Towards a rational design of resolving agents. Part IV. Crystal packing analyses and molecular mechanics calculations for five pairs of diastereomeric salts of ephedrine and a cyclic phosphoric acid

Detailed structural studies of five pairs of diastereomeric salts of ephedrine and halogen-substituted chiral cyclic phosphoric acids indicate a correlation between the efficiency of the resolution process and the lattice energy difference between the salts of a diastereomeric pair. Attempts to model such a correlation quantitatively by lattice energy calculations with Molecular Mechanics (MM) methods have not yet been successful. The MM techniques proved unable to reproduce the crystal structures with sufficient accuracy. However, the results of the analyses qualitatively support the presumed correlation, and show that the five resolutions are directed by different acid-base interactions in the hydrophobic layers.