Catalytic Synthesis of N-Acylsulfonamide Derivatives

The catalytic synthesis of N-acylsulfonamide derivatives has emerged as a versatile strategy for constructing structurally diverse compounds with broad applications in medicinal chemistry, agrochemicals and materials science. Central to these methods is the activation of sulfonamide N–H bonds towards acyl transfer, often achieved under mild conditions by employing transition-metal catalysts (for example Pd, Cu and Ni), Brønsted acids or solid-supported heterogeneous acids. Alternative approaches exploit organocatalytic systems, visible-light photocatalysis or enzyme mimetics to promote acylation using a variety of acyl donors such as acid chlorides, anhydrides or esters. Key mechanistic pathways involve nucleophilic attack of the sulfonamide nitrogen on an activated acyl intermediate, often enabled by in situ generation of electrophilic species or removal of water by a dehydrating agent. Recent advances have focused on sustainability, including solvent-free conditions, recyclable catalysts and green oxidants, while addressing challenges in chemoselectivity, substrate scope and scalability. The resulting N-acylsulfonamides serve as valuable scaffolds for peptidomimetic inhibitors, enzyme-targeting ligands and polymer precursors, underlining their global significance and practical utility.

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Catalytic Synthesis of N-Acylsulfonamide Derivatives publication trend

The graph below shows the total number of articles in catalytic synthesis of n-acylsulfonamide derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

N-Acylsulfonamide: A compound in which an acyl group is bonded to the nitrogen atom of a sulfonamide functional group.

Sulfonamide: An organic moiety featuring a sulfonyl (–SO₂–) group linked to an amine nitrogen, often employed as a pharmacophore.

Dehydrating agent: A reagent that facilitates removal of water to drive condensation reactions, enhancing yield and selectivity.

Radical initiator: A species that generates radical intermediates under thermal or photochemical activation, enabling radical-mediated transformations.

Single-electron transfer (SET): A mechanistic step in which one electron moves between species, forming radical ions that participate in bond-forming processes.

References

1. Eco-friendly and efficient catalyst-free synthesis of N -sulfonylimines from sulfonamides and aldehydes: crucial role of Al 2 O 3 as a reusable dehydrating agent. RSC Advances (2023).
2. Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines. Beilstein Journal of Organic Chemistry (2023).