Studies Of Synthesis Of Benzothiadiazine Derivatives And Palladium-catalyzed C-H Bond Functionalization

Benzothiadiazine dioxides and their derivatives exhibit excellent performance in medicine.It has a wide range of biological and pharmacological activities,including diuretics,antihypertensive,KATP channel activators and anticancer activity,Alzheimer's disease,the early stages of treatment,etc.In this thesis,we mainly studied the synthesis of 3-aryl-2H-benzo[1,2,4]thiadiazine 1,1-dioxides via metal-free sequential dual oxidative amination of sp3 C-H bonds and palladium catalyzed C-H functionlization of 3-aryl-2H-benzo[1,2,4] thiadiazine 1,1-dioxidesFirstly,we studied the synthesis of 2-aryl benzothidiazine-1,1-dioxides by using ortho amino benzene sulfonamide and toluene as substrates.The reaction was well performed with the DTBP/TFA via metal-free sequential dual oxidative amination of sp3 C-H bonds to obtain the desired products in up to 93% yield.This novel protocol shows some distinguished characteristics,such as the lack of any expensive transition metals,excellent functional group tolerance and a broad substrate scope.Secondly,we applied the above synthesized benzothiadiazine-1,1-dioxides products to study the palladium-catalyzed direct arylation of C(sp2)–H bonds reactions.The 3-Aryl-2H-benzo[1,2,4] thiadiazine 1,1-dioxides react with various aryl iodides to give the corresponding mono-arylation products in up to 92% yield with high reactivity and regioselectivity in the presence of AgOAc.Remarkedly,the addition of TFA is crucial to improve the arylation.Finally,we studied the palladium catalyzed C-H alkylation of 2-aryl benzothidiazine-1,1-dioxides by using epoxide as an alkylation partner,and satisfactory results were obtained.