Study of the Characterization and Crystallization of 4-Hydroxy-2-Pyrrolidone

Abstract

A systematic study of the characterization for racemic species of 4-hydroxy-2-pyrrolidone was undertaken. The melting point phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone was determined by differential scanning calorimetry. The ternary phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone with isopropanol was constructed at 15, 20, 25, and 35°C. The crystalline nature of 4-hydroxy-2-pyrrolidone racemate was also characterized by means of comparison of solid-state FTIR spectra and powder X-ray diffraction patterns of the racemic mixture with those of one of the enantiomers. It is shown that (±)-4-hydroxy-2-pyrrolidone is a racemic conglomerate. The enthalpies of fusion of (R)-4-hydroxy-2-pyrrolidone and (±)-4-hydroxy-2-pyrrolidone and entropy of mixing of (R)- and (S)-4-hydroxy-2-pyrrolidone were calculated using the thermodynamic data. The solubility and supersolubility diagrams of (R)- and (S)-4-hydroxy-2-pyrrolidone in isopropanol were determined over a temperature range of 4-35°C. The optical resolution of (± )-4-hydroxy-2-pyrrolidone was successfully achieved by preferential crystallization. © 2004 Wiley-Liss, Inc.