Synthesis and Applications of Sulfonamides

Sulfonamides constitute a versatile class of compounds characterised by the sulfonyl functional group attached to an amine, and they have long been valued for their broad biological activity and synthetic flexibility. Traditional syntheses rely on the reaction of sulfonyl chlorides with amines, yet modern approaches have diversified to include metal-catalysed couplings, organocatalysis and electrochemical protocols that align with green-chemistry principles. Recent advances have emphasised in situ generation of reactive intermediates, minimisation of hazardous reagents and one-pot procedures. In parallel, applications of sulfonamides extend from antibacterial and anticancer agents to enzyme inhibitors, ion-channel modulators and functional materials. Their capacity for structural modification enables fine tuning of pharmacokinetic properties and interaction with biological targets, while emerging uses in polymer sciences and sensing technologies underscore their global significance in both health and industry.

Research from Nature Portfolio

Recent studies have introduced a convergent paired electro-organic synthesis of sulfonamide derivatives under catalyst- and halogen-free conditions. In this method, nitroarenes undergo cathodic reduction to hydroxylamines and anodic oxidation to nitroso intermediates, while sulfonyl hydrazides are oxidised to sulfinic acids at the anode. The simultaneous generation of electrophilic nitroso species and nucleophilic sulfinic acids in a single electrochemical cell yields sulfonamides in a one-pot sequence. This protocol adheres to green-chemistry metrics by eliminating external oxidants and metal catalysts, offering high selectivity and the prospect of scalable, waste-minimised production.

Synthesis and Applications of Sulfonamides publication trend

The graph below shows the total number of articles in synthesis and applications of sulfonamides across all publications each year (not limited to Nature Index journals).

Technical terms

Sulfonamide: An organic compound bearing a –SO2–NH– linkage between a sulfonyl group and an amine.

Nitroso compound: An intermediate containing an –N=O moiety, often formed by oxidation of hydroxylamines.

Sulfinic acid: A compound with the general formula R–SO2H, serving as a nucleophilic precursor in sulfonamide synthesis.

Electro-organic synthesis: A method that uses electrical current to drive redox reactions and generate reactive intermediates in situ.

References

1. A new type of convergent paired electrochemical synthesis of sulfonamides under green and catalyst-free conditions. Scientific Reports (2023).
2. Nitro-sulfinate Reductive Coupling to Access (Hetero)aryl Sulfonamides. The Journal of Organic Chemistry (2024).
3. Construction of Benzenesulfonamide Derivatives via Copper and Visible Light-induced Azides and S(O)2–H Coupling. Molecules (2022).