Wedge-hash diagrams

Wedge-hash (or wedge-dash) diagrams are the most common representation used to show
3D shape as they are ideally suited to showing the structure of sp3 hybridised (tetrahedral
atoms). They are rarely needed for sp2 (e.g. alkenes) or sp systems (e.g. alkynes).

Wedge-hash diagrams are usually drawn with two bonds in the plane of the page, one in front
of the plane, and one behind the plane. This gives the molecule 3D perspective: we envisage
the bold lines being closer to us and the hashes fading away in the background.

Perspective Formulas and Fischer Projections

The stereochemical orientation of compounds can be represented using the wedges and
dashes of perspective formulas. For example, the perspective formula for (R)-Lactic acid is
shown below.

A Fischer projection is a convention used to depict stereochemistry in two dimensions. The

horizontal bonds are seen as wedges and the vertical bonds are seen as dashed lines as
shown below in the example below for glyceraldehyde.
Converting Wedge-Dash Structure to Fischer Projection

The stereochemical formula for (R)-lactic acid can be drawn using the wedge-dashed structure and
Fischer projection method. The conversion from wedge-shaped or bond-line structure to Fischer
projection is done stepwise.
Thus, the Fischer projection of (R)-Lactic acid
Step 1 can be explained in detail as follows:
Hold the molecule so that
a) the chiral center is on the plane of the paper,
b) two bonds are coming out of the plane of the paper and are on a horizontal plane,
c) the two remaining bonds are going into the plane of the paper and are on a vertical plane

Exercise 1

1. Convert each compound into the alternate sterochemical structure

(Perspective Fischer).
 Unit 5: S7 to S9

S-7: Elimination reaction (brief account on types of elimination reactions (E1 and E2) with an
example and mechanism of each)

Oxidation reaction (explanation taking KMnO4 and K2Cr2O7 as oxidizing agents only)

What is Elimination Reaction?

 Elimination reactions are reverse of addition reactions.

 It involves loss of atoms or groups from adjacent carbon atoms resulting in the formation
of a π bond between these carbon atoms.

 Elimination reaction is a type of reaction is mainly used to transform saturated

compounds (organic compounds which contain single carbon-carbon bonds) to
unsaturated compounds (compounds which feature double or triple carbon-carbon
bonds).

 Besides, it is an important method for the preparation of alkenes.

 An elimination reaction is a type of a chemical reaction where several atoms either in

pairs or groups are removed from a molecule. The removal usually takes place due to the
action of acids and bases or action of metals. It can also happen through the process of
heating at high temperatures.

 Normally, elimination reactions are distinguished by the kind of atoms or groups of atoms
that leave the molecule. Due to this, there are two main methods involved in this type of
reaction;

 Dehydration

 Dehydrohalogenation

 In the dehydration method, there is the elimination of a water molecule mostly from
compounds such as alcohol.
 On the other hand, in dehydrohalogenation, there is a removal of a hydrogen atom and
a halogen atom.

Mechanism of Elimination Reaction

The elimination reaction consists of three fundamental events and they are;

1. Proton removal.
2. C-C pi bond is formed.
3. There is a breakage in the bond of the leaving group.

 Depending on the reaction kinetics, elimination reactions can occur mostly by two
mechanisms namely:

 E1: unimolecular elimination

E2: bimolecular elimination

E1 Reaction

 In the E1 mechanism which is also known as unimolecular elimination, there are

usually two steps involved – ionization and deprotonation.

 During ionization, there is a formation of carbocation as an intermediate. In

deprotonation, a proton is lost by the carbocation.

 This happens in the presence of a base which further leads to the formation of a pi-bond
in the molecule.

 In E1, the reaction rate is also proportional to the concentration of the substance to be
transformed. Rate = k[RX]

 It exhibits first-order kinetics.

 E 1 mechanism shares the features of the SN1 reaction. The initial step is the formation
of a carbocation intermediate through the loss of the leaving group. This slow step
becomes the rate-determining step for the whole reaction.

E2 Reaction

 In an E2 mechanism which refers to bimolecular elimination is basically a one-step

mechanism.

 Here, the carbon-hydrogen and carbon-halogen bonds mostly break off to form a new
double bond.

 However, in the E2 mechanism, a base is part of the rate determining step and it has a
huge influence on the mechanism.

 The reaction rate is mostly proportional to the concentrations of both the

eliminating agent and the substrate.

