Semicontinuous Temperature Cycle-Induced Deracemization Using an Axially Chiral Naphthamide

This study outlines a practical, semicontinuous 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 continuity of deracemization, we harvested a part of the suspension after the conventional TCID, and then we fed a new racemic suspension into the enriched suspension and applied 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 a 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 productivity was achieved. Thanks to the simple operation, the method described here is applicable for most batch-mode deracemizations reported to date. In terms of industrial applications, semicontinuous deracemization could be a good option to utilize the existing batch-mode crystallizers.