W0070

A New Enantiomeric Resolution Phenomenon Associated with Polymorphic Transition during Crystallization. Rui Tamura, Graduate School of Human & Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.

We have recently reported the first case of enantiomeric resolution by simple recrystallization of a series of organic racemic crystals, although in principle such a enantiomeric resolution has been believed to be impossible for more than a century since the mechanical resolution of enantiomeric conglomerates (chiral crystals) by Pasteur and the discovery of the preferential crystallization technique by Gernetz. We have referred this new enantiomeric resolution phenomenon as Preferential Enrichment. We assume that a polymorphic transition from a less ordered metastable crystalline phase into a more ordered stable one during crystallization might be closely associated with the mechanism of Preferential Enrichment. In order to predict the mode of this polymorphic transition, it is indispensable to elucidate both metastable and stable crystal structures of the compounds, which show Preferential Enrichment, as well as their molecular association modes in solution.

Here we report that (1) the types of enantiomers mixtures in the stable crystals of the racemates showing Preferential Enrichment should be classified into a fairly ordered racemic mixed crystal (so-called solid solution or pseudoracemate) composed of the two enantiomers, based on their crystal structures and characteristic melting point phase diagrams, (2) the metastable crystalline phase, which is considered to be essential for the phase transition, has been prepared by changing recrystallization conditions and been subjected to phase transition experiments, and (3) the molecular association modes in solution have been estimated by means of molecular mechanics and dynamics calculations. From these results, we propose the mechanism of the polymorphic transition.

References

Angew. Chem. Int. Ed. Engl. 1996, 35, 2372; Chirality 1998, 10, 705-710; Angew. Chem. Int. Ed. Engl. 1998, 37, 2876.