Crystallization-Induced Deracemization: Experiments and Modeling

Abstract

Inspired by deracemization via temperature cycles, which enables the collection of crystals of the desired enantiomer from an initially racemic mixture, we focus in this work on an alternative batch process, namely crystallization-induced deracemization. This process starts with a suspension of enantiomerically pure crystals, which undergoes a simple cooling crystallization, coupled with liquid-phase racemization. The experimental and model-based analysis of such a process, carried out here, revealed that: (i) deracemization via temperature cycles is a safe choice to operate with high enantiomeric purity, although its throughput is limited by the suspension density; (ii) if the distomer is less prone to nucleation, crystallization-induced deracemization is a simple process; however, its performance is strongly limited by the solubility; (iii) the purity achieved with crystallization-induced deracemization can be increased by utilizing large seed mass and by optimizing the cooling profile or catalyst concentration. Alternatively, the purity increases via partial dissolution of the seeds, which resembles the heating part of the deracemization process via temperature cycles.

Abstract

Crystallization-induced deracemization consists of a simple cooling crystallization, coupled with liquid-phase racemization, which, in theory, enables the collection of pure crystals of the desired enantiomer. However, in this work we show that the operating conditions need to be tuned to achieve this goal, thus avoiding the nucleation of the counter enantiomer, which would affect the product purity.