Polymorphism in secondary benzene sulfonamides

Abstract

The role of about 20 different solvents in the crystallization of polymorphs for 13 N-phenyl benzene sulfonamides was studied. Five compounds (1, 2, 3, 7, and 11) are dimorphic, and one is trimorphic (6). All the crystalline solids were characterized by powder and single crystal X-ray diffraction, thermal analysis, hot stage microscopy, and IR and Raman spectroscopy. The phase transition from a metastable form to the stable form was examined visually for two compounds (1, 11) on a HSM and confirmed by differential scanning calorimetry and X-ray diffraction. The N-H···O hydrogen bond catemer (chain) and dimer (cyclic) motifs of the sulfonamide group were analyzed as the main difference between polymorphs of 1, 3, and 6. Weaker C-H···O interactions differentiate the molecular packing of other polymorphic systems. Accordingly, these crystal structures are referred to as synthon polymorphs. The occurrence of N-H···O catemer and dimer synthon in secondary sulfonamides is compared with crystal structures in the Cambridge database. The nearly equal probability of the dimer and catemer motifs for secondary sulfonamides (~19%) is attributed to the possibility of making the catemer synthon via both anti and syn oxygen atoms of the SO₂NH group, with the former acceptor being preferred in two-thirds of the cases.