Construction Of C-C/C-N Bonds By C-H Functionalization And Its Application In The Synthesis Of Aromatic Heterocycles

The construction of C-C and C-N bonds is one of the important methods to obtain potential pharmacologically active heterocyclic compounds.Therefore,C-H bond functionalization has been an attractive topic in the field of pharmaceutical chemistry.Although metal-catalyzed C-H bond activation has gained considerable development,it has disadvantages such as high cost,high toxicity and troublesome post-treatment.With the increase of environmental protection requirements,the study on efficient C-H bond functionalization with nonmetal catalysis is of great significance.In recent years,the rapid development of visible light catalysis,due to the use of clean environmental LED light as a light source,mild reaction conditions,simple operation and green environmental protection,affording a high theoretical research significance and potential application prospects.Aromatic heterocyclic structure exists in many natural products and drug molecules,exhibiting a wide range of biological characteristics and pharmacological activities,such as antibacterial,anti-tumor and so on.Therefore,it is of great value to explore green,efficient,economical and environmentally friendly strategy for the construction of aromatic heterocyclic ring.In this thesis,the functionalization of C-H bond catalyzed by nonmetal or visible light is studied,which mainly includes the following parts:1.The C-H cyanation reaction at the 3-position of the quinoxalin-2（1H）-one derivativesIn this paper,cheap and readily available ammonium thiocyanate was used as a cyanyl source and tert-butyl hydrogen peroxide was used as an oxidant to carry out C-H bond cyanylation of quinoxalin-2（1H）-one at the 3-position under mild conditions for the first time.The reaction avoids the use of noble metal catalysts and has high selectivity and functional group compatibility.The reaction system was carried out at room temperature and the target product could be obtained with good yield.Mechanistic studies have shown that the cyano anion generated by thiocyanate and peroxide,then attacking the quinoxaline-2（1H）-ketone radical cation and finally obtains the cyanation product.2.The C-H trifluoromethylation reaction at the 3-position of the quinoxalin-2（1H）-one derivativesIn this paper,visible light was used as an energy source,and sodium trifluorosulfonic acid was used as a trifluoromethylated source.Under the irradiation of blue light,trifluoromethylated C-H bond on quinoxalin-2（1H）-one was successfully realized.In addition,it was found that the quinoxalin-2（1H）-one substrate and the target product after trifluoromethylation have the ability to absorb blue light（≥400nm）and act as a photocatalyst to achieve an autocatalytic cycle of the reaction,avoiding the addition of an additional photocatalyst.Compared with the previous C-H trifluoromethylation of quinoxalin-2（1H）-ones,The method only uses oxygen in the air as oxidant,and the reaction conditions are simple,efficient and mild.3.C-N coupling reaction of azolesIn this paper,Ru（bpy）₃Cl₂·6H₂O was used as photosensitizer to realize visible-light-mediated C-N coupling reaction between azoles and aromatic.It was found that benzimidazoles,tetrazoliums,triazoles,pyrazols were all compatible under this condition.Aromatic olefins containing various electron deficient and electron substituent groups can also participate in the reaction efficiently.This method provides a simple,efficient and economical approach to synthesize N-alkylazole derivatives.