Polymorphic solvates, ionic cocrystals and C–N bond formation to form ionic cocrystals in sulfamethoxazole and sulfathiazole-derived urea

Abstract

Two polymorphs of a dimethylformamide solvate of N-(5-methyl-1,2-oxazol-3-yl)-4-{[(4-nitrophenyl)carbamoyl]amino}benzene-1-sulfonamide (HSMZU) were studied to elucidate their structures, thermal stability and desolvation. The two synthon polymorphs of the solvate had distinguishable assemblies and the host in the polymorphs had slightly dissimilar geometries. Upon thermal desolvation, both solvates yielded a common form. The HSMZU formed an N-butylated derivative with tetrabutylammonium iodide (TBAI) through an unprecedented C–N bond formation reaction, and this butylated derivative yielded ionic cocrystals with TBAI. DMF and DMSO solvates of 4-{[(4-nitrophenyl)carbamoyl]amino}-N-(1,3-thiazol-2(3H)-ylidene)benzene-1-sulfonamide (HSTZU) had similar dimeric assemblies but had different conformations of the host. Desolvation of these two solvates yielded a common form. TBAI formed an ionic cocrystal with HSTZU, whereas dimers were formed by the host to provide hydrophobic space for the cation. Both the compounds were deprotonated by tetrabutylammonium fluoride to form salts, but HSMZU was unique in that it got deprotonated by tetrabutylammonium bromide under ordinary conditions. The visible spectra of both the salts originating from HSMZU as well as from HSTZU were identical due to the common chromophore in them.