Recent advances in the field of chiral crystallization
Joshua I. Putman, Daniel W. Armstrong
Abstract
Crystallization is one of the largest and most economical bulk purification techniques used in industry today. There has been an increase in demand for enantiomerically pure compound production for research, organic synthesis, pharmaceutical drug production, and other applications. Even after asymmetric synthesis, chiral purification will always be necessary. The focus of this review is on recent advances in chiral crystallization for the purification of enantiomers. A comprehensive discussion of three techniques and their mechanisms is provided, namely: attrition-enhanced deracemization, cocrystallization, and inorganic ionic cocrystallization. Several examples of attrition-enhanced deracemization are discussed. The key advantage of this technique is that it eliminates enantiomeric waste and can be used to produce enantiomeric excesses of greater than 99% from racemic mixtures. Chiral cocrystallization is examined, with over 60 cocrystallizing compounds, as an excellent means for enantiomeric enrichment. Selective chiral inclusion complexation was shown to be a novel approach for the formation of cocrystals. Chiral inorganic ionic cocrystallization is a new technique involving the formation of cocrystals between chiral ligands and certain metal salts in order to produce conglomerate crystal behavior in otherwise racemic compounds.