Other Methods of Resolution

Qne of the major goals in the field of organic chemistry is the development of reagents with the property of "chiral recognition" such that they can effect a clean separation of enantiomers in one operation without destroying either of the enantiomers. We have not achieved that ideal yet, but it may not be far in the future. Chromatographic methods, whereby the stationary phase is a chiral reagent that adsorbs one enantiomer more strongly than the other, have been used to resolve racemic compounds, but such resolutions seldom have led to both pure enantiomers on a preparative scale. Other methods, called kinetic resolutions, are excellent when applicable. The procedure takes advantage of differences in reaction rates of enantiomers with chiral reagents. One enantiomer may react more rapidly, thereby leaving an excess of the other enantiomer behind. For example, racemic tartaric acid
can be resolved with the aid of certain penicillin molds that consume the dextrorotatory enantiomer faster than the levorotatory enantiomer. As a result, almost pure (-)-tartaric acid can be recovered from the mixture:

(±)-tartaric acid + mold →

(-)-tartaric acid + more mold

A disadvantage of resolutions of this type is that the more reactive enantiomer usually is not recoverable from the reaction mixture.

The crystallization procedure employed by Pasteur for his classical resolution of (±)-tartaric acid  has been successful only in a very few cases. This procedure depends on the formation of individual crystals of each enantiomer. Thus if the crystallization of sodium ammonium tartrate is carried out below 27", the usual racemate salt does not form; a mixture of crystals of the (+) and (-) salts forms instead. The two different kinds of crystals, which are related as an object to its mirror image, can be separated manually with the aid of a microscope and subsequently may be converted to the tartaric acid enantiomers by strong acid. A variation on this method of resolution is the seeding of a saturated solution of a racemic mixture with crystals of one pure enantiomer in the hope of causing crystallization of just that one enantiomer, thereby leaving the other in solution. Unfortunately, very few practical resolutions have been achieved in this way.

Even when a successful resolution is achieved, some significant problems remain. For instance, the resolution itself does not provide information on the actual configuration of the (+) or (-) enantiomer. This must be determined by other means.