basic! It turns out that when moving vertically in the periodic table, the size of the atom trumps its electronegativity
with regard to basicity. The atomic radius of iodine is approximately twice that of fluorine, so in an iodide ion, the negative charge
is spread out over a significantly larger volume:

This illustrates a fundamental concept in organic chemistry:

Electrostatic charges, whether positive or negative, are more stable when they are ‘spread out’ over a larger area.

We will see this idea expressed again and again throughout our study of organic reactivity, in many different contexts. For now, we
are applying the concept only to the influence of atomic radius on base strength. Because fluoride is the least stable (most basic) of
the halide conjugate bases, HF is the least acidic of the haloacids, only slightly stronger than a carboxylic acid. HI, with a pKa of
about -9, is almost as strong as sulfuric acid.
More importantly to the study of biological organic chemistry, this trend tells us that thiols are more acidic than alcohols. The pKa
of the thiol group on the cysteine side chain, for example, is approximately 8.3, while the pKa for the alcohol group on the serine
side chain is on the order of 17.
Remember the concept of 'driving force' that we learned about in chapter 6? Recall that the driving force for a reaction is usually
based on two factors: relative charge stability, and relative total bond energy. Let's see how this applies to a simple acid-base
reaction between hydrochloric acid and fluoride ion:
HCl + F- → HF + Cl-
We know that HCl (pKa -7) is a stronger acid than HF (pKa 3.2), so the equilibrium for the reaction lies on the product side: the
reaction is exergonic, and a 'driving force' pushes reactant to product.
What explains this driving force? Consider first the charge factor: as we just learned, chloride ion (on the product side) is more
stable than fluoride ion (on the reactant side). This partially accounts for the driving force going from reactant to product in this
reaction: we are going from less stable ion to a more stable ion.
What about total bond energy, the other factor in driving force? If you consult a table of bond energies, you will see that the H-F
bond on the product side is more energetic (stronger) than the H-Cl bond on the reactant side: 565 kJ/mol vs 427 kJ/mol,
respectively). This also contributes to the driving force: we are moving from a weaker (less stable) bond to a stronger (more stable)
bond.

B: Resonance effects
In the previous section we focused our attention on periodic trends - the differences in acidity and basicity between groups where
the exchangeable proton was bound to different elements. Now, it is time to think about how the structure of different organic
groups contributes to their relative acidity or basicity, even when we are talking about the same element acting as the proton
donor/acceptor. The first model pair we will consider is ethanol and acetic acid, but the conclusions we reach will be equally valid
for all alcohol and carboxylic acid groups.
Despite the fact that they are both oxygen acids, the pKa values of ethanol and acetic acid are strikingly different. What makes a
carboxylic acid so much more acidic than an alcohol? As before, we begin by considering the stability of the conjugate bases,
remembering that a more stable (weaker) conjugate base corresponds to a stronger acid.

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In both species, the negative charge on the conjugate base is located on oxygen, so periodic trends cannot be invoked. For acetic
acid, however, there is a key difference: two resonance contributors can be drawn for the conjugate base, and the negative charge
can be delocalized (shared) over two oxygen atoms. In the ethoxide ion, by contrast, the negative charge is localized, or ‘locked’ on
the single oxygen – it has nowhere else to go. This makes the ethoxide ion much less stable.
Recall the important general statement that we made a little earlier: 'Electrostatic charges, whether positive or negative, are more
stable when they are ‘spread out’ than when they are confined to one location.' Now, we are seeing this concept in another context,
where a charge is being ‘spread out’ (in other words, delocalized) by resonance, rather than simply by the size of the atom
involved.
The delocalization of charge by resonance has a very powerful effect on the reactivity of organic molecules, enough to account for
the difference of over 12 pKa units between ethanol and acetic acid (and remember, pKa is a log expression, so we are talking about
a fator of 1012 between the Ka values for the two molecules!)
The resonance effect also nicely explains why a nitrogen atom is basic when it is in an amine, but not basic when it is part of an
amide group. Recall that in an amide, there is significant double-bond character to the carbon-nitrogen bond, due to a minor but
still important resonance contributor in which the nitrogen lone pair is part of a pi bond.

Whereas the lone pair of an amine nitrogen is ‘stuck’ in one place, the lone pair on an amide nitrogen is delocalized by resonance.
Notice that in this case, we are extending our central statement to say that electron density – in the form of a lone pair – is stabilized
by resonance delocalization, even though there is not a negative charge involved. Here’s another way to think about it: the lone pair
on an amide nitrogen is not available for bonding with a proton – these two electrons are too ‘comfortable’ being part of the
delocalized pi bonding system. The lone pair on an amine nitrogen, by contrast, is not so comfortable - it is not part of a delocalized
pi system, and is available to form a bond with any acidic proton that might be nearby.
If an amide group is protonated, it will be at the oxygen rather than the nitrogen.
Exercise 7.3.1
a) Draw the Lewis structure of nitric acid, HNO3.
b) Nitric acid is a strong acid - it has a pKa of -1.4. Make a structural argument to account for its strength. Your answer should
involve the structure of nitrate, the conjugate base of nitric acid.
Solution

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Exercise 7.3.2
Rank the compounds below from most acidic to least acidic, and explain your reasoning.

Solution
Exercise 7.3.3
(challenging!) Often it requires some careful thought to predict the most acidic proton on a molecule. Ascorbic acid, also known
as Vitamin C, has a pKa of 4.1 - the fact that this is in the range of carboxylic acids suggest to us that the negative charge on the
conjugate base can be delocalized by resonance to two oxygen atoms. Which if the four OH protons on the molecule is most
acidic? Draw the structure of ascorbate, the conjugate base of ascorbic acid, then draw a second resonance contributor showing
how the negative charge is delocalized to a second oxygen atom. Hint - try removing each OH group in turn, then use your
resonance drawing skills to figure out whether or not delocalization of charge can occur.

Solution

C: Inductive effects
Compare the pKa values of acetic acid and its mono-, di-, and tri-chlorinated derivatives:

The presence of the chlorine atoms clearly increases the acidity of the carboxylic acid group, but the argument here does not have
to do with resonance delocalization, because no additional resonance contributors can be drawn for the chlorinated molecules.
Rather, the explanation for this phenomenon involves something called the inductive effect. A chlorine atom is more
electronegative than a hydrogen, and thus is able to ‘induce’, or ‘pull’ electron density towards itself, away from the carboxylate
group. In effect, the chlorine atoms are helping to further spread out the electron density of the conjugate base, which as we know
has a stabilizing effect. In this context, the chlorine substituent can be referred to as an electron-withdrawing group. Notice that
the pKa-lowering effect of each chlorine atom, while significant, is not as dramatic as the delocalizing resonance effect illustrated
by the difference in pKa values between an alcohol and a carboxylic acid. In general, resonance effects are more powerful than
inductive effects.
Because the inductive effect depends on electronegativity, fluorine substituents have a more pronounced pKa-lowered effect than
chlorine substituents.

In addition, the inductive takes place through covalent bonds, and its influence decreases markedly with distance – thus a chlorine
two carbons away from a carboxylic acid group has a decreased effect compared to a chlorine just one carbon away.

3.6.4 https://chem.libretexts.org/@go/page/206466
Exercise 7.3.4
Rank the compounds below from most acidic to least acidic, and explain your reasoning.

Solution

Next section⇒
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

3.6: A Summary of the Factors that Determine Acid Strength is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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3.7: Organic Acids and Bases
This page explains the acidity of simple organic acids and looks at the factors which affect their relative strengths.

Organic acids as weak acids

For the purposes of this topic, we are going to take the definition of an acid as "a substance which donates hydrogen ions (protons)
to other things". We are going to get a measure of this by looking at how easily the acids release hydrogen ions to water molecules
when they are in solution in water.
An acid in solution sets up this equilibrium:

A hydroxonium ion is formed together with the anion (negative ion) from the acid.
This equilibrium is sometimes simplified by leaving out the water to emphasise the ionisation of the acid.

If you write it like this, you must include the state symbols - "(aq)". Writing H+(aq) implies that the hydrogen ion is attached to a
water molecule as H3O+. Hydrogen ions are always attached to something during chemical reactions.
The organic acids are weak in the sense that this ionisation is very incomplete. At any one time, most of the acid will be present in
the solution as un-ionised molecules. For example, in the case of dilute ethanoic acid, the solution contains about 99% of ethanoic
acid molecules - at any instant, only about 1% have actually ionised. The position of equilibrium therefore lies well to the left.

Comparing the strengths of weak acids

The strengths of weak acids are measured on the pKa scale. The smaller the number on this scale, the stronger the acid is.
Three of the compounds we shall be looking at, together with their pKa values are:

Remember - the smaller the number the stronger the acid. Comparing the other two to ethanoic acid, you will see that phenol is
very much weaker with a pKa of 10.00, and ethanol is so weak with a pKa of about 16 that it hardly counts as acidic at all!

Why are these acids acidic?

In each case, the same bond gets broken - the bond between the hydrogen and oxygen in an -OH group. Writing the rest of the
molecule as "X":

So . . . if the same bond is being broken in each case, why do these three compounds have such widely different acid strengths?

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Differences in acid strengths between carboxylic acids, phenols and alcohols
Two of the factors which influence the ionization of an acid are:
the strength of the bond being broken,
the stability of the ions being formed.
In these cases, you seem to be breaking the same oxygen-hydrogen bond each time, and so you might expect the strengths to be
similar. The most important factor in determining the relative acid strengths of these molecules is the nature of the ions formed.
You always get a hydroxonium ion - so that's constant - but the nature of the anion (the negative ion) varies markedly from case to
case.

 Example 3.7.1: Ethanoic Acid

Ethanoic acid has the structure:

The acidic hydrogen is the one attached to the oxygen. When ethanoic acid ionises it forms the ethanoate ion, CH3COO-.
You might reasonably suppose that the structure of the ethanoate ion was as below, but measurements of bond lengths show
that the two carbon-oxygen bonds are identical and somewhere in length between a single and a double bond.

To understand why this is, you have to look in some detail at the bonding in the ethanoate ion. Like any other double bond, a
carbon-oxygen double bond is made up of two different parts. One electron pair is found on the line between the two nuclei -
this is known as a sigma bond. The other electron pair is found above and below the plane of the molecule in a pi bond. Pi
bonds are made by sideways overlap between p orbitals on the carbon and the oxygen.
In an ethanoate ion, one of the lone pairs on the negative oxygen ends up almost parallel to these p orbitals, and overlaps with
them

This leads to a delocalised pi system over the whole of the -COO- group, rather like that in benzene.

All the oxygen lone pairs have been left out of this diagram to avoid confusion. Because the oxygens are more electronegative
than the carbon, the delocalised system is heavily distorted so that the electrons spend much more time in the region of the
oxygen atoms.
So where is the negative charge in all this? It has been spread around over the whole of the -COO- group, but with the greatest
chance of finding it in the region of the two oxygen atoms. Ethanoate ions can be drawn simply as:

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The dotted line represents the delocalisation. The negative charge is written centrally on that end of the molecule to show that
it isn't localised on one of the oxygen atoms. The more you can spread charge around, the more stable an ion becomes. In this
case, if you delocalise the negative charge over several atoms, it is going to be much less attractive to hydrogen ions - and so
you are less likely to re-form the ethanoic acid.

 Example 3.7.2: Phenol

Phenols have an -OH group attached directly to a benzene ring. Phenol itself is the simplest of these with nothing else attached
to the ring apart from the -OH group.

When the hydrogen-oxygen bond in phenol breaks, you get a phenoxide ion, C6H5O-.
Delocalisation also occurs in this ion. This time, one of the lone pairs on the oxygen atom overlaps with the delocalised
electrons on the benzene ring.

This overlap leads to a delocalisation which extends from the ring out over the oxygen atom. As a result, the negative charge is
no longer entirely localised on the oxygen, but is spread out around the whole ion.

Why then is phenol a much weaker acid than ethanoic acid?

Think about the ethanoate ion again. If there wasn't any delocalisation, the charge would all be on one of the oxygen atoms,
like this:

But the delocalisation spreads this charge over the whole of the COO group. Because oxygen is more electronegative than
carbon, you can think of most of the charge being shared between the two oxygens (shown by the heavy red shading in this
diagram).

If there wasn't any delocalisation, one of the oxygens would have a full charge which would be very attractive towards
hydrogen ions. With delocalisation, that charge is spread over two oxygen atoms, and neither will be as attractive to a hydrogen
ion as if one of the oxygens carried the whole charge.
That means that the ethanoate ion won't take up a hydrogen ion as easily as it would if there wasn't any delocalisation. Because
some of it stays ionised, the formation of the hydrogen ions means that it is acidic.
In the phenoxide ion, the single oxygen atom is still the most electronegative thing present, and the delocalised system will be
heavily distorted towards it. That still leaves the oxygen atom with most of its negative charge.

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What delocalisation there is makes the phenoxide ion more stable than it would otherwise be, and so phenol is acidic to an
extent.
However, the delocalisation hasn't shared the charge around very effectively. There is still lots of negative charge around the
oxygen to which hydrogen ions will be attracted - and so the phenol will readily re-form. Phenol is therefore only very weakly
acidic.

 Example 3.7.3: Ethanol

Ethanol, CH3CH2OH, is so weakly acidic that you would hardly count it as acidic at all. If the hydrogen-oxygen bond breaks to
release a hydrogen ion, an ethoxide ion is formed:

This has nothing at all going for it. There is no way of delocalising the negative charge, which remains firmly on the oxygen
atom. That intense negative charge will be highly attractive towards hydrogen ions, and so the ethanol will instantly re-form.
Since ethanol is very poor at losing hydrogen ions, it is hardly acidic at all.

Variations in acid strengths between different carboxylic acids

You might think that all carboxylic acids would have the same strength because each depends on the delocalization of the negative
charge around the -COO- group to make the anion more stable, and so more reluctant to re-combine with a hydrogen ion.
In fact, the carboxylic acids have widely different acidities. One obvious difference is between methanoic acid, HCOOH, and the
other simple carboxylic acids:

pKa

HCOOH 3.75

CH3COOH 4.76

CH3CH2COOH 4.87

CH3CH2CH2COOH 4.82

Remember that the higher the value for pKa, the weaker the acid is.
Why is ethanoic acid weaker than methanoic acid? It again depends on the stability of the anions formed - on how much it is
possible to delocalise the negative charge. The less the charge is delocalised, the less stable the ion, and the weaker the acid.
The methanoate ion (from methanoic acid) is:

The only difference between this and the ethanoate ion is the presence of the CH3 group in the ethanoate.
But that's important! Alkyl groups have a tendency to "push" electrons away from themselves. That means that there will be a small
amount of extra negative charge built up on the -COO- group. Any build-up of charge will make the ion less stable, and more
attractive to hydrogen ions.
Ethanoic acid is therefore weaker than methanoic acid, because it will re-form more easily from its ions.

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The other alkyl groups have "electron-pushing" effects very similar to the methyl group, and so the strengths of propanoic acid and
butanoic acid are very similar to ethanoic acid. The acids can be strengthened by pulling charge away from the -COO- end. You can
do this by attaching electronegative atoms like chlorine to the chain.

As the next table shows, the more chlorines you can attach the better:

pKa

CH3COOH 4.76

CH2ClCOOH 2.86

CHCl2COOH 1.29

CCl3COOH 0.65

Trichloroethanoic acid is quite a strong acid.

Attaching different halogens also makes a difference. Fluorine is the most electronegative and so you would expect it to be most
successful at pulling charge away from the -COO- end and so strengthening the acid.

pKa

CH2FCOOH 2.66

CH2ClCOOH 2.86

CH2BrCOOH 2.90

CH2ICOOH 3.17

The effect is there, but isn't as great as you might expect.

Finally, notice that the effect falls off quite quickly as the attached halogen gets further away from the -COO- end. Here is what
happens if you move a chlorine atom along the chain in butanoic acid.

pKa

CH3CH2CH2COOH 4.82

CH3CH2CHClCOOH 2.84

CH3CHClCH2COOH 4.06

CH2ClCH2CH2COOH 4.52

The chlorine is effective at withdrawing charge when it is next-door to the -COO- group, and much less so as it gets even one
carbon further away.
This page explains why simple organic bases are basic and looks at the factors which affect their relative strengths. For A'level
purposes, all the bases we are concerned with are primary amines - compounds in which one of the hydrogens in an ammonia
molecule, NH3, is replaced either by an alkyl group or a benzene ring.

Ammonia as a weak base

All of the compounds we are concerned with are derived from ammonia and so we'll start by looking at the reason for its basic
properties. For the purposes of this topic, we are going to take the definition of a base as "a substance which combines with
hydrogen ions (protons)". We are going to get a measure of this by looking at how easily the bases take hydrogen ions from water
molecules when they are in solution in water.
Ammonia in solution sets up this equilibrium:

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An ammonium ion is formed together with hydroxide ions. Because the ammonia is only a weak base, it doesn't hang on to the
extra hydrogen ion very effectively and so the reaction is reversible. At any one time, about 99% of the ammonia is present as
unreacted molecules. The position of equilibrium lies well to the left.
The ammonia reacts as a base because of the active lone pair on the nitrogen. Nitrogen is more electronegative than hydrogen and
so attracts the bonding electrons in the ammonia molecule towards itself. That means that in addition to the lone pair, there is a
build-up of negative charge around the nitrogen atom. That combination of extra negativity and active lone pair attracts the new
hydrogen from the water.

Comparing the strengths of weak bases

The strengths of weak bases are measured on the pKb scale. The smaller the number on this scale, the stronger the base is. Three of
the compounds we shall be looking at, together with their pKb values are:

Remember - the smaller the number the stronger the base. Comparing the other two to ammonia, you will see that methylamine is a
stronger base, whereas phenylamine is very much weaker.
Methylamine is typical of aliphatic primary amines - where the -NH2 group is attached to a carbon chain. All aliphatic primary
amines are stronger bases than ammonia.
Phenylamine is typical of aromatic primary amines - where the -NH2 group is attached directly to a benzene ring. These are
very much weaker bases than ammonia.

Explaining the differences in base strengths

Two of the factors which influence the strength of a base are:
the ease with which the lone pair picks up a hydrogen ion,
the stability of the ions being formed.

Why are aliphatic primary amines stronger bases than ammonia?

Methylamine
Methylamine has the structure:

The only difference between this and ammonia is the presence of the CH3 group in the methylamine. But that's important! Alkyl
groups have a tendency to "push" electrons away from themselves. That means that there will be a small amount of extra negative

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charge built up on the nitrogen atom. That extra negativity around the nitrogen makes the lone pair even more attractive towards
hydrogen ions.

Making the nitrogen more negative helps the lone pair to pick up a hydrogen ion. What about the effect on the positive
methylammonium ion formed? Is this more stable than a simple ammonium ion? Compare the methylammonium ion with an
ammonium ion:

In the methylammonium ion, the positive charge is spread around the ion by the "electron-pushing" effect of the methyl group. The
more you can spread charge around, the more stable an ion becomes. In the ammonium ion there isn't any way of spreading the
charge.
To summarize:
The nitrogen is more negative in methylamine than in ammonia, and so it picks up a hydrogen ion more readily.
The ion formed from methylamine is more stable than the one formed from ammonia, and so is less likely to shed the hydrogen
ion again.
Taken together, these mean that methylamine is a stronger base than ammonia.

The other aliphatic primary amines

The other alkyl groups have "electron-pushing" effects very similar to the methyl group, and so the strengths of the other aliphatic
primary amines are very similar to methylamine. For example:

pKb

CH3NH2 3.36

CH3CH2NH2 3.27

CH3CH2CH2NH2 3.16

CH3CH2CH2CH2NH2 3.39

Why are aromatic primary amines much weaker bases than ammonia?
An aromatic primary amine is one in which the -NH2 group is attached directly to a benzene ring. The only one you are likely to
come across is phenylamine. Phenylamine has the structure:

The lone pair on the nitrogen touches the delocalized ring electrons . . .

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. . . and becomes delocalized with them:

That means that the lone pair is no longer fully available to combine with hydrogen ions. The nitrogen is still the most
electronegative atom in the molecule, and so the delocalized electrons will be attracted towards it, but the intensity of charge
around the nitrogen is nothing like what it is in, say, an ammonia molecule.
The other problem is that if the lone pair is used to join to a hydrogen ion, it is no longer available to contribute to the
delocalisation. That means that the delocalization would have to be disrupted if the phenylamine acts as a base. Delocalization
makes molecules more stable, and so disrupting the delocalization costs energy and will not happen easily.
Taken together - the lack of intense charge around the nitrogen, and the need to break some delocalization - this means that
phenylamine is a very weak base indeed.

3.7: Organic Acids and Bases is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Organic Acids by Jim Clark is licensed CC BY-NC 4.0.
Organic Bases by Jim Clark is licensed CC BY-NC 4.0.

3.7.8 https://chem.libretexts.org/@go/page/206467
CHAPTER OVERVIEW

4: Introduction to Alkenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
4.1: The π π Bond
Ethene is the formal IUPAC name for H2C=CH2, but it also goes by a common name: Ethylene. The name Ethylene is used
because it is like an ethyl group (C H C H ) but there is a double bond between the two carbon atoms in it. Ethene has the formula
2 3

C H and is the simplest alkene because it has the fewest carbons (two) necessary for a carbon-carbon double bond.
2 4

Introduction
Bonding in carbon is covalent, containing either sigma or π bonds. Carbon can make single, double, or triple bonds. The number of
bonds it makes determines the structure. With four single bonds, carbon has a tetrahedral structure, while with one double bond it's
structure is trigonal planar, and with a triple bond it has a linear structure.
A solitary carbon atom has four electrons, two in the 2s orbital, and one in each of the 2p and 2p orbitals, leaving the 2p orbital
x y z

empty. A single carbon atom can make up to four bonds, but by looking at its electron configuration this would not be possible
because there are only two electrons available to bond with. The other two are in a lone pair state, making them much less reactive
to another electron that is by itself. Well it is, in order to make the four bonds, the carbon atom promotes one of the 2s electrons
into the empty 2p orbital, leaving the carbon with four unpaired electrons allowing it to now form four bonds. The electron is not
z

promoted spontaneously. It becomes promoted when a photon of light with the correct wavelength hits the carbon atom. When this
photon hits the carbon atom it gives the atom enough energy to promote one of the lone pair electrons to the 2p orbital.
z

Sigma and Pi Bonds

All the bonds in Ethene are covalent, meaning that they are all formed by two adjacent atoms sharing their valence electrons. As
opposed to ionic bonds which hold atoms together through the attraction of two ions of opposite charges.
Sigma bonds are created when there is overlap of similar orbitals, orbitals that are aligned along the inter-nuclear axis. Common
sigma bonds are s + s , p + p and s + p , z is the axis of the bond on the xyz-plane of the atom.
z z z

π bonds are created when there is adequate overlap of similar, adjacent p orbitals, such as p +p and p +p . Each p orbital has two
x x y y

lobes, one usually indicated by a + and the other indicated by a - (sometimes one may be shaded while the other is not). This + and
- (shaded, not shaded) are only meant to indicate the opposite phase ϕ the wave functions, they do not indicate any type of
electrical charge. For a π bond to form both lobes of the p orbital must overlap, + with + and - with -. When a + lobe overlaps with
a - lobe this creates an anti-bonding orbital interaction which is much higher in energy, and therefore not a desirable interaction.
Usually there can be no π bonds between two atoms without having at least one sigma bond present first. But there are special
cases such as dicarbon (C ) where the central bond is a π bond not a sigma bond, but in cases like these the two atoms want to
2

have as much orbital overlap as possible so the bond lengths between the atoms are smaller than what is normally expected.
The π bond in ethene is weak compared to the sigma bond between the two carbons. This weakness makes the π bond and the
overall molecule a site of comparatively high chemical reactivity to an array of different substances. This is due to the high electron
density in the π bond, and because it is a weak bond with high electron density the π bond will easily break in order to form two
separate sigma bonds. Sites such as these are referred to as functional groups or functionalities. These groups have characteristic
properties and they control the reactivity of the molecule as a whole. How these functional groups and other reactants form various
products are an important concept in organic chemistry.

Orbital Bonding in Ethene

Ethene is made up of four 1s1 Hydrogen atoms and two 2s2 2p 1 2p 2 carbon atoms. These carbon atoms already have four
x y

electrons, but they each want to get four more so that they have a full eight in the valence shell. Having eight valence electrons
around carbon gives the atom itself the same electron configuration as neon, a noble gas. Carbon wants to have the same

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configuration as Neon because when it has eight valence electrons carbon is at its most stable, lowest energy state, it has all of the
electrons that it wants, so it is no longer reactive.

Structure of Ethene
Ethene is not a very complicated molecule. It contains two carbon atoms that are double bonded to each other, with each of these
atoms also bonded to two Hydrogen atoms.

This forms a total of three bonds to each carbon atom, giving them an sp hybridization. Since the carbon atom is forming three
2

sigma bonds instead of the four that it can, it only needs to hybridize three of its outer orbitals, instead of four. It does this by using
the 2s electron and two of the 2p electrons, leaving the other unchanged. This new orbital is called an sp hybrid because that's
2

exactly what it is, it is made from one s orbital and two p orbitals.

When atoms are an sp hybrid they have a trigonal planar structure. These structures are very similar to a 'peace' sign, there is a
2

central atom with three atoms around it, all on one plane. Trigonal planar molecules have an ideal bond angle of 120° on each side.

The H-C-H bond angle is 117°, which is very close to the ideal 120° of a carbon with sp hybridization. The other two angles (H-
2

C=C) are both 121.5°.

Rigidity in Ethene
There is rigidity in the Ethene molecule due to the double-bonded carbons. In Ethane there are two carbons that share a single
bond, this allows the two Methyl groups to rotate with respect to each other. These different conformations result in higher and
lower energy forms of Ethane. In Ethene there is no free rotation about the carbon-carbon sigma bond. There is no rotation because
there is also a π bond along with the sigma bond between the two carbons. A π bond is only formed when there is adequate overlap
between both top and bottom p-orbitals. In order for there to be free rotation the p-orbitals would have to go through a phase where
they are 90° from each other, which would break the π bond because there would be no overlap. Since the π bond is essential to the
structure of Ethene it must not break, so there can be not free rotation about the carbon-carbon sigma bond.

References
1. Vollhardt, K. P.C. & Shore, N. (2007). Organic Chemistry (5th Ed.). New York: W. H. Freeman.

Outside Links
Sigma Bond: http://en.Wikipedia.org/wiki/Sigma_bond
Pi Bond: http://en.Wikipedia.org/wiki/Pi_bond

4.1.2 https://chem.libretexts.org/@go/page/205320
Ethene (Ethylene): http://en.Wikipedia.org/wiki/Ethene
Trigonal Planar Structure & Picture: http://en.Wikipedia.org/wiki/Trigonal_planar
http://bcs.whfreeman.com/vollhardtsc...5e/default.asp

Problems
1. Write out the condensed formula for ethene.
2. Write out the Kekulé formula for ethene.
3. Write out the bond-line formula for ethene.
4. What are the distances between carbon and hydrogen atoms when they are bonded? Carbon-carbon single bond? Carbon-carbon
double bond?
5. Why is it that the carbons in ethene cannot freely rotate around the carbon-carbon double bond?

Answers
1. H2CCH2
2.

3. -
4. C-H: 1.076 angstroms, C-C: 1.54 angstroms, C=C: 1.330 angstroms
5. the carbons cannot freely rotate about the carbon-carbon double bond because in order to rotate the p-orbitals would have to pass
through a 90° point where there would no longer be any overlap, so the π bond would have to break for there to be free rotation.

Contributors

4.1: The π Bond is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Structure and Bonding in Ethene: The $\pi$ Bond is licensed CC BY-NC-SA 4.0.

4.1.3 https://chem.libretexts.org/@go/page/205320
4.2: Nomenclature of Alkenes
The molecular formula of a hydrocarbon provides information about the possible structural types it may represent. For example,
consider compounds having the formula C H . The formula of the five-carbon alkane pentane is C H so the difference in
5 8 5 12

hydrogen content is 4. This difference suggests such compounds may have a triple bond, two double bonds, a ring plus a double
bond, or two rings. Some examples are shown here, and there are at least fourteen others!

Hence, as with alkanes, a consistent nomenclature system needs to be adopted that can separate the nature of these unsaturated
chemicals. The simplest are the alkenes, which are hydrocarbons which have carbon-carbon double bond functional groups and are
unsaturated hydrocarbons with the molecular formula is CnH n, which is also the same molecular formula as cycloalkanes.
2

IUPAC Rules for Alkene Nomenclature

1. The ene suffix (ending) indicates an alkene or cycloalkene.
2. The longest chain chosen for the root name must include both carbon atoms of the double bond.
3. The root chain must be numbered from the end nearest a double bond carbon atom. If the double bond is in the center of the
chain, the nearest substituent rule is used to determine the end where numbering starts.
4. The smaller of the two numbers designating the carbon atoms of the double bond is used as the double bond locator.
5. If more than one double bond is present the compound is named as a diene, triene or equivalent prefix indicating the number
of double bonds, and each double bond is assigned a locator number.
6. Substituent groups containing double bonds are:
H2C=CH– Vinyl group
H2C=CH–CH2– Allyl group

Rule 1
Alkenes are named using the same general naming rules for alkanes, except that the suffix is now -ene. Here is a chart containing
the systemic name for the first twenty straight chain alkenes.

Name Molecular formula Name Molecular formula

Ethene C2H4 Undecene C11H22

Propene C3H6 Dodecene C12H24

Butene C4H8 Tridecene C13H26

Pentene C5H10 Tetradecene C14H28

Hexene C6H12 Pentadecene C15H30

Heptene C7H14 Hexadecene C16H32

Octene C8H16 Heptadecene C17H34

Nonene C9H18 Octadecene C18H36

Decene C10H20 Nonadecene C19H38

Did you notice how there is no methene? Because it is impossible for a carbon to have a double bond with nothing.

Rule 2
The parent structure is the longest chain containing both carbon atoms of the double bond. If the alkene contains only one double
bond and that double bond is terminal (the double bond is at one end of the molecule or another) then it is not necessary to place
any number in front of the name.
butane: C4H10 (CH CH CH3 2 2
CH
3
)
butene: C4H8 (CH =CHCH
2 2
CH
3
)

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If the double bond is not terminal (if it is on a carbon somewhere in the center of the chain) then the carbons should be numbered in
such a way as to give the first of the two double-bonded carbons the lowest possible number, and that number should precede the
"ene" suffix with a dash, as shown below.
correct: pent-2-ene (CH CH=CHCH CH )
3 2 3

incorrect: pent-3-ene (CH CH CH=CHCH )

3 2 3

The second one is incorrect because flipping the formula horizontally results in a lower number for the alkene.

Exercise 4.2.1
Name the following compounds:
a:

Answer a
1-pentene or pent-1-ene
Answer b
2-ethyl-1-hexene or 2-ethylhex-1-ene

Exercise 4.2.2
a: Name the following compound (hint: give the double bond the lowest possible numbers regardless of substituent placement).

b. Draw a structure for 4-methyl-2-pentene.

Answer a
4-methylpent-1-ene
Answer b

Rule 4
If there is more than one double bond in an alkene, all of the bonds should be numbered in the name of the molecule - even
terminal double bonds. The numbers should go from lowest to highest, and be separated from one another by a comma. The IUPAC
numerical prefixes are used to indicate the number of double bonds.
octa-2,4-diene: CH CH=CHCH=CHCH CH CH
3 2 2 3

deca-1,5-diene: CH =CHCH CH CH=CHCH CH

2 2 2 2 2
CH CH
2 3

Note that the numbering of "2-4" above yields a molecule with two double bonds separated by just one single bond. Double bonds
in such a condition are called "conjugated", and they represent an enhanced stability of conformation, so they are energetically
favored as reactants in many situations and combinations.

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Rule 4: Geometric Isomers
Double bonds can exist as geometric isomers and these isomers are designated by using either the cis / trans designation or the
more flexible E / Z designation.

cis Isomers have the two largest groups are on the same side of the double bond (left structure above) and trans Isomers have the
two largest groups are on opposite sides of the double bond (right structure above).E/Z nomenclature
If there are 3 or 4 non-hydrogen different atoms attached to the alkene then use the E, Z system.
E (entgegen) means the higher priority groups are opposite one another relative to the double bond.
Z (zusammen) means the higher priority groups are on the same side relative to the double bond.
E = entgegan ("trans") Z = zusamen ("cis")
Priority of groups is based on the atomic mass of attached atoms (not the size of the group). An atom attached by a multiple bond is
counted once for each bond.
fluorine atom > isopropyl group > n-hexyl group
deuterium atom > hydrogen atom
-CH2-CH=CH2 > -CH2CH2CH3

Example 4.2.5
Try to name the following compounds using both cis-trans and E/Z conventions:
a:

Answer a
4-methylpent-1-ene
Answer b

Example 4.2.3
What is the name of this molecule?

Solution

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In this diagram this is a cis conformation. It has both the substituents going upward. This molecule would be called (cis) 5-
chloro-3-heptene.)
Trans would look like this

Example 4.2.4
What is the name of this molecule?

Solution
In this example it is E-4-chloro-3-heptene. It is E because the Chlorine and the CH2CH3 are the two higher priorities and they
are on opposite sides.

Common names
Remove the -ane suffix and add -ylene. There are a couple of unique ones like ethenyl's common name is vinyl and 2-propenyl's
common name is allyl. That you should know are...
vinyl substituent H2C=CH-
allyl substituent H2C=CH-CH2-
allene molecule H2C=C=CH2
isoprene

Endocyclic Alkenes
Endocyclic double bonds have both carbons in the ring and exocyclic double bonds have only one carbon as part of the ring.

Cyclopentene is an example of an endocyclic double bond.

Methylenecylopentane is an example of an exocyclic double bond.

Exercise 4.2.1
Name the following compounds:
a:

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b:

Answer a
1-methylcyclobutene. The methyl group places the double bond. It is correct to also name this compound as 1-
methylcyclobut-1-ene.
Answer b
1-ethenylcyclohexene, the methyl group places the double bond. It is correct to also name this compound as 1-
ethenylcyclohex-1-ene. A common name would be 1-vinylcyclohexene.

Exercise 4.2.1
Name the following compounds:
a:

Exercise 4.2.1
Draw structures for the following 2-vinyl-1,3-cyclohexadiene

Answer

References
1. Vollhardt, Peter, and Neil E. Schore. Organic Chemistry: Structure and Function. 5th Edition. New York: W. H. Freeman &
Company, 2007.

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Problems
Try to name the following compounds...

1-pentene or pent-1-ene

2-ethyl-1-hexene or 2-ethylhex-1-ene
Try to draw structures for the following compounds...
2-pentene
CH3–CH=CH–CH2–CH3
3-heptene
CH3–CH2–CH=CH–CH2–CH2–CH3
b. Give the double bond the lowest possible numbers regardless of substituent placement.
• Try to name the following compound...
J
• Try to draw a structure for the following compound...
4-methyl-2-pentene J
Name the following structures:

v. Draw (Z)-5-Chloro-3-ethly-4-hexen-2-ol.

Answers
I. trans-8-ethyl-3-undecene
II. E-5-bromo-4-chloro-7,7-dimethyl-4-undecene
III. Z-1,2-difluoro-cyclohexene
IV. 4-ethenylcyclohexanol.

Contributors
S. Devarajan (UCD)
Richard Banks (Boise State University)

4.2.6 https://chem.libretexts.org/@go/page/205321
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Jonathan Mooney (McGill University)

4.2: Nomenclature of Alkenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

4.2.7 https://chem.libretexts.org/@go/page/205321
4.3: Degree of Unsaturation
There are many ways one can go about determining the structure of an unknown organic molecule. Although, nuclear magnetic
resonance (NMR) and infrared radiation (IR) are the primary ways of determining molecular structures, calculating the degrees of
unsaturation is useful information since knowing the degrees of unsaturation make it easier for one to figure out the molecular
structure; it helps one double-check the number of π bonds and/or cyclic rings.

Saturated vs. Unsaturated Molecules

In the lab, saturation may be thought of as the point when a solution cannot dissolve anymore of a substance added to it. In terms of
degrees of unsaturation, a molecule only containing single bonds with no rings is considered saturated.

CH3CH2CH3 1-methyoxypentane

Unlike saturated molecules, unsaturated molecules contain double bond(s), triple bond(s) and/or ring(s).

CH3CH=CHCH3 3-chloro-5-octyne

Calculating Degrees of Unsaturation (DoU)

Degree of Unsaturation (DoU) is also known as Double Bond Equivalent. If the molecular formula is given, plug in the numbers
into this formula:
2C + 2 + N − X − H
DoU = (4.3.1)
2

C is the number of carbons

N is the number of nitrogens
X is the number of halogens (F, Cl, Br, I)

H is the number of hydrogens

As stated before, a saturated molecule contains only single bonds and no rings. Another way of interpreting this is that a saturated
molecule has the maximum number of hydrogen atoms possible to be an acyclic alkane. Thus, the number of hydrogens can be
represented by 2C+2, which is the general molecular representation of an alkane. As an example, for the molecular formula C3H4
the number of actual hydrogens needed for the compound to be saturated is 8 [2C+2=(2x3)+2=8]. The compound needs 4 more
hydrogens in order to be fully saturated (expected number of hydrogens-observed number of hydrogens=8-4=4). Degrees of
unsaturation is equal to 2, or half the number of hydrogens the molecule needs to be classified as saturated. Hence, the DoB
formula divides by 2. The formula subtracts the number of X's because a halogen (X) replaces a hydrogen in a compound. For
instance, in chloroethane, C2H5Cl, there is one less hydrogen compared to ethane, C2H6.
For a compound to be saturated, there is one more hydrogen in a molecule when nitrogen is present. Therefore, we add the number
of nitrogens (N). This can be seen with C3H9N compared to C3H8. Oxygen and sulfur are not included in the formula because
saturation is unaffected by these elements. As seen in alcohols, the same number of hydrogens in ethanol, C2H5OH, matches the
number of hydrogens in ethane, C2H6.
The following chart illustrates the possible combinations of the number of double bond(s), triple bond(s), and/or ring(s) for a given
degree of unsaturation. Each row corresponds to a different combination.

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One degree of unsaturation is equivalent to 1 ring or 1 double bond (1 π bond).
Two degrees of unsaturation is equivalent to 2 double bonds, 1 ring and 1 double bond, 2 rings, or 1 triple bond (2 π bonds).
DoU Possible combinations of rings/ bonds

# of rings # of double bonds # of triple bonds

1 1 0 0

0 1 0

2 2 0 0

0 2 0

0 0 1

1 1 0

3 3 0 0

2 1 0

1 2 0

0 1 1

0 3 0

1 0 1

Remember, the degrees of unsaturation only gives the sum of double bonds, triple bonds and/or rings. For instance, a degree of
unsaturation of 3 can contain 3 rings, 2 rings+1 double bond, 1 ring+2 double bonds, 1 ring+1 triple bond, 1 double bond+1 triple
bond, or 3 double bonds.

 Example: Benzene

What is the Degree of Unsaturation for Benzene?

Solution
The molecular formula for benzene is C6H6. Thus,
DoU= 4, where C=6, N=0,X=0, and H=6. 1 DoB can equal 1 ring or 1 double bond. This corresponds to benzene containing 1
ring and 3 double bonds.

However, when given the molecular formula C6H6, benzene is only one of many possible structures (isomers). The following
structures all have DoB of 4 and have the same molecular formula as benzene.

References
1. Vollhardt, K. P.C. & Shore, N. (2007). Organic Chemistry (5thEd.). New York: W. H. Freeman. (473-474)
2. Shore, N. (2007). Study Guide and Solutions Manual for Organic Chemistry (5th Ed.). New York: W.H. Freeman. (201)

Problems
1. Are the following molecules saturated or unsaturated:

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1. (b.) (c.) (d.) C10H6N4
2. Using the molecules from 1., give the degrees of unsaturation for each.
3. Calculate the degrees of unsaturation for the following molecular formulas:
1. (a.) C9H20 (b.) C7H8 (c.) C5H7Cl (d.) C9H9NO4
4. Using the molecular formulas from 3, are the molecules unsaturated or saturated.
5. Using the molecular formulas from 3, if the molecules are unsaturated, how many rings/double bonds/triple bonds are
predicted?

Answers
1.
(a.) unsaturated (Even though rings only contain single bonds, rings are considered unsaturated.)
(b.) unsaturated
(c.) saturated
(d.) unsaturated
2. If the molecular structure is given, the easiest way to solve is to count the number of double bonds, triple bonds and/or rings.
However, you can also determine the molecular formula and solve for the degrees of unsaturation by using the formula.
(a.) 2
(b.) 2 (one double bond and the double bond from the carbonyl)
(c.) 0
(d.) 10
3. Use the formula to solve
(a.) 0
(b.) 4
(c.) 2
(d.) 6
4.
(a.) saturated
(b.) unsaturated
(c.) unsaturated
(d.) unsaturated
5.
(a.) 0 (Remember-a saturated molecule only contains single bonds)
(b.) The molecule can contain any of these combinations (i) 4 double bonds (ii) 4 rings (iii) 2 double bonds+2 rings (iv) 1 double
bond+3 rings (v) 3 double bonds+1 ring (vi) 1 triple bond+2 rings (vii) 2 triple bonds (viii) 1 triple bond+1 double bond+1
ring (ix) 1 triple bond+2 double bonds
(c.) (i) 1 triple bond (ii) 1 ring+1 double bond (iii) 2 rings (iv) 2 double bonds
(d.) (i) 3 triple bonds (ii) 2 triple bonds+2 double bonds (iii) 2 triple bonds+1 double bond+1 ring (iv)... (As you can see, the
degrees of unsaturation only gives the sum of double bonds, triple bonds and/or ring. Thus, the formula may give numerous
possible structures for a given molecular formula.)

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Contributors
Kim Quach (UCD)

4.3: Degree of Unsaturation is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Degree of Unsaturation is licensed CC BY-NC-SA 4.0.

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4.4: Electrophilic Addition Reactions of Alkenes
 Objectives

After completing this section, you should be able to

1. explain the term “electrophilic addition reaction,” using the reaction of a protic acid, HX, with an alkene as an example.
2. write the mechanism for the reaction of a protic acid, HX, with an alkene.
3. sketch a reaction energy diagram for the electrophilic addition of an acid, HX, to an alkene.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
carbocation (carbonium ion)
electrophilic addition reaction

 Study Notes

An electrophilic addition reaction is a reaction in which a substrate is initially attacked by an electrophile, and the overall
result is the addition of one or more relatively simple molecules across a multiple bond.
The mechanism for the addition of hydrogen halide to propene shown in the reading is quite detailed. Normally, an organic
chemist would write the reaction scheme as follows:
H H CH3 CH3
H X
C C C H C X
H3C H H CH3 CH3

However, the more detailed mechanism shown in the reading does allow you to see the exact fate of all the electrons involved
in the reaction.
In your previous chemistry course, you were probably taught the importance of balancing chemical equations. It may come as
a surprise to you that organic chemists usually do not balance their equations, and often represent reactions using a format
which is quite different from the carefully written, balanced equations encountered in general chemistry courses. In fact,
organic chemists are rarely interested in the inorganic products of their reactions; furthermore, most organic reactions are non-
quantitative in nature.
In many of the reactions in this course, the percentage yield is indicated beneath the products: you are not expected to
memorize these figures. The question of yield is very important in organic chemistry, where two, five, ten or even twenty
reactions may be needed to synthesize a desired product. For example, if a chemist wishes to prepare compound D by the
following reaction sequence:

A → B → C → D

and each of the individual steps gives only a 50% yield, one mole of A would give only
50% 50% 50%
1 mol × × × = 0.125 mol of D
100% 100% 100%

You will gain first-hand experience of such situations in the laboratory component of this course.

Introduction
One of the most important reactions for alkenes is called electrophilic addition. In this chapter several variations of the electrophilic
addition reaction will be discussed. Each case will have aspects common among all electrophilic addition. In this section, the
electrophilic addition reaction will be discussed in general to provide a better understanding of subsequent alkene reactions.
As discussed in Section 6-5, the double bond in alkenes is electron rich due to the prescience of 4 electrons instead of the two in a
single bond. Also, the pi electrons are positioned above and below the double bond making them more accessibly for reactions.

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Overall, double bonds can easily donate lone pair electrons to act like a nucleophile (nucleus-loving, electron rich, a Lewis acid).
During an electrophilic addition reactions double bonds donate lone pair electrons to an electrophile (Electron-loving, electron
poor, a Lewis base). There are many types of electrophilic addition, but this section will focus on the addition of hydrogen halides
(HX). Many of the basic ideas discussed will aplicable to subsequent electrophilic addition reactions.

General Reaction
Overall during this reaction the pi bond of the alkene is broken to form two single, sigma bonds. As shown in the reaction
mechanism, one of these sigma bonds is connected to the H and the other to the X of the hydrogen halide. This reaction works well
with HBr and HCl. HI can also but used but is is usually generated during the reaction by reacting potassium iodidie (KI) with
phosphoric acid (H3PO4).

X H
Ether
C C + HX C C

Alkene Hydrogen Alkyl Halide

Halide

 Example 4.4.1
H3C H Br H
Ether
C C + HBr H3C C C H
H3C H H 3C H

Cl H
Ether
H3CH2CH2CH CH2 + HCl H3C C C H
H3C H

I
KI
H3PO4

Addition to symmetrical alkenes

What happens?
All alkenes undergo addition reactions with the hydrogen halides. A hydrogen atom joins to one of the carbon atoms originally in
the double bond, and a halogen atom to the other.
For example, with ethene and hydrogen chloride, you get chloroethane:

H 2C CH2 + HCl H 3C CH2Cl

Figure 4.4.1 Electrophilic addition of HCl to ethene.

With but-2-ene you get 2-chlorobutane:

H H
H 3C C C CH3 + HCl H3C CH2 C CH3
H
Cl

Figure 4.4.2 Electrophilic addition of HCl to but-2-ene.

What happens if you add the hydrogen to the carbon atom at the right-hand end of the double bond, and the chlorine to the left-
hand end? You would still have the same product. The chlorine would be on a carbon atom next to the end of the chain - you would
simply have drawn the molecule flipped over in space. That would be different of the alkene was unsymmetrical - that's why we
have to look at them separately.

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Mechanism
Step 1) Electrophilic Attack
During the first step of the mechanism, the 2 pi electrons from the double bond attack the H in the HBr electrophile which is shown
by a curved arrow. The two pi electrons form a C-H sigma bond between the hydrogen from HBr and a carbon from the double
bond. Simultaneously the electrons from the H-X bond move onto the halogen to form a halide anion. The removal of pi electrons
form the double bond makes one of the carbons become an electron deficient carbocation intermediate. This carbon is sp2
hybridized and the positive charge is contained in an unhybridized p orbital.
Step 2) Nucleophilic attack by halide anion
The formed carbocation now can act as an electrophile and accept an electron pair from the nucleophilic halide anion. The electron
pair becomes a X-C sigma bond to create the neutral alkyl halide product of electrophilic addition.

H X X

H H H H H X
C C H C C H C C H
1 - electrophilic 2 - nucleophilic
H H attack H H trapping H H

Figure 4.4.3 Mechanism of Electrophilic Addition of Hydrogen Halide to Ethene

H X X

H H H H X H
C C C C H H C C H
1 - electrophilic 2 - nucleophilic
H3 C H attack H3C H trapping H H

Figure 4.4.4 Mechanism of Electrophilic Addition of Hydrogen Halide to Propene

All of the halides (HBr, HCl, HI, HF) can participate in this reaction and add on in the same manner. Although different halides do
have different rates of reaction, due to the H-X bond getting weaker as X gets larger (poor overlap of orbitals)s.

Reaction Energy Diagram

An energy diagram for the two-step electrophilic addition mechanism is shown below. The energy diagram has two peaks which
represent the transition state for each mechanistic step. The peaks are separated by a valley which represents the high energy
carbocation reaction intermediate. Because the energy of activation for the first step of the mechanism (ΔE ‡ 1) is much larger than
the second (ΔE ‡ 1), the first step of the mechanism is the rate-determining step. Both the alkene and the hydrogen halide are
reactants in the first step of the mechanism, this electrophilic addition is a second order reaction and the rate law expression can be
written rate = k[Alkene][HX]. Also, any structural feature which can stabilize the transition state between the reactants the
carbocation intermediate will lower ΔE ‡ 1 and thereby increase the reaction rate. Overall, the alkyl halide product of this reaction
more stable than the reactants making the reaction exothermic.

Reaction rates
Variation of rates when you change the halogen
Reaction rates increase in the order HF - HCl - HBr - HI. Hydrogen fluoride reacts much more slowly than the other three, and is
normally ignored in talking about these reactions.
When the hydrogen halides react with alkenes, the hydrogen-halogen bond has to be broken. The bond strength falls as you go
from HF to HI, and the hydrogen-fluorine bond is particularly strong. Because it is difficult to break the bond between the

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hydrogen and the fluorine, the addition of HF is bound to be slow.
Variation of rates when you change the alkene
This applies to unsymmetrical alkenes as well as to symmetrical ones. For simplicity the examples given below are all symmetrical
ones- but they don't have to be.
Reaction rates increase as the alkene gets more complicated - in the sense of the number of alkyl groups (such as methyl groups)
attached to the carbon atoms at either end of the double bond. For example:
H H H CH3 H3C CH3
C C C C C C
H H H3C H H3C CH3

reactivity increases

There are two ways of looking at the reasons for this - both of which need you to know about the mechanism for the reactions.
Alkenes react because the electrons in the pi bond attract things with any degree of positive charge. Anything which increases the
electron density around the double bond will help this.
Alkyl groups have a tendency to "push" electrons away from themselves towards the double bond. The more alkyl groups you
have, the more negative the area around the double bonds becomes.
The more negatively charged that region becomes, the more it will attract molecules like hydrogen chloride.
The more important reason, though, lies in the stability of the intermediate ion formed during the reaction. The three examples
given above produce these carbocations (carbonium ions) at the half-way stage of the reaction:
H H H H
C C H C C
H H H H
a primary carbocation

H CH3 H CH3 ions getting

C C H C C more
energetically
H 3C H H 3C H stable and so
a secondary carbocation easier to form

H 3C CH3 H CH3
C C H 3C C C
H 3C CH3 H 3C CH3
a tertiary carbocation

The stability of the intermediate ions governs the activation energy for the reaction. As you go towards the more complicated
alkenes, the activation energy for the reaction falls. That means that the reactions become faster.

Representing Organic Reactions

Organic reaction equations are often written in one of two ways. The reactant for the reaction is written to the left of the reaction
arrow. The products are written to the right of the arrow. The reagent for the reaction is written above the arrow. Other reaction
conditions such as the solvent or the temperature can be written above or below the reaction arrow.
Reaction solvent

H3 C H Br H
Ether
C C + HBr H3 C C C H
H H 25 oC H
H
Reactant Reagent Product
Reaction temperature

Alternativley the reactant and reagent can both be written to the left of the reaction arrow. This is typically done to highlight the
importance of the reactant. The solvent and reaction temperature are still written above or below the reaction arrow. The reaction
products are still written to the right of the reaction arrow.

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Reagent Reaction solvent

H 3C H HBr, Ether Br H
C C H 3C C C H
25 oC H
H H H
Reactant Product
Reaction temperature

4.4: Electrophilic Addition Reactions of Alkenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
7.8: Electrophilic Addition Reactions of Alkenes by Dietmar Kennepohl, Jim Clark, John Roberts, Krista Cunningham, Marjorie C.
Caserio, Steven Farmer, Tim Soderberg, William Reusch is licensed CC BY-SA 4.0.

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4.5: Carbocation Structure and Stability
 Objectives

After completing this section, you should be able to

1. describe the geometry of a given carbocation.
2. arrange a given series of carbocations in order of increasing or decreasing stability.
3. explain the relative stability of methyl, primary, secondary and tertiary carbocations in terms of hyperconjugation and
inductive effects.

 Study Notes
Although hyperconjugation can be used to explain the relative stabilities of carbocations, this explanation is certainly not the
only one, and is by no means universally accepted. A more common explanation, involving the concept of an inductive effect,
is given below.
It is a general principle in chemistry that the more a charge is dispersed, the more stable is the species carrying the charge. Put
simply, a species in which a positive charge is shared between two atoms would be more stable than a similar species in which
the charge is borne wholly by a single atom. In a tertiary carbocation, the positively charged carbon atom attracts the bonding
electrons in the three carbon-carbon sigma (σ) bonds, and thus creates slight positive charges on the carbon atoms of the three
surrounding alkyl groups (and, indeed, on the hydrogen atoms attached to them). Chemists sometimes use an arrow to
represent this inductive release:
H
H C H 𝛅+
C
H
𝛅+
H C C C C
H 𝛅+
H C H C

Note: These diagrams do not reflect the geometry of the carbocation. The overall charge on the carbocation remains
unchanged, but some of the charge is now carried by the alkyl groups attached to the central carbon atom; that is, the charge
has been dispersed.
In the tertiary carbocation shown above, the three alkyl groups help to stabilize the positive charge. In a secondary carbocation,
only two alkyl groups would be available for this purpose, while a primary carbocation has only one alkyl group available.
Thus the observed order of stability for carbocations is as follows:
tertiary > secondary > primary > methyl.

Stability of carbocation intermediates

The next step in understanding why Markovnikov's rule is often followed in electrophilic additions, involves understanding the
structure and stability of the carboncation intermediate formed during the mechanism.

Carbocation Structure
Carbocations typically have three substituents which makes the carbon sp2 hybridized and gives the overall molecule a trigonal
planar geometry. The carbocation's substituents are all in the same plane and have a bond angle of 120o between them. The carbon
atom in the carbocation is electron deficient; it only has six valence electrons which are used to form three sigma covalent bonds
with the substituents. The carbocation carbon has an unoccupied p orbital which is perpendicular to the plane created by the
substituents. The p orbital can easily accept electron pairs during reactions making carbocations excellent Lewis acids.

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Unoccupied p
orbital

R
120o C R''
R'

Stability of Carbocation Intermediates

By being a reactive intermediate of the electrophilic addition mechanism, the stability of a carbocation has a direct effect on the
reaction.
The critical question now becomes, what stabilizes a carbocation?
A positively charged species such as a carbocation is very electron-poor, and thus anything which donates electron density will help
to stabilize it. Conversely, a carbocation will be destabilized by an electron withdrawing group.
EDG EWG
C C
R R
R R
electron donating group stabilizes a carbocation electron withdrawing group destabilizes a carbocation

Extensive experimental evidence has shown that a carbocation becomes more stable as the number of alkyl substituents increases.
Carbocations can be given a designation based on the number of alkyl groups attached to the carbocation carbon. Three alkyl
groups is called a tertiary (3o) carbocation, 2 alkyl groups is called secondary (2o), and 1 alkyl group is called primary (1o). No
alkyl groups are attached (3 hydrogen substituents) is called a methyl carbocation.
The overall order of stability is as follows:
H CH3 CH3 CH3

H H CH3 CH3
H H H H 3C

methyl primary secondary tertiary

least stable most stable

Alkyl groups stabilized carbocations for two reasons. The first is through inductive effects. As discussed in Section 2-1, inductive
effects occur when the electrons in covalent bonds are shifted towards an nearby atom with a higher electronegativity. In this case,
the positively charged carbocation draws in electron density from the surrounding substituents thereby gaining stabilization by
slightly reducing its positive charge. Alkyl groups are more effective at inductively donating electron density than a hydrogen
because they are larger, more polarizable, and contain more bonding electrons. As more alkyl groups are attached to the
carbocation more inductive electron donation occurs and the carbocation becomes more stable.
The second reason alkyl groups stabilize carbocations is through hyperconjugation. As previously discussed in Section 7.6,
hyperconjugation is an electron donation that occurs from the parallel overlap of p orbitals with adjacent hybridized orbitals
participating in sigma bonds. This electron donation serves to stabilize the carbocation. As the number of alkyl substituents
increases, the number of sigma bonds available for hyperconjugation increases, and the carbocation tends to become more
stabilized.

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In the example of ethyl carbocation shown below, the p orbital from a sp2 hybridized carbocation carbon involved interacts with a
sp3 hybridized orbital participating in an adjacent C-H sigma bond. Electron density from the C-H sigma bond is donated into
carbocation's p orbital providing stabilization.
The molecular orbital of the ethyl carbocation shows the interaction of electrons in methyl group's C-H sigma bonds with the
adjacent empty p orbital from the carbocation. The interaction creates a bonding molecular orbital which extends over the three
atom chain (C-C-H) involved in hyperconjugation. The expanded molecular orbital helps to stabilize the carbocation.

It is not accurate to say, however, that carbocations with higher substitution are always more stable than those with less
substitution. Just as electron-donating groups can stabilize a carbocation, electron-withdrawing groups act to destabilize
carbocations. Carbonyl groups are electron-withdrawing by inductive effects, due to the polarity of the C=O double bond. It is
possible to demonstrate in the laboratory that carbocation A below is more stable than carbocation B, even though A is a primary
carbocation and B is secondary.
O O
CH3 CH3
O O

A: more stable B: less stable

The difference in stability can be explained by considering the electron-withdrawing inductive effect of the ester carbonyl. Recall
that inductive effects - whether electron-withdrawing or donating - are relayed through covalent bonds and that the strength of the
effect decreases rapidly as the number of intermediary bonds increases. In other words, the effect decreases with distance. In
species B the positive charge is closer to the carbonyl group, thus the destabilizing electron-withdrawing effect is stronger than it is
in species A.

In the next chapter we will see how the carbocation-destabilizing effect of electron-withdrawing fluorine substituents can be
used in experiments designed to address the question of whether a biochemical nucleophilic substitution reaction is SN1 or
SN2.

Stabilization of a carbocation can also occur through resonance effects, and as we have already discussed in the acid-base chapter,
resonance effects as a rule are more powerful than inductive effects. Consider the simple case of a benzylic carbocation:

CH2 CH2 CH2 CH2

This carbocation is comparatively stable. In this case, electron donation is a resonance effect. Three additional resonance structures
can be drawn for this carbocation in which the positive charge is located on one of three aromatic carbons. The positive charge is
not isolated on the benzylic carbon, rather it is delocalized around the aromatic structure: this delocalization of charge results in
significant stabilization. As a result, benzylic and allylic carbocations (where the positively charged carbon is conjugated to one or
more non-aromatic double bonds) are significantly more stable than even tertiary alkyl carbocations.

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Because heteroatoms such as oxygen and nitrogen are more electronegative than carbon, you might expect that they would by
definition be electron withdrawing groups that destabilize carbocations. In fact, the opposite is often true: if the oxygen or nitrogen
atom is in the correct position, the overall effect is carbocation stabilization. This is due to the fact that although these heteroatoms
are electron withdrawing groups by induction, they are electron donating groups by resonance, and it is this resonance effect which
is more powerful. (We previously encountered this same idea when considering the relative acidity and basicity of phenols and
aromatic amines in section 7.4). Consider the two pairs of carbocation species below:

O O O

more stable less stable

(no resonance delocalization)

N N N
H H H
more stable less stable
(no resonance delocalization)

In the more stable carbocations, the heteroatom acts as an electron donating group by resonance: in effect, the lone pair on the
heteroatom is available to delocalize the positive charge. In the less stable carbocations the positively-charged carbon is more than
one bond away from the heteroatom, and thus no resonance effects are possible. In fact, in these carbocation species the
heteroatoms actually destabilize the positive charge, because they are electron withdrawing by induction.
Finally, vinylic carbocations, in which the positive charge resides on a double-bonded carbon, are very unstable and thus unlikely
to form as intermediates in any reaction.
R
C C R
R

a vinylic carbocation (very unstable)

 Example 4.5.1
In which of the structures below is the carbocation expected to be more stable? Explain.

O O O O
OH OH
R R

N OH N OH

H H

Answer
In the carbocation on the left, the positive charge is located in a position relative to the nitrogen such that the lone pair of
electrons on the nitrogen can be donated to fill the empty orbital. This is not possible for the carbocation species on the
right.

O O O O
OH OH
R R
×
N OH N OH
H
H H

O O
OH
R

N OH

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 Example 4.5.2

Draw a resonance structure of the crystal violet cation in which the positive charge is delocalized to one of the nitrogen atoms.

Answer

N N N N

N N

When considering the possibility that a nucleophilic substitution reaction proceeds via an SN1 pathway, it is critical to evaluate the
stability of the hypothetical carbocation intermediate. If this intermediate is not sufficiently stable, an SN1 mechanism must be
considered unlikely, and the reaction probably proceeds by an SN2 mechanism. In the next chapter we will see several examples of
biologically important SN1 reactions in which the positively charged intermediate is stabilized by inductive and resonance effects
inherent in its own molecular structure.

 Example 4.5.3

State which carbocation in each pair below is more stable, or if they are expected to be approximately equal. Explain your
reasoning.
1 2 1 2

NH2 NH2
a) d)

F F
b) e)

F F

Answer
a) 1 (tertiary vs. secondary carbocation)
b) 1 (tertiary vs. secondary carbocation)
c) 2 (positive charge is further from electron-withdrawing fluorine)
d) 1 (lone pair on nitrogen can donate electrons by resonance)
e) 1 (allylic carbocation – positive charge can be delocalized to a second carbon)

4.5: Carbocation Structure and Stability is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
7.10: Carbocation Structure and Stability by Dietmar Kennepohl, Krista Cunningham, Steven Farmer, Tim Soderberg is licensed CC BY-
SA 4.0.

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4.6: Carbocation Rearrangements
Earlier in this chapter we introduced the so-called 'Markovnikov rule', which can be used to predict the favored regiochemical
outcome of electrophilic additions to asymmetric alkenes. According to what we have learned, addition of H Br to 3-methyl-1-
butene should result in a secondary bromoalkane. However, the predominant product that is actually be observed in this reaction is
a tertiary alkyl bromide! Little or no secondary alkyl bromide forms.

To explain this result, let's take a look at the mechanism for the reaction:
Electrophilic addition with a hydride shift:

Protonation of the double bond results in a secondary carbocation (step 1). What happens next (step 2 above) is a process called a
carbocation rearrangement, and more specifically, a hydride shift. The electrons in the bond between carbon #3 and a hydrogen are
attracted by the positive charge on carbon #2, and they simply shift over to fill the empty p orbital, pulling the proton over with
them. Notice that the hydride, in shifting, is not acting as an actual leaving group - a hydride ion is a very strong base and a very
poor leaving group.

 An important reminder

A hydride ion (H ) is a proton plus two electrons. Be sure not to confuse a hydride ion with
−
H
+
, which is just a proton
without any electrons.

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As the shift proceeds, a new C −H σ bond is formed at carbon #2, and carbon #3 is left with an empty p orbital and a positive
charge.

What is the thermodynamic driving force for this process? Notice that the hydride shift results in the conversion of a secondary
carbocation to a (more stable) tertiary carbocation - a thermodynamically downhill step. As it turns out, the shift occurs so quickly
that it is accomplished before the bromide nucleophile has time to attack at carbon #2. Rather, the bromide will attack (step 3) at
carbon #3 to complete the addition.
Consider another example. When H Br is added to 3,3-dimethyl-1-butene, the product is a tertiary - rather than a secondary - alkyl
bromide.

Notice that in the observed product, the carbon framework has been rearranged: the methyl carbon indicated by a red dot has
shifted from carbon #3 to carbon #2. This is an example of another type of carbocation rearrangement, called a methyl shift.
Below is the mechanism for the reaction. Once again a secondary carbocation intermediate is formed in step 1. In this case, there is
no hydrogen on carbon #3 available to shift over create a more stable tertiary carbocation. Instead, it is a methyl group that does the
shifting, as the electrons in the carbon-carbon σ bond move over to fill the empty orbital on carbon #2 (step 2 below).
Electrophilic addition with methyl shift:

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The methyl shift results in the conversion of a secondary carbocation to a more stable tertiary carbocation. The end result is a
rearrangement of the carbon framework of the molecule.

 Exercise 14.6.1

Which of the following carbocations are likely to undergo a shift? If a shift is likely, draw the new
carbocation that would result.

 Exercise 14.6.2

In the (non-biochemcial) reactions below, the major product forms as the result of a hydride or
methyl shift from a carbocation intermediate. Predict the structure of the major product for each
reaction, disregarding stereochemistry.

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 Exercise 14.6.3

Draw the most abundant product of this laboratory Friedel-Crafts reaction:

Carbocation rearrangements are involved in many known biochemical reactions. Rearrangements are particularly important in
carbocation-intermediate reactions in which isoprenoid molecules cyclize to form complex multi-ring structures. For example, one
of the key steps in the biosynthesis of cholesterol is the electrophilic cyclization of oxidosqualene to form a steroid called lanosterol
(E.C. 5.4.99.7).

This complex but fascinating reaction has two phases. The first phase is where the actual cyclization takes place, with the formation
of four new carbon-carbon bonds and a carbocation intermediate. This phase is a 'cascade' of electrophilic alkene addition steps,
beginning with addition of an electrophilic functional group called an 'epoxide'.
The epoxide functional group - composed of a three membered ring with two carbons and an oxygen - is relatively rare in
biomolecules and biochemical reactions, and for this reason it is not discussed in detail in this book. However, epoxides are an

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important and versatile intermediate in laboratory organic synthesis, so you will learn much more about how they are made and
how they react if you take a course in chemical synthesis. For now, it is sufficient to recognize that the carbon atoms of an epoxide
are potent electrophiles, due to both the carbon-oxygen bond dipoles and the inherent strain of the three membered ring.
The second phase involves a series of hydride and methyl shifts culminating in a deprotonation. In the exercise below, you will
have the opportunity to work through the entire cyclase reaction mechanism. In section 15.7, we will take a look at how the
epoxide group of oxidosqualene is formed. Trends Pharm. Sci. 2005, 26, 335; J. Phys Chem B., 2012, 116, 13857.

 Exercise 14.6.4

a. The figure below outlines the first, cyclizing phase of the reaction that converts oxidosqualene
to lanosterol. However, the diagram is missing electron movement arrows, and
intermediates 1-4 are all missing formal charges - fill these in.
First phase (ring formation):

b. Next comes the 'shifting' phase of the reaction. Once again, supply the missing
mechanistic arrows.
Second phase: rearrangement and deprotonation

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c. Look at the first and last steps of the entire process: overall, would you describe this as
an electrophilic addition or substitution?

The oxidosqualene cyclization reaction and others like it are truly remarkable examples of the exquisite control exerted by enzymes
over the course of a chemical reaction. Consider: an open-chain starting molecule is converted, by a single enzyme, into a complex
multiple fused-ring structure with seven chiral centers. Oxidosqualene could potentially cyclize in many different ways, resulting in
a great variety of different products. In order for the enzyme to catalyze the formation of a single product with the correct
connectivity and stereochemistry, the enzyme must be able to maintain precise control of the conformation of the starting
compound and all reactive intermediates in the active site, while also excluding water molecules which could attack at any of the
positively charged carbons.

This page titled 4.6: Carbocation Rearrangements is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Tim
Soderberg via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request.
14.6: Carbocation Rearrangements by Tim Soderberg is licensed CC BY-NC-SA 4.0. Original source:
https://digitalcommons.morris.umn.edu/chem_facpubs/1/.

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4.7: Markovnikov Addition
Markovnikov addition, also called Markovnikov's rule, states that a protic acid (HX) will add to an alkene such that the proton will
bond to the less substituted carbon.

Introduction
During this addition, the carbocation intermediate bares a positive charge on the most substituted carbon. The more substituted
carbon, the more stable (tertiary > secondar > primary > methyl). If the reverse occurs, that is the more electronegative atom (X)
ends up bonding to the least substituted carbon, it is termed anti-Markovnikov addition. The figure below shows a figure of both
additions:

Fig. 1. Markovnikov and anti-Markovnikov additions of HBr to 1-methylcyclohexene.

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CHAPTER OVERVIEW

5: Addition Reactions of Alkenes

5.1: Electrophilic Addition of Hydrogen Halides
5.2: Addition of Strong Brønsted Acids
5.3: Electrophilic Addition of Halogens to Alkenes
5.4: Hydration of Alkenes
5.5: Formation of alcohols from alkenes
5.6: Catalytic Hydrogenation
5.7: Hydration- Oxymercuration-Demercuration
5.8: Hydration- Hydroboration-Oxidation
5.9: Oxidative Cleavage of Alkenes
5.10: Free Radicals
5.11: Addition of Radicals to Alkenes
5.12: Anti-Markovnikov Product Formation
5.13: Homolytic Cleavage and Bond Dissociation Energies
5.14: Polymerization of Alkenes

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1
5.1: Electrophilic Addition of Hydrogen Halides
Due to the nature of the π bond, π bonds can act like a nucleophile and undergo addition of electrophiles. The π electrons have a
high electron density in the π electron cloud which can be easily polarized (give up the electrons) and can act like a nucleophile
(nucleus-loving due to too many electrons; wants to give them away to electrophile). This behavior is very similar to the behavior
that the lone pair electrons have on a Lewis base.

Introduction
There are many types of electrophilic addition, but this section will focus on the addition of hydrogen halides.

Reaction
The addition of hydrogen halides is one of the easiest electrophilic addition reactions because it uses the simplest electrophile: the
proton. Hydrogen halides provide both a electrophile (proton) and a nucleophile (halide). First, the electrophile will attack the
double bond and take up a set of π electrons, attaching it to the molecule (1). This is basically the reverse of the last step in the E1
reaction (deprotonation step). The resulting molecule will have a single carbon- carbon bond with a positive charge on one of them
(carbocation). The next step is when the nucleophile (halide) bonds to the carbocation, producing a new molecule with both the
original hydrogen and halide attached to the organic reactant (2). The second step will only occur if a good nucleophile is used.
Mechanism of Electrophilic Addition of Hydrogen Halide to Ethene

Mechanism of Electrophilic Addition of Hydrogen Halide to Propene

HF slowest smallest good

HCl slow small okay

HBr fast large bad

HI fastest largest horrifically bad

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Gaseous hydrogen halides are used and bubbled through the reactant or the hydrogen halide is added in a solvent such as
acetic acid to produce decent amounts of the product. It also helps to do a aqueous work up afterward to get a good yield of
product. This reaction is usually carried out at lower temperatures.

