Metal-free construction of primary sulfonamides through three diverse salts

In this report, the first metal-free construction of primary sulfonamides through a direct three-component reaction of sodium metabisulfite, sodium azide and aryldiazonium has been established. Readily available inorganic Na 2 S 2 O 5 and NaN 3 were applied as the sulfur dioxide surrogate and nitrogen source respectively. The widely used sulfonamide drugs Celecoxib and Sulpiride, which possess multiple heteroatoms and active hydrogen containing functional groups, are efficiently installed with -SO 2 NH 2 groups at a late stage. Control experiments and kinetic studies demonstrated that aryl radicals, sulfonyl radicals and conjugated phosphine imine radicals are involved in this transformation. The first metal-free pathway to access primary sulfonamides has been developed through three diverse salts Na 2 S 2 O 5 , NaN 3 , and aryldiazonium.