 It exhibits second-order kinetics. The rate of the E2 reaction is Rate = k[RX][Base]

 The E2 mechanism can generally be represented as below. In the below-mentioned

representation, B stands for base and X stands for the halogen.

 So the reaction rate depends on both the substrate (RX) and the base involved. In the
elimination reaction, the major product formed is the most stable alkene.
The Zaitsev (Saytseff) Rule
 When alkyl halides have two or more different β carbons, more than one alkene product
is formed. In such cases, the major product is the more stable product—the one with the
more substituted double bond.
 This phenomenon is called the Zaitsev rule. The Zaitsev product or the more substituted
alkene product is more stable than the less substituted product.
 The stability of the more substituted alkene is a result of number of different contributing
factors, including hyperconjugation. Each alkyl group that can involve in hyperconjugation
with the double bond stabilizes it by approximately 6 kcal/mol

 This reaction is both regiospecific and stereospecific. In general, more substituted

alkenes are more stable, and as a result, the product mixture will contain less 1-butene
than 2-butene (this is the regiochemical aspect of the outcome, and is often referred to
as Zaitsev's rule). In addition, we already know that trans (E) alkenes are generally more
stable than cis (Z) alkenes, so we can predict that more of the E product will form
compared to the Z product.
Characteristics E1 elimination E2 Elimination
Kinetics First order Second order
Mechanism Two steps Single step
Identity of R group More substituted halides react More substituted halides react
faster faster
Rate R3CX > R2CHX > RCH2X R3CX > R2CHX > RCH2X
Strength of the base Favored by weaker bases such as Stronger bases favor the reaction
H2O and ROH
Leaving group Better leaving group leads to faster Better leaving group leads to
reaction rates. faster
Just as in SN1 reactions, the rate
determining step involves the C—X
bond cleavage
Type of solvent Favoured by polar protic solvents, Favoured by polar aprotic
which can stabilize the ionic solvents
intermediates
Potential energy
diagram

E2 reactions are stereoselective,

resulting in the formation of trans-
double bonds preferably.

DEFINITIONS OF OXIDATION AND REDUCTION (REDOX)

Oxidation and reduction in terms of oxygen transfer

Definitions

 Oxidation is gain of oxygen.

 Reduction is loss of oxygen.

For example, in the extraction of iron from its ore:

Oxidation and reduction in terms of hydrogen transfer

Definitions

 Oxidation is loss of hydrogen.

 Reduction is gain of hydrogen.

For example, ethanol can be oxidised to ethanal:

You would need to use an oxidising agent to remove the hydrogen from the ethanol. A commonly
used oxidising agent is potassium dichromate(VI) solution acidified with dilute sulphuric acid.

Ethanal can also be reduced back to ethanol again by adding hydrogen to it. A possible reducing
agent is sodium tetrahydridoborate, NaBH4. Again the equation is too complicated to be worth
bothering about at this point.

Oxidation and reduction in terms of electron transfer

Definitions

 Oxidation is loss of electrons.

 Reduction is gain of electrons.

A simple example

 The equation shows a simple redox reaction which can obviously be described in terms
of oxygen transfer.

 Copper(II) oxide and magnesium oxide are both ionic. The metals obviously aren't. If you
rewrite this as an ionic equation, it turns out that the oxide ions are spectator ions and
you are left with:


Oxidation of alkenes with cold dilute potassium manganate(VII) solution

Manganate(VII) ions are a strong oxidising agent, and in the first instance oxidise ethene to
ethane-1,2-diol (old name: ethylene glycol).

Under acidic conditions, the manganate(VII) ions are reduced to manganese(II) ions.

Under alkaline conditions, the manganate(VII) ions are first reduced to green manganate(VI) ions
...

. . . but eventually you get dark brown solid manganese(IV) oxide (manganese dioxide) formed.
The overall equation for the formation of this from the manganate(VII) ions is:

Oxidation of alkenes with hot concentrated acidified potassium manganate(VII) solution

The acidified potassium manganate(VII) solution oxidises the alkene by breaking the carbon-
carbon double bond and replacing it with two carbon-oxygen double bonds.

The products are known as carbonyl compounds because they contain the carbonyl group,
C=O. Carbonyl compounds can also react with potassium manganate(VII), but how they react
depends on what is attached to the carbon-oxygen double bond.
If both attached R groups in the products are alkyl groups

For example:

In this case, you would end up with two identical molecules called propanone. On the other hand,
if one of the methyl groups in the original molecule was replaced by an ethyl group, you would
get a mixture of two different ketones - propanone and butanone.