Regiochemistry
The regiochemistry of this reaction can be explained through Markovnikov's Rule. The basics of this rule states that the proton will
add to the less substituted carbon and the halogen goes to the more substituted carbon. This may seem odd that the larger atom is
going to the more sterically hindered spot, but this rule is more about the stability of the intermediate. The addition will occur in a
way that produces the most stable carbocation after the initial protonation (the intermediate needs to have a stable carbocation).
Tertiary and secondary carbocations are the most stable due to hyperconjugation, so the more substituted the carbon is the more
stable the carbocation will be.
Examples of regioselective behavior in Electrophilic Addition: Markovnikov's Rule

Since the intermediate of this reaction is a carbocation the carbocation wants to be the most stable it can be. In some case this will
mean that the carbocation will rearrange. This is very likely when there are no good nucleophiles present to trap the carbocation in
a certain position. The rearrangement of the carbocation depends on many things but generally rearrangements will occur when
there are no good nucleophiles present such as in a strong acid.

Stereochemistry
The stereochemistry for this reaction is random. The important thing to understand is the regiochemistry and the Markovnikov's
Rule (this will come up a lot!).

References
1. Vollhardt, K. Peter C., and Neil E. Schore. Organic Chemistry: Structure and Function. New York: W.H. Freeman and
Company, 2007.
2. Francis A. Coreg, Richard J. Sundberg. Advanced Organic Chemistry: Part B: Reactions and Synthesis. Springer, 2007.

Problems
Write out the following reactions and think about the rate of the reaction:

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Contributors
Ivy Gardner

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Electrophilic Addition of Hydrogen Halides is licensed CC BY-NC-SA 4.0.

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5.2: Addition of Strong Brønsted Acids
Strong Brønsted acids such as HCl, HBr, HI & H2SO4, rapidly add to the C=C functional group of alkenes to give products in
which new covalent bonds are formed to hydrogen and to the conjugate base of the acid. Using the above equation as a guide, write
the addition products expected on reacting each of these reagents with cyclohexene.

Weak Brønsted acids such as water (pKa = 15.7) and acetic acid (pKa = 4.75) do not normally add to alkenes. However, the
addition of a strong acid serves to catalyze the addition of water, and in this way alcohols may be prepared from alkenes. For
example, if sulfuric acid is dissolved in water it is completely ionized to the hydronium ion, H3O(+), and this strongly acidic (pKa =
-1.74) species effects hydration of ethene and other alkenes.

CH2=CH2 + H3O(+) ——> HCH2–CH2OH + H(+)

The importance of choosing an appropriate solvent for these addition reactions should now be clear. If the addition of HCl, HBr or
HI is desired, water and alcohols should not be used. These strong acids will ionize in such solvents to give ROH2(+) and the
nucleophilic oxygen of the solvent will compete with the halide anions in the final step, giving alcohol and ether products. By using
inert solvents such as hexane, benzene and methylene chloride, these competing solvent additions are avoided. Because these
additions proceed by way of polar or ionic intermediates, the rate of reaction is greater in polar solvents, such as nitromethane and
acetonitrile, than in non-polar solvents, such as cyclohexane and carbon tetrachloride.

Regioselectivity and the Markovnikov Rule

Only one product is possible from the addition of these strong acids to symmetrical alkenes such as ethene and cyclohexene.
However, if the double bond carbon atoms are not structurally equivalent, as in molecules of 1-butene, 2-methyl-2-butene and 1-
methylcyclohexene, the reagent conceivably may add in two different ways. This is shown for 2-methyl-2-butene in the following
equation.

(CH3)2C=CHCH3 + H-Cl (CH3)2CH–CHClCH3 or (CH3)2CCl–CHHCH3

2-methyl-2-butene 2-chloro-3-methylbutane 2-chloro-2-methylbutane

When addition reactions to such unsymmetrical alkenes are carried out, we find that one of the two possible constitutionally
isomeric products is formed preferentially. Selectivity of this sort is termed regioselectivity. In the above example, 2-chloro-2-
methylbutane is nearly the exclusive product. Similarly, 1-butene forms 2-bromobutane as the predominant product on treatment
with HBr.

After studying many addition reactions of this kind, the Russian chemist Vladimir Markovnikov noticed a trend in the structure of
the favored addition product. He formulated this trend as an empirical rule we now call The Markovnikov Rule: When a Brønsted
acid, HX, adds to an unsymmetrically substituted double bond, the acidic hydrogen of the acid bonds to that carbon of the double
bond that has the greater number of hydrogen atoms already attached to it.
In more homelier vernacular this rule may be restated as, "Them that has gits."
It is a helpful exercise to predict the favored product in examples such as those shown below:

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Empirical rules like the Markovnikov Rule are useful aids for remembering and predicting experimental results. Indeed, empirical
rules are often the first step toward practical mastery of a subject, but they seldom constitute true understanding. The Markovnikov
Rule, for example, suggests there are common and important principles at work in these addition reactions, but it does not tell us
what they are. The next step in achieving an understanding of this reaction must be to construct a rational mechanistic model that
can be tested by experiment.

All the reagents discussed here are strong Brønsted acids so, as a first step, it seems sensible to find a base with which the acid can
react. Since we know that these acids do not react with alkanes, it must be the pi-electrons of the alkene double bond that serve as
the base. As shown in the diagram on the right, the pi-orbital extends into the space immediately above and below the plane of the
double bond, and the electrons occupying this orbital may be attracted to the proton of a Brønsted acid. The resulting acid-base
equilibrium generates a carbocation intermediate (the conjugate acid of the alkene) which then combines rapidly with the anionic
conjugate base of the Brønsted acid. This two-step mechanism is illustrated for the reaction of ethene with hydrogen chloride by
the following equations.

First Step: H2C=CH2 + HCl HH2C–CH2(+) + Cl(–)

Second Step: HH2C–CH2(+) +

HH2C–CH2Cl
Cl(–)

An energy diagram for this two-step addition mechanism is shown to the left. From this diagram we see that the slow or rate-
determining step (the first step) is also the product determining step (the anion will necessarily bond to the carbocation site).
Electron donating double bond substituents increase the reactivity of an alkene, as evidenced by the increased rate of hydration of
2-methylpropene (two alkyl groups) compared with 1-butene (one alkyl group). Evidently, alkyl substituents act to increase the rate
of addition by lowering the activation energy, ΔE ‡ 1 of the rate determining step, and it is here we should look for a rationalization
of Markovnikov's rule.
As expected, electron withdrawing substituents, such as fluorine or chlorine, reduce the reactivity of an alkene to addition by acids
(vinyl chloride is less reactive than ethene).
George Hammond formulated a useful principle that relates the nature of a transition state to its location on the reaction path. This
Hammond Postulate states that a transition state will be structurally and energetically similar to the species (reactant,

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intermediate or product) nearest to it on the reaction path. In strongly exothermic reactions the transition state will resemble
the reactant species. In strongly endothermic conversions, such as that shown to the right, the transition state will resemble the
high-energy intermediate or product, and will track the energy of this intermediate if it changes. This change in transition state
energy and activation energy as the stability of the intermediate changes may be observed by clicking the higher or lower buttons to
the right of the energy diagram. Three examples may be examined, and the reference curve is changed to gray in the diagrams for
higher (magenta) and lower (green) energy intermediates.

The carbocation intermediate formed in the first step of the addition reaction now assumes a key role, in that it directly influences
the activation energy for this step. Independent research shows that the stability of carbocations varies with the nature of
substituents, in a manner similar to that seen for alkyl radicals. The exceptional stability of allyl and benzyl cations is the result of
charge delocalization, and the stabilizing influence of alkyl substituents, although less pronounced, has been interpreted in a similar
fashion.

Carbocatio
(CH3)2CH( CH2=CH- C6H5CH2(
n CH3(+) < CH3CH2(+) < +) ≈ < ≈ (CH3)3C(+)
CH2(+) +)
Stability

From this information, applying the Hammond Postulate, we arrive at a plausible rationalization of Markovnikov's rule. When an
unsymmetrically substituted double bond is protonated, we expect the more stable carbocation intermediate to be formed
faster than the less stable alternative, because the activation energy of the path to the former is the lower of the two possibilities.
This is illustrated by the following equation for the addition of hydrogen chloride to propene. Note that the initial acid-base
equilibrium leads to a pi-complex which immediately reorganizes to a sigma-bonded carbocation intermediate. The more stable 2º-
carbocation is formed preferentially, and the conjugate base of the Brønsted acid (chloride anion in the example shown below) then
rapidly bonds to this electrophilic intermediate to form the final product.

The following energy diagram summarizes these features. Note that the pi-complex is not shown, since this rapidly and reversibly
formed species is common to both possible reaction paths.

A more extensive discussion of the factors that influence carbocation stability may be accessed by Clicking Here.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

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5.3: Electrophilic Addition of Halogens to Alkenes
Halogens can act as electrophiles to attack a double bond in alkene. Double bond represents a region of electron density and
therefore functions as a nucleophile. How is it possible for a halogen to obtain positive charge to be an electrophile?

Introduction
As halogen molecule, for example Br2, approaches a double bond of the alkene, electrons in the double bond repel electrons in
bromine molecule causing polarization of the halogen bond. This creates a dipolar moment in the halogen molecule bond.
Heterolytic bond cleavage occurs and one of the halogens obtains positive charge and reacts as an electrophile. The reaction of the
addition is not regioselective but stereoselective.Stereochemistry of this addition can be explained by the mechanism of the
reaction.In the first step electrophilic halogen with a positive charge approaches the double carbon bond and 2 p orbitals of the
halogen, bond with two carbon atoms and create a cyclic ion with a halogen as the intermediate step. In the second step, halogen
with the negative charge attacks any of the two carbons in the cyclic ion from the back side of the cycle as in the SN2 reaction.
Therefore stereochemistry of the product is vicinial dihalides through anti addition.

R C=CR +X → R CX−CR X (5.3.1)

2 2 2 2 2

Halogens that are commonly used in this type of the reaction are: Br and C l. In thermodynamical terms I is too slow for this
reaction because of the size of its atom, and F is too vigorous and explosive.
Solvents that are used for this type of electrophilic halogenation are inert (e.g., CCl4) can be used in this reaction.
Because halogen with negative charge can attack any carbon from the opposite side of the cycle it creates a mixture of steric
products.Optically inactive starting material produce optically inactive achiral products (meso) or a racemic mixture.

Electrophilic addition mechanism consists of two steps.

Before constructing the mechanism let us summarize conditions for this reaction. We will use Br2 in our example for halogenation
of ethylene.

Nucleophile Double bond in alkene

Electrophile Br2, Cl2

Regiochemistry not relevant

Stereochemistry ANTI

Step 1: In the first step of the addition the Br-Br bond polarizes, heterolytic cleavage occurs and Br with the positive charge forms a
intermediate cycle with the double bond.

Step 2: In the second step, bromide anion attacks any carbon of the bridged bromonium ion from the back side of the cycle. Cycle
opens up and two halogens are in the position anti.

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Summary
Halogens can act as electrophiles due to polarizability of their covalent bond.Addition of halogens is stereospecific and produces
vicinial dihalides with anti addition.Cis starting material will give mixture of enantiomers and trans produces a meso compound.

References
1. Vollhard,K.Peter C., and Neil E.Schore.Organic Chemistry:Structure and Function.New Yourk: W.H.Freeman and Company
2007
2. Chemestry-A Europian Journal 9 (2003) :1036-1044

Problems
1.What is the mechanism of adding Cl2 to the cyclohexene?

2.A reaction of Br2 molecule in an inert solvent with alkene follows?

a) syn addition
b) anti addition
c) Morkovnikov rule

4)
Key:
1.

2. b

3. enantiomer

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5.4: Hydration of Alkenes
This page looks at the production of alcohols by the direct hydration of alkenes - adding water directly to the carbon-carbon double
bond.

Manufacturing ethanol
Ethanol is manufactured by reacting ethene with steam. The reaction is reversible.

Only 5% of the ethene is converted into ethanol at each pass through the reactor. By removing the ethanol from the equilibrium
mixture and recycling the ethene, it is possible to achieve an overall 95% conversion. A flow scheme for the reaction looks like
this:

Manufacturing other alcohols

If you start from an unsymmetrical alkene like propene, you have to be careful to think about which way around the water adds
across the carbon-carbon double bond. Markovnikov's Rule says that when you add a molecule HX across a carbon-carbon double
bond, the hydrogen joins to the carbon atom which already has the more hydrogen atoms attached to it.
Thinking of water as H-OH, the hydrogen will add to the carbon with the more hydrogens already attached. That means that in the
propene case, you will get propan-2-ol rather than propan-1-ol.

The conditions used during manufacture vary from alcohol to alcohol.

Contributors
Jim Clark (Chemguide.co.uk)

This page titled 5.4: Hydration of Alkenes is shared under a CC BY-NC 4.0 license and was authored, remixed, and/or curated by Jim Clark.

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5.5: Formation of alcohols from alkenes
Alkenes can be converted to alcohols by the net addition of water across the double bond. There are multiple ways that are
commonly used to do this transformation.

Hydration of Alkenes
The net addition of water to alkenes is known as hydration.

The result involves breaking the pi bond in the alkene and an OH bond in water and the formation of a C-H bond and a C-OH
bond. The reaction is typically exothermic by 10 - 15 kcal/mol,1 but has an entropy change of -35 - -40 cal/mol K. Consequently,
the net free energy change for the process tends to close to 0, and the equilibrium constant for the direct addition is close to 1.
Nonetheless, there are multiple approaches that allow this transformation to be carried out to completion.

Acid-Catalyzed Hydration
The direct addtion of water to an alkene is too slow to be of any significance. However, the addition can be catayzed by Lewis or
Bronsted acids.

The mechanism of hydration involves electrophlic addition of the proton (or acid) to the double bond to form a carbocation
intermediate. Addition of water in the second step results in formation of an oxonium ion, which, upon deprotonation, gives the
alcohol.

The proton in the oxonium intermediate can be deprotonated by any base present, including the conjugate base of the acid used as a
catalyst, or even by another alkene molecule, which would generate another carbocation intermediate and propagate the chain
mechanism.

Using Le Châtelier's Principle to get the product

The extent of reaction of the acid catalyzed hydration of alkenes is determined by the equilibrium constant, which, as noted above,
is near unity. Consequently, the reaction can be carried out by adding excess water to increase the yield of products, an application
of Le Châtelier's Principle. Alternatively, the reverse reaction, acid-catalyzed dehydration of the alcohol to form the alkene can
promoted by removing water from the reaction by using a Dean-Stark trap.

Regioselectivity of addition
Protonation of the alkene in the first step of the reaction can occur at either carbon. However, the more stable carbocation is
preferably formed. The order of stability of alkyl cations is
3o > 2o > 1o
Therefore, protonation will occur at the less substituted carbon, to create the more substituted carbocation, where the water adds.
The addition of a proton at the less substituted carbon and the -OH to the more substituted carbon is known as Markovnikov's Rule.
The carbocation formed in the reaction is prone to rearrangement, if possible. Therefore, hydration of an olefiin next to a branched
aliphatic center will result in the alcohol forming in a position that was not part of the original double bond.

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Oxymercuration
Transition metals can also be used as the acids for hydration reactions. In some cases, coordination of the alkene to a metal leaves it
susceptible to reaction with a nucleophile such as water. The classic case of nucleophilic donation to a coordinated alkene occurs
with mercury (II) salts such as mercuric chloride, H gC l , or mercuric acetate, H g(OAc) . The reaction, or rather the sequence of
2 2

reactions, is called oxymercuration - demercuration or oxymercuration - reduction.

We will break the two different reactions in this sequence apart and focus only on the first one: oxymercuration. This reaction
qualifies as an electrophilic addition because, as in the previous cases, it begins with donation of a π-bonding pair to an
electrophile. In this case, we will consider the electrophile to be aqueous H g ion.
2+

That electrophilic addition (from the alkene's perspective) results in the formation of an alkene complex. In reality, the mercury ion
is also coordinated by several water molecules, but we will ignore them for simplicity.
The complex formed by addition of mercury is not a localized carbocation, as is formed by protonation, but is better considered a
bridged or cyclic structure, which results from addition of d electrons to the empty orbital in the cation.

This situation is something like formation of a cyclic bromonium ion formed in the bromination of alkenes. As with bromination,
the cyclic intermediate can be opened by attack of a nucleophile, in this case, water.

The final part of the reaction sequence is displacement of mercury from the hydroxyalkylmercury complex, effected through
addition of sodium borohydride. The details of the reaction are usually dismissed in textbooks because they have little to do with
electrophilic addition, the topic we are focusing on. However, the result is that the mercury is replaced by a hydrogen atom. The
metal is converted to silvery, liquid, elemental mercury.

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Regioselectivy of hydration by oxymercuration
As shown above, oxymercuration leads to Markovnikov addition of water to the double bond. The reason for this can be seen by
considering the electronic structure of the cyclic cation. The electronic structure of the cyclic intermediate can be deduced by using
resonance structures as shown below.

By considering these resonance structures, it can be seen that the postive charge is distributed over both of the carbons of the olefin.
However, because the resonance structure on the left has the positive charge on a secondary carbon, it is energetically more
favorable than the structure in the middle, where the charge is a primary cation. Consequently, although the charge is distributed
over both carbons, the more substituted carbon has more positive charge density in the overall resonance hybrid. Therefore, it is
more electrophilic, and is more susceptibleable to nucleophlic attack.
An important advantage of oxymercuration over simple acid catalysis is that the cyclic structure is not prone to rearrangement, and
can therefore is amenable to hydration of alkenes with branched substituents.

Hydroboration-Oxidation
Hydroboration Oxidation

References
1. http://webbook.nist.gov/chemistry/

Contributors
Prof. Paul G. Wenthold (Purdue University)

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5.6: Catalytic Hydrogenation
 Objectives

After completing this section, you should be able to

1. write an equation for the catalytic hydrogenation of an alkene.
2. identify the product obtained from the hydrogenation of a given alkene.
3. identify the alkene, the reagents, or both, required to prepare a given alkane by catalytic hydrogenation.
4. describe the mechanism of the catalytic hydrogenation of alkenes.
5. explain the difference between a heterogeneous reaction and a homogeneous reaction.
6. recognize that other types of compounds containing multiple bonds, such as ketones, esters, nitriles and aromatic
compounds, do not react with hydrogen under the conditions used to hydrogenate alkenes.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
Adams’ catalyst
hydrogenation

 Study Notes

Chemical reactions that are heterogeneous have reactants that are in at least two different phases (e.g. gas with a solid),
whereas homogeneous reactions occur in a single phase (e.g. gas with another gas).
Some confusion may arise from the description of the catalyst used in the reaction between alkenes and hydrogen. Three
metals—nickel, platinum and palladium—are commonly used, but a chemist cannot simply place a piece of one of these metals
in a mixture of the alkene and hydrogen and get a reaction. Each metal catalyst must be prepared in a special way:
nickel is usually used in a finely divided form called “Raney nickel.” It is prepared by reacting a Ni-Al alloy with NaOH.
palladium is obtained commercially “supported” on an inert substance, such as charcoal, (Pd/C). The alkene is usually
dissolved in ethanol when Pd/C is used as the catalyst.
platinum is used as PtO2, Adams’ catalyst, although it is actually platinum metal that is the catalyst. The hydrogen used to
add to the carbon-carbon double bond also reduces the platinum(IV) oxide to finely divided platinum metal. Ethanol or
acetic acid is used as the solvent for the alkene.
Other types of compounds containing multiple bonds, such as ketones, esters, and nitriles, do not react with hydrogen under the
conditions used to hydrogenate alkenes. The examples below show reduction of an alkene, but the ketone and nitrile groups
present remain intact and are not reduced.
O O
H2, Pd/C

CN CN
H2, Pd/C

Aromatic rings are also not reduced under the conditions used to reduce alkenes, although these rings appear to contain three
carbon-carbon double bonds. As you will see later, aromatic rings do not really contain any double bonds, and many chemists
prefer to represent the benzene ring as a hexagon with a circle inside it

rather than as a hexagon with three alternating double bonds.

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The representation of the benzene ring will be discussed further in Section 15.2.
The reaction between carbon-carbon double bonds and hydrogen provides a method of determining the number of double
bonds present in a compound. For example, one mole of cyclohexene reacts with one mole of hydrogen to produce one mole of
cyclohexane:

PtO2
+ H2

but one mole of 1,4-cyclohexadiene reacts with two moles of hydrogen to form one mole of cyclohexane:
PtO2
+ 2 H2

A chemist would say that cyclohexene reacts with one equivalent of hydrogen, and 1,4-cyclohexadiene reacts with two
equivalents of hydrogen. If you take a known amount of an unknown, unsaturated hydrocarbon and determine how much
hydrogen it will absorb, you can readily determine the number of double bonds present in the hydrocarbon (see question 2,
below).

Addition of hydrogen to a carbon-carbon double bond is called hydrogenation. The overall effect of such an addition is the
reductive removal of the double bond functional group. Regioselectivity is not an issue, since the same group (a hydrogen atom) is
bonded to each of the double bond carbons. The simplest source of two hydrogen atoms is molecular hydrogen (H2), but mixing
alkenes with hydrogen does not result in any discernible reaction. Although the overall hydrogenation reaction is exothermic, a
high activation energy prevents it from taking place under normal conditions. This restriction may be circumvented by the use of a
catalyst, as shown in the reaction coordinate diagram below.
An example of an alkene addition reaction is a process called hydrogenation. In a hydrogenation reaction, two hydrogen atoms are
added across the double bond of an alkene, resulting in a saturated alkane. Hydrogenation of a double bond is a thermodynamically
favorable reaction because it forms a more stable (lower energy) product. In other words, the energy of the product is lower than
the energy of the reactant; thus it is exothermic (heat is released). The heat released is called the heat of hydrogenation, which is an
indicator of a molecule’s stability.

hydrogenation of ethene hydrogenation of cyclohexene

H H
H H Pd/C Pd/C
C C + H2 H C C H + H2
H H H H
ethene ethane cyclohexene cyclohexane

Catalysts are substances that changes the rate (velocity) of a chemical reaction without being consumed or appearing as part of the
product. Catalysts act by lowering the activation energy of reactions, but they do not change the relative potential energy of the
reactants and products. Finely divided metals, such as platinum, palladium and nickel, are among the most widely used
hydrogenation catalysts. Catalytic hydrogenation takes place in at least two stages, as depicted in the diagram. First, the alkene
must be adsorbed on the surface of the catalyst along with some of the hydrogen. Next, two hydrogens shift from the metal surface
to the carbons of the double bond, and the resulting saturated hydrocarbon, which is more weakly adsorbed, leaves the catalyst
surface. The exact nature and timing of the last events is not well understood.

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As shown in the energy diagram, the hydrogenation of alkenes is exothermic, and heat is released corresponding to the ΔH in the
diagram. This heat of reaction can be used to evaluate the thermodynamic stability of alkenes having different numbers of alkyl
substituents on the double bond. For example, the following table lists the heats of hydrogenation for three C5H10 alkenes which
give the same alkane product (2-methylbutane). Since a larger heat of reaction indicates a higher energy reactant, these heats are
inversely proportional to the stabilities of the alkene isomers. To a rough approximation, we see that each alkyl substituent on a
double bond stabilizes this functional group by a bit more than 1 kcal/mole.

(CH3)2CHCH=CH2 CH2=C(CH3)CH2CH3 (CH3)2C=CHCH3

Alkene Isomer
3-methyl-1-butene 2-methyl-1-butene 2-methyl-2-butene

Heat of Reaction
–30.3 kcal/mole –28.5 kcal/mole –26.9 kcal/mole
( ΔHº )

Catalytic Hydrogenation Mechanism

Alkene attaches to the
metal catalyst surface.

Hydrogen atoms attach to

H H
the metal catalyst surface. C C
H H H H A hydrogen atom is transferred
to the alkene.

H H H H
H H H H C C H H H H C C
H H H H

Metal catalyst surface Metal catalyst surface

Two hydrogen atoms have

added to the same face of the A second hydrogen atom is
double bond (syn addition). The transferred to the alkene.
product is a saturated alkane. H H H
H C C H H C
H
H H H H H H H H C
H

Metal catalyst surface Metal catalyst surface

From the mechanism shown here we would expect the addition of hydrogen to occur with syn-stereoselectivity. This is often true,
but the hydrogenation catalysts may also cause isomerization of the double bond prior to hydrogen addition, in which case
stereoselectivity may be uncertain.
CH3
CH3
H2 H
Pt H
CH3
CH3
(cis product only)

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 Exercise 1
1. In the reaction
PtO2
H2C CH2 + H2 H3C CH3

a. 0.500 mol of ethene reacts with _______ mol of hydrogen. Thus a chemist might say that ethene reacts with one
_______ of hydrogen.
b. ethene is being _______; while _______ is being oxidized.
c. the oxidation number of carbon in ethene is _______; in ethane it is _______.

Answer
a. 0.500 mol of ethene reacts with 0.500 mol of hydrogen. Thus a chemist might say that ethene reacts with one equivalent
of hydrogen.
b. ethene is being reduced; while hydrogen is being oxidized.
c. the oxidation number of carbon in ethene is −2; in ethane it is −3.

 Exercise 2

When 1.000 g of a certain triglyceride (fat) is treated with hydrogen gas in the presence of Adams’ catalyst, it is found that the
volume of hydrogen gas consumed at 99.8 kPa and 25.0°C is 162 mL. A separate experiment indicates that the molar mass of
the fat is 914 g mol−1. How many carbon-carbon double bonds does the compound contain?

Answer
Amount of hydrogen consumed
= n mol

PV
−1
=
RT ⋅ K−1 ×298 K =6.53× 10−3 mol H2
99.8 kPa × 0.162 L
=
8.31 kPa ⋅ mol

Amount of fat used

(1.000 g) × (1 mol)
=
(914 g)

Unknown node type: sup Unknown node type: sup

= 1.09 × 10 mol fat

Ratio of moles of hydrogen consumed to moles of fat

Unknown node type: sup Unknown
Unknownnode
node
type:
type:
sup
sup Unknown node type: sup
= 6.53 × 10 : 1.09 × 10

=6 : 1

Thus, the fat contains six carbon-carbon double bonds per molecule.

Questions
Q8.6.1
Predict the products if the following alkenes were reacted with catalytic hydrogen.

5.6.4 https://chem.libretexts.org/@go/page/205349
Solutions
S8.6.1

Contributors and Attributions

Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)
Layne Morsch (University of Illinois Springfield)
Dr. Krista Cunningham

5.6: Catalytic Hydrogenation is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
8.6: Reduction of Alkenes - Hydrogenation by Dietmar Kennepohl, Steven Farmer is licensed CC BY-SA 4.0.

5.6.5 https://chem.libretexts.org/@go/page/205349
5.7: Hydration- Oxymercuration-Demercuration
Learning Objective
apply the principles of regioselectivity and stereoselectivity to the addition reactions of alkenes
predict the products, specify the reagents, and discern most efficient reaction for hydration of alkenes (acid catalyzed
hydration; or oxymercuration/demercuration; or hydroboration/oxidation)

Introduction
Acid-catalyzed hydration of alkenes is limited by carbocation stability. Carbocation rearrangement can occur to form a more stable
ion as shown in the example below.

Alkene hydration using the oxymercuration-demercuration reaction pathway reliably produces the Markovnikov product without
carbocation rearrangment as shown in the example below.

Oxymercuration-Demercuration is a two step pathway used to produce alcohols.

Oxymercuration-Demercuration Mechanism
This mechanism is similar to the previous electrophilic addition reactions. The major difference is that a mercurium ion bridge
stabilizes the carbocation intermediate so that it cannot rearrange. Metals are electropositive. Mercury carries a partial positive
charge in the acetate complex and is the electrophile. During the first step of this mechanism, the pi electrons form a bond to
mercury while the lone pair on the mercury simultaneously bonds to the other vinyl carbon creating a mercurium ion bridge. The
mercurium ion forms in conjunction with the loss of an acetate ion. The mercurium ion stabilizes the carbocation so that it does not
rearrange. In the second step of this mechanism, a water molecule reacts with the most substituted carbon to open the mercurium
ion bridge. The third step of this mechanism is a proton transfer to a solvent water molecule to neutralize the addition product. The
fourth step of the reaction pathway is the reduction of the organomercury intermediate with sodium borohydride under basic
conditions. The mechanism of the fourth step is beyond the scope of first year organic chemistry.

Notice that overall, the oxymercuration - demercuration mechanism follows Markovnikov's Regioselectivity with the OH group
attached to the most substituted carbon and the H attached to the least substituted carbon. The reaction is useful, because strong
acids are not required and carbocation rearrangements are avoided because no discreet carbocation intermediate forms.

Exercise
1. Show how to prepare 3-methyl2-pentanol from 3-methyl-1-pentene.
Note: Questions 2-5 have not shown the water present in the sulfuric acid solution and have indicated a second neutralization
step. Some authors simply write H+/H2O as a single step.

5.7.1 https://chem.libretexts.org/@go/page/205350
2. Draw the bond-line structure for the product.

3. Draw the bond-line structure for the product. How does the cyclopropane group affect the reaction?

4. Draw the bond-line structure for the product. (Hint: What is different about this problem?)

5. Draw the bond-line structure for the product(s). Indicate any shifts as well as the major product:

6. In each case, predict the product(s) of these reactants of oxymercuration.

7. Propose the alkene that was the reactant for each of these products of oxymercuration.

Answer

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1.

2. This reaction is electrophilic hydration.

3. The answer is additional side products, but the major product formed is still the same (the product shown).
Depending on the temperatures used, the cyclopropane may open up into a straight chain, which makes it unlikely
that the major product will form (after the reaction, it is unlikely that the 3º carbon will remain as such).

4. A hydride shift actually occurs from the top of the 1-methylcyclopentane to where the carbocation had formed.

5. In the first picture shown below, an alkyl shift occurs but a hydride shift (which occurs faster) is possible. Why
doesn't a hydride shift occur? The answer is because the alkyl shift leads to a more stable product. There is a
noticeable amount of side product that forms where the two methyl groups are, but the major product shown below is
still the most significant due to the hyperconjugation that occurs by being in between the two cyclohexanes.

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References
1. Vollhardt, K. Peter C. Organic chemistry structure and function. New York: W.H. Freeman, 2007.
2. Smith, Michael B., and Jerry March. March's Advanced Organic Chemistry Reactions, Mechanisms, and Structure (March's
Advanced Organic Chemistry). New York: Wiley-Interscience, 2007 2007.
3. Roderic P. Quirk , Robert E. Lea, Reductive demercuration of hex-5-enyl-1-mercuric bromide by metal hydrides.
Rearrangement, isotope effects, and mechanism, J. Am. Chem. Soc., 1976, 98 (19), pp 5973–5978.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Lance Peery (UCD), Duyen Dao-Tran (UCD)
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)
Jim Clark (Chemguide.co.uk)
Prof. Steven Farmer (Sonoma State University)

5.7: Hydration- Oxymercuration-Demercuration is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

5.7.4 https://chem.libretexts.org/@go/page/205350
5.8: Hydration- Hydroboration-Oxidation
Learning Objectives
apply the principles of regioselectivity and stereoselectivity to the addition reactions of alkenes
predict the products, specify the reagents, and discern most efficient reaction for hydration of alkenes (acid catalyzed
hydration; or oxymercuration/demercuration; or hydroboration/oxidation)

Hydroboration-Oxidation is a two step pathway used to produce alcohols. The reaction proceeds in an anti-Markovnikov manner,
where the hydrogen (from BH or BHR ) attaches to the more substituted carbon and the boron attaches to the least substituted
3 2

carbon in the alkene double bond. Furthermore, the borane acts as the electrophile by accepting two electrons in its empty p orbital
from an alkene that is electron rich. This process allows boron to have an electron octet. A very interesting characteristic of this
process is that it does not require any activation by a catalyst. The hydroboration mechanism has the elements of both
hydrogenation and electrophilic addition and it is a stereospecific (syn addition), meaning that the hydroboration takes place on the
same face of the double bond, this leads cis stereochemistry.

The Borane Complex

It is very important to understand the structure and properties of the borane molecule. Borane exists naturally as a very toxic gas
and it exists as dimer of the general formula B H (diborane).
2 6

BH → B H
3 2 6

Since diborane dimer ignites spontaneously in air, it commercially distributed in ether or tetrahydrofuran (THF) solutions. In these
solutions, the borane can exist as a Lewis acid-base complex which allows boron to have an octet of electrons.

The Mechanism
Step #1: Hydroboration of the alkene
The addition of the borane to the alkene is initiated and proceeds as a concerted reaction because bond breaking and bond
formation occur at the same time. The vacant 2p orbital of the boron takes the role of electrophile and accepts the pi electrons from
the nucleophilic alkene. The boron adds to the less substituted carbon of the alkene, which then places the hydrogen on the more
substituted carbon. Both, the boron and the hydrogen add simultaneously on the same face of the double bond (syn addition). With
a concerted mechanism, there is no carbocation formation.

Transition state

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* Note that a carbocation is not formed. Therefore, no rearrangement takes place.

It is important to note that reaction continues two more times until all three hydrogens on the borane have reacted with alkenes to
create the trialkylborane intermediate R3B.

Step #2: Oxidation of the Trialkylborane by Hydrogen Peroxide

The hydrogen peroxide (HOOH ) is the nucleophile in this reaction because it is the electron donor to the newly formed
trialkylborane that resulted from the previous hydroboration.
− −
HOOH + OH ⟶ HOO + HOH (5.8.1)

In this second part of the mechanism, a rearrangement of an R group with its pair of bonding electrons to an adjacent oxygen
results in the loss of a hydroxide ion.

Two more of these reactions with hydroperoxide will occur in order give a trialkylborate

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In the final step of the oxidation process, the trialkylborate reacts with aqueous NaOH to give the alcohol and sodium borate
(\ce{Na3BO3}\).

(RO )B + 3 NaOH ⟶ 3 OH + Na BO (5.8.2)

3 3 3

If you need additional visuals to aid you in understanding the mechanism, click on the outside links provided at the end of this
section.

Stereochemistry of the Hydroboration Step

The hydroboration reaction is among the few simple addition reactions that proceed cleanly in a syn fashion. As noted above, this
is a single-step reaction. Since the bonding of the double bond carbons to boron and hydrogen is concerted, it follows that the
geometry of this addition must be syn. Furthermore, rearrangements are unlikely inasmuch as a discrete carbocation intermediate is
never formed. These features are illustrated for the hydroboration of α-pinene.

Since the hydroboration procedure is most commonly used to hydrate alkenes in an anti-Markovnikov fashion, we also need to
know the stereoselectivity of the second oxidation reaction, which substitutes a hydroxyl group for the boron atom. Independent
study has shown this reaction takes place with retention of configuration so the overall addition of water is also syn.
The hydroboration of α-pinene also provides a nice example of steric hindrance control in a chemical reaction. In the less complex
alkenes used in earlier examples the plane of the double bond was often a plane of symmetry, and addition reagents could approach
with equal ease from either side. In this case, one of the methyl groups bonded to C-6 (colored blue in the equation) covers one face
of the double bond, blocking any approach from that side. All reagents that add to this double bond must therefore approach from
the side opposite this methyl.

Exercises
1. Draw the bond-line structure of the product(s) for these following reactions?
a)

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2. Draw the structural formulas for the alcohols that result from hydroboration-oxidation of the alkenes shown.
a)

b) (E)-3-methyl-2-pentene
3. Write out the reagents or products (A–D) shown in the following reaction schemes.

Answer
1.

c)
2.

5.8.4 https://chem.libretexts.org/@go/page/205351
b)
3.

References
1. Vollhardt, Peter, and Neil Shore. Organic Chemistry: Structure and Function. 5th. New York: W.H. Freeman and Company,
2007.
2. Foote, S. Christopher, and William H. Brown. Organic Chemistry. 5th. Belmont, CA: Brooks/Cole Cengage Learning, 2005.
3. Bruice, Paula Yurkanis. Oragnic Chemistry. 5th. CA. Prentice Hall, 2006.
4. Bergbreiter E. David , and David P. Rainville. Stereochemistry of hydroboration-oxidation of terminal alkenes. J. Org. Chem.,
1976, 41 (18), pp 3031–3033
5. Ilich, Predrag-Peter; Rickertsen, Lucas S., and Becker Erienne. Polar Addition to C=C Group: Why Is Anti-Markovnikov
Hydroboration-Oxidation of Alkenes Not "Anti-"? Journal of Chemical Education., 2006, v83, n11, pg 1681-1685

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)
Jim Clark (Chemguide.co.uk)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

5.8: Hydration- Hydroboration-Oxidation is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

5.8.5 https://chem.libretexts.org/@go/page/205351
5.9: Oxidative Cleavage of Alkenes
Learning Objective
predict the products/specify the reagents for oxidative cleavage of alkenes

Overview
Oxidative cleavage can occur by several different reaction pathways. The cleavage can be strong or gentle depending on the
reaction conditions and/or the work-up of the initial reaction product. Both alkenes and alkynes can undergo cleavage reactions.
This section will focus on alkenes.

Gentle cleavage of alkenes occurs by two primary reaction pathways: ozolysis with a reductive work-up or syn-dihydroxylation
followed by oxidation with perioidc acid. Gentle cleavage will leave terminal carbons partially oxidized to aldehydes. Strong
cleavage of alkenes will fully oxidize terminal carbons to carboxylic acids. Internal carbons become ketones by either reaction
pathway.

Why so many reactions?

At first glance, it may seem silly to have more than more reaction pathway for the same functional group conversion. As this course
proceeds, it will become necessary to target reactions to a single functional group of an organic compound with multiple functional
groups. A particular reaction pathway can be advantageous when the reactivity of the entire molecule is considered, not just a
single functional group.

Gentle Cleavage: Syn-Dihydroxylation followed by Periodic Acid

Alkenes can also be gently cleavage in a two-step reaction sequence in which the alkene first undergoes syn-dihydroxylation using
cold, slightly basic KMnO4 or OsO4/H2O2 followed by oxidation with periodic acid (HIO4). Both reaction sequences are shown
below using 1-methylcyclohexene as an example.

Gentle Cleavage: Ozonolysis with a Reduction Work-up

Ozonolysis is a method of oxidatively cleaving alkenes or alkynes using ozone (O ), a reactive allotrope of oxygen. The process
3

allows for carbon-carbon double or triple bonds to be replaced by double bonds with oxygen. This reaction is often used to identify
the structure of unknown alkenes by breaking them down into smaller, more easily identifiable pieces. Ozonolysis also occurs
naturally and would break down repeated units used in rubber and other polymers. On an industrial scale, azelaic acid and
pelargonic acids are produced from ozonolysis.

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Ozonolysis Reaction Mechanism
The gaseous ozone is first passed through the desired alkene solution in either methanol or dichloromethane. The first intermediate
product is an ozonide molecule which is then further reduced to carbonyl products. This results in the breaking of the carbon-
carbon double bond and is replaced by a carbon-oxygen double bond instead.
Step 1:

The first step in the mechanism of ozonolysis is the initial electrophilic addition of ozone to the carbon-carbon double bond to form
the molozonide intermediate. Due to low stablility of molozonide, it continues reacting and breaks apart to form a carbonyl and a
carbonyl oxide molecule.
Step 2:

The electrons of the carbonyl and the carbonyl oxide form the stable ozonide intermediate which can then undergo an oxidative or
reductive work-up to form the products of interest. A reductive workup converts the ozonide molecule into the desired carbonyl
products with aldehyde on terminal carbons. An oxidative workup converts the ozonide molecule into the desired carbonyl
products with carboxylic acids on terminal carbons. The two reaction workup conditions are summarized below.

Exercises

Answers

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Strong Cleavage from Strong Oxidative Reactions
When the reaction conditions for potassium permanganate are warm, then the oxidation reaction is stronger and cleavage occurs at
the alkene with any terminal carbons fully oxidizing to carboxylic acids. When the ozonolysis reaction is followed by an oxidative
work-up, then any terminal carbons will oxidize fully to the carboxylic acid as shown in the example below. The example for 1-
methylcycohexene is shown below.

Exercise
5. What would you expect the products to be from the reaction of cis-2-pentene with m-chloro-peroxybenzoic acid? Show the
stereochemistry of the final product.
6. Give a reaction scheme with starting alkenes and required reagents to produce the following compounds.

Answer
5.

5.9.3 https://chem.libretexts.org/@go/page/205352
6.

References
1. Vollhardt, K., Schore, N. Organic Chemistry: Structure and Function. 5th ed. New York, NY: W. H. Freeman and Company,
2007.
2. Shore, N. Study Guide and Solutions Manual for Organic Chemistry. 5th ed. New York, NY: W.H. Freeman and Company,
2007.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)
John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. ,
Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission
for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any
format."

5.9: Oxidative Cleavage of Alkenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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5.10: Free Radicals
In chemistry, a radical (more precisely, a free radical) is an atom, molecule, or ion that has unpaired valence electrons or an open electron shell, and therefore may be seen as having
one or more "dangling" covalent bonds.
With some exceptions, these "dangling" bonds make free radicals highly chemically reactive towards other substances, or even towards themselves: their molecules will often
spontaneously dimerize or polymerize if they come in contact with each other. Most radicals are reasonably stable only at very low concentrations in inert media or in a vacuum.
A notable example of a free radical is the hydroxyl radical (HO•), a molecule that is one hydrogen atom short of a water molecule and thus has one bond "dangling" from the oxygen.
Two other examples are the carbene molecule (:CH2), which has two dangling bonds; and the superoxide anion (•O−2), the oxygen molecule O2 with one extra electron, which has one
dangling bond. In contrast, the hydroxyl anion (HO−), the oxide anion (O2−) and thecarbenium cation (CH+3) are not radicals, since the bonds that may appear to be dangling are in fact
resolved by the addition or removal of electrons.
Free radicals may be created in a number of ways, including synthesis with very dilute or rarefied reagents, reactions at very low temperatures, or breakup of larger molecules. The latter
can be affected by any process that puts enough energy into the parent molecule, such as ionizing radiation, heat, electrical discharges, electrolysis, and chemical reactions. Indeed,
radicals are intermediate stages in many chemical reactions.
Free radicals play an important role in combustion, atmospheric chemistry, polymerization, plasma chemistry, biochemistry, and many other chemical processes. In living organisms, the
free radicals superoxide and nitric oxideand their reaction products regulate many processes, such as control of vascular tone and thus blood pressure. They also play a key role in the
intermediary metabolism of various biological compounds. Such radicals can even be messengers in a process dubbed redox signaling. A radical may be trapped within a solvent cage or
be otherwise bound.
Until late in the 20th century the word "radical" was used in chemistry to indicate any connected group of atoms, such as a methyl group or a carboxyl, whether it was part of a larger
molecule or a molecule on its own. The qualifier "free" was then needed to specify the unbound case. Following recent nomenclature revisions, a part of a larger molecule is now called
a functional group or substituent, and "radical" now implies "free". However, the old nomenclature may still occur in the literature.

History
The first organic free radical identified was triphenylmethyl radical. This species was discovered by Moses Gomberg in 1900 at the University of Michigan USA. Historically, the term
radical in radical theory was also used for bound parts of the molecule, especially when they remain unchanged in reactions. These are now called functional groups. For example,
methyl alcohol was described as consisting of a methyl "radical" and a hydroxyl "radical". Neither are radicals in the modern chemical sense, as they are permanently bound to each
other, and have no unpaired, reactive electrons; however, they can be observed as radicals in mass spectrometry when broken apart by irradiation with energetic electrons.

Depiction in chemical reactions

In chemical equations, free radicals are frequently denoted by a dot placed immediately to the right of the atomic symbol or molecular formula as follows:

Chlorine gas can be broken down by ultraviolet light to form atomic chlorine radicals.

Radical reaction mechanisms use single-headed arrows to depict the movement of single electrons:

The homolytic cleavage of the breaking bond is drawn with a 'fish-hook' arrow to distinguish from the usual movement of two electrons depicted by a standard curly arrow. It should be
noted that the second electron of the breaking bond also moves to pair up with the attacking radical electron; this is not explicitly indicated in this case.
Free radicals also take part in radical addition and radical substitution as reactive intermediates. Chain reactions involving free radicals can usually be divided into three distinct
processes. These are initiation, propagation, and termination.
Initiation reactions are those that result in a net increase in the number of free radicals. They may involve the formation of free radicals from stable species as in Reaction 1 above or
they may involve reactions of free radicals with stable species to form more free radicals.
Propagation reactions are those reactions involving free radicals in which the total number of free radicals remains the same.
Termination reactions are those reactions resulting in a net decrease in the number of free radicals. Typically two free radicals combine to form a more stable species, for example:
2Cl·→ Cl2

Formation
The formation of radicals may involve breaking of covalent bonds homolytically, a process that requires significant amounts of energy. For example, splitting H2 into 2H· has a ΔH° of
+435 kJ/mol, and Cl2 into 2Cl· has a ΔH° of +243 kJ/mol. This is known as the homolytic bond dissociation energy, and is usually abbreviated as the symbol ΔH°. The bond energy
between two covalently bonded atoms is affected by the structure of the molecule as a whole, not just the identity of the two atoms. Likewise, radicals requiring more energy to form are
less stable than those requiring less energy. Homolytic bond cleavage most often happens between two atoms of similar electronegativity. In organic chemistry this is often the O-O bond
in peroxide species or O-N bonds. Sometimes radical formation is spin-forbidden, presenting an additional barrier. However, propagation is a very exothermic reaction. Likewise,
although radical ions do exist, most species are electrically neutral. Radicals may also be formed by single electron oxidation or reduction of an atom or molecule. An example is the
production of superoxide by the electron transport chain. Early studies of organometallic chemistry, especially tetra-alkyl lead species by F.A. Paneth and K. Hahnfeld in the 1930s
supported heterolytic fission of bonds and a radical based mechanism.

Persistence and stability

The radical derived from α-tocopherol

Although radicals are generally short-lived due to their reactivity, there are long-lived radicals. These are categorized as follows:

Stable radicals

The prime example of a stable radical is molecular dioxygen (O2). Another common example is nitric oxide (NO). Organic radicals can be long lived if they occur in a conjugated π
system, such as the radical derived from α-tocopherol (vitamin E). There are also hundreds of examples of thiazyl radicals, which show low reactivity and remarkable thermodynamic
stability with only a very limited extent of π resonance stabilization.[1][2]

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Persistent radicals

Persistent radical compounds are those whose longevity is due to steric crowding around the radical center, which makes it physically difficult for the radical to react with another
molecule.[3] Examples of these include Gomberg's triphenylmethyl radical, Fremy's salt(Potassium nitrosodisulfonate, (KSO3)2NO·), nitroxides, (general formula R2NO·) such as
TEMPO, TEMPOL, nitronyl nitroxides, and azephenylenyls and radicals derived from PTM (perchlorophenylmethyl radical) and TTM (tris(2,4,6-trichlorophenyl)methyl radical).
Persistent radicals are generated in great quantity during combustion, and "may be responsible for the oxidative stress resulting in cardiopulmonary disease and probably cancer that has
been attributed to exposure to airborne fine particles."[4]

Diradicals

Diradicals are molecules containing two radical centers. Multiple radical centers can exist in a molecule. Atmospheric oxygen naturally exists as a diradical in its ground state as triplet
oxygen. The low reactivity of atmospheric oxygen is due to its diradical state. Non-radical states of dioxygen are actually less stable than the diradical. The relative stability of the
oxygen diradical is primarily due to the spin-forbidden nature of the triplet-singlet transition required for it to grab electrons, i.e., "oxidize". The diradical state of oxygen also results in
its paramagnetic character, which is demonstrated by its attraction to an external magnet.[5]

Reactivity
Radical alkyl intermediates are stabilized by similar physical processes to carbocations: as a general rule, the more substituted the radical center is, the more stable it is. This directs their
reactions. Thus, formation of a tertiary radical (R3C·) is favored over secondary (R2HC·), which is favored over primary (RH2C·). Likewise, radicals next to functional groups such as
carbonyl, nitrile, and ether are more stable than tertiary alkyl radicals.
Radicals attack double bonds. However, unlike similar ions, such radical reactions are not as much directed by electrostatic interactions. For example, the reactivity of nucleophilic ions
with α,β-unsaturated compounds (C=C–C=O) is directed by the electron-withdrawing effect of the oxygen, resulting in a partial positive charge on the carbonyl carbon. There are two
reactions that are observed in the ionic case: the carbonyl is attacked in a direct addition to carbonyl, or the vinyl is attacked in conjugate addition, and in either case, the charge on the
nucleophile is taken by the oxygen. Radicals add rapidly to the double bond, and the resulting α-radical carbonyl is relatively stable; it can couple with another molecule or be oxidized.
Nonetheless, the electrophilic/neutrophilic character of radicals has been shown in a variety of instances. One example is the alternating tendency of the copolymerization of maleic
anhydride (electrophilic) and styrene (slightly nucleophilic).
In intramolecular reactions, precise control can be achieved despite the extreme reactivity of radicals. In general, radicals attack the closest reactive site the most readily. Therefore,
when there is a choice, a preference for five-membered rings is observed: four-membered rings are too strained, and collisions with carbons six or more atoms away in the chain are
infrequent.
Carbenes and nitrenes, which are diradicals, have distinctive chemistry.

Combustion

Spectrum of the blue flame from a butane torch showing excited molecular radical band emission and Swan bands
A familiar free-radical reaction is combustion. The oxygen molecule is a stable diradical, best represented by ·O-O·. Because spins of the electrons are parallel, this molecule is stable.
While the ground stateof oxygen is this unreactive spin-unpaired (triplet) diradical, an extremely reactive spin-paired (singlet) state is available. For combustion to occur, the energy
barrier between these must be overcome. This barrier can be overcome by heat, requiring high temperatures. The triplet-singlet transition is also "forbidden". This presents an additional
barrier to the reaction. It also means molecular oxygen is relatively unreactive at room temperature except in the presence of a catalytic heavy atom such as iron or copper.
Combustion consists of various radical chain reactions that the singlet radical can initiate. The flammability of a given material strongly depends on the concentration of free radicals
that must be obtained before initiation and propagation reactions dominate leading to combustion of the material. Once the combustible material has been consumed, termination
reactions again dominate and the flame dies out. As indicated, promotion of propagation or termination reactions alters flammability. For example, because lead itself deactivates free
radicals in the gasoline-air mixture, tetraethyl lead was once commonly added to gasoline. This prevents the combustion from initiating in an uncontrolled manner or in unburnt residues
(engine knocking) or premature ignition (preignition).
When a hydrocarbon is burned, a large number of different oxygen radicals are involved. Initially, hydroperoxyl radical (HOO·) are formed. These then react further to give organic
hydroperoxides that break up into hydroxyl radicals (HO·).

Polymerization
In addition to combustion, many polymerization reactions involve free radicals. As a result many plastics, enamels, and other polymers are formed through radical polymerization. For
instance, drying oils and alkyd paints harden due to radical crosslinking by oxygen from the atmosphere.
Recent advances in radical polymerization methods, known as living radical polymerization, include:
Reversible addition-fragmentation chain transfer (RAFT)
Atom transfer radical polymerization (ATRP)
Nitroxide mediated polymerization (NMP)
These methods produce polymers with a much narrower distribution of molecular weights.

Atmospheric radicals
The most common radical in the lower atmosphere is molecular dioxygen. Photodissociation of source molecules produces other free radicals. In the lower atmosphere, the most
important examples of free radical production are the photodissociation of nitrogen dioxide to give an oxygen atom and nitric oxide (see eq. 1 below), which plays a key role in smog
formation—and the photodissociation of ozone to give the excited oxygen atom O(1D) (see eq. 2 below). The net and return reactions are also shown (eq. 3 and 4, respectively).

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In the upper atmosphere, a particularly important source of radicals is the photodissociation of normally unreactive chlorofluorocarbons (CFCs) by solar ultraviolet radiation, or by
reactions with other stratospheric constituents (see eq. 1 below). These reactions give off the chlorine radical, Cl•, which reacts with ozone in a catalytic chain reaction ending in Ozone
depletion and regeneration of the chlorine radical, allowing it to reparticipate in the reaction (see eq. 2–4 below). Such reactions are believed to be the primary cause of depletion of the
ozone layer (the net result is shown in eq. 5 below), and this is why the use of chlorofluorocarbons as refrigerants has been restricted.

In biology
Free radicals play an important role in a number of biological processes. Many of these are necessary for life, such as the intracellular killing of bacteria by phagocytic cells such as
granulocytes and macrophages. Researchers have also implicated free radicals in certain cell signalling processes,[6] known as redox signaling.
The two most important oxygen-centered free radicals are superoxide and hydroxyl radical. They derive from molecular oxygen under reducing conditions. However, because of their
reactivity, these same free radicals can participate in unwanted side reactions resulting in cell damage. Excessive amounts of these free radicals can lead to cell injury and death, which
may contribute to many diseases such as cancer, stroke, myocardial infarction, diabetes and major disorders.[7] Many forms of cancer are thought to be the result of reactions between
free radicals and DNA, potentially resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy.[8] Some of the symptoms of aging such as
atherosclerosis are also attributed to free-radical induced oxidation of cholesterol to 7-ketocholesterol.[9] In addition free radicals contribute to alcohol-induced liver damage, perhaps
more than alcohol itself. Free radicals produced by cigarette smoke are implicated in inactivation of alpha 1-antitrypsin in the lung. This process promotes the development of
emphysema.
Free radicals may also be involved in Parkinson's disease, senile and drug-induced deafness, schizophrenia, and Alzheimer's.[10] The classic free-radical syndrome, the iron-storage
disease hemochromatosis, is typically associated with a constellation of free-radical-related symptoms including movement disorder, psychosis, skin pigmentary melanin abnormalities,
deafness, arthritis, and diabetes mellitus. The free-radical theory of aging proposes that free radicals underlie the aging process itself. Similarly, the process of mitohormesis suggests
that repeated exposure to free radicals may extend life span.
Because free radicals are necessary for life, the body has a number of mechanisms to minimize free-radical-induced damage and to repair damage that occurs, such as the enzymes
superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. In addition, antioxidants play a key role in these defense mechanisms. These are often the three
vitamins, vitamin A, vitamin C and vitamin E and polyphenol antioxidants. Furthermore, there is good evidence indicating that bilirubin and uric acid can act as antioxidants to help
neutralize certain free radicals. Bilirubin comes from the breakdown of red blood cells' contents, while uric acid is a breakdown product of purines. Too much bilirubin, though, can lead
to jaundice, which could eventually damage the central nervous system, while too much uric acid causes gout.[11]

Reactive oxygen species

Reactive oxygen species or ROS are species such as superoxide, hydrogen peroxide, and hydroxyl radical and are associated with cell damage. ROS form as a natural by-product of the
normal metabolism of oxygen and have important roles in cell signaling.
Oxybenzone has been found to form free radicals in sunlight, and therefore may be associated with cell damage as well. This only occurred when it was combined with other ingredients
commonly found in sunscreens, like titanium oxide and octyl methoxycinnamate.[12]

Loose definition of radicals

In most fields of chemistry, the historical definition of radicals contends that the molecules have nonzero spin. However in fields including spectroscopy, chemical reaction, and
astrochemistry, the definition is slightly different. Gerhard Herzberg, who won the Nobel prize for his research into the electron structure and geometry of radicals, suggested a looser
definition of free radicals: "any transient (chemically unstable) species (atom, molecule, or ion)".[13] The main point of his suggestion is that there are many chemically unstable
molecules that have zero spin, such as C2, C3, CH2 and so on. This definition is more convenient for discussions of transient chemical processes and astrochemistry; therefore
researchers in these fields prefer to use this loose definition.[14]

Diagnostics
Free radical diagnostic techniques include:
Electron spin resonance

A widely used technique for studying free radicals, and other paramagnetic species, is electron spin resonance spectroscopy (ESR). This is alternately referred to as "electron
paramagnetic resonance" (EPR) spectroscopy. It is conceptually related to nuclear magnetic resonance, though electrons resonate with higher-frequency fields at a given fixed
magnetic field than do most nuclei.

Nuclear magnetic resonance using a phenomenon called CIDNP

Chemical labelling

Chemical labelling by quenching with free radicals, e.g. with nitric oxide (NO) or DPPH (2,2-diphenyl-1-picrylhydrazyl), followed by spectroscopic methods like X-ray
photoelectron spectroscopy (XPS) or absorption spectroscopy, respectively.

Use of free radical markers

Stable, specific or non-specific derivates of physiological substances can be measured e.g. lipid peroxidation products (isoprostanes, TBARS), amino acid oxidation products (meta-
tyrosine, ortho-tyrosine, hydroxy-Leu, dityrosine etc.), peptide oxidation products (oxidized glutathione – GSSG)
2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) is a chemical compound used to study the chemistry of the oxidation of drugs.[15] It is a free radical-generating azo
compound. It is gaining prominence as a model oxidant in small molecule and proteintherapeutics for its ability to initiate oxidation reactions via both nucleophilic and free radical
mechanisms.[16]

Indirect method

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Measurement of the decrease in the amount of antioxidants (e.g. TAS, reduced glutathione – GSH)

Trapping agents

Using a chemical species that reacts with free radicals to form a stable product that can then be readily measured (Hydroxyl radical and salicylic acid)

See also
-yl
Electron pair
Globally Harmonized System of Classification and Labelling of Chemicals
Hofmann–Löffler reaction

References
1. Jump up^ Oakley, Richard T. (1988). "Cyclic and Heterocyclic Thiazenes" (PDF). Progress in Inorganic Chemistry. Progress in Inorganic Chemistry 36. pp. 299–
391.doi:10.1002/9780470166376.ch4. ISBN 978-0-470-16637-6.
2. Jump up^ Rawson, J; Banister, A; Lavender, I (1995). "The Chemistry of Dithiadiazolylium and Dithiadiazolyl Rings". Advances in Heterocyclic Chemistry Volume 62. Advances
in Heterocyclic Chemistry 62. pp. 137–247. doi:10.1016/S0065-2725(08)60422-5. ISBN 978-0-12-020762-6.
3. Jump up^ Griller, David; Ingold, Keith U. (1976). "Persistent carbon-centered radicals". Accounts of Chemical Research 9: 13.doi:10.1021/ar50097a003.
4. Jump up^ Lomnicki S.; Truong H.; Vejerano E.; Dellinger B. (2008). "Copper oxide-based model of persistent free radical formation on combustion-derived particulate matter".
Environ. Sci. Technol. 42 (13): 4982–4988. doi:10.1021/es071708h.PMID 18678037.
5. Jump up^ However, paramagnetism does not necessarily imply radical character.
6. Jump up^ Pacher P, Beckman JS, Liaudet L (2007). "Nitric oxide and peroxynitrite in health and disease". Physiol. Rev. 87 (1): 315–424. doi:10.1152/physrev.00029.2006. PMC
2248324.PMID 17237348.
7. Jump up^ Rajamani Karthikeyan, Manivasagam T, Anantharaman P, Balasubramanian T, Somasundaram ST (2011). "Chemopreventive effect of Padina boergesenii extracts on
ferric nitrilotriacetate (Fe-NTA)-induced oxidative damage in Wistar rats". J. Appl. Phycol. 23, Issue 2, Page 257 (2): 257–263.doi:10.1007/s10811-010-9564-0.
8. Jump up^ Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N., & Bazan, N. G. (2004). Neuroprotecin D1: A docosahexanoic acid-derived docosatriene protects human retinal
pigment epithelial cells from oxidative stress. Proceedings of the National Academy of Sciences of the USA, 101(22), 8491–8496.doi:10.1073/pnas.0402531101
9. Jump up^ http://www.ncbi.nlm.nih.gov/pubmed/10224662
10. Jump up^ Floyd, R. A., (1999). Neuroinflammatory processes are important in neurodegenerative diseases: An hypothesis to explain the increased formation of reactive oxygen and
nitrogen species as major factors involved in neurodegenerative disease development. Free Radical Biology and Medicine, 26(9–10), 1346–1355. doi:10.1016/S0891-
5849(98)002937
11. Jump up^ An overview of the role of free radicals in biology and of the use of electron spin resonance in their detection may be found in Rhodes C.J. (2000). Toxicology of the
Human Environment – the critical role of free radicals. London: Taylor and Francis.ISBN 0-7484-0916-5.
12. Jump up^ Serpone N, Salinaro A, Emeline AV, Horikoshi S, Hidaka H, Zhao JC. 2002. An in vitro systematic spectroscopic examination of the photostabilities of a random set of
commercial sunscreen lotions and their chemical UVB/UVA active agents. Photochemical & Photobiological Sciences 1(12): 970-981.
13. Jump up^ G. Herzberg (1971), "The spectra and structures of simple free radicals", ISBN 0-486-65821-X.
14. Jump up^ 28th International Symposium on Free Radicals.
15. Jump up^ Betigeri, Seema; Thakur, Ajit; Raghavan, Krishnaswamy (2005). "Use of 2,2?-Azobis(2-Amidinopropane) Dihydrochloride as a Reagent Tool for Evaluation of
Oxidative Stability of Drugs".Pharmaceutical Research 22 (2): 310–7. doi:10.1007/s11095-004-1199-x. PMID 15783080.
16. Jump up^ Werber, Jay; Wang, Y. John; Milligan, Michael; Li, Xiaohua; Ji, Junyan A. (2011). "Analysis of 2,2′-azobis (2-amidinopropane) dihydrochloride degradation and
hydrolysis in aqueous solutions". Journal of Pharmaceutical Sciences 100(8): 3307–15. doi:10.1002/jps.22578. PMID 21560126.

5.10: Free Radicals is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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5.11: Addition of Radicals to Alkenes
Protons and other electrophiles are not the only reactive species that initiate addition reactions to carbon-carbon double bonds.
Curiously, this first became evident as a result of conflicting reports concerning the regioselectivity of HBr additions. As noted
earlier, the acid-induced addition of HBr to 1-butene gave predominantly 2-bromobutane, the Markovnikov Rule product.
However, in some early experiments in which peroxide contaminated reactants were used, 1-bromobutane was the chief product.
Further study showed that an alternative radical chain-reaction, initiated by peroxides, was responsible for the anti-Markovnikov
product. This is shown by the following equations.

The weak O–O bond of a peroxide initiator is broken homolytically by thermal or hight energy. The resulting alkoxy radical then
abstracts a hydrogen atom from HBr in a strongly exothermic reaction. Once a bromine atom is formed it adds to the π-bond of the
alkene in the first step of a chain reaction. This addition is regioselective, giving the more stable carbon radical as an intermediate.
The second step is carbon radical abstraction of another hydrogen from HBr, generating the anti-Markovnikov alkyl bromide and a
new bromine atom. Each of the steps in this chain reaction is exothermic, so once started the process continues until radicals are
lost to termination events.
This free radical chain addition competes very favorably with the slower ionic addition of HBr described earlier, especially in non-
polar solvents. It is important to note, however, that HBr is unique in this respect. The radical addition process is unfavorable for
HCl and HI because one of the chain steps becomes endothermic (the second for HCl & the first for HI).
Other radical addition reactions to alkenes have been observed, one example being the peroxide induced addition of carbon
tetrachloride shown in the following equation

RCH=CH2 + CCl4 (peroxide initiator) —> RCHClCH2CCl3

The best known and most important use of free radical addition to alkenes is probably polymerization. Since the addition of carbon
radicals to double bonds is energetically favorable, concentrated solutions of alkenes are prone to radical-initiated polymerization,
as illustrated for propene by the following equation. The blue colored R-group represents an initiating radical species or a growing
polymer chain; the propene monomers are colored maroon. The addition always occurs so that the more stable radical intermediate
is formed.

RCH2(CH3)CH· + CH3CH=CH2 —> RCH2(CH3)CH-CH2(CH3)CH· + CH3CH=CH2 —> RCH2(CH3)CHCH2(CH3)CH-

CH2(CH3)CH· —> etc.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

This page titled 5.11: Addition of Radicals to Alkenes is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by
William Reusch.
Addition of Radicals to Alkenes by William Reusch is licensed CC BY-NC-SA 4.0.

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5.12: Anti-Markovnikov Product Formation
Anti-Markovnikov rule describes the regiochemistry where the substituent is bonded to a less substituted carbon, rather than the
more substitued carbon. This process is quite unusual, as carboncations which are commonly formed during alkene, or alkyne
reactions tend to favor the more substitued carbon. This is because substituted carbocation allow more hyperconjugation and
indution to happen, making the carbocation more stable.

Introduction
This process was first explained by Morris Selig Karasch in his paper: 'The Addition of Hydrogen Bromide to Allyl Bromide' in
1933.1 Examples of Anti-Markovnikov includes Hydroboration-Oxidation and Radical Addition of HBr. A free radical is any
chemical substance with unpaired electron. The more substituents the carbon is connected to, the more substituted is that carbon.
For example: Tertiary carbon (most substituted), Secondary carbon (medium substituted), primary carbon (least substituted)
Anti-Markovnikov Radical Addition of Haloalkane can ONLY happen to HBr and there MUST be presence of Hydrogen Peroxide
(H2O2). Hydrogen Peroxide is essential for this process, as it is the chemical which starts off the chain reaction in the initiation
step. HI and HCl cannot be used in radical reactions, because in their radical reaction one of the radical reaction steps: Initiation is
Endothermic, as recalled from Chem 118A, this means the reaction is unfavorable. To demonstrate the anti-Markovnikov
regiochemistry, I will use 2-Methylprop-1-ene as an example below:

Initiation Steps
Hydrogen Peroxide is an unstable molecule, if we heat it, or shine it with sunlight, two free radicals of OH will be formed. These
OH radicals will go on and attack HBr, which will take the Hydrogen and create a Bromine radical. Hydrogen radical do not form
as they tend to be extremely unstable with only one electron, thus bromine radical which is more stable will be readily formed.

Propagation Steps
The Bromine Radical will go on and attack the LESS SUBSTITUTED carbon of the alkene. This is because after the bromine
radical attacked the alkene a carbon radical will be formed. A carbon radical is more stable when it is at a more substituted carbon
due to induction and hyperconjugation. Thus, the radical will be formed at the more substituted carbon, while the bromine is
bonded to the less substituted carbon. After a carbon radical is formed, it will go on and attack the hydrogen of a HBr, which a
bromine radical will be formed again.

Termination Steps
There are also Termination Steps, but we do not concern about the termination steps as they are just the radicals combining to
create waste products. For example two bromine radical combined to give bromine. This radical addition of bromine to alkene by
radical addition reaction will go on until all the alkene turns into bromoalkane, and this process will take some time to finish.

References
1. K. Peter C. Vollhardt, Neil E. Schore; Organic Chemistry: Structure and Function Fifth Edition; W. H. Freeman and Campany,
2007
2. Micheal Vokin; Nuffield Advance Chemistry Student's Book Forth Edition; Person Education Limited, 2004

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Problems
Please give the product(s) of the reactions below:
1. CH 3
−C(CH )=CH−CH
3 3
+ HBr + H O
2 2
→

2. CH 3
C(CH )=CH−CH
3 3
+ HI + H O
2 2
→

3. CH 3
C(CH )=CH−CH
3 3
+ HCl + H O
2 2
→

4. CH 3
CH=CH−CH
3
+ HBr + H O
2 2
→

5. CH 3
C(CH )=CH−CH
3 3
+ HBr →

Answers
1. CH3-CH(CH3)-CHBr-CH3 (Anti-Markovnikov)
2. CH3-C(CH3)I-CH2-CH3 (Markovnikov)
3. CH3-C(CH3)Cl-CH2-CH3 (Markovnikov)
4. CH3-CHBr-CH-CH3 or CH3-CH-CHBr-CH3 (Both molecules are the same)
5. CH3-C(CH3)Br-CH2-CH3 (Markovnikov)

References
1. http://uncyclopedia.wikia.com/wiki/Organic_chemistry
2. http://uncyclopedia.wikia.com/wiki/Chemistry

Contributors
Kelvin Kan (UCD)

5.12: Anti-Markovnikov Product Formation is shared under a CC BY-NC-ND license and was authored, remixed, and/or curated by LibreTexts.
Radical Additions: Anti-Markovnikov Product Formation is licensed CC BY-NC-ND 4.0.

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5.13: Homolytic Cleavage and Bond Dissociation Energies

Learning Objective
calculate reaction enthalpies from bond dissociation energies

Introduction
The homolytic bond dissociation energy is the amount of energy needed to break apart one mole of covalently bonded gases into a
pair of radicals. The SI units used to describe bond energy are kiloJoules per mole of bonds (kJ/Mol). It indicates how strongly the
atoms are bonded to each other. Solvation is the interaction between solvent molecules and the ions or molecules dissolved in that
solvent.
Breaking a covalent bond between two partners, A-B, can occur either heterolytically, where the shared pair of electron goes with
one partner or another
+ −
A−B → A +B : (5.13.1)

or
− +
A−B → A : +B (5.13.2)

or homolytically, where one electron stays with each partner.

∙ ∙
A−B → A +B (5.13.3)

The products of homolytic cleavage are radicals and the energy that is required to break the bond
homolytically is called the Bond Dissociation Energy (BDE) and is a measure of the strength of the
bond.
Calculation of the BDE
The BDE for a molecule A-B is calculated as the difference in the enthalpies of formation of the products and reactants for
homolysis
∙ ∙
BDE = Δf H (A ) + Δf H (B ) − Δf H (A − B) (5.13.4)

Officially, the IUPAC definition of bond dissociation energy refers to the energy change that occurs at 0 K, and the symbol is D . o

However, it is commonly referred to as BDE, the bond dissociation energy, and it is generally used, albeit imprecisely,
interchangeably with the bond dissociation enthalpy, which generally refers to the enthalpy change at room temperature (298K).
Although there are technically differences between BDEs at 0 K and 298 K, those difference are not large and generally do not
affect interpretations of chemical processes.

Bond Breakage/Formation
Bond dissociation energy (or enthalpy) is a state function and consequently does not depend on the path by which it occurs.
Therefore, the specific mechanism in how a bond breaks or is formed does not affect the BDE. Bond dissociation energies are
useful in assessing the energetics of chemical processes. For chemical reactions, combining bond dissociation energies for bonds
formed and bonds broken in a chemical reaction using Hess's Law can be used to estimate reaction enthalpies.

