Semi-continuous temperature cycle-induced deracemization using an axially chiral naphthamide

This study outlines a practical semi-continuous method for temperature cycle-induced deracemization (TCID) using a batch mode crystallizer. We employed an axially chiral naphthamide derivative as a model compound, and deracemized the crystalline phase by conventional TCID. To achieve a continuity of deracemization, we harvested a part of the suspension after the conventional TCID, then feeding a new racemic suspension into the enriched suspension and applying temperature cycles. By leaving a highly enriched crystalline phase as seed crystals to direct the chirality of the following enrichment, the enrichment process was significantly accelerated, verifying the stable and high production efficiency. Furthermore, from the perspective of process productivity, the moderate suspension density is optimal for efficient deracemization. In the naphthamide system, up to 7.71 g·L−1·h−1 of the productivity was achieved. Thanks to the simple operation, the method described here is applicable for most of batch mode deracemization reported to date. In terms of industrial application, the semi-continuous deracemization could be a good option to utilize the existing batch crystallizers.