Intrinsic MSZW characteristics of racemic species: Implication for chiral crystallization

Abstract

The metastable zone widths (MSZWs) of different racemic species in solutions were experimentally and theoretically investigated. It was found that the MSZWs of racemic conglomerates 4-hydroxy-2-pyrrolidone and N-methylephedrine were independent of enantiomeric excess, while the MSZWs of the racemic compound propranolol hydro-chloride in different solvents were associated with the solubility ratio a. of racemate to pure enantiomer. Crystal lattice properties were attributed to this difference. This can be used as the additional guideline for the characterization of racemic species. More interesting, abnormal apparent orders of primary nucleation rate at different enantiomeric excess were observed for conglomerate 4-hydroxy-2-pyrrolidone. It suggests a critical supersaturation exists beyond which the nucleation of the opposite isomer could occur. This phenomenon reveals particular implication of MSZW on the crucial supersaturation control during preferential crystallization, which was demonstrated in the preferential crystallization of 4-hydroxy-2-pyrrolidone with detailed modeling and in situ monitoring. © 2008 American Institute of Chemical Engineers.