Example: Chlorination of Methane

Consider the chlorination of methane
C H4 + C l2 → C H3 C l + H C l (5.13.5)

the overall reaction thermochemistry can be calculated exactly by combining the BDEs for the bonds broken and bonds formed
CH4 → CH3• + H• BDE(CH3-H)

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Cl2 → 2Cl• BDE(Cl2)\]
H• + Cl• → HCl -BDE(HCl)
CH3• + Cl• → CH3Cl -BDE(CH3-Cl)
---------------------------------------------------

C H4 + C l2 → C H3 C l + H C l (5.13.6)

ΔH = BDE(R − H ) + BDE(C l2 ) − BDE(H C l) − BDE(C H3 − C l) (5.13.7)

Because reaction enthalpy is a state function, it does not matter what reactions are combined to make up the overall process
using Hess's Law. However, BDEs are convenient to use because they are readily available.

Alternatively, BDEs can be used to assess individual steps of a mechanism. For example, an important step in free radical
chlorination of alkanes is the abstraction of hydrogen from the alkane to form a free radical.
RH + Cl• → R• + HCl
The energy change for this step is equal to the difference in the BDEs in RH and HCl

ΔH = BDE(R − H ) − BDE(H C l) (5.13.8)

This relationship shows that the hydrogen abstraction step is more favorable when BDE(R-H) is smaller. The difference in energies
accounts for the selectivity in the halogenation of hydrocarbons with different types of C-H bonds.
Table 6.8.1: Representative C-H BDEs in Organic Molecules
R-H Do, kJ/mol D298, kJ/mol R-H Do, kJ/mol D298, kJ/mol

CH3-H 432.7±0.1 439.3±0.4 H2C=CH-H 456.7±2.7 463.2±2.9

CH3CH2-H 423.0±1.7 C6H5-H 465.8±1.9 472.4±2.5

(CH3)2CH-H 412.5±1.7 HCCH 551.2±0.1 557.8±0.3

(CH3)3C-H 403.8±1.7

H2C=CHCH2-H 371.5±1.7

HC(O)-H 368.6±0.8 C6H5CH2-H 375.3±2.5

CH3C(O)-H 374.0±1.2

Trends in C-H BDEs

It is important to remember that C-H BDEs refer to the energy it takes to break the bond, and is the difference in energy between
the reactants and the products. Therefore, it is not appropriate to interpret BDEs solely in terms of the "stability of the radical
products" as is often done.
Analysis of the BDEs shown in the table above shows that there are some systematic trends:
1. BDEs vary with hybridization: Bonds with sp3 hybridized carbons are weakest and bonds with sp hybridized carbons are
much stronger. The vinyl and phenyl C-H bonds are similar, reflecting their sp2 hybridization. The correlation with
hybridization can be viewed as a reflection of the C-H bond lengths. Longer bonds formed with sp3 orbitals are consequently
weaker. Shorter bonds formed with orbitals that have more s-character are similarly stronger.
2. C-H BDEs vary with substitution: Among sp3 hybridized systems, methane has the strongest C-H bond. C-H bonds on
primary carbons are stronger than those on secondary carbons, which are stronger than those on tertiary carbons.

Interpretation of C-H BDEs for sp3 Hybridized Carbons

The interpretation of the BDEs in saturated molecules has been subject of recent controversy. As indicated above, the variation in
BDEs with substitution has traditionally been interpreted as reflecting the stabilities of the alkyl radicals, with the assessment that
more highly substituted radicals are more stable, as with carbocations. Although this is a popular explanation, it fails to account fo
the fact the bonds to groups other than H do not show the same types of variation.

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R BDE(R-CH3) BDE(R-Cl) BDE(R-Br) BDE(R-OH)

CH3- 377.0±0.4 350.2±0.4 301.7±1.3 385.3±0.4

CH3CH2- 372.4±1.7 354.8±2.1 302.9±2.5 393.3±1.7

(CH3)2CH- 370.7±1.7 356.5±2.1 309.2±2.9 399.6±1.7

(CH3)3C- 366.1±1.7 355.2±2.9 303.8±2.5 400.8±1.7

Therefore, although C-CH3 bonds get weaker with more substitution, the effect is not nearly as large as that observed with C-H
bonds. The strengths of C-Cl and C-Br bonds are not affected by substitution, despite the fact that the same radicals are formed as
when breaking C-H bonds, and the C-OH bonds in alcohols actually increase with more substitution.
Gronert has proposed that the variation in BDEs is alternately explained as resulting from destabilization of the reactants due to
steric repulsion of the substituents, which is released in the nearly planar radicals.1 Considering that BDEs reflect the relative
energies of reactants and products, either explanation can account for the trend in BDEs.
Another factor that needs to be considered is the electronegativity. The Pauling definition of electronegativity says that the bond
dissociation energy between unequal partners is going to be dependent on the difference in electrongativities, according to the
expression
Do (A − A) + Do (B − B)
2
Do (A − B) = + (XA − XB ) (5.13.9)
2

where X and X are the electronegativities and the bond energies are in eV. Therefore, the variation in BDEs can be interpreted
A B

as reflecting variation in the electronegativities of the different types of alkyl fragments.

There is likely some merit in all three interpretations. Since Gronert's original publication of his alternate explanation, there have
been many desperate attempts to defend the radical stability explanation.

Exercise
1. Given that ΔH° for the reaction
CH4(g) + 4F2(g) -> CF4(g) + 4HF(g)
is −1936 kJ, use the following data to calculate the average bond energy of the \(\ce{{\sf{C-F}}$ bonds in CF4.

Bond Average Bond Energy

C−H 413 kJ · mol−1

F−F 155 kJ · mol−1

H−F 567 kJ · mol−1

2. Calculate ΔH° for the reactions given below.

a. CH3CH2OCH3 + HI -> CH3CH2OH + CH3I
b. CH3Cl + NH3 -> CH3NH2 + HCl

Answer
1. CH4(g) + 4 F2(g) → CF4(g) + 4HF(g) ΔH°=−416 kcal
Bonds broken:
(413 kJ)
4 mol C-H bonds × = 1652 kJ
(1 mol)

(155 kJ)
4 mol F-F bonds × = 620 kJ
(1 mol)

Bonds formed:

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(x kJ)
4 mol C-F bonds × = 4x kJ
(1 mol)

(where x = the average energy of one mole of C-F bonds in CF4, expressed in kJ)
(567 kJ)
4 mol H-F bonds × = 2268 kJ
(1 mol)

ΔH ° = ΔH °(bonds broken) − ΔH °(bonds formed)

= (1652 kJ + 620 kJ) − (4x + 2268 kJ)

= 1652 kJ + 620 kJ − 4x − 2268 kJ

= −1936 kJ

Thus,
4x = 1936 kJ − 2268 kJ + 620 kJ + 1652 kJ

= 1940 kJ

and
1940 kJ
x =
4 mol
−1
= 385 kJ ⋅ mol

The average energy of a C-F bond in CF4 is 385 kJ · mol-1

2. CH3Cl + NH3 -> CH3NH2 + HCl
Reactant bonds broken D Product bonds formed D

CH −Cl 351 kJ/mol CH −NH 335 kJ/mol

3 3 2

NH −H 449 kJ/mol H−Cl 432 kJ/mol

2
$$ $$
800 kJ/mol 767 kJ/mol

∘
ΔH = Dbonds broken + Dbonds formed

= 800 kJ/mol − 767 kJ/mol

= +33 kJ/mol

References
1. Gronert, S. J. Org. Chem. 2006, 13, 1209

Further Reading
MasterOrganicChemistry
Bond Strengths And Radical Stability

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
Prof. Paul G. Wenthold (Purdue University)

5.13: Homolytic Cleavage and Bond Dissociation Energies is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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5.14: Polymerization of Alkenes
One of the most important technical reactions of alkenes is their conversion to higher-molecular-weight compounds or polymers
(Table 10-4). A polymer is defined as a long-chain molecule with recurring structural units. Thus polymerization of propene gives

a long-chain hydrocarbon with recurring units:

Table 10-4: Alkene Monomers and Their Polymers

Most technically important polymerizations of alkenes occur by chain mechanisms and may be classed as anion, cation, or radical
reactions, depending upon the character of the chain-carrying species. In each case, the key steps involve successive additions to
molecules of the alkene, the differences being in the number of electrons that are supplied by the attacking agent for formation of
the new carbon-carbon bond. For simplicity, these steps will be illustrated by using ethene, even though it does not polymerize very
easily by any of them:

Anionic Polymerization
Initiation of alkene polymerization by the anion-chain mechanism may be formulated as involving an attack by a nucleophilic
reagent Y on one end of the double bond and formation of a carbanion:
⊖

Attack by the carbanion on another alkene molecule would give a four-carbon carbanion, and subsequent additions to further
alkene molecules would lead to a high-molecular-weight anion:

The growing chain can be terminated by any reaction (such as the addition of a proton) that would destroy the carbanion on the end
of the chain:

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Anionic polymerization of alkenes is quite difficult to achieve because few anions (or nucleophiles) are able to add readily to
alkene double bonds (see Section 10-6). Anionic polymerization occurs readily only with alkenes substituted with sufficiently
powerful electron-attracting groups to expedite nucleophilic attack. By this reasoning, alkynes should polymerize more readily than
alkenes under anionic conditions, but there appear to be no technically important alkyne polymerizations in operation by this or any
other mechanism. Perhaps this is because the resultant polymer would be highly conjugated, and therefore highly reactive, and may
not survive the experimental conditions:

Cationic Polymerization
Polymerization of an alkene by acidic reagents can be formulated by a mechanism similar to the addition of hydrogen halides to
alkene linkages. First, a proton from a suitable acid adds to an alkene to yield a carbocation. Then, in the absence of any other
reasonably strong nucleophilic reagent, another alkene molecule donates an electron pair and forms a longer-chain cation.
Continuation of this process can lead to a high-molecular-weight cation. Termination can occur by loss of a proton. The following
equations represent the overall reaction sequence:

Ethene does not polymerize by the cationic mechanism because it does not have sufficiently electron-donating groups to permit
easy formation of the intermediate growing-chain cation. 2-Methylpropene has electron-donating alkyl groups and polymerizes
much more easily than ethene by this type of mechanism. The usual catalysts for cationic polymerization of 2-methylpropene are
sulfuric acid, hydrogen fluoride, or a complex of boron trifluoride and water. Under nearly anhydrous conditions a very long chain
polymer called polyisobutylene is formed.

Polyisobutylene fractions of particular molecular weights are very tacky and are used as adhesives for pressure-sealing tapes.
In the presence of 60% sulfuric acid, 2-methylpropene is not converted to a long-chain polymer, but to a mixture of eight-carbon
alkenes. The mechanism is like that of the polymerization of 2-methylpropene under nearly anhydrous conditions, except that chain
termination occurs after only one 2-methylpropene molecule has been added:

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The short chain length is due to the high water concentration; the intermediate carbocation loses a proton to water before it can
react with another alkene molecule.
The proton can be lost in two different ways, and a mixture of alkene isomers is obtained. The alkene mixture is known as
"diisobutylene" and has a number of commercial uses. Hydrogenation yields 2,2,4-trimethylpentane (often erroneously called
"isooctane"), which is used as the standard "100 antiknock rating" fuel for internal-combustion gasoline engines:

Radical Polymerization
Ethene can be polymerized with peroxide catalysts under high pressure (1000 atm or more, literally in a cannon barrel) at
temperatures in excess of 100 . The initiation step involves formation of radicals, and chain propagation entails stepwise addition
o

of radicals to ethene molecules.

Chain termination can occur by any reaction resulting in combination or disproportionation of free radicals.

The polyethene produced in this way has from 100 to 1000 ethene units in the hydrocarbon chain. The polymer possesses a number
of desirable properties as a plastic and is used widely for electrical insulation, packaging films, piping, and a variety of molded
articles. Propene and 2-methylpropene do not polymerize satisfactorily by radical mechanisms.

Coordination Polymerization
A relatively low-pressure, low-temperature ethene polymerization has been achieved with an aluminum-molybdenum oxide
catalyst, which requires occasional activation with hydrogen (Phillips Petroleum process). Ethene also polymerizes quite rapidly at
atmospheric pressure and room temperature in an alkane solvent containing a suspension of the insoluble reaction product from
triethylaluminum and titanium tetrachloride (Ziegler process). Both the Phillips and Ziegler processes produce very high-
molecular-weight polyethene with exceptional physical properties. The unusual characteristics of these reactions indicate that no

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simple anion, cation, or radical mechanism can be involved. It is believed that the catalysts act by coordinating with the alkene
molecules in somewhat the same way that hydrogenation catalysts combine with alkenes (Section 11-2A).
Polymerization of propene by the Ziegler process gives a very useful plastic material. It can be made into durable fibers or molded
into a variety of shapes. Copolymers (polymers with more than one kind of monomer unit in the polymer chains) of ethene and
propene made by the Ziegler process have highly desirable rubberlike properties and are potentially the cheapest useful elastomers
(elastic polymers). A Nobel Prize was shared in 1963 by K. Ziegler and G. Natta for their work on alkene polymerization.
The properties and uses of polymers are discussed in greater detail in Chapters 13 and 29. The most important alkene monomers
used in addition polymerizations are listed in Table 10-4 along with some names and uses of the corresponding polymers.

References
John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. ,
Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission
for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any
format."

5.14: Polymerization of Alkenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
10.9: Polymerization of Alkenes by John D. Roberts and Marjorie C. Caserio is licensed CC BY-NC-SA 4.0.

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CHAPTER OVERVIEW

6: Principles of Stereochemistry is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
6.1: Chirality and Stereoisomers
Stereoisomers are isomers that differ in spatial arrangement of atoms, rather than order of atomic connectivity. One of their most
interesting type of isomer is the mirror-image stereoisomers, a non-superimposable set of two molecules that are mirror image of
one another. The existence of these molecules are determined by concept known as chirality.

Introduction
Organic compounds, molecules created around a chain of carbon atom (more commonly known as carbon backbone), play an
essential role in the chemistry of life. These molecules derive their importance from the energy they carry, mainly in a form of
potential energy between atomic molecules. Since such potential force can be widely affected due to changes in atomic placement,
it is important to understand the concept of an isomer, a molecule sharing same atomic make up as another but differing in
structural arrangements. This article will be devoted to a specific isomers called stereoisomers and its property of chirality (Figure
1).

Figure 1: Two enantiomers of a tetrahedral complex.

The concepts of steroisomerism and chirality command great deal of importance in modern organic chemistry, as these ideas helps
to understand the physical and theoretical reasons behind the formation and structures of numerous organic molecules, the main
reason behind the energy embedded in these essential chemicals. In contrast to more well-known constitutional isomerism, which
develops isotopic compounds simply by different atomic connectivity, stereoisomerism generally maintains equal atomic
connections and orders of building blocks as well as having same numbers of atoms and types of elements.
What, then, makes stereoisomers so unique? To answer this question, the learner must be able to think and imagine in not just two-
dimensional images, but also three-dimensional space. This is due to the fact that stereoisomers are isomers because their atoms are
different from others in terms of spatial arrangement.

Spatial Arrangement
First and foremost, one must understand the concept of spatial arrangement in order to understand stereoisomerism and chirality.
Spatial arrangement of atoms concern how different atomic particles and molecules are situated about in the space around the
organic compound, namely its carbon chain. In this sense, spatial arrangement of an organic molecule are different another if an
atom is shifted in any three-dimensional direction by even one degree. This opens up a very broad possibility of different
molecules, each with their unique placement of atoms in three-dimensional space .

Stereoisomers
Stereoisomers are, as mentioned above, contain different types of isomers within itself, each with distinct characteristics that
further separate each other as different chemical entities having different properties. Type called entaniomer are the previously-
mentioned mirror-image stereoisomers, and will be explained in detail in this article. Another type, diastereomer, has different
properties and will be introduced afterwards.
Enantiomers
This type of stereoisomer is the essential mirror-image, non-superimposable type of stereoisomer introduced in the beginning of the
article. Figure 3 provides a perfect example; note that the gray plane in the middle demotes the mirror plane.

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Figure 2: Comparison of Chiral and Achiral Molecules. (a) Bromochlorofluoromethane is a chiral molecule whose stereocenter is
designated with an asterisk. Rotation of its mirror image does not generate the original structure. To superimpose the mirror
images, bonds must be broken and reformed. (b) In contrast, dichlorofluoromethane and its mirror image can be rotated so they are
superimposable.
Note that even if one were to flip over the left molecule over to the right, the atomic spatial arrangement will not be equal. This is
equivalent to the left hand - right hand relationship, and is aptly referred to as 'handedness' in molecules. This can be somewhat
counter-intuitive, so this article recommends the reader try the 'hand' example. Place both palm facing up, and hands next to each
other. Now flip either side over to the other. One hand should be showing the back of the hand, while the other one is showing the
palm. They are not same and non-superimposable.
This is where the concept of chirality comes in as one of the most essential and defining idea of stereoisomerism.
Chirality
Chirality essentially means 'mirror-image, non-superimposable molecules', and to say that a molecule is chiral is to say that its
mirror image (it must have one) is not the same as it self. Whether a molecule is chiral or achiral depends upon a certain set of
overlapping conditions. Figure 4 shows an example of two molecules, chiral and achiral, respectively. Notice the distinct
characteristic of the achiral molecule: it possesses two atoms of same element. In theory and reality, if one were to create a plane
that runs through the other two atoms, they will be able to create what is known as bisecting plane: The images on either side of the
plan is the same as the other (Figure 4).

Figure 4.
In this case, the molecule is considered 'achiral'. In other words, to distinguish chiral molecule from an achiral molecule, one must
search for the existence of the bisecting plane in a molecule. All chiral molecules are deprive of bisecting plane, whether simple or
complex.
As a universal rule, no molecule with different surrounding atoms are achiral. Chirality is a simple but essential idea to support the
concept of stereoisomerism, being used to explain one type of its kind. The chemical properties of the chiral molecule differs from
its mirror image, and in this lies the significance of chilarity in relation to modern organic chemistry.

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Compounds with Multiple Chiral Centers
We turn our attention next to molecules which have more than one stereocenter. We will start with a common four-carbon sugar
called D-erythrose.

A note on sugar nomenclature: biochemists use a special system to refer to the stereochemistry of sugar molecules, employing
names of historical origin in addition to the designators 'D' and 'L'. You will learn about this system if you take a biochemistry
class. We will use the D/L designations here to refer to different sugars, but we won't worry about learning the system.
As you can see, D-erythrose is a chiral molecule: C2 and C3 are stereocenters, both of which have the R configuration. In addition,
you should make a model to convince yourself that it is impossible to find a plane of symmetry through the molecule, regardless of
the conformation. Does D-erythrose have an enantiomer? Of course it does – if it is a chiral molecule, it must. The enantiomer of
erythrose is its mirror image, and is named L-erythrose (once again, you should use models to convince yourself that these mirror
images of erythrose are not superimposable).

Notice that both chiral centers in L-erythrose both have the S configuration. In a pair of enantiomers, all of the chiral centers are of
the opposite configuration.
What happens if we draw a stereoisomer of erythrose in which the configuration is S at C2 and R at C3? This stereoisomer, which is
a sugar called D-threose, is not a mirror image of erythrose. D-threose is a diastereomer of both D-erythrose and L-erythrose.

The definition of diastereomers is simple: if two molecules are stereoisomers (same molecular formula, same connectivity, different
arrangement of atoms in space) but are not enantiomers, then they are diastereomers by default. In practical terms, this means that
at least one - but not all - of the chiral centers are opposite in a pair of diastereomers. By definition, two molecules that are
diastereomers are not mirror images of each other.
L-threose, the enantiomer of D-threose, has the R configuration at C2 and the S configuration at C3. L-threose is a diastereomer of
both erythrose enantiomers.
In general, a structure with n stereocenters will have 2n different stereoisomers. (We are not considering, for the time being, the
stereochemistry of double bonds – that will come later). For example, let's consider the glucose molecule in its open-chain form
(recall that many sugar molecules can exist in either an open-chain or a cyclic form). There are two enantiomers of glucose, called

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D-glucose and L-glucose. The D-enantiomer is the common sugar that our bodies use for energy. It has n = 4 stereocenters, so
therefore there are 2n = 24 = 16 possible stereoisomers (including D-glucose itself).

In L-glucose, all of the stereocenters are inverted relative to D-glucose. That leaves 14 diastereomers of D-glucose: these are
molecules in which at least one, but not all, of the stereocenters are inverted relative to D-glucose. One of these 14 diastereomers, a
sugar called D-galactose, is shown above: in D-galactose, one of four stereocenters is inverted relative to D-glucose. Diastereomers
which differ in only one stereocenter (out of two or more) are called epimers. D-glucose and D-galactose can therefore be refered
to as epimers as well as diastereomers.

 Example 3.10

Draw the structure of L-galactose, the enantiomer of D-galactose.

Solution

 Example 3.11

Draw the structure of two more diastereomers of D-glucose. One should be an epimer.
Solution

Erythronolide B, a precursor to the 'macrocyclic' antibiotic erythromycin, has 10 stereocenters. It’s enantiomer is that molecule in
which all 10 stereocenters are inverted.

In total, there are 210 = 1024 stereoisomers in the erythronolide B family: 1022 of these are diastereomers of the structure above,
one is the enantiomer of the structure above, and the last is the structure above.
We know that enantiomers have identical physical properties and equal but opposite degrees of specific rotation. Diastereomers, in
theory at least, have different physical properties – we stipulate ‘in theory’ because sometimes the physical properties of two or
more diastereomers are so similar that it is very difficult to separate them. In addition, the specific rotations of diastereomers are
unrelated – they could be the same sign or opposite signs, and similar in magnitude or very dissimilar.

Constitutional isomers
Constitutational isomers or structural isomers are molecules with the same chemical formula but different structures of atoms
and bonds. For example, both 3-methylpentane and hexane have the same chemical formula, C6H14, yet they clearly have different

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structures:

3-methylpentane hexane

Another example involves functional groups. Methoxy methane, an ether, and ethanol, an alcohol, both have the chemical formula
C2H6O:

Methoxy methane Ethanol

External Resources
1. Further Details of Stereochemistry: For those interested in the topic further!
2. MIT Online-Lecture including basic Organic Chemistry : Good background lecture to introduce Organic Chemistry.
3. Chirality Rap: Good way to understand the concept? Decide for yourself!

References
1. Anslyn, Eric V. and Dougherty, Dennis A. Modern Physical Organic Chemistry. Chicago, IL.: University Science. 2005
2. Hick, Janice M. The Physical Chemistry of Chirality. New York, N.Y.: An American Chemical Society Publication. 2001.
3. Vollhardt, K. Peter C. and Schore, Neil E. Organic Chemistry: Structure and Function. Fifth Edition. New York, N.Y.: W. H.
Freeman Company, 2007.

Problems
Identify the following as either a constitutional isomer or stereoisomer. If stereoisomer, determine if it is an enantiomer or
diastereomer. Explain the reason behind the answer. Also mark chirality for each molecule.

1. 2. 3.

Contributors
Dan Chong
Jonathan Mooney (McGill University)

6.1: Chirality and Stereoisomers is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Chirality and Stereoisomers is licensed CC BY-NC-SA 4.0.

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6.2: R-S Sequence Rules
To name the enantiomers of a compound unambiguously, their names must include the "handedness" of the molecule. The method
for this is formally known as R/S nomenclature.

Introduction
The method of unambiguously assigning the handedness of molecules was originated by three chemists: R.S. Cahn, C. Ingold, and
V. Prelog and is also often called the Cahn-Ingold-Prelog rules. In addition to the Cahn-Ingold system, there are two ways of
experimentally determining the absolute configuration of an enantiomer:
1. X-ray diffraction analysis. Note that there is no correlation between the sign of rotation and the structure of a particular
enantiomer.
2. Chemical correlation with a molecule whose structure has already been determined via X-ray diffraction.
However, for non-laboratory purposes, it is beneficial to focus on the R/S system. The sign of optical rotation, although different
for the two enantiomers of a chiral molecule, at the same temperature, cannot be used to establish the absolute configuration of an
enantiomer; this is because the sign of optical rotation for a particular enantiomer may change when the temperature changes.

Stereocenters are labeled R or S

The "right hand" and "left hand" nomenclature is used to name the enantiomers of a chiral compound. The stereocenters are labeled
as R or S.

Consider the first picture: a curved arrow is drawn from the highest priority (1) substituent to the lowest priority (4) substituent. If
the arrow points in a counterclockwise direction (left when leaving the 12 o' clock position), the configuration at stereocenter is
considered S ("Sinister" → Latin= "left"). If, however, the arrow points clockwise,(Right when leaving the 12 o' clock position)
then the stereocenter is labeled R ("Rectus" → Latin= "right"). The R or S is then added as a prefix, in parenthesis, to the name of
the enantiomer of interest. For example: (R)-2-Bromobutane and (S)-2,3- Dihydroxypropanal.

Sequence rules to assign priorities to substituents

Before applying the R and S nomenclature to a stereocenter, the substituents must be prioritized according to the following rules:

Rule 1
First, examine at the atoms directly attached to the stereocenter of the compound. A substituent with a higher atomic number takes
precedence over a substituent with a lower atomic number. Hydrogen is the lowest possible priority substituent, because it has the
lowest atomic number.
1. When dealing with isotopes, the atom with the higher atomic mass receives higher priority.
2. When visualizing the molecule, the lowest priority substituent should always point away from the viewer (a dashed line
indicates this). To understand how this works or looks, imagine that a clock and a pole. Attach the pole to the back of the clock,
so that when when looking at the face of the clock the pole points away from the viewer in the same way the lowest priority
substituent should point away.
3. Then, draw an arrow from the highest priority atom to the 2nd highest priority atom to the 3rd highest priority atom. Because
the 4th highest priority atom is placed in the back, the arrow should appear like it is going across the face of a clock. If it is
going clockwise, then it is an R-enantiomer; If it is going counterclockwise, it is an S-enantiomer.
When looking at a problem with wedges and dashes, if the lowest priority atom is not on the dashed line pointing away, the
molecule must be rotated.
Remember that

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Wedges indicate coming towards the viewer.
Dashes indicate pointing away from the viewer.

Rule 2
If there are two substituents with equal rank, proceed along the two substituent chains until there is a point of difference. First,
determine which of the chains has the first connection to an atom with the highest priority (the highest atomic number). That chain
has the higher priority.
If the chains are similar, proceed down the chain, until a point of difference.
For example: an ethyl substituent takes priority over a methyl substituent. At the connectivity of the stereocenter, both have a
carbon atom, which are equal in rank. Going down the chains, a methyl has only has hydrogen atoms attached to it, whereas the
ethyl has another carbon atom. The carbon atom on the ethyl is the first point of difference and has a higher atomic number than
hydrogen; therefore the ethyl takes priority over the methyl.

Rule 3
If a chain is connected to the same kind of atom twice or three times, check to see if the atom it is connected to has a greater atomic
number than any of the atoms that the competing chain is connected to.
If none of the atoms connected to the competing chain(s) at the same point has a greater atomic number: the chain bonded to the
same atom multiple times has the greater priority
If however, one of the atoms connected to the competing chain has a higher atomic number: that chain has the higher priority.

 Example 2

A 1-methylethyl substituent takes precedence over an ethyl substituent. Connected to the first carbon atom, ethyl only has one
other carbon, whereas the 1-methylethyl has two carbon atoms attached to the first; this is the first point of difference.
Therefore, 1-methylethyl ranks higher in priority than ethyl, as shown below:

However:

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Remember that being double or triple bonded to an atom means that the atom is connected to the same atom twice. In such a
case, follow the same method as above.

Caution!!
Keep in mind that priority is determined by the first point of difference along the two similar substituent chains. After the first
point of difference, the rest of the chain is irrelevant.

When looking for the first point of difference on similar substituent chains, one may encounter branching. If there is branching,
choose the branch that is higher in priority. If the two substituents have similar branches, rank the elements within the branches
until a point of difference.

After all your substituents have been prioritized in the correct manner, you can now name/label the molecule R or S.
1. Put the lowest priority substituent in the back (dashed line).
2. Proceed from 1 to 2 to 3. (it is helpful to draw or imagine an arcing arrow that goes from 1--> 2-->3)
3. Determine if the direction from 1 to 2 to 3 clockwise or counterclockwise.
i) If it is clockwise it is R.
ii) if it is counterclockwise it is S.

USE YOUR MODELING KIT: Models assist in visualizing the structure. When using a model, make sure the lowest priority is
pointing away from you. Then determine the direction from the highest priority substituent to the lowest: clockwise (R) or
counterclockwise (S).

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IF YOU DO NOT HAVE A MODELING KIT: remember that the dashes mean the bond is going into the screen and the wedges
means that bond is coming out of the screen. If the lowest priority bond is not pointing to the back, mentally rotate it so that it is.
However, it is very useful when learning organic chemistry to use models.
If you have a modeling kit use it to help you solve the following practice problems.

 Exercise 6.2.1

Are the following R or S?

Answer
1. S: I > Br > F > H. The lowest priority substituent, H, is already going towards the back. It turns left going from I to Br
to F, so it's a S.
2. R: Br > Cl > CH3 > H. You have to switch the H and Br in order to place the H, the lowest priority, in the back. Then,
going from Br to Cl, CH3 is turning to the right, giving you a R.
3. Neither R or S: This molecule is achiral. Only chiral molecules can be named R or S.
4. R: OH > CN > CH2NH2 > H. The H, the lowest priority, has to be switched to the back. Then, going from OH to CN to
CH2NH2, you are turning right, giving you a R. (5)
5. S: −COOH > −CH OH > C≡CH > H. Then, going from −COOH to −CH OH to −C≡CH you are turning left,
2 2

giving you a S configuration.

References
1. Schore and Vollhardt. Organic Chemistry Structure and Function. New York:W.H. Freeman and Company, 2007.
2. McMurry, John and Simanek, Eric. Fundamentals of Organic Chemistry. 6th Ed. Brooks Cole, 2006.

6.2: R-S Sequence Rules is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Absolute Configuration - R-S Sequence Rules by Ekta Patel, Ifemayowa Aworanti is licensed CC BY-NC-SA 4.0.

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6.3: Optical Activity
Optical activity is an effect of an optical isomer's interaction with plane-polarized light.

Introduction
Optical isomers, or enantiomers, have the same sequence of atoms and bonds but are different in their 3D shape. Two enantiomers
are nonsuperimposible mirror images of one another (i.e., chiral), with the most common cited example being our hands. Our left
hand is a mirror image of our right, yet there is no way our left thumb can be over our right thumb if our palms are facing the same
way and placed over one another. Optical isomers also have no axis of symmetry, which means that there is no line that bisects the
compound such that the left half is a mirror image of the right half.
Optical isomers have basically the same properties (melting points, boiling points, etc.) but there are a few exceptions (uses in
biological mechanisms and optical activity). There are drugs, called enantiopure drugs, that have different effects based on whether
the drug is a racemic mixture or purely one enantiomer. For example, d-ethambutol treats tuberculosis, while l-ethambutol causes
blindness. Optical activity is the interaction of these enantiomers with plane-polarized light.

A Brief History
Optical activity was first observed by the French physicist Jean-Baptiste Biot. He concluded that the change in direction of plane-
polarized light when it passed through certain substances was actually a rotation of light, and that it had a molecular basis. His
work was supported by the experimentation of Louis Pasteur. Pasteur observed the existence of two crystals that were mirror
images in tartaric acid, an acid found in wine. Through meticulous experimentation, he found that one set of molecules rotated
polarized light clockwise while the other rotated light counterclockwise to the same extent. He also observed that a mixture of both,
a racemic mixture (or racemic modification), did not rotate light because the optical activity of one molecule canceled the effects of
the other molecule. Pasteur was the first to show the existence of chiral molecules.

Rotation of Light
An enantiomer that rotates plane-polarized light in the positive direction, or clockwise, is called dextrorotary [(+), or d-], while the
enantiomer that rotates the light in the negative direction, or counterclockwise, is called levorotary [(-), or l-]. When both d- and l-
isomers are present in equal amounts, the mixture is called a racemic mixture.

image source

In the picture above, you can see that unpolarized light passes through a filter so that only waves that oscillate in a certain direction
can pass through. When these waves interact with an optically active material, they are rotated either clockwise or
counterclockwise, depending on the enantiomer. In the case of the image above, the light is rotated clockwise so the substance is
the dextrorotary enantiomer.

Measuring Optical Activity

Optical activity is measured by a polarimeter, and is dependent on several factors: concentration of the sample, temperature, length
of the sample tube or cell, and wavelength of the light passing through the sample. Rotation is given in +/- degrees, depending on
whether the sample has d- (positive) or l- (negative) enantiomers. The standard measurement for rotation for a specific chemical
compound is called the specific rotation, defined as an angle measured at a path length of 1 decimeter and a concentration of 1g/ml.
The specific rotation of a pure substance is an intrinsic property. In solution, the formula for specific rotation is:
α
T
[α ] = (6.3.1)
λ
I ⋅c

where
[α] is the specific rotation in degrees cm3 dm-1 g-1.
λ is the wavelength in nanometers,
α is the measured angle of rotation of a substance,
T is the temperature in degrees,
l is the path length in decimeters,

6.3.1 https://chem.libretexts.org/@go/page/206996
c is the concentration in g/ml, and

References
1. Pettrucci, Ralph H., Harwood, Herring, Madura. General Chemistry: Principles and Modern Applications. 9th. Upper Saddle
River: Pearson Prentice Hall, 2007.
2. Raymond, Kenneth W. General Organic and Biological Chemistry. 3rd. Hoboken: John Wiley & Sons, Inc. 2010.

Practice Questions
1. Why doesn’t a racemic mixture show optical activity?
2. Does the following image show optically active molecules (image source)?

3. What would happen if your feet were not optical isomers of each other?
4. Your friend has tuberculosis. Assuming you like your friend and you want him to live, which isomer of ethambutol do you give
him and why?
5. Draw each compound's enantiomer.

Answers
1. In a racemic mixture, both dextrorotary and levorotary enantiomers are present in equal amounts,
so the overall rotation of polarized light is zero. The clockwise rotation is canceled by the
counterclockwise rotation.
2. Yes, because the molecules are mirror images of one another.
3. You'd be a terrible dancer. (Get it? Two left feet? Haha.)
4. Dextrorotary ethambutol, because l-ethambutol would not only fail to cure him, but it would also
leave him blind.
5. Enantiomers
http://en.Wikipedia.org/wiki/Enantiopure_drug

Contributors
Nanki J Natt (UCD), Anna Zhu (UCD)

6.3: Optical Activity is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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6.4: Optical Activity - more detail
 Objectives

After completing this section, you should be able to

1. describe the nature of plane-polarized light.
2. describe the features and operation of a simple polarimeter.
3. calculate the specific rotation of a compound, given the relevant experimental data.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
analyzer
dextrorotatory
levorotatory
optically active
plane-polarized light
polarimeter
polarizer
specific rotation, [α]20
D

 Study Notes

A polarizer is a device through which only light waves oscillating in a single plane may pass. A polarimeter is an instrument
used to determine the angle through which plane-polarized light has been rotated by a given sample. You will have the
opportunity to use a polarimeter in the laboratory component of the course. An analyzer is the component of a polarimeter that
allows the angle of rotation of plane-polarized light to be determined.
Specific rotations are normally measured at 20°C, and this property may be indicated by the symbol [α]
20
D
. Sometimes the
solvent is specified in parentheses behind the specific rotation value, for example,
20 o
[α ] = +12 (chloroform)
D

For liquids, the specific rotation may be obtained using the neat liquid rather than a solution; in such cases the formula is
temp
[α ] (neat) = α × l × d
D

where α is the observed rotation, l is the path length of the cell (measured in decimetres, dm), and d is the density of the liquid.

Identifying and distinguishing enantiomers is inherently difficult, since their physical and chemical properties are largely identical.
Fortunately, a nearly two hundred year old discovery by the French physicist Jean-Baptiste Biot has made this task much easier.
This discovery disclosed that the right- and left-handed enantiomers of a chiral compound perturb plane-polarized light in opposite
ways. This perturbation is unique to chiral molecules, and has been termed optical activity.

Polarimetry
Plane-polarized light is created by passing ordinary light through a polarizing device, which may be as simple as a lens taken from
polarizing sun-glasses. Such devices transmit selectively only that component of a light beam having electrical and magnetic field
vectors oscillating in a single plane. The plane of polarization can be determined by an instrument called a polarimeter (Figure
6.4.1).

Monochromatic (single wavelength) light, is polarized by a fixed polarizer next to the light source. A sample cell holder is located
in line with the light beam, followed by a movable polarizer (the analyzer) and an eyepiece through which the light intensity can be
observed. In modern instruments an electronic light detector takes the place of the human eye. In the absence of a sample, the light

6.4.1 https://chem.libretexts.org/@go/page/206997
intensity at the detector is at a maximum when the second (movable) polarizer is set parallel to the first polarizer (α = 0º). If the
analyzer is turned 90º to the plane of initial polarization, all the light will be blocked from reaching the detector.

6 8
4
2 7

1
Figure 6.4.1 : Operating principle of an optical polarimeter. 1. Light source 2. Unpolarized light 3. Linear polarizer 4. Linearly
polarized light 5. Sample tube containing molecules under study 6. Optical rotation due to molecules 7. Rotatable linear analyzer 8.
Detector. (CC BY-SA 3.0 Unported; Kaidor via Wikipedia)
Chemists use polarimeters to investigate the influence of compounds (in the sample cell) on plane polarized light. Samples
composed only of achiral molecules (e.g. water or hexane), have no effect on the polarized light beam. However, if a single
enantiomer is examined (all sample molecules being right-handed, or all being left-handed), the plane of polarization is rotated in
either a clockwise (positive) or counter-clockwise (negative) direction, and the analyzer must be turned an appropriate matching
angle, α, if full light intensity is to reach the detector. In the above illustration, the sample has rotated the polarization plane
clockwise by +90º, and the analyzer has been turned this amount to permit maximum light transmission.
The observed rotations (α ) of enantiomers are opposite in direction. One enantiomer will rotate polarized light in a clockwise
direction, termed dextrorotatory or (+), and its mirror-image partner in a counter-clockwise manner, termed levorotatory or (–).
The prefixes dextro and levo come from the Latin dexter, meaning right, and laevus, for left, and are abbreviated d and l
respectively. If equal quantities of each enantiomer are examined , using the same sample cell, then the magnitude of the rotations
will be the same, with one being positive and the other negative. To be absolutely certain whether an observed rotation is positive
or negative it is often necessary to make a second measurement using a different amount or concentration of the sample. In the
above illustration, for example, α might be –90º or +270º rather than +90º. If the sample concentration is reduced by 10%, then the
positive rotation would change to +81º (or +243º) while the negative rotation would change to –81º, and the correct α would be
identified unambiguously.
Since it is not always possible to obtain or use samples of exactly the same size, the observed rotation is usually corrected to
compensate for variations in sample quantity and cell length. Thus it is common practice to convert the observed rotation, α , to a
specific rotation, by the following formula:
α
[α ]D = (5.3.1)
lc

where
[α]D is the specific rotation
lis the cell length in dm
c is the concentration in g/ml

D designates that the light used is the 589 line from a sodium lamp

Compounds that rotate the plane of polarized light are termed optically active. Each enantiomer of a stereoisomeric pair is
optically active and has an equal but opposite-in-sign specific rotation. Specific rotations are useful in that they are experimentally
determined constants that characterize and identify pure enantiomers. For example, the lactic acid enantiomers have the following
specific rotations:
Carvone from caraway: [α ] 20
D
= +62.5
o
(this isomer may be referred to as (+)-carvone or d-carvone)
Carvone from spearmint: [α ] 20
D
= −62.5
o
(this isomer may be referred to as (–)-carvone or l-carvone)
and carvone enantiomers have the following specific rotations:

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Lactic acid from muscle tissue: [α ] = +2.5 (this isomer may be referred to as (+)-lactic acid or d-lactic acid)
20
D
o

Lactic acid from sour milk: [α ] = −2.5 (this isomer may be referred to as (–)-lactic acid or l-lactic acid)
20
D
o

A 50:50 mixture of enantiomers has no observable optical activity. Such mixtures are called racemates or racemic modifications,
and are designated (±). When chiral compounds are created from achiral compounds, the products are racemic unless a single
enantiomer of a chiral co-reactant or catalyst is involved in the reaction. The addition of HBr to either cis- or trans-2-butene is an
example of racemic product formation (the chiral center is colored red).

CH CH=CHCH + HBr ⟶ (±)CH CH C HBrCH

3 3 3 2 3

Chiral organic compounds isolated from living organisms are usually optically active, indicating that one of the enantiomers
predominates (often it is the only isomer present). This is a result of the action of chiral catalysts we call enzymes, and reflects the
inherently chiral nature of life itself. Chiral synthetic compounds, on the other hand, are commonly racemates, unless they have
been prepared from enantiomerically pure starting materials.
There are two ways in which the condition of a chiral substance may be changed:
1. A racemate may be separated into its component enantiomers. This process is called resolution.
2. A pure enantiomer may be transformed into its racemate. This process is called racemization.

Enantiomeric Excess
The "optical purity" is a comparison of the optical rotation of a pure sample of unknown stereochemistry versus the optical rotation
of a sample of pure enantiomer. It is expressed as a percentage. If the sample only rotates plane-polarized light half as much as
expected, the optical purity is 50%.
specific rotation of mixture
% optical purity = × 100%
specific rotation of pure enantiomer

Because R and S enantiomers have equal but opposite optical activity, it naturally follows that a 50:50 racemic mixture of two
enantiomers will have no observable optical activity. If we know the specific rotation for a chiral molecule, however, we can easily
calculate the ratio of enantiomers present in a mixture of two enantiomers, based on its measured optical activity. When a mixture
contains more of one enantiomer than the other, chemists often use the concept of enantiomeric excess (ee) to quantify the
difference. Enantiomeric excess can be expressed as:
(% more abundant enantiomer − 50) × 100%
ee =
50

For example, a mixture containing 60% R enantiomer (and 40% S enantiomer) has a 20% enantiomeric excess of R: ((60-50) x
100) / 50 = 20 %.

 Exercise 6.4.1

The specific rotation of (S)-carvone is (+)61°, measured 'neat' (pure liquid sample, no solvent). The optical rotation of a neat
sample of a mixture of R and S carvone is measured at (-)23°. Which enantiomer is in excess, and what is its ee? What are the
percentages of (R)- and (S)-carvone in the sample?

Answer
The observed rotation of the mixture is levorotary (negative, counter-clockwise), and the specific rotation of the pure S
enantiomer is given as dextrorotary (positive, clockwise), meaning that the pure R enantiomer must be levorotary, and the
mixture must contain more of the R enantiomer than of the S enantiomer.
Rotation (R/S Mix) = [Fraction(S) × Rotation (S)] + [Fraction(R) × Rotation (R)]
Let Fraction (S) = x, therefore Fraction (R) = 1 – x.
Rotation (R/S Mix) = x[Rotation (S)] + (1 – x)[Rotation (R)].
–23 = x(+61) + (1 – x)(–61)
Solve for x: x = 0.3114 and (1 – x) = 0.6885
Therefore the percentages of (R)- and (S)-carvone in the sample are 68.9% and 31.1%, respectively.

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ee = [(% more abundant enantiomer – 50) × 100]/50. = [68.9 – 50) × 100]/50 = 37.8%.
Chiral molecules are often labeled according to the sign of their specific rotation, as in (S)-(+)-carvone and (R)-(-)-carvone,
or (±)-carvone for the racemic mixture. However, there is no relationship whatsoever between a molecule's R/S designation
and the sign of its specific rotation. Without performing a polarimetry experiment or looking in the literature, we would
have no idea that (-)-carvone has the R configuration and (+)-carvone has the S configuration

Chiral molecules are often labeled according to the sign of their specific rotation, as in (S)-(+)-carvone and (R)-(-)-carvone, or (±)-
carvone for the racemic mixture. However, there is no relationship whatsoever between a molecule's R/S designation and the sign
of its specific rotation. Without performing a polarimetry experiment or looking in the literature, we would have no idea that (-)-
carvone has the R configuration and (+)-carvone has the S configuration.

Separation of Chiral Compounds

 Exercise 6.4.2

A 3.20 g sample of morphine ([α]D = -132) was dissolved in 10.0 mL of acetic acid ([α]D = 0). If it is put into a sample tube
with a path length of 2.00 cm, what would be its observed rotation (α)?

Answer
The specific rotation, [α]D = (observed rotation, α (degrees))/ [(pathlength, l (dm)) x (concentration, c (g/cm3))] = α/(l x c)
Solving for α, α = [α]D x l x c
([α]D = -132) x (l = 2.00 cm = 0.200 dm) x (c = 3.20 g / 10.0 cm3 = 0.320 g/cm3)
α = -132 x 0.200 dm x 0.320 g/cm3 = -8.45 o

 Exercise 6.4.3
Is the morphine in the previous excercise dextrorotatory or levorotatory?

Answer
Since morphine has a (-) rotation, it indicates that it rotates light to the left (counterclockwise) and morphine is levorotatory.

 Exercise 6.4.4

Label the following compounds as dextrorotatory or levorotatory.

a. sucrose ([α]D = + 66.7)
b. cholesterol ([α]D = - 31.5)
c. cocaine ([α]D = - 16)
d. chloroform ([α]D = 0)

Answer
a. sucrose ([α]D = + 66.7) dextrorotatory

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b. cholesterol ([α]D = - 31.5) levorotatory
c. cocaine ([α]D = - 16) levorotatory
d. chloroform ([α]D = 0) neither, not optically active

 Exercise 6.4.5a

The specific rotation of (S)-carvone is (+) 61o when measured neat (pure liquid sample with no solvent). The optical rotation of
a neat sample of a mixture of R and S carvone is measured at (-) 23 o.
a) Which enantiomer is in excess?

Answer
Since the pure S enantiomer ((+) 61o) is dextrorotatory (positive, clockwise), the R enantiomer must be levorotatory. The
observed rotation of the mixture is levorotatory since its negative (counterclockwise). This means the mixture must contain
more of the R enantiomer than the S enantiomer.

 Exercise 6.4.5b

b) What are the percentages of (S)- and (R)- carvone in the sample mixture?

Answer
Optical rotation (α) of the (R/S mixture) = [fraction (S) x [α]D (S)] + [fraction (R) x [α]D (R)]
To determine the fraction of S and R, we make y = fraction (S) and 1 – y = fraction (R)
-23o = y x (61o) + (1 – y) x (-61o) solving for y: y = 0.3114 and (1-y) = 0.6885
Therefore the percentage of (S)-carvone is 31.1 % and (R)-carvone is 68.9 %

 Exercise 6.4.5c

c) What is the ee (enantiomeric excess)?

Answer
ee = [(% more abundant isomer – 50) x 100]/50 = [(68.9 – 50) x100]/50 = 37.8 % ee

 Exercise 6.4.6a

Determine the ee’s of the following from the percentages

95 % (R)- tartaric acid and 5.0 % (S)- tartaric acid

Answer
[(95 – 50) x 100] / 50 = 90 % ee (R)-tartaric acid

 Exercise 6.4.6b

Determine the ee’s of the following from the percentages

75 % (S)- limonene and 25 % (R)- limonene

Answer
[(75 – 50) x 100] / 50 = 50 % ee (S)- limonene

6.4.5 https://chem.libretexts.org/@go/page/206997
 Exercise 6.4.6c

Determine the ee’s of the following from the percentages

85 % (R) cysteine

Answer
(85 – 50) x 100] / 50 = 70 % ee (R)-cysteine

 Exercise 6.4.6d

Determine the ee’s of the following from the percentages

50 % (S) alanine

Answer
(50 – 50) x 100] / 50 = 0 % ee, racemic mixture

6.4: Optical Activity - more detail is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
5.3: Optical Activity by Dietmar Kennepohl, Krista Cunningham, Steven Farmer, Tim Soderberg, Zachary Sharrett is licensed CC BY-SA
4.0.

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6.5: Racemic Mixtures and the Resolution of Enantiomers
 Objectives

After completing this section, you should be able to

1. describe a common process for separating a mixture of enantiomers.
2. explain why racemic mixtures do not rotate plane-polarized light.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
racemic mixture (or racemate)
resolve

 Study Notes

A racemic mixture is a 50:50 mixture of two enantiomers. Because they are mirror images, each enantiomer rotates plane-
polarized light in an equal but opposite direction and is optically inactive. If the enantiomers are separated, the mixture is said
to have been resolved. A common experiment in the laboratory component of introductory organic chemistry involves the
resolution of a racemic mixture.
The dramatic biochemical consequences of chirality are illustrated by the use, in the 1950s, of the drug Thalidomide, a sedative
given to pregnant women to relieve morning sickness. It was later realized that while the (+)‑form of the molecule, was a safe
and effective sedative, the (−)‑form was an active teratogen. The drug caused numerous birth abnormalities when taken in the
early stages of pregnancy because it contained a mixture of the two forms.

As noted earlier, chiral compounds synthesized from achiral starting materials and reagents are generally racemic (i.e. a 50:50
mixture of enantiomers). Separation of racemates into their component enantiomers is a process called resolution. Since
enantiomers have identical physical properties, such as solubility and melting point, resolution is extremely difficult.
Diastereomers, on the other hand, have different physical properties, and this fact is used to achieve resolution of racemates.
Reaction of a racemate with an enantiomerically pure chiral reagent gives a mixture of diastereomers, which can be separated. For
example, if a racemic mixture of a chiral alcohol is reacted with a enantiomerically pure carboxylic acid, the result is a mixture of
diastereomers: in this case, because the pure (R) entantiomer of the acid was used, the product is a mixture of (R-R) and (R-S)
diastereomeric esters, which can, in theory, be separated by their different physical properties. Subsequent hydrolysis of each
separated ester will yield the 'resolved' (enantiomerically pure) alcohols. The used in this technique are known as 'Moscher's esters',
after Harry Stone Moscher, a chemist who pioneered the method at Stanford University.
As noted earlier, chiral compounds synthesized from achiral starting materials and reagents are generally racemic (i.e. a 50:50
mixture of enantiomers). Separation of racemates into their component enantiomers is a process called resolution. Since
enantiomers have identical physical properties, such as solubility and melting point, resolution is extremely difficult.
Diastereomers, on the other hand, have different physical properties, and this fact is used to achieve resolution of racemates.
Reaction of a racemate with an enantiomerically pure chiral reagent gives a mixture of diastereomers, which can be separated.
Reversing the first reaction then leads to the separated enantiomers plus the recovered reagent.

Figure 5.8.1:

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Many kinds of chemical and physical reactions, including salt formation, may be used to achieve the diastereomeric intermediates
needed for separation. Figure 5.8.1 illustrates this general principle by showing how a nut having a right-handed thread (R) could
serve as a "reagent" to discriminate and separate a mixture of right- and left-handed bolts of identical size and weight. Only the two
right-handed partners can interact to give a fully-threaded intermediate, so separation is fairly simple. The resolving moiety, i.e. the
nut, is then removed, leaving the bolts separated into their right and left-handed forms. Chemical reactions of enantiomers are
normally not so dramatically different, but a practical distinction is nevertheless possible.
Because the physical properties of enantiomers are identical, they seldom can be separated by simple physical methods, such as
fractional crystallization or distillation. It is only under the influence of another chiral substance that enantiomers behave
differently, and almost all methods of resolution of enantiomers are based upon this fact. We include here a discussion of the
primary methods of resolution.

Chiral Amines as Resolving Agents and Resolution of Racemic Acids

The most commonly used procedure for separating enantiomers is to convert them to a mixture of diastereomers that will have
different physical properties: melting point, boiling point, solubility, and so on (Section 5-5). For example, if you have a racemic or
(R)/(S) mixture of enantiomers of a carboxylic acid and convert this to a salt with a chiral amine base having the (R) configuration,
the salt will be a mixture of two diastereomers, ((R)-acid (R)-base) and ((S)-acid (R)-base). These diastereomeric salts are not
identical and they are not mirror images. Therefore they will differ to some degree in their physical properties, and a separation by
physical methods, such as crystallization, may be possible. If the diastereomeric salts can be completely separated, the carboxylic
acid regenerated from each salt will be either exclusively the (R) or the (S) enantiomer.
(R )-acid (R )-base pure (R )-carboxylic acid

(R )-carboxylic acid (R )-amine base (R )-acid (R )-base resolution regeneration

(S )-carboxylic acid (S )-acid (R )-base

racemic mixture diastereomers

(S )-acid (R )-base pure (S )-carboxylic acid

Resolution of chiral acids through the formation of diastereomeric salts requires adequate supplies of suitable chiral bases. Brucine,
strychnine, and quinine frequently are used for this purpose because they are readily available, naturally occurring chiral bases.
Simpler amines of synthetic origin, such as 2-amino-1-butanol, amphetamine, and 1-phenylethanamine, also can be used, but first
they must be resolved themselves.
NH2

* * *
OH
NH2 NH2

2-amino-1-butanol 1-phenyl-2-propanamine 1-phenylethanamine

(amphetamine)

N OH
H H
N
R H
H H N
R N O

O
O
R = H,strychnine quinine
(antimicrobial)
R = OCH3, brucine
(antimalarial)

 Worked Example 6.5.1

Show how (S)-1-phenylethylamine can be used to resolve a racemic mixture of lactic acid. Please draw all the structures
involved.

Answer

6.5.2 https://chem.libretexts.org/@go/page/206998
O OH
C
O O H3N H C H
O OH C H3C
C C OH
C H H3 C
C H H3C pure (S )-lactic acid
H3C OH
OH
CH3
(S )-lactic acid C (S,R )-diastereomeric
H NH2 ammonium salt
+
(S )-1-phenylethylamine
O O H3N H
O OH C
C C
C H H3 C O OH
C OH H3C C
H3C OH
H
C OH
(R )-lactic acid (R,R )-diastereomeric H3 C
H
ammonium salt
pure (R )-lactic acid
racemic mixture
of lactic acid

Resolution of Racemic Bases

Chiral acids, such as (+)-tartaric acid, (-)-malic acid, (-)-mandelic acid, and (+)-camphor- 10-sulfonic acid, are used for the
resolution of a racemic base.
CO2H CO2H CH3
CO2H H3 C
CHOH CHOH SO3H
CHOH
CHOH CH2 O
C6 H5
CO2H CO2H

tartaric acid malic acid mandelic acid camphor-10-

(2,3-dihydroxy- (2-hydroxybutane- (2-hydroxy-2- sulfonic acid
butanedioic acid) dioic acid) phenylethanoic acid)

The principle is the same as for the resolution of a racemic acid with a chiral base, and the choice of acid will depend both on the
ease of separation of the diastereomeric salts and, of course, on the availability of the acid for the scale of the resolution involved.
Resolution methods of this kind can be tedious, because numerous recrystallizations in different solvents may be necessary to
progressively enrich the crystals in the less-soluble diastereomer. To determine when the resolution is complete, the mixture of
diastereomers is recrystallized until there is no further change in the measured optical rotation of the crystals. At this stage it is
hoped that the crystalline salt is a pure diastereomer from which one pure enantiomer can be recovered. The optical rotation of this
enantiomer will be a maximum value if it is "optically" pure because any amount of the other enantiomer could only reduce the
magnitude of the measured rotation α .

Resolution of Racemic Alcohols

To resolve a racemic alcohol, a chiral acid can be used to convert the alcohol to a mixture of diastereomeric esters. This is not as
generally useful as might be thought because esters tend to be liquids unless they are very high-molecularweight compounds. If the
diastereomeric esters are not crystalline, they must be separated by some other method than fractional crystallization (for instance,
by chromatography methods, Section 9-2). Two chiral acids that are useful resolving agents for alcohols are:

The most common method of resolving an alcohol is to convert it to a half-ester of a dicarboxylic acid, such as butanedioic
(succinic) or 1,2-benzenedicarboxylic (phthalic) acid, with the corresponding anhydride. The resulting half-ester has a free
carboxyl function and may then be resolvable with a chiral base, usually brucine:

6.5.3 https://chem.libretexts.org/@go/page/206998
O O
CH3
* O
* CHOH brucine
+ O
CH2
HO
CH3
O
O
tartaric acid 1,2-benzenedicarboxylic half-ester
(2,3-dihydroxy- anhydride
butanedioic acid)

alkaline
hydrolysis D-2-butanol

separation by
crystallization
diastereomeric salts
alkaline
hydrolysis
L-2-butanol

Other Methods of Resolution

One of the major goals in the field of organic chemistry is the development of reagents with the property of "chiral recognition"
such that they can affect a clean separation of enantiomers in one operation without destroying either of the enantiomers. We have
not achieved that ideal yet, but it may not be far in the future. Chromatographic methods, whereby the stationary phase is a chiral
reagent that adsorbs one enantiomer more strongly than the other, have been used to resolve racemic compounds, but such
resolutions seldom have led to both pure enantiomers on a preparative scale. Other methods, called kinetic resolutions, are
excellent when applicable. The procedure takes advantage of differences in reaction rates of enantiomers with chiral reagents. One
enantiomer may react more rapidly, thereby leaving an excess of the other enantiomer behind. For example, racemic tartaric acid
can be resolved with the aid of certain penicillin molds that consume the dextrorotatory enantiomer faster than the levorotatory
enantiomer. As a result, almost pure (-)-tartaric acid can be recovered from the mixture:
(±)-tartaric acid + mold → (-)-tartaric acid + more mold
The crystallization procedure employed by Pasteur for his classical resolution of (±)-tartaric acid (Section 5.4) has been successful
only in a very few cases. This procedure depends on the formation of individual crystals of each enantiomer. Thus if the
crystallization of sodium ammonium tartrate is carried out below 27", the usual racemate salt does not form; a mixture of crystals
of the (+) and (-) salts forms instead. The two different kinds of crystals, which are related as an object to its mirror image, can be
separated manually with the aid of a microscope and subsequently may be converted to the tartaric acid enantiomers by strong acid.
A variation on this method of resolution is the seeding of a saturated solution of a racemic mixture with crystals of one pure
enantiomer in the hope of causing crystallization of just that one enantiomer, thereby leaving the other in solution. Unfortunately,
very few practical resolutions have been achieved in this way.

Predicating the Chirality of the Product of a Reaction

It important to understand the changes in chirality which occur during the formation of product during a reaction. A chiral reaction
product, has the possibility of forming multiple stereoisomers which all need to be considered. Changes in chirality, if possible, will
be discussed with each individual reaction as this textbook moves forward. Some possible situations which can occur are:
A new chiral carbon is formed during a reaction. This commonly occurs when an sp2 hybridized carbon in the reactant is
converted to sp3 hybridized chiral carbon in the product. When this occurs, a racemic mixture of the new chiral carbon is
formed.
A chiral carbon is lost during a reaction. This commonly occurs when an sp3 hybridized chiral carbon in the reactant is
converted to either a sp2 or sp hybridized carbon in the product.
An enantiomerically pure starting material is converted to a racemic mixture in the product. This commonly occurs when
a sp3 hybridized chiral carbon is temporarily converted to an sp2 hybridized carbon during a reaction's mechanism. The chiral
carbon is reformed as a racemic mixture.
Chiral carbons remain unchanged during a reaction. If a chiral carbon is not directly involved in a reaction, it will move
from a reactant to a product unchanged.
Determining if a chiral carbon is involved in a given reaction is vital for determining which of these four situations is occurring.

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 Worked Example 6.5.2

The following reaction involves the conversion of a carboxylic acid reacting with an alcohol to form an ester. If a pure sample
of (R)-2-methylbutanoic acid is reacted with methanol to form an ester, what would be the stereochemistry of the product?
O O
acid
+ HO R’ + H2O
C C R’
R OH R O
carboxylic acid alcohol ester

Answer
First it is important to identify the location of the chiral carbon and determine if it is directly involved in the reaction. In
this case, the chiral carbon is not involved so the stereochemistry will be carried over into the product unchanged.
O O
H2 H2
acid
C * C + HO CH3 C * C CH3 + H2 O
H3C C OH H3C C O
H CH3 H CH3
(R )-2-methylbutanoic methanol methyl (R )-2-methyl
acid butanoate

 Exercise 6.5.1

Indicate the reagents you could use to resolve the following compounds. Show the reactions involved and specify the physical
method you believe would be the best to separate the diastereomers of 1 -phenyl-2-propanamine.

Answer
You could react the 1-phenyl-2-propanamine racemic mixture with a chiral acid such as (+)-tartaric acid (R, R). The
reaction will produce a mixture of diastereomeric salts (i.e. R, R, R and S, R, R). You can separate the diastereomers through
crystallization and treat the salt with a strong base (e.g. KOH) to recover the pure enantiomeric amine.

 Exercise 6.5.2

Indicate the reagents you would use to resolve the following and discuss the reactions involved and specify the physical
method you believe would be the best to separate the diastereomers of 2,3-pentadienedioic acid.

Answer
You could react the 2,3-pentadienedioic acid mixture with a chiral base such as (R)‑1‑phenylethylamine. The reaction will
produce a mixture of diastereomeric salts. Separate the diastereomers through crystallization and treat the resulting salt with
strong acid (e.g. HCl) to recover the pure enantiomeric acid.

 Exercise 6.5.3

Answer
You could react the 1-phenylethanol mixture with 1,2-benzenedicarboxylic anhydride. The reaction will produce a mixture
of diastereomeric salts. You could then separate the diastereomers through crystallization and then alkaline hydrolysis
treatment should recover the pure enantiomeric alcohol.

6.5: Racemic Mixtures and the Resolution of Enantiomers is shared under a not declared license and was authored, remixed, and/or curated by
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Steven Farmer, Zachary Sharrett is licensed CC BY-SA 4.0.

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6.6: Diastereomers
Diastereomers are stereoisomers that are not related as object and mirror image and are not enantiomers. Unlike enatiomers which
are mirror images of each other and non-sumperimposable, diastereomers are not mirror images of each other and non-
superimposable. Diastereomers can have different physical properties and reactivity. They have different melting points and
boiling points and different densities. They have two or more stereocenters.

Introduction
It is easy to mistake between diasteromers and enantiomers. For example, we have four steroisomers of 3-bromo-2-butanol. The
four possible combination are SS, RR, SR and RS (Figure 1). One of the molecule is the enantiomer of its mirror image molecule
and diasteromer of each of the other two molecule (SS is enantiomer of RR and diasteromer of RS and SR). SS's mirror image is
RR and they are not superimposable, so they are enantiomers. RS and SR are not mirror image of SS and are not superimposable to
each other, so they are diasteromers.

Figure 1

Diastereomers vs. Enantiomers vs. Meso Compounds

Tartaric acid, C4H6O6, is an organic compound that can be found in grape, bananas, and in wine. The structures of tartaric acid
itself is really interesting. Naturally, it is in the form of (R,R) stereocenters. Artificially, it can be in the meso form (R,S), which is
achiral. R,R tartaric acid is enantiomer to is mirror image which is S,S tartaric acid and diasteromers to meso-tartaric acid (figure
2).
(R,R) and (S,S) tartaric acid have similar physical properties and reactivity. However, meso-tartaric acid have different physical
properties and reactivity. For example, melting point of (R,R) & (S,S) tartaric is about 170 degree Celsius, and melting point of
meso-tartaric acid is about 145 degree Celsius.

6.6.1 https://chem.libretexts.org/@go/page/206999
Figure 2
To identify meso, meso compound is superimposed on its mirror image, and has an internal plane that is symmetry (figure 3).
Meso-tartaric acid is achiral and optically unactive.

Problems
Identify which of the following pair is enantiomers, diastereomers or meso compounds.

6.6.2 https://chem.libretexts.org/@go/page/206999
Answer
a. Diasteromers
b. Identical
c. Meso
d. Enantiomers

Outside Links
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http://en.Wikipedia.org/wiki/Diastereomer
http://en.Wikipedia.org/wiki/Tartaric_acid

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6.7: Diastereomers - more detail
 Objectives

After completing this section, you should be able to

1. calculate the maximum number of stereoisomers possible for a compound containing a specified number of chiral carbon
atoms.
2. draw wedge-and-broken-line structures for all possible stereoisomers of a compound containing two chiral carbon atoms,
with or without the aid of molecular models.
3. assign (R)/(S) configurations to wedge-and-broken-line structures containing two chiral carbon atoms, with or without the
aid of molecular models.
4. determine, with or without the aid of molecular models, whether two wedge-and-broken-line structures containing two
chiral carbon atoms are identical, represent a pair of enantiomers, or represent a pair of diastereomers.
5. draw the wedge-and-broken-line structure of a specific stereoisomer of a compound containing two chiral carbon atoms,
given its IUPAC name and (R)/(S) configuration.

 Key Terms
Make certain that you can define, and use in context, the key term below.
diastereomer

Diastereomers are two molecules which are stereoisomers (same molecular formula, same connectivity, different arrangement of
atoms in space) but are not enantiomers. Unlike enantiomers which are mirror images of each other and non-superimposable,
diastereomers are not mirror images of each other and non-superimposable. Diastereomers can have different physical properties
and reactivity. They have different melting points and boiling points and different densities. In order for diastereomer stereoisomers
to occur, a compound must have two or more stereocenters.

Introduction
So far, we have been analyzing compounds with a single chiral center. Next, we turn our attention to those which have multiple
chiral centers. We'll start with some stereoisomeric four-carbon sugars with two chiral centers.
chiral center #1
O OH
OH
H
OH
chiral center #2

We will start with a common four-carbon sugar called D-erythrose.

H OH O
C2: (R )
HO 4 2
3 1
H C3: (R )
HO H
D-erythrose

A note on sugar nomenclature: biochemists use a special system to refer to the stereochemistry of sugar molecules, employing
names of historical origin in addition to the designators 'D' and 'L'. You will learn about this system if you take a biochemistry
class. We will use the D/L designations here to refer to different sugars, but we won't worry about learning the system.
As you can see, D-erythrose is a chiral molecule: C2 and C3 are stereocenters, both of which have the (R) configuration. In
addition, you should make a model to convince yourself that it is impossible to find a plane of symmetry through the molecule,
regardless of the conformation. Does D-erythrose have an enantiomer? Of course it does – if it is a chiral molecule, it must. The
enantiomer of erythrose is its mirror image, and is named L-erythrose (once again, you should use models to convince yourself that
these mirror images of erythrose are not superimposable).

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enantiomers

H OH O O HO H
HO (R ) (S ) OH
(R ) H H (S )

HO H H OH
D-erythrose L-erythrose

Notice that both chiral centers in L-erythrose both have the (S) configuration. To avoid confusion, we will simply refer to the
different stereoisomers by capital letters.
Now let's consider all the possible stereoisomers.
Look first at compound A below. Both chiral centers in have the (R) configuration (you should confirm this for yourself!). The
mirror image of Compound A is compound B, which has the (S) configuration at both chiral centers. If we were to pick up
compound A, flip it over and put it next to compound B, we would see that they are not superimposable (again, confirm this for
yourself with your models!). A and B are nonsuperimposable mirror images: in other words, enantiomers.
mirror plane

O HO H H OH O
enantiomers
(R ) OH HO (S )
H (R ) (S ) H diastereomers
H OH HO H
A B

O HO H H OH O
(S ) OH HO (R )
H (R ) (S ) H
HO H H OH
C D

Now, look at compound C, in which the configuration is (S) at chiral center 1 and (R) at chiral center 2. Compounds A and C are
stereoisomers: they have the same molecular formula and the same bond connectivity, but a different arrangement of atoms in
space (recall that this is the definition of the term 'stereoisomer). However, they are not mirror images of each other (confirm this
with your models!), and so they are not enantiomers. By definition, they are diastereomers of each other.
Notice that compounds C and B also have a diastereomeric relationship, by the same definition.
So, compounds A and B are a pair of enantiomers, and compound C is a diastereomer of both of them. Does compound C have its
own enantiomer? Compound D is the mirror image of compound C, and the two are not superimposable. Therefore, C and D are a
pair of enantiomers. Compound D is also a diastereomer of compounds A and B.
This can also seem very confusing at first, but there some simple shortcuts to analyzing stereoisomers:

Stereoisomer Shortcuts
If all of the chiral centers are of opposite (R)/(S) configuration between two stereoisomers, they are enantiomers.
If at least one, but not all of the chiral centers are opposite between two stereoisomers, they are diastereomers.

These shortcuts to not take into account the possibility of additional stereoisomers due to alkene groups: we will come to that
later

Here's another way of looking at the four stereoisomers, where one chiral center is associated with red and the other blue. Pairs of
enantiomers are stacked together.

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chiral center #1
O OH
possible configurations:
OH (R ,R ) (R ,S )
H
(S ,S ) (S ,R )
OH
chiral center #2

We know, using the shortcut above, that the enantiomer of (R,R) must be (S,S) - both chiral centers are different. We also know that
(R,S) and (S,R) are diastereomers of (R,R), because in each case one - but not both - chiral centers are different.

Determining the Maximum Number of Stereoisomers for a Compound

In general, a structure with n stereocenters will have a maximum of 2n different stereoisomers. (We are not considering, for the time
being, the stereochemistry of double bonds – that will come later). For example, let's consider the glucose molecule in its open-
chain form (recall that many sugar molecules can exist in either an open-chain or a cyclic form). There are two enantiomers of
glucose, called D-glucose and L-glucose. The D-enantiomer is the common sugar that our bodies use for energy. It has n = 4
stereocenters, so therefore there are 2n = 24 = 16 possible stereoisomers (including D-glucose itself).
enantiomers

OH OH O OH OH O
HO (R ) (R ) HO (S ) (S )
(R ) (S ) H (S ) (R ) H
OH OH OH OH
D-glucose L-glucose

diastereomers
OH OH O diastereomers
HO (S ) (R )
(R ) (S ) H
OH OH

D-galactose

 Example 6.7.1
Draw the structure of L-galactose, the enantiomer of D-galactose.
Draw the structure of two more diastereomers of D-glucose. One should be an epimer.

