Stability of Heteroaromatic Sulfonyl Chlorides and Fluorides

Stability of five- and six-membered heteroaromatic sulfonyl halides—essential reactants in various fields of chemistry—has been comprehensively studied. Based on experimental data obtained for 236 representatives (165 of them were specially synthesized for this work for the first time), several decomposition pathways were established, along with the stability trends for each heterocyclic system. These pathways include formal SO₂ extrusion (characteristic of pyridine-2- and pyridine-4-sulfonyl chlorides and most diazine derivatives), hydrolysis by trace water (typical for pyridine-3-sulfonyl chlorides and some azoles), reactions at other functional groups (specific to the substrate), and complex decomposition likely related to the limited stability of the heterocycle itself in the presence of electrophilic moieties (observed for furan, isoxazole, and some isothiazole derivatives). Based on these results, simple rules of thumb are proposed for selecting an appropriate heterocyclic sulfonyl halide to use in chemical synthesis, that is, chloride versus more stable but less reactive fluoride.