N-(acridin-9-yl)arenesulfonamides: Synthesis, quantum chemical studies and crystal structure analysis to establish the tautomeric preferences

Abstract

The potentiality of the N-(acridin-9-yl)arenesulfonamide moiety as a hybrid pharmacophore due to the distinct pharmacological activities of acridines and aryl/heteroaryl sulfonamides prompts to synthesise N-(acridin-9-yl)arenesulfonamides and study their structural properties. Various N-(acridin-9-yl)arene/heteroarenesulfonamides were obtained through the development of a new methodology adopting the Pd2(dba)3-catalyzed C–N bond formation strategy for the reaction of 9-chloloroacridine with arene/heteroarenesulfonamides. The 1H and 13C NMR spectra suggest these N-(acridin-9-yl)arene/heteroarenesulfonamides to exist solely as the sulfonimide tautomer rather than anticipated sulfonamide form and was confirmed by the single crystal XRD analysis of one of the newly synthesized compounds. The quantum chemical studies rationalized this tautomeric preference revealing that the sulfonimide tautomers are more stable than the sulfonamide tautomers by −0.67 to −5.12 kcal/mol in the gas phase. In the solid state, the sulfonimide tautomer is stabilized by intermolecular hydrogen bond between N–H⋯O–S and π− π stacking between the acridine rings.