Optical isomerism and chirality, the synthesis of organic compounds through multi-step routes, choosing reagents and conditions, and the importance of single enantiomers in the pharmaceutical industry.

What this topic is asking

Edexcel Topic 19 wants you to recognise chirality and optical isomerism, plan multi-step syntheses by choosing the correct reagents and conditions for each functional-group conversion, predict when a reaction gives a racemate, and explain why single enantiomers matter in medicines.

The answer

Chirality and optical isomerism

To identify a chiral centre, look for a carbon with four genuinely different substituents. For example, in 2-hydroxypropanoic acid the central carbon carries $\text{CH}_3$, $\text{OH}$, $\text{COOH}$ and $\text{H}$, four different groups, so it is chiral. A carbon bearing two identical groups (such as the central carbon of propan-2-ol, which has two $\text{CH}_3$) is not a chiral centre.

When reactions give a racemate

Whenever a chiral centre is created by attack on a planar group, both products form equally. The classic case is nucleophilic addition to a carbonyl: the $\text{C=O}$ is planar, so a nucleophile such as $\text{CN}^-$ can attack from either face with equal probability, producing equal amounts of each enantiomer, that is a racemic mixture. Recognising this is a common exam requirement.

Planning a multi-step synthesis

Multi-step synthesis joins individual functional-group conversions into a route. Useful conversions to combine include:

• alkene to alcohol (steam, $\text{H}_3\text{PO}_4$ catalyst) or to haloalkane (HX);
• haloalkane to alcohol (warm aqueous $\text{OH}^-$), to nitrile (ethanolic $\text{KCN}$, adding a carbon), or to amine (excess ammonia);
• nitrile to amine ($\text{LiAlH}_4$) or to carboxylic acid (acid hydrolysis);
• primary alcohol to aldehyde (distil with acidified dichromate) then to acid (reflux);
• acid to ester (alcohol, conc $\text{H}_2\text{SO}_4$) or to acyl chloride ($\text{SOCl}_2$).

At each step you must state the reagent and the conditions (temperature, solvent, catalyst). Plan by working backwards from the target functional group and checking the carbon count, remembering that the nitrile route is the standard way to lengthen the chain.

Single enantiomers in pharmaceuticals

Examples in context

Example 1. Ibuprofen. Ibuprofen has one chiral centre and is active mainly as a single enantiomer, yet it is sold as a racemate because the body slowly converts the inactive form into the active one. This illustrates the central message of the topic: a single enantiomer is usually preferred, but the economics of synthesis and the body's own chemistry decide whether selling a racemate is acceptable.

Example 2. Limonene and the smell of citrus. The two enantiomers of limonene smell different: one of oranges, the other of lemons. Because our olfactory receptors are chiral, they respond differently to each mirror image. This everyday example shows why enantiomers, identical in most physical properties, can behave completely differently in a chiral biological environment, exactly the principle behind single-enantiomer drugs.

Try this

Q1. State what is meant by a chiral centre. [1 mark]

• Cue. A carbon atom bonded to four different groups.

Q2. Explain why the pharmaceutical industry prefers to use a single enantiomer of a drug. [2 marks]

• Cue. Enantiomers can have different biological effects; using one reduces side effects and the required dose.