Synthesis of 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides via ortho lithiation of protected benzaldehyde derivatives

Variously substituted 2-phenyl-1,3-dioxolanes and 2-(2-bromophenyl)-1,3-dioxolanes, prepared from the corresponding benzaldehydes, were lithiated ortho to the acetal group. Reaction of the lithio derivatives with sulfur dioxide led to the lithium sulfinate salts, which gave, upon oxidative chlorination with sulfuryl chloride, the corresponding benzenesulfonyl chlorides. Then, depending on the aromatic substitution pattern of the molecule, several protocols were elaborated for the functional group transformations leading to the target compounds. Ring closure was performed with hydrazine hydrate or acetylhydrazine, in the latter case with one-pot removal of the acetyl group. The 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides thus obtained are potential drug candidates based on their structural similarity to biologically active phthalazinones.