Nucleation and Growth Kinetics of (R)-Mandelic Acid from Aqueous Solution in the Presence of the Opposite Enantiomer

Abstract

Resolution of mandelic acid (MA), a racemic compound, is presented in this article using direct crystallization from enantiomeric enriched water solutions. Final crystals with enantiomeric excess (ee) of (R)-MA higher than 96.4% were obtained. Because of the presence of the opposite enantiomer ((S)-MA), it was reported that nucleation and growth of (R)-MA was inhibited at the initial stage of the experiment (Perlberg, et al. Ind. Eng. Chem. Res. 2005, 44, 1012−1020). In order to understand the nucleation and growth kinetics of (R)-MA in the presence of (S)-MA, batch crystallization experiments were performed for controlled linear cooling mode with various operating conditions. Nucleation and growth parameters were then estimated by nonlinear fitting the measured liquid concentrations obtained from the signals of in situ attenuated total reflectance infrared (ATR-IR) spectroscopy and online polarimetry with model predictions. The effects of supersaturation, seed amount, cooling rate, and the presence of opposite enantiomer on the growth and nucleation rate of (R)-MA were discussed.