Chirality and synthesis

Question 1

What are stereoisomers?

Answer 1

Species with the same structural formulae but different arrangement of atoms in space.

Question 2

What are optical isomers (enantiomers)?

Answer 2

Two non-superimposable mirror images of a compound that have the same structural formula (stereoisomers), but arise due to having a chiral carbon (carbon with four different groups attached).

Question 3

What are the physical properties of optical isomers?

Answer 3

One enantiomer has a clockwise plane of polarisation for light while the other has an anticlockwise plane of polarisation, but both with the same angle.

Question 4

What is a racemic mixture?

Answer 4

A mixture of both enantiomers in equal proportions, which results in the mixture having no overall effect of the polarisation of light due to the polarisation effects of the 2 enzntiomers cancelling out.

Question 5

Why do α-amino acids have optical isomers and what is their significance?

Answer 5

Different enantiomers of amino acids have a dramatic impact on the final shape of a polypeptide/ protein. This is why only one enantiomer of an amino acid is synthesised by enzymes in the body, which act as chiral catalysts.

Question 6

What are the advantages of producing a single active enantiomer of a pharmaseutical product?

Answer 6

• The other non-active enantiomer may actually induce negative side-effects. Having only the active enantiomer means that negative side-effects if a drug may be reduced.
• If one enantiomer is active while the other one simply has no effects on the body, a larger dose of a drug containing the mixture of the two enantiomers (by mass) is needed to produce the same effects as a drug containing only the active enantiomer. Thus having a single enantiomer drug decreases dosage.

Question 7

Why are enantiomers difficult to separate?

Answer 7

Enantiomers are basically the same compound. They have very similar melting points, boiling points, solubilites and chemical properties. This means that separation techniques are often complex and expensive, while the waste enantiomer often cannot be sold for a different use.

Question 8

How can single enantiomers be synthesised?

Answer 8

• Using enzymes: Enzymes are good biological chiral catalysts as they produce only single enantiomers. This means that the use of enzymes in a synthesis stage of a compound will result in only s single enantiomer being produced.
• Chiral pool synthesis: If molecules that already have the desired chirality are used to make the desired products, the products will also have the desired chirality.
• Using transition metal compexes: Chiral transition metal comlexes can be used as artificial chiral catalysts and transfert their chirality to their products, thus only producing a single enantiomer.

Question 9

What are the aliphatic synthesis reactions required, their conditions and their main products?

Answer 9

1. Conversion of halogenoalkanes into aliphatic amines: Excess NH₃, gently heated in ethanol solvent - aliphatic amines.
2. Conversion of halogenoalkanes into alcohols: Heated under reflux - alcohols.
3. Oxidation of primary alcohols into aldehydes: Gently heated and distilled immediately - aldehydes.
4. Oxidation of aldehydes : Heated under reflux - carboxylic acid.
5. Reduction of aldehydes into primary alcohols.
6. Oxidation of secondary alcohols: Heated under reflux - ketones.
7. Reduction of ketones into secondary alcohols.
8. Esterification using alcohols and carboxylic acids: Heated to 80°C in presence of conc. sulfuric acid catalyst - ester.
9. Acid hydrolysis of esters: Heated under reflux with dilute acid catalyst - alcohol + carboxylic acid.
10. Alkaline hydrolysis of esters: Heated under reflux - alcohol + carboxylate salt.

Question 10

What are the aromatic synthesis reactions, their conditions and their main products?

Answer 10

1. Halogenation of benzene: Halogen carrier catalyst - halogenobenzene.
2. Nitration of benzene: Heated to 50°C in presence of conc. sulfuric acid catalyst - nitrobenzene.
3. Reduction of nitrobenzene: Heated under reflux - phenylamine.
4. Diazotisation of phenylamine: Reaction mixture kept between 0-10°C - diazonium salt.
5. Coupling of diazonium salts: Reaction mixture placed in an alkaline environment - azo dyes.
6. Bromination of phenol - 2,4,6-tribromophenol.
7. Reaction of phenol with alkali - phenoxide salt.
8. Reaction of phenol with reactive metals - phenoxide salt.