Study Of Synthesis Of Nitrogen Heterocycle Compounds As Antiviral Drugs

Nitrogen heterocycles exhibit diverse biological and pharmacological activities. In recent years, copper, iron-catalyzed Ullmann coupling reactions have attracted much attention, and some useful domino processes have been developed to construct nitrogen heterocycles via Cu-catalyzed Ullmann-type reactions. In this thesis, we have developed new copper or iron-catalyzed cascade processes for the formation of three kinds of nitrogen heterocycles, and some results were obtained as follows:An efficient method for synthesis of benzimidazoles and 2-substituted 1H-benzimidazoles has been developed via copper-catalyzed cascade reactions of o-haloacetoanilide derivatives with amidine hydrochlorides. The protocol uses 10 mol% CuI as the catalyst, Cs2CO3 as the base and DMSO as the solvent, and no ligand is required because of ortho-substituent effect of -NHCOCH3 group.An efficient method for synthesis of 1,2,4-benzothiadiazine-1,1-dioxide derivatives has been developed. The protocol uses readily available substituted 2-halobenzenesulfonamides and amidine hydrochlorides as starting materials, 10 mol% CuI as the catalyst, Cs2CO3 as the base and DMF as the solvent, and no any ligand or additive was required because of ortho-substituent effect of -SO2NH2 group.We have developed an iron-catalyzed approach to 1,2,4-benzothiadiazine-1,1- dioxide and quinazolinone derivatives. The method uses readily available substituted 2-halobenzenesulfonamides, 2-bromobenzoic acids and amidine hydrochlorides as starting materials, and inexpensive and environmentally friendly FeCl3 as the catalyst, and no any ligand and additive was required because of ortho-substituent effect of -SO2NH2 and–COOH groups. The method is of practical applications for synthesis of the two kinds of nitrogen-containing heterocycles, and shows simple, economical and practical advantages over the previous methods. This is the first example for construction of nitrogen-containing heterocycles via iron-catalyzed N-arylation in the absence of ligand.