If a product has one hydrocarbon group and one hydrogen

For example, suppose the first stage of the reaction was:

Aldehydes are readily oxidised to give carboxylic acids, containing the -COOH group. So this
time, the reaction will go on a further step to give ethanoic acid, CH3COOH.

The overall effect of the potassium manganate(VII) on this kind of alkene is therefore:

If a product has two hydrogens but no hydrocarbon group

You might have expected that this would produce methanoic acid, as in the equation:
But it doesn't! That's because methanoic acid is also easily oxidised by potassium
manganate(VII) solution. In fact, it oxidises it all the way to carbon dioxide and water.

So the equation in a case like this might be, for example:

Summary

Think about both ends of the carbon-carbon double bond separately, and then combine the
results afterwards.

 If there are two alkyl groups at one end of the bond, that part of the molecule will give a
ketone.
 If there is one alkyl group and one hydrogen at one end of the bond, that part of the
molecule will give a carboxylic acid.
 If there are two hydrogens at one end of the bond, that part of the molecule will give
carbon dioxide and water.

Few more examples:

Oxidation with K2Cr2O7/Chromic acid

Oxidizing agent
 K2Cr2O7 potassium dichromate
 CrO3 Chromium Trioxide
Both of these are used along with H2SO4, H2O
 1o alcohol → Carboxylic acid
 2o alcohol → Ketone
 3o alcohol → No reaction

Primary alcohols
Secondary alcohols

Tertiary alcohols
S-8: Reduction reactions: (explanation taking LiAlH4 and NaBH4 as reducing agents only)

Reduction reactions using LiAlH4

Functional group conversion

Aldehydes, ketones -------> Alcohols

Carboxylic acids -------> Alcohols

Esters, acid halides -------> Alcohols

Amides -------> amines

Nitriles -------> amines

oxiranes (epoxides) -------> alcohols

lactones -------> diols

haloalkanes, haloarenes -------> alkanes,

arenes
(1) Reduction of Aldehydes or Ketones to 10 or 20 alcohols:

(2) Reduction of Amides to amines:

(3) The nitriles are reduced to primary amines by LiAlH4.

E.g. Acetonitrile is reduced to ethyl amine by LiAlH4.

(3) LiAlH4 does not affect the isolated carbon-carbon double or triple bonds.
 *However, the double bonds in conjugation at α,β positions of carbonyl group may also be
reduced by Lithium aluminium hydride depending on the reaction conditions.
E.g. Cinnamaldehyde is reduced to Hydrocinnamyl alcohol when reduced with excess of
LiAlH4 (roughly more than 2 equivalents) by normal addition method. In this method, a solution of
cinnamaldehyde is added to the solution of lithium aluminium hydride. Both the double bond and
carbonyl group are reduced.

(6) The carboxylic acids, esters and acid halides are reduced to corresponding
primary alcohols by Lithium aluminium hydride.
E.g. The reduction of Acetic acid, methyl acetate and acetyl chloride by LiAlH4 furnish
the same ethyl alcohol.

(7) Lithium aluminium hydride reduces the oxiranes (epoxides) to alcohols. The hydride
attack occurs at less hindered side of the epoxide.
E.g. 2-methyloxirane gives 2-propanol predominantly.

(8) The lactones are reduced to α,ω-diols by LiAlH4.

E.g.
(9) The haloalkanes and haloarenes are reduced to corresponding
hydrocarbons by Lithium aluminium hydride.

Reduction reactions using NaBH4

  Addition of sodium borohydride (NaBH4) to ketones gives secondary alcohols (after
addition of acid).

Selective reduction: If a compound contains some functional group besides the carbonyl group,
then only the latter is reduced.

e.g. 1) CH3-CH=CH-CHO → CH3-CH=CH-CH2OH

2) NO2-CH2-CH2-CHO → NO2-CH2-CH2-CH2OH

3)
S-9: Cyclization: (Dieckmann condensation)

Ring Opening reactions: (Addition of Cl2/Br2/HI/H2SO4/H2 to cyclopropane)

Cyclization: (Dieckmann condensation)

 It is base catalysed intramolecular condensation of a diester.

 It works well to produce 5/6 membered cyclic β keto ester.
 Usually effected with sodium alkoxide in alchoholic solvent.

 e.g. when an ester of adipic acid (diethyl hexanedioate) treated with Na or Na ethoxide,
intramolecular change produces cyclic β keto ester (ethyl 2-oxocyclopentanecarboxylate).

