Construction Of Imidazo[1,5-a]heterocyclic Ring Based On Cyclization Strategy Of 2-methylquinoline And Its Thioformylation Reaction

Imidazole heterocyclic compounds have a wide range of applications in the field of medicine,pesticides and optical materials,and chemists have been working on the development of efficient and simple synthesis strategies to build imidazole heterocyclic skeleton.2-Methylquinoline as a kind of material widely used in organic synthesis,plays a very important role in the field of heterocyclic synthesis.In this paper,a series of imidazo[1,5-a]quinoline compounds were constructed through the[2+3]cyclization pathway,based on the strategy of sp3C-H bond functionalization 2-methylquinoline.In addition the sulfur group is introduced on the imidazo[1,5-a]N-heterocycle under metal-free catalysis,and a series of sulfated imidazo[1,5-a]N-heterocyclic compounds were synthesized.The main contents are as follows:1.Cu-promoted construction of imidazo[1,5-a]quinoline ring based on 2-methylquinoline cyclization strategyWe have developed a stoichiometric copper-promoted strategy for synthesis of imidazo[1,5-a]quinoline compounds,2-methylquinoline compounds and benzylamine compounds as materials,through double oxidative amination of sp3C-H bonds pathway,under the conditions of di-t-butyl peroxide oxidation.After exploring the mechanism,we found that the sp3 C-H bond amination of 2-methyl quinoline is not through the quinoline-2-formaldehyde reaction intermediate.The strategy for synthesis of imidazo[1,5-a]quinoline based on cyclization of 2-methylquinoline is simpler and more efficient than the existing method.And the substrate does not require pre-carbonylation or pre-introduction of electron-withdrawing activating groups.Shortening the synthesis cycle of imidazo[1,5-a]N-heterocyclic compounds effectively.2.Iodine-catalyzed synthesis of thiomethylated imidazo[1,5-a]N-heterocycleThe introduction of sulfur groups to nitrogen-containing heterocyclic skeletons can improve their biochemical and physicochemical properties effectively.We have developed an iodine-catalyzed synthesis of imidazo[1,5-a]N-heterocycles.Diaryl disulfide,thiophenol and sulfonylhydrazide can all serve as the thioylation reagent to achieve the sulfonylation of the imidazo[1,5-a]N-heterocycl for this reaction.Using this method,we synthesized a series of arylthio-substituted and simple aliphatic thio-substituted imidazo[1,5-a]N-heterocycles.This simple and efficient method does not require the participation of transition metals,which greatly enriches the molecular libraries of imidazo[1,5-a]heterocycles and has great significance for screening effective new drugs and new types of fluorescent materials.In addition,we used pyridine-2-formaldehyde,amino acid and disulfide as materials to achieve the three-component one-pot strategy for synthesis of thiomethylated imidazo[1,5-a]N-heterocyclic compounds under the condition of the stoichiometric iodine.We have also selected a wide range of compounds with high antitumor activity from the newly synthesized thioylated imidazo[1,5-a]N-heterocyclic compounds.