<i>N</i> -Chlorination of Sulfonamides: DFT Study of the Reaction Mechanism

Sulfonamides are frequently detected as emerging pollutants in an aqueous environment. In wastewaters, their chemical fate is affected by a reaction with a chlorinating agent. In this study, the <i>N</i>-chlorination of sulfonamides has been explored computationally using density functional theory. This oxidation is the initial step that triggers other rearrangements of the parent structure. All sulfonamides contain three or more nitrogen atoms, which may serve as chlorination sites. According to the calculated results, the aniline moiety is the most reactive site, which supports the experimental findings. The observed regioselectivity of <i>N</i>-chlorination in sulfonamides has been interpreted in terms of kinetic and thermodynamic profiles of the reaction. It is demonstrated that protonation states and tautomer forms of sulfonamides should be considered to accurately calculate the mechanism underlying the chlorination. In a neutral aqueous medium, only the anion is reactive species, whereas in an acidic medium, both neutral form and its tautomers may react with the chlorinating agent. Along with the <i>N</i>-chlorinated intermediate, quantum chemical calculations have been employed to describe the formation of the ring-chlorinated product, which is frequently observed as a by-product during chlorination of sulfonamides.