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 sim-ilar 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 crystal-lization conditions. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Two new hydrate cocrystals, (RS)-arginine-fumaric acid-H2O (2) and (S)-arginine-2 fumaric acid-H2O (3), obtained from the slow evaporation of saturated aqueous ethanol solution, play a crucial role in the enrichment of arginine in the mother liquor due to their unstable formation.