ORGANIC

SYNTHESIS

KNOCKHARDY PUBLISHING
2008
SPECIFICATIONS
 KNOCKHARDY PUBLISHING

ORGANIC SYNTHESIS
INTRODUCTION
This Powerpoint show is one of several produced to help students
understand selected topics at AS and A2 level Chemistry. It is based on the
requirements of the AQA and OCR specifications but is suitable for other
examination boards.
Individual students may use the material at home for revision purposes or it
may be used for classroom teaching with an interactive white board.
Accompanying notes on this, and the full range of AS and A2 topics, are
available from the KNOCKHARDY SCIENCE WEBSITE at...

www.knockhardy.org.uk/sci.htm

Navigation is achieved by...

either clicking on the grey arrows at the foot of each page
or using the left and right arrow keys on the keyboard
ORGANIC SYNTHESIS
CONTENTS
• Introduction
• Functional groups
• Chiral synthesis - introduction
• Nucleophilic addition
• Nucleophilic substitution
• Synthetic methods
 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.
 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.

When planning a synthetic route, chemists must consider...

 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.

When planning a synthetic route, chemists must consider...

• the reagents required to convert one functional group into another

• the presence of other functional groups - in case also they react
 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.

When planning a synthetic route, chemists must consider...

• the reagents required to convert one functional group into another

• the presence of other functional groups - in case also they react
• the conditions required - temperature, pressure, catalyst
• the rate of the reaction
• the yield - especially important for equilibrium reactions
• atom economy
 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.

When planning a synthetic route, chemists must consider...

• the reagents required to convert one functional group into another

• the presence of other functional groups - in case also they react
• the conditions required - temperature, pressure, catalyst
• the rate of the reaction
• the yield - especially important for equilibrium reactions
• atom economy
• safety - toxicity and flammability of reactants and products
• financial economy - cost of chemicals, demand for product
• problems of purification
• possibility of optically active products
 ORGANIC SYNTHESIS

Involves the preparation of new compounds from others.

Many industrial processes involve a multi stage process where functional

groups are converted into other functional groups.

When planning a synthetic route, chemists must consider...

• the reagents required to convert one functional group into another

• the presence of other functional groups - in case also they react
• the conditions required - temperature, pressure, catalyst
• the rate of the reaction
• the yield - especially important for equilibrium reactions
• atom economy
• safety - toxicity and flammability of reactants and products
• financial economy - cost of chemicals, demand for product
• problems of purification
• possibility of optically active products
 ORGANIC SYNTHESIS

Functional groups

Common functional groups found in organic molecules include...

alkene

hydroxyl (alcohols)

halogenoalkane

carbonyl (aldehydes & ketones)

amine

nitrile

carboxylic acid

ester
 CHIRAL SYNTHESIS

Rationale

Pharmaceutical synthesis often requires the production of just one optical

isomer. This is because...
 CHIRAL SYNTHESIS

Rationale

Pharmaceutical synthesis often requires the production of just one optical

isomer. This is because...

• one optical isomer usually works better than the other

• the other optical isomer may cause dangerous side effects

• laboratory reactions usually produce both optical isomers

• naturally occurring reactions usually produce just one optical isomer

 CHIRAL SYNTHESIS

Rationale

Pharmaceutical synthesis often requires the production of just one optical

isomer. This is because...

• one optical isomer usually works better than the other

• the other optical isomer may cause dangerous side effects

• laboratory reactions usually produce both optical isomers

• naturally occurring reactions usually produce just one optical isomer

Example Aldehydes and ketones undergo nucleophilic addition

with cyanide (nitrile) ions;

CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile
 CHIRAL SYNTHESIS

Example

Aldehydes and ketones undergo nucleophilic addition with cyanide ions

CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile
 CHIRAL SYNTHESIS

Example

Aldehydes and ketones undergo nucleophilic addition with cyanide ions

CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

Problem - the C=O bond is planar

- the nucleophile can attack from above and below
- there is an equal chance of each possibility
- a mixture of optically active isomers is produced
- only occurs if different groups are attached to the C=O
 CHIRAL SYNTHESIS

Example

Aldehydes and ketones undergo nucleophilic addition with cyanide ions

CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

Problem - the C=O bond is planar

- the nucleophile can attack from above and below
- there is an equal chance of each possibility
- a mixture of optically active isomers is produced
- only occurs if different groups are attached to the C=O

CN¯ attacks
from above
 CHIRAL SYNTHESIS

Example

Aldehydes and ketones undergo nucleophilic addition with cyanide ions

CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

Problem - the C=O bond is planar

- the nucleophile can attack from above and below
- there is an equal chance of each possibility
- a mixture of optically active isomers is produced
- only occurs if different groups are attached to the C=O

CN¯ attacks
from below
 CHIRAL SYNTHESIS

Example CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

CN¯ attacks
from above

MIRROR
IMAGES
CN¯ attacks
from below
 CHIRAL SYNTHESIS

Example CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

CN¯ attacks
from above

CN¯ attacks
from below
 CHIRAL SYNTHESIS

Example CH3CHO + HCN ——> CH3CH(OH)CN

ethanal 2-hydroxypropanenitrile

ANIMATION
 CHIRAL SYNTHESIS

Consequences • isomers have to be separated to obtain the effective one

• separation can be expensive and complicated
• non-separation leads to
 CHIRAL SYNTHESIS

Consequences • isomers have to be separated to obtain the effective one

• separation can be expensive and complicated
• non-separation leads to
larger doses needed
possible dangerous side effects
possible legal action
 CHIRAL SYNTHESIS

Consequences • isomers have to be separated to obtain the effective one

• separation can be expensive and complicated
• non-separation leads to
larger doses needed
possible dangerous side effects
possible legal action

Solution • use natural chiral molecules as starting materials

• use stereoselective reactions which give one isomer
• use catalysts which give a specific isomer
• use enzymes or bacteria which are stereoselective
 CHIRAL SYNTHESIS

Consequences • isomers have to be separated to obtain the effective one

• separation can be expensive and complicated
• non-separation leads to
larger doses needed
possible dangerous side effects
possible legal action

Solution • use natural chiral molecules as starting materials

• use stereoselective reactions which give one isomer
• use catalysts which give a specific isomer
• use enzymes or bacteria which are stereoselective

Other examples Nucleophilic substitution of halogenoalkanes

 NUCLEOPHILIC SUBSTITUTION

Problems There are two possible mechanisms

S N2

This produces just one optical isomer with reversed optical activity
Called SN2 because two species are involved in the rate determining step.
 NUCLEOPHILIC SUBSTITUTION

Problems There are two possible mechanisms

S N1

This produces a racemic mixture of two optical isomers

Called SN1 because one species is involved in the rate determining step.
 NUCLEOPHILIC SUBSTITUTION

Problems There are two possible mechanisms

S N2

This produces just one optical isomer with reversed optical activity
Called SN2 because two species are involved in the rate determining step.

S N1

This produces a racemic mixture of two optical isomers

Called SN1 because one species is involved in the rate determining step.
 MODERN SYNTHETIC METHODS

The following methods can be used to synthesise a single optical isomer

Enzymes / bacteria

Chiral chemicals

Chiral catalysts

Natural chiral molecules

 ORGANIC
SYNTHESIS

THE END

©2009 JONATHAN HOPTON & KNOCKHARDY PUBLISHING