Model-Based Analysis of Continuous Crystallization/Reaction Processes Separating Conglomerate Forming Enantiomers

Abstract

The separation of conglomerate forming chiral molecules is investigated in continuous processes combining crystallization, milling, and a racemization reaction in solution. Two process configurations that increase enantiomeric purity starting from racemic mixtures are presented and assessed with respect to attainable enantiopurities, achievable yields, and productivities. The two processes differ in their feeding strategy: one is fed with a supersaturated solution of racemic composition, and one is fed with a racemic mixture of solids. The two cases are studied using a consistent mathematical model based on population balance equations. A parameteric analysis on the key operating parameters of the processes is conducted, and operating regions leading to high enantiomeric purity are identified. By combining the crystallization/mill/reaction process with appropriate filtration and solvent removal units, as well as recycle operations, we show that full enantiomeric purity at 100% yield is theoretically attai...