Epalrestat tetra-hydro-furan monosolvate: crystal structure and phase transition.

Abstract

The title compound, epalrestat {systematic name: (5Z)-5-[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl-idene]-4-oxo-2-sulfanyl-idene-1,3-thia-zolidine-3-acetic acid}, crystallized as a tetra-hydro-furan monosolvate, C15H13NO3S2·C4H8O. Epalrestat, an important drug for diabetic neuropathy, has been reported to exist in polymphic, solvated and co-crystal forms. In the mol-ecule reported here, the phenyl ring is inclined to the rhodamine ring by 22.31 (9)°, and the acetic acid group is almost normal to the rhodamine ring, making a dihedral angle of 88.66 (11)°. In the crystal, pairs of O-H⋯O hydrogen bonds are observed between the carb-oxy-lic acid groups of epalerstat mol-ecules, forming inversion dimers with an R22(8) loop. The dimers are linked by pairs of C-H⋯O hydrogen bonds, forming chains along [101]. The solvate mol-ecules are linked to the chain by a C-H⋯O(tetra-hydro-furan) hydrogen bond. A combination of thermal analysis and powder X-ray diffraction revealed that title compound desolvated into epalerstat Form II. One C atom of the tetra-hydro-furan solvate mol-ecule is positionally disordered and has a refined occupancy ratio of 0.527 (18):0.473 (18).