ORGANIC

CHEMISTRY
FOR ASPIRING PHARMACISTS
A S S T. P R O F. R A M O N C I T O G A B R I E L O . P A R A G A S , B S P H A R M , R P H

P H I L I P P I N E A S S O C I AT I O N O F C O L L E G E S O F P H A R M A C Y
BREX PHARMACY REVIEW

WHAT IS CARBON?
Carbon is the head of the Carbon
Family (IV-A) in the periodic table.
Carbon is the basic component of
ALL ORGANIC COMPOUNDS.
What then makes Carbon so
special that it is the subject of
interest of this course?

WHAT IS CARBON?
Carbon is always on excited
state.
Having basic knowledge of its
location in the periodic table,
lets take a look on its
electronic configuration to
assess this property.

WHAT IS CARBON?
Carbon is always on excited
state, making it want the
maximum reactions.
Carbon as a part of IV-A Family
has four valence (outer)
electrons; it can share all the
valence electrons, forming four
strong COVALENT BONDS.

WHAT IS CARBON?
Carbon atoms can bond
with one another, forming
long chains and even rings.
Of all other elements, carbon
alone has the ability to
form an immense diversity
of compounds.

WHY STUDY ABOUT CARBON?

Studying the properties of carbon and the different
reactions it can have with other elements is important.
Why? Simple. Carbon had been an unexplainable vital
force that puzzled many scientists centuries and decades
ago.

WHY STUDY ABOUT CARBON?

Carbon has been the basic component of all the organic compounds that
build you.Your cells are made up of some carbon-containing compounds.
Reactions in your body cannot proceed without interference of carboncontaining compounds. The food you eat; the meat, the vegetables, the fruits they are made of carbon-containing products. The aroma of coffee, or the taste
of fresh apples are all sensed because of some carbon-containing products.
Even organic compounds cause you to cry, fear, laugh and fight.
Why study Organic Chemistry?
Simple. Because, youll need it to pass your course.

GENERAL OVERVIEW
History

Jons Jacob Berzelius

organic

Vital Force Theory or life-force theory

compounds ONLY originate from living things

Friedrich Wohler

Torbern Bergman

Ammonia + cyanic acid

org vs inorg

So what is ORGANIC CHEMISTRY?

organic
urea

ORGANIC CHEMISTRY VS
INORGANIC CHEMISTRY
Property

Flammability
Boiling Point

Solubility in Water
Solubility in Non-polar Solvents

Types of Bonding
Isomerism

Atoms per Molecules

Structure
Electrical Conductivity

ORGANIC
FLAMMABLE

INORGANIC

LOW
INSOLUBLE

High

SOLUBLE
COVALENT BOND
EXHIBITS
SEVERAL
COMPLEX
POOR

Not Flammable

Soluble
Insoluble

Ionic Bonding
Does not exhibit

Few
Simple
Good

WHAT ARE ORGANIC COMPOUNDS?

Carbon-containing compounds

Naturally occurring; mostly of life origin, and nature based.

However, not all organic compounds are not derived from living
organisms, of course. Newly discovered organic compounds
were merely synthesized even derived from non-organic
compounds, or products of laboratory tests.
Exceptions: CO2, H2CO3, CO3-, CN-

NATURE OF ORGANIC MOLECULES

Of all the hundred plus elements in the periodic table, Organic
Chemistry is mostly concerned only for ten! Okay, so Carbon is
given. The other nine are:
Hydrogen:

Carbon Group: C, Si
Nitrogen Group: N, P
Oxygen Group: O, S

Halogen Group: F, Cl, Br, I

NATURE OF ORGANIC MOLECULES

There are about 37 million known organic molecules.
There are rules that nature follow that help us
understand that organic molecules rest largely on
understanding of small combinations of atoms. So instead
of 37 million separate compounds that we study for some
random reactivity, there are only about a dozen families of
chemistry whose chemistry is predictable.

