Potential of Chiral Solvents for Enantioselective Crystallization. 1. Evaluation of Thermodynamic Effects

It can be expected that a chiral solvent possesses a certain potential to discriminate between two enantiomers by creating specific weak interactions and forming diastereomeric complexes which have different physical properties. Thus, for chiral solvents, there might be an asymmetry in the solubility phase diagrams that could be employed for resolution purposes. In this work, investigations were carried out to identify appropriate chiral solvents for the discrimination of enantiomers with the aid of nuclear magnetic resonance (NMR) spectroscopy and Raman spectroscopy. The ¹H NMR and Raman spectra results of mandelic acid in the chiral solvents did not show any significant chiral recognition. The effect of (S)-ethyl lactate and (2R, 3R)-diethyl tartrate on solubility was examined by measuring the ternary phase diagrams of mandelic acid and N-methylephedrine. The phase diagrams determined at different temperatures were symmetric indicating again that the used chiral solvents have less or no influence on the thermodynamics of solution. However, in additional experiments, it was found that there can be significant differences in the nucleation behavior of the two enantiomers in a chiral solvent. Copyright © 2008 American Chemical Society [accessed October 8, 2008