Chiral Resolution via Cocrystallization with Inorganic Salts

crystal engineering, cocrystals, chirality

The coordination mode to lithium, magnesium, calcium and zinc cations of racemic vs. enantiopure amino acids and racetam APIs is analysed and its effect on chiral selection critically reviewed. It is shown that chiral resolution in the solid state can be obtained via cocrystallization of racemic compounds with an achiral inorganic salt coformer, such as LiX (X=Cl, Br, I) or ZnCl2, which favour tetrahedral coordination in the solid state. The chiral selection may take the form of conglomerate crystal formation or of selective homochiral aggregation in racemic crystals. When cocrystallization involves alkaline earth metal cations, such as Ca2+ and Mg2+, which favour octahedral coordination, heterochiral complexation is observed in most cases, with formation of racemic crystals.