25.3 Synthesis of optically active compounds

Question 1

What is a racemate or racemic mixture

Answer 1

Most reactions that are used in organic synthesis actually produce a 50-50 mixture of the two optical isomers

It is not optically active because the two cancel out

Question 2

How is lactic acid aka
2-hydroxypropanoic acid

synthesised?

Stage 1

Using nucleophilic addition

Answer 2

It can be made in two stages from ethanal

. Hydrogen cyanide H-C=N where there is a triple bond between C and N

This is added across the C=O bond to form 2-hydroxypropanenitrile in a nucleophilic addition reaction

. This has a chiral centre so a racemic mixture is formed as the reaction doesn’t favour one isomer over the other so the CN can be added on above or below the chiral centre with equal probability

Question 3

What is stage 2 of the synthesis of 2-hydroxypropanoic acid

Answer 3

The nitrile group is then converted into a carboxylic acid group.

This happens by reacting the 2-hydroxypropanenitrile with water acidified with dilute HCl in a hydrolysis reaction

The 2-hydroxypropanoic acid produced still has a chiral centre that has not been affected by the hydrolysis reaction which only involves CN group

SO a racemic mixture of the two isomers is formed

Question 4

Often, a molecule made synthetically with a chiral centre ends up as a mixture of optical isomers

However the same molecule produced naturally only ends up with one isomer, why?

Answer 4

Most naturally occurring molecules are made with enzyme catalysts which only produce one of the possible optical isomer

Question 5

In the drug industry, does it matter which optical isomer is used as the drug

Answer 5

Yes, because drugs often work by a molecule of the active ingredient attaching themselves to cells receptors

Because receptors are 3D, only one of a pair of optical isomers will fit

So sometimes only one of the pair of optical isomers is an effective drug and the other is inactive or is even toxic

Question 6

Sometimes only one of the pair of optical isomers is an effective drug and the other is inactive

what are 3 options to overcome this

Answer 6

1) Separate out the two isomers however it is difficult and expensive as optical isomers have very similar properties

2) Sell the mixture as a drug however it is wasteful because only half of it is effective

3) Design an alternative synthesis of the drug that only contains the required isomer