Resolution of Conglomerates with the Assistance of Tailor-made Impurities. Generality and Mechanistic Aspects of the "Rule of Reversal". A New Method for Assignment of Absolute Cofiguration

Article abstract of DOI:10.1021/ja00381a018

A new general and efficient method for kinetic resolution of racemic conglomerates by crystallization in the presence of "tailor-made" additives is described.The process is explained in terms of stereoselective adsorption of the resolved additive at the surface of the growing crystals of the enantiomer of the same absolute configuration, resulting in a drastic decrease in their rate of growth and thus allowing preferential crystallization of the opposite enantiomer ("rule of reversal").Some empirical resolutions reported in the literature are rationalized through this mechanism, and appropriate additives for the resolution of new systems are designed and successfully applied.The crystallization of the conglomerates (R,S)-glutamic acid hydrochloride (Glu*HCl), (R,S)-threonine (Thr), (R,S)-(p-hydroxyphenyl)glycine p-toluenesulfonate (pHpgpTs), and (R,S)-asparagine hydrate (Asn*H2O) in the presence of other amino acids, used as additives, has been studied in particular.It is demonstrated that the additives are occluded in the bulk of the homochiral crystal in typical amounts of 0.5-1.5percent, while they are not found in the bulk of the crystals of the antipode.The possible role of the additives in nucleation and dissolution of the affected crystals is considered.A new method for the assignment of absolute configuration of chiral molecules is proposed.