Solvent Effect on the Preparation of Ionic Cocrystals of <scp>dl</scp>-Amino Acids with Lithium Chloride: Conglomerate versus Racemate Formation

The hydrophobic dl-amino acids alanine, valine, leucine, and isoleucine have been cocrystallized with LiCl via solid-state solution methods, the effect of preparation conditions solvent choice on racemic versus conglomerate formation has investigated. For sake comparison, enantiopure l-amino also reacted in same experimental conditions. With dl-alanine only, a ionic cocrystal formula dl-alanine·LiCl·H2O is obtained, irrespective conditions, while amino dl-valine dl-leucine undergo spontaneous chiral resolution when MeOH used ball milling yielding monohydrated conglomerates, which at ambient convert over time into cocrystals dl-Val·LiCl·H2O dl-Leu·LiCl·1.5H2O; these (ICCs) are otherwise obtained single step if water employed instead MeOH, both dl-Isoleucine behaves differently, product characterization complicated by presence dl-alloisoleucine (dl-aIle) commercial starting material; crystallization excess LiCl, however, unexpectedly results alloisoleucine d-aIle·LiCl·H2O l-aIle·LiCl·H2O, together unreacted dl-isoleucine. Solid-state syntheses proceed most cases intermediate metastable polymorphs; phase identification structural for all ICCs conducted crystal and/or powder X-ray diffraction.