2. 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
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KNOCKHARDY PUBLISHING
ORGANIC SYNTHESIS
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)
haloalkane
carbonyl (aldehydes & ketones)
amine
nitrile
carboxylic acid
ester
12. ORGANIC SYNTHESIS
Involves the preparation of new compounds from others, for example…
ESTERS
ALKANES ALKENES
HALOGENOALKANES
ALCOHOLS
AMINES
ALDEHYDES
KETONES
CARBOXYLIC ACIDS
POLYMERS
NITRILES
DIBROMOALKANES
13. EXTENDING A CARBON CHAIN
Rationale
Methods Haloalkanes
Carbonyl compounds (aldehydes and ketones)
Aromatic (benzene) rings
15. POTASSIUM CYANIDE
Reagent Aqueous, alcoholic potassium (or sodium) cyanide
Conditions Reflux in aqueous , alcoholic solution
Product Nitrile (cyanide)
Nucleophile cyanide ion (CN¯)
Equation e.g. C2H5Br + KCN (aq/alc) ——> C2H5CN + KBr(aq)
Mechanism
Importance extends the carbon chain by one carbon atom
the CN group can be converted to carboxylic acids or amines.
Hydrolysis C2H5CN + 2H2O ———> C2H5COOH + NH3
Reduction C2H5CN + 4[H] ———> C2H5CH2NH2
NUCLEOPHILIC SUBSTITUTION
16. CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION
Reagent potassium cyanide – followed by dilute acid
Conditions reflux
Nucleophile cyanide ion CN¯
Product(s) hydroxynitrile (cyanohydrin)
Equation CH3CHO + HCN ——> CH3CH(OH)CN
2-hydroxypropanenitrile
Notes HCN is a weak acid and has difficulty dissociating into ions
HCN H+ + CN¯
Using ionic KCN produces more of the nucleophilic CN¯
Alternative reagent: HCN catalysed by alkali which shifts
the above equilibrium in favour of CN¯
HIGHLY TOXIC
TAKE GREAT CARE
17. CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION
Mechanism Nucleophilic addition
Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C
One of the C=O bonds breaks; a pair of electrons goes onto the O
STEP 1
18. CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION
Mechanism Nucleophilic addition
Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C
One of the C=O bonds breaks; a pair of electrons goes onto the O
Step 2 A pair of electrons is used to form a bond with H+
Overall, there has been addition of HCN
STEP 2
STEP 1
19. CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION
Mechanism Nucleophilic addition
Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C
One of the C=O bonds breaks; a pair of electrons goes onto the O
Step 2 A pair of electrons is used to form a bond with H+
Overall, there has been addition of HCN
STEP 2
STEP 1
20. CARBONYL COMPOUNDS - NUCLEOPHILIC ADDITION
Mechanism Nucleophilic addition
Step 1 CN¯ acts as a nucleophile and attacks the slightly positive C
One of the C=O bonds breaks; a pair of electrons goes onto the O
Step 2 A pair of electrons is used to form a bond with H+
Overall, there has been addition of HCN
STEP 2
STEP 1
21. FRIEDEL-CRAFTS REACTIONS OF BENZENE - ALKYLATION
Overview Alkylation involves substituting an alkyl (methyl, ethyl) group
Reagents a halogenoalkane (RX) and anhydrous aluminium chloride AlCl3
Conditions room temperature; dry inert solvent (ether)
Electrophile a carbocation ion R+ (e.g. CH3
+)
Equation C6H6 + C2H5Cl ———> C6H5C2H5 + HCl
Mechanism
General A catalyst is used to increase the positive nature of the electrophile
and make it better at attacking benzene rings.
AlCl3 acts as a Lewis Acid and helps break the C—Cl bond.
22. FRIEDEL-CRAFTS REACTIONS OF BENZENE - ACYLATION
Overview Acylation involves substituting an acyl (methanoyl, ethanoyl) group
Reagents an acyl chloride (RCOX) and anhydrous aluminium chloride AlCl3
Conditions reflux 50°C; dry inert solvent (ether)
Electrophile RC+= O ( e.g. CH3C+O )
Equation C6H6 + CH3COCl ———> C6H5COCH3 + HCl
Mechanism
Product A carbonyl compound (aldehyde or ketone)
23. EXTENDING A CARBON CHAIN
Rationale
Methods Haloalkanes
Carbonyl compounds (aldehydes and ketones)
Aromatic (benzene) rings
25. 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
26. 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
27. CHIRAL SYNTHESIS
Example
Aldehydes and ketones undergo nucleophilic addition with cyanide ions
CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
28. 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
29. 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
30. 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
31. CHIRAL SYNTHESIS
Example CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
CN¯ attacks
from above
CN¯ attacks
from below
MIRROR
IMAGES
32. CHIRAL SYNTHESIS
Example CH3CHO + HCN ——> CH3CH(OH)CN
ethanal 2-hydroxypropanenitrile
CN¯ attacks
from above
CN¯ attacks
from below
34. CHIRAL SYNTHESIS
Consequences • isomers have to be separated to obtain the effective one
• separation can be expensive and complicated
• non-separation leads to
35. 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
36. 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
37. 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 haloalkanes
38. 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.
39. 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.
40. 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.
41. MODERN SYNTHETIC METHODS
The following methods can be used to synthesise a single optical isomer
Enzymes / bacteria
Chiral chemicals
Chiral catalysts
Natural chiral molecules
