Advances in Catalytic and Metal-Free Synthesis of Benzothiadiazine 1-Oxides, 1,1-Dioxides, and 1-Imines.

Benzothiadiazine derivatives are an important class of sulfur-nitrogen heterocycles widely recognized in medicinal chemistry for their structural flexibility and varied biological effects. This review highlights recent developments in the synthesis of benzothiadiazine-derived compounds, including 1-oxides, 1,1-dioxides, and newly explored 1-imines. It focuses on contemporary synthetic methods, including transition-metal catalysis, cascade reactions, heterogeneous catalysis (polyoxometalates and metal-organic frameworks), and environmentally friendly metal-free approaches. The review discusses the scope, effectiveness, and limitations of these techniques, alongside their key biological applications in cardiovascular, anticancer, antiviral, and neurological fields. Additionally, it underscores existing challenges and future research directions to foster the development of more efficient and sustainable synthetic strategies.