4.8 : Racemic Mixtures and the Resolution of Enantiomers

A racemic mixture, also referred to as a racemate, is an equimolar mixture of enantiomers of a molecule. Racemic mixtures are denoted with the (±) prefix, as they consist of an enantiomeric pair, and the corresponding optical rotation descriptor applies to the whole solution rather than a specific stereoisomer.

Recall that enantiomers can exhibit different properties when they interact with chiral media. For instance, enantiomers of the carvone molecule interact differently with the chiral olfactory receptors in our body. While (R)-carvone smells like spearmint, (S)-carvone smells of caraway or dill.

Similarly, enantiomers in a racemic mixture can react differently with other chiral molecules, such that the addition of a chiral molecule to a racemic mixture results in the formation of two or more different products.

For example, when N-propylglucosamine, a chiral glucose derivative, is added to a racemic mixture of the drug naproxen, two different salts are formed. These salts are diastereomers of each other and exhibit different physical properties.

When the reactants are stirred in an aqueous solution, the salt of (S)-naproxen crystallizes out of the solution, while the salt of (R)-naproxen remains dissolved in the solution. Accordingly, these salts can be easily separated and converted back to obtain enantiomerically pure (R)- and (S)-naproxen.

This process of separating the enantiomers is termed ‘enantiomeric resolution’. Here, N-propylglucosamine is referred to as a chiral resolving agent owing to its ability to react differently with the enantiomers of naproxen in the racemic mixture.

Some molecules, such as tartaric acid, can undergo spontaneous enantiomeric resolution without the addition of any chiral resolving agent. Here, upon cooling the racemic mixture, each enantiomer selectively crystallizes with itself. This results in the separation of the enantiomers into different crystals.

In general, the resolution of racemic mixtures into separate enantiomers requires the application of special techniques such as chiral chromatography.