Three Nimesulide Derivatives: Synthesis, Ab Initio Structure Determination from Powder X-ray Diffraction, and Quantitative Analysis of Molecular Surface Electrostatic Potential

Abstract

Three nimesulide derivatives, N-[4-(2,5-dioxo-pyrrolidin-1-yl)-2-phenoxyphenyl] methanesulfonamide (2), N-[4-(4-methanesulfonylamino-3-phenoxy phenylsulfamoyl) phenyl] acetamide (3), and 4-(4-methanesulfonylamino-3-phenoxyphenyl-carbamoyl)-butanoic acid (4), have been synthesized, and their crystal structures have been determined from laboratory powder X-ray diffraction data. The nature of intermolecular interactions in 2–4 has been analyzed through Hirshfeld surfaces and two-dimensional fingerprint plots and compared with that in the nimesulide polymorphs (1a and 1b). The crystal packing in 2–4 exhibits an interplay of N–H···O, O–H···O (in 4), C–H···O, and C–H···π (in 2) hydrogen bonds, which assemble molecules into a supramolecular framework. Hydrogen-bond based interactions in 2–4 have been complemented by calculating molecular electrostatic potential surfaces. In a competitive molecular recognition situation, the effectiveness of the -NH moiety as a hydrogen bond donor is comparable to that of the -CO...