Deracemization in a Complex Quaternary System With a Second-Order Asymmetric Transformation by Using Phase Diagram Studies

Chemistry. 2019 Nov 4;25(61):13890-13898. doi: 10.1002/chem.201903338. Epub 2019 Sep 10.

Abstract

A productive deracemization process based on a quaternary phase diagram study of a naphthamide derivative is reported. New racemic compounds of an atropisomeric naphthamide derivative have been discovered, and a quaternary phase diagram has been constructed that indicated that four solids are stable in a methanol/H2 O solution. Based on the results of a heterogeneous equilibria study showing the stable domain of the conglomerate, a second-order asymmetric transformation was achieved with up to 97 % ee. Furthermore, this methodology showcases the chiral separation of a stable racemic compound forming system and does not suffer from any of the typical limitations of deracemization, although application is still limited to conglomerate-forming systems. We anticipate that this present study will serve as a fundamental model for the design of sophisticated chiral separation processes.

Keywords: atropisomerism; chiral resolution; deracemization; phase diagrams; second-order asymmetric transformation.