Acidity of arylsulfonamides as function of quantum chemical parameters of sulfonamide nitrogen

Abstract

The structures of aromatic sulfonamide molecules XPhSO₂NH₂ (X = H, 4-Me, 4-F, 4-Cl, 4-Br, 4-MeO, 4-OH, 4-NH₂, 4-CN, 3-NO₂, 4-NO₂, 3,5-(NO₂)₂, 3,4-Cl₂, 3-Cl-4-Me, 3,4-Me₂, 3-Me-4-F, 2-Me) were calculated at the M06/6-311++G** (SMD) level of theory. The atomic electrostatic potentials (AEP) and the Hirshfeld charges of the sulfonamide nitrogen atoms were determined. Correlation equations relating the AEP to Bronsted acidities (pK_a) of these compounds were obtained using published data and the previously unknown pK_a values for a number of arylsulfonamides were calculated. These pK_a values are consistent with independently determined free energies of acid dissociation of sulfonamides.