CARBON
THE KING OF ALL ELEMENTS

CARBON: CHARACTERISTICS
CATENATION: bonding successively with other carbons
to form chains and rings varying in sizes

CHARACTERISTICS OF COVALENT
BONDS
Bond

Bond Strength

Bond Length

Bond Angle

Hybridization

CC

340 kJ/mol

154 pm

109.5

sp-sp

C=C

610 kJ/mol

133 pm

120

sp-sp

C=C

830 kJ/mol

120 pm

180

sp-sp

Covalent bonds are bonds exhibiting equal sharing of electrons between

atoms. These bonds are stable, and they have limitations to attractions.
Condition: Atoms cannot stay close together (repulsion) and cannot go to far
from one another (loss of attraction). Just the right distance.

What can you infer from the table above?

CHARACTERISTICS OF COVALENT
BONDS
Given that Carbon is
tetravalent, and always at
excited state, take a look at the
equal sharing of electrons in
Methane; the most fundamental
and saturated organic
compound.

DEFINING
BOND LENGTH AND BOND STRENGTH
Bond

Bond Strength

Bond Length

Bond Angle

Hybridization

CC

340 kJ/mol

154 pm

109.5

sp-sp

C=C

610 kJ/mol

133 pm

120

sp-sp

C=C

830 kJ/mol

120 pm

180

sp-sp

Bond strength is the energy requirement to form a bond between

two atoms. It is also the energy requirement necessary to break
the bond between atoms.
Bond length is the optimum distance between that enables two
atoms to attract each other. Not too close, and not to far.

THE PRINCIPLE OF BOND ANGLE

Bond

Bond Strength

Bond Length

Bond Angle

Hybridization

CC

340 kJ/mol

154 pm

109.5

sp-sp

C=C

610 kJ/mol

133 pm

120

sp-sp

C=C

830 kJ/mol

120 pm

180

sp-sp

Remember the person that irritates you? Carbon also wants to

maintain a distance to other carbons. They get irritated if they stay too
close than tolerable for each other. Thus, when a chain is formed, a slight
bending of bonds occur.
Bond angle is the measure of bending that occurs shall bonding be
present. The more bonds, the straighter the chain (see the C=C bond).

CARBON: CHARACTERISTICS
HYBRIDIZATION- mixing of 2 or more non-equivalent
atomic orbitals to form new set of equivalent orbital
TYPES:

sp3
sp2

sp

HYBRIDIZATION
sp3-sp3: single bond between atoms. The
sp3 orbital is shaped long enough, giving
you a long sigma bond.

sp2-sp2: double bond between atoms.

sp-sp: triple bonds between atoms
All these hybridization statuses are
depending on the number of valence/
outer electrons.

HYBRIDIZATION: CHARACTER
S
character

sp3
sp2
sp
s

P
Character

px

py

pz

25%

25%

25%

25%

33%

33%

33%

-------

50%

50%

-------

-------

100%

-------

-------

-------

Always treat the bond as a 100% character then divide.

Question: Which hybrid has the least s character?, the
greatest y character?

HYBRIDIZATION
Direction: Identify the hybridization of the carbons present in the
molecular structure of 2,2-dimethylbut-2-ene.
Draw the structure:

Tip: To assess, always prioritize the stronger bond (double/ triple).

BOND ANGLE
Single bond
Double bond
Triple bond

BOND TYPES
Sigma bond: the first bond with any other atom
Pi bond: any 2nd and third bond with any other atom

SHAPE PREDICTION
Steric number = sigma+ lone pair
Based on VSEPR Theory

SHAPE PREDICTION
Predict the shape of:
H2O

NH3
CH4

FUNCTIONAL GROUPS
The chemistry of every molecule is determined by the
functional group it contains
A group of atoms within a larger molecule that has a
characteristic chemical behavior.

Simpler: a certain group, or part of a molecule that has

specific function. That function is to react, and behave in a
certain manner the time an attack of another
molecule comes.

FUNCTIONAL GROUPS:
C-C MULTIPLE BONDS
Alkanes: most basic bonding of carbon to another carbon. Single
bonds (sigma bonds/ ) connect these carbons, and mostly
hydrogen atoms take the place of empty spaces. H3C-CH3
Alkenes: double bond between carbons (one sigma, one pi bond/
). H2C=CH2
Alkynes: triple bond between carbons (one sigma, two pi). HC=CH

FUNCTIONAL GROUPS:
CYCLICS AND AROMATICS
Given again, Carbons can form long chains, it can also branch and join
together, forming chains or rings. Hydrogen atoms take the place of
remaining spots of the tetrahedron. These are called cyclics.
Notice the conformation of cyclohexane. In the past, it has been a big mystery
on what differentiates organic compounds with odor and without. August
Kekule noticed in his experiments that there is such a compound having six
carbons matching with 6 hydrogen atoms, forming a ring with three
double bonds; exhibiting odor, but doesnt have the characters of alkenes.
This was later called benzene. This is the base functional group of aromatic
compounds.

