Efficient Resolution of Enantiomers by Coupling Preferential Crystallization and Dissolution. Part 2: A Parametric Simulation Study to Identify Suitable Process Conditions

Abstract

For pairs of enantiomers crystallizing as a conglomerate, several process strategies can be used to resolve them by preferential crystallization (PC). Usually, a main limitation is the nucleation of the counter enantiomer, which restricts productivities. The performance of PC can be strongly increased, when crystallization and selective dissolution are combined by coupling two crystallizers via the liquid phase. In doing so, one crystallizer contains a saturated racemic suspension, while the other is in a supersaturated state and initially seeded with pure enantiomer. The crystallization of the seeds in the corresponding tank leads to a transient undersaturation in the other tank and, thus, to a selective dissolution from the racemate. Due to the exchange of solution, crystallization is accelerated, while the solid racemate is purified.The process described, has been investigated in detail using a well-established population balance model, which was shown to be in good agreement with experimental results presented recently in ref 1. A parametric study was done, which revealed regions, in which the process can be operated at high productivity, yielding both enantiomers in pure form. The achieved understanding of the influence of the investigated process parameters on the performance can help to further improve and optimize the process.