1. KNOCKHARDY PUBLISHING
ORGANIC
SYNTHESIS
2008 SPECIFICATIONS
KNOCKHARDY PUBLISHING

2. KNOCKHARDY PUBLISHING
ORGANIC SYNTHESIS
INTRODUCTION
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3. ORGANIC SYNTHESIS CONTENTS Introduction Functional groups
Chiral synthesis - introduction
Nucleophilic addition
Nucleophilic substitution
Synthetic methods

4. ORGANIC SYNTHESIS
Involves the preparation of new compounds from others.

5. 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.

6. 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...

7. 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

8. 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

9. 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

10. 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

11. ORGANIC SYNTHESIS Functional groups
Common functional groups found in organic molecules include...
alkene
hydroxyl (alcohols)
halogenoalkane
carbonyl (aldehydes & ketones)
amine
nitrile
carboxylic acid
ester

12. CHIRAL SYNTHESIS Rationale
Pharmaceutical synthesis often requires the production of just one optical isomer. This is because...

13. 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

14. 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

15. CHIRAL SYNTHESIS Example
Aldehydes and ketones undergo nucleophilic addition with cyanide ions
CH3CHO HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile

16. 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

17. 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

18. 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

19. CHIRAL SYNTHESIS Example CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
CN¯ attacks
from above
from below
MIRROR IMAGES

20. CHIRAL SYNTHESIS Example CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
CN¯ attacks
from above
from below

21. CHIRAL SYNTHESIS ANIMATION Example CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
ANIMATION

22. CHIRAL SYNTHESIS
Consequences • isomers have to be separated to obtain the effective one
• separation can be expensive and complicated
• non-separation leads to

23. 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

24. 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

25. 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

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

27. NUCLEOPHILIC SUBSTITUTION
Problems There are two possible mechanisms
SN1
This produces a racemic mixture of two optical isomers
Called SN1 because one species is involved in the rate determining step.

28. NUCLEOPHILIC SUBSTITUTION
Problems There are two possible mechanisms
SN2
This produces just one optical isomer with reversed optical activity
Called SN2 because two species are involved in the rate determining step.
SN1
This produces a racemic mixture of two optical isomers
Called SN1 because one species is involved in the rate determining step.

29. MODERN SYNTHETIC METHODS
The following methods can be used to synthesise a single optical isomer
Enzymes / bacteria
Chiral chemicals
Chiral catalysts
Natural chiral molecules

30. ©2009 JONATHAN HOPTON & KNOCKHARDY PUBLISHING
ORGANIC
SYNTHESIS
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©2009 JONATHAN HOPTON & KNOCKHARDY PUBLISHING