Diastereomeric resolution rationalized by phase diagrams under the actual conditions of the experimental process

Abstract

A brief survey on phase diagrams involved in Pasteurian resolutions in solution is proposed. Various heterogeneous equilibria (limited to ternary systems involving two diastereomers with a nonchiral solvent as a third component) are depicted including stoichiometric intermediate compounds and solid solutions. Polymorphism is not considered in this study. A collection of adapted investigations on these heterogeneous systems are presented; they aim at defining the optimum process under the actual experimental conditions prevailing during the resolution. A new technique (discontinuous isoperibolic thermal analysis: DITA) designed to access to these relevant data is presented. Two typical examples of Pasteurian resolution are given as illustrations: (±)-mandelic acid resolved by (−)-ephedrine in ethanol at 24.7 °C and (±)-mandelic acid resolved by quinine in methanol at 20 °C.