How can we separate enantiomers?

1 Answer
Oct 28, 2014

You can separate the enantiomers from racemic mixtures by (a) mechanical separation, (b) reaction with enzymes, (c) formation of diastereomers, and (d) chromatography.

Mechanical Separation

If the enantiomers are solids, you can use tweezers to separate the crystals based on their shapes (rather labour intensive!).

Reaction with Enzymes

Enzymes are stereospecific chiral protein molecules that act as catalysts.

Because of their chirality, they react with only one enantiomer in a racemic mixture.

The enantiomer that bonds to an enzyme undergoes reaction. The enantiomer that does not bond remains unchanged.

You can then remove the unreacted enantiomer from the reaction mixture by ordinary separation methods such as distillation or recrystallization. But you lose the other half of the original mixture.

Formation of Diastereomers

You can separate the components of a racemic mixture by reacting them with an optically active reagent. The product is a mixture of diastereomers.

Diastereomers have different physical properties. You can separate them by ordinary separation techniques such as fractional crystallization.

Then you treat the separated diastereomers with appropriate reagents to regenerate the original enantiomers.

For example, you can separate a racemic mixture of a lactic acid by reacting it with a chiral base such as morphine.

The product is a mixture of two diastereomeric salts. The R-acid reacts with an S-base to form an R,S-salt. The S-acid reacts with an S-base to form an S,S-salt.

You separate the diastereomers by recrystallization. Then you regenerate the original acids by adding hydrochloric acid.


Finally, you can separate enantiomers by chromatography using a chiral stationary phase.

The R enantiomer will interact more strongly with an R stationary phase. It will be more retarded than the S enantiomer. They will pass through the column at different times.