Answer
OH OH O
HO (R ) (S ) L-galactose
(S ) (R ) H
OH OH

OH OH O
HO (R ) (S ) L-mannose
(R ) (S ) H (epimer of D-glucose)
OH OH

OH OH O
HO (S ) (R ) L-gulose
(R ) (R ) H (diasteromer of D-glucose)
OH OH

6.7.3 https://chem.libretexts.org/@go/page/207000
Erythronolide B, a precursor to the 'macrocyclic' antibiotic erythromycin, has 10 stereocenters. It’s enantiomer is that molecule in
which all 10 stereocenters are inverted.
O
H 3C CH3
CH3
H3C
OH OH
H3C H3C
O OH

O OH
CH3

erythronolide B

 Exercise 6.7.1

Determine the number of stereoisomers a molecule can have with…

a. 3 chiral centers
b. 1 chiral center
c. 6 chiral centers

Answer
Since a molecule with n chiral centers can have 2n stereoisomers…
a. 23 = 8 possible stereoisomers
b. 21 = 2 possible stereoisomers
c. 26 = 64 possible stereoisomers

 Exercise 6.7.2a

What is the relationship between enantiomers?

Answer
They are mirror images of each other and when 2 or more chiral centers are present, every stereocenter is the opposite in its
enantiomer.

 Exercise 6.7.2b
How does the stereochemistry in diastereomers differ from each other?

Answer
In diastereomers, one or more of the chiral centers is the opposite but they all can’t be the opposite or else they’d be
enantiomers.

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 Exercise 6.7.2c

What are epimers?

Answer
Epimers are when only one chiral center is the opposite (in molecules with 2 or more chiral centers) in its diastereomer.

 Exercise 6.7.3a

Draw the structure of (2R,3R) 2-fluoro-3-methylhexane.

Answer
H
F
H
2R,3R

 Exercise 6.7.3b

Draw both diastereomers of (2R,3R) 2-fluoro-3-methylhexane.

Answer
H
H
F H
H F
2R,3S 2S,3R

 Exercise 6.7.3c

Draw the enantiomer of (2R,3R) 2-fluoro-3-methylhexane.

Answer

H
H
F
2S,3S

 Exercise 6.7.4a

Draw the structure of L-galactose, the enantiomer of D-galactose.

OH OH O
HO
H
OH OH

S, R, R, S
D-galactose

Answer

6.7.5 https://chem.libretexts.org/@go/page/207000
OH OH O
HO
H
OH OH

S, R, R, S
L-galactose

 Exercise 6.7.4b

Draw a diastereomer of D-galactose that is an epimer.

Answer
You can draw an epimer by drawing D-galactose with 1 (and only 1) of its chiral centers reversed. Here’s an example when
you switch only the first chiral center (in red). (There are 3 other epimers that could be drawn as long as you only swap a
single chiral center in the diastereomer that you use.)
OH OH O
HO
H
OH OH

R, R, R, S

 Exercise 6.7.4c

Identify if the following diastereomer of galactose is an epimer of D- galactose or L- galactose.

OH OH O
HO
H
OH OH

Answer
OH OH O
HO
H
OH OH

S, R, S, S

Since the diastereomer above only varies from L-galactose by 1 chiral center, the above is an epimer in relationship to L-
galactose. Since it varies from D-galactose by 3 chiral centers, it is not an epimer but a diastereomer. Since not all of the
chiral centers are swapped, it is not an enantiomer!

 Exercise 6.7.5a
For the compound shown below, label each chiral center as R or S.
OH

Answer
S OH

R F
S

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 Exercise 6.7.5b
How many stereoisomers are possible for the compound in part a)?

Answer
Since there are 3 chiral centers, 23 = 8 possible stereoisomers.

 Exercise 6.7.6

Consider the stereoisomers below.

OH OH OH OH

i ii iii iv

a. Which is/are an enantiomer of i?

b. Which is/are a diastereomer of ii?
c. Which is/are an epimer of i?

Answer
a. iv is an enantiomer of i since both chiral centers are switched and they are non superimposable mirror images.
b. i & iv are diastereomers of ii since they are stereoisomers that are not mirror images.
c. ii and iii are epimers of i since they are diastereomers with only 1 chiral center switched and the other one the same.

 Exercise 6.7.7

Consider the 8 stereoisomers below.

OH OH OH
OH

OH OH OH
OH
i ii iii iv

OH OH OH
OH

OH OH OH
OH
v vi vii viii

a. Which is/are an enantiomer of i?

b. Which is/are a diastereomer of i?
c. Which is/are an epimer of i?

Answer
a. v is an enantiomer since all three chiral centers are switched and they are non superimposable mirror images.
b. ii, iii, iv, vi, vii & viii are diastereomers of i since they are stereoisomers that are not mirror images.
c. ii,iii & viii are epimers of i since they are diastereomers with only 1 chiral center switched and the other chiral centers
the same.

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5.6: Diastereomers by Dietmar Kennepohl, Steven Farmer, Tim Soderberg, Zachary Sharrett is licensed CC BY-SA 4.0.

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6.8: Meso Compounds
Meso compounds are achiral compounds that has multiple chiral centers. It is superimposed on its mirror image and is optically
inactive despite its stereocenters.

Introduction
In general, a meso compound should contain two or more identical substituted stereocenters. Also, it has an internal symmetry
plane that divides the compound in half. These two halves reflect each other by the internal mirror. The stereochemistry of
stereocenters should "cancel out". What it means here is that when we have an internal plane that splits the compound into two
symmetrical sides, the stereochemistry of both left and right side should be opposite to each other, and therefore, result in optically
inactive. Cyclic compounds may also be meso.

Identification
If A is a meso compound, it should have two or more stereocenters, an internal plane, and the stereochemistry should be R and S.
1. Look for an internal plane, or internal mirror, that lies in between the compound.
2. The stereochemistry (e.g. R or S) is very crucial in determining whether it is a meso compound or not. As mentioned above, a
meso compound is optically inactive, so their stereochemistry should cancel out. For instance, R cancels S out in a meso
compound with two stereocenters.

trans-1,2-dichloro-1,2-ethanediol

(meso)-2,3-dibromobutane
Tips: An interesting thing about single bonds or sp3-orbitals is that we can rotate the substituted groups that attached to a
stereocenter around to recognize the internal plane. As the molecule is rotated, its stereochemistry does not change. For example:

Another case is when we rotate the whole molecule by 180 degree. Both molecules below are still meso.

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Remember the internal plane here is depicted on two dimensions. However, in reality, it is three dimensions, so be aware of it when
we identify the internal mirror.

 Example

This molecule has a plane of symmetry (the horizontal plane going through the red broken line) and, therefore, is achiral;
However, it has two chiral carbons and is consequentially a meso compound.

 Example 2

This molecules has a plane of symmetry (the vertical plane going through the red broken line perpendicular to the plane of the
ring) and, therefore, is achiral, but has has two chiral centers. Thus, its is a meso compound.

Other Examples of meso compounds

Meso compounds can exist in many different forms such as pentane, butane, heptane, and even cyclobutane. They do not
necessarily have to be two stereocenters, but can have more.

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Optical Activity Analysis
When the optical activity of a meso compound is attempted to be determined with a polarimeter, the indicator will not show (+) or
(-). It simply means there is no certain direction of rotation of the polarized light, neither levorotatory (-) and dexorotatory (+).

Problems
Beside meso, there are also other types of molecules: enantiomer, diastereomer, and identical. Determine if the following molecules
are meso.

Answer key: A C, D, E are meso compounds.

References
1. Vollhardt, K. P.C. & Shore, N. (2007). Organic Chemistry (5thEd.). New York: W. H. Freeman. (190-192)
2. Shore, N. (2007). Study Guide and Solutions Manual for Organic Chemistry (5th Ed.). New York: W.H. Freeman. (70-80)

Contributors
Duy Dang
Gamini Gunawardena from the OChemPal site (Utah Valley University)

6.8: Meso Compounds is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Meso Compounds is licensed CC BY-NC-SA 4.0.

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CHAPTER OVERVIEW

7: Cyclic Compounds - Stereochemistry of Reactions

7: Cyclic Compounds - Stereochemistry of Reactions is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

1
7.1: Ring Strain and the Structure of Cycloalkanes
Cycloalkanes are very important in components of food, pharmaceutical drugs, and much more. However, to use cycloalkanes in
such applications, we must know the effects, functions, properties, and structures of cycloalkanes. Cycloalkanes are alkanes that are
in the form of a ring; hence, the prefix cyclo-. Stable cycloalkanes cannot be formed with carbon chains of just any length. Recall
that in alkanes, carbon adopts the sp3 tetrahedral geometry in which the angles between bonds are 109.5°. For some cycloalkanes to
form, the angle between bonds must deviate from this ideal angle, an effect known as angle strain. Additionally, some hydrogen
atoms may come into closer proximity with each other than is desirable (become eclipsed), an effect called torsional strain. These
destabilizing effects, angle strain and torsional strain are known together as ring strain. The smaller cycloalkanes, cyclopropane
and cyclobutane, have particularly high ring strains because their bond angles deviate substantially from 109.5° and their
hydrogens eclipse each other. Cyclopentane is a more stable molecule with a small amount of ring strain, while cyclohexane is able
to adopt the perfect geometry of a cycloalkane in which all angles are the ideal 109.5° and no hydrogens are eclipsed; it has no ring
strain at all. Cycloalkanes larger than cyclohexane have ring strain and are not commonly encountered in organic chemistry.

Ring Strain and the Structures of Cycloalkanes

There are many forms of cycloalkanes, such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, among others. The process
of naming cycloalkanes is the same as naming alkanes but the addition of the prefix cyclo- is required. Cyclobutane is in a form of
a square, which is highly unfavorable and unstable (this will be explained soon). There are different drawings for cyclobutane, but
they are equivalent to each other. Cyclobutane can reduce the ring string by puckering the square cyclobutane. Cyclopentane takes
the shape of a pentagon and cyclohexane is in the shape of a hexagon.

Chair Conformation of Cyclohexane - Equitorial and Axial

There are two ways to draw cyclohexane because it can be in a hexagon shape or in a different conformational form called the
chair conformation and the boat conformation.
The chair conformation drawing is more favored than the boat because of the energy, the steric hindrance, and a new strain
called the transannular strain.
The boat conformation is not the favored conformation because it is less stable and has a steric repulsion between the two H's,
shown with the pink curve. This is known as the transannular strain, which means that the strain results from steric crowding of
two groups across a ring. The boat is less stable than the chair by 6.9 kcal/mol. The boat conformation, however, is flexible, and
when we twist one of the C-C bonds, it reduces the transannular strain.
When we twist the C-C bond in a boat, it becomes a twisted boat.

Some Conformations of Cyclohexane Rings. (William Reusch, MSU)

Although there are multiple ways to draw cyclohexane, the most stable and major conformer is the chair because is has a lower
activation barrier from the energy diagram.

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Conformational Energy Profile of Cyclohexane. (William Reusch, MSU).
The transition state structure is called a half chair. This energy diagram shows that the chair conformation is lower in energy;
therefore, it is more stable. The chair conformation is more stable because it does not have any steric hindrance or steric repulsion
between the hydrogen bonds. By drawing cyclohexane in a chair conformation, we can see how the H's are positioned. There are
two positions for the H's in the chair conformation, which are in an axial or an equitorial formation.

This is how a chair conformation looks, but you're probably wondering which H's are in the equitorial and axial form. Here are
more pictures to help.

These are hydrogens in the axial form.

These hydrogens are in an equitorial form. Of these two positions of the H's, the equitorial form will be the most stable because the
hydrogen atoms, or perhaps the other substituents, will not be touching each other. This is the best time to build a chair
conformation in an equitorial and an axial form to demonstrate the stability of the equitorial form.

Ring Strain
Cycloalkanes tend to give off a very high and non-favorable energy, and the spatial orientation of the atoms is called the ring strain.
When atoms are close together, their proximity is highly unfavorable and causes steric hindrance. The reason we do not want ring
strain and steric hindrance is because heat will be released due to an increase in energy; therefore, a lot of that energy is stored in
the bonds and molecules, causing the ring to be unstable and reactive. Another reason we try to avoid ring strain is because it will
affect the structures and the conformational function of the smaller cycloalkanes. One way to determine the presence of ring strain
is by its heat of combustion. By comparing the heat of combustion with the value measured for the straight chain molecule, we can
determine the stability of the ring. There are two types of strain, which are eclipsing/torsional strain and bond angle strain. Bond
angle strain causes a ring to have a poor overlap between the atoms, resulting in weak and reactive C-C bonds. An eclipsed spatial
arrangement of the atoms on the cycloalkanes results in high energy.
With so many cycloalkanes, which ones have the highest ring strain and are very unlikely to stay in its current form? The figures
below show cyclopropane, cyclobutane, and cyclopentane, respectively. Cyclopropane is one of the cycloalkanes that has an
incredibly high and unfavorable energy, followed by cyclobutane as the next strained cycloalkane. Any ring that is small (with

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three to four carbons) has a significant amount of ring strain; cyclopropane and cyclobutane are in the category of small rings. A
ring with five to seven carbons is considered to have minimal to zero strain, and typical examples are cyclopentane, cyclohexane,
and cycloheptane. However, a ring with eight to twelve carbons is considered to have a moderate strain, and if a ring has beyond
twelve carbons, it has minimal strain.
There are different types of ring strain:
Transannular strain isdefined as the crowding of the two groups in a ring.
Eclipsing strain, also known as torsional strain, is intramolecular strain due to the bonding interaction between two eclipsed
atoms or groups.
Bond angle strain is present when there is a poor overlap between the atoms. There must be an ideal bond angle to achieve the
maximum bond strength and that will allow the overlapping of the atomic/hybrid orbitals.

Cyclohexane
Most of the time, cyclohexane adopts the fully staggered, ideal angle chair conformation. In the chair conformation, if any
carbon-carbon bond were examined, it would be found to exist with its substituents in the staggered conformation and all bonds
would be found to possess an angle of 109.5°.

Cyclohexane in the chair conformation. (William Reusch, MSU).

In the chair conformation, hydrogen atoms are labeled according to their location. Those hydrogens which exist above or below the
plane of the molecule (shown with red bonds above) are called axial. Those hydrogens which exist in the plane of the molecule
(shown with blue bonds above) are called equatorial.
Although the chair conformation is the most stable conformation that cyclohexane can adopt, there is enough thermal energy for it
to also pass through less favorable conformations before returning to a different chair conformation. When it does so, the axial and
equatorial substituents change places. The passage of cyclohexane from one chair conformation to another, during which the axial
substituents switch places with the equatorial substituents, is called a ring flip.

Methylcyclohexane
Methylcyclohexane is cyclohexane in which one hydrogen atom is replaced with a methyl group substituent. Methylcyclohexane
can adopt two basic chair conformations: one in which the methyl group is axial, and one in which it is equatorial.
Methylcyclohexane strongly prefers the equatorial conformation. In the axial conformation, the methyl group comes in close
proximity to the axial hydrogens, an energetically unfavorable effect known as a 1,3-diaxial interaction (Figure 3). Thus, the
equatorial conformation is preferred for the methyl group. In most cases, if the cyclohexane ring contains a substituent, the
substituent will prefer the equatorial conformation.

Methylcyclohexane in the chair conformation. (William Reusch, MSU).

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References
1. Bachrach, Steven M. Computational Organic Chemistry. Wiley- Interscience. (2007).
2. McMurray, John E. Organic Chemistry Sixth Edition. Brooks Cole. (2003).
3. Vollhardt and Schore. Organic Chemistry Structure and Function Fifth Edition. New York. (2007).

Problems
1. Trans- 1,2-dimethylcyclopropane is more stable than cis-1,2-dimethylcyclopropane. Why? Drawing a picture of the two will
help your explanation.
2. Out of all the cycloalkanes, which one has the most ring strain and which one is strain free? Explain.
3. Which of these chair conformations are the most stable and why?

3.
4. What does it mean when people say "increase in heat leads to increase in energy" and how does that statement relate to ring
strains?
5. Why is that the bigger rings have lesser strains compared to smaller rings?

Answers
1. The cis isomer suffers from steric hindrance and has a larger heat of combustion.
2. Cyclopropane- ring strain. Cyclohexane chair conformation- ring strain free.
3. Top one is more stable because it is in an equitorial conformation. When assembling it with the OChem Molecular Structure
Tool Kit, equitorial formation is more spread out.
4. When there is an increase in heat there will be an increase of energy released therefore there will be a lot of energy stored in the
bond and molecule making it unstable.
5. Smaller rings are more compacts, which leads to steric hindrance and the angles for these smaller rings are harder to get ends to
meet. Bigger rings tend to have more space and that the atoms attached to the ring won't be touching each other as much as
atoms attached to the smaller ring.

Contributors
Jonathan Mooney (McGill University)

7.1: Ring Strain and the Structure of Cycloalkanes is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.
Ring Strain and the Structure of Cycloalkanes is licensed CC BY-NC-SA 4.0.

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7.2: Cycloalkanes and Ring Strain
Learning Objective
explain the partial rotation of carbon-carbon single bonds in rings
explain ring strain and its relationship to cycloalkane stability

Cycloalkanes (aka Rings)

Cycloalkanes have one or more rings of carbon atoms. The simplest examples of this class consist of a single, unsubstituted carbon
ring, and these form a homologous series similar to the unbranched alkanes. The IUPAC names of the first five members of this
series are given in the following table. The last column gives the general formula for a cycloalkane of any size. If a simple
unbranched alkane is converted to a cycloalkane two hydrogen atoms, one from each end of the chain, must be lost. Hence the
general formula for a cycloalkane composed of n carbons is CnH2n. Although a cycloalkane has two fewer hydrogens than the
equivalent alkane, each carbon is bonded to four other atoms so such compounds are still considered to be saturated with
hydrogen.
Table: Examples of Simple Cycloalkanes
Name Cyclopropane Cyclobutane Cyclopentane Cyclohexane Cycloheptane Cycloalkane

Molecular
C3H6 C4H8 C5H10 C6H12 C7H14 CnH2n
Formula

Structural
(CH2)n
Formula

Line
Formula

Although the customary line drawings of simple cycloalkanes are geometrical polygons, the actual shape of these compounds in
most cases is very different. Cyclic systems are a little different from open-chain systems. In an open chain, any bond can be
rotated 360 degrees, going through many different conformations. Complete rotation isn't possible in a cyclic system, because the
parts that you would be trying to twist away from each other would still be connected together. Cyclic systems have fewer "degrees
of freedom" than aliphatic systems; they have "restricted rotation". Because of the restricted rotation of cyclic systems, most of
them have much more well-defined shapes than their aliphatic counterparts. Let's take a look at the basic shapes of some common
rings. Many biologically important compounds are built around structures containing rings, so it's important that we become
familiar with them. In nature, three- to six-membered rings are frequently encountered, so we'll focus on those.

The Baeyer Theory and the Experimental Evidence of Ring Strain

Many of the properties of cyclopropane and its derivatives are similar to the properties of alkenes. In 1890, the famous German
organic chemist, A. Baeyer, suggested that cyclopropane and cyclobutane derivatives are different from cyclopentane and
cyclohexane, because their C—C—C angles cannot have the tetrahedral value of 109.5°. At the same time, Baeyer hypothesized
that the difficulties encountered in synthesizing cycloalkane rings from C7 upward was the result of the angle strain that would be
expected if the large rings were regular planar polygons (see Table 12-3). Baeyer also believed that cyclohexane had a planar
structure like that shown in Figure 12-2, which would mean that the bond angles would have to deviate 10.5° from the tetrahedral
value. However, in 1895, the then unknown chemist H. Sachse suggested that cyclohexane exists in the strain-free chair and boat
forms discussed in Section 12-3. This suggestion was not accepted at the time because it led to the prediction of several possible

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isomers for compounds such as chlorocyclohexane (cf. Exercise 12-4). The idea that such isomers might act as a single substance,
as the result of rapid equilibration, seemed like a needless complication, and it was not until 1918 that E. Mohr proposed a
definitive way to distinguish between the Baeyer and Sachse cyclohexanes. As will be discussed in Section 12-9, the result, now
known as the Sachse-Mohr theory, was complete confirmation of the idea of nonplanar large rings.
Table: Strain in Cycloalkane Rings and Heats of Combustion of Cycloalkanes
Heat of Combustion
Angle Strain at each Heat of Combustion
Compound n ΔHo per CH2/N Total Strain (kcal/mol)
CH2 ΔHo (kcal/mol)
(kcal/mol)

ethene 2 109.5 337.2 168.6 22.4

cyclopropane 3 49.5 499.9 166.6 27.7

cyclobutane 4 19.5 655.9 164.0 26.3

cyclopentane 5 1.5 793.4 158.7 6.5

cyclohexane 6 10.5 944.8 157.5 0.4

cycloheptane 7 19.1 1108.1 158.4 6.3

cyclooctane 8 25.5 1268.9 158.6 9.7

cyclononane 9 30.5 1429.5 158.8 12.9

cyclodecane 10 34.5 1586.1 158.6 12.1

cyclopentadecane 15 46.5 2362.5 157.5 1.5

open chain alkane 157.4 -

Ring Strain in Cycloalkanes

Ring Strain occurs because the carbons in cycloalkanes are sp3 hybridized, which means that they do not have the expected ideal
bond angle of 109.5o ; this causes an increase in the potential energy because of the desire for the carbons to be at an ideal 109.5o.
An example of ring strain can be seen in the diagram of cyclopropane below in which the bond angle is 60o between the carbons.

The reason for ring strain can be seen through the tetrahedral carbon model. The C-C-C bond angles in cyclopropane (diagram
above) (60o) and cyclobutane (90o) are much different than the ideal bond angle of 109.5o. This bond angle causes cyclopropane
and cyclobutane to have a high ring strain. However, molecules, such as cyclohexane and cyclopentane, would have a much lower
ring strain because the bond angle between the carbons is much closer to 109.5o.
Below are some examples of cycloalkanes. Ring strain can be seen more prevalently in the cyclopropane and cyclobutane models

Below is a chart of cycloalkanes and their respective heats of combustion ( ΔHcomb). The ΔHcomb value increases as the number of
carbons in the cycloalkane increases (higher membered ring), and the ΔHcomb/CH2 ratio decreases. The increase in ΔHcomb can be
attributed to the greater amount of London Dispersion forces. However, the decrease in ΔHcomb/CH2can be attributed to a decrease
in the ring strain.

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Certain cycloalkanes, such as cyclohexane, deal with ring strain by forming conformers. A conformer is a stereoisomer in which
molecules of the same connectivity and formula exist as different isomers, in this case, to reduce ring strain. The ring strain is
reduced in conformers due to the rotations around the sigma bonds.
Other Types of Strain
There are many different types of strain that occur with cycloalkanes. In addition to ring strain, there is also transannular strain,
eclipsing, or torsional strain and bond angle strain.Transannular strain exists when there is steric repulsion between atoms.
Eclipsing (torsional) strain exists when a cycloalkane is unable to adopt a staggered conformation around a C-C bond, and bond
angle strain is the energy needed to distort the tetrahedral carbons enough to close the ring. The presence of angle strain in a
molecule indicates that there are bond angles in that particular molecule that deviate from the ideal bond angles required (i.e., that
molecule has conformers).

Cyclopropane
A three membered ring has no rotational freedom whatsoever, so the three carbon atoms in cyclopropane are all constrained to lie
in the same plane at the corners of an equilateral triangle. The 60º bond angles are much smaller than the optimum 109.5º angles of
a normal tetrahedral carbon atom, and the resulting angle strain dramatically influences the chemical behavior of this cycloalkane.
Cyclopropane also suffers substantial eclipsing strain, since all the carbon-carbon bonds are fully eclipsed.

Furthermore, if you look at a model you will find that the neighboring C-H bonds (C-C bonds, too) are all held in eclipsed
conformations.
Cyclopropane is always at maximum torsional strain. This strain can be illustrated in a line drawing of cyclopropane as shown from
the side. In this oblique view, the dark lines mean that those sides of the ring are closer to you.

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However, the ring isn't big enough to introduce any steric strain, which does not become a factor until we reach six membered
rings. Until that point, rings are not flexible enough for two atoms to reach around and bump into each other.
The really big problem with cyclopropane is that the C-C-C bond angles are all too small.
All the carbon atoms in cyclopropane appear to be tetrahedral.
These bond angles ought to be 109 degrees.
The angles in an equilateral triangle are actually 60 degrees, about half as large as the optimum angle.
This factor introduces a huge amount of strain in the molecule, called ring strain.

Cyclobutane
Cyclobutane is a four membered ring. In two dimensions, it is a square, with 90 degree angles at each corner. Cyclobutane reduces
some bond-eclipsing strain by folding (the out-of-plane dihedral angle is about 25º), but the total eclipsing and angle strain remains
high. Cyclopentane has very little angle strain (the angles of a pentagon are 108º), but its eclipsing strain would be large (about 10
kcal/mol) if it remained planar. Consequently, the five-membered ring adopts non-planar puckered conformations whenever
possible.

However, in three dimensions, cyclobutane is flexible enough to buckle into a "butterfly" shape, relieving torsional strain a little
bit. When it does that, the bond angles get a little worse, going from 90 degrees to 88 degrees.
In a line drawing, this butterfly shape is usually shown from the side, with the near edges drawn using darker lines.

With bond angles of 88 rather than 109 degrees, cyclobutane has a lot of ring strain, but less than in cyclopropane.
Torsional strain is still present, but the neighbouring bonds are not exactly eclipsed in the butterfly.
Cyclobutane is still not large enough that the molecule can reach around to cause crowding. Steric strain is very low.
Cyclobutanes are a little more stable than cyclopropanes and are also a little more common in nature.

Cyclopentane
Cyclopentanes are even more stable than cyclobutanes, and they are the second-most common paraffinic ring in nature, after
cyclohexanes. In two dimensions, a cyclopentane appears to be a regular pentagon.

In three dimensions, there is enough freedom of rotation to allow a slight twist out of this planar shape. In a line drawing, this
three-dimensional shape is drawn from an oblique view, just like cyclobutane.

The ideal angle in a regular pentagon is about 107 degrees, very close to a tetrahedral bond angle.

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Cyclopentane distorts only very slightly into an "envelope" shape in which one corner of the pentagon is lifted up above the
plane of the other four, and as a result, ring strain is entirely removed.
The envelope removes torsional strain along the sides and flap of the envelope. However, the neighbouring carbons are eclipsed
along the "bottom" of the envelope, away from the flap. There is still some torsional strain in cyclopentane.
Again, there is no steric strain in this system.
Rings larger than cyclopentane would have angle strain if they were planar. However, this strain, together with the eclipsing strain
inherent in a planar structure, can be relieved by puckering the ring. Cyclohexane is a good example of a carbocyclic system that
virtually eliminates eclipsing and angle strain by adopting non-planar conformations. Cycloheptane and cyclooctane have greater
strain than cyclohexane, in large part due to transannular crowding (steric hindrance by groups on opposite sides of the ring).

Exercise 7.2.1

1. If cyclobutane were to be planar how many H-H eclipsing interactions would there be, and assuming 4 kJ/mol per H-H
eclipsing interaction what is the strain on this “planar” molecule?
2. In the two conformations of cis-cyclopentane one is more stable than the other. Explain why this is.

Answer
1. There are 8 eclipsing interactions (two per C-C bond). The extra strain on this molecule would be 32 kJ/mol (4 kJ/mol x
8).
2. The first conformation is more stable. Even though the methyl groups are cis in the model on the left, they are eclipsing
due the conformation, therefore increasing the strain within the molecule.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

7.2: Cycloalkanes and Ring Strain is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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7.3: Cyclohexane Conformations
Learning Objective
draw cyclohexane conformations (chair & boat)
correlate energies of conformations with rotational energy diagrams and predict the most stable conformations for
cyclohexane

Introduction
Rings larger than cyclopentane would have angle strain if they were planar. However, this strain, together with the eclipsing strain
inherent in a planar structure, can be relieved by puckering the ring. Cyclohexane is a good example of a carbocyclic system that
virtually eliminates eclipsing and angle strain by adopting non-planar conformations. Cycloheptane and cyclooctane have greater
strain than cyclohexane, in large part due to transannular crowding (steric hindrance by groups on opposite sides of the ring).

Cyclohexane Conformations (aka Chair Flips)

Cyclohexane is rapidly rotating between the two most stable conformations known as the chair conformations in what is called the
"Chair Flip" shown below.

Several other notable cyclohexane conformations occur during the transition from one chair conformer to the other - the boat, the
twist, and the half-chair. The relative energies of the conformations is a direct reflection of their relative stabilities. These structural
and energetic relationships are summarized in the conformational energy diagram for cyclohexane below.

The Chair Conformation - a closer look

Since the chair conformation has the lowest potential energy, it is the most relevant to the conformation of cyclohexane. On careful
examination of a chair conformation of cyclohexane, we find that the twelve hydrogens are not structurally equivalent. Six of them
are located about the periphery of the carbon ring, and are termed equatorial. The other six are oriented above and below the
approximate plane of the ring (three in each location), and are termed axial because they are aligned parallel to the symmetry axis
of the ring.

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In the figure above, the equatorial hydrogens are colored blue, and the axial hydrogens are in bold. Since there are two equivalent
chair conformations of cyclohexane in rapid equilibrium, all twelve hydrogens have 50% equatorial and 50% axial character. The
figure below illustrates how to convert a molecular model of cyclohexane between two different chair conformations - this is
something that you should practice with models. Notice that a 'ring flip' causes equatorial hydrogens to become axial, and vice-
versa.

How to draw stereo bonds ("up" and "down" bonds)

There are various ways to show these orientations. The solid (dark) "up wedge" I used is certainly common. Some people use an
analogous "down wedge", which is light, to indicate a down bond; unfortunately, there is no agreement as to which way the wedge
should point, and you are left relying on the lightness of the wedge to know it is "down". The "down bond" avoids this wedge
ambiguity, and just uses some kind of light line. The down bond I used (e.g., in Figure 5B) is a dashed line; IUPAC encourages a
series of parallel lines, something like What I did is a variation of what is recommended by IUPAC:
In ISIS/Draw, the "up wedge" and "down bond" that I used, along with other variations, are available from a tool button that
may be labeled with any of them, depending on most recent use. It is located directly below the tool button for ordinary C-C
bonds.
In Symyx Draw, the "up wedge" and "down bond", along with other variations, are available from a tool button that may be
labeled with any of them, depending on most recent use. It is located directly below the "Chain" tool button.
ChemSketch provides up and down wedges, but not the simple up and down bonds discussed above. The wedges are available
from the second toolbar across the top. For an expanded discussion of using these wedges, see the section of my ChemSketch
Guide on Stereochemistry: Wedge bonds.
As always, the information provided on these pages in intended to help you get started. Each program has more options for drawing
bonds than discussed here. When you feel the need, look around!

How to Draw chairs

Most of the structures shown on this page were drawn with the free program ISIS/Draw. I have posted a guide to help you get
started with ISIS/Draw. ISIS/Draw provides a simple cyclohexane (6-ring) hexagon template on the toolbar across the top. It
provides templates for various 6-ring chair structures from the Templates menu; choose Rings. There are templates for simple
chairs, without substituents (e.g., Fig 1B), and for chairs showing all the substituents (e.g., Fig 2B). In either case, you can add,
delete, or change things as you wish. Various kinds of stereo bonds (wedges and bars) are available by clicking the left-side tool
button that is just below the regular C-C single bond button. It may have a wedge shown on it, but this will vary depending on how
it has been used. To choose a type of stereo bond, click on the button and hold the mouse click; a new menu will appear to the right
of the button.
The free drawing program Symyx Draw, the successor to ISIS/Draw, provides similar templates and tools. A basic chair structure
is provided on the default template bar that is shown. More options are available by choosing the Rings template. See my page
Symyx Draw for a general guide for getting started with this program.
The free drawing program ChemSketch provides similar templates and tools. To find the special templates for chairs, go to the
Templates menu, choose Template Window, and then choose "Rings" from the drop-down menu near upper left. See my page
ChemSketch for a general guide for getting started with this program.

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If you want to draw chair structures by hand (and if you are going on in organic chemistry, you should)... Be careful. The precise
zigs and zags, and the angles of substituents are all important. Your textbook may offer you some hints for how to draw chairs. A
short item in the Journal of Chemical Education offers a nice trick, showing how the chair can be thought of as consisting of an M
and a W. The article is V Dragojlovic, A method for drawing the cyclohexane ring and its substituents. J Chem Educ 78:923, 7/01.
(I thank M Farooq Wahab, Chemistry, Univ Karachi, for suggesting that this article be noted here.)
Aside from drawing the basic chair, the key points in adding substituents are:
Axial groups alternate up and down, and are shown "vertical".
Equatorial groups are approximately horizontal, but actually somewhat distorted from that, so that the angle from the axial
group is a bit more than a right angle -- reflecting the common 109 degree bond angle.
As cautioned before, it is usually easier to draw and see what is happening at the four corners of the chair than at the two middle
positions. Try to use the corners as much as possible.
Because axial bonds are parallel to each other, substituents larger than hydrogen generally suffer greater steric crowding when they
are oriented axial rather than equatorial. Consequently, substituted cyclohexanes will preferentially adopt conformations in which
the larger substituents assume equatorial orientation.

When the methyl group in the structure above occupies an axial position it suffers steric crowding by the two axial hydrogens
located on the same side of the ring.

The conformation in which the methyl group is equatorial is more stable, and thus the equilibrium lies in this direction

Exercise
Questions
1. Consider the conformations of cyclohexane, chair, boat, twist boat. Order them in increasing strain in the molecule.
2. Draw two conformations of cyclohexyl amine (C6H11NH2). Indicate axial and equatorial positions.
3. Draw the two isomers of 1,4-dihydroxylcyclohexane, identify which are equatorial and axial.
4. In the following molecule, label which are equatorial and which are axial, then draw the chair flip (showing labels 1,2,3).

Answer
1. Chair < Twist Boat < Boat (most strain)
2.

7.3.3 https://chem.libretexts.org/@go/page/207375
3.

4. Original conformation: 1 = axial, 2 = equatorial, 3 = axial

Flipped chair now looks like this.

Contributors and Attributions

7.3: Cyclohexane Conformations is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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7.4: Conformations of Monosubstituted Cyclohexanes
Learning Objective
draw mono-substituted cyclohexane conformers (chair only)
correlate energies of conformations with rotational energy diagrams and predict the most stable conformations for butane,
higher alkanes, cyclohexane, mono-substituted cyclohexanes, and disubstituted cyclohexanes

Introduction
Because axial bonds are parallel to each other, substituents larger than hydrogen generally suffer greater steric crowding when they
are oriented axial rather than equatorial. Consequently, substituted cyclohexanes will preferentially adopt conformations in which
the larger substituents assume equatorial orientation.

When the methyl group in the structure above occupies an axial position it suffers steric crowding by the two axial hydrogens
located on the same side of the ring. The conformation in which the methyl group is equatorial is more stable, and thus the
equilibrium lies in this direction.

In examining possible structures for monosubstituted cyclohexanes, it is useful to follow two principles:
i. Chair conformations are generally more stable than other possibilities.
ii. Substituents on chair conformers prefer to occupy equatorial positions due to the increased steric hindrance of axial locations.

Experimental Measurements of Steric Hindrance

The relative steric hindrance experienced by different substituent groups oriented in an axial versus equatorial location on
cyclohexane may be determined by the conformational equilibrium of the compound. The corresponding equilibrium constant is
related to the energy difference between the conformers and collecting such data allows us to evaluate the relative tendency of
substituents to exist in an equatorial or axial location.
Looking at the energy values the table, it is clear that the apparent "size" of a substituent (in terms of its preference for equatorial
over axial orientation) is influenced by its width and bond length to cyclohexane, as evidenced by the fact that an axial vinyl group
is less hindered than ethyl, and iodine slightly less than chlorine.
A Selection of AG° Values for the Change from Axial to Equatorial Orientation of Substituents for Monosubstituted Cyclohexanes
Substituent −ΔG
o
kcal/mol Substituent −ΔG
o
kcal/mol

CH −
3
1.7 O N−
2
1.1

CH H −
2 5
1.8 N≡C− 0.2

(CH ) CH−
3 2
2.2 CH O−
3
0.5

(CH ) C−
3 3
≥ 5.0 (CH3)3C- 0.7

F− 0.3 F- 1.3

Cl− 0.5 C H −
6 5
3.0

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Substituent −ΔG
o
kcal/mol Substituent −ΔG
o
kcal/mol

Br− 0.5

I− 0.5

Exercise
1. In the molecule, cyclohexyl ethyne there is little steric strain, why?

Answer
1.
The ethyne group is linear and therefore does not affect the hydrogens in the 1,3 positions to say to the extent as a bulkier
or a bent group (e.g. ethene group) would. This leads to less of a strain on the molecule.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
>Robert Bruner (http://bbruner.org)
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

7.4: Conformations of Monosubstituted Cyclohexanes is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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7.5: Conformations of Disubstituted Cyclohexanes
Learning Objective
draw di-substituted cyclohexane conformers (chair only)
correlate energies of conformations with rotational energy diagrams and predict the most stable conformations for
disubstituted cyclohexanes

Conformational Structures of Disubstituted Cyclohexanes

In a sample of cyclohexane, the two identical chair conformers are present in equal concentration, and the hydrogens are all
equivalent (50% equatorial & 50% axial) due to rapid interconversion of the conformers. When the cyclohexane ring bears a
substituent, the two chair conformers are not the same. In one conformer the substituent is axial, in the other it is equatorial. Due to
steric hindrance in the axial location, substituent groups prefer to be equatorial and that chair conformer predominates in the
equilibrium.
When cycloalkanes have two substituents on different ring carbon atoms, then a pair of configurational stereoisomers exist. Now
we must examine the way in which favorable ring conformations influence the properties of the configurational isomers.
Remember, configurational stereoisomers are stable, unique chemical compounds, whereas, conformational isomers are different
rotations of the same compound. In examining possible structures for disubstituted cyclohexane, it is useful to follow two
principles:

1. Substituents on chair conformers prefer to occupy equatorial positions due to the increased steric
hindrance of axial locations.
The following equations and formulas illustrate how the presence of two or more substituent on a cyclohexane ring perturbs the
interconversion of the two chair conformers in ways that can be predicted. When there is a potential energy difference between the
conformers, then the lower energy conformation is favored as indicated by the equilibrium reaction arrows.

1,1-dimethylcyclohexane

1-t-butyl-1-methylcyclohexane

cis-1,2-dimethylcyclohexane

trans-1,2-dimethylcyclohexane

cis-1,3-dimethylcyclohexane

trans-1,3-dimethylcyclohexane

cis-1,4-dimethylcyclohexane

trans-1,4-dimethylcyclohexane

7.5.1 https://chem.libretexts.org/@go/page/207377
In the case of 1,1-disubstituted cyclohexanes, one of the substituents must necessarily be axial and the other equatorial,
regardless of which chair conformer is considered. Since the substituents are the same in 1,1-dimethylcyclohexane, the
two conformers are identical and present in equal concentration. In 1-t-butyl-1-methylcyclohexane the t-butyl group is
much larger than the methyl, and that chair conformer in which the larger group is equatorial will be favored in the
equilibrium( > 99%). Consequently, the methyl group in this compound is almost exclusively axial in its orientation.
In the cases of 1,2-, 1,3- and 1,4-disubstituted compounds the analysis is a bit more complex. It is always possible to have both
groups equatorial, but whether this requires a cis-relationship or a trans-relationship depends on the relative location of the
substituents. As we count around the ring from carbon #1 to #6, the uppermost bond on each carbon changes its orientation from
equatorial (or axial) to axial (or equatorial) and back. It is important to remember that the bonds on a given side of a chair ring-
conformation always alternate in this fashion. Therefore, it should be clear that for cis-1,2-disubstitution, one of the substituents
must be equatorial and the other axial; in the trans-isomer both may be equatorial. Because of the alternating nature of equatorial
and axial bonds, the opposite relationship is true for 1,3-disubstitution (cis is all equatorial, trans is equatorial/axial). Finally, 1,4-
disubstitution reverts to the 1,2-pattern.

The conformations of some substituted cyclohexanes may be examined as interactive models by Clicking Here .

It can be helpful to add the hydrogen atoms at the axial positions to help recognize the equatorial position.

Exercise

1. Draw the two chair conformations for cis-1-ethyl-2-methylcyclohexane using bond-line structures and indicate the more
energetically favored conformation.
2. Draw the most stable conformation for trans-1-ethyl-3-methylcyclohexane using bond-line structures.
3. Draw the most stable conformation for trans-1-t-butyl-4-methylcyclohexane using bond-line structures.

Answer

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

7.5: Conformations of Disubstituted Cyclohexanes is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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7.6: Polycyclic Alkanes
 Objective

After completing this section, you should be able to draw the structures and construct molecular models of simple polycyclic
molecules.

 Key Terms

Make certain that you can define, and use in context, the key terms below.
bridgehead carbon atom
polycyclic molecule

 Study Notes
A bridgehead carbon atom is a carbon atom which is shared by at least two rings. The hydrogen atom which is attached to a bridgehead
carbon may be referred to as a bridgehead hydrogen.
Note that bicyclo[2.2.1]heptane is the systematic name of norborane. You need not be concerned over the IUPAC name of norbornane.
The nomenclature of compounds of this type is beyond the scope of this course.

Nomenclature of Bicyclic Ring Systems

There are many hydrocarbons and hydrocarbon derivatives with two rings having common carbon atoms. There are three main ways that
the two rings can be connected. The first is called a fused bicyclic ring structure where the two rings share a covalent bond and a have two
bridgehead carbons (marked in red on the structures below). A bridgehead is defined as a carbon that is part of two or more rings.
Hydrogens attached to bridge head carbons are often referred to as bridge head hydrogens. The two rings can also be connected by a bridge
containing one or more carbons to form a bridged bicyclic molecule. Lastly, the two rings can be joined with a singe bridge head carbon to
form spiro bicyclic molecules.

fused bridged spiro

= bridgehead carbons

Bicyclic Isomers of C10H18

Naming Fused and Bridged Compounds

Fused and bridged bicyclic compounds are follow similar naming conventions:
1. Count the total number of carbons in both rings. This is the parent name. (eg. ten carbons in the system would be decane)
2. Count the number of carbons between the bridgeheads, then place the numbers in square brackets in descending order separated by
periods. Fused and bridged bycyclic compounds should have three numbers such as [2.2.0]. For fused compounds one of the numbers
should be zero.
3. Place the word bicyclo at the beginning of the name.
1 1 1
1 2
2 2
0 2 1
3 3
3 3
4 4 4

bicyclo[4.4.0]decane bicyclo[4.3.1]decane

Examples with carbons and hydrogens explicitly shown:

H
H C H
C H 2C CH2 C
H 2C CH2 H 2C H 2C CH2
CH2 H 2C CH C
H 2C CH2 C H
H2
bicyclo[2.2.1]heptane bicyclo[3.1.1]heptane bicyclo[1.1.0]butane

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Naming Spiro Compounds
Spiro bicyclics are named using the same basic rules. Because there is only one bridgehead carbon only two numbers will be required in the
brackets. Also, the word spiro is placed at the beginning.
2 1 1
2
3
3
4 5 4

spiro[5.4]decane

Examples

spiro[4.4]nonane spiro[3.2]hexane

Conformations in Bicyclic Ring Systems

As expected, the connection of two rings has defined effects on the possible conformations. However, the ideas previously discussed in this
chapter can be used for conformational analysis. Fused rings have the possibility of two isomers where the bridgehead hydrogens are either
cis or trans along the shared bond. These two isomers have significant differences in flexibility and stability as seen in bicyclo[4,4,0]decane
more commonly known as decalin. If the positioning of the bridgehead hydrogens are shown in a fused ring the prefix cis or trans should be
included in the name.
The trans-isomer is the easiest to describe because the fusion of the two rings creates a rigid, roughly planar, structure made up of two chair
conformations. Unlike cyclohexane, the two rings cannot flip from one chair form to another. Accordingly, the orientation of the any
substituents is fixed in either an axial or equatorial position in trans-decalin. This means that the C-C bonds coming away from the fused
edge are held in equatorial positions relative to each ring thus preventing the possibility of any 1,3-diaxial interactions occurring between
ring atoms.
H H

H H
trans -decalin
(rigid)

2kcal mol−1" id="MathJax-Element-1-Frame" role="presentation" style="position:relative;" tabindex="0">

The two rings in cis-decalin are also both held in a chair conformations. In comparison, the chair-chair forms of cis-decalin are relatively
flexible, and inversion of both rings at once occurs fairly easily.
H H H
H
H

H
cis -decalin
(more flexible)

The flexibility of cis-decalin allows for a substituent to interconvert between axial and equatorial conformations. In much the same fashion
as cyclohexane, equatorial substituents tend to create less steric strain and create a more stable conformer.
CH3 CH3
2 3 4
1 3
2
1 6 5
6 5 4

(Note: atoms are mapped in blue for clarity.)

A major difference in cis-decalin is the fact that one of C-C bonds coming away from the fused edge is held an an axial position. This is true
in both ring-flip conformations. This axial C-C bond causes 1,3-diaxial interactions to occur in cis-decalin making it roughly 8.4 kJ/mol less
stable than trans-decalin. This amount of 1,3-diaxial steric strain is roughly equivalent to that of an ethyl substituent attached to a
cyclohexane ring (8.0 kJ/mol)

H H
H H

= steric strain

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Bicyclic compounds with a bridge typically have very little flexibility and are often held in a ridged conformation. The molecule
norbornane represent a cyclohexane ring connected by a single carbon bridge.

norbornane, or
bicyclo[2.2.1]heptane

Norbornane is estimated to have 72 kJ/mol of ring strain which can be understood when viewing the contained rings. The carbon bridge in
norbornane holds the cyclohexane ring at the bottom in a boat conformation creating torsional strain from eclipsing bonds along the edge.

H H
H H
H H
H H
(green arrows used to illustrate
eclipsing hydrogens)

Also, the carbon bridge forms a cyclopentane ring (shown in red below making up the right side of the structure) with increased angle strain
throughout the whole molecule.

Polycyclic Systems in Nature

Fused ring systems like decalin are very common in natural products. In fact, similar ring systems are found in steroids, which are an
important class of lipids. Steroids generally have structures that include three six-membered rings and a five-membered ring connected by
three fused bonds. Most natural steroids have a trans configuration at all three fusion points. This tends to give steroids a rigid and semi-flat
structure.
H
H H

H H
H

basic steroid ring confguration trans-trans-trans

(fused bonds highlighted in purple)

Sex hormones are an example of steroids. The primary male hormone, testosterone, is responsible for the development of secondary sex
characteristics. Two female sex hormones, progesterone and estrogen (or estradiol) control the ovulation cycle. Notice that the male and
female hormones have only slight differences in structures, but yet have very different physiological effects. Testosterone promotes the
normal development of male genital organs and is synthesized from cholesterol in the testes. It also promotes secondary male sexual
characteristics such as deep voice, facial and body hair.
OH OH

H H

H H H H
O HO
testosterone estradiol

The best known and most abundant steroid in the body is cholesterol. Cholesterol is formed in brain tissue, nerve tissue, and the blood
stream. It is the major compound found in gallstones and bile salts. Cholesterol also contributes to the formation of deposits on the inner
walls of blood vessels. These deposits harden and obstruct the flow of blood. This condition, known as atherosclerosis, results in various
heart diseases, strokes, and high blood pressure.

H H
HO
cholesterol

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Exercises
1)

3) The following molecule is cholic acid. Determine if the three fused bonds have a cis or trans configuration.

Solutions
1)
a) Bicyclo[2.1.1]hexane
b) Bicyclo[3.2.1]octane
c) Bicyclo[2.1.0]pentane (more commonly called "housane")
d) Bicyclo[2.2.2]octane
e) cis-Bicyclo[3.3.0]octane
f) cis-Bicyclo[1.1.0]butane
g) Bicyclo[1.1.1]pentane
h) Bicyclo[4.3.3]dodecane
i) Spiro[5.2]octane
j) Spiro[3.3]heptane
2)

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Questions
Q4.9.1
Someone stated that trans-decalin is more stable than cis-decalin. Explain why this is incorrect.
Solutions
S4.9.1
Cis-decalin has fewer steric interactions than trans-decalin.

7.6: Polycyclic Alkanes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
4.9: Conformations of Polycyclic Molecules by Chris Schaller, Dietmar Kennepohl, Gamini Gunawardena, Krista Cunningham, Layne Morsch,
Marjorie C. Caserio, Steven Farmer is licensed CC BY-SA 4.0.

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7.7: Carbocyclic Products in Nature
The important class of lipids called steroids are actually metabolic derivatives of terpenes, but they are customarily treated as a
separate group. Steroids may be recognized by their tetracyclic skeleton, consisting of three fused six-membered and one five-
membered ring, as shown in the diagram to the right. The four rings are designated A, B, C & D as noted, and the peculiar
numbering of the ring carbon atoms (shown in red) is the result of an earlier misassignment of the structure. The substituents
designated by R are often alkyl groups, but may also have functionality. The R group at the A:B ring fusion is most commonly
methyl or hydrogen, that at the C:D fusion is usually methyl. The substituent at C-17 varies considerably, and is usually larger than
methyl if it is not a functional group. The most common locations of functional groups are C-3, C-4, C-7, C-11, C-12 & C-17. Ring
A is sometimes aromatic. Since a number of tetracyclic triterpenes also have this tetracyclic structure, it cannot be considered a
unique identifier.

Steroids are widely distributed in animals, where they are associated with a number of physiological processes. Examples of some
important steroids are shown in the following diagram. Norethindrone is a synthetic steroid, all the other examples occur naturally.
A common strategy in pharmaceutical chemistry is to take a natural compound, having certain desired biological properties
together with undesired side effects, and to modify its structure to enhance the desired characteristics and diminish the undesired.
This is sometimes accomplished by trial and error.
The generic steroid structure drawn above has seven chiral stereocenters (carbons 5, 8, 9, 10, 13, 14 & 17), which means that it
may have as many as 128 stereoisomers. With the exception of C-5, natural steroids generally have a single common configuration.
This is shown in the last of the toggled displays, along with the preferred conformations of the rings.

Chemical studies of the steroids were very important to our present understanding of the configurations and conformations of six-
membered rings. Substituent groups at different sites on the tetracyclic skeleton will have axial or equatorial orientations that are
fixed because of the rigid structure of the trans-fused rings. This fixed orientation influences chemical reactivity, largely due to the

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greater steric hindrance of axial groups versus their equatorial isomers. Thus an equatorial hydroxyl group is esterified more
rapidly than its axial isomer.
It is instructive to examine a simple bicyclic system as a model for the fused rings of the steroid molecule. Decalin, short for
decahydronaphthalene, exists as cis and trans isomers at the ring fusion carbon atoms. Planar representations of these isomers are
drawn at the top of the following diagram, with corresponding conformational formulas displayed underneath. The numbering
shown for the ring carbons follows IUPAC rules, and is different from the unusual numbering used for steroids. For purposes of
discussion, the left ring is labeled A (colored blue) and the right ring B (colored red). In the conformational drawings the ring
fusion and the angular hydrogens are black.

The trans-isomer is the easiest to describe because the fusion of the A & B rings creates a rigid, roughly planar, structure made up
of two chair conformations. Each chair is fused to the other by equatorial bonds, leaving the angular hydrogens (Ha) axial to both
rings. Note that the bonds directed above the plane of the two rings alternate from axial to equatorial and back if we proceed around
the rings from C-1 to C-10 in numerical order. The bonds directed below the rings also alternate in a complementary fashion.
Conformational descriptions of cis- decalin are complicated by the fact that two energetically equivalent fusions of chair
cyclohexanes are possible, and are in rapid equilibrium as the rings flip from one chair conformation to the other. In each of these
all chair conformations the rings are fused by one axial and one equatorial bond, and the overall structure is bent at the ring fusion.
In the conformer on the left, the red ring (B) is attached to the blue ring (A) by an axial bond to C-1 and an equatorial bond to C-6
(these terms refer to ring A substituents). In the conformer on the right, the carbon bond to C-1 is equatorial and the bond to C-6 is
axial. Each of the angular hydrogens (Hae or Hea) is oriented axial to one of the rings and equatorial to the other. This relationship
reverses when double ring flipping converts one cis-conformer into the other.
Cis-decalin is less stable than trans-decalin by about 2.7 kcal/mol (from heats of combustion and heats of isomerization data). This
is due to steric crowding (hindrance) of the axial hydrogens in the concave region of both cis-conformers, as may be seen in the
model display activated by the following button. This difference is roughly three times the energy of a gauche butane conformer
relative to its anti conformer. Indeed three gauche butane interactions may be identified in each of the cis-decalin conformations, as
will be displayed by clicking on the above conformational diagram. These gauche interactions are also shown in the model.
Steroids in which rings A and B are fused cis, such as the example on the right, do not have the sameconformational mobility
exhibited by cis-decalin. The fusion of ring C to ring B in a trans configuration prevents ring B from undergoing a conformational
flip to another chair form. If this were to occur, ring C would have to be attached to ring B by two adjacent axial bonds directed
180º apart. This is too great a distance to be bridged by the four carbon atoms making up ring C. Consequently, the steroid

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molecule is locked in the all chair conformation shown here. Of course, all these steroids and decalins may have one or more six-
membered rings in a boat conformation. However the high energy of boat conformers relative to chairs would make such structures
minor components in the overall ensemble of conformations available to these molecules.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Compounds classified as terpenes constitute what is arguably the largest and most diverse class of natural products. A majority of
these compounds are found only in plants, but some of the larger and more complex terpenes (e.g. squalene & lanosterol) occur in
animals. Terpenes incorporating most of the common functional groups are known, so this does not provide a useful means of
classification. Instead, the number and structural organization of carbons is a definitive characteristic. Terpenes may be considered
to be made up of isoprene (more accurately isopentane) units, an empirical feature known as the isoprene rule. Because of this,
terpenes usually have 5n carbon atoms (n is an integer), and are subdivided as follows:

Classification Isoprene Units Carbon Atoms

monoterpenes 2 C10

sesquiterpenes 3 C15

diterpenes 4 C20

sesterterpenes 5 C25

triterpenes 6 C30

Isoprene itself, a C5H8 gaseous hydrocarbon, is emitted by the leaves of various plants as a natural byproduct of plant metabolism.
Next to methane it is the most common volatile organic compound found in the atmosphere. Examples of C10 and higher terpenes,
representing the four most common classes are shown in the following diagrams. Most terpenes may be structurally dissected into
isopentane segments. How this is done can be seen in the diagram directly below.

Figure: Monoterpenes and diterpenes

The isopentane units in most of these terpenes are easy to discern, and are defined by the shaded areas. In the case of the
monoterpene camphor, the units overlap to such a degree it is easier to distinguish them by coloring the carbon chains. This is also
done for alpha-pinene. In the case of the triterpene lanosterol we see an interesting deviation from the isoprene rule. This thirty
carbon compound is clearly a terpene, and four of the six isopentane units can be identified. However, the ten carbons in center of
the molecule cannot be dissected in this manner. Evidence exists that the two methyl groups circled in magenta and light blue have
moved from their original isoprenoid locations (marked by small circles of the same color) to their present location. This
rearrangement is described in the biosynthesis section. Similar alkyl group rearrangements account for other terpenes that do not
strictly follow the isoprene rule.

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Figure: Triterpenes
Polymeric isoprenoid hydrocarbons have also been identified. Rubber is undoubtedly the best known and most widely used
compound of this kind. It occurs as a colloidal suspension called latex in a number of plants, ranging from the dandelion to the
rubber tree (Hevea brasiliensis). Rubber is a polyene, and exhibits all the expected reactions of the C=C function. Bromine,
hydrogen chloride and hydrogen all add with a stoichiometry of one molar equivalent per isoprene unit. Ozonolysis of rubber
generates a mixture of levulinic acid ( C H C OC H C H C O H ) and the corresponding aldehyde. Pyrolysis of rubber produces
3 2 2 2

the diene isoprene along with other products.

The double bonds in rubber all have a Z-configuration, which causes this macromolecule to adopt a kinked or coiled conformation.
This is reflected in the physical properties of rubber. Despite its high molecular weight (about one million), crude latex rubber is a
soft, sticky, elastic substance. Chemical modification of this material is normal for commercial applications. Gutta-percha
(structure above) is a naturally occurring E-isomer of rubber. Here the hydrocarbon chains adopt a uniform zig-zag or rod like
conformation, which produces a more rigid and tough substance. Uses of gutta-percha include electrical insulation and the covering
of golf balls.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

7.7: Carbocyclic Products in Nature is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Steroids by William Reusch is licensed CC BY-NC-SA 4.0.
Terpenes by William Reusch is licensed CC BY-NC-SA 4.0.

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7.8: Steroids
 Objectives

After completing this section, you should be able to

1. draw the tetracyclic ring system on which the structure of all steroids is based.
2. identify the occurrence and biological roles of at least two common steroids.
3. sketch the stereochemical conformation of a steroid, given an adequate wedge and dash structure, and determine whether
the ring substituents in such a compound occupy axial or equatorial positions.
4. construct a molecular model of a steroid, given a suitable written description or a wedge and dash structure from which to
work.

 Key Terms
Make certain that you can define, and use in context, the key term below.
steroid

 Study Notes

Since the 1988 Olympic Games in Seoul, even individuals who have no interest in chemistry or sport have heard the word
“steroid” and are aware that some athletes use these substances to enhance their athletic abilities. Stanozolol, the substance
which Canadian sprinter, Ben Johnson, was found to have used, has the structure shown below:

General Steroid Structure

The important class of lipids called steroids are actually metabolic derivatives of terpenes, but they are customarily treated as a
separate group. Steroids may be recognized by their tetracyclic skeleton, consisting of three fused six-membered and one five-
membered ring, as shown in the diagram below. The four rings are designated A, B, C & D as noted, and the peculiar numbering of
the ring carbon atoms (shown in red) is the result of an earlier misassignment of the structure. The substituents designated by R are
often alkyl groups, but may also have functionality. The R group at the A:B ring fusion is most commonly methyl or hydrogen, that
at the C:D fusion is usually methyl. The substituent at C-17 varies considerably, and is usually larger than methyl. The most
common locations of functional groups are C-3, C-4, C-7, C-11, C-12 & C-17. Ring A is sometimes aromatic. Since a number of
tetracyclic triterpenes also have this tetracyclic structure, it cannot be considered a unique identifier.

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Common Steroids
Steroids are widely distributed in animals, where they are associated with a number of physiological processes. Examples of some
important steroids are shown in the following diagram. Norethindrone is a synthetic steroid, all the other examples occur naturally.
The generic steroid structure drawn above has seven chiral stereocenters (carbons 5, 8, 9, 10, 13, 14 & 17), which means that it
may have as many as 128 stereoisomers. With the exception of C-5, natural steroids generally have a single common configuration.

Decalin as a model system

It is instructive to examine a simple bicyclic system as a model for the fused rings of the steroid molecule. Decalin, short for
decahydronaphthalene, exists as cis and trans isomers at the ring fusion carbon atoms. Planar representations of these isomers are
drawn at the top of the following diagram, with corresponding conformational formulas displayed underneath. The numbering
shown for the ring carbons follows IUPAC rules, and is different from the unusual numbering used for steroids. For purposes of
discussion, the left ring is labeled A (colored blue) and the right ring B (colored red). In the conformational drawings the ring
fusion and the angular hydrogens are black.

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The trans-isomer is the easiest to describe because the fusion of the A & B rings creates a rigid, roughly planar, structure made up
of two chair conformations. Each chair is fused to the other by equatorial bonds, leaving the angular hydrogens (Ha) axial to both
rings. Note that the bonds directed above the plane of the two rings alternate from axial to equatorial and back if we proceed around
the rings from C-1 to C-10 in numerical order. The bonds directed below the rings also alternate in a complementary fashion.
Conformational descriptions of cis- decalin are complicated by the fact that two energetically equivalent fusions of chair
cyclohexanes are possible, and are in rapid equilibrium as the rings flip from one chair conformation to the other. In each of these
all chair conformations the rings are fused by one axial and one equatorial bond, and the overall structure is bent at the ring fusion.
In the conformer on the left, the red ring (B) is attached to the blue ring (A) by an axial bond to C-1 and an equatorial bond to C-6
(these terms refer to ring A substituents). In the conformer on the right, the carbon bond to C-1 is equatorial and the bond to C-6 is
axial. Each of the angular hydrogens (Hae or Hea) is oriented axial to one of the rings and equatorial to the other. This relationship
reverses when double ring flipping converts one cis-conformer into the other.
Cis-decalin is less stable than trans-decalin by about 2.7 kcal/mol (from heats of combustion and heats of isomerization data). This
is due to steric crowding (hindrance) of the axial hydrogens in the concave region of both cis-conformers, as may be seen in the
model display activated by the following button. This difference is roughly three times the energy of a gauche butane conformer
relative to its anti conformer. Indeed three gauche butane interactions may be identified in each of the cis-decalin conformations, as
will be displayed by clicking on the above conformational diagram. These gauche interactions are also shown in the model.

Steroid Conformations
Steroids in which rings A and B are fused cis, such as the example on the right, do not have the same conformational mobility
exhibited by cis-decalin. The fusion of ring C to ring B in a trans configuration prevents ring B from undergoing a conformational
flip to another chair form. If this were to occur, ring C would have to be attached to ring B by two adjacent axial bonds directed
180º apart. This is too great a distance to be bridged by the four carbon atoms making up ring C. Consequently, the steroid
molecule is locked in the all chair conformation shown here. Of course, all these steroids and decalins may have one or more six-

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membered rings in a boat conformation. However the high energy of boat conformers relative to chairs would make such structures
minor components in the overall ensemble of conformations available to these molecules.

Much like cyclohexanes substituents (Section 4-7) on a steroid ring system can be either an axial or equatorial position. Fused
rings makes steroids ridge and unable to undergo cyclohexane ring-flips Because of sterics, substituents in the equatorial posltion
tend to be more energetically favorable. The -OH group present in cholesterol is in the more stable equatorial position while the
two -CH3 groups on the steroid ring are both in an axial position.

Axial
Axial
H 3C Equatorial
CH3 H CH3
CH3
Equatorial H
CH3 H
HO H
H H H
H
HO

GLmol

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Steroid Hormones
Hormones are chemical messengers that are released in one tissue and transported through the circulatory system to one or more
other tissues. One group of hormones is known as steroid hormones because these hormones are synthesized from cholesterol,
which is also a steroid. There are two main groups of steroid hormones: adrenocortical hormones and sex hormones.
The adrenocortical hormones, such as aldosterone and cortisol (Table 27.6.1), are produced by the adrenal gland, which is located
adjacent to each kidney. Aldosterone acts on most cells in the body, but it is particularly effective at enhancing the rate of
reabsorption of sodium ions in the kidney tubules and increasing the secretion of potassium ions and/or hydrogen ions by the
tubules. Because the concentration of sodium ions is the major factor influencing water retention in tissues, aldosterone promotes
water retention and reduces urine output. Cortisol regulates several key metabolic reactions (for example, increasing glucose
production and mobilizing fatty acids and amino acids). It also inhibits the inflammatory response of tissue to injury or stress.
Cortisol and its analogs are therefore used pharmacologically as immunosuppressants after transplant operations and in the
treatment of severe skin allergies and autoimmune diseases, such as rheumatoid arthritis.
Table 27.6.1 Representative Steroid Hormones and Their Physiological Effects
Hormone Effect

regulates salt metabolism; stimulates kidneys to retain sodium and

excrete potassium

stimulates the conversion of proteins to carbohydrates

regulates the menstrual cycle; maintains pregnancy

stimulates female sex characteristics; regulates changes during the

menstrual cycle

stimulates and maintains male sex characteristics

The sex hormones are a class of steroid hormones secreted by the gonads (ovaries or testes), the placenta, and the adrenal glands.
Testosterone and androstenedione are the primary male sex hormones, or androgens, controlling the primary sexual characteristics
of males, or the development of the male genital organs and the continuous production of sperm. Androgens are also responsible
for the development of secondary male characteristics, such as facial hair, deep voice, and muscle strength. Two kinds of sex
hormones are of particular importance in females: progesterone, which prepares the uterus for pregnancy and prevents the further
release of eggs from the ovaries during pregnancy, and the estrogens, which are mainly responsible for the development of female
secondary sexual characteristics, such as breast development and increased deposition of fat tissue in the breasts, the buttocks, and
the thighs. Both males and females produce androgens and estrogens, differing in the amounts of secreted hormones rather than in
the presence or absence of one or the other.
Sex hormones, both natural and synthetic, are sometimes used therapeutically. For example, a woman who has had her ovaries
removed may be given female hormones to compensate. Some of the earliest chemical compounds employed in cancer
chemotherapy were sex hormones. For example, estrogens are one treatment option for prostate cancer because they block the
release and activity of testosterone. Testosterone enhances prostate cancer growth. Sex hormones are also administered in

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preparation for sex-change operations, to promote the development of the proper secondary sexual characteristics. Oral
contraceptives are synthetic derivatives of the female sex hormones; they work by preventing ovulation.

Adrenocorticoid Hormones
The adrenocorticoid hormones are products of the adrenal glands ("adrenal" means adjacent to the renal (kidney). The most
important adrenocorticoid is aldosterone, which regulates the reabsorption of sodium and chloride ions in the kidney tubules and
increases the loss of potassium ions. Aldosterone is secreted when blood sodium ion levels are too low to cause the kidney to retain
sodium ions. If sodium levels are elevated, aldosterone is not secreted, so that some sodium will be lost in the urine. Aldosterone
also controls swelling in the tissues.
Cortisol, the most important glucocortinoid, has the function of increasing glucose and glycogen concentrations in the body. These
reactions are completed in the liver by taking fatty acids from lipid storage cells and amino acids from body proteins to make
glucose and glycogen.
In addition, cortisol and its ketone derivative, cortisone, have the ability to inflammatory effects. Cortisone or similar synthetic
derivatives such as prednisolone are used to treat inflammatory diseases, rheumatoid arthritis, and bronchial asthma. There are
many side effects with the use of cortisone drugs, so there use must be monitored carefully.

Synthetic Steroids
In the hope of producing new drugs, thousands of steroid derivatives have been synthesized and test by pharmaceutical companies.
The two classes of synthetic steroids most commonly know by the public are oral contraceptives and anabolic steroids. Oral
contraceptives contain synthetic versions of the hormones estrogen (ethynylestradiol) and progestin (norethindrone). They prevent
pregnancy by interfering with ovulation, fertilization, and/or implantation of the fertilized egg. Anabolic steroids
(methandrostenolone) mimic the effects of natural testosterone.
OH OH OH
CH3 CH3 CH3
C CH C CH CH3
H H H CH3 H

H H H H H H
HO O O
Ethynylestradiol Norethindrone Methandrostenolone
(A synthetic estrogen) (A synthetic progestin) (A synthetic androgen)

 Exercise 7.8.1
The following molecule is cholic acid. Draw it showing the chair conformations. Determine if the three fused bonds have a cis
or trans configuration. Determine if the OH groups are axial or equatorial.

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Answer

 Exercise 7.8.2
Draw the following decalin molecules in chair conformations. Determine if the -CH3 groups are axial or equatorial.
a)

Answer
a)

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CHAPTER OVERVIEW

8: Introduction to Alkyl Halides, Alcohols, Ethers, Thiols, and Sulfides

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1
8.1: Alkyl Halides
A class of simple alkyl halides called chlorofluorocarbons (CFCs) was once very widely used in aerosol sprays and as refrigerants.
One such example is CCl F, or trichlorofluoromethane. Unfortunately, CFCs are harmful to the ozone layer of our upper
3

atmosphere. Ozone is critical in limiting the amount of damaging ultraviolet radiation that reaches the Earth. CFCs react with the
ozone and damage it, leaving the earth less protected.
Beginning in the late 1970s, ozone depletion was recognized as a significant environmental issue. The most dramatic decrease in
ozone occurs seasonally over the continent of Antarctica. The size and duration of the ozone hole steadily increased, with the
largest hole recorded in 2006. Fortunately, most countries have recognized the danger of CFCs and dramatically curtailed their use
in recent years. It is hoped that ozone depletion will slow, and that the ozone layer may eventually be restored to its earlier levels.

Alkyl Halides
An alkyl halide is an organic compound in which one or more halogen atoms are substituted for one or more hydrogen atoms in a
hydrocarbon. The general formulas for organic molecules with functional groups use the letter R to stand for the rest of the
molecule outside of the functional group. Because there are four possible halogen atoms (fluorine, chlorine, bromine, or iodine)
that can act as the functional group, we use the general formula R−X to represent an alkyl halide. The rules for naming simple
alkyl halides are listed below.
1. Name the parent compound by finding the longest continuous carbon atom chain that also contains the halogen. Add a prefix
for the particular halogen atom. The prefixes for each of the four halogens are fluoro-, chloro-, bromo-, and iodo-. If more than
one kind of halogen atom is present, put them in alphabetical order. If there is more than one of the same halogen on a given
carbon atom, use the prefixes di-, tri-, or tetra- before the prefix for the halogen.
2. As with hydrocarbons, number the carbon chain in a way that makes the sum of halogen numbers as low as possible. If different
halogens are in equivalent positions, give the lower number to the one that comes first in alphabetical order.
3. Add the numerical prefix into the name before the halogen prefix.
4. Separate numbers with commas, and separate numbers from names or prefixes with a hyphen. There are no spaces in the name.
Listed below are some examples of names and structural formulas of a few alkyl halides.

Note that for the structure based on methane, no number needs to be used, since there is only one carbon atom. In the third
example, the chloro- is listed first alphabetically and the chain is numbered so that the sum of the numbers is as low as possible.

Uses of Alkyl Halides

Alkyl halides are often used as synthetic intermediates in the laboratory. Although these compounds were once widely used as dry
cleaning solvents, coolants in refrigerators and air conditioners, and propellants in hairsprays and deodorants, increasing awareness
of their toxicity has led to a widespread decrease in applications for these materials. Some specific compounds are still used.
Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) is still used in some situations as an inhalation anesthetic. The compound DDT
is a very effective pesticide, but is only used when nothing else works, because of its harmful effects on the environment.

Summary
An alkyl halide is an organic compound in which one or more halogen atoms are substituted for one or more hydrogen atoms in
a hydrocarbon.
Alkyl halides are often used as synthetic intermediates in the laboratory.

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SECTION OVERVIEW

8.2: Haloalkanes
Topic hierarchy

8.2.1: Alkyl Halide Occurrence

The haloalkanes, also known as alkyl halides, are a group of chemical compounds comprised of an alkane with one or more
hydrogens replaced by a halogen atom (fluorine, chlorine, bromine, or iodine).
There is a fairly large distinction between the structural and physical properties of haloalkanes and the structural and physical
properties of alkanes. As mentioned above, the structural differences are due to the replacement of one or more hydrogens with a
halogen atom. The differences in physical properties are a result of factors such as electronegativity, bond length, bond strength,
and molecular size.

