Chiral separation using a novel combination of cooling crystallization and a membrane barrier: Resolution of DL-glutamic acid

Abstract

Chiral separation of racemic mixtures is essential in the production of many pharmaceutical compounds. The present work describes a novel chiral separation technique that combines cooling crystallization and a membrane separation that is used in DL-glutamic acid resolution. The process utilizes two crystallization chambers that are separated by a membrane that prevents transport of crystals from one chamber to another. Importantly, conditions must be controlled so that only a pure species crystallizes in each of the chambers. This is done by appropriate addition of seed crystals to each chamber and by restricting the formation of new crystals to secondary nucleation mechanisms. The seed crystals may grow or participate in secondary nucleation, but conditions must be controlled so as to prevent primary nucleation, which would result in the formation of both crystal species in each chamber. Experiments were conducted with different amounts of seed crystals to determine operating conditions that produce the high product yield and purity. The results show that this novel chiral separation process is promising: the product purity was over 94% (with a separation factor of 16) and the product yield was increased by as much as 56% more than could be obtained with simple cooling crystallization.