Continuous Preferential Crystallization of Chiral Molecules in Single and Coupled Mixed-Suspension Mixed-Product-Removal Crystallizers

In several industrial fields, the existence of chiral molecules causes challenges when only one enantiomer is the desired active ingredient in the final product. The separation of pairs of enantiomers can be achieved with different techniques. Once these enantiomers crystallize as conglomerates, preferential crystallization (PC) is a very attractive alternative. So far, various batchwise operating strategies have been developed and applied successfully. Very likely, however, it can be more beneficial to use PC in a continuous manner, since continuous processes can often outrun their batch counterpart in terms of productivity, product quality, and process complexity. In this contribution, chiral separation is investigated and performed in a continuous manner adapting the concept of mixed-suspension mixed-product-removal (MSMPR) to the requirements of preferential crystallization. Continuous PC could be realized successfully in two different experimental setups involving only one MSMPR crystallizer and two MSMPR crystallizers coupled via an exchange of their liquid phases. For the model system d-/l-threonine/water, this first experimental demonstration of the concept proves that the process can continuously separate enantiomers with purities >99%. The agreement of the experimental results with results of process simulation indicates the strength and usefulness of a previously published mathematical model.