Construction Of Nitrogen-containing Heterocyclic Skeletons Via Oxidative Cyclization Of N-aryl Amidines

Nitrogen-containing heterocyclic compounds, such as, benzimidazoles, pyrido[1,2-a]benzimidazoles, and quinazolines, possess a wide range of biological activities and certain fluorescence properties. Therefore, construction of these heterocyclic frameworks has been a hot research topic. In past decade, significant progress has been made in their synthesis via transition-metal-catalyzed C–H bond functionaliztion or hypervalent iodine-mediated oxidative cyclization. Meanwhile, as an inexpensive, readily available, and eco-friendly oxidant, utilization of molecular iodine in heterocycle synthesis has drawn considerable attention from organic and medicinal chemists.In this thesis, we have successfully developped three I2-mediated oxidative cyclization reactions of different N-aryl amidines to synthesize the three classes of heterocyclic compounds mentioned above, respectively:（1） Sixteen benzimidazoles were synthesized through I2/KI-mediated aryl sp₂ C–H bond amination from N-aryl amidines in 44–82% yields. The required substrates could be readily prepared via addition of substituted anilines to nitriles. The features of this synthetic method include eviromental friendliness, simple operation proceudures, and broad substrate scope to access to both 2-aryl and 2-alkyl subsituted benzimidazoles.（2） Similarly, twelve pyrido[1,2-a]benzimidazoles were prepared from Nphenylpyridin-2-amines in 65–99% yields. Some of these deriavitives exhibited promising fluorescence properties.（3） Twenty-three quinazoline derivatives were synthesized via I2/KI-mediated oxidative C–C bond construction from N-benzyl-N′-phenyl/alkyl amidines in 37–99% yields. This transition-metal-free reaction is efficient, operationally simple, and applicable to broad substrate scope. Moreover, the four-step synthetic process can be successfully conducted in gram scale from simple amines and acyl chlorides without purification of the intermediates.