How to Use Pasteur’s Tweezers

Abstract

Pasteur introduced two techniques to separate enantiomers. The common visual imagery is that of the first technique, which pertains to the use of tweezers to separate the mirror image crystals of a tartaric acid salt. A second method discovered thereafter, not restricted to the conglomerates necessary for the tweezer approach, is diastereomeric resolution. In this chapter, a short discussion is given of the basic principles of diastereomeric resolutions followed by short analysis of Dutch Resolution, a method based on the use of families of resolving agents. The role of specific nucleation inhibition is discussed. Attention is then turned to conglomerates. Preferential crystallisation is discussed briefly. Particular attention is paid to the discovery of near-equilibrium methods to separate (racemisable) conglomerates by employment of constant attrition of the growing crystals. This methodology has been extended to preparation of the chiral components of some major drugs, and the methodology has also been adapted to separation of non-racemisable conglomerates.