Halogens and the Character of the Carbon-Halogen Bond

With respect to electronegativity, halogens are more electronegative than carbons. This results in a carbon-halogen bond that is
polarized. As shown in the image below, carbon atom has a partial positive charge, while the halogen has a partial negative charge.

The following image shows the relationship between the halogens and electronegativity. Notice, as we move up the periodic table
from iodine to fluorine, electronegativity increases.

The following image shows the relationships between bond length, bond strength, and molecular size. As we progress down the
periodic table from fluorine to iodine, molecular size increases. As a result, we also see an increase in bond length. Conversely, as
molecular size increases and we get longer bonds, the strength of those bonds decreases.

Haloalkanes Have Higher Boiling Points than Alkanes

When comparing alkanes and haloalkanes, we will see that haloalkanes have higher boiling points than alkanes containing the same
number of carbons. London dispersion forces are the first of two types of forces that contribute to this physical property. You might
recall from general chemistry that London dispersion forces increase with molecular surface area. In comparing haloalkanes with
alkanes, haloalkanes exhibit an increase in surface area due to the substitution of a halogen for hydrogen. The incease in surface
area leads to an increase in London dispersion forces, which then results in a higher boiling point.
Dipole-dipole interaction is the second type of force that contributes to a higher boiling point. As you may recall, this type of
interaction is a coulombic attraction between the partial positive and partial negative charges that exist between carbon-halogen
bonds on separate haloalkane molecules. Similar to London dispersion forces, dipole-dipole interactions establish a higher boiling
point for haloalkanes in comparison to alkanes with the same number of carbons.

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The table below illustrates how boiling points are affected by some of these properties. Notice that the boiling point increases when
hydrogen is replaced by a halogen, a consequence of the increase in molecular size, as well as an increase in both London
dispersion forces and dipole-dipole attractions. The boiling point also increases as a result of increasing the size of the halogen, as
well as increasing the size of the carbon chain.

Contributors
Rachael Curtis (UC Davis)

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8.2.1: Alkyl Halide Occurrence
Halogen containing organic compounds are relatively rare in terrestrial plants and animals. The thyroid hormones T3 and T4 are
exceptions; as is fluoroacetate, the toxic agent in the South African shrub Dichapetalum cymosum, known as "gifblaar". However,
the halogen rich environment of the ocean has produced many interesting natural products incorporating large amounts of halogen.
Some examples are shown below. The ocean is the largest known source for atmospheric methyl bromide and methyl iodide.
Furthermore, the ocean is also estimated to supply 10-20% of atmospheric methyl chloride, with other significant contributions
coming from biomass burning, salt marshes and wood-rotting fungi. Many subsequent chemical and biological processes produce
poly-halogenated methanes.

Synthetic organic halogen compounds are readily available by direct halogenation of hydrocarbons and by addition reactions to
alkenes and alkynes. Many of these have proven useful as intermediates in traditional synthetic processes. Some halogen
compounds, shown in the box. have been used as pesticides, but their persistence in the environment, once applied, has led to
restrictions, including banning, of their use in developed countries. Because DDT is a cheap and effective mosquito control agent,
underdeveloped countries in Africa and Latin America have experienced a dramatic increase in malaria deaths following its
removal, and arguments are made for returning it to limited use. 2,4,5-T and 2,4-D are common herbicides that are sold by most
garden stores. Other organic halogen compounds that have been implicated in environmental damage include the polychloro- and
polybromo-biphenyls (PCBs and PBBs), used as heat transfer fluids and fire retardants; and freons (e.g. CCl2F2 and other
chlorofluorocarbons) used as refrigeration gases and fire extinguishing agents.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

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8.3: Nomenclature of Alcohols
In the IUPAC system of nomenclature, functional groups are normally designated in one of two ways. The presence of the function
may be indicated by a characteristic suffix and a location number. This is common for the carbon-carbon double and triple bonds
which have the respective suffixes -ene and -yne. Halogens, on the other hand, do not have a suffix and are named as substituents,
for example: (CH3)2C=CHCHClCH3 is 4-chloro-2-methyl-2-pentene.
Alcohols are usually named by the first procedure and are designated by an -ol suffix, as in ethanol, CH3CH2OH (note that a
locator number is unnecessary on a two-carbon chain). On longer chains the location of the hydroxyl group determines chain
numbering. For example: (CH3)2C=CHCH(OH)CH3 is 4-methyl-3-penten-2-ol. Other examples of IUPAC nomenclature are shown
below, together with the common names often used for some of the simpler compounds. For the mono-functional alcohols, this
common system consists of naming the alkyl group followed by the word alcohol. Alcohols may also be classified as primary, 1º,
secondary, 2º, and tertiary, 3º, in the same manner as alkyl halides. This terminology refers to alkyl substitution of the carbon atom
bearing the hydroxyl group (colored blue in the illustration).

Many functional groups have a characteristic suffix designator, and only one such suffix (other than "-ene" and "-yne") may be
used in a name. When the hydroxyl functional group is present together with a function of higher nomenclature priority, it must be
cited and located by the prefix hydroxy and an appropriate number. For example, lactic acid has the IUPAC name 2-
hydroxypropanoic acid.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

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8.3.1: Nomenclature of Alcohols
Alcohols are one of the most important functional groups in organic chemistry. Alcohols are a good source of reagents for synthesis
reactions. The ability to identify alcohols is important especially when looking at IR and NMR spectra. The alcohol signal is very
easy to spot on IR graphs, because they have a strong signal near the 3200 cm-1 region.

Introduction
The following is list of some common primary alcohols based on the IUPAC naming system.

Name Molecular Formula

Methanol (methyl alcohol) CH3OH

Ethanol (ethyl alcohol) C2H5OH
Propanol C3H7OH
Butanol C4H9OH
Pentanol C5H11OH
Hexanol C6H13OH
Heptanol C7H15OH
Octanol C8H17OH

Rules for naming the alcohols

1. Find the longest chain containing the hydroxy group (OH). If there is a chain with more carbons than the one containing the OH
group it will be named as a subsitutent.
2. Place the OH on the lowest possible number for the chain. With the exception of carbonyl groups such as ketones and
aldehydes, the alcohol or hydroxy groups have first priority for naming.
3. When naming a cyclic structure, the -OH is assumed to be on the first carbon unless the carbonyl group is present, in which
case the later will get priority at the first carbon.
4. When multiple -OH groups are on the cyclic structure, number the carbons on which the -OH groups reside.
5. Remove the final e from the parent alkane chain and add -ol. When multiple alcohols are present use di, tri, et.c before the ol,
after the parent name. ex. 2,3-hexandiol. If a carbonyl group is present, the -OH group is named with the prefix "hydroxy," with
the carbonyl group attached to the parent chain name so that it ends with -al or -one.

Examples
Ethane: CH3CH3 ----->Ethanol: (the alcohol found in beer, wine and other consumed sprits)

Secondary alcohol: 2-propanol

Other functional groups on an alcohol: 3-bromo-2-pentanol

Cyclic alcohol (two -OH groups): cyclohexan-1,4-diol

Other functional group on the cyclic structure: 3-hexeneol (the alkene is in bold and indicated by numbering the carbon
closest to the alcohol)

A complex alcohol: 4-ethyl-3hexanol (the parent chain is in red and the substituent is in blue)

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Outside Links
http://en.wikipedia.org/wiki/Alcohol#Simple_alcohols

References
Thurlow, K.J.. Chemical Nomenclature. Netherlands: Kluwer Academic Publishers, 1998.

Problems
Name the following alchols:
1.

Contributors
Abhiram Kondajji (UCD)

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8.4: Thiols (Mercaptans)
 Objectives

After completing this section, you should be able to

1. Nomenclature and Reactivity
a. write the IUPAC name of a thiol, given its Kekulé, condensed or shorthand structure.
b. draw the structure of a thiol, given its IUPAC name.
c. write an equation to represent the formation of a thiol by the reaction of hydrosulfide anion with an alkyl halide.
d. write an equation to illustrate the preparation of a thiol by the reaction of thiourea with an alkyl halide.
2. write an equation to show the interconversion between thiols and disulfides.
3. a. write the name of a sulfide, given its structure.
b. draw the structure of a sulfide, given its name.
c. write an equation showing how a sulfide may be prepared by the reaction of a thiolate anion on an alkyl halide.
d. identify the product from the reaction of a given alkyl halide with a given thiolate anion.
e. identify the reagents necessary to prepare a given sulfide.
f. write an equation to illustrate the formation of a trialkylsulfonium salt from a sulfide and an alkyl halide.

 Key Terms
disulfide
mercapto group
(organic) sulfide
sulfone
sulfoxide
thiol
thiolate anion
trialkylsulfonium ion (trialkylsulfonium salt)

 Study Notes
The chemistry of sulfur-containing organic compounds is often omitted from introductory organic chemistry courses. However,
we have included a short section on these compounds, not for the sake of increasing the amount of material to be digested, but
because much of the chemistry of these substances can be predicted from a knowledge of their oxygen-containing analogues. A
thiol is a compound which contains an SH functional group. The -SH group itself is called a mercapto group. A disulfide is a
compound containing an -S-S- linkage. (Organic) sulfides have the structure R-S-R′, and are therefore the sulfur analogues of
ethers. The nomenclature of sulfides can be easily understood if one understands the nomenclature of the corresponding ethers.
Notice that the term “thio” is also used in inorganic chemistry. For example, SO42− is the sulfate ion; while S2O32−, in which
one of the oxygen atoms of a sulfate ion has been replaced by a sulfur atom, is called thiosulfate. Thiolate anions, RS- , are
analogous to alkoxy anions, RO- . Thiolate anions are better nucleophiles than are alkoxy anions (see Section 11.5, pages 389-
394 of the textbook). If you have trouble understanding why trialkylsulfonium ions are formed, think of them as being
somewhat similar to the hydronium ions that are formed by protonating water:

Later we shall see examples of tetraalkylammonium ions, R4N+, which again may be regarded as being similar to hydronium
ions. sulfoxides and sulfones are obtained by oxidizing organic sulfides. You need not memorize the methods used to carry out
these oxidations.

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Table 18.1, below, provides a quick comparison of oxygen-containing and sulfur-containing organic compounds.

Oxidation States of Sulfur Compounds

Oxygen assumes only two oxidation states in its organic compounds (–1 in peroxides and –2 in other compounds). Sulfur, on the
other hand, is found in oxidation states ranging from –2 to +6, as shown in the following table (some simple inorganic compounds
are displayed in orange).

Thiols
Thiols, which are also called mercaptans, are analogous to alcohols. They are named in a similar fashion as alcohols except the
suffix -thiol is used in place of -ol. By itself the -SH group is called a mercapto group.

Thiols are usually prepared by using the hydrosulfide anion (-SH) as a neucleophile in an SN2 reaction with alkyl halides.

On problem with this reaction is that the thiol product can undergo a second SN2 reaction with an additional alkyl halide to produce
a sulfide side product. This problem can be solved by using thiourea, (NH2)2C=S, as the nucleophile. The reaction first produces an
alkyl isothiourea salt and an intermediate. This salt is then hydrolyzed by a reaction with aqueous base.

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Disulfides
Oxidation of thiols and other sulfur compounds changes the oxidation state of sulfur rather than carbon. We see some
representative sulfur oxidations in the following examples. In the first case, mild oxidation converts thiols to disufides. An
equivalent oxidation of alcohols to peroxides is not normally observed. The reasons for this different behavior are not hard to
identify. The S–S single bond is nearly twice as strong as the O–O bond in peroxides, and the O–H bond is more than 25 kcal/mole
stronger than an S–H bond. Thus, thermodynamics favors disulfide formation over peroxide.

Disulfide bridges in proteins

Disulfide (sulfur-sulfur) linkages between two cysteine residues are an integral component of the three-dimensional structure of
many proteins. The interconversion between thiols and disulfide groups is a redox reaction: the thiol is the reduced state, and the
disulfide is the oxidized state.

Notice that in the oxidized (disulfide) state, each sulfur atom has lost a bond to hydrogen and gained a bond to a sulfur - this is why
the disulfide state is considered to be oxidized relative to the thiol state.
The redox agent that mediates the formation and degradation of disulfide bridges in most proteins is glutathione, a versatile
coenzyme that we have met before in a different context (section 14.2A). Recall that the important functional group in glutathione
is the thiol, highlighted in blue in the figure below. In its reduced (free thiol) form, glutathione is abbreviated 'GSH'.

In its oxidized form, glutathione exists as a dimer of two molecules linked by a disulfide group, and is abbreviated 'GSSG'.
A new disulfide in a protein forms via a 'disulfide exchange' reaction with GSSH, a process that can be described as a combination
of two SN2-like attacks. The end result is that a new cysteine-cysteine disulfide forms at the expense of the disulfide in GSSG.

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In its reduced (thiol) state, glutathione can reduce disulfides bridges in proteins through the reverse of the above reaction.
Disulfide bridges exist for the most part only in proteins that are located outside the cell. Inside the cell, cysteines are kept in their
reduced (free thiol) state by a high intracellular concentration of GSH, which in turn is kept in a reduced state (ie. GSH rather than
GSSG) by a flavin-dependent enzyme called glutathione reductase.
Disulfide bridges in proteins can also be directly reduced by another flavin-dependent enzyme called 'thioredoxin'. In both cases,
NADPH is the ultimate electron donor, reducing FAD back to FADH2 in each catalytic cycle.
In the biochemistry lab, proteins are often maintained in their reduced (free thiol) state by incubation in buffer containing an excess
concentration of b-mercaptoethanol (BME) or dithiothreitol (DTT). These reducing agents function in a manner similar to that of
GSH, except that DTT, because it has two thiol groups, forms an intramolecular disulfide in its oxidized form.

Sulfides
Sulfur analogs of ethers are called sulfides. The chemical behavior of sulfides contrasts with that of ethers in some important ways.
Since hydrogen sulfide (H2S) is a much stronger acid than water (by more than ten million fold), we expect, and find, thiols to be
stronger acids than equivalent alcohols and phenols. Thiolate conjugate bases are easily formed, and have proven to be excellent
nucleophiles in SN2 reactions of alkyl halides and tosylates.
R–S(–) Na(+) + (CH3)2CH–Br (CH3)2CH–S–R + Na(+) Br(–)
Although the basicity of ethers is roughly a hundred times greater than that of equivalent sulfides, the nucleophilicity of sulfur is
much greater than that of oxygen, leading to a number of interesting and useful electrophilic substitutions of sulfur that are not
normally observed for oxygen. Sulfides, for example, react with alkyl halides to give ternary sulfonium salts (equation # 1) in the
same manner that 3º-amines are alkylated to quaternary ammonium salts. Although equivalent oxonium salts of ethers are known,
they are only prepared under extreme conditions, and are exceptionally reactive.

sulfides are named using the same rules as ethers except sulfide is used in the place of ether. For more complex substance alkylthio
is used instead of alkoxy.

SAM methyltransferases
The most common example of sulfonium ions in a living organism is the reaction of S-Adenosylmethionine. Some of the most
important examples of SN2 reactions in biochemistry are those catalyzed by S-adenosyl methionine (SAM) – dependent

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methyltransferase enzymes. We have already seen, in chapter 6 and again in chapter 8, how a methyl group is transferred in an SN2
reaction from SAM to the amine group on the nucleotide base adenosine:

(Nucleic Acids Res. 2000, 28, 3950).

Another SAM-dependent methylation reaction is catalyzed by an enzyme called catechol-O-methyltransferase. The substrate here
is epinephrine, also known as adrenaline.

Notice that in this example, the attacking nucleophile is an alcohol rather than an amine (that’s why the enzyme is called an O-
methyltransferase). In both cases, though, a basic amino acid side chain is positioned in the active site in just the right place to
deprotonate the nucleophilic group as it attacks, increasing its nucleophilicity. The electrophile in both reactions is a methyl carbon,
so there is little steric hindrance to slow down the nucleophilic attack. The methyl carbon is electrophilic because it is bonded to a
positively-charged sulfur, which is a powerful electron withdrawing group. The positive charge on the sulfur also makes it an
excellent leaving group, as the resulting product will be a neutral and very stable sulfide. All in all, in both reactions we have a
reasonably good nucleophile, an electron-poor, unhindered electrophile, and an excellent leaving group.
Because the electrophilic carbon in these reactions is a methyl carbon, a stepwise SN1-like mechanism is extremely unlikely: a
methyl carbocation is very high in energy and thus is not a reasonable intermediate to propose. We can confidently predict that this
reaction is SN2. Does this SN2 reaction occur, as expected, with inversion of stereochemistry? Of course, the electrophilic methyl
carbon in these reactions is achiral, so inversion is not apparent. To demonstrate inversion, the following experiment has been
carried out with catechol-O-methyltransferase:

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Here, the methyl group of SAM was made to be chiral by incorporating hydrogen isotopes tritium (3H, T) and deuterium (2H, D).
The researchers determined that the reaction occurred with inversion of configuration, as expected for an SN2 displacement (J.
Biol. Chem. 1980, 255, 9124).
Sulfides can be easily oxidized. Reacting a sulfide with hydrogen peroxide, H2O2, as room termpeature produces a sulfoxide
(R2SO). The oxidation can be continued by reaction with a peroxyacid to produce the sulfone (R2SO2)

A common example of a sulfoxide is the solvent dimethyl sulfoxide (DMSO). DMSO is polar aprotic solvent.

Figure AB16.3. DMSO is a very polar, aprotic solvent.

Contributors
Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)

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Thiols and Sulfides is licensed CC BY-NC-SA 4.0.

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8.5: Nomenclature of Ethers
Ethers are compounds having two alkyl or aryl groups bonded to an oxygen atom, as in the formula R1–O–R2. The ether functional
group does not have a characteristic IUPAC nomenclature suffix, so it is necessary to designate it as a substituent. To do so the
common alkoxy substituents are given names derived from their alkyl component (below):

Alkyl Group Name Alkoxy Group Name

CH3– Methyl CH3O– Methoxy

CH3CH2– Ethyl CH3CH2O– Ethoxy

(CH3)2CH– Isopropyl (CH3)2CHO– Isopropoxy

(CH3)3C– tert-Butyl (CH3)3CO– tert-Butoxy

C6H5– Phenyl C6H5O– Phenoxy

Ethers can be named by naming each of the two carbon groups as a separate word followed by a space and the word ether. The -OR
group can also be named as a substituent using the group name, alkox

 Example 8.5.1
CH3-CH2-O-CH3 is called ethyl methyl ether or methoxyethane.

The smaller, shorter alkyl group becomes the alkoxy substituent. The larger, longer alkyl group side becomes the alkane base name.
Each alkyl group on each side of the oxygen is numbered separately. The numbering priority is given to the carbon closest to the
oxgen. The alkoxy side (shorter side) has an "-oxy" ending with its corresponding alkyl group. For example, CH3CH2CH2CH2CH2-
O-CH2CH2CH3 is 1-propoxypentane. If there is cis or trans stereochemistry, the same rule still applies.

 Examples 8.5.2
C H3 C H2 OC H2 C H3 , diethyl ether (sometimes referred to as just ether)
C H3 OC H2 C H2 OC H3 , ethylene glycol dimethyl ether (glyme).

 Exercises 8.5.2

Try to name the following compounds using these conventions:

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Try to draw structures for the following compounds:
2-pentyl 1-propyl ether J
1-(2-propoxy)cyclopentene J

Common names
Simple ethers are given common names in which the alkyl groups bonded to the oxygen are named in alphabetical order followed
by the word "ether". The top left example shows the common name in blue under the IUPAC name. Many simple ethers are
symmetrical, in that the two alkyl substituents are the same. These are named as "dialkyl ethers".
anisole (try naming anisole by the other two conventions. J )

oxirane

1,2-epoxyethane, ethylene oxide, dimethylene oxide, oxacyclopropane,

furan (this compound is aromatic)

tetrahydrofuran

oxacyclopentane, 1,4-epoxybutane, tetramethylene oxide,

dioxane

1,4-dioxacyclohexane

 Exercise 8.5.2

Try to draw structures for the following compounds-

3-bromoanisole J
2-methyloxirane J
3-ethylfuran J

Heterocycles
In cyclic ethers (heterocycles), one or more carbons are replaced with oxygen. Often, it's called heteroatoms, when carbon is
replaced by an oxygen or any atom other than carbon or hydrogen. In this case, the stem is called the oxacycloalkane, where the
prefix "oxa-" is an indicator of the replacement of the carbon by an oxygen in the ring. These compounds are numbered starting at
the oxygen and continues around the ring. For example,

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If a substituent is an alcohol, the alcohol has higher priority. However, if a substituent is a halide, ether has higher priority. If there
is both an alcohol group and a halide, alcohol has higher priority. The numbering begins with the end that is closest to the higher
priority substituent. There are ethers that are contain multiple ether groups that are called cyclic polyethers or crown ethers. These
are also named using the IUPAC system.

Sulfides
Sulfur analogs of ethers (R–S–R') are called sulfides, e.g., (CH3)3C–S–CH3 is tert-butyl methyl sulfide. Sulfides are chemically
more reactive than ethers, reflecting the greater nucleophilicity of sulfur relative to oxygen.

References
1. Schore, Neil E. and Vollhardt, K. Peter C. Organic Chemistry: Structure and Function. New York: Bleyer, Brennan, 2007.
2. Winter, Arthur. Organic Chemistry for Dummies. Hoboken, New Jersey: Wiley, 2005.
3. Pellegrini, Frank. Cliffs QuickReview Organic Chemistry II. Foster City, CA: Wiley, 2000

Problems
Name the following ethers:

(Answers to problems above: 1. diethyl ether; 2. 2-ethoxy-2-methyl-1-propane; 3. cis-1-ethoxy-2-methoxycyclopentane; 4. 1-

ethoxy-1-methylcyclohexane; 5. oxacyclopropane; 6. 2,2-Dimethyloxacyclopropane)

 Exercise 8.5.3
What would you call

(CC-BY; Dan Johnson via Twitter)

Answer
A one-eyed one-horned flying propyl people ether

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Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Richard Banks (Boise State University)

8.5: Nomenclature of Ethers is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Nomenclature of Ethers by William Reusch is licensed CC BY-NC-SA 4.0.

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8.6: Solvents
Solvents
Introduction
The vast majority of chemical reactions are performed in solution. The solvent fulfills several functions during a chemical reaction. It solvates the reactants
and reagents so that they dissolve. This facilitates collisions between the reactant(s) and reagents that must occur in order to transform the reactant(s) to
product(s). The solvent also provides a means of temperature control, either to increase the energy of the colliding particles so that they will react more
quickly, or to absorb heat that is generated during an exothermic reaction. The selection of an appropriate solvent is guided by theory and experience.
Generally a good solvent should meet the following criteria.
It should be inert to the reaction conditions.
It should dissolve the reactants and reagents.
It should have an appropriate boiling point.
It should be easily removed at the end of the reaction.
The second criterion invokes the adage "Like dissolves like". Non-polar reactants will dissolve in non-polar solvents. Polar reactants will dissolve in polar
solvents. For our purposes there are three measures of the polarity of a solvent:
1. Dipole moment
2. Dielectric constant
3. Miscibility with water
Molecules with large dipole moments and high dielectric constants are considered polar. Those with low dipole moments and small dielectric constants are
classified as non-polar. On an operational basis, solvents that are miscible with water are polar, while those that are not are non-polar; remember the saying
"Oil and water don't mix".
Chemists have classified solvents into three categories according to their polarity.
1. polar protic
2. dipolar aprotic
3. non-polar.

Polar Protic Solvents

Let's start with the meaning of the adjective protic. In the context used here, protic refers to a hydrogen atom attached to an electronegative atom. For our
purposes that electronegative atom is almost exclusively oxygen. In other words, polar protic solvents are compounds that can be represented by the general
formula ROH. The polarity of the polar protic solvents stems from the bond dipole of the O−H bond. The large difference in electronegativities of the
oxygen and the hydrogen atom, combined with the small size of the hydrogen atom, warrant separating molecules that contain an OH group from those
polar compounds that do not. Examples of polar protic solvents are water (HOH ), methanol (CH OH ), and acetic acid (CH CO H ).
3 3 2

Dipolar Aprotic Solvents

Here the key word is aprotic. In the context used here, aprotic describes a molecule that does not contain an O−H bond. Solvents in this class all contain a
bond that has a large bond dipole. Typically this bond is a multiple bond between carbon and either oxygen or nitrogen. Most dipolar aprotic solvents
contain a C−O double bond. Examples are acetone, (CH ) C=O, and ethyl acetate, CH CO CH CH .
3 2 3 2 2 3

Non-Polar Solvents
Non-polar solvents are compounds that have low dielectric constants and are not miscible with water. Examples include benzene (ceC 6H 6), carbon
tetrachloride (CCl ), and diethyl ether (CH CH OCH CH ).
4 3 2 2 3

Table 1 presents a list of solvents that are commonly used in chemical reactions. The boiling point, dipole moment, and dielectric constant of each solvent
is included. All of these solvents are clear, colorless liquids. The hydrogen atoms of the protic solvents are highlighted in red.
Click on the name of a solvent in Table 1 to load a model of it from the MO menu of the JSMol VMK. Then, use the Model Tools to get a sense of the
compound's polarity by loading partial charge information and/or the electrostatic potential map for the solvent in question.

Name Structure bp, oC dipole moment dielectric constant

water HO−H 100 1.85 80

methanol CH O−H
3
68 1.70 33

ethanol CH CH O−H
3 2
78 1.69 24.3

1-propanol CH CH CH O−H
3 2 2
97 1.68 20.1

1-butanol CH CH CH CH O−H
3 2 2 2
118 1.66 17.8

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formic acid formic acid 100 1.41 58

acetic acid acetic acid 118 1.74 6.15

formamide formamide 210 3.73 109

.... .... .... .... ....

acetone acetone 56 2.88 20.7

tetrahydrofuran THF 66 1.63 7.52

2-butanone (MEK) MEK 80 2.78 18.5

ethyl acetate ethyl acetate 78 1.78 6.02

acetonitrile H C−C≡N
3
81 3.92 36.6

dimethyl formamide (DMF) DMF 153 3.82 38.3

dimethyl sulfoxide (DMSO) DMSO 189 3.96 47.2

.... .... .... .... ....

hexane CH ( CH ) CH
3 2 4 3
69 ---- 2.02

benzene benzene 80 0 2.28

diethyl ether CH CH OCH CH

3 2 2 3
35 1.15 4.34

methylene chloride CH Cl
2 2
40 1.60 9.08

carbon tetrachloride CCl

4
76 0 2.24

Table 1: Common Solvents for Organic Reactions

It should be apparent from the table that there are no sharp boundaries between polar and non-polar solvents, at least if you use dielectric constants or
dipole moments as a measure. There is, however, a correlation between chemical structure and dielectric constant that provides a useful way to think about
polarity. Look at the series of polar protic compounds water, methanol, ethanol, 1-propanol, and 1-butanol. As Figure 1 demonstrates, each compound in
the series differs from the ones before and after it by one CH group. 2

Figure 1: Structure-Property Correlations

As the number of CH groups in ROH increases, the dielectric constant decreases. If you think of these molecules as containing a polar component (OH)
2

and a non-polar component (R), then the polarity of a compound reflects the balance between these two components. As the relative amount of
hydrocarbon character increases, the polarity decreases. Note that hexane, which is 100% hydrocarbon, is the least polar solvent in the table.

Exercise 1 Classify each of the following solvents as polar protic (P) , dipolar aprotic (D) , or non-polar (N) by entering the appropriate letter in the text
field next to each structure.

CHCl C H Cl HCO CH CH
3 6 5 2 2 3

HFA HFIPA HMPA

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dioxane NH NH TFAA
2 2

CF CO H C H CH CH CH CN
3 2 6 5 3 3 2

Now that we've looked at the various types of solvents that you can expect to see, let's examine how those solvents interact with solutes.

Contributors
Otis Rothenberger (Illinois State University) and Thomas Newton University of Southern Maine)

8.6: Solvents is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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8.6.1: Boiling Points
Correlating Polarity and Physical Properties: Boiling Points
Introduction
Understanding the nature of intermolecular interactions enables us to understand many chemical and physical phenomena. In fact,
it was the investigation of such phenomena that led to our understanding of intermolecular interactions in the first place. In the
discussion that follows, we will refer to Coulomb's law several times, so it may be worthwhile to review the mathematical
statement of that law:
Coulomb's Law
q q
1 2
Fc ∝ 2
r

In terms of intermolecular interactions, the law says that the force of attraction between two molecules increases as the distance
between them decreases. It also states that the force of attraction increases as the magnitude of the opposite charges increase.

Boiling Points
In the gas phase, the distance between molecules is large in comparison to the size of the molecules. Since the distance is very
large, Coulomb's law tells us that the force of attraction between the molecules is very small. In gases it is essentially zero.
In the liquid state, the separation between molecules is much smaller, and the interactions between them much larger than in the gas
phase. The boiling point of a liquid is a measure of the amount of energy required to overcome these intermolecular Coulombic
attractions. Let's compare the boiling points of three small molecules, dihydrogen, methane and water. Dihydrogen boils at -259oC,
methane boils at -164oC, water at +100oC. Obviously the intermolecular forces holding water molecules together are much stronger
than those holding dihydrogen or methane molecules together. If we assume that in the liquid phase the intermolecular distances are
about the same for all three molecules, then it must be differences in the values of q1 and q2 that are responsible for the differences
in boiling points. It is important to remember that in this situation q1 and q2 are the charges associated with the bond dipoles. Figure
1 serves as a reminder of the interactions that we are considering. Here X represents any atom or group and the dashed red lines
indicate the Coulombic attractions between opposite charges.

Figure 1: Even Partial Charges Attract

Let's compare water and methane first. Because oxygen is more electronegative than carbon, an O−H bond has a larger bond
dipole than a C−H bond. Hence the force of attraction between two water molecules is greater than it is between two methane
molecules. Water has the higher boiling point.
Now let's compare methane and dihydrogen. We could invoke the same argument here that we did in comparing methane and
water. The C−H bond has a larger bond dipole than the H−H bond. Therefore, methane has the higher boiling point. The real
question is why does dihydrogen become a liquid at any temperature? It has no permanent bond dipole, so the values of q1 and q2
should be zero, and the force of attraction between dihydrogen molecules should also be zero. The key word here is permanent. As
we have seen, the motion of the electrons in the H-H bond induces transient dipoles. The distortion of the electron distribution in
one molecule of dihydrogen induces complementary distortions in other , nearby dihydrogen molecules. It is this fleeting
development of charge that we call upon to rationalize the fact that dihydrogen does finally liquefy at -259oC.
Finally, let's consider the boiling points of a series of alkanes and a comparable series of alcohols. Figure 2 presents plots of the
boiling points of a homologous series of linear alkanes and linear alcohols.

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Figure 2: Comin' to a Boil
There are several trends in this figure that are noteworthy.
First, it's obvious that alcohols have higher boiling points than alkanes of comparable size.
Second, the differences in boiling points become smaller as n increases. (When n = 1, the difference in boiling points is 156oC.
When n = 10, the difference is 26 oC.)
Third, in both series, the boiling points increase as n increases.

Exercise 1 What factor is responsible for the first trend?

Figure 3 offers a pictorial rationalization of the correlation between boiling points and n.

Figure 3: Touch Me, Touch Me

Here the dashed red lines represent the induced dipole-induced dipole interactions between molecules. The more interactions, the
higher the boiling point.
Finally, it's important to understand that the different types of interactions we have been discussing are not mutually exclusive. It is
possible to have several types of intermolecular interactions occuring simultaneously. In discussing the solubility of 1-bromobutane
in ethanol, we alluded to the idea that there were intermolecular forces in addition to dipole-dipole interactions. Figure 4 illustrates
the idea.

Figure 4: Different Strokes

Here the narrow dashed red lines represent induced dipole-induced dipole interactions, while the broad dashed lines highlight the
stronger dipole-dipole interactions.

Contributors
Otis Rothenberger (Illinois State University) and Thomas Newton University of Southern Maine)

8.6.1: Boiling Points is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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8.6.2: Solvent-Solutes
Solvent-Solute Interactions
Introduction
Now that you understand how chemists classify solvents, it's time to consider a similar classification system for the compounds that
dissolve in them, i.e. for solutes. At the risk of oversimplifying, we will divide solutes into 3 groups:
1. ionic
2. polar covalent
3. non-polar covalent
We will use the adage "like dissolves like" as our guide to understanding the forces that enable a solute to dissolve in a solvent.
Remember that this adage is really a variation on the statement of Coulomb's law that says "opposite charges attract". The force of
attraction depends upon the nature of the solvent and the nature of the solute. We will look at four types of interactions:
charge-dipole
dipole-dipole
dipole-induced dipole
induced dipole-induced dipole
It is important here to distinguish between intermolecular interactions and the intramolecular interactions that we call covalent
bonding. The strengths of covalent sigma bonds range from a low of about 50 kcal/mol to a high of around 125 kcal/mol. The
interactive forces described below range from 2-10 kcal/mol. Because they are so much less than typical covalent bonding forces,
these interactions are sometimes called secondary bonding interactions.

Charge-Dipole Interactions
This is the classic case of an ionic salt such as sodium chloride dissolving in water. Figure 1 presents a picture of the Coulombic
interactions between a positively charged sodium ion and 6 water molecules as well as the corresponding interactions between a
negatively charged chloride ion and 6 other water molecules. In the case of the sodium ion, the positive charge attracts the negative
end of each water molecule's dipole. The negative charge of the chloride ion attracts the positive end of the O−H bond dipole. The
straight dashed lines indicate these charge-dipole interactions. Each ion is encased in a shell of water molecules. The shells insulate
the ions from each other, allowing the oppositely charged particles to separate. Molecules that have high dielectric constants are
good electrical insulators because of their ability to shield the oppositely charged ions in this way.

Figure 1: You're All Wet

The image of solutes surrounded by solvents is a useful one to keep in mind. However, it does not lend itself to a compact
representation of intermolecular interactions. We'll use an alternative notation to depict dipole-dipole interactions.

Dipole-Dipole Interactions
Equation 1 describes the dehydrobromination of 1-bromobutane, a classic example of a 1,2-elimination reaction.
CH CH CH CH Br + KOH ⟶ CH CH CH=CH + KBr + H O(1)
3 2 2 2 3 2 2 2

As an experimentalist you would have to select an appropriate solvent for this reaction. Considering only solubility for the moment,
you would want a solvent in which both the 1-bromobutane and the KOH would dissolve. While KOH is very soluble in water, 1-
bromobutane is not. Conversely, while 1-bromobutane will dissolve in hexane, KOH is completely insoluble. What's needed is a
solvent that has just the right balance of polar and non-polar character. In fact, both methanol and ethanol are suitable choices.
Figure 2 uses the δ+-δ- notation to focus on the Coulombic attraction between the C−Br bond dipole of 1-bromobutane and the
H−O bond dipole of an ethanol molecule. Because the opposite charges that are attracting each other are only partial charges,

dipole-dipole interactions are inherently weaker than charge-dipole interactions.

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Figure 2: Dipole-Dipole Interactions
When one of the bonds involved in a dipole-dipole interaction is an O−H bond, the interaction is given the special, but common,
designation hydrogen bonding.
As we'll see shortly, there are additional intermolecular interactions between these two molecules. Before we look at them,
however, we're going to consider intermolecular forces that are even weaker than dipole-dipole interactions.

Dipole-Induced Dipole Interactions

Polar protic and dipolar aprotic molecules both have permanent bond dipoles. Non-polar molecules do not, or if they do, their
dipole moments are very small. However, when a molecule with a permanent bond dipole comes close to one with no bond dipole,
the electric field associated with the permanent dipole can temporarily distort the electron distribution in the non-polar molecule,
thereby inducing a temporary bond dipole. This concept is animated in Figure 3.
DipoleInuced

Figure 3: Try To See Things My Way

Dipole-induced dipole interactions are invoked when a non-polar molecule dissolves in a polar or a dipolar solvent. The
assumption is that the solute dissolves because the forces of attraction between the solvent and the solute are stronger than the
intermolecular forces holding the non-polar solute molecule together. The interactions between non-polar molecules are the
weakest secondary bonding forces we will consider. They are called induced dipole-induced dipole interactions or London forces.

Induced Dipole-Induced Dipole Interactions

Imagine that you have a camera with macro lens that allows you to see electrons and a shutter speed so fast it can freeze their
motion. If you were to take a series of slides of the electrons in dihydrogen, each slide would be different because each picture
would catch the electrons at different positions between the hydrogen nuclei. If you superimposed the slides, the composite image
would show that electron distribution between the two nuclei was symmetrical, i.e. that dihydrogen is non-polar. However, each
individual slide would reveal the electron distribution between the nuclei was not symmetrical. In other words, there is an
instantaneous dipole moment induced by the movement of the electrons. Furthermore, the induced dipole in one molecule
influences the electron distribution in other, nearby molecules. This is called an induced dipole-induced dipole interaction. Figure 4
simulates this process.
LondonForces

Figure 4: Dance with Me Henry

Since these induced dipoles are transient, the intermolecular interactions between them, the London forces, are very weak.
Chemists invoke these very weak forces to rationalize the interactions between non-polar molecules. We'll see an example of that
when we discuss the relationship between intermolecular interactions and boiling points.

Contributors
Otis Rothenberger (Illinois State University) and Thomas Newton University of Southern Maine)

8.6.2: Solvent-Solutes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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8.7: Acidity of Alcohols and Phenols
Overview - Aqueous vs Organic Solvents
In aqueous solutions, phenols are weakly acidic and lower the pH of a solution. Sodium hydroxide can be used to fully deprotonate
a phenol. Water soluble alcohols do not change the pH of the solution and are considered neutral. Aqueous solutions of sodium
hydroxide can NOT deprotonate alcohols to a high enough concentration to be synthetically useful.
In solutions of organic solvents, more extreme reaction conditions can be created. Sodium metal can be added to an alcohol in an
organic solvent system to fully deprotonate the alcohol to form alkoxide ions.

Acidity of Alcohols
Several important chemical reactions of alcohols involving the O-H bond or oxygen-hydrogen bond only and leave the carbon-
oxygen bond intact. An important example is salt formation with acids and bases. Alcohols, like water, are both weak bases and
weak acids. The acid ionization constant (Ka) of ethanol is about 10~18, slightly less than that of water. Ethanol can be converted
to its conjugate base by the conjugate base of a weaker acid such as ammonia {Ka — 10~35), or hydrogen (Ka ~ 10-38). It is
convenient to employ sodium metal or sodium hydride, which react vigorously but controllably with alcohols:

The order of acidity of various liquid alcohols generally is water > primary > secondary > tertiary ROH. By this we mean that the
equilibrium position for the proton-transfer reaction lies more on the side of ROH as R is changed from primary to secondary to
tertiary; therefore, tert-butyl alcohol is considered less acidic than ethanol:
− −
ROH + OH ⇌ RO + H OH (8.7.1)

However, in the gas phase the order of acidity is reversed, and the equilibrium position for lies increasingly on the side of the
alkoxide as R is changed from primary to secondary to tertiary, tert-butyl alcohol is therefore more acidic than ethanol in the gas
phase. This seeming contradiction appears more reasonable when one considers what effect solvation (or the lack of it) has on
equilibria. In solution, the larger alkoxide ions, probably are less well solvated than the smaller ions, because fewer solvent
molecules can be accommodated around the negatively charged oxygen in the larger ions:

Acidity of alcohols therefore decreases as the size of the conjugate base increases. However, “naked” gaseous ions are more stable
the larger the associated R groups, probably because the larger R groups can stabilize the charge on the oxygen atom better than the
smaller R groups. They do this by polarization of their bonding electrons, and the bigger the group, the more polarizable it is.

Basicity of Alcohols
Alcohols are bases similar in strength to water and accept protons from strong acids. An example is the reaction of methanol with
hydrogen bromide to give methyloxonium bromide, which is analogous to the formation of hydroxonium bromide with hydrogen
bromide and water:

Acidity of Phenol
Compounds like alcohols and phenol which contain an -OH group attached to a hydrocarbon are very weak acids. Alcohols are so
weakly acidic that, for normal lab purposes, their acidity can be virtually ignored. However, phenol is sufficiently acidic for it to

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have recognizably acidic properties - even if it is still a very weak acid. A hydrogen ion can break away from the -OH group and
transfer to a base. For example, in solution in water:

Phenol is a very weak acid and the position of equilibrium lies well to the left. Phenol can lose a hydrogen ion because the
phenoxide ion formed is stabilised to some extent. The negative charge on the oxygen atom is delocalised around the ring. The
more stable the ion is, the more likely it is to form. One of the lone pairs on the oxygen atom overlaps with the delocalised
electrons on the benzene ring.

This overlap leads to a delocalization which extends from the ring out over the oxygen atom. As a result, the negative charge is no
longer entirely localized on the oxygen, but is spread out around the whole ion.

Spreading the charge around makes the ion more stable than it would be if all the charge remained on the oxygen. However,
oxygen is the most electronegative element in the ion and the delocalized electrons will be drawn towards it. That means that there
will still be a lot of charge around the oxygen which will tend to attract the hydrogen ion back again. That is why phenol is only a
very weak acid.
Why is phenol a much stronger acid than cyclohexanol? To answer this question we must evaluate the manner in which an oxygen
substituent interacts with the benzene ring. As noted in our earlier treatment of electrophilic aromatic substitution reactions, an
oxygen substituent enhances the reactivity of the ring and favors electrophile attack at ortho and para sites. It was proposed that
resonance delocalization of an oxygen non-bonded electron pair into the pi-electron system of the aromatic ring was responsible for
this substituent effect. A similar set of resonance structures for the phenolate anion conjugate base appears below the phenol
structures.
The resonance stabilization in these two cases is very different. An important principle of resonance is that charge separation
diminishes the importance of canonical contributors to the resonance hybrid and reduces the overall stabilization. The contributing
structures to the phenol hybrid all suffer charge separation, resulting in very modest stabilization of this compound. On the other
hand, the phenolate anion is already charged, and the canonical contributors act to disperse the charge, resulting in a substantial
stabilization of this species. The conjugate bases of simple alcohols are not stabilized by charge delocalization, so the acidity of
these compounds is similar to that of water. An energy diagram showing the effect of resonance on cyclohexanol and phenol
acidities is shown on the right. Since the resonance stabilization of the phenolate conjugate base is much greater than the
stabilization of phenol itself, the acidity of phenol relative to cyclohexanol is increased. Supporting evidence that the phenolate
negative charge is delocalized on the ortho and para carbons of the benzene ring comes from the influence of electron-withdrawing
substituents at those sites.

In this reaction, the hydrogen ion has been removed by the strongly basic hydroxide ion in the sodium hydroxide solution.

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Acids react with the more reactive metals to give hydrogen gas. Phenol is no exception - the only difference is the slow reaction
because phenol is such a weak acid. Phenol is warmed in a dry tube until it is molten, and a small piece of sodium added. There is
some fizzing as hydrogen gas is given off. The mixture left in the tube will contain sodium phenoxide.

Acidity of Substituted Phenols

Substitution of the hydroxyl hydrogen atom is even more facile with phenols, which are roughly a million times more acidic than
equivalent alcohols. This phenolic acidity is further enhanced by electron-withdrawing substituents ortho and para to the hydroxyl
group, as displayed in the following diagram. The alcohol cyclohexanol is shown for reference at the top left. It is noteworthy that
the influence of a nitro substituent is over ten times stronger in the para-location than it is meta, despite the fact that the latter
position is closer to the hydroxyl group. Furthermore additional nitro groups have an additive influence if they are positioned in
ortho or para locations. The trinitro compound shown at the lower right is a very strong acid called picric acid.

Comparing the Acidity of Alcohols with Phenols

Why is phenol a much stronger acid than cyclohexanol? To answer this question we must evaluate the manner in which an oxygen
substituent interacts with the benzene ring. As noted in our earlier treatment of electrophilic aromatic substitution reactions, an
oxygen substituent enhances the reactivity of the ring and favors electrophile attack at ortho and para sites. It was proposed that
resonance delocalization of an oxygen non-bonded electron pair into the pi-electron system of the aromatic ring was responsible for
this substituent effect. Formulas illustrating this electron delocalization will be displayed when the "Resonance Structures" button
beneath the previous diagram is clicked. A similar set of resonance structures for the phenolate anion conjugate base appears below
the phenol structures.

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The resonance stabilization in these two cases is very different. An important principle of resonance is that charge separation
diminishes the importance of canonical contributors to the resonance hybrid and reduces the overall stabilization. The contributing
structures to the phenol hybrid all suffer charge separation, resulting in very modest stabilization of this compound. On the other
hand, the phenolate anion is already charged, and the canonical contributors act to disperse the charge, resulting in a substantial
stabilization of this species. The conjugate bases of simple alcohols are not stabilized by charge delocalization, so the acidity of
these compounds is similar to that of water. An energy diagram showing the effect of resonance on cyclohexanol and phenol
acidities is shown on the right. Since the resonance stabilization of the phenolate conjugate base is much greater than the
stabilization of phenol itself, the acidity of phenol relative to cyclohexanol is increased. Supporting evidence that the phenolate
negative charge is delocalized on the ortho and para carbons of the benzene ring comes from the influence of electron-withdrawing
substituents at those sites.

Exercise
9. Arrange the following compounds in order of decreasing acidity when they are in solution.

10. Specify the base needed to deprotonate each reactant.

Answer
9. B > C > A
10. a) Na or NaH or NNH2
b) NaOH or KOH or LiOH

Contributors
Prof. Steven Farmer (Sonoma State University)
Jim Clark (Chemguide.co.uk)
John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. ,
Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission
for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any
format."

8.7: Acidity of Alcohols and Phenols is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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8.8: Grignard and Organolithium Reagents
The alkali metals (Li, Na, K etc.) and the alkaline earth metals (Mg and Ca, together with Zn) are good reducing agents, the former
being stronger than the latter. These same metals reduce the carbon-halogen bonds of alkyl halides. The halogen is converted to a
halide anion, and the carbon bonds to the metal which has characteristics similar to a carbanion (R:-).

Formation of Organometallic Reagents

Many organometallic reagents are commercially available, however, it is often necessary to make then. The following equations
illustrate these reactions for the commonly used metals lithium and magnesium (R may be hydrogen or alkyl groups in any
combination).
An Alkyl Lithium Reagent

R C−X + 2 Li → R C−Li + LiX (8.8.1)

3 3

A Grignard Regent

R C−X + Mg → R C−MgX (8.8.2)

3 3

Halide reactivity in these reactions increases in the order: Cl < Br < I and Fluorides are usually not used. The alkyl magnesium
halides described in the second reaction are called Grignard Reagents after the French chemist, Victor Grignard, who discovered
them and received the Nobel prize in 1912 for this work. The other metals mentioned above react in a similar manner, but Grignard
and Alky Lithium Reagents most widely used. Although the formulas drawn here for the alkyl lithium and Grignard reagents
reflect the stoichiometry of the reactions and are widely used in the chemical literature, they do not accurately depict the structural
nature of these remarkable substances. Mixtures of polymeric and other associated and complexed species are in equilibrium under
the conditions normally used for their preparation.
A suitable solvent must be used. For alkyl lithium formation pentane or hexane are usually used. Diethyl ether can also be used but
the subsequent alkyl lithium reagent must be used immediately after preparation due to an interaction with the solvent. Ethyl ether
or THF are essential for Grignard reagent formation. Lone pair electrons from two ether molecules form a complex with the
magnesium in the Grignard reagent (As pictured below). This complex helps stabilize the organometallic and increases its ability to
react.

These reactions are obviously substitution reactions, but they cannot be classified as nucleophilic substitutions, as were the earlier
reactions of alkyl halides. Because the functional carbon atom has been reduced, the polarity of the resulting functional group is
inverted (an originally electrophilic carbon becomes nucleophilic). This change, shown below, makes alkyl lithium and Grignard
reagents excellent nucleophiles and useful reactants in synthesis.

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 Example 8.8.1:

Common Organometallic Reagents

Reaction of Organometallic Reagents with Various Carbonyls

Because organometallic reagents react as their corresponding carbanion, they are excellent nucleophiles. The basic reaction
involves the nucleophilic attack of the carbanionic carbon in the organometallic reagent with the electrophilic carbon in the
carbonyl to form alcohols.

Both Grignard and Organolithium Reagents will perform these reactions.

Addition to formaldehyde gives 1° alcohols

Addition to aldehydes gives 2° alcohols

Addition to ketones gives 3° alcohols

Addition to carbon dioxide (CO2) forms a carboxylic acid

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 Example 8.8.1:

Going from Reactants to Products Simplified

Mechanism for the Addition to Carbonyls

The mechanism for a Grignard agent is shown; the mechanism for an organometallic reagent is the same.
1) Nucleophilic attack

2) Protonation

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Organometallic Reagents as Bases
These reagents are very strong bases (pKa's of saturated hydrocarbons range from 42 to 50). Although not usually done with
Grignard reagents, organolithium reagents can be used as strong bases. Both Grignard reagents and organolithium reagents react
with water to form the corresponding hydrocarbon. This is why so much care is needed to insure dry glassware and solvents when
working with organometallic reagents.

In fact, the reactivity of Grignard reagents and organolithium reagents can be exploited to create a new method for the conversion
of halogens to the corresponding hydrocarbon (illustrated below). The halogen is converted to an organometallic reagent and then
subsequently reacted with water to from an alkane.

Limitation of Organometallic Reagents

As discussed above, Grignard and organolithium reagents are powerful bases. Because of this they cannot be used as nucleophiles
on compounds which contain acidic hydrogens. If they are used they will act as a base and deprotonate the acidic hydrogen rather
than act as a nucleophile and attack the carbonyl. A partial list of functional groups which cannot be used are: alcohols, amides, 1o
amines, 2o amines, carboxylic acids, and terminal alkynes.

Problems
1) Please write the product of the following reactions.

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2) Please indicate the starting material required to produce the product.

3) Please give a detailed mechanism and the final product of this reaction

4) Please show two sets of reactants which could be used to synthesize the following molecule using a Grignard reaction.

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Answers
1)

3)
Nucleophilic attack

Protonation

Contributors
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

8.8: Grignard and Organolithium Reagents is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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8.9: Grignard Reagents
This page takes an introductory look at how Grignard reagents are made from halogenoalkanes (haloalkanes or alkyl halides), and
introduces some of their reactions.

Introduction
A Grignard reagent has a formula RMgX where X is a halogen, and R is an alkyl or aryl (based on a benzene ring) group. For the
purposes of this page, we shall take R to be an alkyl group. A typical Grignard reagent might be CH CH MgBr . Grignard
3 2

reagents are made by adding the halogenoalkane to small bits of magnesium in a flask containing ethoxyethane (commonly called
diethyl ether or just "ether"). The flask is fitted with a reflux condenser, and the mixture is warmed over a water bath for 20 - 30
minutes.

Everything must be perfectly dry because Grignard reagents react with water (see below). Any reactions using the Grignard
reagent are carried out with the mixture produced from this reaction. You can't separate it out in any way.

Grignard reagents and water

Grignard reagents react with water to produce alkanes. This is the reason that everything has to be very dry during the preparation
above. For example:
C H3 C H2 M gBr + H2 O → C H3 C H3 + M g(OH )Br (8.9.1)

The inorganic product, M g(OH )Br , is referred to as a "basic bromide" and is a sort of half-way stage between

magnesium bromide and magnesium hydroxide.

Grignard reagents and carbon dioxide

Grignard reagents react with carbon dioxide in two stages. In the first, you get an addition of the Grignard reagent to the carbon
dioxide. Dry carbon dioxide is bubbled through a solution of the Grignard reagent in ethoxyethane, made as described
above. For example:

The product is then hydrolyzed (reacted with water) in the presence of a dilute acid. Typically, you would add dilute sulfuric acid or
dilute hydrochloric acid to the solution formed by the reaction with the CO2. A carboxylic acid is produced with one more carbon
than the original Grignard reagent. The usually quoted equation is (without the red bits):

Almost all sources quote the formation of a basic halide such as Mg(OH)Br as the other product of the reaction. That is actually
misleading because these compounds react with dilute acids. What you end up with would be a mixture of ordinary hydrated
magnesium ions, halide ions and sulfate or chloride ions - depending on which dilute acid you added.

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Grignard reagents and carbonyl compounds
Carbonyl compounds contain the C=O double bond. The simplest ones have the form:

R and R' can be the same or different, and can be an alkyl group or hydrogen. If one (or both) of the R groups are hydrogens, the
compounds are called aldehydes. For example:

If both of the R groups are alkyl groups, the compounds are called ketones. Examples include:

General Reaction between Grignards and carbonyls

The reactions between the various sorts of carbonyl compounds and Grignard reagents can look quite complicated, but in fact they
all react in the same way - all that changes are the groups attached to the carbon-oxygen double bond. It is much easier to
understand what is going on by looking closely at the general case (using "R" groups rather than specific groups) - and
then slotting in the various real groups as and when you need to.
The reactions are essentially identical to the reaction with carbon dioxide - all that differs is the nature of the organic product. In the
first stage, the Grignard reagent adds across the carbon-oxygen double bond:

Dilute acid is then added to this to hydrolyse it. (I am using the normally accepted equation ignoring the fact that the Mg(OH)Br
will react further with the acid.)

An alcohol is formed. One of the key uses of Grignard reagents is the ability to make complicated alcohols easily. What sort of
alcohol you get depends on the carbonyl compound you started with - in other words, what R and R' are.

Reaction between Grignard reagents and methanal

In methanal, both R groups are hydrogen. Methanal is the simplest possible aldehyde.

Assuming that you are starting with CH3CH2MgBr and using the general equation above you get always has the form:

Since both R groups are hydrogen atoms, the final product will be:

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A primary alcohol is formed. A primary alcohol has only one alkyl group attached to the carbon atom with the -OH group on it.
You could obviously get a different primary alcohol if you started from a different Grignard reagent.

Reaction between Grignards and other aldehydes

The next biggest aldehyde is ethanal. One of the R groups is hydrogen and the other CH3.

Again, think about how that relates to the general case. The alcohol formed is:

So this time the final product has one CH3 group and one hydrogen attached:

A secondary alcohol has two alkyl groups (the same or different) attached to the carbon with the -OH group on it. You could
change the nature of the final secondary alcohol by either:
changing the nature of the Grignard reagent - which would change the CH3CH2 group into some other alkyl group;
changing the nature of the aldehyde - which would change the CH3 group into some other alkyl group.

The reaction between Grignard reagents and ketones

Ketones have two alkyl groups attached to the carbon-oxygen double bond. The simplest one is propanone.

This time when you replace the R groups in the general formula for the alcohol produced you get a tertiary alcohol.

A tertiary alcohol has three alkyl groups attached to the carbon with the -OH attached. The alkyl groups can be any combination of
same or different. You could ring the changes on the product by
changing the nature of the Grignard reagent - which would change the CH3CH2 group into some other alkyl group;
changing the nature of the ketone - which would change the CH3 groups into whatever other alkyl groups you choose to have in
the original ketone.

Why do Grignard reagents react with carbonyls?

The bond between the carbon atom and the magnesium is polar. Carbon is more electronegative than magnesium, and so the
bonding pair of electrons is pulled towards the carbon. That leaves the carbon atom with a slight negative charge.

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The carbon-oxygen double bond is also highly polar with a significant amount of positive charge on the carbon atom. The nature of
this bond is described in detail elsewhere on this site. The Grignard reagent can therefore serve as a nucleophile because of the
attraction between the slight negativeness of the carbon atom in the Grignard reagent and the positiveness of the carbon in the
carbonyl compound. A nucleophile is a species that attacks positive (or slightly positive) centers in other molecules or ions.

Contributors
Jim Clark (Chemguide.co.uk)

This page titled 8.9: Grignard Reagents is shared under a CC BY-NC 4.0 license and was authored, remixed, and/or curated by Jim Clark.
Grignard Reagents by Jim Clark is licensed CC BY-NC 4.0.

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CHAPTER OVERVIEW

9: The Chemistry of Alkyl Halides

9.1: An Overview of Nucleophilic Substitution
9.2: Elimination Reactions
9.3: Rate Laws in Nucleophilic Substitution
9.4: Reaction Rates and Rate Laws
9.5: The SN2 Reaction
9.6: E2 Elimination
9.7: SN1 Reaction
9.7.1: 6.06.1 Kinetics, Stereochemistry and Energy Diagram
9.8: E1 Eliminations
9.9: Comparison of SN2 and SN1
9.10: Comparing E1 and E2
9.11: Determining SN2, SN¬1, E2 or E1
9.12: Carbenes
9.13: Cyclopropane Synthesis

9: The Chemistry of Alkyl Halides is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
9.1: An Overview of Nucleophilic Substitution
NS1. Introduction to Aliphatic Nucleophilic Substitution
Aliphatic nucleophilic substitution is a mouthful, but each piece tells you something important about this kind of reaction.
In substitution reactions, one piece of a molecule is replaced by another. For example, ligands can be replaced in transition metal
complexes. Oxygen atoms in organic carbonyl compounds can be replaced by nitrogen atoms or sulfur atoms, in a particular
variation of carbonyl addition reactions.
These reactions all involve the addition of a nucleophile to an electrophilic atom or ion. They are all nucleophilic substitution
reactions.
Aliphatic systems involve chains of saturated hydrocarbons, in which carbons are attached to each other only through single bonds.
Aliphatic nucleophilic substitution is the substitution of a nucleophile at a tetrahedral or sp3 carbon.
Aliphatic nucleophilic substitutions do not play a glamourous, central role in the world of chemistry. They don't happen in every
important process, the way carbonyl additions and carboxyloid substitutions appear to in biochemistry. Instead, they are ubiquitous
little reactions that play important, small roles in all kinds of places.
For example, polyethylene gloycol (PEG) is a commonly used polymer in lots of biomedical applications. PEG frequently has
hydroxyl groups at each end of the polymer. Capping the ends of the polymer through reaction with another group can lead to very
different physical properties.
For another example, many biochemical processes require prenylation of proteins. That would involve a nucleophilic substitution
in which a sulfur in a cysteine residue adds to a tetrahedral carbon in a prenyl group, replacing a phosphate group.
In order to be an electrophile, that tetrahedral carbon should have at least some partial positive charge on it. In the simplest cases,
this electrophilic carbon is attached to a halogen: chlorine, bromine or iodine. These compounds are called alkyl halides (or alkyl
chlorides, alkyl bromides and alkyl iodides).
Problem NS1.1.
Draw structures of the following alkyl halides.
a) 2-bromopentane b) 2-methyl-2-chlorobutane c) benzyl iodide d) allyl chloride
Lots of things can be nucleophiles in these reactions. Sometimes, the nucleophile is a neutral compound with a lone pair, such as
ammonia or water (or, by extension, an amine or an alcohol).

Problem NS1.2.
Sometimes, addition of a mild base is helpful in reactions of neutral nucleophiles. Show, with mechanistic arrows, how sodium
carbonate (K2CO3) would play a role in the reaction.
The third row analogs of these nucleophiles, in which the nucleophlic atom is a phosphorus or a sulfur, are also good nucleophiles
in these reactions.

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Sometimes, the nucleophile is an anion. Cyanide anion is a good nucleophile, as are the structurally similar acetylides.

Enols, enolates and enamines are also very good nucleophiles in this type of reaction.
Semi-anionic nucleophiles such as Grignard (or organomagnesium) reagents and alkyl lithium reagents can sometimes act as
nucleophiles in this reactions, but they are not very reliable. Complications often lead to other reactions instead. Gilman (or
organocopper) reagents, in which a carbon atom is attached to a copper atom, can usually react with alkyl halides. However, they
probably act via a different mechanism from the ones described in this chapter.

Contributors
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)

Given the mechanism in NS12.2., other products would also be expected.

1. What are they?
2. What does their absence suggest about the mechanism of the reaction?
Why might a reaction undergo elimination rather than substitution? The most important reason concerns the nature of the
nucleophile. The more basic the nucleophile, the more likely it will induce elimination.
Basic nucleophiles lead to elimination.
Very strong bases include carbon and nitrogen anions and semi-anions. Examples include butyllithium and sodium amide. Very
strong bases are highly likely to engage in elimination, rather than substitution.

Strong bases include non-stabilized oxygen anions. Examples include sodium hydroxide as well as alkoxides such as potassium
tert-butoxide or sodium ethoxide. Strong bases favour elimination, too. Nevertheless, they can sometimes undergo either
elimination or substitution, depending on other factors (see below).

Weak bases include cyanide, stabilized oxygen anions such as carboxylates and aryloxides, fluoride ion and neutral amines. Weak
bases are much more likely to undergo substitution than elimination.

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Very weak bases include heavy halides such as chloride, bromide or iodide, as well as phosphorus and sulfur nucleophiles. Very
weak bases undergo elimination only rarely.
Problem NS12.4.
Typically, strong bases and very strong bases are more likely to react via the E2 mechanism; they react so quickly that the
deprotonation step triggers C-LGp ionization, rather than the other way around. However, E1 mechanisms also occur with these
bases, especially at low concentrations. Explain why.
Problem NS12.5.
Why is it that an anion such as cyanide is a weak base, whereas CH3Li is a strong base? Give two reasons.
Another factor is sterics. The more crowded the electyrophile, the more likely the nucleophile will encounter a proton on its way to
the electrophilic carbon.
As a nucleophile approaches tert-butyl bromide, coming from the side opposite the bromine in order to undergo nucleophilic
substitution, it is pretty likely to collide with a proton on its way to the electrophilic carbon. The same thing has a good chance of
happening with iso-propyl bromide. However, it is much less likely to happen with bromoethane. Finally, bromomethane doesn't
even have a beta-hydrogen, so the chance of elimination in that case is zero.

Crowding leads to elimination.

Note that the crowding could involve either the structure of the base or the structure of the electrophile. A large, bulky base may be
more likely to deprotonate than find its way in to the electrophilic carbon atom.
Problem NS12.6.
Given the following pairs of nucleophiles, which one is more likely to undergo elimination?

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Problem NS12.7.
Although acetylides (such as sodium acetylide, Na CCH) are actually more basic than alkoxides (such as sodium isopropoxide, Na
OCH(CH3)2), acetylides frequently undergo substitution rather than elimination. Propose a reason for this difference.
A third factor is temperature. An elimination reaction involves the cleavage of two bonds, whereas a substitution reaction requires
only one bond to break. Thus, an elimination reaction is more energy-intensive, and it is more likely to occur at higher
temperatures, when more energy is available.
Higher temperatures lead to elimination.
Problem NS12.8.
An additional factor in the energy dependence of eliminations and substitutions is entropy.
1. Use simple rules about to determine which products are favoured by entropy: Elimination or substitution?
2. Given the relationship ΔG = ΔH - T ΔS, which thermodynamic factor dominates free energy change at high temperature?
3. Therefore, which product is favoured at high temperature?

Contributors
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)

This page titled 9.2: Elimination Reactions is shared under a CC BY-NC 3.0 license and was authored, remixed, and/or curated by Chris Schaller.
NS12. Elimination Reactions by Chris Schaller is licensed CC BY-NC 3.0.

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9.3: Rate Laws in Nucleophilic Substitution
Aliphatic Nucleophilic Substitution: Rate Laws
In aliphatic nucleophilic substitution, a nucleophile (abbreviated Nu) replaces a halogen "leaving group" (abbreviated LGp) from a
tetrahedral carbon. Aliphatic nucleophilic substitution may take place through two different mechanisms:
C-LGp bond breaking, followed by C-Nu bond formation.
or
C-Nu bond formation at the same time as C-LGp bond breaking.
A look at the reaction progress diagrams for these two reactions illustrates some big differences. We will look at cyanide anion, a
nucleophile, substituting for chloride in 2-chloropropane.

In the first case, some energy must be added in order to break the carbon-chlorine bond. The chlorine forms an anion, leaving a
cation on the carbon. This ion pair is an intermediate along the reaction pathway. The cyanide ion then connects with this cation to
form the nitrile product. Thus, there are two elementary steps in this mechanism.
Most likely, the first step is the rate-determining step. Breaking bonds costs energy, whereas making bonds releases energy. It is
hard to imagine that there could be a significant barrier to the second step; the anion and cation should come together almost
automatically.
The rate law for this stepwise mechanism is:
i
Rate = k[ P rC l] (9.3.1)

that is, the rate depends on the first elementary step, but not on the second one. The second step happens pretty much automatically
as soon as the first one has finally gotten around to happening.
In the second case, the nucleophile displaces the chloride directly in one step. There is only one elementary step in this reaction,
and it requires both compounds to come together at once.

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The rate law for this concerted mechanism is:
i −
Rate = k[ P rC l] [ CN ] (9.3.2)

These two rate laws are very different, and offer an additional way for us to tell how this reaction is taking place. In principle, if we
try the reaction with different concentrations of cyanide (but keep the 2-chloropropane concentration constant), we can see whether
that has an effect on how quickly the product appears. If it has the predictable effect, maybe the reaction happens in one step. If not,
maybe it is a two-step reaction.
Because the rate laws for these two mechanisms are so different, there has arisen a catchy shorthand for describing these reactions
based on their rate laws, coined by C.K. Ingold. The rate of the stepwise reaction depends only on one concentration and is referred
to as a "unimolecular reaction"; Ingold's shorthand for this kind of nucleophilic substitution was "SN1".
The rate of the concerted reaction depends on two different concentrations and is referred to as a bimolecular reaction; Ingold's
shorthand for this reaction was "SN2".
Problem NS3.1.
Suppose you run this reaction with three different concentrations of cyanide: 0.1 mol/L, 0.2 mol/L and 0.3 mol/L. You keep the 2-
chloropropane concentration constant at 0.05 mol/L.
a. The reaction turns out to be proceeding via a SN1 mechanism. Plot a graph of rate vs.[-CN].
b. The reaction turns out to be proceeding via a SN2 mechanism. Plot a graph of rate vs.[-CN].
Now you switch things up and run this reaction with three different concentrations of 2-chloropropane: 0.1 mol/L, 0.2 mol/L and
0.3 mol/L. You keep the 2-chloropropane concentration constant at 0.05 mol/L.
c. The reaction turns out to be proceeding via a SN1 mechanism. Plot a graph of rate vs.[iPrCl].
d. The reaction turns out to be proceeding via a SN2 mechanism. Plot a graph of rate vs.[iPrCl].
Why would the mechanism proceed in one way and not the other? Molecular choices between pathways like this are often
described on the basis of "steric and electronic effects"; in other words, it's either something to do with charge or something to do
with crowdedness. We will see soon how these effects can influence the course of the reaction, and how the mechanism can itself
have consequences in the formation of different products.
Problem NS3.2.
How might crowdedness or steric effects influence the pathway taken by the reaction between cyanide and 2-chloropropane?
Problem NS3.3.
How might charge stability influence the pathway taken by the reaction between cyanide and 2-chloropropane?

Contributors
Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)

This page titled 9.3: Rate Laws in Nucleophilic Substitution is shared under a CC BY-NC 3.0 license and was authored, remixed, and/or curated
by Chris Schaller.

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Rate Laws in Nucleophilic Substitution by Chris Schaller is licensed CC BY-NC 3.0.

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9.4: Reaction Rates and Rate Laws
Learning Objective
To determine the reaction rate.
To understand the meaning of a rate law.

The factors discussed in Section 13.1 affect the reaction rate of a chemical reaction, which may determine whether a desired
product is formed. In this section, we will show you how to quantitatively determine the reaction rate.

Reaction Rates
Reaction rates are usually expressed as the concentration of reactant consumed or the concentration of product formed per unit
time. The units are thus moles per liter per unit time, written as M/s, M/min, or M/h. To measure reaction rates, chemists initiate the
reaction, measure the concentration of the reactant or product at different times as the reaction progresses, perhaps plot the
concentration as a function of time on a graph, and then calculate the change in the concentration per unit time.
The progress of a simple reaction (A → B) is shown in Figure 13.2.1 where the beakers are snapshots of the composition of the
solution at 10 s intervals. The number of molecules of reactant (A) and product (B) are plotted as a function of time in the graph.
Each point in the graph corresponds to one beaker in Figure 13.2.1. The reaction rate is the change in the concentration of either the
reactant or the product over a period of time. The concentration of A decreases with time, while the concentration of B increases
with time.

Figure 13.2.1 The Progress of a Simple Reaction (A → B) The mixture initially contains only A molecules (purple). With
increasing time, the number of A molecules decreases and more B molecules (green) are formed (top). The graph shows the change
in the number of A and B molecules in the reaction as a function of time over a 1 min period (bottom).
d [B] d [A]
rate = =− (13.2.1)
dt dt

Square brackets indicate molar concentrations. We use derivatives to indicate infinitesmal changes with respect to time. On
occassion we will use the capital Greek delta (Δ) for a large change over considerable time. Because chemists follow the
convention of expressing all reaction rates as positive numbers, however, a negative sign is inserted in front of d[A]/dt to convert
that expression to a positive number. The reaction rate we would calculate for the reaction A → B using Equation 13.2.1 would be
different for each interval. (This is not true for every reaction, as you will see later.) A much greater change occurs in [A] and [B]
during the first 10 s interval, for example, than during the last, which means that the reaction rate is fastest at first. This is
consistent with the concentration effects described in Section 13.1 because the concentration of A is greatest at the beginning of the
reaction.

Note the Pattern

Reaction rates generally decrease with time as reactant concentrations decrease.

Determining the Reaction Rate of Hydrolysis of Aspirin

We can use Equation 13.2.1 to determine the reaction rate of hydrolysis of aspirin, probably the most commonly used drug in the
world. (More than 25,000,000 kg are produced annually worldwide.) Aspirin (acetylsalicylic acid) reacts with water (such as water
in body fluids) to give salicylic acid and acetic acid.

