Towards a rational design of resolving agents. Part III. structural study of two pairs of diastereomeric salts of ephedrine and a cyclic phosphoric acid

The crystal structures of two pairs of diastereomeric salts consisting of ephedrine and a cyclic phosphoric acid were analyzed in detail. One pair (R = H; Figure 1) shows no difference in solubility, as reflected in identical non‐bonded interaction patterns in the two salts. The other pair (R = CI; Figure 1) shows a significant solubility difference; the crystal packings of these two salts differ considerably. The less soluble salt shows far more favorable Van der Waals interactions, presenting further evidence that the result of optical resolutions by selective crystallization are determined by these weak interactions. This study, in combination with the results presented in the previous paper (Towards a rational design of resolving agents, Part II), suggests that a model might be developed describing a (quantitative) relationship between the lattice energy difference in a diastereomeric pair and the resolution efficiency of the resolving agent.