On the model-based design and comparison of crystallization-based deracemization techniques

Abstract

• Novel continuous seeded crystallization process with racemization is designed. • A steady state model is developed based on the thermodynamic features. • With this process, in total four techniques are identified for deracemization. • The qualitative and quantitative comparison of the four processes are carried out. Deracemization techniques produce target enantiomer (eutomer) by converting the undesired enantiomer (distomer) through a racemization reaction. We identify four techniques differing in operation mode and temperature profile. The novel ”MSMPR-type deracemization” process consists of continuous seeded crystallization process coupled with racemization. A steady state model enables us to identify the feasible operating region spanned by feed concentration and residence time, at different racemization kinetics and temperatures. The analysis shows that the most productive operating point corresponds to the least robust operating conditions, thus revealing the trade-off between productivity and purity. Based on this study, which complements and integrates our previous contributions on crystallization-based deracemization, we clarify the characteristic features of each process and compare the four processes in a case study. The results demonstrate that cooling processes outperform temperature cycles techniques in terms of productivity and yield, but the latter provides larger purity if the distomer nucleation cannot be avoided.