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Figure 13.2.2 Because salicylic acid is the actual substance that relieves pain and reduces fever and inflammation, a great deal of
research has focused on understanding this reaction and the factors that affect its rate. Data for the hydrolysis of a sample of aspirin
are in Table 13.2.1 and are shown in the graph in Figure 13.2.3. These data were obtained by removing samples of the reaction
mixture at the indicated times and analyzing them for the concentrations of the reactant (aspirin) and one of the products (salicylic
acid).
Table 13.2.1 Data for Aspirin Hydrolysis in Aqueous Solution at pH 7.0 and 37°C*

Time (h) [Aspirin] (M) [Salicylic Acid] (M)

0 5.55 × 10−3 0

2.0 5.51 × 10−3 0.040 × 10−3

5.0 5.45 × 10−3 0.10 × 10−3

10 5.35 × 10−3 0.20 × 10−3

20 5.15 × 10−3 0.40 × 10−3

30 4.96 × 10−3 0.59 × 10−3

40 4.78 × 10−3 0.77 × 10−3

50 4.61 × 10−3 0.94 × 10−3

100 3.83 × 10−3 1.72 × 10−3

200 2.64 × 10−3 2.91 × 10−3

300 1.82 × 10−3 3.73 × 10−3

*The reaction at pH 7.0 is very slow. It is much faster under acidic conditions, such as those found in the stomach.

Figure 13.2.3 The Hydrolysis of Aspirin This graph shows the concentrations of aspirin and salicylic acid as a function of time,
based on the hydrolysis data in Table 13.2.1. The time dependence of the concentration of the other product, acetate, is not shown,

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but based on the stoichiometry of the reaction, it is identical to the data for salicylic acid. Since the difference between points is
hours we use Δ[A]/Δt.
We can calculate the average reaction rateThe reaction rate calculated for a given time interval from the concentrations of either the
reactant or one of the products at the beginning of the interval time
[salicylic acid] − [salicylic acid]
2 0
rate(t=0−2.0 h) =
2.0 h − 0.0 h

−3
0.040 × 10 M − 0.000 M
−5
= = 2 × 10 M /h
2.0 h − 0.0 h

We can also calculate the reaction rate from the concentrations of aspirin at the beginning and the end of the same interval,
remembering to insert a negative sign, because its concentration decreases:
[aspirin] − [aspirin]
2 0
rate(t=0−2.0 h)
=
2.0 h − 0.0 h

−3 −3
5.51 × 10 M − 5.55 × 10 M
rate(t=0−2.0 h) = = 2.0 × 10
−5
M /h \;h} \)
2.0 h − 0.0 h

If we now calculate the reaction rate during the last interval given in Table 13.2.1 (the interval between 200 h and 300 h after the
start of the reaction), we find that the reaction rate is significantly slower than it was during the first interval (t = 0–2.0 h):
[salicylic acid] − [salicylic acid]
300 200
rate(t=200−300 h) =
300 h − 200 h

−3 −3
3.73 × 10 M − 2.91 × 10 M
−6
= = 8.2 × 10 M /h
100; h

(You should verify from the data in Table 13.2.1 that you get the same rate using the concentrations of aspirin measured at 200 h
and 300 h.)

Calculating the Reaction Rate of Fermentation of Sucrose

In the preceding example, the stoichiometric coefficients in the balanced chemical equation are the same for all reactants and
products; that is, the reactants and products all have the coefficient 1. Let us look at a reaction in which the coefficients are not all
the same: the fermentation of sucrose to ethanol and carbon dioxide.
C12 H22 O11 (aq) + H2 O (l) → 4 C2 H5 OH (aq) + $C O2 (g) (13.2.2)
sucrose

The coefficients show us that the reaction produces four molecules of ethanol and four molecules of carbon dioxide for every one
molecule of sucrose consumed. As before, we can find the reaction rate by looking at the change in the concentration of any
reactant or product. In this particular case, however, a chemist would probably use the concentration of either sucrose or ethanol
because gases are usually measured as volumes and, as you learned in Chapter 6, the volume of CO2 gas formed will depend on the
total volume of the solution being studied and the solubility of the gas in the solution, not just the concentration of sucrose. The
coefficients in the balanced chemical equation tell us that the reaction rate at which ethanol is formed is always four times faster
than the reaction rate at which sucrose is consumed:
d [ C2 H5 OH ] 4d [sucrose])
rate = =− (13.2.3)
dt dt

The concentration of the reactant—in this case sucrose—decreases with increasing time, so the value of Δ[sucrose] is negative.
Consequently, a minus sign is inserted in front of Δ[sucrose] in Equation 13.2.3 so that the rate of change of the sucrose
concentration is expressed as a positive value. Conversely, the ethanol concentration increases with increasing time, so its rate of
change is automatically expressed as a positive value.
Often the reaction rate is expressed in terms of the reactant or product that has the smallest coefficient in the balanced chemical
equation. The smallest coefficient in the sucrose fermentation reaction (Equation 13.2.2) corresponds to sucrose, so the reaction
rate is generally defined as follows:
d [sucrose] 1 d [ C2 H5 OH ]
rate = − = ( ) (13.2.4)
dt 4 dt

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Example 13.2.1
Consider the thermal decomposition of gaseous N2O5 to NO2 and O2 via the following equation:
Δ
2 N2 O5 (g) → 4N O2 (g) + O2 (g)

Write expressions for the reaction rate in terms of the rates of change in the concentrations of the reactant and each product with
time.
Given: balanced chemical equation
Asked for: reaction rate expressions
Strategy:
A Choose the species in the equation that has the smallest coefficient. Then write an expression for the rate of change of that
species with time.
B For the remaining species in the equation, use molar ratios to obtain equivalent expressions for the reaction rate.
Solution:
A Because O2 has the smallest coefficient in the balanced chemical equation for the reaction, we define the reaction rate as the rate
of change in the concentration of O2 and write that expression.
B We know from the balanced chemical equation that 2 mol of N2O5 must decompose for each 1 mol of O2 produced and that 4
mol of NO2 are produced for every 1 mol of O2 produced. The molar ratios of O2 to N2O5 and to NO2 are thus 1:2 and 1:4,
respectively. This means that we divide the rate of change of [N2O5] and [NO2] by its stoichiometric coefficient to obtain
equivalent expressions for the reaction rate. For example, because NO2 is produced at four times the rate of O2, we must divide the
rate of production of NO2 by 4. The reaction rate expressions are as follows:
d [ O2 ] d [N O2 ] d [ N2 O5 ]
rate = = =−
dt 4dt 2dt

Exercise
The key step in the industrial production of sulfuric acid is the reaction of SO2 with O2 to produce SO3.
2S O2 (g) + O2 (g) → 2S O3 (g)

Write expressions for the reaction rate in terms of the rate of change of the concentration of each species.
Answer:
d [ O2 ] d [S O2 ] d [S O3 ]
rate = − =− =
dt dt 2dt

Example 13.2.2
Using the reaction shown in Example 1, calculate the reaction rate from the following data taken at 56°C:

2N2O5(g) → 4NO2(g) + O2(g)

Time (s) [N2O5] (M) [NO2] (M) [O2] (M)

240 0.0388 0.0314 0.00792

600 0.0197 0.0699 0.0175

Given: balanced chemical equation and concentrations at specific times

Asked for: reaction rate
Strategy:
A Using the equations in Example 1, subtract the initial concentration of a species from its final concentration and substitute that
value into the equation for that species.

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B Substitute the value for the time interval into the equation. Make sure your units are consistent.
Solution:
A We are asked to calculate the reaction rate in the interval between t1 = 240 s and t2 = 600 s. From Example 1, we see that we can
evaluate the reaction rate using any of three expressions:
Δ [ O2 ] Δ [N O2 ] Δ [ N2 O5 ]
rate = = =−
Δt 4Δt 2Δt

Subtracting the initial concentration from the final concentration of N2O5 and inserting the corresponding time interval into the rate
expression for N2O5,
Δ [ N2 O5 ] [ N2 O5 ] − [ N2 O5 ]
600 240
rate = − =−
2Δt 2 (600 s − 240 s)

B Substituting actual values into the expression,

0.197 M − 0.0388 M
rate = −
2 (360 s)

Similarly, we can use NO2 to calculate the reaction rate:

Δ [N O2 ] [N O2 ] − [N O2 ] 0.0699 M − 0.0314 M
600 240 −5
rate = − =− = = 2.67 × 10 M /s
4Δt 4 (600 s − 240 s) 4 (360)

If we allow for experimental error, this is the same rate we obtained using the data for N2O5, as it should be because the reaction
rate should be the same no matter which concentration is used. We can also use the data for O2:
Δ [ O2 ] [ O2 ]600 − [ O2 ]240 0.0175 M − 0.00792 M
−5
rate = − =− = = 2.66 × 10 M /s
Δt (600 s − 240 s) 360 s

Again, this is the same value we obtained from the N2O5 and NO2 data. Thus the reaction rate does not depend on which reactant
or product is used to measure it.
Exercise
Using the data in the following table, calculate the reaction rate of SO2(g) with O2(g) to give SO3(g).

2SO2(g) + O2(g) → 2SO3(g)

Time (s) [SO2] (M) [O2] (M) [SO3] (M)

300 0.0270 0.0500 0.0072

720 0.0194 0.0462 0.0148

Answer: 9.0 × 10−6 M/s

Instantaneous Rates of Reaction

So far, we have determined average reaction rates over particular intervals of time. We can also determine the instantaneous
rateThe reaction rate of a chemical reaction at any given point in time. of a reaction, which is the reaction rate at any given point in
time. As the period of time used to calculate an average rate of a reaction becomes shorter and shorter, the average rate approaches
the instantaneous rate. If you have studied calculus, you may recognize that the instantaneous rate of a reaction at a given time
corresponds to the slope of a line tangent to the concentration-versus-time curve at that point—that is, the derivative of
concentration with respect to time.
Think of the distinction between the instantaneous and average rates of a reaction as being similar to the distinction between the
actual speed of a car at any given time on a trip and the average speed of the car for the entire trip. Although you may travel for a
long time at 65 mph on an interstate highway during a long trip, there may be times when you travel only 25 mph in construction
zones or 0 mph if you stop for meals or gas. Thus your average speed on the trip may be only 50 mph, whereas your instantaneous
speed on the interstate at a given moment may be 65 mph. Whether you are able to stop the car in time to avoid an accident
depends on your instantaneous speed, not your average speed. There are important differences between the speed of a car during a

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trip and the speed of a chemical reaction, however. The speed of a car may vary unpredictably over the length of a trip, and the
initial part of a trip is often one of the slowest. In a chemical reaction, the initial interval normally has the fastest rate (though this is
not always the case), and the reaction rate generally changes smoothly over time.
In chemical kinetics, we generally focus on one particular instantaneous rate, which is the initial reaction rate, t = 0. Initial rates are
determined by measuring the reaction rate at various times and then extrapolating a plot of rate versus time to t = 0.

Rate Laws
In Section 13.1, you learned that reaction rates generally decrease with time because reactant concentrations decrease as reactants
are converted to products. You also learned that reaction rates generally increase when reactant concentrations are increased. We
now examine the mathematical expressions called rate lawsMathematical expressions that describe the relationships between
reactant rates and reactant concentrations in a chemical reaction., which describe the relationships between reactant rates and
reactant concentrations. Rate laws are laws as defined in Chapter 1; they are mathematical descriptions of experimentally verifiable
data.
Rate laws may be written from either of two different but related perspectives. A differential rate lawA rate law that expresses the
reaction rate in terms of changes in the concentration of one or more reactants (Δ[R]) over a specific time interval (Δt) expresses
the reaction rate in terms of changes in the concentration of one or more reactants (Δ[R]) over a specific time interval (Δt). In
contrast, an integrated rate lawA rate law that expresses the reaction rate in terms of the initial concentration [R]0 and the measured
concentration of one or more reactants ([R]) after a given amount of time (t) describes the reaction rate in terms of the initial
concentration ([R]0) and the measured concentration of one or more reactants ([R]) after a given amount of time (t); we will discuss
integrated rate laws in Section 13.3. The integrated rate law can be found by using calculus to integrate the differential rate law.
Whether you use a differential rate law or integrated rate law, always make sure that the rate law gives the proper units for the
reaction rate, usually moles per liter per second (M/s).

Reaction Orders
For a reaction with the general equation
aA + bB → cC + dD (13.2.5)

the experimentally determined rate law usually has the following form:
m n
rate = k[A] [B] (13.2.6)

The proportionality constant (k) is called the rate constantA proportionality constant whose value is characteristic of the reaction
and the reaction conditions and whose numerical value does not change as the reaction progresses under a given set of conditions.,
and its value is characteristic of the reaction and the reaction conditions. A given reaction has a particular value of the rate constant
under a given set of conditions, such as temperature, pressure, and solvent; varying the temperature or the solvent usually changes
the value of the rate constant. The numerical value of k, however, does not change as the reaction progresses under a given set of
conditions.
Thus the reaction rate depends on the rate constant for the given set of reaction conditions and the concentration of A and B raised
to the powers m and n, respectively. The values of m and n are derived from experimental measurements of the changes in reactant
concentrations over time and indicate the reaction orderNumbers that indicate the degree to which the reaction rate depends on the
concentration of each reactant., the degree to which the reaction rate depends on the concentration of each reactant; m and n need
not be integers. For example, Equation 13.2.6 tells us that Equation 13.2.5 is mth order in reactant A and nth order in reactant B. It
is important to remember that n and m are not related to the stoichiometric coefficients a and b in the balanced chemical equation
and must be determined experimentally. The overall reaction order is the sum of all the exponents in the rate law: m + n.

Note the Pattern

Under a given set of conditions, the value of the rate constant does not change as the reaction progresses.
Although differential rate laws are generally used to describe what is occurring on a molecular level during a reaction, integrated
rate laws are used to determine the reaction order and the value of the rate constant from experimental measurements. (We present
general forms for integrated rate laws in Section 13.3.) To illustrate how chemists interpret a differential rate law, we turn to the
experimentally derived rate law for the hydrolysis of t-butyl bromide in 70% aqueous acetone. This reaction produces t-butanol
according to the following equation:

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(C H3 ) C Br (soln) + H2 O (soln) → (C H3 ) C OH (soln) + H Br (soln) (13.7.7)
3 3

Combining the rate expression in Equation 13.2.1 and Equation 13.2.6 gives us a general expression for the differential rate law:
d [A] m n
rate = − = k[A] [B] (13.2.8)
dt

Inserting the identities of the reactants into Equation 13.2.8 gives the following expression for the differential rate law for the
reaction:
d [ (C H3 ) C Br]
3 m n
rate = − = k[ (C H3 )3 C Br] [ H2 O] (13.2.9)
dt

Experiments done to determine the rate law for the hydrolysis of t-butyl bromide show that the reaction rate is directly proportional
to the concentration of (CH3)3CBr but is independent of the concentration of water. Thus m and n in Equation 13.2.9 are 1 and 0,
respectively, and
1 0
rate = k[ (C H3 ) C Br] [ H2 O] = k [ (C H3 ) C Br] (13.2.10)
3 3

Because the exponent for the reactant is 1, the reaction is first order in (CH3)3CBr. It is zeroth order in water because the exponent
for [H2O] is 0. (Recall that anything raised to the zeroth power equals 1.) Thus the overall reaction order is 1 + 0 = 1. What the
reaction orders tell us in practical terms is that doubling the concentration of (CH3)3CBr doubles the reaction rate of the hydrolysis
reaction, halving the concentration of (CH3)3CBr halves the reaction rate, and so on. Conversely, increasing or decreasing the
concentration of water has no effect on the reaction rate. (Again, when you work with rate laws, there is no simple correlation
between the stoichiometry of the reaction and the rate law. The values of k, m, and n in the rate law must be determined
experimentally.) Experimental data show that k has the value 5.15 × 10-4 s−1 at 25°C. The rate constant has units of reciprocal
seconds (s−1) because the reaction rate is defined in units of concentration per unit time (M/s). The units of a rate constant depend
on the rate law for a particular reaction.
Under conditions identical to those for the t-butyl bromide reaction, the experimentally derived differential rate law for the
hydrolysis of methyl bromide (CH3Br) is as follows:
d [C H3 Br]
′
rate = − = k [C H3 Br] (13.2.11)
dt

This reaction also has an overall reaction order of 1, but the rate constant in Equation 13..2.11 is approximately 106 times smaller
than that for t-butyl bromide. Thus methyl bromide hydrolyzes about 1 million times more slowly than t-butyl bromide, and this
information tells chemists how the reactions differ on a molecular level.
Frequently, changes in reaction conditions also produce changes in a rate law. In fact, chemists often change reaction conditions to
obtain clues about what is occurring during a reaction. For example, when t-butyl bromide is hydrolyzed in an aqueous acetone
solution containing OH− ions rather than in aqueous acetone alone, the differential rate law for the hydrolysis reaction does not
change. For methyl bromide, in contrast, the differential rate law becomes rate = k″[CH3Br][OH−], with an overall reaction order of
2. Although the two reactions proceed similarly in neutral solution, they proceed very differently in the presence of a base, which
again provides clues as to how the reactions differ on a molecular level.

Note the Pattern

Differential rate laws are generally used to describe what is occurring on a molecular level during a reaction, whereas integrated
rate laws are used for determining the reaction order and the value of the rate constant from experimental measurements.

Example 13.2.3
We present three reactions and their experimentally determined differential rate laws. For each reaction, give the units of the rate
constant, give the reaction order with respect to each reactant, give the overall reaction order, and predict what happens to the
reaction rate when the concentration of the first species in each chemical equation is doubled.
Pt 1 d [H I ] 2
1. 2H I (g) → H 2 (g) + I2 (g) rate = − = k[H I ]
2 dt

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Δ
2. 2N 2O (g) → 2 N2 (g) + O2 (g)

1 d [ N2 O]
rate = =k
2 dt
Δ

3. cyclopropane (g) → propane (g)

1 d [cyclopropance]
rate = = k [cyclopropane]
2 dt

Given: balanced chemical equations and differential rate laws

Asked for: units of rate constant, reaction orders, and effect of doubling reactant concentration
Strategy:
A Express the reaction rate as moles per liter per second [mol/(L·s), or M/s]. Then determine the units of each chemical species in
the rate law. Divide the units for the reaction rate by the units for all species in the rate law to obtain the units for the rate constant.
B Identify the exponent of each species in the rate law to determine the reaction order with respect to that species. Sum all
exponents to obtain the overall reaction order.
C Use the mathematical relationships as expressed in the rate law to determine the effect of doubling the concentration of a single
species on the reaction rate.
Solution:
1. A [HI]2 will give units of (moles per liter)2. For the reaction rate to have units of moles per liter per second, the rate constant
must have reciprocal units [1/(M·s)]:
M M /s 1
2 −1 −1
= kM ⇒ k = = =M s
2
s M M ⋅s

B The exponent in the rate law is 2, so the reaction is second order in HI. Because HI is the only reactant and the only species
that appears in the rate law, the reaction is also second order overall.
C If the concentration of HI is doubled, the reaction rate will increase from k[HI]02 to k(2[HI])02 = 4k[HI]02. The reaction rate
will therefore quadruple.
2. A Because no concentration term appears in the rate law, the rate constant must have M/s units for the reaction rate to have M/s
units.
B The rate law tells us that the reaction rate is constant and independent of the N2O concentration. That is, the reaction is zeroth
order in N2O and zeroth order overall.
C Because the reaction rate is independent of the N2O concentration, doubling the concentration will have no effect on the
reaction rate.
3. A The rate law contains only one concentration term raised to the first power. Hence the rate constant must have units of
reciprocal seconds (s−1) to have units of moles per liter per second for the reaction rate: M·s−1 = M/s.
B The only concentration in the rate law is that of cyclopropane, and its exponent is 1. This means that the reaction is first order
in cyclopropane. Cyclopropane is the only species that appears in the rate law, so the reaction is also first order overall.
C Doubling the initial cyclopropane concentration will increase the reaction rate from k[cyclopropane]0 to 2k[cyclopropane]0.
This doubles the reaction rate.
Exercise
Given the following two reactions and their experimentally determined differential rate laws: determine the units of the rate
constant if time is in seconds, determine the reaction order with respect to each reactant, give the overall reaction order, and
predict what will happen to the reaction rate when the concentration of the first species in each equation is doubled.
1. C H 3N = C H3 N (g) → C2 H6 (g) + N2 (g)

d [C H3 N = C H3 N ]
rate = − = k [C H3 N = C H3 N ]
dt

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2. 2N O 2 (g) + F2 (g) → 2N O2 F (g)

d [ F2 ] 1 d [N O2 ]
rate = − =− = k [N O2 ] [ F2 ]
dt 2 dt

Answer:
1. s−1; first order in CH3N=NCH3; first order overall; doubling [CH3N=NCH3] will double the reaction rate.
2. M−1·s−1; first order in NO2, first order in F2; second order overall; doubling [NO2] will double the reaction rate.

Summary
Reaction rates are reported either as the average rate over a period of time or as the instantaneous rate at a single time.
The rate law for a reaction is a mathematical relationship between the reaction rate and the concentrations of species in solution.
Rate laws can be expressed either as a differential rate law, describing the change in reactant or product concentrations as a
function of time, or as an integrated rate law, describing the actual concentrations of reactants or products as a function of time.
The rate constant (k) of a rate law is a constant of proportionality between the reaction rate and the reactant concentration. The
power to which a concentration is raised in a rate law indicates the reaction order, the degree to which the reaction rate depends
on the concentration of a particular reactant.

Key Takeaways
Reaction rates can be determined over particular time intervals or at a given point in time.
A rate law describes the relationship between reactant rates and reactant concentrations.

Key Equations
general definition of rate for A → B
d [B] d [A]
Equation 13.2.1: rate = =−
dt dt

general form of rate law when A and B are reactants

Equation 13.2.6: rate = k[A] m
[B]
n

Conceptual Problems
1. Explain why the reaction rate is generally fastest at early time intervals. For the second-order A + B → C, what would the plot
of the concentration of C versus time look like during the course of the reaction?
2. Explain the differences between a differential rate law and an integrated rate law. What two components do they have in
common? Which form is preferred for obtaining a reaction order and a rate constant? Why?
3. Diffusion-controlled reactions have rates that are determined only by the reaction rate at which two reactant molecules can
diffuse together. These reactions are rapid, with second-order rate constants typically on the order of 1010 L/(mol·s). Would you
expect the reactions to be faster or slower in solvents that have a low viscosity? Why? Consider the reactions H3O+ + OH− →
2H2O and H3O+ + N(CH3)3 → H2O + HN(CH3)3+ in aqueous solution. Which would have the higher rate constant? Why?
4. What information can you get from the reaction order? What correlation does the reaction order have with the stoichiometry of
the overall equation?
5. During the hydrolysis reaction A + H2O → B + C, the concentration of A decreases much more rapidly in a polar solvent than
in a nonpolar solvent. How do you expect this effect to be reflected in the overall reaction order?

Answers
1. Reactant concentrations are highest at the beginning of a reaction. The plot of [C] versus t is a curve with a slope that becomes
steadily less positive.
2.
3. Faster in a less viscous solvent because the rate of diffusion is higher; the H3O+/OH− reaction is faster due to the decreased
relative size of reactants and the higher electrostatic attraction between the reactants.
4.

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5.

Numerical Problems
1. The reaction rate of a particular reaction in which A and B react to make C is as follows:
Δ [A] 1 d [C ]
rate = − =
Δt 2 dt

Write a reaction equation that is consistent with this rate law. What is the rate expression with respect to time if 2A are
converted to 3C?
2. While commuting to work, a person drove for 12 min at 35 mph, then stopped at an intersection for 2 min, continued the
commute at 50 mph for 28 min, drove slowly through traffic at 38 mph for 18 min, and then spent 1 min pulling into a parking
space at 3 mph. What was the average rate of the commute? What was the instantaneous rate at 13 min? at 28 min?
3. Why do most studies of chemical reactions use the initial rates of reaction to generate a rate law? How is this initial rate
determined? Given the following data, what is the reaction order? Estimate.

Time (s) [A] (M)

120 0.158

240 0.089

360 0.062

4. Predict how the reaction rate will be affected by doubling the concentration of the first species in each equation.
1. C2H5I → C2H4 + HI: rate = k[C2H5I]
2. SO + O2 → SO2 + O: rate = k[SO][O2]
3. 2CH3 → C2H6: rate = k[CH3]2
4. ClOO → Cl + O2: rate = k
5. Cleavage of C2H6 to produce two CH3· radicals is a gas-phase reaction that occurs at 700°C. This reaction is first order, with k
= 5.46 × 10−4 s−1. How long will it take for the reaction to go to 15% completion? to 50% completion?
6. Three chemical processes occur at an altitude of approximately 100 km in Earth’s atmosphere.
k1
+ +
N + O2 → N2 + O
2 2

k2
+ +
O + O → O2 + O
2

k3
+ +
O + N2 → N + N O

Write a rate law for each elementary reaction. If the rate law for the overall reaction were found to be rate = k[N2+][O2], which
one of the steps is rate limiting?
7. The oxidation of aqueous iodide by arsenic acid to give I3− and arsenous acid proceeds via the following reaction:
kf
− + −
H3 AsO4 (aq) + 3 I (aq) + 2 H (aq) ⇌ H3 AsO3 (aq) + I (aq) + H2 O (l)
3

Write an expression for the initial rate of decrease of [I3−], Δ[I3−]/Δt. When the reaction rate of the forward reaction is equal to
that of the reverse reaction: kf/kr = [H3AsO3][I3−]/[H3AsO4][I−]3[H+]2. Based on this information, what can you say about the
nature of the rate-determining steps for the reverse and the forward reactions?

Answer
1.
2.
3.
4.

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5. 298 s; 1270 s
6.
7.

Contributors
Anonymous
Modified by Joshua Halpern (Howard University), Scott Sinex, and Scott Johnson (PGCC)

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SECTION OVERVIEW

9.5: The SN2 Reaction

Topic hierarchy

Nucleophilic Substitution
Previously (Physical Properties of Haloalkanes), we learned that haloalkanes contain a polarized C-X bond, leaving a carbon that is
partially positive and a halogen that is partially negative.
An electrophile is an electron poor species that can accept a pair of electrons. A carbon that is connected to a halogen in a
haloalkane, for example, is an electrophilic carbon.
A nucleophile is an electron rich species that can donate a pair of electrons. You will be exposed to many different kinds of
nucleophiles throughout your course of study. Some nucleophiles will be negatively charged species; others will be neutral.
Nucleophiles can react with electrophiles. One way in which this occurs is through a process called nucleophilic
substitution. In nucleophilic substitution reactions, an electron rich nucleophile bonds with or attacks an electron poor
electrophile, resulting in the displacement of a group or atom called the leaving group.
Nucleophilic substitution of haloalkanes can be described by two reactions. These two types of reactions are shown in the
diagram below. In the first reaction, a negatively charged nucleophile attacks the electrophilic carbon of a haloalkane. Upon
attack, the leaving group, which is the halogen of the haloalkane, leaves. The end result is a neutral R-Nu species and an anion.
In the second reaction, a neutral nucleophile attacks the electrophilic carbon of a haloalkane. The end result of this attack
however, is positively charged product and an anion.

Examples of Negatively Charged and Neutral Nucleophiles

In the SN2 reaction, the addition of the nucleophile and the departure of the leaving group occur in a concerted(taking place in a
single step) manner, hence the name SN2: substitution, nucleophilic, bimolecular. In the SN2 reaction, the nucleophile approaches
the carbon atom to which the leaving group is attached. As the nucleophile forms a bond with this carbon atom, the bond between
the carbon atom and the leaving group breaks. The bond making and bond breaking actions occur simultaneously. Eventually, the

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nucleophile has formed a complete bond to the carbon atom and the bond between the carbon atom and the leaving group is
completely broken.
In the image below, we introduce the concepts of arrow pushing and of a reaction mechanism. Recall that electrons compose the
bonds in molecules. Hence for any reaction to occur, electrons must move. In arrow pushing, the movement of electrons is
indicated by arrows. Arrows may show electrons forming or breaking bonds or traveling as lone pairs or negative charges on
atoms. A complete schematic showing all steps in a reaction, including arrow pushing to indicate the movement of electrons,
constitutes a reaction mechanism. In the reaction mechanism below, observe that the electrons from a negative charge on the
nucleophile "attack" or form a bond with the carbon atom to which the leaving group is attached. In the center image, the partially
formed bond is visible, as well as the partially broken bond to the leaving group. In the final image, the bond to the leaving group is
broken when its electrons become a negative charge on the leaving group.

Figure 1: SN2 reaction showing concerted, bimolecular participation of nucleophile and leaving group
A consequence of the concerted, bimolecular nature of the SN2 reaction is that the nucleophile must attack from the side of the
molecule opposite to the leaving group. This geometry of reaction is called back side attack. In a back side attack, as the
nucleophile approaches the molecule from the side opposite to the leaving group, the other three bonds move away from the
nucleophile and its attacking electrons. Eventually, these three bonds are all in the same plane as the carbon atom (center image).
As the bond to the leaving group breaks, these bonds retreat farther away from the nucleophile and its newly formed bond to
carbon atom. As a result of these geometric changes, the stereochemical configuration of the molecule is inverted during an SN2
reaction to the opposite enantiomer. This stereochemical change is called inversion of configuration.
The concerted mechanism and nature of the nucleophilic attack in an SN2 reaction give rise to several important results:
1. The rate of the reaction depends on the concentration of both the nucleophile and the molecule undergoing attack. The reaction
requires a collision between the nucleophile and the molecule, so increasing the concentration of either will increase the rate of
the reaction.
2. Since the unique geometry of back side attack is required, the most important factor in determining whether an SN2 reaction
will occur is steric effects. Steric effects refer to the unfavorable interaction created when atoms are brought too close together.
In effect, if the nucleophile or the molecule undergoing attack have too many substituents or substituents which are too bulky,
the reaction cannot occur since the nucleophile will be unable to get close enough to the molecule to do a backside attack.
Now let's look at two actual examples of these two general equations. In the first reaction shown below, the negative nucleophile,
hydroxide, reacts with methyl iodide. Hydroxide takes the place of the leaving group, iodide, forming neutral methanol and an
iodide ion. This reaction is the same as the first type of nucleophilic substitution shown above. In the second reaction shown below,
the nuetral nucleophile, ammonia, reacts with iodoethane. Ammonia takes the place of the leaving group, iodide, forming the
positively charged product, ethylammonium iodide, and an iodide ion. This reaction is the same as the second type of nucleophilic
substitution shown above.

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Figure 2. SN2 reaction of methyl chloride and hydroxide ion (left) and ammonia reaction with HCl (right).

Four Factors to Consider in Determining the Relative Ease at Which SN2 Displacement Occurs
The nature of the leaving group (SN2 Reactions-The Leaving Group)
The reactivity of the nucleophile (SN2 Reactions-The Nucleophile)
The solvent (SN2 Reactions-The Nucleophile)
The structure of the alkyl portion of the substrate (SN2 Reactions-The Substrate)
Next section: Using Electron-Pushing Arrows

Contributors
Rachael Curtis (UCD)
Jonathan Mooney (McGill University)
Richard Banks (Boise State University)

Additional Resources
Michigan State Virtual Textbook of Organic Chemistry
Second-Order Nucleophilic Substitution: The SN2 Reaction
MasterOrganicChemistry
The SN2 Mechanism
Why The SN2 Is Powerful
Carey 4th Edition On-Line Activity
Second-Order Nucleophilic Substitution: The SN2 Reaction
Khan Academy
The SN2 Reaction
Leah4Sci
SN2 Reaction Rate and Mechanism (vid 1 of 3) Bimolecular Substitution
SN2 Reaction (vid 2 of 3) Chirality and Mechanism of Bimolecular Substitution
SN2 Reaction vid (3 of 3) Bimolecular Nucleophilic Substitution
Cliffs Notes
Mechanism
Web Pages
SN2 reaction description
All about the SN2 reactions
SN2 reaction information
Videos
Reaction examples

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SN2 reaction description
Video on SN2 Reactions
Tutorial
SN2 Handout

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9.6: E2 Elimination
E2 reactions are typically seen with secondary and tertiary alkyl halides, but a hindered base is necessary with a primary halide.
The mechanism by which it occurs is a single step concerted reaction with one transition state. The rate at which this mechanism
occurs is second order kinetics, and depends on both the base and alkyl halide. A good leaving group is required because it is
involved in the rate determining step. The leaving groups must be coplanar in order to form a pi bond; carbons go from sp3 to sp2
hybridization states.

General Reaction
In this reaction Ba represents the base and X represents a leaving group, typically a halogen. There is one transition state that shows
the concerted reaction for the base attracting the hydrogen and the halogen taking the electrons from the bond. The product be both
eclipse and staggered depending on the transition states. Eclipsed products have a synperiplanar transition states, while staggered
products have antiperiplanar transition states. Staggered conformation is usually the major product because of its lower energy
confirmation.

An E2 reaction has certain requirements to proceed:

Secondary and tertiary alkyl halides will proceed with E2 in the presence of a base (OH-, RO-, R2N-)
Both leaving groups should be on the same plane, this allows the double bond to form in the reaction. In the reaction above you
can see both leaving groups are in the plane of the carbons.
Follows Zaitsev's rule, the most substituted alkene is usually the major product.
Hoffman Rule, if a sterically hindered base will result in the least substituted product.

Reaction Coordinate

Problems
1.

2. What is the major product and why?

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3. What is the major prodcut when 2-bromo-2-methylbutane reacts with with sodium ethoxide?
4.

Further Reading
Michigan State Virtual Textbook of Organic Chemistry
E2 Elimination
MasterOrganicChemistry
The E2 Mechanism
Elimination Reactions And Cyclohexane Rings
Carey 4th Edition On-Line Activity
E2 mechanism
Khan Academy
Mechanism
Regioselectivity
Stereoselectivity
Stereospecificity
Substituted Cyclohexanes
Leah4Sci
E2 Reaction Rate & Mechanism (vid 1 of 4) Bimolecular Beta-Elimination by Leah Fisch
E2 Reaction (vid 2 of 4) Using Newman Projections To Predict Products by Leah4sci
E2 reaction (vid 3 of 4) using chair conformations for anti coplanar reactions
E2 Reaction (vid 4 of 4) Big Bulky Base for Anti-Zaitsev Product
Cliffs Notes
Slide Presentations
Web Pages
Sparknotes on SN2 and E2
basics of e2 elmination
Videos
E2 elimination video
E2 elimination and examples

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9.6: E2 Elimination is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
E2 Reactions is licensed CC BY-NC-SA 4.0.

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9.7: SN1 Reaction
SN1 Mechanism
Reaction 7, is clearly different from the other cases we have examined. It not only shows first order kinetics, but the chiral 3º-alkyl
bromide reactant undergoes substitution by the modest nucleophile water with extensive racemization. In all of these features this
reaction fails to meet the characteristics of the SN2 mechanism. A similar example is found in the hydrolysis of tert-butyl chloride,
shown below. Note that the initial substitution product in this reaction is actually a hydronium ion, which rapidly transfers a proton
to the chloride anion. This second acid-base proton transfer is often omitted in writing the overall equation, as in the case of
reaction 7.
(CH3)3C-Cl + H2O → (CH3)3C-OH2(+) + Cl(–) → (CH3)3C-OH + HCl
Although the hydrolysis of tert-butyl chloride, as shown above, might be interpreted as an SN2 reaction in which the high and
constant concentration of solvent water does not show up in the rate equation, there is good evidence this is not the case. First, the
equivalent hydrolysis of ethyl bromide is over a thousand times slower, whereas authentic SN2 reactions clearly show a large rate
increase for 1º-alkyl halides. Second, a modest increase of hydroxide anion concentration has no effect on the rate of hydrolysis of
tert-butyl chloride, despite the much greater nucleophilicity of hydroxide anion compared with water.
The first order kinetics of these reactions suggests a two-step mechanism in which the rate-determining step consists of the
ionization of the alkyl halide, as shown in the diagram below. In this mechanism, a carbocation is formed as a high-energy
intermediate, and this species bonds immediately to nearby nucleophiles. If the nucleophile is a neutral molecule, the initial product
is an "onium" cation, as drawn above for t-butyl chloride, and presumed in the energy diagram. In evaluating this mechanism, we
may infer several outcomes from its function.

1. The only reactant that is undergoing change in the first (rate-determining) step is the alkyl halide, so we expect such reactions
would be unimolecular and follow a first-order rate equation. Hence the name SN1 is applied to this mechanism.
2. Since nucleophiles only participate in the fast second step, their relative molar concentrations rather than their nucleophilicities
should be the primary product-determining factor. If a nucleophilic solvent such as water is used, its high concentration will
assure that alcohols are the major product. Recombination of the halide anion with the carbocation intermediate simply reforms
the starting compound. Note that SN1 reactions in which the nucleophile is also the solvent are commonly called solvolysis
reactions. The hydrolysis of t-butyl chloride is an example.
3. The Hammond postulate suggests that the activation energy of the rate-determining first step will be inversely proportional to
the stability of the carbocation intermediate. The stability of carbocations was discussed earlier, and a qualitative relationship is
given below.

Carbocatio
(CH3)2CH( CH2=CH- C6H5CH2(
n CH3(+) < CH3CH2(+) < +) ≈ < ≈ (CH3)3C(+)
CH2(+) +)
Stability

Consequently, we expect that 3º-alkyl halides will be more reactive than their 2º and 1º-counterparts in reactions that follow an SN1
mechanism. This is opposite to the reactivity order observed for the SN2 mechanism. Allylic and benzylic halides are exceptionally
reactive by either mechanism.
Fourth, in order to facilitate the charge separation of an ionization reaction, as required by the first step, a good ionizing solvent
will be needed. Two solvent characteristics will be particularly important in this respect. The first is the ability of solvent molecules
to orient themselves between ions so as to attenuate the electrostatic force one ion exerts on the other. This characteristic is related
to the dielectric constant, ε, of the solvent. Solvents having high dielectric constants, such as water (ε=81), formic acid (ε=58),
dimethyl sulfoxide (ε=45) & acetonitrile (ε=39) are generally considered better ionizing solvents than are some common organic
solvents such as ethanol (ε=25), acetone (ε=21), methylene chloride (ε=9) & ether (ε=4). The second factor is solvation, which
refers to the solvent's ability to stabilize ions by encasing them in a sheath of weakly bonded solvent molecules. Anions are
solvated by hydrogen-bonding solvents, as noted earlier. Cations are often best solvated by nucleophilic sites on a solvent molecule
(e.g. oxygen & nitrogen atoms), but in the case of carbocations these nucleophiles may form strong covalent bonds to carbon, thus
converting the intermediate to a substitution product. This is what happens in the hydrolysis reactions described above.

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Fifth, the stereospecificity of these reactions may vary. The positively-charged carbon atom of a carbocation has a trigonal (flat)
configuration (it prefers to be sp2 hybridized), and can bond to a nucleophile equally well from either face. If the intermediate from
a chiral alkyl halide survives long enough to encounter a random environment, the products are expected to be racemic (a 50:50
mixture of enantiomers). On the other hand, if the departing halide anion temporarily blocks the front side, or if a nucleophile is
oriented selectively at one or the other face, then the substitution might occur with predominant inversion or even retention of
configuration.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

Additional Resources
Michigan State Virtual Textbook of Organic Chemistry
SN1 Reaction
MasterOrganicChemistry
The SN1 Mechanism
Carey 4th Edition On-Line Activity
SN1 Reaction
Khan Academy
SN1 Reaction
Mechanism
Leah4Sci
SN1 Reaction Rate and Mechanism - Unimolecular Nucleophilic Substitution Part 1
SN1 Reaction Mechanism (vid 2 of 3) Examples of Unimolecular Substitution
SN1 Reaction Mechanism (vid 3 of 3) with Hydride Shift and Carbocation Rearrangement
Cliffs Notes
Mechanism
Slide Presentations
Web Pages
SN1 Mechanism
SN1 Basics
Videos
SN1 video
SN1 video

9.7: SN1 Reaction is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
SN1 Substitution Reactions by William Reusch is licensed CC BY-NC-SA 4.0.

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9.7.1: 6.06.1 Kinetics, Stereochemistry and Energy Diagram
Additional Resources
Khan Academy
Stereochemistry
Web Pages
Details of SN1 reaction
Rate law and the SN1 mechanism
Videos
SN1 energy diagram

9.7.1: 6.06.1 Kinetics, Stereochemistry and Energy Diagram is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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9.8: E1 Eliminations
Unimolecular Elimination (E1) is a reaction in which the removal of an HX substituent results in the formation of a double bond. It
is similar to a unimolecular nucleophilic substitution reaction (SN1) in various ways. One being the formation of a carbocation
intermediate. Also, the only rate determining (slow) step is the dissociation of the leaving group to form a carbocation, hence the
name unimolecular. Thus, since these two reactions behave similarly, they compete against each other. Many times, both these
reactions will occur simultaneously to form different products from a single reaction. However, one can be favored over another
through thermodynamic control. Although Elimination entails two types of reactions, E1 and E2, we will focus mainly on E1
reactions with some reference to E2.

General Reaction
An E1 reaction involves the deprotonation of a hydrogen nearby (usually one carbon away, or the beta position) the carbocation
resulting in the formation of an alkene product. In order to accomplish this, a Lewis base is required. For a simplified model, we’ll
take B to be a Lewis base, and LG to be a halogen leaving group.

As can be seen above, the preliminary step is the leaving group (LG) leaving on its own. Because it takes the electrons in the bond
along with it, the carbon that was attached to it loses its electron, making it a carbocation. Once it becomes a carbocation, a Lewis
Base (B ) deprotonates the intermediate carbocation at the beta position, which then donates its electrons to the neighboring C-C
−

bond, forming a double bond. Unlike E2 reactions, which require the proton to be anti to the leaving group, E1 reactions only
require a neighboring hydrogen. This is due to the fact that the leaving group has already left the molecule. The final product is an
alkene along with the HB byproduct.

Reactivity
Due to the fact that E1 reactions create a carbocation intermediate, rules present in S
N 1 reactions still apply.

As expected, tertiary carbocations are favored over secondary, primary and methyl’s. This is due to the phenomena of
hyperconjugation, which essentially allows a nearby C-C or C-H bond to interact with the p orbital of the carbon to bring the
electrons down to a lower energy state. Thus, this has a stabilizing effect on the molecule as a whole. In general, primary and
methyl carbocations do not proceed through the E1 pathway for this reason, unless there is a means of carbocation rearrangement
to move the positive charge to a nearby carbon. Secondary and Tertiary carbons form more stable carbocations, thus this formation
occurs quite rapidly.
Secondary carbocations can be subject to the E2 reaction pathway, but this generally occurs in the presence of a good / strong base.
Adding a weak base to the reaction disfavors E2, essentially pushing towards the E1 pathway. In many instances, solvolysis occurs
rather than using a base to deprotonate. This means heat is added to the solution, and the solvent itself deprotonates a hydrogen.
The medium can effect the pathway of the reaction as well. Polar protic solvents may be used to hinder nucleophiles, thus
disfavoring E2 / Sn2 from occurring.

Acid catalyzed dehydration of secondary / tertiary alcohols

We’ll take a look at a mechanism involving solvolysis during an E1 reaction of Propanol in Sulfuric Acid.

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Step 1: The OH group on the pentanol is hydrated by H2SO4. This allows the OH to become an H2O, which is a better leaving
group.
Step 2: Once the OH has been hydrated, the H2O molecule leaves, taking its electrons with it. This creates a carbocation
intermediate on the attached carbon.
Step 3: Another H2O molecule comes in to deprotonate the beta carbon, which then donates its electrons to the neighboring C-C
bond. The carbons are rehybridized from sp3 to sp2, and thus a pi bond is formed between them.

Mechanism for Alkyl Halides

This mechanism is a common application of E1 reactions in the synthesis of an alkene.

Once again, we see the basic 2 steps of the E1 mechanism.

1. The leaving group leaves along with its electrons to form a carbocation intermediate.
2. A base deprotonates a beta carbon to form a pi bond.
In this case we see a mixture of products rather than one discrete one. This is the case because the carbocation has two nearby
carbons that are capable of being deprotonated, but that only one forms a major product (more stable).

How are Regiochemistry & Stereochemistry involved?

In terms of regiochemistry, Zaitsev's rule states that although more than one product can be formed during alkene synthesis, the
more substituted alkene is the major product. This infers that the hydrogen on the most substituted carbon is the most probable to
be deprotonated, thus allowing for the most substituted alkene to be formed.
Unlike E2 reactions, E1 is not stereospecific. Thus, a hydrogen is not required to be anti-periplanar to the leaving group.

In this mechanism, we can see two possible pathways for the reaction. One in which the methyl on the right is deprotonated, and
another in which the CH2 on the left is deprotonated. Either one leads to a plausible resultant product, however, only one forms a
major product. As stated by Zaitsev's rule, deprotonation of the most substituted carbon results in the most substituted alkene. This
then becomes the most stable product due to hyperconjugation, and is also more common than the minor product.

Outside Sources
1. Vollhardt, K. Peter C., and Neil E. Schore. Organic Chemistry Structure and Function. New York: W. H. Freeman, 2007.
2. McMurry, J., Simanek, E. Fundamentals of Organic Chemistry, 6th edition. Cengage Learning, 2007.

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Problems
1) Which of these steps is the rate determining step (A or B)?
What is the major product formed (C or D)?

2) In order to produce the most stable alkene product, from which carbon should the base deprotonate (A, B, or C)?
If the carbocation were to rearrange, on which carbon would the positive charge go onto without sacrificing stability (A, B, or C)?

3) Predict the major product of the following reaction.

4) (True or False) – There is no way of controlling the product ratio of E1 / Sn1 reactions.
5) Explain why the presence of a weak base / nucleophile favors E1 reactions over E2.

Answers
1. A , C
2. B, B
3.

4. False - They can be thermodynamically controlled to favor a certain product over another.
5. By definition, an E1 reaction is a Unimolecular Elimination reaction. This means the only rate determining step is that of the
dissociation of the leaving group to form a carbocation. Since E2 is bimolecular and the nucleophilic attack is part of the rate
determining step, a weak base/nucleophile disfavors it and ultimately allows E1 to dominate. (Don't forget about Sn1 which still
pertains to this reaction simultaneously).

Contributors
Satish Balasubramanian

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Additional Resources
Michigan State Virtual Textbook of Organic Chemistry
E1 Elimination
MasterOrganicChemistry
Walkthrough of Elimination Reactions (1) – Introduction
Two Types of Elimination Reactions
The E1 Mechanism
Comparing The SN1 and E1 Reactions
E1 Reactions With Rearrangements
Carey 4th Edition On-Line Activity
Elimination overview
E1 mechanism
Khan Academy
E1 Elimination
Leah4Sci
E1 Reaction Rate and Mechanism - Unimolecular beta-elimination (vid 1 of 3) by Leah4sci
Cliffs Notes
Elimination Reactions
Mechanism of Elimination Reactions
Web Pages
Sparknotes on SN1 and E1
Videos
E1 Video

9.8: E1 Eliminations is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
E1 Reactions is licensed CC BY-NC-SA 4.0.

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9.9: Comparison of SN2 and SN1
8.5A: What makes a good leaving group?
In our general discussion of nucleophilic substitution reactions, we have until now been designating the leaving group simply as
“X". As you may imagine, however, the nature of the leaving group is an important consideration: if the C-X bond does not break,
the new bond between the nucleophile and electrophilic carbon cannot form, regardless of whether the substitution is SN1 or SN2.
When the C-X bond breaks in a nucleophilic substitution, the pair of electrons in the bond goes with the leaving group. In this way,
the leaving group is analogous to the conjugate base in a Brønsted-Lowry acid-base reaction. When we were evaluating the
strength of acids in chapter 7, what we were really doing was evaluating the stability of the conjugate base that resulted from the
proton transfer. All of the concepts that we used to evaluate the stability of conjugate bases we can use again to evaluate leaving
groups – essentially they are one and the same. In other words, the trends in basicity are parallel to the trends in leaving group
potential - the weaker the base, the better the leaving group. Just as with conjugate bases, the most important question regarding
leaving groups is this: when a leaving group leaves and takes a pair of electrons with it, how well is the extra electron density
stabilized?
In laboratory synthesis reactions, halides often act as leaving groups. Iodide, which is the least basic of the four main halides, is
also the best leaving group – it is the most stable as a negative ion. Fluoride is the least effective leaving group among the halides,
because fluoride anion is the most basic.
Exercise 8.14: Predict the structures of A and B in the following reaction:

Solution
Template:ExampleEnd

8.5D: Predicting SN1 vs. SN2 mechanisms; competition between nucleophilic substitution and
elimination reactions
When considering whether a nucleophilic substitution is likely to occur via an SN1 or SN2 mechanism, we really need to consider
three factors:
1) The electrophile: when the leaving group is attached to a methyl group or a primary carbon, an SN2 mechanism is
favored (here the electrophile is unhindered by surrounded groups, and any carbocation intermediate would be high-
energy and thus unlikely). When the leaving group is attached to a tertiary, allylic, or benzylic carbon, a carbocation
intermediate will be relatively stable and thus an SN1 mechanism is favored.
2) The nucleophile: powerful nucleophiles, especially those with negative charges, favor the SN2 mechanism. Weaker
nucleophiles such as water or alcohols favor the SN1 mechanism.
3) The solvent: Polar aprotic solvents favor the SN2 mechanism by enhancing the reactivity of the nucleophile. Polar
protic solvents favor the SN1 mechanism by stabilizing the carbocation intermediate. SN1 reactions are frequently
solvolysis reactions.
For example, the reaction below has a tertiary alkyl bromide as the electrophile, a weak nucleophile, and a polar protic solvent
(we’ll assume that methanol is the solvent). Thus we’d confidently predict an SN1 reaction mechanism. Because substitution occurs
at a chiral carbon, we can also predict that the reaction will proceed with racemization.

In the reaction below, on the other hand, the electrophile is a secondary alkyl bromide – with these, both SN1 and SN2 mechanisms
are possible, depending on the nucleophile and the solvent. In this example, the nucleophile (a thiolate anion) is strong, and a polar

9.9.1 https://chem.libretexts.org/@go/page/210469
protic solvent is used – so the SN2 mechanism is heavily favored. The reaction is expected to proceed with inversion of
configuration.

Template:ExampleStart
Exercise 8.15: Determine whether each substitution reaction shown below is likely to proceed by an SN1 or SN2 mechanism.

Solution
Template:ExampleEnd
In all of our discussion so far about nucleophilic substitutions, we have ignored another important possibility. In many cases,
including the two examples above, substitution reactions compete with a type of reaction known as elimination. Consider, for
example, the two courses that a reaction could take when tert-butyl bromide reacts with water:

We begin with formation of the carbocation intermediate. In pathway ‘a’, water acts as a nucleophile – this is, of course, the
familiar SN1 reaction. However, a water molecule encountering the carbocation intermediate could alternatively act as a base rather
than as a nucleophile, plucking a proton from one of the methyl carbons and causing the formation of a new carbon-carbon p bond.
This alternative pathway is called an elimination reaction, and in fact with the conditions above, both the substitution and the
elimination pathways will occur in competition with each other.
We will have lots more to say about elimination reactions in chapter 14, focusing on biochemical eliminations but also thinking
about the competition between substitution and elimination that occurs with many nonenzymatic reactions.
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

Further Reading
MasterOrganicChemistry
Steric Hindrance is Like A Fat Goalie
Khan Academy
Steric Hinderance
Solvent Effects
Another Solvent Effect Video
Summary

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Leah4Sci
Choosing Between SN1 and SN2 Reactions (vid 1 of 2) By Leah4sci
SN1 vs SN2 Practice Examples (vid 2 of 2) by Leah4sci
Cliffs Notes
Comparison of SN2 and SN1
Slide Presentations
SN1 and SN2 workshop
Substitution lectures powerpoint files
Web Pages
Handout comparing SN1 and SN2
Transtutors SN1 and SN2
Summary of SN1 and SN2
Summary of nucleophilic substitution
Comparison of SN1 and SN2
Comparing stereochemistry of substitution reactions
Substitution overview
Nucleophilic Substitution mechanisms
Substitution overview
Busy page on nucleophilic substitution mechanisms
Two mechanisms
*Sloppy handout
All about substuttion reactions
Great discussion of SN2 and SN1 reactions
Handout about substitution reactions
Videos
Comparing SN2 and SN1
SN1 vs SN2 made easy
Intro to SN1 and SN2
SN2 and SN1 mechanisms
Intro to Nucleophilic reactions
Nucleophilic substitution explained
Yale lecture on substitution reactions
SN2 and SN1 made easy
Comparing SN1 and SN2 video
summary of SN1 and SN2
Nucleophilic substitution video
Comparison of SN1 and SN2 video
SN1 vs SN2 video

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Factors that affect SN2 and SN1
Tutorial
Nuggets of Knowledge on SN1 and SN2
Guide to comparing SN1 and SN2
Practice Problems
Good quiz
Good problem set
Nucleophilic Substitution reactions

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9.10: Comparing E1 and E2
Having discussed the many factors that influence nucleophilic substitution and elimination reactions of alkyl halides, we must now consider the
practical problem of predicting the most likely outcome when a given alkyl halide is reacted with a given nucleophile. As we noted earlier, several
variables must be considered, the most important being the structure of the alkyl group and the nature of the nucleophilic reactant.In general, in
order for an SN1 or E1 reaction to occur, the relevant carbocation intermediate must be relatively stable. Strong nucleophile favor substitution, and
strong bases, especially strong hindered bases (such as tert-butoxide) favor elimination.
The nature of the halogen substituent on the alkyl halide is usually not very significant if it is Cl, Br or I. In cases where both SN2 and E2 reactions
compete, chlorides generally give more elimination than do iodides, since the greater electronegativity of chlorine increases the acidity of beta-
hydrogens. Indeed, although alkyl fluorides are relatively unreactive, when reactions with basic nucleophiles are forced, elimination occurs (note the
high electronegativity of fluorine).
The following table summarizes the expected outcome of alkyl halide reactions with nucleophiles. It is assumed that the alkyl halides have one or
more beta-hydrogens, making elimination possible; and that low dielectric solvents (e.g. acetone, ethanol, tetrahydrofuran & ethyl acetate) are used.
When a high dielectric solvent would significantly influence the reaction this is noted in red. Note that halogens bonded to sp2 or sp hybridized
carbon atoms do not normally undergo substitution or elimination reactions with nucleophilic reagents.

Nucleophile

A
l
kAnionic Nucleophiles
y( Weak Bases: I–, Br–, SCN–, N –, Anionic Nucleophiles Neutral Nucleophiles
3
lCH CO – , RS–, CN– etc. ) ( Strong Bases: HO–, RO– ) ( H2O, ROH, RSH, R3N )
3 2
G pKa's > 15 pKa's ranging from -2 to 11
pKa's from -9 to 10 (left to right)
r
o
u
p

P
r
i
m
a Rapid SN2 substitution. E2 elimination may also occur.
Rapid SN2 substitution. The rate may be reduced by e.g.
r SN2 substitution. (N ≈ S >>O)
substitution of β-carbons, as in the case of neopentyl.
y ClCH2CH2Cl + KOH ——> CH2=CHCl
R
C
H
2
–

S
e
c
o
nSN2 substitution and / or E2 elimination (depending on the
SN2 substitution. (N ≈ S >>O)
dbasicity of the nucleophile). Bases weaker than acetate (pKa
In high dielectric ionizing solvents, such as water,
a= 4.8) give less elimination. The rate of substitution may be E2 elimination will dominate.
dimethyl sulfoxide & acetonitrile, SN1 and E1 products
rreduced by branching at the β-carbons, and this will
may be formed slowly.
yincrease elimination.
R
2
C
H
–

9.10.1 https://chem.libretexts.org/@go/page/210470
T
e
r
tE2 elimination will dominate with most nucleophiles (even
iif they are weak bases). No SN2 substitution due to steric E2 elimination will dominate. No SN2 substitution will E2 elimination with nitrogen nucleophiles (they are
ahindrance. In high dielectric ionizing solvents, such as occur. In high dielectric ionizing solvents SN1 and E1 bases). No SN2 substitution. In high dielectric ionizing
rwater, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be formed. solvents SN1 and E1 products may be formed.
yproducts may be expected.
R
3
C
–

A
l
l
y
l Nitrogen and sulfur nucleophiles will give SN2
Rapid SN2 substitution for 1º and 2º-halides. For 3º-halides
H Rapid SN2 substitution for 1º halides. E2 elimination substitution in the case of 1º and 2º-halides. 3º-halides
a very slow SN2 substitution or, if the nucleophile is
2 will compete with substitution in 2º-halides, and will probably give E2 elimination with nitrogen
moderately basic, E2 elimination. In high dielectric ionizing
C dominate in the case of 3º-halides. In high dielectric nucleophiles (they are bases). In high dielectric
solvents, such as water, dimethyl sulfoxide & acetonitrile,
= ionizing solvents SN1 and E1 products may be formed. ionizing solvents SN1 and E1 products may be formed.
S 1 and E1 products may be observed.
CN Water hydrolysis will be favorable for 2º & 3º-halides.
H
C
H
2
–

B
e
n
z
Nitrogen and sulfur nucleophiles will give SN2
yRapid SN2 substitution for 1º and 2º-halides. For 3º-halides Rapid SN2 substitution for 1º halides (note there are no
substitution in the case of 1º and 2º-halides. 3º-halides
la very slow SN2 substitution or, if the nucleophile is β hydrogens). E2 elimination will compete with
will probably give E2 elimination with nitrogen
Cmoderately basic, E2 elimination. In high dielectric ionizing substitution in 2º-halides, and dominate in the case of
nucleophiles (they are bases). In high dielectric
6solvents, such as water, dimethyl sulfoxide & acetonitrile, 3º-halides. In high dielectric ionizing solvents SN1 and
ionizing solvents SN1 and E1 products may be formed.
HSN1 and E1 products may be observed. E1 products may be formed.
Water hydrolysis will be favorable for 2º & 3º-halides.
5
C
H
2
–

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

Further Reading
MasterOrganicChemistry
Comparing the E1 and E2 Reactions
Elimination Reactions Are Favored By Heat
Comparing the E1 and E2 Reactions
Bulky Bases In Elimination Reactions
Web Pages
Elimination mechanisms
Videos
E1 and E2 made easy
E1 and E2
E1 and E2 elimination video

9.10.2 https://chem.libretexts.org/@go/page/210470
E1 and E2 Elimination Reaction video
Comparing E1 and E2 reactions
Practice Problems
Carey problems

9.10: Comparing E1 and E2 is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Competition between substitution and elimination is licensed CC BY-NC-SA 4.0.

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SECTION OVERVIEW

9.11: Determining SN2, SN¬1, E2 or E1

Topic hierarchy

The functional group of alkyl halides is a carbon-halogen bond, the common halogens being fluorine, chlorine, bromine and iodine. With the exception
of iodine, these halogens have electronegativities significantly greater than carbon. Consequently, this functional group is polarized so that the carbon
is electrophilic and the halogen is nucleophilic, as shown in the drawing below.

Two characteristics other than electronegativity also have an important influence on the chemical behavior of these compounds. The first of these is
covalent bond strength. The strongest of the carbon-halogen covalent bonds is that to fluorine. Remarkably, this is the strongest common single bond
to carbon, being roughly 30 kcal/mole stronger than a carbon-carbon bond and about 15 kcal/mole stronger than a carbon-hydrogen bond. Because of
this, alkyl fluorides and fluorocarbons in general are chemically and thermodynamically quite stable, and do not share any of the reactivity
patterns shown by the other alkyl halides. The carbon-chlorine covalent bond is slightly weaker than a carbon-carbon bond, and the bonds to the other
halogens are weaker still, the bond to iodine being about 33% weaker. The second factor to be considered is the relative stability of the corresponding
halide anions, which is likely the form in which these electronegative atoms will be replaced. This stability may be estimated from the relative acidities
of the H-X acids, assuming that the strongest acid releases the most stable conjugate base (halide anion). With the exception of HF (pKa = 3.2), all the
hydrohalic acids are very strong, small differences being in the direction HCl < HBr < HI.
The characteristics noted above lead us to anticipate certain types of reactions that are likely to occur with alkyl halides. The following table
summarizes the expected outcome of alkyl halide reactions with nucleophiles. It is assumed that the alkyl halides have one or more beta-hydrogens,
making elimination possible; and that low dielectric solvents (e.g. acetone, ethanol, tetrahydrofuran & ethyl acetate) are used. When a high dielectric
solvent would significantly influence the reaction this is noted in red.
Note that halogens bonded to sp2 or sp hybridized carbon atoms do not normally undergo substitution or elimination reactions with
nucleophilic reagents.

Nucleophile

A
l
kIonic Nucleophiles
y( Weak Bases: I–, Br–, SCN–, N –, Anionic Nucleophiles Neutral Nucleophiles
3
lCH CO – , RS–, CN– etc. ) ( Strong Bases: HO–, RO– ) ( H2O, ROH, RSH, R3N )
3 2
G pKa's > 15 pKa's ranging from -2 to 11
pKa's from -9 to 10 (left to right)
r
o
u
p

P
r
i
m
a Rapid SN2 substitution. E2 elimination may also occur.
Rapid SN2 substitution. The rate may be reduced by
r e.g. SN2 substitution. (N ≈ S >>O)
substitution of β-carbons, as in the case of neopentyl.
y ClCH2CH2Cl + KOH → CH2=CHCl
R
C
H
2
–

9.11.1 https://chem.libretexts.org/@go/page/210471
S
e
c
o
nSN2 substitution and / or E2 elimination (depending on the
SN2 substitution. (N ≈ S >>O)
dbasicity of the nucleophile). Bases weaker than acetate (pKa
In high dielectric ionizing solvents, such as water,
a= 4.8) give less elimination. The rate of substitution may be E2 elimination will dominate.
dimethyl sulfoxide & acetonitrile, SN1 and E1 products
r reduced by branching at the β-carbons, and this will
may be formed slowly.
y increase elimination.
R
2
C
H
–

T
e
r
t E2 elimination will dominate with most nucleophiles (even
i if they are weak bases). No SN2 substitution due to steric E2 elimination will dominate. No SN2 substitution will E2 elimination with nitrogen nucleophiles (they are
a hindrance. In high dielectric ionizing solvents, such as occur. In high dielectric ionizing solvents SN1 and E1 bases). No SN2 substitution. In high dielectric ionizing
r water, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be formed. solvents SN1 and E1 products may be formed.
y products may be expected.
R
3
C
–

A
l
l
y
l Nitrogen and sulfur nucleophiles will give SN2
Rapid SN2 substitution for 1º and 2º-halides. For 3º-halides
H Rapid SN2 substitution for 1º halides. E2 elimination substitution in the case of 1º and 2º-halides. 3º-halides
a very slow SN2 substitution or, if the nucleophile is
2 will compete with substitution in 2º-halides, and will probably give E2 elimination with nitrogen
moderately basic, E2 elimination. In high dielectric ionizing
C dominate in the case of 3º-halides. In high dielectric nucleophiles (they are bases). In high dielectric
solvents, such as water, dimethyl sulfoxide & acetonitrile,
= ionizing solvents SN1 and E1 products may be formed. ionizing solvents SN1 and E1 products may be formed.
SN1 and E1 products may be observed.
C Water hydrolysis will be favorable for 2º & 3º-halides.
H
C
H
2
–

B
e
n
z
Nitrogen and sulfur nucleophiles will give SN2
yRapid SN2 substitution for 1º and 2º-halides. For 3º-halides Rapid SN2 substitution for 1º halides (note there are no
substitution in the case of 1º and 2º-halides. 3º-halides
l a very slow SN2 substitution or, if the nucleophile is β hydrogens). E2 elimination will compete with
will probably give E2 elimination with nitrogen
Cmoderately basic, E2 elimination. In high dielectric ionizing substitution in 2º-halides, and dominate in the case of
nucleophiles (they are bases). In high dielectric
6 solvents, such as water, dimethyl sulfoxide & acetonitrile, 3º-halides. In high dielectric ionizing solvents SN1 and
ionizing solvents SN1 and E1 products may be formed.
H SN1 and E1 products may be observed. E1 products may be formed.
Water hydrolysis will be favorable for 2º & 3º-halides.
5
C
H
2
–

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

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Additional Resources
MasterOrganicChemistry
Trapped In SN1/SN2/E1/E2 Hell? Some Resources
Deciding SN1/SN2/E1/E2 (1) – The Substrate
Deciding SN1/SN2/E1/E2 (2) – The Nucleophile/Base
Deciding SN1/SN2/E1/E2 (3) – The Solvent
Deciding SN1/SN2/E1/E2 (4) – The Temperature
Wrapup – The Quick N’ Dirty Guide To SN1/SN2/E1/E2
Khan Academy
Nucleophilicity and Basicity
Primary and tertiary alkyl halides
Secondary Alkyl Halides
Leah4Sci
Alkyl Halide Carbon Chain Analysis for SN1 SN2 E1 E2 Reactions
Slide Presentations
SN1 SN2 E1 E2 comparison slides
Web Pages
Elimination vs Substitution
SN1, SN2, E1, E2 Summary
Summary of SN1, SN2, E1 and E2
*Comparison of SN1, SN2, E1, E2
Substituation vs elimination considerations
Relationship between Sn1 and E1
Substitution vs Elimination summary
Good summation of SN2/SN1/E1/E2 reaction properties
Good handouts of substitution and elimination
Good summary of SN1, Sn2, E1, E2
SN1 SN2 E1 E2 comparison
Videos
SN1, SN2, E1, E2
Role of solvent in SN1, SN2, E1, E2
LONG video on SN1 SN2 E1 E2
Practice Problems
Answers to elimination questions

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9.12: Carbenes
A carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general
formula is R-(C:)-R' or R=C:. The term "carbene" may also refer to the specific compound H2C:, also called methylene, the parent
hydride from which all other carbene compounds are formally derived. Carbenes are classified as either singlets or triplets
depending upon their electronic structure. Most carbenes are very short lived, although persistent carbenes are known. One well
studied carbene is Cl2C:, or dichlorocarbene, which can be generated in situ from chloroform and a strong base.

Singlet and triplet carbenes

The two classes of carbenes are singlet and triplet carbenes. Singlet carbenes are spin-paired. In the language of valence bond
theory, the molecule adopts an sp2 hybrid structure. Triplet carbenes have two unpaired electrons. They may be either linear or
bent, i.e. sp or sp2 hybridized, respectively. Most carbenes have a nonlinear triplet ground state, except for those with nitrogen,
oxygen, or sulfur atoms, and halides directly bonded to the divalent carbon.

Figure 1: Image used with permission from Wikipedia

Carbenes are called singlet or triplet depending on the electronic spins they possess. Triplet carbenes are paramagnetic and may be
observed by electron spin resonance spectroscopy if they persist long enough. The total spin of singlet carbenes is zero while that
of triplet carbenes is one (in units of [\hbar] ). Bond angles are 125-140° for triplet methylene and 102° for singlet methylene (as
determined by EPR). Triplet carbenes are generally stable in the gaseous state, while singlet carbenes occur more often in aqueous
media.
For simple hydrocarbons, triplet carbenes usually have energies 8 kcal/mol (33 kJ/mol) lower than singlet carbenes (see also
Hund's rule of maximum multiplicity), thus, in general, triplet is the more stable state (the ground state) and singlet is the excited
state species.Substituents that can donate electron pairs may stabilize the singlet state by delocalizing the pair into an empty p-
orbital. If the energy of the singlet state is sufficiently reduced it will actually become the ground state. No viable strategies exist
for triplet stabilization. The carbene called 9-fluorenylidene has been shown to be a rapidly equilibrating mixture of singlet and
triplet states with an approximately 1.1 kcal/mol (4.6 kJ/mol) energy difference.[3] It is, however, debatable whether diaryl
carbenes such as the fluorene carbene are true carbenes because the electrons can delocalize to such an extent that they become in
fact biradicals. In silico experiments suggest that triplet carbenes can be thermodynamically stabilized with electropositive
heteroatoms such as in silyl and silyloxy carbenes, especially trifluorosilyl carbenes.[4]

Reactivity

Carbene addition to alkenes

Singlet and triplet carbenes exhibit divergent reactivity. Singlet carbenes generally participate in cheletropic reactions as either
electrophiles or nucleophiles. Singlet carbenes with unfilled p-orbital should be electrophilic. Triplet carbenes can be considered to
be diradicals, and participate in stepwise radical additions. Triplet carbenes have to go through an intermediate with two unpaired
electrons whereas singlet carbene can react in a single concerted step.
Due to these two modes of reactivity, reactions of singlet methylene are stereospecific whereas those of triplet methylene are
stereoselective. This difference can be used to probe the nature of a carbene. For example, the reaction of methylene generated
from photolysis of diazomethane with cis-2-butene or with trans-2-butene each give a single diastereomer of the 1,2-
dimethylcyclopropane product: cis from cis and trans from trans, which proves that the methylene is a singlet.[5] If the methylene

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were a triplet, one would not expect the product to depend upon the starting alkene geometry, but rather a nearly identical mixture
in each case.
Reactivity of a particular carbene depends on the substituent groups. Their reactivity can be affected by metals. Some of the
reactions carbenes can do are insertions into C-H bonds, skeletal rearrangements, and additions to double bonds. Carbenes can be
classified as nucleophilic, electrophilic, or ambiphilic. For example, if a substituent is able to donate a pair of electrons, most likely
carbene will not be electrophilic. Alkyl carbenes insert much more selectively than methylene, which does not differentiate
between primary, secondary, and tertiary C-H bonds.

Cyclopropanation
Carbenes add to double bonds to form cyclopropanes. A concerted mechanism is available for singlet carbenes. Triplet carbenes do
not retain stereochemistry in the product molecule. Addition reactions are commonly very fast and exothermic. The slow step in
most instances is generation of carbene. A well-known reagent employed for alkene-to-cyclopropane reactions is Simmons-Smith
reagent. This reagent is a system of copper, zinc, and iodine, where the active reagent is believed to be iodomethylzinc iodide.
Reagent is complexed by hydroxy groups such that addition commonly happens syn to such group.

Carbene cyclopropanation

C—H insertion

Carbene insertion
Insertions are another common type of carbene reactions. The carbene basically interposes itself into an existing bond. The order of
preference is commonly: 1. X–H bonds where X is not carbon 2. C–H bond 3. C–C bond. Insertions may or may not occur in single
step.
Intramolecular insertion reactions present new synthetic solutions. Generally, rigid structures favor such insertions to happen.
When an intramolecular insertion is possible, no intermolecular insertions are seen. In flexible structures, five-membered ring
formation is preferred to six-membered ring formation. Both inter- and intramolecular insertions are amendable to asymmetric
induction by choosing chiral ligands on metal centers.

