Crystal growth rates and optical resolution of dl-methionine hydrochloride by preferential crystallization from aqueous solution

Optical resolution of dl-methionine hydrochloride (dl-met·HCl) by preferential crystallization was studied for the purification of l-met·HCl (the desired enantiomer) from supersaturated solutions of dl-met·HCl. The nucleation thresholds (NT) of dl-met·HCl affect the maximum resolution time suitable for preferential crystallization and also the percentage purity of the product crystals. Crystal growth rates of l-met·HCl single crystals both in supersaturated solutions of dl-met·HCl and in supersaturated solutions of pure l-met·HCl were measured in order to model the preferential crystallization more effectively. Results showed that the growth rate depends strongly on the relative supersaturation (especially from pure l-met·HCl solutions), that there is a wide crystal growth rate distribution in growth from both types of solution, and that the growth is faster from pure l-met·HCl solutions, as expected. A batch crystallizer seeded with l-met·HCl crystals was used to study the preferential crystallization, and to study the behavior of purity decrease of the product crystals during the crystallization process. The purity of the l-met·HCl product decreased to the equilibrium value over time, with almost no plateau at 100% purity (as is hoped for in preferential crystallizations). This is explainable by the very short induction times for nucleation in these solutions, and also that the l-met·HCl seed crystals may act as a template for the nucleation of the counter-enantiomer.

► Crystal growth kinetics measured for l-methionine hydrochloride in pure l– solution.
► Crystal growth kinetics measured for l-methionine hydrochloride in racemic solution.
► Optical resolution of the enantiomers by preferential crystallization investigated.
► Counter-enantiomer appears to nucleate on the surface of the seed.
► Counter-enantiomer inhibits growth of l-methionine hydrochloride.