FUNCTIONAL GROUPS:
CYCLICS AND AROMATICS
C Y C L OA L K A N E

B E N Z E N E / A RO M AT I C

C6H12

C6H6

Has the same formula as a typical hexene.

Has the unusual case of equal number of carbon

and Hydrogen.

Has no smell.

Has odor/ fragrance.

FUNCTIONAL GROUPS:
CARBON SINGLY BONDED TO AN
ELECTRONEGATIVE ATOM
Name

Structure

Name
Ending

Example

Alkyl Halide

R-X

---------------

CH3Br

Alcohol

R-OH

-ol

CH3CH2OH

Ether

R-O-R

ether
(alkoxy
alkane)

CH3OCH3

Amine

R-NH2

-amine

CH3NH2

Thiol

R-SH

-thiol

CH3SH

Sulfide

R-S-R

sulfide

CH3SCH3

Carbon
Bond

FUNCTIONAL GROUPS:
CARBONYL GROUPS
These are functional groups
with a C=O group, called the
carbonyl group (car-boneel).

P R IO R IT Y GRO UP S: IN
DECR EASING P R IO R IT Y

Carboxylic acid
Acid Anhydrides
Esters
Thioesters
Acid halides
Amides
Nitriles
Aldehydes
Ketones

NOMENCLATURE
Common

IUPAC

Uses the name given when it was

discovered

Most systematic

Uses the source: wood alcohol

Uses prefixes: -n, iso, -neo

Derived name
derived from a parent compound

Eg. 2-methylhexane

GREEK PREFIXES IN NAMING

COMPOUNDS
Number of Carbons

Prefix

Example

Meth-

Methane

Eth-

Ethene

Prop-

Propene

But-

Butene

Pent-

Pentane

Hex-

Hexyne

Hept-

Heptyne

Oct-

Octane

Non-

Nonane

10

Dec-

Decane

11

Undec-

Undecene

12

Dodec-

Dodecane

HYDROCARBONS
Composition
Combustion process
Types
Aliphatic (straight or branched; saturated or unsaturated)
Aromatic
Alicyclic or carbocyclic

DERIVATIVES
Halogen -containing
Alkyl halide

Aryl halide

Oxygen -containing
Alcohol, phenol, ether, aldehyde
and ketone, carboxylic acid and
derivatives

Nitrogen- containing
Amines and amides

Sulfur containing
Thiols or ________
Thioethers
Thiophenols

SATURATED HYDROCARBONS
Alkanes or _______
SINGLE BOND ONLY

General formula: __________

Type of bond: __________

Suffix: -ane

Alkyl group: removal of 1 hydrogen; ends with yl

Example: Methane (when 1 hydrogen is removed: _______)

ALKANES: PROPERTIES
Little chemical affinity for other substances
Inert to most laboratory reagents
Show regular increase in boiling point and melting point as
weight increases

NOMENCLATURE
Determine the longest possible chain and name the corresponding
alkane name
Substituents are numbered with the lowest position number
If 2 or more substituents are present, use prefixes di-, tri-and so on.
When several different alkyl groups are attached to the parent
chain, use alphabetical arrangement

EXAMPLES
2,3-dimethylpentane: correct or incorrect?
1,2-dimethylbutane: correct or incorrect?
4-methyl-3-ethyl-octane: correct or incorrect?

SATURATED HC
Cycloalkanes
Carbon rings; can be written in geometric figure
General formula: ______________ named with the prefix
cyclo- in front of the corresponding alkane name

NOMENCLATURE
Additional Rule in Naming Cycloalkane
Step 1: Use the cycloalkane name as the parent chain.
Step 2: Number the substituents starting at the group
that has alphabetical priority, and proceed around the
ring in the direction that gives the second substituent
the lower possible number.