Ring Opening reactions: (Addition of Cl2/Br2/HI/H2SO4/H2 to cyclopropane)

 Cycloalkanes are saturated compounds like alanes and therefore exhibit substitution reactions.
But cycloalkanes having ring of 3 or 4 carbon atoms are unstable and tend to for open chain
aliphatic compounds by the additon of reagent.
 Thus they exhibit chemical properties of both alkanes and alkenes.
 Reaction with halogen (Substitution with Cl2 and Br2):
 Generally cycloalkanes undergo free radical substitution with halogens at high
temperature or in presence of light.
 Whereas in case of cyclopropane, Cl2 and Br2 break the ring system and give open chain
addition products in dark.
 Cyclobutane and higher members do not give this reaction.
 Reaction with halogen acids (HX):
 Cyclopropane add on halogen acids to give open chain alkyl halides.
 Cyclobutane and higher alkanes do not give this reaction.
 Reaction with hydrogen (H2):
 When heated with H2 in presence of Ni catalyst, cyclopropane and cyclobutane give
addition products
 whereas higher members do not give this reaction.
 Hence it may be pointed out that cyclopropane is the most reactive cycloalkane as it exhibits many
addition reactions accompaned by ring cleavage. Then comes cyclobutane which shows some

addition reactions. The rest of the cycloalkanes do not form addition products.
 DRUGS Introduction
&
Synthesis of Paracetamol and
Aspirin
 Introduction to Drugs
What is a drug?
• A drug is a chemical that interacts with proteins in the body to
affect a physiological function.
• Once these chemicals are absorbed into the systemic circulation they
bind with certain proteins and this changes the functioning of the cell
slightly.
• For example, anticancer drugs bind to proteins on the surface of
cancer cells this stimulates the cells to die. In this case cell death is
the physiological action of the drug.
• No drugs are specific to interacting with just one type of cell or one
type of protein and this is what causes side effects. Again using an
anticancer drug as an example, the medication works by binding to
very rapidly dividing cells, such as cancer cells, however hair cells
are also rapidly dividing and that is why one of the side effects of
anticancer drugs is hair loss.
• The study of drugs or chemicals and the effects they have on living
animals is called pharmacology.
How do drugs work?
• Our bodies are largely controlled by proteins. Proteins exist in many
different forms in the body and have many different functions. Each
protein has a specific function and is quite specific to the cell type that
it acts on. For example, there are specific types of proteins called
receptors.
• Proteins also act as drug targets. In order for a drug to exert an effect it
needs to be bound to a protein. This can be thought of as a lock and key
system; where the drugs are the key and the protein is the lock. Once
the drug is bound in this lock and key mechanism it can have one of
two main influences over the cell. It can produce a change in response
or it can stop a normal response of the cell.
• Drugs that produce a change in the cell functioning are called agonists.
Drugs that stop a normal function of the cell are called antagonists.
PARACETAMOL (ACETAMINOPHEN)
• Paracetamol was first synthesized by Joseph von
Mering in 1893.
• The systematic IUPAC name is
N-(4-hydroxyphenyl)ethanamide or
N-(4-hydroxyphenyl)acetamide.
• It is also known as N-acetyl-p-aminophenol.
• It is a weak acid.
• It is a white solid with a melting point of 170oC which
is slightly soluble in water.
PARACETAMOL - SYNTHESIS
• It can be prepared from phenol in a three step process
involving:
(i) nitration - Phenol with sodium nitrate (an oxidizing agent)
in the presence of sulfuric acid
(ii) reduction – formed Nitrophenol by sodium borohydride
(iii) formation of the amide – formed aminophenol with acetic
anhydride

PARACETAMOL - USES
It is widely used as
• an analgesic (pain reliever)
• an antipyretic (for reducing fever).
 PARACETAMOL-Synthesis
(i) Nitration

p-nitro phenol
(74%)

Phenol o-nitro phenol

(ii) reduction (iii) Amide formation,

Room Temp, water
p-amino phenol paracetamol
p-nitro phenol
 ASPIRIN
• Aspirin, an acetyl derivative of salicylic acid,
• It is also known as acetylsalicylic acid (ASA),
• It is a white, crystalline, weakly acidic
substance
• The melting point of aspirin is 136 °C
(277 °F),[4] and its boiling point is 140 °C
(284 °F).
Aspirin