A Novel Strategy for Deracemization Using Periodic Fluctuations of Concentration

Abstract

AbstractA novel concept of deracemization via periodic fluctuations of solute concentration is demonstrated. Fluctuation of concentration under isothermal conditions was induced by vacuum evaporation followed by re‐addition of solvent. Complete deracemization of a scalemic suspension of N‐(2‐methylbenzylidene)‐phenylglycine amide (NMPA) was achieved. The effects of initial enantiomeric excess, vacuum pressure, and duration of evaporation on the evolution of the solid phase enantiomeric excess and the mechanism of this strategy were studied. Pure enantiomorph NMPA could be achieved by this technique in an efficient and novel procedure. The process has advantages for compounds that have solubility with a weak temperature dependence or compounds that start to decompose at low temperature.