Substituent position effect on the crystal structures of N-phenyl-2-phthalimidoethanesulfonamide derivatives

In order to determine the impact of different substituents and their positions on intermolecular interactions and ultimately on the crystal packing, unsubstituted N-phenyl-2-phthalimidoethanesulfonamide, C₁₆H₁₄N₂O₄S, (I), and the N-(4-nitrophenyl)-, C₁₆H₁₃N₃O₆S, (II), N-(4-methoxyphenyl)-, C₁₆H₁₆N₃O₆S, (III), and N-(2-ethylphenyl)-, as the monohydrate, C₁₈H₁₈N₂O₄S·H₂O, (IV), derivatives have been characterized by single-crystal X-ray crystallography. Sulfonamides (I) and (II) have triclinic crystal systems, while (III) and (IV) are monoclinic. Although the molecules differ from each other only with respect to small substituents and their positions, they crystallized in different space groups as a result of differing intra- and intermolecular hydrogen-bond interactions. The structures of (I), (II) and (III) are stabilized by intermolecular N-H...O and C-H...O hydrogen bonds, while that of (IV) is stabilized by intermolecular O-H...O and C-H...O hydrogen bonds. All four structures are of interest with respect to their biological activities and have been studied as part of a program to develop anticonvulsant drugs for the treatment of epilepsy.