Electrochemical <i>N</i>-sulfonylation of <i>in situ</i> generated indole-based hydrazones and antimicrobial evaluation

Herein, we report a novel metal-free electrochemical strategy for regioselective <i>N</i>-sulfonylation of <i>in situ</i> generated indole-based hydrazones using readily available sodium sulfinates. The feasibility of the protocol was demonstrated by employing differently substituted aldehydes, hydrazines, and sodium sulfinates to access <i>N</i>-sulfonylated products in up to 81% isolated yield. Furthermore, various control experiments and cyclic voltammetry studies were performed to get valuable mechanistic insights. These studies suggested the formation of indole-phenyldiazenium as an intermediate while ruling out the possibility of any radical formation during this transformation. In addition, the synthesized compounds were tested for antibacterial activity against Gram-positive and Gram-negative pathogens. Among them, compounds 5d, 5e, 5l, and 5q were found to have strong and selective antibacterial activity against <i>Staphylococcus aureus</i>, with 5d being the most potent (MIC = 6.87 μM), while showing only moderate activity against Gram-negative pathogens. Furthermore, scanning electron microscopy (SEM) analysis revealed that the most promising hit (5d) causes significant morphological alterations and exerts its effects by causing considerable cellular damage.