Piloty's acid and its hydrazide analogue: Insights from the density functional theory and vibrational spectroscopy on the conformational stability and chemical reactivity

N-hydroxybenzenesulfonamide (commonly known as Piloty's acid) is considered a major source for nitroxyl (HNO) species which has potential biological and medicinal applications. In the present study, the conformational preferences and chemical reactivity of Piloty's acid (PA) and its hydrazide analogue (benzenesulfonylhydrazide, BSH) were studied using spectroscopic and computational tools. Six stable conformations of each molecule were theoretically identified, and their structures were fully optimized at the DFT-B3LYP and MP2 levels. Both molecules in their most stable forms adopt the anti configuration with the N[sbnd]H bond of the secondary amine pointing away from the terminal hydroxyl and amine moieties in the acid and hydrazide molecules, respectively. Three stable gauche states facilitated by weak intramolecular interactions of the S[dbnd]O⋯H[sbnd]O and S[dbnd]O⋯H[sbnd]N types arise due to the internal rotation about the S[sbnd]N linkage. Reliable assignments of the vibrational modes and the calculated reaction coordinates support a two-step mechanistic pathway of the Piloty's acid dissociation leading to the production of the nitroxyl (HNO) intermediate with moderate transition state barriers. Frontier molecular orbitals distributions, molecular electrostatic potential maps and condensed Fukui functions analysis of the molecules were employed to elucidate the agility of PA to dissociate to produce HNO and the absence of such a dissociation of BSH that would produce diazene (N₂H₂).