UNSATURATED HCS
Alkenes or _______
Double bonds
Bond angle: _______

Type of bond: _______

General Formula: __________
Same nomenclature as alkane but change ane to -ene

IUPAC NAMING
Nomenclature:
Determine the longest change having the DOUBLE
bond

Number the longest continuous chain so the double

bond will receive the lowest possible number
If more than one same substituents are present, use
prefixes di-, tri- tetra- and so on.

IUPAC NAMING
Alkadienes: 2 carbon-carbon double bonds;
indicate the position of double bond + prefix + diene
1,3-butadiene

Isoprene units

AROMATICS
Pleasant odor possessed by there substances (this meaning
has been dropped)
Benzene is the parent substance >> Isolated by
____________ in 1825.

AROMATICS
According to August Kekule, carbon atoms in a benzene
molecule are arranged in a six-membered ring with one
hydrogen atom bonded to each carbon atom and with
three carbon-carbon double bonds
Orbital hybridization is sp2.
For convenience, benzene is written either in the following
ways

HUCKELS RULE OF AROMATICITY

4n + 2 = e (electrons in double bond); if n is whole
number, then aromatic!
Benzene: Aromatic or not?

What is the name of the compound/s if e = 10?

Cyclobutadiene: aromatic or not?

REFRESH!
Is the figure below an aromatic compound?

Is it cyclic? YES.
Are the pi bonds conjugated/ non-successive? YES.
Does it follow Hckels rule? NO.
4 pi electrons = 4n + 2
4n = 2
n = (NOT A WHOLE NUMBER.)

MONOSUBSTITUTED
Nitrobenzene
Ethylbenzene
Chlorobenzene

Bromobenzene

MONOSUBSTITUTED BENZENES
Toluene

Phenol
Aniline
Acetophenone

Benzaldehyde
Benzoic acid
Benzonitrile

Styrene

DISUSBTITUTED BENZENES
The prefixes ortho , meta and para (o- , m- and p-)
are used as prefixes
Ortho adjacent

Meta one carbon apart

Para opposite

POLYSUBSTITUTED BENZENES
Monosubsituted aromatic compounds will serve as a
parent name, with the principal substituents assumed to be
the carbon 1.
Examples
1,3,5 trinitrobenzene

1,2,4 tribromobenzene
2,4,6 trinitrotoluene

5 bromo 2 chlorophenol

POLYCYCLIC AROMATIC COMPOUNDS

/ FUSED AROMATIC RING SYSTEM

Napthalene

Anthracene

Correlation: Benzopyrene

Phenanthrene

Pyrene

REACTION MECHANISM
Reaction mechanism a process by which a chemical
reaction occurs.

ADDITION REACTION
Two reactants react together to form a single new
product with no atoms left over
Ex: ethylene + HCl

ELIMINATION REACTION
Opposite of addition reaction
Single reactant splits into two products
Ex: chloroethane

SUBSTITUTION REACTION
Two reactants exchange parts to give two new
products
Ex: methane + chlorine

REARRANGEMENT REACTIONS
Single product undergoes a reorganization of bonds and
atoms to yield a single isomeric products
Ex: conversion of cis-butene to trans-butene

REACTIONS OF AROMATIC
COMPOUNDS
Electrophilic aromatic substitution
Bromination
Chlorination

Nitration
Sulfonation

ALKANE REACTIONS
The main type of reaction for alkanes is substitution. Presence
of initiator is as well needed. Alkanes are strong and stable, so it
takes special conditions before they can react. Initiators may include
UV or any Light.
Example:

AROMATIC REACTIONS

AROMATIC REACTIONS
So let us introduce to you the reactivity of
aromatic compounds. In General Organic Chemistry, we
are only talking about Benzene (C6H6), and sometimes
Naphthalene (C10H8).
Resonance makes a benzene ring stable. Anything that
is stable is hard to react with, because they want to
remain stable. It takes special conditions before
aromatics react, and attain once more stability.