Carbene intramolecular reaction

Carbene intermolecular reaction

Alkylidene carbenes are alluring in that they offer formation of cyclopentene moieties. To generate an alkylidene carbene a ketone
can be exposed to trimethylsilyl diazomethane.

Alkylidene carbene

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Carbene dimerization
Carbenes and carbenoid precursors can undergo dimerization reactions to form alkenes. While this is often an unwanted side
reaction, it can be employed as a synthetic tool and a direct metal carbene dimerization has been used in the synthesis of
polyalkynylethenes. Persistent carbenes exist in equilibrium with their respective dimers. This is known as the Wanzlick
equilibrium.

Figure : Wanzlick equilibrium

Carbene ligands in organometallic chemistry

In organometallic species, metal complexes with the formulae LnMCRR' are often described as carbene complexes. Such species
do not however react like free carbenes and are rarely generated from carbene precursors, except for the persistent carbenes. The
transition metal carbene complexes can be classified according to their reactivity, with the first two classes being the most clearly
defined:
Fischer carbenes, in which the carbene is bonded to a metal that bears an electron-withdrawing group (usually a carbonyl). In
such cases the carbenoid carbon is mildly electrophilic.
Schrock carbenes, in which the carbene is bonded to a metal that bears an electron-donating group. In such cases the carbenoid
carbon is nucleophilic and resembles Wittig reagent (which are not considered carbene derivatives).
Persistent carbenes, also known as Arduengo or Wanzlick carbenes. These include the class of N-heterocyclic carbenes (NHCs)
and are often are used as ancillary ligands in organometallic chemistry. Such carbenes are spectator ligands of low reactivity.

Generation of carbenes
A method that is broadly applicable to organic synthesis is induced elimination of halides from gem-dihalides employing
organolithium reagents. It remains uncertain if under these conditions free carbenes are formed or metal-carbene complex.
Nevertheless, these metallocarbenes (or carbenoids) give the expected organic products.

R2CBr2 + BuLi → R2CLi(Br) +

BuBr
R
2CLi(Br) → R2C + LiBr

For cyclopropanations, zinc is employed in the Simmons–Smith reaction. In a specialized but instructive case, alpha-
halomercury compounds can be isolated and separately thermolyzed. For example, the "Seyferth reagent" releases CCl2 upon
heating.

C6H5HgCCl3 → CCl2 + C6H5HgCl

Most commonly, carbenes are generated from diazoalkanes, via photolytic, thermal, or transition metal-catalyzed routes.
Catalysts typically feature rhodium and copper. The Bamford-Stevens reaction gives carbenes in aprotic solvents and
carbenium ions in protic solvents.
Base-induced elimination HX from haloforms (CHX3) with under phase-transfer conditions.
Photolysis of diazirines and epoxides can also be employed. Diazirines are cyclic forms of diazoalkanes. The strain of the small
ring makes photoexcitation easy. Photolysis of epoxides gives carbonyl compounds as side products. With asymmetric
epoxides, two different carbonyl compounds can potentially form. The nature of substituents usually favors formation of one
over the other. One of the C-O bonds will have a greater double bond character and thus will be stronger and less likely to
break. Resonance structures can be drawn to determine which part will contribute more to the formation of carbonyl. When one
substituent is alkyl and another aryl, the aryl-substituted carbon is usually released as a carbene fragment.
Carbenes are intermediates in the Wolff rearrangement

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See also
Transition metal carbene complexes, also known as carbenoids
Atomic carbon a single carbon atom with the chemical formula :C:, in effect a twofold carbene. Also has been used to make
"true carbenes" in situ.
Foiled carbenes derive their stability from proximity of a double bond (i.e. their ability to form conjugated systems).
Carbene analogs
Carbenium ions, protonated carbenes
Ring opening metathesis polymerization

References
1. Hoffmann, Roald (2005). Molecular Orbitals of Transition Metal Complexes. Oxford. p. 7. ISBN 0-19-853093-5.
2. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–)
"carbenes".
3. Grasse, P. B.; Brauer, B. E.; Zupancic, J. J.; Kaufmann, K. J.; Schuster, G. B. (1983). "Chemical and physical properties of
fluorenylidene: equilibration of the singlet and triplet carbenes". Journal of the American Chemical Society 105 (23):
6833.doi:10.1021/ja00361a014. edit
4. Nemirowski, A; Schreiner, P. R. (November 2007). "Electronic Stabilization of Ground State Triplet Carbenes". J. Org. Chem.
72 (25): 9533–9540. doi:10.1021/jo701615x.PMID 17994760.
5. Skell, P. S.; Woodworth, R. C. (1956). Journal of the American Chemical Society 78(17): 4496. doi:10.1021/ja01598a087. edit
6. Bajzer, W. X. (2004). "Fluorine Compounds, Organic". Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley &
Sons.doi:10.1002/0471238961.0914201802011026.a01.pub2. edit
7. Buchner, E.; Feldmann, L. (1903). "Diazoessigester und Toluol". Berichte der deutschen chemischen Gesellschaft 36 (3): 3509.
doi:10.1002/cber.190303603139.edit
8. Staudinger, H.; Kupfer, O. (1912). "Über Reaktionen des Methylens. III. Diazomethan".Berichte der deutschen chemischen
Gesellschaft 45: 501.doi:10.1002/cber.19120450174. edit
9. Von E. Doering, W.; Hoffmann, A. K. (1954). "The Addition of Dichlorocarbene to Olefins". Journal of the American Chemical
Society 76 (23): 6162.doi:10.1021/ja01652a087. edit

9.12: Carbenes is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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9.13: Cyclopropane Synthesis
Objectives
After completing this section, you should be able to
1. describe, and write the detailed mechanism for, the formation of a carbene, such as dichlorocarbene.
2. describe the structure of a carbene in terms of the hybridization of the central carbon atom.
3. write an equation for the formation of a substituted cyclopropane from an alkene and a carbene.
4. identify the reagents, the alkene, or both, needed to prepare a given substituted cyclopropane by addition of a carbene to a
double bond.
5. identify the substituted cyclopropane formed from the reaction of a given alkene with the reagents necessary to form a
carbene.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
carbene (R2C:)
carbenoid
Simmons-Smith reaction
stereospecific

 Study Notes

A carbenoid is best considered to be a reagent which, while not actually a carbene, behaves as if it were an intermediate of this
type.
Dichlorocarbenes can also form cyclopropane structures and are created in situ from reagents such as chloroform and KOH.

The detailed mechanism of the formation of dichlorocarbene is given below. Note that the deprotonation of chloroform
generates the trichloromethanide anion, which spontaneously expels the chloride anion.

The highly strained nature of cyclopropane compounds makes them very reactive and interesting synthetic targets. Additionally
cyclopropanes are present in numerous biological compounds. One common method of cyclopropane synthesis is the reaction of
carbenes with the double bond in alkenes or cycloalkenes. Methylene, H2C, is simplest carbene, and in general carbenes have the

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formula R2C. Other species that will also react with alkenes to form cyclopropanes but do not follow the formula of carbenes are
referred to as carbenoids.

Introduction
Carbenes were once only thought of as short lived intermediates. The reactions of this section only deal with these short lived
carbenes which are mostly prepared in situ, in conjunction with the main reaction. However, there do exist so called persistent
carbenes. These persistent carbenes are stabilized by a variety of methods often including aromatic rings or transition metals. In
general a carbene is neutral and has 6 valence electrons, 2 of which are non bonding. These electrons can either occupy the same
sp2 hybridized orbital to form a singlet carbene (with paired electrons), or two different sp2 orbitals to from a triplet carbene (with
unpaired electrons). The chemistry of triplet and singlet carbenes is quite different but can be oversimplified to the statement:
singlet carbenes usually retain stereochemistry while triplet carbenes do not. The carbenes discussed in this section are singlet and
thus retain stereochemistry.
The reactivity of a singlet carbene is concerted and similar to that of electrophilic or nucleophilic addition (although, triplet
carbenes react like biradicals, explaining why sterochemistry is not retained). The highly reactive nature of carbenes leads to very
fast reactions in which the rate determining step is generally carbene formation.

Preparation of methylene
The preparation of methylene starts with the yellow gas diazomethane, CH2N2. Diazomethane can be exposed to light, heat or
copper to facilitate the loss of nitrogen gas and the formation of the simplest carbene methylene. The process is driven by the
formation of the nitrogen gas which is a very stable molecule.

Carbene reaction with alkenes

A carbene such as methlyene will react with an alkene which will break the double bond and result with a cyclopropane. The
reaction will usually leave stereochemistry of the double bond unchanged. As stated before, carbenes are generally formed along
with the main reaction; hence the starting material is diazomethane not methylene.

In the above case cis-2-butene is converted to cis-1,2-dimethylcyclopropane. Likewise, below the trans configuration is
maintained.

Additional Types of Carbenes and Carbenoids

In addition to the general carbene with formula R2C there exist a number of other compounds that behave in much the same way as
carbenes in the synthesis of cyclopropane. Halogenated carbenes are formed from halomethanes. An example is dicholorcarbene,
Cl2C. These halogenated carbenes will form cyclopropanes in the same manner as methylene but with the interesting presence of
two halogen atoms in place of the hydrogen atoms.
Carbenoids are substances that form cyclopropanes like carbenes but are not technically carbenes. One common example is the
stereospecific Simmons-Smith reaction which utilizes the carbenoid ICH2ZnI. The carbenoid is formed in situ via the mixing of a
Zn-Cu couple with CH2I2.Since this reacts the same as a carbene, the same methods can be applied to determine the product. An
example of this is given as problem 5.

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Outside links
http://en.Wikipedia.org/wiki/Simmons-Smith_reaction
http://en.Wikipedia.org/wiki/Carbene

References
1. Vollhardt, K. Peter C. and Schore, Neil E. Organic Chemistry: Structure and Function. New York: Bleyer, Brennan, 2007.
2. Abdel-Wahab, Aboel-Magd A. Ahmed, Saleh A. and Dürr, Heinz. "Carbene Formation by Extrusion of Nitrogen" in CRC
Handbook of Organic Photochemistry and Photobiology. CRC Press, 2004.

Exercises

 Exercise 9.13.1

Predict the resulting products. Will they be the same product?

Answer
No they will not be the same product, they will be isomers of each other.

 Exercise 9.13.2

What would be the result of a Simmons-Smith reaction that used trans-3-pentene as a reagent?

Answer
The stereochemistry will be retained making a cyclopropane with trans methyl and ethyl groups. Trans-1-ethyl-2-
methylcyclopropane

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 Exercise 9.13.3
Draw the product of this reaction. What type of reaction is this?

Answer
This is a Simmons-Smith reaction which uses the carbenoid formed by the CH2I2 and Zu-Cu. The reaction results in the
same product as if methylene was used and retains stereospecificity. Iodine metal and the Zn-Cu are not part of the product.
The product is trans-1,2-ethyl-methylcyclopropane.

 Exercise 9.13.4

What would the following reaction yield?

Answer
The halogenated carbene will react the same as methylene yielding, cis-1,1-dichloro-2,3dimethylcyclopropane.

Questions
Q8.9.1
Predict the following products. Will they be the same product?

Solutions
S8.9.1
No they will not be the same product, they will be isomers of each other.

9.13.4 https://chem.libretexts.org/@go/page/210476
Contributors and Attributions
Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
Paul Tisher

9.13: Cyclopropane Synthesis is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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CHAPTER OVERVIEW

10: The Chemistry of Alcohols and Thiols

10: The Chemistry of Alcohols and Thiols is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

1
10.1: Dehydration Reactions of Alcohols
Dehydration of Alcohols to Yield Alkenes
One way to synthesize alkenes is by dehydration of alcohols, a process in which alcohols undergo E1 or E2 mechanisms to lose
water and form a double bond. The dehydration reaction of alcohols to generate alkene proceeds by heating the alcohols in the
presence of a strong acid, such as sulfuric or phosphoric acid, at high temperatures.

The required range of reaction temperature decreases with increasing substitution of the hydroxy-containing carbon:
1° alcohols: 170° - 180°C
2° alcohols: 100°– 140 °C
3° alcohols: 25°– 80°C
If the reaction is not sufficiently heated, the alcohols do not dehydrate to form alkenes, but react with one another to form ethers
(e.g., the Williamson Ether Synthesis).

Alcohols are amphoteric; they can act as both acid or base. The lone pair of electrons on oxygen atom makes the –OH group
weakly basic. Oxygen can donate two electrons to an electron-deficient proton. Thus, in the presence of a strong acid, R—OH acts
as a base and protonates into the very acidic alkyloxonium ion +OH2 (The pKa value of a tertiary protonated alcohol can go as low
as -3.8). This basic characteristic of alcohol is essential for its dehydration reaction with an acid to form alkenes.

Mechanism for the Dehydration of Alcohol into Alkene

Different types of alcohols may dehydrate through a slightly different mechanism pathway. However, the general idea behind each
dehydration reaction is that the –OH group in the alcohol donates two electrons to H+ from the acid reagent, forming an
alkyloxonium ion. This ion acts as a very good leaving group which leaves to form a carbocation. The deprotonated acid (the base)
then reacts with the hydrogen adjacent to the carbocation and form a double bond.
Primary alcohols undergo bimolecular elimination (E2 mechanism) while secondary and tertiary alcohols undergo unimolecular
elimination (E1 mechanism). The relative reactivity of alcohols in dehydration reactions is ranked as follows:
Methanol < primary < secondary < tertiary
Primary alcohols dehydrate through the E2 mechanism. The hydroxyl oxygen donates two electrons to a proton from sulfuric acid
(H2SO4), forming an alkyloxonium ion. Then the conjugate base, HSO4–, reacts with one of the adjacent (beta) hydrogen atoms
while the alkyloxonium ion leaves in a concerted process, forming a double bond.

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Secondary and tertiary alcohols dehydrate through the E1 mechanism. Similarly to the reaction above, secondary and tertiary –OH
protonate to form alkyloxonium ions. However, in this case the ion leaves first and forms a carbocation as the reaction
intermediate. The water molecule (which is a stronger base than the HSO4- ion) then abstracts a proton from an adjacent carbon to
form a double bond. Notice in the mechanism below that the alkene formed depends on which proton is abstracted: the red arrows
show formation of the more substituted 2-butene, while the blue arrows show formation of the less substituted 1-butene. Recall that
according to Zaitsev's Rule, the more substituted alkenes are formed preferentially because they are more stable than less
substituted alkenes. Additinally, trans alkenes are more stable than cis alkenes and are also the major product formed. For the
example below, the trans diastereomer of the 2-butene product is most abundant.

Dehydration reaction of secondary alcohol

The dehydration mechanism for a tertiary alcohol is analogous to that shown above for a secondary alcohol.

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The E2 elimination of 3º-alcohols under relatively non-acidic conditions may be accomplished by treatment with phosphorous
oxychloride (POCl3) in pyridine. This procedure is also effective with hindered 2º-alcohols, but for unhindered and 1º-alcohols an
SN2 chloride ion substitution of the chlorophosphate intermediate competes with elimination. Examples of these and related
reactions are given in the following figure. The first equation shows the dehydration of a 3º-alcohol. The predominance of the non-
Zaitsev product (less substituted double bond) is presumed due to steric hindrance of the methylene group hydrogen atoms, which
interferes with the approach of base at that site. The second example shows two elimination procedures applied to the same 2º-
alcohol. The first uses the single step POCl3 method, which works well in this case because SN2 substitution is retarded by steric
hindrance. The second method is another example in which an intermediate sulfonate ester confers halogen-like reactivity on an
alcohol. In every case the anionic leaving group is the conjugate base of a strong acid.

Practice Problems (aka Exercises)

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Exercises
6. Starting with cyclohexanol, describe how you would prepare cyclohexene.
7. In the dehydration of 1-methylcyclohexanol, which product is favored?

8.
In the dehydration of this diol the resulting product is a ketone. Draw the mechanism of its formation. (Hint a rearrangement
occurs)

9.
Draw an arrow pushing mechanism for the acid catalyzed dehydration of the following alcohol, make sure to draw both
potential mechanisms. Assume no rearrangement for the first two product mechanisms. Which of these two would likely be the
major product? If there was a rearrangement, draw the expected major product.

Answer

6. H2SO4 with heat since there are no concerns about C+ rearrangement

7. The more substituted alkene is favored, as more substituted alkenes are relatively lower in energy.

8.
This reaction is known as the Pinacol rearrangement.

Note how the carbocation after the rearrangement is resonance stabilized by the oxygen

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9. Note: While the mechanism is instructive for the first part of the this answer. The carbocation rearrangement would occur
and determine the major and minor products as explained in the second part of this answer.

The major product of this mechanism would be the more highly substituted alkene, or the product formed from the red
arrows.
Note: With the secondary carbocation adjacent a tertiary carbon center, a 1,2 hydride shift (rearrangement) would occur to
form a tertiary carbocation and vcompound below would be the major product. The minor product being the same product
as the one formed from the red arrows.

Contributors and Attributions

Jeffrey Ma

10.1: Dehydration Reactions of Alcohols is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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10.2: Reactions of Alcohols with Hydrohalic Acids
Conversion of Alcohols into Alkyl Halides
When alcohols react with a hydrogen halide, a substitution takes place producing an alkyl halide and water:

The order of reactivity of alcohols is 3° > 2° > 1° methyl.

The order of reactivity of the hydrogen halides is HI > HBr > HCl (HF is generally unreactive).
The reaction is acid catalyzed. Alcohols react with the strongly acidic hydrogen halides HCl, HBr, and HI, but they do not react
with nonacidic NaCl, NaBr, or NaI. Primary and secondary alcohols can be converted to alkyl chlorides and bromides by allowing
them to react with a mixture of a sodium halide and sulfuric acid:

Because Cl- is a weaker nucleophile than Br-, the reaction with HCl requires a catalyst such as ZnCl2 as shown below.

Mechanisms of the Reactions of Alcohols with HX

Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation, in an
S 1 reaction with the protonated alcohol acting as the substrate.
N

The S 1 mechanism is illustrated by the reaction tert-butyl alcohol and aqueous hydrochloric acid (H O , C l ). The first two
N 3
+ −

steps in this S 1 substitution mechanism are protonation of the alcohol to form an oxonium ion. Although the oxonium ion is
n

formed by protonation of the alcohol, it can also be viewed as a Lewis acid-base complex between the cation (R ) and H O.+
2

Protonation of the alcohol converts a poor leaving group (OH-) to a good leaving group water, H2O, which makes the dissociation
step of the S 1 mechanism more favorable.
N

In step 3, the carbocation reacts with a nucleophile (a halide ion) to complete the substitution.

When we convert an alcohol to an alkyl halide, we carry out the reaction in the presence of acid and in the presence of halide ions,
and not at elevated temperature. Halide ions are good nucleophiles (they are much stronger nucleophiles than water), and since
halide ions are present in high concentration, most of the carbocations react with an electron pair of a halide ion to form a more
stable species, the alkyl halide product. The overall result is an SN1 reaction.
Not all acid-catalyzed conversions of alcohols to alkyl halides proceed through the formation of carbocations. Primary alcohols and
methanol react to form alkyl halides under acidic conditions by an SN2 mechanism.

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In these reactions the function of the acid is to produce a protonated alcohol. The halide ion then displaces a molecule of water (a
good leaving group) from carbon; this produces an alkyl halide:

Again, acid is required. Although halide ions (particularly iodide and bromide ions) are strong nucleophiles, they are not strong
enough to carry out substitution reactions with alcohols themselves. Direct displacement of the hydroxyl group does not occur
because the leaving group would have to be a strongly basic hydroxide ion:

We can see now why the reactions of alcohols with hydrogen halides are acid-promoted.
Carbocation rearrangements are extremely common in organic chemistry reactions are are defined as the movement of a
carbocation from an unstable state to a more stable state through the use of various structural reorganizational "shifts" within the
molecule. Once the carbocation has shifted over to a different carbon, we can say that there is a structural isomer of the initial
molecule. However, this phenomenon is not as simple as it sounds.

The most common methods for converting 1º- and 2º-alcohols to the corresponding chloro and bromo alkanes (i.e. replacement of
the hydroxyl group) are treatments with thionyl chloride and phosphorus tribromide, respectively. These reagents are generally
preferred over the use of concentrated HX due to the harsh acidity of these hydrohalic acids and the carbocation rearrangements
associated with their use. The alcohol reactions with thionyl chloride or phosphorus tribromide are discussed in the next section.

Exercises

1. Predict the product of each reaction below.

Answer
1.

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Contributors and Attributions
Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

10.2: Reactions of Alcohols with Hydrohalic Acids is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

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10.3: Converting an Alcohol to a Sulfonate Ester
Nucleophilic Substitution of the Hydroxyl Group
The chemical behavior of alkyl halides can be used as a reference in discovering analogous substitution and elimination reactions of
alcohols. The chief difference, of course, is a change in the leaving anion from halide to hydroxide. Because oxygen is slightly more
electronegative than chlorine (3.5 vs. 2.8 on the Pauling scale), the C-O bond is expected to be more polar than a C-Cl bond. Furthermore,
an independent measure of the electrophilic characteristics of carbon atoms from their NMR chemical shifts (both 13C and alpha protons)
indicates that oxygen and chlorine substituents exert a similar electron-withdrawing influence when bonded to sp3 hybridized carbon
atoms. Despite this promising background evidence, alcohols do not undergo the same SN2 reactions commonly observed with alkyl
halides. For example, the rapid SN2 reaction of 1-bromobutane with sodium cyanide, shown below, has no parallel when 1-butanol is
treated with sodium cyanide. In fact, ethyl alcohol is often used as a solvent for alkyl halide substitution reactions such as this.

CH3CH2CH2CH2–Br + Na(+) CN(–) CH3CH2CH2CH2–CN + Na(+) Br(–)

CH3CH2CH2CH2–OH + Na(+) CN(–) No Reaction

The key factor here is the stability of the leaving anion (bromide vs. hydroxide). HBr is a much stronger acid than water (by more than 18
orders of magnitude), and this difference is reflected in reactions that generate their respective conjugate bases. The weaker base, bromide,
is more stable, and its release in a substitution or elimination reaction is much more favorable than that of hydroxide ion, a stronger and
less stable base.
A clear step toward improving the reactivity of alcohols in SN2 reactions would be to modify the –OH functional group in a way that
improves its stability as a leaving anion. One such modification is to conduct the substitution reaction in a strong acid, converting –OH to –
OH2(+). Because the hydronium ion (H3O(+)) is a much stronger acid than water, its conjugate base (H2O) is a better leaving group than
hydroxide ion. The only problem with this strategy is that many nucleophiles, including cyanide, are deactivated by protonation in strong
acids, effectively removing the nucleophilic co-reactant required for the substitution. The strong acids HCl, HBr and HI are not subject to
this difficulty because their conjugate bases are good nucleophiles and are even weaker bases than alcohols. The following equations
illustrate some substitution reactions of alcohols that may be affected by these acids. As with alkyl halides, the nucleophilic substitution of
1º-alcohols proceeds by an SN2 mechanism, whereas 3º-alcohols react by an SN1 mechanism. Reactions of 2º-alcohols may occur by both
mechanisms and often produce some rearranged products. The numbers in parentheses next to the mineral acid formulas represent the
weight percentage of a concentrated aqueous solution, the form in which these acids are normally used.

CH3CH2CH2CH2–OH + HBr (48%) CH3CH2CH2CH2–OH2(+) Br(–) CH3CH2CH2CH2–Br + H2O SN2

(CH3)3C–OH + HCl (37%) (CH3)3C–OH2(+) Cl(–) (CH3)3C(+) Cl(–) + H2O (CH3)3C–Cl + H2O SN1

Although these reactions are sometimes referred to as "acid-catalyzed," this is not strictly correct. In the overall transformation, a strong
HX acid is converted to water, a very weak acid, so at least a stoichiometric quantity of HX is required for a complete conversion of
alcohol to alkyl halide. The necessity of using equivalent quantities of very strong acids in this reaction limits its usefulness to simple
alcohols of the type shown above. Alcohols with acid-sensitive groups do not, of course, tolerate such treatment. Nevertheless, the idea of
modifying the -OH functional group to improve its stability as a leaving anion can be pursued in other directions. The following diagram
shows some modifications that have proven effective. In each case the hydroxyl group is converted to an ester of a strong acid. The first
two examples show the sulfonate esters described earlier. The third and fourth examples show the formation of a phosphite ester (X
represents the remaining bromines or additional alcohol substituents) and a chlorosulfite ester, respectively. All of these leaving groups
(colored blue) have conjugate acids that are much stronger than water (by 13 to 16 powers of ten); thus, the leaving anion is
correspondingly more stable than the hydroxide ion. The mesylate and tosylate compounds are particularly useful because they may be
used in substitution reactions with a wide variety of nucleophiles. The intermediates produced in reactions of alcohols with phosphorus
tribromide and thionyl chloride (last two examples) are seldom isolated, and these reactions continue to produce alkyl bromide and chloride
products.

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The importance of sulfonate ester intermediates in general nucleophilic substitution reactions of alcohols may be illustrated by the
following conversion of 1-butanol to pentanenitrile (butyl cyanide), a reaction that does not occur with the alcohol alone. The phosphorus
and thionyl halides, on the other hand, only act to convert alcohols to the corresponding alkyl halides.

pyridine Na(+) CN(–)

CH3CH2CH2CH2–OH + CH3SO2Cl CH3CH2CH2CH2–OSO2CH3 CH3CH2CH2CH2–CN + CH3SO2O(

Some examples of alcohol substitution reactions using this approach to activating the hydroxyl group are shown in the following diagram.
The first two cases serve to reinforce the fact that sulfonate ester derivatives of alcohols may replace alkyl halides in a variety of SN2
reactions. The next two cases demonstrate the use of phosphorus tribromide in converting alcohols to bromides. This reagent may be used
without added base (e.g. pyridine) because the phosphorous acid product is a weaker acid than HBr. Phosphorus tribromide is best used
with 1º-alcohols because 2º-alcohols often yield rearrangement by-products resulting from competing SN1 reactions. Note that the ether
oxygen in reaction 4 is not affected by this reagent, whereas the alternative synthesis using concentrated HBr cleaves ethers. Phosphorus
trichloride (PCl3) converts alcohols to alkyl chlorides in a similar manner, but thionyl chloride is usually preferred for this transformation
because the inorganic products are gases (SO2 & HCl). Phosphorus triiodide is not stable but may be generated in situ from a mixture of
red phosphorus and iodine and acts to convert alcohols to alkyl iodides. The last example shows the reaction of thionyl chloride with a
chiral 2º-alcohol. The presence of an organic base such as pyridine is important because it provides a substantial concentration of chloride
ion required for the final SN2 reaction of the chlorosufite intermediate. In the absence of a base, chlorosufites decompose upon heating to
yield the expected alkyl chloride with retention of configuration
Tertiary alcohols are not commonly used for substitution reactions of the type discussed here because SN1 and E1 reaction paths are
dominant and are difficult to control.

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The importance of sulfonate esters as intermediates in many substitution reactions cannot be overstated. A rigorous proof of the
configurational inversion that occurs at the substitution site in SN2 reactions makes use of such reactions. An example of such a proof is
displayed below. Abbreviations for the more commonly used sulfonyl derivatives are given in the following table.

Sulfonyl Group CH3SO2– CH3C6H4SO2– BrC6H4SO2– CF3SO2–

Name & Abbrev. Mesyl or Ms Tosyl or Ts Brosyl or Bs Trifyl or Tf

Inversion Proof

For a more complete discussion of hydroxyl substitution reactions and a description of other selective methods for this transformation,
Click Here.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

10.3: Converting an Alcohol to a Sulfonate Ester is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Hydroxyl Group Substitution by William Reusch is licensed CC BY-NC-SA 4.0.

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10.4: Oxidation and Reduction in Organic Chemistry
 Objectives

After completing this section, you should be able to

1. identify organic reactions as being oxidations, reductions, or neither.
2. rank given compounds in order of their oxidation level.

 Key Terms
Make certain that you can define, and use in context, the terms below.
oxidation
reduction
heteroatom

General Redox Reactions

General chemistry courses describe oxidation and reduction - when a compound or atom is oxidized it loses electrons, and when it
is reduced it gains electrons. Also, oxidation and reduction half reactions occur in pairs: if one species is oxidized, another must be
reduced at the same time. Thus, the combination of an oxidation and a reduction half reaction is termed a 'redox reaction.' Most of
the redox reactions you have seen previously in general chemistry typically involved the flow of electrons from one metal to
another, such as the reaction between copper ion in solution and metallic zinc:
+2 +2
Cu + Z n(s) → C u(s) + Z n
(aq) (aq)

+2
Cu + 2e− → C u(s)
(aq)

Reduction
+2
Z n(s) → Z n + 2e−
(aq)

Oxidation
In order, to keep track of electrons in organic molecules an oxidation state formalism is used. Oxidation states do not represent the
actual charge on an atom, but it will allow the number of electrons being gained or lost by a particular atom to be determined
during a reaction.
To calculate the oxidation state of a carbon atom the following rules are used:
1. A C-C bond does not affect the oxidation state of a carbon. So a carbon attached to 4 carbons has an oxidation state of zero.
2. Every C-H bond will decrease the oxidation state of the carbon by 1.
3. Each C-X bond will increase the oxidation state of the carbon by 1. Where X is an electronegative atom, such as nitrogen,
oxygen, sulfur, or a halogen.
When looking at the oxidation states of carbon in the common functional groups shown below it can be said that carbon loses
electron density as it becomes more oxidized. We'll take a series of single carbon compounds as an example. Methane (CH4) is at
the lowest oxidation level of carbon because is has the maximum possible number of bonds to hydrogen. Carbon dioxide (CO2) is
at the highest oxidation level because it has the maximum number of bonds to an electronegative atom.
H OH O O O
H C H H C H C C C
H H H H H OH O

methane methanol formaldehyde methanoic Acid carbon dioxide

Oxidation State: 4(−1) + 0 = −4 3(−1) + 1 = −2 2(−1) + 2(+1) = 0 1(−1) + 3(+1) = +2 0(−1) + 4(+1) = +4

most reduced most oxidized

This pattern holds true for the relevant functional groups on organic molecules with two or more carbon atoms:

10.4.1 https://chem.libretexts.org/@go/page/211350
H OH O O O
H 3C C H H 3C C H C C C
H H H 3C H H 3C CH3 H 3C OH

ethane ethanol ethanal propanone ethanoic acid

Oxidation State: 3(−1) + 0 = −3 2(−1) + 1 + 0 = −1 2(+1) − 1 + 0 = +1 2(+1) + 2(0) = +2 3(+1) + 0 = +3

most reduced most oxidized

Organic Redox Reactions

It is important to be able to recognize when an organic molecule is being oxidized or reduced, because this information tells you to
look for the participation of a corresponding redox agent that is being reduced or oxidized. If a reaction converts a compound to a
higher oxidation level that is an oxidation. If it converts a compound to a lower oxidation level it is a reduction. If the oxidation
level of the reactant does not change it is not a redox reaction.
Two examples of organic redox reactions are shown below. The conversion of an alcohol to a ketone is considered an oxidation
because the oxidation level of the carbon increases from 0 to +2. This implies that the reaction would require an oxidizing agent.
Likewise, the conversion of a ketone to an alcohol is a reduction and would require a reducing agent. The conversion of an alkane
to alkene is an oxidation because the oxidation state on both carbons is increasing while the reverse reaction would be a reduction.
H OH oxidation O
C C
R 0 R reduction R +2 R
alcohol ketone

H H H H
oxidation
H C C H C C
R H reduction R H
−2 −3 −1 −2
alkane alkene

Now reaction previously discussed in this textbook can be considered to determine if they are in fact redox reaction. The free
radical bromination of methane to bromomethane would be an oxidation because the oxidation level of carbon is raised from -4 to
-3.
H Br
C + Br2 C + HBr
H H H H
H H
−4 −3
free radical halogenation: oxidation

The electrophilic addition of Br2 to an alkene to provide a 1,2-dibromide is an oxidation because both carbons increase their
oxidation level from -2 to -1. However, the electrophilic addion of HBr to an alkene to provide an alkyl halide is not a redox
reaction because the overall oxidation state of carbons involved are not changed. One carbon has its oxidation level decreased from
-2 to -3 while the other carbon's oxidation level is increased from -2 to -1. Overall, the change in oxidation level cancels out to
leave an overall change of oxidcation level in the compound of 0.
H H Br Br
C C + Br2 C C
H H
H H H H
−2 −2 −1 −1

electrophilic addition of Br2: oxidation

H H H Br
C C + HBr C C
H H
H H H H
−2 −2 −3 −1

electrophilic addition of HBr: not redox

You should learn to recognize when a reaction involves a change in oxidation state in an organic reactant . Looking at the following
transformation, for example, you should be able to quickly recognize that it is an oxidation: an alcohol functional group is
converted to a ketone, which is one step up on the oxidation ladder.

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HO CO2 HO CO2

O O

OH OH
OP OH OP O

Likewise, this next reaction involves the transformation of a carboxylic acid derivative (a thioester) first to an aldehyde, then to an
alcohol: this is a double reduction, as the substrate loses two bonds to heteroatoms and gains two bonds to hydrogens.

HO CH3 O HO CH3 O HO CH3 OH

O 2C O2C O 2C H
SCoA H H
thioester aldehyde alcohol

An acyl transfer reaction (for example the conversion of an acyl phosphate to an amide) is not considered to be a redox reaction -
the oxidation state of the organic molecule is does not change as substrate is converted to product, because a bond to one
heteroatom (oxygen) has simply been traded for a bond to another heteroatom (nitrogen).
O O
C C
H3C OP H3C NR2

carbon is in same oxidation state: not redox

It is important to be able to recognize when an organic molecule is being oxidized or reduced, because this information tells you to
look for the participation of a corresponding redox agent that is being reduced or oxidized- remember, oxidation and reduction
always occur in tandem! We will soon learn in detail about the most important biochemical and laboratory redox agents.

Worked Example 10.4.1

1) Rank the following compounds in order of increasing oxidation level:

H H
H3C OH HC N C N CCl4
H

Answer
The easiest way to solve this problem is to calculate the oxidation level of the carbon in each compound. Remembering that
hydrogens decrease the oxidation level by one, electronegative elements increase the oxidation level by one, and carbons do
not change the oxidation level, the oxidation level of each carbon can be calculate. The carbon in CH3OH has three bonds
to hydrogens and one bond to oxygen so it oxidation level is 3(-1) + 1(+1) = -2. The carbon in HCN has one bond to
hydrogens and three bonds to nitrogen so it oxidation level is 1(-1) + 3(+1) = +2. The carbon in CH2NH has two bonds to
hydrogens and two bond to nitrogen so it oxidation level is 2(-1) + 2(+1) = 0. The carbon in CCl4 has zero bonds to
hydrogens and four bonds to chlorine so it oxidation level is o(-1) + 4(+1) = +4. The compounds now can be listing in the
following order of increasing oxidation level.
H H
H3C OH N C N CH CCl4
−2 0 H +2 +4

 Exercise 10.4.1

1) In each case state whether the reaction is an oxidation or reduction of the organic compound.
O OH

A-
1. BH3
OH
2. NaOH, H2O2
B-

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Answer
1)
A – Reduction
B – Oxidation

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10.5: Oxidation of Alcohols
 Objectives

After completing this section, you should be able to

1. write an equation to represent the oxidation of an alcohol.
2. identify the reagents that may be used to oxidize a given alcohol.
3. identify the specific reagent that is used to oxidize primary alcohols to aldehydes rather than to carboxylic acids.
4. identify the product formed from the oxidation of a given alcohol with a specified oxidizing agent.
5. identify the alcohol needed to prepare a given aldehyde, ketone or carboxylic acid by simple oxidation.
6. write a mechanism for the oxidation of an alcohol using a chromium(VI) reagent.

 Study Notes
The reading mentions that pyridinium chlorochromate (PCC) is a milder version of chromic acid that is suitable for converting
a primary alcohol into an aldehyde without oxidizing it all the way to a carboxylic acid. This reagent is being replaced in
laboratories by Dess‑Martin periodinane (DMP), which has several practical advantages over PCC, such as producing higher
yields and requiring less rigorous reaction conditions. DMP is named after Daniel Dess and James Martin, who developed it in
1983.

Oxidation States of Carbon

The general idea of oxidation and reduction reactions learned in general chemistry is that when a compound or atom is oxidized it
loses electrons, and when it is reduced it gains electrons. In order, to keep track of electrons in organic molecules a oxidation state
formalism is used. Oxidation states to not represent the actual charge but it will allow the number of electrons being gained or lost
by a particular atom during a reaction.
To calculate the oxidation state of a carbon atom the following rules are used:
1. A C-C bond does not affect the oxidation state of a carbon. So a carbon attached to 4 carbons has an oxidation state of zero.
2. Every C-H bond will decrease the oxidation state of the carbon by 1.
3. Each C-X bond will increase the oxidation state of the carbon by 1. Where X is an electronegative, such as nitrogen, oxygen,
sulfur, or a halogen.
When looking at the oxidation states of carbon in the common functional groups shown below it can be said that carbon loses
electron density as it becomes more oxidized.
H OH O O O
H 3C C H H 3C C H H 3C C C H 3C C
H H H H 3C CH3 OH

Ethane Ethanol Ethanal Propanone Ethanoic Acid

Oxidation State: 3(-1) + O = -3 2(-1) +1 +0 = -1 2(+1) -1 +0 = +1 2(+1) + 2(0) = +2 3(+1) +0 = +3

Most Reduced Most Oxidized

For this section, a simpler way to consider this process is to say that when a carbon atom in an organic compound loses a bond to
hydrogen and gains a new bond to a oxygen it has been oxidized. A very commonly example is the oxidation of an alcohol to a
ketone or aldehyde. Notice that during this process the carbon atom loses a hydrogen and gains a bond to oxygen.

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Oxidation of Alcohols
On of the most important reactions of alcohols is their oxidation to carbonyl containing compounds such as aldehyde, ketones, and
carboxylic acid. Typically primary alcohols, depending on the reagent used, produce aldehydes or carboxylic acids during
oxidations. Secondary alcohols are oxidized to produce ketones, and tertiary alcohols are usually not affected by oxidations.

OH O O
[O] [O]
Primary Alcohol C
R H C C
H R H R OH

Aldehyde Carboxylic Acid

OH O
[O]
Secondary Alcohol C
R H C
R' R R'
Ketone

OH
[O]
Teritary Alcohol C No Reacton
R R''
R'

Alcohol Oxidizing Agents

Oxidation and reduction reactions always occurs in tandem: when one compound is oxidized, another compound must be reduced.
For an alcohol to be oxidized in a reaction there must also be a compound being reduced. This reduced compound is also called the
oxidizing agent. For example, chromium trioxide (CrO3) is a common oxidizing agent used by organic chemists to oxidize a
secondary alcohol to a ketone. During this reaction CrO3 is being reduced to form H2CrO3. A common method for oxidizing
secondary alcohols to ketones uses chromic acid (H2CrO4) as the oxidizing agent. Chromic acid, also known as Jones reagent, is
prepared by adding chromium trioxide (CrO3) to aqueous sulfuric acid.

There is a wide selection of oxidizing agents available for use in the organic chemistry laboratory, each with its own particular
properties and uses. In addition to CrO3, other commonly used oxidizing agents include potassium permanganate (KMnO4) and
sodium dichromate (Na2Cr2O7). Any of these reagents can be used to oxidize secondary alcohols to form ketones and primary
alcohols to form carboxylic acids. Tertiary alcohols remain unreactive to oxidation.

General Reactions

H OH CrO3 O
C C
R R' H2SO4 R R'
2o Alcohol Ketone

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OH Na2Cr2O7 O
C H C
R H2O, Heat R OH
H

1o Alcohol Carboylic Acid

R CrO3
R' C OH No Reaction
R'' H2SO4

3o Alcohol

 Example 10.5.1

OH O
CrO3
CH2 C
OH
H2SO4

Oxidation of Benzyl Alcohol to Benzoic Acid

OH Na2Cr2O7 O

H2O, Heat

Oxidation of 2-Pentanol to 2-Pentanone

H 3C CrO3
H3C C OH No Reaction
H 3C H2SO4

Mechanism
During this reaction mechanism the chromium atom is being reduced from Cr(VI) in the CrO3 starting material to Cr(IV) in the
H2CrO3 product. Also, notice the the C=O bond is formed in the third step of the mechanism through an E2 reaction. Although E2
reaction are generally know for forming C=C double bonds thought the elimination of a halide leaving group, in this case they are
use to generate a C=O through the elimination of a reduced metal as a leaving group.

Examples
Oxidation of 1o Alcohols with PCC to form Aldehydes
Pyridinium chlorochromate (PCC) is a milder version of chromic acid. PCC oxidizes 1o alcohols one rung up the oxidation
ladder, turning primary alcohols into aldehydes and secondary alcohols into ketones. Unlike chromic acid, PCC will not oxidize
aldehydes to carboxylic acids. Cr(IV) as well as pyridinium chloride are produced as byproducts of this reaction.

10.5.3 https://chem.libretexts.org/@go/page/211351
O
Cl Cr O
N
O
H
Pyridinium chlorochromate (PCC)

General Reactions

H2 PCC O O
R
C
OH C + Cr + N Cl
CH2Cl2 R H HO OH
H
o Aldehyde Cr(IV) Pyridinium Chloride
1 Alcohol

OH PCC O O
C
H
CH2Cl2 C + Cr + N
R R' R R' HO OH Cl
H
2o Alcohol Ketone Cr(IV) Pyridinium Chloride

 Example 10.5.2

OH PCC O

CH2Cl2 H

Oxidation of 2-Phenylethanol to Phenylacetaldehyde

OH O
PCC
CH2Cl2

Oxidation of Cyclohexanol to Cyclohexanone

Mechanism
The first step of the mechanism is attack of alcohol oxygen on the chromium atom to form the Cr-O bond. Secondly, a proton on
the (now positive) OH is transferred to one of the oxygens of the chromium, possibly through the intermediacy of the pyridinium
salt. A chloride ion is then displaced, in a reaction reminiscent of a 1,2 elimination reaction, to form what is known as a chromate
ester.
The C-O double bond is formed when a base removes the proton on the carbon adjacent to the oxygen. It is also possible for
pyridine to be used as the base here, although only very low concentrations of the deprotonated form will be present under these
acidic conditions. In an E2 reaction, the electrons from the C-H bond move to form the C=O bond, and in the process break the O-
Cr bond. During this step Cr(VI) gains two electrons to become Cr(IV) (drawn here as O=Cr(OH)2).

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Oxidation of 1o Alcohols with Dess‑Martin Periodinane (DMP) to form Aldehydes
PCC is being replaced in laboratories by Dess‑Martin periodinane (DMP) in dichloromethane solvent, which has several practical
advantages over PCC, such as producing higher yields and requiring less rigorous conditions (lower reaction temperature and a
nonacidic medium). DMP is named after Daniel Dess and James Martin, who developed it in 1983.
O

O
I OAc
AcO OAc

Dess‑Martin periodinane (DMP)

General Reactions
OH O
H DMP
C C
R H CH2Cl2 R R'
2o Alcohol Ketone

OH O
H DMP
C C
R H CH2Cl2 R R'
2o Alcohol Ketone

 Example 10.5.3

OH O
DMP

CH2Cl2

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Oxidation of Cyclohexanol to Cyclohexanone

OH O
CH2 DMP C
H
CH2Cl2

Oxidation of Benzyl Alcohol to Benzaldehyde

Mechanism
The first step of the mechanism involves the reactant alcohol attacking the Iodine (V) atom and eliminating an acetate (Ac-) leaving
group to form a periodinate intermediate. The next step is a concerted E2-like reaction where a hydrogen is removed from the
alcohol, the C=O bond is formed, an acetate group is eliminated from the iodine atom, and the iodine (V) atom gains two electrons
to be reduced to iodine (III).
O O O
O
R1 R1
O O O
OH R2 O R2 R1 R2
I I I
AcO OAcOAc AcO OAcO H AcO O O H
R1 R2 O
O

Byproducts
O
O

O OH
I
OAc

Biological Alcohol Oxidations

There are many biological oxidations that convert a primary or secondary alcohol to a carbonyl compound. These reactions cannot
possibly involve the extreme pH conditions and vigorous inorganic oxidants used in typical laboratory oxidations. Rather, they
occur at nearly neutral pH values and they all require enzymes as catalysts, which for these reactions usually are called
dehydrogenases. An important group of biological oxidizing agents includes the pyridine nucleotides, of which nicotinamide
adenine dinucleotide (NAD+) is an example. This very complex molecule functions to accept hydride (H:-) or the equivalent (H++
2e−) from the α carbon of an alcohol. The reduced form of NAD+ is abbreviated as NADH and the H:- is added at the 4-position of
the pyridine ring. It is important to note that the hydride adds exclusively to the Re face of the pyridine ring giving NADH a pro-R
stereochemistry.
An example of the remarkable specificity of this kind of redox system. One of the last steps in the metabolic breakdown of glucose
is the reduction of 2-oxopropanoic (pyruvic) acid to L-2-hydroxypropanoic (lactic) acid. The reverse process is oxidation of L-
lactic acid. The enzyme lactic acid dehydrogenase catalyses this reaction, and it functions only with the L-enantiomer of lactic
acid. During this reaction a base removes the alcohol hydrogen. The resulting alkoxide ion then forms the C=O bond causing a
hydride ion to transfer to NAD+.

10.5.6 https://chem.libretexts.org/@go/page/211351
O
H NH2 NH2
N N
O O
N O O P O P O O N N
O O
Nicotinamide Group
HO OH HO OH

The Structure of NAD+

From an outside source. Convert mechanism to use lactic acid.

Another example is provided by one of the steps in metabolism by way of the Krebs citric acid cycle, is the oxidation of L-2-
hydroxy-butanedioic (L-malic) acid to 2-oxobutanedioic (oxaloacetic) acid. This enzyme functions only with L-malic acid:

Exercises

 Exercise 10.5.1
Draw the alcohol that the following ketones/aldehydes would have resulted from if oxidized. What oxidant could be used?
O
O
O
a) b) c)
H

Answer
1)
a) Any oxidant capable of oxidizing an alcohol to a ketone would work, such as the Jones reagent (CrO3, H2SO4, H2O),
PCC, or Dess-Martin periodinane.
OH

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b) Since this is a primary alcohol, there are some precautions necessary to avoid formation of the carboxyllic acid. Milder
oxidants such as the Dess-Martin periodinane, and also PCC (there is no water to form the carboxyllic acid) would work
OH

c) Any oxidant capable of oxidizing an alcohol to a ketone would work, such as the Jones reagent (CrO3, H2SO4, H2O),
PCC, or Dess-Martin periodinane.
OH

 Exercise 10.5.2

Show the products of the oxidation of 1-propanol and 2-propanol with chromic acid in aqueous solution.

Answer
O
O

 Exercise 10.5.3

Show the products of the oxidation of 1-propanol and 2-propanol with Dess-Martin periodinane.

Answer
O
O

10.5: Oxidation of Alcohols is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
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10.6: The Formation of Carboxylic Acids
 Learning Objectives
To describe the preparation of carboxylic acids.

As we noted previously, the oxidation of aldehydes or primary alcohols forms carboxylic acids:

In the presence of an oxidizing agent, ethanol is oxidized to acetaldehyde, which is then oxidized to acetic acid.

This process also occurs in the liver, where enzymes catalyze the oxidation of ethanol to acetic acid.
alcohol dehydrogenase alcohol dehydrogenase

C H3 C H2 OH −−−−−−−−−−−−→ C H3 CHO −−−−−−−−−−−−→ C H3 COOH

oxidizing agent oxidizing agent

Acetic acid can be further oxidized to carbon dioxide and water.

Summary
Whether in the laboratory or in the body, the oxidation of aldehydes or primary alcohols forms carboxylic acids.

10.6: The Formation of Carboxylic Acids is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.
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10.7: Nicotinamide Adenine Dinucleotide (NAD)
Nicotinamide is from the niacin vitamin. The NAD+ coenzyme is involved with many types of oxidation reactions where alcohols
are converted to ketones or aldehydes. It is also involved in the first enzyme complex 1 of the electron transport chain.The structure
for the coenzyme, NAD+, Nicotinamide Adenine Dinucleotide is shown in Figure 10.7.1.

Role of NAD+
One role of N AD is to initiate the electron transport chain by the reaction with an organic metabolite (intermediate in metabolic
+

reactions). This is an oxidation reaction where 2 hydrogen atoms (or 2 hydrogen ions and 2 electrons) are removed from the
organic metabolite. (The organic metabolites are usually from the citric acid cycle and the oxidation of fatty acids--details in
following pages.) The reaction can be represented simply where M = any metabolite.
+ +
M H2 + N AD → N ADH + H + M : +energy (10.7.1)

One hydrogen is removed with 2 electrons as a hydride ion (H ) while the other is removed as the positive ion (H +). Usually the
−

metabolite is some type of alcohol which is oxidized to a ketone.

Figure 10.7.1

Alcohol Dehydrogenase
The NAD+ is represented as cyan in Figure 10.7.2. The alcohol is represented by the space filling red, gray, and white atoms. The
reaction is to convert the alcohol, ethanol, into ethanal, an aldehyde.
+ +
C H3 C H2 OH + N AD → C H3 C H = O + N ADH + H (10.7.2)

This is an oxidation reaction and results in the removal of two hydrogen ions and two electrons which are added to the NAD+,
converting it to NADH and H+. This is the first reaction in the metabolism of alcohol. The active site of ADH has two binding
regions. The coenzyme binding site, where NAD+ binds, and the substrate binding site, where the alcohol binds. Most of the
binding site for the NAD+ is hydrophobic as represented in green. Three key amino acids involved in the catalytic oxidation of
alcohols to aldehydes and ketones. They are ser-48, phe 140, and phe 93.

Figure 10.7.2 : Active site of Alcohol Dehydrogenase

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Contributors and Attributions
Charles Ophardt, Professor Emeritus, Elmhurst College; Virtual Chembook

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10.8: Dehydrogenases
Dehydrogenases enzymes usually involve NAD+/NADH and are named for the substrate that is oxidized by NAD+. For instance in the
reaction:
+
pyruvate + NADH ⇌ lactate + NAD (10.8.1)

which is used to regenerate NAD+ under anerobic conditions, the enzyme is named lactate dehydrogenase. As in acid/base reactions, when the
preferred direction for the reaction (from a ΔGo perspective) is from stronger acid to weaker (conjugate) acid, the preferred direction for a
redox reaction is in the direction from strong to weak oxidizing/reducing agents. This can easily be determined from charts of standard
reduction potentials, and using the equation:
o o
ΔG = −nF ΔE (10.8.2)

where F is the Faraday constant (96,494 Coulombs/mol e- = 96, 494 J/(V.mol) = 23.06 kcal/(V.mol). One Faraday is the charge per one mol
of electrons).
and $ΔEô$, the standard EMF or standard cell potential (total voltage at standard state conditions), which can be determined by adding the
standard reduction potentials (Eo) for the two appropriate half-reactions, after reversing the equation for the half-reaction that represents the
oxidation.
When n=2 (number of electrons) which is common for oxidations of organic molecules,
\[ΔGô (kcal/mol) = - 46.12\,ΔEô \]
or for government work
\[ΔGo (kcal/mol) \approx - 50ΔEô\]
Notice when ΔEo > 0, ΔGo < 0, the reaction as written is favored under standard conditions. Note in the table below that many of the half
reactions involve protons. For biological reactions involving free protons, the standard state concentration for the protons are not 1 M as for
other solutes in solution, but defined to be the hydronium ion concentration at pH 7.0. The ΔEo and ΔGo values for the reactions involving
hydrogen ions at a standard state of pH 7.0 are usually written as ΔEo' and ΔGo'
Table: Standard Reduction Potential Table (E0'), 25oC
oxidant reductant n (electrons) Eoï¿½ (volts)

Acetate + carbon dioxide pyruvate 2 -0.70

succinate + CO2 + 2H+ α−ketoglutarate + H2O 2 -0.67

acetate acetaldehyde 2 -0.60

glycerate-3-P glyceraldehyde-3-P + H2O 2 -0.55

O2 O2- 1 -0.45

ferredoxin (ox) ferredoxin (red) 1 -0.43

Carbon dioxide formate 2 -0.42

2H+ H2 2 -0.42

α-ketoglutarate + CO2 + 2H+ isocitrate 2 -0.38

acetoacetate β-hydroxybutyrate 2 -0.35

Cystine cysteine 2 -0.34

Pyruvate + CO2 malate 2 -0.33

NAD+ + 2H+ NADH + H+ 2 -0.32

NADP+ + 2H+ NADPH + H+ 2 -0.32

FMN (enzyme bound) FMNH2 2 -0.30

Lipoic acid, ox Lipoic acid, red 2 -0.29

1,3 bisphosphoglycerate + 2H+ glyceraldehyde-3-P + Pi 2 -0.29

Glutathione, ox red 2 -0.23

FAD (free) + 2H+ FADH2 2 -0.22

Acetaldehyde + 2H+ ethanol 2 -0.20

10.8.1 https://chem.libretexts.org/@go/page/211669
oxidant reductant n (electrons) Eoï¿½ (volts)

Pyruvate + 2H+ lactate 2 -0.19

Oxalacetate + 2H+ malate 2 -0.17

α-ketoglutarate + NH4+ glutamate 2 -0.14

FAD + 2H+ (bound) FADH2 (bound) 2 0.003-0.09

Methylene blue, ox Methylene blue, red 2 0.01

Fumarate + 2H+ succinate 2 0.03

CoQ (Ubiquinone - UQ + H+ UQH. 1 0.031

UQ + 2H+ UQH2 2 0.06

Dehydroascorbic acid ascorbic acid 2 0.06

Ubiquinone; ox red 2 0.10

Cytochrome b2; Fe3+ Cytochrome b2; Fe2+ 1 0.12

Cytochrome c1; Fe3+ Cytochrome c1; Fe2+ 1 0.22

Cytochrome c; Fe3+ Cytochrome c; Fe2+ 1 0.25

Cytochrome a; Fe3+ Cytochrome a; Fe2+ 1 0.29

1/2 O2 + H2O H2O2 2 0.30

Cytochrome a3; Fe3+ Cytochrome a3; Fe2+ 1 0.35

Ferricyanide ferrocyanide 2 0.36

Cytochrome f; Fe3+ Cytochrome f; Fe2+ 1 0.37

Nitrate nitrite 1 0.42

Photosystem P700 . . 0.43

Fe3+ Fe2+ 1 0.77

1/2 O2 + 2H+ H2O 2 0.816

Recommendations for nomenclature and tables in biochemical thermodynamics (from the International Union of Biochemistry and
Molecular Biology and the IUPAC)
The mechanism for the oxidation of a substrate by NAD + involves concerted hydride transfer to one face of NAD+.
Consider for example the oxidation of ethanol to acetaldehyde by alcohol dehydrogenase.

10.8.2 https://chem.libretexts.org/@go/page/211669
Figure: oxidation of ethanol to acetaldehyde by alcohol dehydrogenase
For substrates like ethanol that loses a hydride from a methylene carbon atom that has two H's, only one of the H's is lost (either the proR or
proS) from the prochiral center. (Remember the reaction of prochiral glycerol to give phospholipids.)

10.8.3 https://chem.libretexts.org/@go/page/211669
Figure: STEREOCHEMISTRY OF NAD+/NADH REDOX REACTIONS WITH ALCOHOL DEHYDROGENASE
FAD has a more positive reduction potential than NAD+ so it is used for more "demanding" oxidation reactions, such as dehydrogenation of a
C-C bond to form an alkene. You
will notice on standard reduction potential tables that the potential of FAD is often listed several times and depends on the enzyme. This is
because the FAD is tightly bound to the enzyme so its tendency to acquire electrons depends on its environment, in much the same fashion as
the pKa of an amino acid side chain (which reflects is tendency to release protons) is affected by the environment of the amino acid side chain
in the protein. The standard reduction potential for flavin enzymes varies from -465 mV to + 149 mV. Compare this to the reduction potential
of free FAD/FADH2, which in aqueous solution is -208 mV. The standard reduction potential of the flavin in D-amino acid oxidase, a
flavoprotein, is about 0.0 V. Remember, the more positive the standard reduction potential, the more likely the reactant will be reduced and
hence act as an oxidizing agent. Hence the FAD in D-amino acid oxidase is a better oxidizing agent than free FAD. The Kd for binding of FAD
to the enzyme is 10-7M compared to the Kd for binding of FADH2, which is 10-14M. By gaining electrons, the flavin binds more tightly,
which preferentially stabilizes the bound FADH2 compared to the bound FAD. This shifts the equilibrium of FAD <=> FADH2 to the right,
making the bound FAD a stronger oxidizing agent.
Figure: FAD AND OXIDATIONS: MECHANISM

10.8.4 https://chem.libretexts.org/@go/page/211669
Jmol: Updated Flavin dehydrogenase Jmol14 (Java) | JSMol (HTML5)
Can the standard reduction potential of a redox active center in a protein be tuned by changing the environment of that center, much as the pKa
of an acid side chain can by changing the polarity of the environment? The answer is yes. The active site of azurin, a cupredoxin, has a redox
active copper ion coordinated by a Cys and two His residues in a trigonal planar fashion. Met 121 serves as a weak axial ligand. Marshall et al.
have reported a feasible method to manipulate the redox potential (Eo) of this active site. The wild type azurin was mutated to alter the
hydrophobicity and hydrogen bonding capabilities, while maintaining the overall architecture of the metal binding site. Ser 46 was selected for
mutation since it occupied a position similar to Asn in another curedoxin that was involved in an important H bond binding two ligand binding
loops. An N47S-mutation, which strengthened the hydrogen bond between the two ligand-containing loops increased Eo by ~130 mV while
preserving metal binding site architecture as determined by UV-Vis spectroscopy. They also compared a M121Q mutant with wild-type M121
and with a M121L mutant. A plot of Eo vs log partition coefficient for transfer of the side chain from water to octanol was essentially linear
with a positive slope, showing that the standard reduction potential depended on the hydrophobicity of the weakly coordinating ligand in the
metal binding region. This behavior extended to double mutants (where one set of mutants involved M121). The investigators were able to tune
the Eo over a 700 mv range! New Role for NAD.

Contributors and Attributions

Prof. Henry Jakubowski (College of St. Benedict/St. John's University)

This page titled 10.8: Dehydrogenases is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Henry Jakubowski.
B3. Dehydrogenases by Henry Jakubowski is licensed CC BY-NC-SA 4.0.

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10.9: Prochirality
 Objectives

After completing this section, you should be able to

1. identify a compound as being prochiral.
2. identify the Re and Si faces of prochiral sp2 centre.
3. identify atoms (or groups of atoms) as pro-R or pro-S on a prochiral sp3 centre.

 Key Terms
Make certain that you can define, and use in context, the key terms below.
prochiral
pro-R
pro-S
Re
Si

Prochiral Carbons
When a tetrahedral carbon can be converted to a chiral center by changing only one of the attached groups, it is referred to as a
‘prochiral' carbon. The two hydrogens on the prochiral carbon can be described as 'prochiral hydrogens'.
prochiral hydrogens

H H H D
change H to D
R R’ R R’

prochiral carbon chiral carbon

Note that if, in a 'thought experiment', we were to change either one of the prochiral hydrogens on a prochiral carbon center to a
deuterium (the 2H isotope of hydrogen), the carbon would now have four different substituents and thus would be a chiral center.
Prochirality is an important concept in biological chemistry, because enzymes can distinguish between the two ‘identical’ groups
bound to a prochiral carbon center due to the fact that they occupy different regions in three-dimensional space. Consider the
isomerization reaction below, which is part of the biosynthesis of isoprenoid compounds. We do not need to understand the reaction
itself (it will be covered in chapter 14); all we need to recognize at this point is that the isomerase enzyme is able to distinguish
between the prochiral 'red' and the 'blue' hydrogens on the isopentenyl diphosphate (IPP) substrate. In the course of the left to right
reaction, IPP specifically loses the 'red' hydrogen and keeps the 'blue' one.
H H H
O O O O O O
P P P P
O O O O O O O O

isopentenyl diphosphate dimethylallyl diphosphate

Prochiral hydrogens can be unambiguously designated using a variation on the R/S system for labeling chiral centers. For the sake
of clarity, we'll look at a very simple molecule, ethanol, to explain this system. To name the 'red' and 'blue' prochiral hydrogens on
ethanol, we need to engage in a thought experiment. If we, in our imagination, were to arbitrarily change red H to a deuterium, the
molecule would now be chiral and the chiral carbon would have the R configuration (D has a higher priority than H).
change H to D
H H stereocenter is now (R ) H D
(R )
H3 C OH H3 C OH

Hs HR

H3C OH

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For this reason, we can refer to the red H as the pro-R hydrogen of ethanol, and label it HR. Conversely, if we change the blue H to
D and leave red H as a hydrogen, the configuration of the molecule would be S, so we can refer to blue H as the pro-S hydrogen of
ethanol, and label it HS.
Looking back at our isoprenoid biosynthesis example, we see that it is specifically the pro-R hydrogen that the isopentenyl
diphosphate substrate loses in the reaction.
HS HR H
O O O O O O
P P P P
O O O O O O O O

isopentenyl diphosphate dimethylallyl diphosphate

Prochiral hydrogens can be designated either enantiotopic or diastereotopic. If either HR or HS on ethanol were replaced by a
deuterium, the two resulting isomers would be enantiomers (because there are no other stereocenters anywhere on the molecule).
CH3 CH3 CH3
HR C H C(S ) D C(R )
OH OH OH
HS D H

enantiotopic
hydrogens enantiomers

Thus, these two hydrogens are referred to as enantiotopic.

In (R)-glyceraldehyde-3-phosphate ((R)-GAP), however, we see something different:
diastereotopic
hydrogens

HR HS O H D O D H O
(R ) (R ) (R )
PO H PO (S ) H PO (R ) H
OH OH OH
(R )-GAP
diastereomers

R)-GAP already has one chiral center. If either of the prochiral hydrogens HR or HS is replaced by a deuterium, a second chiral
center is created, and the two resulting molecules will be diastereomers (one is S,R, one is R,R). Thus, in this molecule, HR and HS
are referred to as diastereotopic hydrogens.
Finally, hydrogens that can be designated neither enantiotopic nor diastereotopic are called homotopic. If a homotopic hydrogen is
replaced by deuterium, a chiral center is not created. The three hydrogen atoms on the methyl (CH3) group of ethanol (and on any
methyl group) are homotopic. An enzyme cannot distinguish among homotopic hydrogens.
H homotopic hydrogens
H
C H
HR C
OH
HS

 Example 10.9.1

Identify in the molecules below all pairs/groups of hydrogens that are homotopic, enantiotopic, or diastereotopic. When
appropriate, label prochiral hydrogens as HR or HS.

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O
a) b)
H OP
N
O
O N CO2

H O
dihydroorotate phosphoenolpyruvate
(a nucleotide biosynthesis intermediate) (a glycolysis intermediate)

O
c) d) C O
CO2
O 2C H 3C C
O
succinate pyruvate
(a citric acid cycle intermediate) (endpoint of glycolysis)

Answer
(no pro-R or pro-S
designation is possible)
O
a) HR diastereotopic b)
H H OP
N HS
diastereotopic
O
O N H CO2

H O

enantiotopic
HR HS O
c) d) C O
CO2
O2 C H3 C C
HS HR homotopic O
enantiotopic

Groups other than hydrogens can be considered prochiral. The alcohol below has two prochiral methyl groups - the red one is pro-
R, the blue is pro-S. How do we make these designations? Simple - just arbitrarily assign the red methyl a higher priority than the
blue, and the compound now has the R configuration - therefore red methyl is pro-R.
methyl B (pro-S)
OH
H3C C
CH2CH3
H 3C

methyl A (pro-R)

Citrate is another example. The central carbon is a prochiral center with two 'arms' that are identical except that one can be
designated pro-R and the other pro-S.
HO CO2
O 2C CO2

pro-R arm pro-S arm

citrate

In an isomerization reaction of the citric acid (Krebs) cycle, a hydroxide is shifted specifically to the pro-R arm of citrate to form
isocitrate: again, the enzyme catalyzing the reaction distinguishes between the two prochiral arms of the substrate (we will study
this reaction in chapter 13).

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CO2 CO2
pro-S arm pro-R arm

O2 C OH
(draw from a different

=
perspective)
CO2
HO CO2 O2 C CO2
O2 C CO2
pro-R arm pro-S arm OH

citrate isocitrate
(hydroxide moved
specifically to the
pro-R arm)

 Exercise 10.9.1

Assign pro-R and pro-S designations to all prochiral groups in the amino acid leucine. (Hint: there are two pairs of prochiral
groups!). Are these prochiral groups diastereotopic or enantiotopic?

O
H3N
O
leucine

Answer
pro-R
H CH3
HR
HS b CH pro-S
a 3
O
H 3N
O

Prochiral Carbonyl and Imine Groups

Trigonal planar, sp2-hybridized carbons are not, as we well know, chiral centers– but they can be prochiral centers if they are
bonded to three different substitutuents. We (and the enzymes that catalyze reactions for which they are substrates) can distinguish
between the two planar ‘faces’ of a prochiral sp2 - hybridized group. These faces are designated by the terms re and si. To
determine which is the re and which is the si face of a planar organic group, we simply use the same priority rankings that we are
familiar with from the R/S system, and trace a circle: re is clockwise and si is counterclockwise.

1
1 1
re face si face

3 2 3 2 2 3

looking at the re face looking at the si face

When the two groups adjacent to a carbonyl (C=O) are not the same, we can distinguish between the re and si 'faces' of the planar
structure. The concept of a trigonal planar group having two distinct faces comes into play when we consider the stereochemical
outcome of a nucleophilic addition reaction. Nucleophilic additions to carbonyls will be covered in greater detail in Chapter 19.
Notice that in the course of a carbonyl addition reaction, the hybridization of the carbonyl carbon changes from sp2 to sp3, meaning
that the bond geometry changes from trigonal planar to tetrahedral. If the two R groups are not equivalent, then a chiral center is
created upon addition of the nucleophile. The configuration of the new chiral center depends upon which side of the carbonyl plane
the nucleophile attacks from. Reactions of this type often result in a 50:50 racemic mixture of stereoisomers, but it is also possible
that one stereoisomer may be more abundant, depending on the structure of the reactants and the conditions under which the
reaction takes place.

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H OH OH H
O O
C R' R' C
Nu R' C Nu Nu C Nu
R R R R' R
attack at re face enantiomers attack at si face

Note: R is higher priority than R’

Below, for example, we are looking down on the re face of the ketone group in pyruvate. If we flipped the molecule over, we would
be looking at the si face of the ketone group. Note that the carboxylate group does not have re and si faces, because two of the three
substituents on that carbon are identical (when the two resonance forms of carboxylate are taken into account).
priority #1

O
C O
priority #3 H3 C C priority #2

As we will see in chapter 10, enzymes which catalyze reactions at carbonyl carbons act specifically from one side or the other.

HO CO2 HS HR O HO CO2
H O

NH2 NH2
+ +
(R )
H2C OH N H 2C OH N

O R HO H R
looking at the si face
of the ketone

We need not worry about understanding the details of the reaction pictured above at this point, other than to notice the
stereochemistry involved. The pro-R hydrogen (along with the two electrons in the C-H bond) is transferred to the si face of the
ketone (in green), forming, in this particular example, an alcohol with the R configuration. If the transfer had taken place at the re
face of the ketone, the result would have been an alcohol with the S configuration.

 Exercise 10.9.2

For each of the carbonyl groups in uracil, state whether we are looking at the re or the si face in the structural drawing below.
O
H
N

N O
H
uracil

Answer
1

O
H looking at the re face
3
N 2 of this carbonyl group

N O
H

O
2
H
N looking at the si face
of this carbonyl group
N O
3 1
H

10.9.5 https://chem.libretexts.org/@go/page/211670
 Exercise 10.9.3

a) State which of the following hydrogen atoms are pro-R or pro-S.

Ha Hb Ha Hb
HO OH
HO H H2N H

b) Identify which side is Re or Si.

C
A

O H OH

B
D

Answer
a) Left compound: Ha = pro-S and Hb = pro-R; Right compound: Ha = pro-R and Hb = pro-S
b) A – Re; B – Si; C – Re; D – Si\)

 Exercise 10.9.4

State whether the H's indicated below are pro-R or pro-S for the following structures.
a) Ha Hb b) Ha Hb

HO H O

Answer
a) Ha is pro-R; Hb is pro-S
Ha is pro-R; Hb is pro-S

 Exercise 10.9.5
In the structures below, determine if the H's are homotopic, enantiotopic, or diastereotopic.
a) Ha Hb b) Ha Hb

HO H O

Answer
In a), the CH2 is diastereotopic since there is another chiral center on the molecule. Both CH3's are homotopic since
replacing one of them doesn't create a chiral center.
IN b), the CH2's are enantiotopic since it would create the only chiral center on the molecule. Both CH3's are homotopic
since replacing one of them doesn't create a chiral center.
diastereotopic enantiotopic enantiotopic
a) b)
Ha Hb H2 H a Hb
CH3 C
H 3C H 3C CH3
homotopic
HO H homotopic homotopic
homotopic O

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 Exercise 10.9.6
State whether you are looking down at the molecule from the re face or si face.
a) b)
O HOH2C H

HOH2C CH2CH3 H H

Answer
a. You are looking at the si face. The re face would be if you were facing the molecule from the back.
b. You are looking at the re face. The si face would be if you were facing the molecule from the back.

10.9: Prochirality is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
5.11: Prochirality by Dietmar Kennepohl, Steven Farmer, Zachary Sharrett is licensed CC BY-SA 4.0.
3.12: Prochirality by Tim Soderberg is licensed CC BY-NC-SA 4.0. Original source:
https://digitalcommons.morris.umn.edu/chem_facpubs/1/.

