The Role of Water-Solvation in the Optical Resolution of Dl-Leucine with (S)-(−)-1-Phenylethanesulfonic Acid. Characterization and X-Ray Crystal Structures of Their Diastereomeric Salts

Abstract

Abstract In the optical resolution by diasteromeric salt formation of Dl-leucine with (S)-(−)-1-phenylethanesulfonic acid (PES), the less-soluble l-Leu·(−)-PES salt preferentially crystallized from acetonitrile–methanol and, in contrast, the same resolution from acetonitrile–water afforded the monohydrated d-salt [d-Leu·(−)-PES·H2O]. The role of the water of crystallization formed during this resolution system has been explored through a comparison of the crystalline characteristics of d-, monohydrated d-, and l-Leu·(−)-PES by thermoanalysis (DSC) and spectroscopy. The DSC indicated that d-Leu·(−)-PES had a polymorphic form with the water of crystallization; that is, d-Leu·(−)-PES·H2O was thoroughly dehydrated at 60—90 °C and simultaneously converted into the d-Leu·(−)-PES form. However, l-Leu·(−)-PES does not have the water of crystallization even in 75% relative humidity. Detailed comparisons among the X-ray crystal structures of three salts have revealed that in all of the salts the conformations of the PES anion and the Leu cation, respectively, were approximately the same, and their crystal structures comprised specific interaction modes having characteristic hydrogen-bond networks. In particular, in d-Leu·(−)-PES·H2O the PES and Leu ions are cross-linked to each other through water molecules. These observations suggested that the water of crystallization, together with the formation of a stable crystal-packing mode by cross-linking the PES and Leu ions, presumably plays an important role in the selective crystallization in the resolution.