AROMATIC REACTIONS: SUBSTITUTION

1. NITRATION
Reagents: Benzene
+
HNO3
H2SO4
General Reaction Scheme:

Mechanism:
As illustrated
Product:
Nitrobenzene
Examples:

AROMATIC REACTIONS: SUBSTITUTION

2. SULFONATION
Reagents: Benzene
+
SO3
H2SO4

Mechanism:
As illustrated
Product:
Benzenesulfonic Acid

General Reaction Scheme:

Examples:

AROMATIC REACTIONS: SUBSTITUTION

3. BROMINATION
Reagents: Benzene
+
Br-Br
FeBr3 Catalyst
General Reaction Scheme:

Mechanism:
See Next Slide

Product:
Bromobenzene
Examples:

AROMATIC REACTIONS: SUBSTITUTION

3. BROMINATION

AROMATIC REACTIONS: SUBSTITUTION

4. HALOGENATION (CHLORINATION, IODIN)
Reagents: Benzene
+
X-X (Cl, I)
FeCl3 or FeI3
Catalyst
General Reaction Scheme:

Mechanism:
As illustrated
Product:
Halobenzene
Examples:

FRIEDEL-CRAFTS ALKYLATIONACYLATION
Yes, these two geniuses discovered the process. Today, in the
industry, alkylation and acylation of aromatics are two of the
most useful processes of electrophilic aromatic substitution.
Alkylation is done by the introduction of an alkyl to replace one
H around the benzene ring. Acyl means Carboxylic Acid
Chloride, thus acylation is the introduction of carboxylic acid
chloride (RCOOCl), or acid anhydride.
Remember: It is crucial to remember that only the FriedelCrafts Aromatic Reactions utilize Aluminum-halide catalysts.

FRIEDEL-CRAFTS ALKYLATION
General Reaction Scheme:

FRIEDEL-CRAFTS ACYLATION
Closely related with the alkylation, it has the same mechanism, but
different reagents.
Example:

General Reaction Scheme:

REDUCTION OF BENZENE:
HYDROGENATION
If the Benzene Ring is introduced with Hydrogen Gas (H-H), take note:
THERE IS NO REACTION. The reason is the inertia/ inert character of
benzene, and the pressure requirements of H2
H2

No Reaction (NR)
If however, Benzene reacts with H-H under some blah-blah conditions,
or any condition regarding pressure, a reaction occurs, producing
cyclohexane.

REDUCTION OF BENZENE:
HYDROGENATION
H2

No Reaction (NR)
If however, Benzene reacts with H-H under some blah-blah conditions,
or any condition regarding pressure, a reaction occurs, producing
cyclohexane.

Exam Technique: If you see any blah-blah conditions, let the reaction proceed
by copying the whole structure without the aromatic ring.

OXIDATION OF BENZENE: KMNO 4

Same as Reduction/ Hydrogenation of the Benzene ring, Benzene will not
react as well with KMnO4, a strong oxidizing agent, under simple
conditions.
KMnO4
No Reaction
Only with Water, will benzene react with and oxidant.
Benzoic Acid is always the product.

Exam Tip: Aromatic Redox is really tricky. Always remember that only at
blah-blah conditions, benzene is reduced, oxidized. Dont get confused!

STEREOCHEMISTRY
AND
REGIOSPECIFICITY
T H E S C I E N C E O F E L E M E N TA L
POSITIONING AND STRUCTURES

CONCEPTS
Chirality
Chiral carbon: four different substituents attached to carbon atom
optically _______

Optical Activity:
Instrument: __________

Rotations:
Clockwise: _________
Anticlockwise: __________
Racemic

Chiral carbon is

BASICS OF STEREOCHEMISTRY
CHIRAL

ACHIRAL

Chirals are any compounds

with carbon (chiral center)
that has 4 different groups
surrounding it.

Achirals have two or more

identical groups around its
chiral center. (Carbon that
causes chirality)

TO THE LEFT OR TO THE RIGHT?

Configuration is the term used to name the drawing of
specific three-dimensional representation of a chiral
molecule with the chirality center surrounded by R-groups.
Steps follow:
RULE 1 Look at the four atoms directly attached to the
chirality center, and rank them according to atomic number.
The atom with the highest atomic number has the highest
ranking (first), and the atom with the lowest atomic
number (usually hydrogen) has the lowest ranking (fourth).

TO THE LEFT OR TO THE RIGHT?

RULE 2 If a decision cant be reached by ranking the first atoms in
the substituent, look at the second, third, or fourth atoms away
from the chirality center until the first difference is found.

RULE 3 Multiple-bonded atoms are equivalent to the same

number of single bonded atoms.
Configuration tells you of the rotation of chirals. The two
classifications are S (sinister, Left) and R (rectus, Right).

