Construction of Melting Phase Diagram of Chiral Compounds and Application to Resolution

Abstract

The aim of the tutorial is to explain how to construct the binary melting phase diagram and solid-liquid ternary phase diagram of chiral systems and how to use it for resolution by crystallization. Phase diagram represents the phase information of a substance when it reaches thermodynamic equilibrium. To establish the reproducible resolution by crystallization, phase diagrams are extremely helpful because it indicates the crystallization pathways necessary for obtaining the desired crystalline phase. Herein, we described the types of racemic crystal structures, corresponding binary and ternary phase diagrams, and how to construct them based on the thermal analysis and solubility measurements. Furthermore, we introduced the definition of ‘deracemization’, which has been paid attention to as a productive resolution process. We also described our recent achievements about resolution enabled by phase diagrams.