Thermodynamics in the prediction of the solubilities of binary mixtures of the diastereoisomers and enantiomers of ephedrine

Abstract

Equations derived from the Clausius-Clapeyron and Prigogine-Defay equations were used to determine the free energy of mixing for diastereoisomers and enantiomers from heats of fusion and transition temperature data. These equations are applied to the thermodynamics of mixing of the six binary equimolar combinations of (1R,2S)-ephedrine, (1S,2R)-ephedrine; and (1R,2R)- and (1S,2S)-pseudoephedrine isomers. The relative equilibrium solubility of the binary mixtures in water is consistent with thermodynamic calculations.