Charge and energy redistribution in sulfonamides undergoing conformational changes. Hybridization as a controlling influence over conformer stability

Abstract

The redistribution of charge and electronic kinetic energy was studied during rotation about the S—N bonds of sulfonamide and fluorosulfonamide. The rotational potentials and electronic topological features of both compounds were evaluated at the HF/6-3 1G* level of theory and their electron densities partitioned into atomic contributions using FASTINT, an updated version of the PROAIM program. The results indicate that the stability of each rotamer is strongly dependent upon the hybridization of the sulfonamide nitrogen. The hybridization of the nitrogen was determined by examination of the positions and magnitudes of the electrostatic and Laplacian minima in the nonbonded region of the sulfonamide nitrogen atom. Independent assessments of hybridization were made using nitrogen pyramidalization altitudes. The rotational barriers in these compounds were found to arise mainly from energetic penalties resulting from adding electrons to already electron-rich sulfonyl oxygens while removing electron density from other more electronegative atoms. The fluorine-substituted analogue provided an example in which the sulfur and oxygen atoms were much less electron rich, causing an enhancement of the nitrogen rehybridization effects. The extent of covalent bonding between pertinent pairs of atoms in sulfonamide and fluorosulfonamide was assessed throughout the rotational pathway using the BONDER program. In contrast with much existing dogma, all of these findings were consistent with the same general model of charge and energy flow that has been shown to determine the internal rotational barriers in amides. Key words: sulfonamide, electron density analysis, rotational barrier, hybridization, atoms-in-molecules calculations.