Copper-Catalyzed Synthesis Of Quinazoline Derivatives

Nitrogen-containing heterocycles widely exist in nature, and many nitrogen–containing compounds show good biological and pharmaceutical activity. Quinazolinederivatives are a kind of important nitrogen-containing heterocyclic compounds, andthey are common constituents of natural products. Recently, quinazoline derivativeshave attracted much attention because of their biologically and pharmacologicallyactivities and diversity of structures. In this dissertation, the copper-catalyzed synthesisof quinazoline derivatives were performed, and some important results were obtained asfollows:An efficient copper-catalyzed method for synthesis of quinazoline derivatives hasbeen developed via cascade reactions of (2-bromophenyl)methanamine derivatives witharyl amides. Reaction of (2-bromophenyl)methylamine with benzamide was used as themodel to optimize reaction conditions including catalysts, bases and solvents. Theprotocol uses CuI as the catalyst, K2CO3as the base, and isopropanol as the solventafter optimization of reaction conditions. The corresponding quinazoline derivativeswere obtained in good yields under mild conditions without the addition of ligands oradditive. The results showed that the substituted (2-bromophenyl)methylaminescontaining electron-donating groups showed slightly lower reactivity. The cascadereactions could tolerate various functional groups including C-F bond, nitro, ether bondand heterocycle in the amides. The reaction mechanism underwent N-arylation,intramolecular cycliazation, and aerobic oxidation process.A convenient and efficient copper-catalyzed method for synthesis of substitutedbenzimidazoquinazoline derivatives has been developed via cascade reactions ofsubstituted2-(2-halophenyl)-1H-benzo[d]imidazoles with arylmethanamines.2-(2-Bromophenyl)-1H-benzo[d]imidazole and phenylmethanamine were chosen as themodel substrates to optimize reaction conditions including catalysts, bases and solvents.The protocol uses CuI as the catalyst, K2CO3as the base, and DMSO as the solventafter optimization of reaction conditions. The corresponding benzimidazoquinazolinederivatives were prepared without addition of any ligand or additive. The substratescontaining ortho-methyl group showed a lower yield because of steric hindrance. Thearyl iodides showed higher reactivity than the aryl bromides for substituted 2-(2-halophenyl)-1H-benzo[d]imidazoles. The reaction mechanism underwent thesequential process: N-arylation, aerobic oxidation to formation of C=N bond,intramolecular cycliazation, and final aerobic oxidation to the target product. Thepresent method can provide a new route for construction of N-heterocycles.