Heats of solution in dimethyl sulfoxide (DMSO) have been determined for the diastereomeric salts (-)-(R)-methamphetammonium (+)-(RR)-bitartrate and (-)-(R)-methamphetammonium (-)-(SS)-bitartrate, (+)-(R)-โฃ-phenethylammonium (-)-(R)-2phenylbutyrate and (-)-(S)-โฃ-phenethylammonium (-)-(R)-2-phenylbutyrate, and of a new polymorph of (+)-(1S2R)-ephedrinium (-)-(R)-mandelate. The heats of solution for these salts were found to be 11.4 and 10.0 kcal/mol, 15.6 and 14.0 kcal/mol, and 7.4 kcal/mol, respectively.
Differential enthalpy contributions to chiral discrimination computed from these numbers are 1.4, 1.6, and 2.1 kcal/mol for the methamphetammonium bitartrates, โฃ-phenethylammonium (-)-2-phenylbutyrates, and ephedrinium mandelates, respectively. The new and previously observed (Zingg et al. J Am Chem Soc 110:1565-1580, 1988) polymorphs of the (+)-(1S2R)-ephedrinium (-)-(R)-mandelate are separated by nearly 1 kcal/mol.
Comparison of differential heats of solution with the corresponding differential heats of fusion suggests that heats of fusion differences do not properly represent the energy differences useful for diastereomeric salt separations.