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 nonracemisable conglomerates.

Chiral discrimination in nuclear magnetic resonance spectroscopy

“…However, Pasteur developed a viable alternative methodology to obtain substantial amounts of the desired enantiomer via diastereomeric recrystallization, i.e. chiral resolution of enantiomers from a racemic mixture, based on the different physical characteristics of conglomerates containing them [234]. In fact, physical properties such as solubility, melting point and boiling point of the enantiomers in a racemate are the same, but significantly different in diastereomers, which can be separated by recrystallization like any two distinct molecules.…”

Asymmetric Anisoin Synthesis Involving Benzoin Condensation Followed by Deracemization

“…Finally, the racemic mixture converges into one-handed enantiomeric crystals. This asymmetric amplification method includes gradually growing crystals from a supersaturated solution (crystallization-induced enantiomer transformation) − or attrition-enhanced deracemization (Viedma ripening), which is performed by suspending and stirring the crystals with glass beads in a small amount of solvent . In either method, the products must crystallize as a conglomerate, and rapid racemization must proceed under the conditions of crystal growth.…”

Chiral Symmetry Breaking of Racemic 3-Phenylsuccinimides via Crystallization-Induced Dynamic Deracemization

“…Optically pure materials are essential in organic chemistry, pharmaceuticals, and functional materials, and much effort has been devoted to their asymmetric synthesis from prochiral materials and to the optical resolution of racemic mixtures. Among optical resolution by crystallization methods, dynamic optical resolution efficiently provides enantiomeric crystals by simple filtration without requiring cumbersome separations, as shown in Figure . , This method involves dynamic deracemization of racemic conglomerate crystals under racemization conditions in the mother liquor, resulting in the convergence of the racemic mixture to single enantiomer crystals. − This method is also highly attractive because spontaneous chiral symmetry breaking is closely linked to homochirality of biomolecules on Earth. − Recently, successful examples of deracemization have been reported for many reaction systems, such as amino acids, − heterocyclic compounds, − and pharmaceutically valuable materials; however, this is an emerging field and new molecular systems are eagerly needed.…”