TO THE LEFT OR TO THE RIGHT?

OPTICALLY
As pharmacists, the rotation of compounds are very important for us. In
Physical Pharmacy, potency is discovered with rotation. Two rotations are seen in a
polarizer; the Levorotatory (left) and the Dextrorotatory (Right). These two are
very important in drug formulations.
Dextrometorphan, an antitussive, is more potent than its levorotatory
counterpart.
Levothyroxine Sodium, a reformulated thyroid hormone is more effective in
treatment of acute hyperthyroidism.
Esomeprazole is the equal formulation of the levo-dextro rotatories of the drug.
This is non-potent, because dextro counteracts the effect of levo, the more potent.
Omeprazole, the marketed drug that is potent is more levorotatory.

ISOMERS
Same molecular formula, different in structure

STRUCTURAL ISOMERS
Structural Isomers differ in order of arrangement of
the atoms or bond
a] Chain Isomers
Differ in the arrangement of C atoms

(n-butane) and Isobutane

b] Position Isomers
Differ in position of the substituent or unsaturated bonds (C=C, C =C)
1-butene and 2-butene

c] Functional Isomers
Differ in their functional group
Dimethyl ether and Ethanol

STEREOISOMERS
Stereoisomers atoms are in
the same order but different
orientation in space.

Geometric Isomers
Cis-Trans Isomers
Cis : same side

Trans: opposite side

Optical Isomers
Enantiomer
Non-superimposable MIRRORIMAGE
Same physicochemical properties

D and L isomers
Ex. D and L-glyceraldehyde

Diastereomer
With at least 2 chiral centers,
NOT MIRROR IMAGE, not
superimposable; different
physico-chemical properties

CONFORMATIONAL ISOMERS OR
CONFORMERS
Conformational Isomers or conformers
Involves single bond only
Eg. CH3CH3

Sawhorse representation
Newman

Ball and stick model

CONSTITUTIONAL ISOMER
STRUCTURES
Constitutional Isomers are isomers with relationship to a functional group. This
functional group plays a big role on giving the compound an identity.

Skeletal: Atom-stick model.

Branched: when substituents attach to the main chain.

Straight: you form a straight chain.

Tip: In the exam, if you are asked to give the isomer of a straight chain, give a branched
structure; vise-versa. Same goes with the next.

CONSTITUTIONAL ISOMER
STRUCTURES
Positional Isomer: the position of the R Group, or the functional group is differed.
CH3CH2COOH =

CH3COOCH3

Functional Group: give a derivative.

Alkenes Cycloalkanes
Alcohol Ether
Aldehyde Ketone
Alkynes Cycloalkenes Alkadienes
Carboxylic Acid Ester

(Alco-Et)
(Alco-Ket)
(Carbo-ster)

CONFORMERS
Conformers are a result in the twist of one component of an organic compound. There are two types of
structures.
Sawhorse: Slant and line bonded.Take note of steric effect, prevent nearing of two identical elements to
form bulk. Instability occurs when there is steric effect. The Right conformer is more stable.
Cl
C
H
H

Cl

C
H

C
H

Cl
H
H

C
Cl

CONFORMERS
Newman: a structure where the front and back of the compound is emphasized.
There are two types of Newman Projection.
Eclipsed and Staggered (Stable).

STEREOISOMERS
Same connection, different representation in 3D.
Geometric: the similarity of sides of two identical/ unidentical substituents.
Cis: same side
Trans: opposite sides

The rule is that you cut the middle of double bond, then you see if the compound has the substituents are
on the same side or not (ex: UP - UP). Prioritize the one with a larger atom. no.

STEREOISOMERS
E-Z Rule/ Convention/ Notation: used when there is a long chain and more than three
or more substituents surrounding the carbons of a double bond.
Entgegen: (ent-gay-guhn) opposite sides. Prioritize the one with a higher atomic number.
(German for Opposite)
Zusammen: (tsu-zah-mhn) same side. Still prioritize the atoms with higher atomic number.
(German for Together)

TAUTOMERIZATION
Tautomerization
Tauto same; meros part
Special kind of isomerism

Rapid interconversion between two substances

KETO-ENOL TAUTOMERS

Eg. Propanone to 2-propanol