Efficient Cu-Catalyzed Synthesis of 1,2,4-Benzothiadiazine-1,1-dioxides

Significance

A Cu-catalyzed method for the synthesis of 1,2,4-benzothiadiazine-1,1-dioxides by heteroannulation of amidine hydrochlorides to 2-halobenzenesulfonamides has been developed. Other copper sources afforded low yields of product, but CuBr was found to be the best catalyst. Use of toluene as a solvent led to no reaction. The substrate scope was moderately studied, the yields were found to be high, and both bromo- and iodosulfonamides participated well in the reaction. No chloro substrates were tested, and X = H substrates showed no reaction. Using ^¹5N-labeled amidine for the reaction allowed the conclusion that attack of the amidine on the sulfonamide can be ruled out.