Crystal structure analysis of highly efficient chiral resolution of (RS)-arginine-fumaric acid cocrystal under preferential enrichment conditions

Two new hydrate cocrystals, (RS)-arginine-fumaric acid-H2O (2) and (S)-arginine-2 fumaric acid-H2O (3), were obtained by the slow evaporation of the saturated aqueous ethanol solution of a 1:1 mixture of S-enriched arginine (33% ee) and fumaric acid or (S)-arginine and fumaric acid, respectively. Cocrystals 2 and 3 possess an isostructural molecular organization containing homochiral 1D chains of arginine similar to that of the anhydrous cocrystal of (RS)-arginine-fumaric acid (1). The latter showed an efficient “preferential enrichment (PE)”, a unique spontaneous enantiomeric resolution phenomenon by simple recrystallization from the highly supersaturated solution. The formation of unstable cocrystals 2 and 3 seems to have played a crucial role in the enrichment of arginine in the mother liquor under PE crystallization conditions.