Nickle-catalyzed Thioetherification Of Aza-arenes Without The Assistance Of Directing Groups

Nitrogen-containing heterocycles are widely present in natural products and synthetic drugs,and play an irreplaceable role in disease treatment;in addition,they also have excellent application prospects in the field of optoelectronic functional materials.Similarly,the synthesis and application value of thioether compounds in medicine,biology and polymer materials cannot be underestimated.Therefore,the synthesis of nitrogen-containing heterocyclic sulfide compounds is very important.In recent years,with the rapid increase of resource input in the field of biomedicine and n ew energy industries,related industries have put forward higher requirements for the large-scale and efficient synthesis of biologically active compounds and new functional molecules.The traditional methods of synthesizing sulfide compounds can not meet the requirements of efficiency and environmental protection.In recent years,transition metal-catalyzed C-H bond activation and functionalization have provided new ideas for the convenient and efficient synthesis of nitrogen-containing heterocyclic sulfide compounds.However,some problems are obvious.For example,excessively high reaction temperature leads to the formation of more by-products and the use of precious metal catalysts increases production costs.Therefore,the development of a cheap metal-catalyzed nitrogen-containing heterocyclic thioetherification method with mild conditions and rapid reaction is of great significance in the field of organic synthesis.The second chapter of this paper reports a method of thioetherification of nitrogen-containing heterocyclic aromatic hydrocarbons.The reaction conditions are mild and the reaction can be completed in a short time.It can realize thioetherification for various heterocycles such as quinoline,isoquinoline,7,8-benzoquinoline,benzothiazole and Nmethylbenzimidazole.In addition,both aromatic disulfide and alkyl disulfide can be used as thioetherification reagents,and the reaction are compatible with various substituents such as methyl,methoxy,fluorine,chlorine,bromine,acyl,and cyano.Related control experiments show that the reaction mechanism involves the formation of the anionic complex intermediates and the electrophilic attack of disulfide.The gram-level synthesis of potential Alzheimer's disease drugs reveals the synthetic application value of this method.The third chapter of this thesis developed a nickel-catalyzed direct thioetherification method of 8-aminoquinoline with high site selectivity for C3-H.The reaction can be conducted at room temperature within a short period of time.This reaction is compatible with a series of 8-aminoquinolines protected by amide groups,and the protective group can be removed in excellent yield.For disulfide substrates,diphenyl disulfide,heterocyclic aryl disulfide and alkyl disulfide with vari ous electron donating groups and electron withdrawing groups,the reaction can all be completed with good to outstanding yields.