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10.10: Thiols and Sulfides
1. Nucleophilicity of Sulfur Compounds
Sulfur analogs of alcohols are called thiols or mercaptans, and ether analogs are called sulfides. The chemical behavior of thiols
and sulfides contrasts with that of alcohols and ethers in some important ways. Since hydrogen sulfide (H2S) is a much stronger
acid than water (by more than ten million fold), we expect, and find, thiols to be stronger acids than equivalent alcohols and
phenols. Thiolate conjugate bases are easily formed, and have proven to be excellent nucleophiles in SN2 reactions of alkyl halides
and tosylates.
R–S(–) Na(+) + (CH3)2CH–Br (CH3)2CH–S–R + Na(+) Br(–)
Although the basicity of ethers is roughly a hundred times greater than that of equivalent sulfides, the nucleophilicity of sulfur is
much greater than that of oxygen, leading to a number of interesting and useful electrophilic substitutions of sulfur that are not
normally observed for oxygen. Sulfides, for example, react with alkyl halides to give ternary sulfonium salts (equation # 1) in the
same manner that 3º-amines are alkylated to quaternary ammonium salts. Although equivalent oxonium salts of ethers are known,
they are only prepared under extreme conditions, and are exceptionally reactive. Remarkably, sulfoxides (equation # 2), sulfinate
salts (# 3) and sulfite anion (# 4) also alkylate on sulfur, despite the partial negative formal charge on oxygen and partial positive
charge on sulfur.

2. Oxidation States of Sulfur Compounds

Try drawing Lewis-structures for the sulfur atoms in these compounds. If you restrict your formulas to valence shell electron octets,
most of the higher oxidation states will have formal charge separation, as in equation 2 above. The formulas written here neutralize
this charge separation by double bonding that expands the valence octet of sulfur. Indeed, the S=O double bonds do not consist of
the customary σ & π-orbitals found in carbon double bonds. As a third row element, sulfur has five empty 3d-orbitals that may be

10.10.1 https://chem.libretexts.org/@go/page/211671
used for p-d bonding in a fashion similar to p-p (π) bonding. In this way sulfur may expand an argon-like valence shell octet by two
(e.g. sulfoxides) or four (e.g. sulfones) electrons. Sulfoxides have a fixed pyramidal shape (the sulfur non-bonding electron pair
occupies one corner of a tetrahedron with sulfur at the center). Consequently, sulfoxides having two different alkyl or aryl
substituents are chiral. Enantiomeric sulfoxides are stable and may be isolated.
Thiols also differ dramatically from alcohols in their oxidation chemistry. Oxidation of 1º and 2º-alcohols to aldehydes and ketones
changes the oxidation state of carbon but not oxygen. Oxidation of thiols and other sulfur compounds changes the oxidation state of
sulfur rather than carbon. We see some representative sulfur oxidations in the following examples. In the first case, mild oxidation
converts thiols to disufides. An equivalent oxidation of alcohols to peroxides is not normally observed. The reasons for this
different behavior are not hard to identify. The S–S single bond is nearly twice as strong as the O–O bond in peroxides, and the O–
H bond is more than 25 kcal/mole stronger than an S–H bond. Thus, thermodynamics favors disulfide formation over peroxide.
Mild oxidation of disufides with chlorine gives alkylsulfenyl chlorides, but more vigorous oxidation forms sulfonic acids (2nd
example). Finally, oxidation of sulfides with hydrogen peroxide (or peracids) leads first to sulfoxides and then to sulfones.

The nomenclature of sulfur compounds is generally straightforward. The prefix thio denotes replacement of a functional oxygen by
sulfur. Thus, -SH is a thiol and C=S a thione. The prefix thia denotes replacement of a carbon atom in a chain or ring by sulfur,
although a single ether-like sulfur is usually named as a sulfide. For example, C2H5SC3H7 is ethyl propyl sulfide and
C2H5SCH2SC3H7 may be named 3,5-dithiaoctane. Sulfonates are sulfonate acid esters and sultones are the equivalent of lactones.
Other names are noted in the table above.

10.10: Thiols and Sulfides is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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10.11: Nucleophilicity of Sulfur Compounds
Compounds incorporating a C–S–H functional group are named thiols or mercaptans. Despite their similarity, they are stronger
acids and more powerful nucleophiles than alcohols. The IUPAC name of (CH3)3C–SH is 2-methyl-2-propanethiol, commonly
called tert-butyl mercaptan.

Nucleophilicity of Sulfur Compounds

Sulfur analogs of alcohols are called thiols or mercaptans, and ether analogs are called sulfides. The chemical behavior of thiols
and sulfides contrasts with that of alcohols and ethers in some important ways. Since hydrogen sulfide (H2S) is a much stronger
acid than water (by more than ten million fold), we expect, and find, thiols to be stronger acids than equivalent alcohols and
phenols. Thiolate conjugate bases are easily formed, and have proven to be excellent nucleophiles in SN2 reactions of alkyl halides
and tosylates.
R–S(–) Na(+) + (CH3)2CH–Br (CH3)2CH–S–R + Na(+) Br(–)
Although the basicity of ethers is roughly a hundred times greater than that of equivalent sulfides, the nucleophilicity of sulfur is
much greater than that of oxygen, leading to a number of interesting and useful electrophilic substitutions of sulfur that are not
normally observed for oxygen. Sulfides, for example, react with alkyl halides to give ternary sulfonium salts (equation # 1) in the
same manner that 3º-amines are alkylated to quaternary ammonium salts. Although equivalent oxonium salts of ethers are known,
they are only prepared under extreme conditions, and are exceptionally reactive. Remarkably, sulfoxides (equation # 2), sulfinate
salts (# 3) and sulfite anion (# 4) also alkylate on sulfur, despite the partial negative formal charge on oxygen and partial positive
charge on sulfur.

Oxidation States of Sulfur Compounds

10.11.1 https://chem.libretexts.org/@go/page/211672
Try drawing Lewis-structures for the sulfur atoms in these compounds. If you restrict your formulas to valence shell electron octets,
most of the higher oxidation states will have formal charge separation, as in equation 2 above. The formulas written here neutralize
this charge separation by double bonding that expands the valence octet of sulfur. Indeed, the S=O double bonds do not consist of
the customary σ & π-orbitals found in carbon double bonds. As a third row element, sulfur has five empty 3d-orbitals that may be
used for p-d bonding in a fashion similar to p-p (π) bonding. In this way sulfur may expand an argon-like valence shell octet by two
(e.g. sulfoxides) or four (e.g. sulfones) electrons. Sulfoxides have a fixed pyramidal shape (the sulfur non-bonding electron pair
occupies one corner of a tetrahedron with sulfur at the center). Consequently, sulfoxides having two different alkyl or aryl
substituents are chiral. Enantiomeric sulfoxides are stable and may be isolated.
Thiols also differ dramatically from alcohols in their oxidation chemistry. Oxidation of 1º and 2º-alcohols to aldehydes and ketones
changes the oxidation state of carbon but not oxygen. Oxidation of thiols and other sulfur compounds changes the oxidation state of
sulfur rather than carbon. We see some representative sulfur oxidations in the following examples. In the first case, mild oxidation
converts thiols to disufides. An equivalent oxidation of alcohols to peroxides is not normally observed. The reasons for this
different behavior are not hard to identify. The S–S single bond is nearly twice as strong as the O–O bond in peroxides, and the O–
H bond is more than 25 kcal/mole stronger than an S–H bond. Thus, thermodynamics favors disulfide formation over peroxide.
Mild oxidation of disufides with chlorine gives alkylsulfenyl chlorides, but more vigorous oxidation forms sulfonic acids (2nd
example). Finally, oxidation of sulfides with hydrogen peroxide (or peracids) leads first to sulfoxides and then to sulfones.

Oxidation of Alcohols by DMSO

The conversion of 1º and 2º-alcohols to aldehydes and ketones is an important reaction which, in its simplest form, can be
considered a dehydrogenation (loss of H2). By providing an oxygen source to fix the product hydrogen as water, the endothermic
dehydrogenation process may be converted to a more favorable exothermic one. One source of oxygen that has proven effective for
the oxidation of alcohols is the simple sulfoxide solvent, DMSO. The reaction is operationally easy: a DMSO solution of the
alcohol is treated with one of several electrophilic dehydrating reagents (E). The alcohol is oxidized; DMSO is reduced to dimethyl
sulfide; and water is taken up by the electrophile. Due to the exothermic nature of the reaction, it is usually run at -50 ºC or lower.
Co-solvents such as methylene chloride or THF are needed, since pure DMSO freezes at 18º. The reaction of oxalyl chloride with
DMSO may generate chlorodimethylsulfonium chloride which then oxidizes the alcohol (Swern Oxidation). Alternatively, a
plausible general mechanism for this interesting and useful reaction is drawn below.

Because so many different electrophiles have been used to effect this oxidation, it is difficult to present a single general mechanism.
Most of the electrophiles are good acylating reagents, so it is reasonable to expect an initial acylation of the sulfoxide oxygen. (The
use of DCC as an acylation reagent was described elsewhere.) The electrophilic character of the sulfur atom is enhanced by
acylation. Bonding of sulfur to the alcohol oxygen atom then follows. The remaining steps are eliminations, similar in nature to

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those proposed for other alcohol oxidations. In some cases triethyl amine is added to provide an additional base. Three examples of
these DMSO oxidations are given in the following diagram. Note that this oxidation procedure is very mild and tolerates a variety
of other functional groups, including those having oxidizable nitrogen and sulfur atoms.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

10.11: Nucleophilicity of Sulfur Compounds is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
Nucleophilicity of Sulfur Compounds by William Reusch is licensed CC BY-NC-ND 3.0.

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10.12: Redox Reactions of Thiols and Disulfides
A disulfide bond is a sulfur-sulfur bond, usually formed from two free thiol groups.

The interconversion between dithiol and disulfide groups is a redox reaction: the free dithiol form is in the reduced state, and the
disulfide form is in the oxidized state. Notice that in the oxidized (disulfide) state, each sulfur atom has lost a bond to hydrogen and
gained a bond to sulfur.
As you should recall from your Biology courses, disulfide bonds between cysteine residues are an integral component of the three-
dimensional structure of many extracellular proteins and signaling peptides.

A thiol-containing coenzyme called glutathione is integrally involved in many thiol-disulfide redox processes (recall that
glutathione was a main player in this chapter's introductory story about concussion research). In its reduced (thiol) form,
glutathione is abbreviated 'GSH'. In its oxidized form, glutathione exists as a dimer of two molecules linked by a disulfide group,
and is abbreviated 'GSSG'.

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Disulfide bonds and free thiol groups in both proteins and smaller organic molecules like glutathione can 'trade places' through a
disulfide exchange reaction. This process is essentially a combination of two direct displacement (S 2-like) events, with sulfur
N

atoms acting as nucleophile, electrophile and leaving group.

Disulfide exchange reaction

Mechanism:

In eukaryotes, the cysteine side chains of intracellular (inside the cell) proteins are almost always in the free thiol (reduced) state
due to the high concentration of reduced glutathione (GSH) in the intracellular environment. A disulfide bond in an intracellular
protein will be rapidly reduced in a disulfide exchange reaction with excess glutathione.

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The interconversion of free thiols and disulfides is also mediated by flavin in some enzymes.
Flavin-mediated reduction of a protein disulfide bond

Flavin-mediated oxidation of a protein disulfide bond

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As was stated earlier, a high intracellular concentration of reduced glutathione (GSH) serves to maintain proteins in the free thiol
(reduced) state. An enzyme called glutathione reductase catalyzes the reduction of GSSG in a flavin-mediated process, with
N ADH acting as the ultimate hydride donor.

Gluthione reductase reaction:

This figure shows oxidized glutathione converted to reduced glutathione by NADPH.

The mechanism for this and other similar reactions is not yet completely understood, but evidence points to an initial thiol-disulfide
exchange reaction with a pair of cysteines from the enzyme, (phase 1 below) followed by flavin-dependent reduction of the
cysteine-cysteine disulfide (phase 2). Finally, (phase 3) F AD is reduced back to F ADH by N ADH . Frey and Hegeman,
2

Enzymatic Reaction Mechanisms, p. 699

Phase 1: thiol-disulfide exchange (see earlier figure for mechanism):

Phase 2: Reduction of protein disulfide by F ADH (see earlier figure for mechanism)
2

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Phase 3: regeneration of F ADH by N ADH (see section 15.4B for mechanism)
2

In the biochemistry lab, proteins are often maintained in their reduced (free thiol) state by incubation in buffer containing an excess
concentration of β-mercaptoethanol (BME) or dithiothreitol (DTT). These reducing agents function in a manner similar to that of
GSH, except that DTT, because it has two thiol groups, can form an intramolecular disulfide in its oxidized form.

 Exercise 15.7.1

Draw structures of the oxidized (disulfide) forms of BME and DTT.

This page titled 10.12: Redox Reactions of Thiols and Disulfides is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or
curated by Tim Soderberg via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is
available upon request.
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https://digitalcommons.morris.umn.edu/chem_facpubs/1/.

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10.13: An Introduction to Organic Synthesis
 Objective

After completing this section, you should be able to design a multistep synthesis to prepare a given product from a given
starting material, using any of the reactions introduced in the textbook up to this point.

 Study Notes

You should have noticed that some of the assigned problems have required that you string together a number of organic
reactions to convert one organic compound to another when there is no single reaction to achieve this goal. Such a string of
reactions is called an “organic synthesis.” One of the major objectives of this course is to assist you in designing such
syntheses. To achieve this objective, you will need to have all of the reactions described in the course available in your
memory. You will need to recall some reactions much more frequently than others, and the only way to master this objective is
to practise. The examples given in this chapter will be relatively simple, but you will soon see that you can devise some quite
sophisticated syntheses using a limited number of basic reactions.

Introduction
The study of organic chemistry introduces students to a wide range of interrelated reactions. Alkenes, for example, may be
converted to structurally similar alkanes, alcohols, alkyl halides, epoxides, glycols and boranes; cleaved to smaller aldehydes,
ketones and carboxylic acids; and enlarged by carbocation and radical additions as well as cycloadditions. Most of these reactions
are shown in the Alkene Reaction Map below. All of these products may be subsequently transformed into a host of new
compounds incorporating a wide variety of functional groups. Consequently, the logical conception of a multi-step synthesis for the
construction of a designated compound from a specified starting material becomes one of the most challenging problems that may
be posed. Functional group reaction maps like the one below for alkenes can be helpful in designing multi-step syntheses. It can be
helpful to build and design your own reaction maps for each functional group studied.

Alkene Reaction Map

Please note: The reagents for each chemical transformation have been intentionally omitted so that this map can be used as a study
tool. The answers are provided at the end of this section as part of the exercises.

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CH3 OH
OH + CH3
CH3 OH
OH OH OH CH3
+

OH OH

CH3

O O O
H HO
CH3 CH3
O O

CH3 CH3
Br
CH3
Br

CH3 CH3
OH

CH3 CH3 Br CH3

+ CH3 + Br

OH OH Br Br

OH CH3
CH3 + OH

Br Br

Simple Multi-Step Syntheses

A one or two step sequence of simple reactions is not that difficult to deduce. For example, the synthesis of meso-3,4-hexanediol
from 3-hexyne can occur by more than one multi-step pathway.
? HO OH

One approach would be to reduce the alkyne to cis or trans-3-hexene before undertaking glycol formation. Permanaganate or
osmium tetroxide hydroxylation of cis-3-hexene would form the desired meso isomer.
cold KMnO4 / H2O /
H H HO OH
H2 / Lindlar’s pH > 8
OR
OsO4 / H2O2

From trans-3-hexene, it would be necessary to first epoxidize the alkene with a peracid followed by ring opening with acidic or
basic hydrolysis.
H HO OH
Na0 / NH3 1. m-CPBA

H 2. H3 O+

Longer multi-step syntheses require careful analysis and thought, since many options need to be considered. Like an expert chess
player evaluating the long range pros and cons of potential moves, the chemist must appraise the potential success of various
possible reaction paths, focusing on the scope and limitations constraining each of the individual reactions being employed. The
skill is acquired by practice, experience, and often trial and error.

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Thinking it Through with 3 Examples
The following three examples illustrate strategies for developing multi-step syntheses from the reactions studied in the first ten
chapters of this text. It is helpful to systematically look for structural changes beginning with the carbon chain and brainstorm
relevant functional group conversion reactions. Retro-synthesis is the approach of working backwards from the product to the
starting material.
In the first example, we are asked to synthesize 1-butanol from acetylene.
?
H C C H OH

The carbon chain doubles in size indicating an acetylide SN2 reaction with an alkyl halide. Primary alcohol formation from an anti-
Markovnikov alkene hydration reaction (hydroboration-oxidation) is more likely than a substitution reaction. Applying retro-
synthesis, we work backwards from the alcohol to the alkene to the alkyne from an acetylide reaction that initially builds the carbon
chain.
Retro-Synthesis

OH H C C +
Br

Working forwards, we specify the reagents needed for each transformation identified from the retro-synthesis. The ethylbromide
must also be derived from acetylene so multiple reaction pathways are combined as shown below.
H C C H H C C H

1. H2 / Lindlar’s or Na0 / NH3

Na0 / NH3
2. HBr

S N2 H2 / Lindlar’s 1. BH3 / THF

H C C + OH
Br or 2. H2O2 / NaOH
Na0 / NH3

In the second example, we are asked to synthesize 1,2-dibromobutane from acetylene.

?
H C C H
Br Br

Once again there is an increase in the carbon chain length indicating an acetylide SN2 reaction with an alkyl halide similar to the
first example. The hydrohalogenation can be subtle to discern because the hydrogen atoms are not shown in bond-line structures.
Comparing the chemical formulas of 1-butyne with 1,2-dibromobutane, there is a difference of two H atoms and two Br atoms
indicating hydrohalogenation and not halogenation. The addition of both bromine atoms to the same carbon atom also supports the
idea that hydrohalogenation occurs on an alkyne and not an alkene. The formation of the geminal dihalide also indicates
hydrohalogenation instead of halogenation because halogenation produces vicinal dihalides. With this insight, the retro-synthesis
indicates the following series of chemical transformations.
Retro-Synthesis

H C C +
Br Br Br

Working forwards, we specify the reagents needed for each transformation.

H C C H H C C H

1. H2 / Lindlar’s or Na0 / NH3

Na0 / NH3
2. HBr

SN 2 excess HBr
H C C +
Br Br Br

In the third example, we are asked to produce 6-oxoheptanal from methylcyclohexane.

O
CH3
? CH3
H
O

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Counting the carbons, the starting material and product both contain seven carbon atoms and there is a cleavage reaction of an
alkene under reductive conditions. One important missing aspect of this reaction is a good leaving group (LG). Alkanes are
chemically quite boring. We can burn them as fuel or perform free-radical halogenation to create alkyl halides with excellent
leaving groups. With these observations, the following retro-synthesis is reasonable.
Retro-Synthesis
O CH3
CH3 CH3
CH3 Br
H
O

Working forwards, we specify the reagents needed for each reaction. For the initial free-radical halogenation of the alkane, we have
the option of chlorine (Cl2) or bromine (Br2). Because methylcyclohexane has several different classifications of carbons, the
selectivity of Br2 is more important than the faster reactivity of Cl2. A strong base with heat can be used for the second step to
follow an E2 mechanism and form 1-methylcyclohexene. The aldehyde group on the final product indicates gentle oxidative
cleavage by any of several reaction pathways. These reactions can be combined in to the following multi-step synthesis.
1. cold KMnO4/H2O/pH>8, then 2. HIO4
CH3 OR O
CH3 CH3
Br2 Br CH3CH2ONa 1. OsO4/H2O2, then 2. HIO4 CH3
heat or light OR H
CH3CH2OH
1. O3, then 2. S(CH3)2 or Zn/H2O O

Reaction Maps to Build Functional Group Conversion Mastery

After working through the examples above, we can see how important it is to memorize all of the functional group reactions
studied in the first ten chapters. We can apply the knowledge of these reactions to the wisdom of multi-step syntheses.
Please note: The reagents for each chemical transformation have been intentionally omitted so that these maps can be used as a
study tools. The answers are provided at the end of this section as part of the exercises.

Alkane and Alkyl Halide Reaction Map

OH Cl

NH2 CN

SH N3

OCH3 SCH3

Alkyne Reaction Map

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Br
O

Br Br

Br
Br
Br Br

O
CH
C
H

Br Br Br Br

C C O
C C + CO2
C CH OH

O
H H
H
O

 Exercise

1) Starting at 3-hexyne predict synthetic routes to achieve:

a) trans-3-hexene
b) 3,4-dibromohexane
c) 3-hexanol.
2) Starting with acetylene and any alkyl halides propose a synthesis to make
a) pentanal
b) hexane.
3) Show how you would accomplish the following synthetic transformations.
a)

O
b)

Answer
1)
Br
(B)
Br

Br2

Lindlar’s
(A)
H2

H2SO4
H2O

OH
(C)

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2)
a)
O

1. BH3
2. H2O

NaNH2/
NH3

Br +

H2
Pd/C

NaNH2/
NH3

Br +

3)
a)
1. xs. NaNH2 1. xs. NaNH2 Na0, NH3
2. CH3Br 2. CH3Br

b)
1. xs. NaNH2 H2SO4, H2O O

2. CH3CH2CH2Br HgSO4

10.13: An Introduction to Organic Synthesis is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
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CHAPTER OVERVIEW

11: The Chemistry of Ethers, Epoxides, Glycols, and Sulfides

11: The Chemistry of Ethers, Epoxides, Glycols, and Sulfides is shared under a not declared license and was authored, remixed, and/or curated by
LibreTexts.

1
11.1: Williamson Ether Synthesis
 Objectives

After completing this section, you should be able to

1. write an equation to illustrate the industrial preparation of simple symmetrical ethers.
2. write an equation to illustrate the Williamson synthesis of ethers.
a. identify the ether obtained from the reaction of a given alkyl halide with a given alkoxide ion.
b. identify the reagents needed to prepare a given ether through a Williamson synthesis.
c. identify the limitations of the Williamson synthesis, and make the appropriate choices when deciding how best to
synthesize a given ether.
d. write an equation to describe the formation of an alkoxide from an alcohol.
e. identify silver(I) oxide as a reagent which can be used in a Williamson synthesis.
3. write an equation to show how an ether can be prepared by the alkoxymercuration-demercuration of an alkene.
a. identify the product formed from the alkoxymercuration-demercuration of a given alkene.
b. identify the alkene, the reagents, or both, needed to prepare a given ether by the alkoxymercuration-demercuration
process.
c. write the detailed mechanism of the reaction between an alkene, an alcohol and mercury(II) trifluoroacetate.

 Key Terms

Make certain that you can define, and use in context, the key terms below.
alkoxymercuration
oxymercuration
Williamson ether synthesis

 Study Notes
We studied oxymercuration as a method of converting an alkene to an alcohol in Section 8.5. “Alkoxymercuration” is a very
similar process, except that we are now converting an alkene into an ether. The two processes are compared below.

Description oxymercuration alkoxymercuration

we react an alkene alkene

with water an alcohol

in the presence of Hg(O2CCH3)2 Hg(O2CCF3)2

followed by treatment with NaBH4 NaBH4

to produce an alcohol ether

Review the mechanism of the oxymercuration reaction in Section 8.5, paying particular attention to the regiochemistry and the
stereochemistry of the reaction. The mechanism is identical to alkoxymercuration.

Ether Formation Though Dehydration

Acid-catalyzed dehydration of small 1º-alcohols constitutes a specialized industrial method of preparing symmetrical ethers. This
reaction cannot be employed to prepare unsymmetrical ethers because a mixture of products is likely to be obtained. Also, 2o and
3o alcohols cannot be used for this reaction because they dehydrate to form alkenes by an E1 mechanism (Section 17-6).
o
130 C

2 CH CH −OH + H SO −−−−→ CH CH −O−CH CH +H O (18.2.1)

3 2 2 4 3 2 2 3 2

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Mechanism
In the first step of the reaction mechanism, one alcohol is protonated to become a good leaving group. In the second step, a second
alcohol displaces water from the protonated alcohol during an SN2 reaction yielding a protonated ether. In the final step, this
intermediate is deprotonated to yield the symmetrical ether.

H H
O
H H H H H H H H H H H
O H O H3 O+
H +
H H3C O CH3 H3C O CH3
H CH3 H CH3 CH3 H H
O O
H H H H

Williamson Ether Synthesis

One important procedure, known as the Williamson Ether Synthesis, proceeds by an SN2 reaction of an alkoxide nucleophile with
a primary alkyl halide or tosylate. As previously discussed in Section 17-2, alkoxides are commonly created by deprotonating an
alcohol with a strong base, such as sodium hydride (NaH). Simple alcohols can be used a solvent during a Williamson ether
synthesis and with their alkoxide created through the addition of sodium metal (Na(s)).

Planning a Williamson Ether Synthesis

The Williamson ether synthesis has the same limitations as other SN2 reactions, as discussed in Section 11-3. Since alkoxide anions
are strong bases, utilizing 2o or 3o halogen leaving groups could possibly produce an E2 elimination product. When considering the
synthesis of an unsymmetrical ether, there are two different combinations of reactants possible and each should be carefully
considered. In general, the pathway which utilizes the least sterically hindered halogen will be preferred.
The key bond cleavage in the target molecule involves a C-O bond. Because unsymmetrical ethers have two unique C-O bonds,
each can be broken to provide a unique set of reactants. After cleavage, the fragment with the oxygen will become an alkoxide. The
other fragment will become a halogen or tosylate.

 Worked Example 11.1.1

How would you prepare the following molecule using a Williamson Ether Synthesis?

Answer
Analysis: The ether is asymmetrical so each of the C-O bonds can be broken to create a different set of possible reactants.
After cleavage of the C-O bond, pathway 1 shows a 3o halogen as the starting material. This reaction will most likely not be

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effective due to alkoxides reacting with 3o halogens to preferable form an alkenes by E2 elimination. Pathway 2 shows a 1o
halogen as a starting material which is favorable for SN2 reactions.
Pathway 1

Solution 1

Pathway 2

Solution 2

Ether Synthesis Using Silver Oxide

A variation of the Williamson ether synthesis uses silver oxide (Ag2O) in the place of the strong base. The conditions of this
variation are milder than the typical Willamson synthesis because a strong base and the formation of an alkoxide intermediate are
not necessary. This reaction is particually useful when converting the -OH groups on a sugar into ethers.

Mechanism
During this reaction a partial positively charged silver in Ag2O gives draws electron density from the iodine in CH3I. This
correspondingly removes electron density from the adjacent carbon increasing its partial positive charge which increases its
electrophlicity. This allows the alcohol to act as a nucleophile in the subsequent SN2 reaction.

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Ether Synthesis Using Alkoxymercuration
Alkoxymercuration, is patterned after the oxymercuration reaction discussed in Section 8-4. Reaction of an alkene with an
alcohol in the presence of a trifluoroacetate mercury (II) salt [(CF3CO2)2Hg] prodcues an alkoxymercuration product.
Demercuration using sodium borohydride (NaBH4) yields an ether product. Overall, this reaction allows for the Markovnikov
addition of an alcohol to an alkene to create an ether. Note that the alcohol reactant is used as the solvent, and a trifluoroacetate
mercury (II) salt is used in preference to the mercuric acetate (trifluoroacetate anion is a poorer nucleophile than acetate). Most 1o,
2o, 3o alcohols can be successfully used for this reaction.

Mechanism
The mechanism of alkoxymercuration is similar to that of oxymercuration, with electrophillic addition of the mercuric species to
the alkene. The alcohol nucleophile attacks the more substituted carbon of the three-membered ring via a SN2 reaction. Finally,
sodium borohydride (NaBH4) provides a reductive demercuration to form the ether product.

Planning the Synthesis of an Ether using Alkoxymercuration

The key bond cleavage in the target molecule involves a C-O bond. Because unsymmetrical ethers have two unique C-O bonds,
each can be broken to provide a unique set of reactants. After cleavage, the fragment with the oxygen will become an alcohol. The
alkyl fragment will lose a hydrogen from a adjacent carbon to form an alkene. The main point to consider when choosing a possible
synthesis pathways is the ability of the alkyl fragment to form an alkene.

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 Worked Example 11.1.2

How would you prepare the following molecule using a alkoxymercuration?

Answer
Analysis: The ether is symmetrical so each C-O bond of the ether can be cleaved to produce a set of starting materials for
consideration. Pathway one shows a set of starting material which should work well for this reaction. The alcohol,
methanol, can easily be used as a solvent. Although the alkene does not have a defined more and less substituted side, its
symmetry will prevent a mixture of product from forming. The fragmentation for pathway 2 shows starting material which
are not viable for this reaction. The alkyl fragment only has one carbon which cannot be used to form an alkene starting
material. This means pathway 2 is not a viable method for the synthesis of the target molecule.
Pathway 1

Solution 1

Pathway 2

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Exercises

 Exercise 11.1.1

When preparing ethers using the Williamson ether synthesis, what factors are important when considering the nucleophile and
the electrophile?

Answer
The nucleophile ideally should be very basic, yet not sterically hindered. This will minimize any elimination reactions from
occurring. The electrophile should have the characteristics of a good SN2 electrophile, preferably primary to minimize any
elimination reactions from occurring.

 Exercise 11.1.2

How would you synthesize the following ethers? Keep in mind there are multiple ways. The Williamson ether synthesis,
alkoxymercuration of alkenes, and also the acid catalyzed substitution.

(a) (b) (c) (d) (e)

Answer
The Williamson ether syntheses require added catalytic base. Also, most of the halides can be interchanged, say for
example for a -Br or a -Cl. Although, typically -I is the best leaving group.

(a)

(b)

(c)

(d)
Note, there is only one ether (also called a silyl ether, and often used as an alcohol protecting group.) The other group is an
ester.

(e)

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 Exercise 11.1.3
Draw the electron arrow pushing mechanism for the formation of diethyl ether in the previous problem.

Answer

 Exercise 11.1.4

t-butoxycyclohexane can be prepared two different ways from an alkene and an alcohol, draw both possible reactions.

Answer

While both are possible, the top route is likely easier because both starting materials are a liquid.

 Exercise 11.1.5

Epoxides are often formed intramolecularly. Take for example this large ring, in a publication from 2016 [J. Org. Chem., 2016,
81 (20), pp 10029–10034]. If subjected to base, what epoxide would be formed? (Include stereochemistry)

Answer

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 Exercise 11.1.6
What reagents would you use to perform the following transformations?

(a)

(b)

(c)

Answer

(a)

(b) Note the cis addition

(c)
An oxidation to an alcohol through hydroboration, and subsequent substitution with 2-bromopropane could also work, but
this route provides the least likelihood of an elimination reaction occurring.

 Exercise 11.1.7

Predict the product of the following.

Answer

The result is the production of dioxane, a common solvent.

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Contributors and Attributions

William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
Layne Morsch (University of Illinois Springfield)

11.1: Williamson Ether Synthesis is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.
18.2: Preparing Ethers by Dietmar Kennepohl, Steven Farmer is licensed CC BY-SA 4.0.

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11.2: Synthesis of Epoxides
Epoxides (also known as oxiranes) are three-membered ring structures in which one of the vertices is an oxygen and the other two
are carbons.

The most important and simplest epoxide is ethylene oxide which is prepared on an industrial scale by catalytic oxidation of
ethylene by air.

Ethylene oxide is used as an important chemical feedstock in the manufacturing of ethylene glycol, which is used as antifreeze,
liquid coolant and solvent. In turn, ethylene glycol is used in the production of polyester and polyethylene terephthalate (PET) the
raw material for plastic bottles.

Peroxyacid reactions with Alkenes

Oxacyclopropane synthesis by peroxycarboxylic acid requires an alkene and a peroxycarboxylic acid as well as an appropriate
solvent. The peroxycarboxylic acid has the unique property of having an electropositive oxygen atom on the COOH group. The
reaction is initiated by the electrophilic oxygen atom reacting with the nucleophilic carbon-carbon double bond. The mechanism
involves a concerted reaction with a four-part, circular transition state. The result is that the originally electropositive oxygen atom
ends up in the oxacyclopropane ring and the COOH group becomes COH.

Intramolecular Williamson Ether Synthesis via Halohydrins

Epoxides can also be synthesized by the treatment of a halohydrin with a base. This causes an intramolecular Williamson ether
synthesis.

Exercise
8. What reagents would you use to perform the following transformations?

(a)

(b)

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(c)

(d)

Answer
8.

(a)

(b) Note the cis addition

(d)
Lindlar's catalyst reduces alkynes to cis/Z alkenes. This stereochemistry is retained after epoxidation.

Contributors and Attributions

11.2: Synthesis of Epoxides is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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11.3: Acidic Cleavage of Ethers
The most common reaction of ethers is cleavage of the C–O bond by strong acids. This may occur by SN1 or E1 mechanisms for
3º-alkyl groups or by an SN2 mechanism for 1º-alkyl groups.

Some examples are shown in the following diagram. The conjugate acid of the ether is an intermediate in all these reactions, just as
conjugate acids were intermediates in certain alcohol reactions.

The first two reactions proceed by a sequence of SN2 steps in which the iodide or bromide anion displaces an alcohol in the first
step, and then converts the conjugate acid of that alcohol to an alkyl halide in the second. Since SN2 reactions are favored at least
hindered sites, the methyl group in example #1 is cleaved first. The 2º-alkyl group in example #3 is probably cleaved by an SN2
mechanism, but the SN1 alternative cannot be ruled out. The phenol formed in this reaction does not react further, since SN2, SN1
and E1 reactions do not take place on aromatic rings. The last example shows the cleavage of a 3º-alkyl group by a strong acid.
Acids having poorly nucleophilic conjugate bases are often chosen for this purpose so that E1 products are favored.

Exercise
7. Draw the bond-line structures of the product(s) for each reaction below.

Answer
7.

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Contributors and Attributions
11.3: Acidic Cleavage of Ethers is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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11.4: Opening of Epoxides
Epoxide ring-opening reactions - SN1 vs. SN2, regioselectivity, and stereoselectivity
The ring-opening reactions of epoxides provide an excellent review of the differences between SN1 and SN2 reactions. Both
mechanisms are good examples of regioselective reactions. In a regioselective reaction, two (or more) different constitutional
isomers are possible as products, but one is formed preferentially (or sometimes exclusively). Ring-opening reactions can proceed
by either SN2 or SN1 mechanisms, depending on the nature of the epoxide and on the reaction conditions. For the SN1 mechanism,
the stability of the charged intermediate determines the regioselectivity. For the concerted SN2 mechanism, sterics are the
dominating consideration. If the epoxide is asymmetric, the structure of the product will vary according to which mechanism
dominates. When an asymmetric epoxide undergoes solvolysis in basic methanol, ring-opening occurs by an SN2 mechanism, and
the less substituted carbon is the site of nucleophilic reaction, leading to what we will refer to as product B:

Conversely, when solvolysis occurs in acidic methanol, the reaction occurs by a mechanism with substantial SN1 character, and the
more substituted carbon is the site of reaction. As a result, product A predominates.

Let us examine the basic, SN2 case first. The leaving group is an alkoxide anion, because there is no acid available to protonate the
oxygen prior to ring opening. An alkoxide is a poor leaving group, and thus the ring is unlikely to open without a 'push' from the
nucleophile.

The nucleophile itself is a potent, deprotonated, negatively charged methoxide ion. When a nucleophilic substitution reaction
involves a poor leaving group and a powerful nucleophile, it is very likely to proceed by an SN2 mechanism.
What about the electrophile? There are two electrophilic carbons in the epoxide, but the best target for the nucleophile in an SN2
reaction is the carbon that is least hindered. This accounts for the observed regiochemical outcome. Like in other SN2 reactions,
bimolecular, nucleophilic substitution reactions take place from the backside, resulting in inversion at the electrophilic carbon.
The acid-catalyzed epoxide ring-opening reaction mechanism is analogous to the formation of the bromonium ion in halogenation
of alkenes and mercurium ion formation in oxymercuration/demercuratioin or alkoxymercuration/demercuration. First, the oxygen
is protonated, creating a good leaving group (step 1 below) . Then the carbon-oxygen bond begins to break (step 2) and positive
charge begins to build up on the more substituted carbon (recall carbocation stability).

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Unlike in an SN2 reaction, the nucleophile reacts with the electrophilic carbon (step 3) before a complete carbocation intermediate
has a chance to form.

The reaction takes place preferentially from the backside (like in an SN2 reaction) because the carbon-oxygen bond is still to some
degree in place, and the oxygen blocks reaction from the front side. Notice, however, how the regiochemical outcome is different
from the base-catalyzed reaction: in the acid-catalyzed process, the nucleophile reacts with the more substituted carbon because this
carbon that holds a greater degree of positive charge.

Example
Predict the major product(s) of the ring opening reaction that occurs when the epoxide shown below is treated with:
a. ethanol and a small amount of sodium hydroxide
b. ethanol and a small amount of sulfuric acid

Hint: be sure to consider both regiochemistry and stereochemistry!

Answer

Anti Dihydroxylation
Epoxides may be cleaved by aqueous acid to give glycols that are often diastereomeric with those prepared by the syn-
hydroxylation reaction. Proton transfer from the acid catalyst generates the conjugate acid of the epoxide, which is attacked by
nucleophiles such as water in the same way that the cyclic bromonium ion described above undergoes reaction. The result is anti-
hydroxylation of the double bond. In the following equation this procedure is illustrated for a cis-disubstituted epoxide, which can
be prepared from the corresponding cis-alkene. This hydration of an epoxide does not change the oxidation state of any atoms or
groups.

Addition of HX
Epoxides can also be opened by other anhydrous acids (HX) to form a trans halohydrin. When both the epoxide carbons are either
primary or secondary the halogen anion will react with the less substituted carbon and an SN2 like reaction. However, if one of the

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epoxide carbons is tertiary, the halogen anion will primarily react with the tertiary carbon in a SN1 like reaction.

Example
In the first example, the epoxide is formed by a secondary and primary carbon. The reaction with the Cl- nucleophile proceeds
via the SN2 mechanism and reacts with the least substituted carbon.

In the second example, the epoxide is formed by a tertiary and primary carbon. The reaction with Cl- nucleophile proceeds via
the SN1 like mechanism and reacts with the most substituted carbon because it carries the greater partial positive charge.

Exercise

9. Given the following, predict the product assuming only the epoxide is affected. (Remember stereochemistry)

10. Predict the product of the following, similar to above but a different nucleophile is used and not in acidic conditions.
(Remember stereochemistry)

11. Epoxides are often very useful reagents to use in synthesis when the desired product is a single stereoisomer. If the
following alkene were reacted with an oxyacid to form an epoxide, would the result be a enantiomerically pure? If not, what
would it be?

Answer

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9.

Note that the stereochemistry has been inverted

10.

11.
First, look at the symmetry of the alkene. There is a mirror plane, shown here.

Then, think about the mechanism of epoxidation with an oxyacid, take for example mCPBA. The
mechanism is concerted, so the original cis stereochemistry is not changed. This leads to "two" epoxides.

However, these two mirror images are actually identical due to the mirror plane of the cis
geometry. It is a meso compound, so the final result is a single stereoisomer, but not a single enantiomer.

Contributors and Attributions

Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)
Prof. Steven Farmer (Sonoma State University)
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

11.4: Opening of Epoxides is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

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11.5: Dihydroxylation of Alkenes
Learning Objective
predict the products/specify the reagents for dihydroxylation of alkenes

Dihydroxylation of alkenes
Alkenes can be dihydroxylated by two different stereochemical pathways: anti-dihydroxylation or syn-dihydroxylation. The
opening of epoxides follows the anti-dihydroxylation mechanism, while potassium permanganate or osmium tetroxide produce the
syn-dihydroxylated products. The osmium tertroxide reaction can also take place by a two-step process: 1) OsO4 in pyridine
followed by 2) H2S or NaHSO3. It is important to note that different professors will emphasize different reagent systems to
accomplish the same chemical reaction. In these situations, it can be helpful to recognize the role of each reagent to discern
patterns.

Anti Dihydroxylation
Epoxides may be cleaved by aqueous acid to give glycols that are often diastereomeric with those prepared by the syn-
hydroxylation reaction described above. Proton transfer from the acid catalyst generates the conjugate acid of the epoxide, which is
attacked by nucleophiles such as water in the same way that the cyclic bromonium ion described above undergoes reaction. The
result is anti-hydroxylation of the double bond, in contrast to the syn-stereoselectivity of the earlier method. In the following
equation this procedure is illustrated for a cis-disubstituted epoxide, which, of course, could be prepared from the corresponding
cis-alkene. This hydration of an epoxide does not change the oxidation state of any atoms or groups. The mechanism for the ring
opening of epoxides depends on the reaction conditions and is discussed in more detail in the next section of this chapter.

Syn Dihydroxylation
Osmium tetroxide oxidizes alkenes to give glycols through syn addition. A glycol, also known as a vicinal diol, is a compound with
two -OH groups on adjacent carbons.

Dihydroxylated products (glycols) are obtained by reaction with aqueous potassium permanganate (pH > 8) or osmium tetroxide in
pyridine solution. Both reactions appear to proceed by the same mechanism (shown below); the metallocyclic intermediate may be
isolated in the osmium reaction. In basic solution the purple permanganate anion is reduced to the green manganate ion, providing a
nice color test for the double bond functional group. From the mechanism shown here we would expect syn-stereoselectivity in the
bonding to oxygen, and regioselectivity is not an issue.
When viewed in context with the previously discussed addition reactions, the hydroxylation reaction might seem implausible.
Permanganate and osmium tetroxide have similar configurations, in which the metal atom occupies the center of a tetrahedral

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grouping of negatively charged oxygen atoms. How, then, would such a species interact with the nucleophilic pi-electrons of a
double bond? A possible explanation is that an empty d-orbital of the electrophilic metal atom extends well beyond the surrounding
oxygen atoms and initiates electron transfer from the double bond to the metal, in much the same fashion noted above for platinum.
Back-bonding of the nucleophilic oxygens to the antibonding π*-orbital completes this interaction. The result is formation of a
metallocyclic intermediate, as shown above.

The reaction with OsO is a concerted process that has a cyclic intermediate and no rearrangements. Vicinal syn dihydroxylation
4

complements the epoxide-hydrolysis sequence which constitutes an anti dihydroxylation of an alkene. When an alkene reacts with
osmium tetroxide, stereocenters can form in the glycol product. Cis alkenes give meso products and trans alkenes give racemic
mixtures.

OsO4 is formed slowly when osmium powder reacts with gasoues O2 at ambient temperature. Reaction of bulk solid requires
heating to 400 °C:
Os(s) + 2 O2 (g)
→ OS4 (11.5.1)

Since Osmium tetroxide is expensive and highly toxic, the reaction with alkenes has been modified. Catalytic amounts of OsO4 and
stoichiometric amounts of an oxidizing agent such as hydrogen peroxide are now used to eliminate some hazards. Also, an older
reagent that was used instead of OsO4 was potassium permanganate, KM nO . Although syn diols will result from the reaction of
4

KMnO4 and an alkene, potassium permanganate is less useful since it gives poor yields of the product because of overoxidation.

Chemical Highlight
Antitumor drugs have been formed by using dihydroxylation. This method has been applied to the enantioselective synthesis of
ovalicin, which is a class of fungal-derived products called antiangiogenesis agents. These antitumor products can cut off the blood
supply to solid tumors. A derivative of ovalicin, TNP-470, is chemically stable, nontoxic, and noninflammatory. TNP-470 has been
used in research to determine its effectiveness in treating cancer of the breast, brain, cervix, liver, and prostate.

Exercise

1. Give the major product.

2. What is the product in the dihydroxylation of (Z)-3-hexene?

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3. What is the product in the dihydroxylation of (E)-3-hexene?

4. Draw the intermediate of this reaction.

5. Fill in the missing reactants, reagents, and product.

Answer
1. A syn-1,2-ethanediol is formed. There is no stereocenter in this particular reaction. The OH groups are on the same side.

2. Meso-3,4-hexanediol is formed. There are 2 stereocenters in this reaction.

3. A racemic mixture of 3,4-hexanediol is formed. There are 2 stereocenters in both products.

4. A cyclic osmic ester is formed.

5. The Diels-Alder cycloaddition reaction is needed in the first box to form the cyclohexene. The second box needs a
reagent to reduce the intermediate cyclic ester (not shown). The third box has the product: 1,2-cyclohexanediol.

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References
1. Dehestani, Ahmad et al. (2005). Ligand-assisted reduction of osmium tetroxide with molecular hydrogen via a [3+2]
mechanism. Journal of the American Chemical Society, 2005, 127 (10), 3423-3432.
2. Sorrell, Thomas, N. Organic Chemistry. New York: University Science Books, 2006.
3. Vollhardt, Peter, and Neil E. Schore. Organic Chemistry: Structure and Function. 5th Edition. New York: W. H. Freeman &
Company, 2007.

Contributors and Attributions

Shivam Nand

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11.6: Periodate cleavage of 1,2-diols (glycols)
Ozonolysis
In determining the structural formula of an alkene, it is often necessary to find the location of the double bond within a given
carbon framework. One way of accomplishing this would be to selectively break the double bond and mark the carbon atoms that
originally formed that bond. For example, there are three isomeric alkenes that all give 2-methylbutane on catalytic hydrogenation.
These are 2-methyl-2-butene (compound A), 3-methyl-1-butene (compound B) and 2-methyl-1-butene (compound C), shown in the
following diagram. If the double bond is cleaved and the fragments marked at the cleavage sites, the location of the double bond is
clearly determined for each case. A reaction that accomplishes this useful transformation is known. It is called ozonolysis.

Ozone, O3, is an allotrope of oxygen that adds rapidly to carbon-carbon double bonds. Since the overall change in ozonolysis is
more complex than a simple addition reaction, its mechanism has been extensively studied. Reactive intermediates called ozonides
have been isolated from the interaction of ozone with alkenes, and these unstable compounds may be converted to stable products
by either a reductive workup (Zn dust in water or alcohol) or an oxidative workup (hydrogen peroxide). The results of an oxidative
workup may be seen by clicking the "Show Reaction" button a second time. Continued clicking of this button repeats the cycle.
The chief difference in these conditions is that reductive workup gives an aldehyde product when hydrogen is present on a double
bond carbon atom, whereas oxidative workup gives a carboxylic acid or carbon dioxide in such cases. The following equations
illustrate ozonide formation, a process that is believed to involve initial syn-addition of ozone, followed by rearrangement of the
extremely unstable molozonide addition product. They also show the decomposition of the final ozonide to carbonyl products by
either a reductive or oxidative workup.

From this analysis and the examples given here, you should be able to deduce structural formulas for the alkenes that give the
following ozonolysis products:

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Glycol Cleavage
The vicinal glycols prepared by alkene hydroxylation (reaction with osmium tetroxide or permanganate) are cleaved to aldehydes
and ketones in high yield by the action of lead tetraacetate (Pb(OAc)4) or periodic acid (HIO4). This oxidative cleavage of a
carbon-carbon single bond provides a two-step, high-yield alternative to ozonolysis, that is often preferred for small scale work
involving precious compounds. A general equation for these oxidations is shown below. As a rule, cis-glycols react more rapidly
than trans-glycols, and there is evidence for the intermediacy of heterocyclic intermediates (as shown), although their formation is
not necessary for reaction to occur.

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

Carey 5th Ed Online

Oxidative Cleavage of 1,2-Diols

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Chemtube3D
Periodate Cleavage of 1,2-Diol

MasterOrganicChemistry
Sodium Periodate
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Oxidative Cleavage of Double Bonds is licensed CC BY-NC-SA 4.0.

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11.7: Epoxidation
Epoxidation is the addition of a single oxygen atom across a C=C double bond.

Earlier, we saw that alkenes can donate their pi electrons to electrophiles such as "Br+". In the bromonium ion that results, a lone
pair on the bromine can donate back to the incipient carbocation, leading to a more stable intermediate.

We have also seen that addition to alkenes can sometimes be concerted, happening all at once, rather than one step at a time. For
example, in hydroboration, the boron and the hydrogen add to the double bond at the same time.

The boron is adding just slightly ahead of the hydrogen. The initial interaction is donation from the pi bond to the Lewis acidic
boron. However, as soon as positive charge starts to build up on carbon, and negative charge starts to build up on boron, the
hydride is immediately donated. Time is not allowed for the charged intermediate to fully form before proceeding.

Really, that's what is happening to the bromine, too. As the alkene starts to donate its pi electrons to the bromine and begins to
build up positive charge, the bromine's lone pair is drawn back to the alkene. As a result, the intermediate that we imagine with a
full positive charge on carbon and no charge on bromine exists too fleetingly to be considered an intermediate at all. As soon as it
begins to form, it is already turning into something else.

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That sort of concerted addition happens with some other electrophiles, too. If an atom is electrophilic, but also has a lone pair to
donate, that cyclic transition state can lead to the product in one step.
Alkene epoxidation is another example of this kind of reaction. An epoxidation is the transfer of an oxygen atom from a peroxy
compound to an alkene. Peroxides contain O-O bonds, which are relatively weak and reactive.

To simplify a little bit, just look at the reaction from the point of view of the alkene. It's just picking up an oxygen atom, because
the peroxide had an extra one.

When the oxygen atom is transferred, it forms an epoxide (sometimes called an oxirane). It is a three-membered ring containing
two carbons and an oxygen.
Epoxidation results in transfer of an oxygen atom from a peroxide to an alkene.
Peroxides are compounds containing weak O-O bonds.
Like in a bromination, the electrophile is deceptive. It is an oxygen atom, which we more naturally think of as a nucleophile.
However, just as Br2 contains an atom attached to a good leaving group (Br -), so do the kinds of oxygen compounds used in
epoxidation. Most often, these are "peroxy acids", carboxylic acids containing an extra oxygen.

As in the bromination, as soon as the alkene begins donating to the electrophile, a lone pair can donate back, so that an unstable
cation does not have to form.

The entire mechanism is believed to be concerted, based on a number of lines of experimental evidence. A number of things need
to be accomplished; in addition to the oxygen donation, the leaving group must leave, and a proton must be transferred.

The reaction mechanism can be cleaned up slightly because it is thought to be an example of a pericyclic reaction. Pericylcic
reactions frequently involving three pairs of electrons moving in a circle. Like the three pairs of electrons in a benzene ring, this
structure is thought to be unusually stable.

Apart from peroxy acids, many other peroxides can be involved in epoxidations, as well as some metal oxides. In some cases, the
reaction is extremely slow, but works better in the presence of a catalyst.

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 Exercise 11.7.1

Predict the products of the following reactions.

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Answer

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Epoxidation reactions display an almost counter-intuitive selectivity. Unlike hydrogenation reactions, which are generally easier
with less-substituted alkenes, epoxidations are much faster with more-substituted alkenes. In the case of hydrogenations, the
selectivity can be understood as a combination of steric factors (the alkene must bind to a catalyst) as well as thermodynamicic
factors (more substituted alkenes are more stable, so they are less likely to react). However, in epoxidations, the more electron-rich
the alkene, the more easily it can be induced to react with the peroxide. More substituted alkenes are generally more electron-rich
than those that are substituted only with electron-poor hydrogens.

 Exercise 11.7.2

Predict the products of the following reactions.

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Answer

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The Sharpless epoxidation is one of the most common methods of catalytically adding an oxygen across a double bond. The
method generally employs a titanium catalyst; similar approaches use vanadium catalysts or other metallic species. As mentioned
before, metal ions can sometimes accelerate epoxidations.

The Sharpless epoxidation is important partly because it selectively epoxidizes allylic alcohols: compounds containing a C=C-C-
OH unit. That means that, in addition to being able to selectively epoxidize more-substituted double bonds in the presence of less-
substituted double bonds, we can also select double bonds that are close to alcohols.

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 Exercise 11.7.3
Circle the allylic alcohol in each of the following compounds.

Answer

How does the metal catalysis selectively identify that position? Remember, one of the important strategies in enzyme catalysis is
approximation: the act of bringing two things together. An alcohol is a potential lone pair donor, so it could become a ligand for a
metal ion. Ti4+ and V4+ happen to be very oxophilic -- they bind well to oxygen -- and so they are particularly suited for this task.

In this scheme, we're not worrying about exactly how the titanium ion gets to peroxide to give up its extra oxygen to the alkene;
that's complicated. However, the fact that both the allylic alcohol and the peroxide can bind to the titanium gets them closer
together, and makes them more likely to react with each other.

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That's only part of the story of the Sharpless epoxidation. The other reason this method is important is its stereoselectivity. To get
stereoselectivity, a chiral ligand is added for the titanium. It's usually diethyl tartrate (DET) or diisopropyl tartrate (DIT). Tartrate is
chiral; there is a D-(-)-enantiomer and a L-(+)-enantiomer. The D and L are common symbols used to designate enantiomers in
sugars; they relate the structure back to the biochemical grandparents of all sugars, D-glyceraldehyde and L-glyceraldehyde. The
(-) and (+) symbols refer to the characteristics of this particular compound in polarimetry; the (+) enantiomer rotates plane
polarized light in a clockwise direction, whereas the (-) enantiomer rotates plane polarized light in a counter-clockwise direction.

 Exercise 11.7.4

Assign stereochemical configurations (R and S) to the tartrates to confirm that they are enantiomers of each other.

Answer
D-(-)-tartrate is the (2S,3S)-isomer. L-(+)-tartrate is the (2R,3R)-isomer.Each chiral center is configured opposite to the
corresponding one in the other molecule, so the molecules are enantiomers.

If the D-(-)-isomer is added, one possible enantiomer of the product is obtained. If the L-(+)-isomer is added, the other possible
enantiomer is obtained.

In general, we would get one enantiomer if the oxygen were added to one face of the alkene and the other enantiomer if the oxygen
were added to the other face. In the drawing below, the face of the alkene towards us is sometimes called the "re face" (pronounced,
ray face). The face of the alkene away from us is called the "si face" (see face). These words sound related to R and S
configuration, and they sort of are like that, but they are used to describe two different faces of a flat molecule. Adding oxygen to
the re face gives on enantiomer; addign oxygen to the si face gives another.

How does this preferred reactivity work? How does the metal manage to add the oxygen to one face but not to the other? Tartrates
are oxygen-rich and so they bind very well to titanium. Remember, if we have a reaction site and we make it chiral, one enantiomer
of the product is generally preferred. Enzymes are very compicated, chiral molecules, and they are good at producing one
enantiomer of a product. By comparison, the titanium DET complex is a relatively simple chiral molecule, but it uses the same
idea.

Now, it is really very difficult to look at these conditions and predict exactly which enantiomer would be formed in a reaction.
However, we can look at a factor that might illustrate an underlying reason for the preference. In quadrant analysis, we look at the
general shape formed by that bidentate tartrate ligand on the metal. In the pictures below, the red ball is the metal atom. The tartrate
ligand extends up and to the right as it sits on the metal, and also down and to the left; it is cartooned in blue. As a result, if we
think of the metal as sitting in the middle of a square, alternating corners of that square are filled, and the other corners are empty.

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Imagine the alkene approaching that metal. The alkene will probably have a preferred orientation in which it will bind. Just for
example, maybe it needs to bind with the double bond in the same plane as the ring formed by the titanium and the oxygens
(horizontally in the picture). If it does that, it can reduce steric interactions with the ligand by binding one face of the alkene
preferentially to the metal, keeping the biggest substituent on the alkane (the black ball) in a relatively open space. The alkene
could also bind if rotated upside down compared to the first picture, but the same face would still be towards the titanium.
On the other hand, if the alkene tries to bind through the other face of the pi bond, the largest substituent would be in a more
crowded space. That might be less favorable.
Overall, if the alkene has a preferred face that it will bind to the metal, then anything delivered from that metal will land on that
face, and not the opposite one.
There are lots of variations on this model. Maybe it isn't steric interactions that influence how the alkene approaches the metal.
Maybe it is some other factor, like hydrogen bonding, that pulls in the alkene oriented in one direction and not another.
Nevertheless, although the details of a particular case make the outcome very difficult to predict, the general idea is a familiar one:
a chiral molecule will fit preferentially one way with another molecule, because of its asymmetric shape.

 Exercise 11.7.5

Although you may not be able to predict off the top of your head which enantiomer is formed in a Sharpless epoxidation, given
one result, you may be able to guess another. Given the reaction on the left, see what you can tell about the reaction on the
right.

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Answer

 Exercise 11.7.6
Fill in the boxes in the following synthesis.

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Answer

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 Exercise 11.7.7

Fill in the boxes in the following synthesis.

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Answer

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 Exercise 11.7.8

Fill in the boxes in the following synthesis.

11.7.16 https://chem.libretexts.org/@go/page/211683
Answer

11.7.17 https://chem.libretexts.org/@go/page/211683
11.7.18 https://chem.libretexts.org/@go/page/211683
This page titled 11.7: Epoxidation is shared under a CC BY-NC license and was authored, remixed, and/or curated by Chris Schaller.
6.8: Epoxidation by Chris Schaller is licensed CC BY-NC 3.0. Original source: https://employees.csbsju.edu/cschaller/ROBI2.htm.

11.7.19 https://chem.libretexts.org/@go/page/211683
11.8: Sharpless Epoxidation
Epoxides are very useful intermediates in organic synthesis. Because most naturally occurring molecules (including those with
medicinal properties) are chiral, control of stereochemistry is one of the most important challenges facing a synthetic chemist
attempting to synthesize a naturally occurring molecule in the laboratory. In what was arguably one of the most important
discoveries in synthetic organic chemistry in recent decades, Barry Sharpless of Stanford University reported in 1980 that he and
his colleagues had developed a method to stereoselectively epoxidize asymmetric alkenes which contained an alcohol in the allylic
position. The ‘Sharpless asymmetric oxidation’ is achieved with the use of a chiral catalyst composed of (+) or (-) diethyltartrate
and an organotitanium compound (J. Am. Chem. Soc. 1980, 102, 5974). Depending on which stereoisomer of diethyltartrate is
used, the peroxyacid oxygen tends to add to either the top or bottom plane of the alkene.

This technique allows for the specific introduction of two new stereocenters at an alkene position, which as you can imagine makes
it an extremely useful synthetic tool.
Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

11.8: Sharpless Epoxidation is shared under a not declared license and was authored, remixed, and/or curated by LibreTexts.

11.8.1 https://chem.libretexts.org/@go/page/211684
Index
A frequency factor proton acceptor
activated complex 2.10: Activation Energy and Rate 3.3: Classification of Reagents as Electrophiles and
Nucleophiles. Acids and Bases
2.10: Activation Energy and Rate
G proton donor
activation energy
3.3: Classification of Reagents as Electrophiles and
2.10: Activation Energy and Rate Gibbs Free Energy Nucleophiles. Acids and Bases
Anionic Polymerization 2.7: Gibbs Free Energy (review)
5.14: Polymerization of Alkenes R
Arrhenius equation L
racemic mixture
2.10: Activation Energy and Rate Lewis Acid 6.5: Racemic Mixtures and the Resolution of
3.3: Classification of Reagents as Electrophiles and Enantiomers
C Nucleophiles. Acids and Bases
radical polymerization
Carbocation Rearrangements Lewis base 5.14: Polymerization of Alkenes
3.3: Classification of Reagents as Electrophiles and
4.6: Carbocation Rearrangements
Nucleophiles. Acids and Bases
rate law
cationic polymerization Lewis structures 9.4: Reaction Rates and Rate Laws
5.14: Polymerization of Alkenes
1.2: Electron-Dot Model of Bonding - Lewis
Reaction order
chirality Structures 9.4: Reaction Rates and Rate Laws
6.1: Chirality and Stereoisomers Lower reaction rate
clark 2.2: Physical Properties of Alkanes 9.4: Reaction Rates and Rate Laws
2.2: Physical Properties of Alkanes Redox Reactions (Organic Chemistry)
2.4: Nomenclature of Cycloalkanes
M 10.4: Oxidation and Reduction in Organic Chemistry
Coordination Polymerization Resolution of Enantiomers
5.14: Polymerization of Alkenes
Markovnikov Addition
4.7: Markovnikov Addition 6.5: Racemic Mixtures and the Resolution of
Cyclohexane Conformations Enantiomers
Meso Compounds
7.3: Cyclohexane Conformations resonance
6.8: Meso Compounds
1.5: Resonance
D retrosynthetic analysis
N
Dehydration of Alcohols 10.13: An Introduction to Organic Synthesis
10.1: Dehydration Reactions of Alcohols
needs vmk
Dehydrogenases 8.6: Solvents
S
Nomenclature of Alkenes
10.8: Dehydrogenases staggared conformer
4.2: Nomenclature of Alkenes
diastereomers 2.6: Ethane Conformers
nucleophilic
6.7: Diastereomers - more detail standard free energy change
3.3: Classification of Reagents as Electrophiles and
Dihydroxylation of Alkenes Nucleophiles. Acids and Bases 2.7: Gibbs Free Energy (review)
11.5: Dihydroxylation of Alkenes standard molar entropy
O 2.9: Entropy Changes in Chemical Reactions
E optical activity stereoisomers
eclipsed conformer 6.4: Optical Activity - more detail
6.1: Chirality and Stereoisomers
2.6: Ethane Conformers
ozonolysis Steric Factor
electrophilic 5.9: Oxidative Cleavage of Alkenes
2.10: Activation Energy and Rate
3.3: Classification of Reagents as Electrophiles and Steroids
Nucleophiles. Acids and Bases 7.8: Steroids
Enthalpy change P
2.8: Enthalpy Changes in Reactions polymerization T
5.14: Polymerization of Alkenes
polymers thiol
F 8.4: Thiols (Mercaptans)
5.14: Polymerization of Alkenes
free energy change transition state
2.7: Gibbs Free Energy (review)
Prochirality
2.10: Activation Energy and Rate
10.9: Prochirality

1 https://chem.libretexts.org/@go/page/212250
Glossary
Sample Word 1 | Sample Definition 1

1 https://chem.libretexts.org/@go/page/279521
Detailed Licensing
Overview
Title: Fundamental Organic Chemistry I
Webpages: 130
Applicable Restrictions: Noncommercial, No Derivatives
All licenses found:
Undeclared: 83.1% (108 pages)
CC BY-NC-SA 4.0: 10% (13 pages)
CC BY-NC 4.0: 4.6% (6 pages)
CC BY-NC 3.0: 1.5% (2 pages)
CC BY-NC-ND 4.0: 0.8% (1 page)

By Page
Fundamental Organic Chemistry I - Undeclared 3.1: Acids and Bases - The Brønsted-Lowry
Front Matter - Undeclared Definition - Undeclared
TitlePage - Undeclared 3.2: Acids and Bases - The Lewis Definition -
InfoPage - Undeclared Undeclared
Table of Contents - Undeclared 3.3: Classification of Reagents as Electrophiles and
Licensing - Undeclared Nucleophiles. Acids and Bases - Undeclared
3.4: Using Curved Arrows in Polar Reaction
1: Intro to Chemical Structure and Resonance -
Mechanisms - Undeclared
Undeclared
3.5: Acid Strength and $pK_{a}$ - Undeclared
1.1: Drawing Chemical Structures - Undeclared 3.6: A Summary of the Factors that Determine Acid
1.2: Electron-Dot Model of Bonding - Lewis Strength - Undeclared
Structures - Undeclared 3.7: Organic Acids and Bases - Undeclared
1.3: VSPER Theory- The Effect of Lone Pairs - CC
4: Introduction to Alkenes - Undeclared
BY-NC-SA 4.0
4.1: The $\pi$ Bond - Undeclared
1.4: Electronegativity and Bond Polarity (Review) -
4.2: Nomenclature of Alkenes - Undeclared
Undeclared
4.3: Degree of Unsaturation - Undeclared
1.5: Resonance - Undeclared
4.4: Electrophilic Addition Reactions of Alkenes -
1.6: Molecular Orbitals and Covalent Bonding -
Undeclared
Undeclared
4.5: Carbocation Structure and Stability - Undeclared
1.7: Hybrid Orbitals- Bonding in Complex Molecules
4.6: Carbocation Rearrangements - CC BY-NC-SA 4.0
and Practice Problems - Undeclared
4.7: Markovnikov Addition - Undeclared
2: Alkanes - Undeclared
5: Addition Reactions of Alkenes - Undeclared
2.1: Chemical Properties of Alkanes - Undeclared
2.2: Physical Properties of Alkanes - CC BY-NC 4.0 5.1: Electrophilic Addition of Hydrogen Halides -
2.3: Nomenclature of Alkanes - Undeclared Undeclared
2.4: Nomenclature of Cycloalkanes - CC BY-NC 4.0 5.2: Addition of Strong Brønsted Acids - CC BY-NC-
2.5: Practice - Alkane Nomenclature - Undeclared SA 4.0
2.6: Ethane Conformers - CC BY-NC-SA 4.0 5.3: Electrophilic Addition of Halogens to Alkenes -
2.7: Gibbs Free Energy (review) - CC BY-NC-SA 4.0 Undeclared
2.8: Enthalpy Changes in Reactions - Undeclared 5.4: Hydration of Alkenes - CC BY-NC 4.0
2.9: Entropy Changes in Chemical Reactions - CC 5.5: Formation of alcohols from alkenes - Undeclared
BY-NC-SA 4.0 5.6: Catalytic Hydrogenation - Undeclared
2.10: Activation Energy and Rate - CC BY-NC-SA 4.0 5.7: Hydration- Oxymercuration-Demercuration -
Undeclared
3: Acids, Bases, and Arrow Pushing - Undeclared
5.8: Hydration- Hydroboration-Oxidation -
Undeclared

1 https://chem.libretexts.org/@go/page/428133
5.9: Oxidative Cleavage of Alkenes - Undeclared 9.1: An Overview of Nucleophilic Substitution -
5.10: Free Radicals - Undeclared Undeclared
5.11: Addition of Radicals to Alkenes - CC BY-NC- 9.2: Elimination Reactions - CC BY-NC 3.0
SA 4.0 9.3: Rate Laws in Nucleophilic Substitution - CC BY-
5.12: Anti-Markovnikov Product Formation - CC BY- NC 3.0
NC-ND 4.0 9.4: Reaction Rates and Rate Laws - Undeclared
5.13: Homolytic Cleavage and Bond Dissociation 9.5: The SN2 Reaction - Undeclared
Energies - Undeclared 9.6: E2 Elimination - Undeclared
5.14: Polymerization of Alkenes - Undeclared 9.7: SN1 Reaction - Undeclared
6: Principles of Stereochemistry - Undeclared 9.7.1: 6.06.1 Kinetics, Stereochemistry and
6.1: Chirality and Stereoisomers - Undeclared Energy Diagram - Undeclared
6.2: R-S Sequence Rules - Undeclared 9.8: E1 Eliminations - Undeclared
6.3: Optical Activity - Undeclared 9.9: Comparison of SN2 and SN1 - Undeclared
6.4: Optical Activity - more detail - Undeclared 9.10: Comparing E1 and E2 - Undeclared
6.5: Racemic Mixtures and the Resolution of 9.11: Determining SN2, SN¬1, E2 or E1 -
Enantiomers - Undeclared Undeclared
6.6: Diastereomers - Undeclared 9.12: Carbenes - Undeclared
6.7: Diastereomers - more detail - Undeclared 9.13: Cyclopropane Synthesis - Undeclared
6.8: Meso Compounds - Undeclared 10: The Chemistry of Alcohols and Thiols - Undeclared
7: Cyclic Compounds - Stereochemistry of Reactions - 10.1: Dehydration Reactions of Alcohols -
Undeclared Undeclared
7.1: Ring Strain and the Structure of Cycloalkanes - 10.2: Reactions of Alcohols with Hydrohalic Acids -
Undeclared Undeclared
7.2: Cycloalkanes and Ring Strain - Undeclared 10.3: Converting an Alcohol to a Sulfonate Ester -
7.3: Cyclohexane Conformations - Undeclared Undeclared
7.4: Conformations of Monosubstituted 10.4: Oxidation and Reduction in Organic Chemistry
Cyclohexanes - Undeclared - Undeclared
7.5: Conformations of Disubstituted Cyclohexanes - 10.5: Oxidation of Alcohols - Undeclared
Undeclared 10.6: The Formation of Carboxylic Acids - CC BY-
7.6: Polycyclic Alkanes - Undeclared NC-SA 4.0
7.7: Carbocyclic Products in Nature - Undeclared 10.7: Nicotinamide Adenine Dinucleotide (NAD) -
7.8: Steroids - Undeclared Undeclared
8: Introduction to Alkyl Halides, Alcohols, Ethers, 10.8: Dehydrogenases - CC BY-NC-SA 4.0
Thiols, and Sulfides - Undeclared 10.9: Prochirality - Undeclared
8.1: Alkyl Halides - CC BY-NC 4.0 10.10: Thiols and Sulfides - Undeclared
8.2: Haloalkanes - Undeclared 10.11: Nucleophilicity of Sulfur Compounds -
Undeclared
8.2.1: Alkyl Halide Occurrence - CC BY-NC-SA
10.12: Redox Reactions of Thiols and Disulfides -
4.0
CC BY-NC-SA 4.0
8.3: Nomenclature of Alcohols - CC BY-NC-SA 4.0 10.13: An Introduction to Organic Synthesis -
8.3.1: Nomenclature of Alcohols - Undeclared Undeclared
8.4: Thiols (Mercaptans) - Undeclared 11: The Chemistry of Ethers, Epoxides, Glycols, and
8.5: Nomenclature of Ethers - Undeclared Sulfides - Undeclared
8.6: Solvents - Undeclared 11.1: Williamson Ether Synthesis - Undeclared
8.6.1: Boiling Points - Undeclared 11.2: Synthesis of Epoxides - Undeclared
8.6.2: Solvent-Solutes - Undeclared 11.3: Acidic Cleavage of Ethers - Undeclared
8.7: Acidity of Alcohols and Phenols - Undeclared 11.4: Opening of Epoxides - Undeclared
8.8: Grignard and Organolithium Reagents - 11.5: Dihydroxylation of Alkenes - Undeclared
Undeclared 11.6: Periodate cleavage of 1,2-diols (glycols) -
8.9: Grignard Reagents - CC BY-NC 4.0 Undeclared
9: The Chemistry of Alkyl Halides - Undeclared 11.7: Epoxidation - CC BY-NC 4.0

2 https://chem.libretexts.org/@go/page/428133
11.8: Sharpless Epoxidation - Undeclared Glossary - Undeclared
Back Matter - Undeclared Detailed Licensing - Undeclared
Index - Undeclared

3 https://chem.libretexts.org/@go/page/428133

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