4.8: Racemic Mixtures and the Resolution of Enantiomers
A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit different properties when they interact with chiral media. For instance, enantiomers of a molecule can interact differently with the chiral olfactory receptors in our body so that each enantiomer smells unique.
Racemic mixtures can therefore be separated using a unique process called enantiomeric resolution. Here, the enantiomers react with a chiral resolving agent to produce diastereomers. These diastereomers can be easily separated and reconverted to obtain the enantiomerically pure molecules. Depending on the molecular structure, the interaction between the chiral resolving agents and enantiomers can be either covalent, ionic, or a weak intermolecular interaction involving van der Waals forces. However, some racemic mixtures can undergo spontaneous resolution without the presence of a chiral resolving agent. For example, the racemic mixture of an N-trifluoroacetylated α-amino alcohol in carbon tetrachloride undergoes spontaneous resolution.
The resolution processes can be classified in general into chiral and kinetic resolution. In a chiral resolution, the interaction of the racemic mixture with a pure enantiomer forms diastereomers. These are then separated owing to the difference in their physical properties. In the kinetic resolution, the separation of enantiomers is based on the difference in reaction rates of enantiomers with a chiral catalyst. Unlike the former, kinetic resolution takes advantage of the difference in the chemical properties of the starting materials in the racemic mixture.