Chiral Resolution via Cocrystallization with Inorganic Salts
Oleksii Shemchuk, Fabrizia Grepioni, Tom Leyssens, Dario Braga
Abstract
Abstract 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 ZnCl 2 , 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 Ca 2+ and Mg 2+ , which favour octahedral coordination, heterochiral complexation is observed in most cases, with formation of racemic crystals.