Pitfalls and rewards of preferential crystallization

The mirror symmetry relationship between enantiomers makes their separations by ‘classical’ separation methods difficult. When applicable, preferential crystallization is a productive and cost effective process which consists of alternate crystallizations of both enantiomers crystallizing as a conglomerate. Addition of in situ racemization to ‘classical’ preferential crystallization allows the yield to increase up to 100% in a single batch operation. Furthermore, the implementation of continuous ‘gentle’ grinding can solve the main problem of this method, i.e. the nucleation of the counter enantiomer. Preferential crystallization methodology can be also applied to any system composed of non symmetrical species. However, a set of thermodynamic and kinetic parameters must be determined for every compound that is supposed to crystallize selectively. This ‘highlight’ details the basic principles and the limitations of ‘classical’ preferential crystallization and its applications on ‘exotic’ systems by an extensive usage of phase diagrams.