Study On The Synthesis Of 2-(3,4-dichlorophenyl)-4-fluoroaniline

Suzuki coupling reaction,one of the cross coupling reactions catalyzed by palladium,has many advantages,such as a strong adaptability to substrate,a wide applicability to functional group,high reaction activity and so on.It is commonly used in the synthesis of biphenyl derivatives as well as a large number of organic materials in natural products,which won the 2010 Nobel Prize in chemistry.Cross coupling reaction catalyzed by palladium is one of the most advanced tools owned by today's chemists,which can effectively help chemists get new substances.2-(3,4-dichlorophenyl)-4-fluoroaniline,an important intermediate in the synthesis of Bixafen,is widely used in pesticide,medicine,electronic materials and other fields.The study of its synthesis method is of great significance to the industrialization of Bixafen.In this paper,cross coupling catalyzed by organometallic was chosen to be main method,after deeply studied(Intramolecular coupling,electrochemical coupling and organometallic coupling).4-fluoroaniline and 1,2-dichlorobenzene were chosen as raw materials.4-fluoroaniline was acetylated and brominated.1,2-dichlorobenzene was brominated then synthesized to 3,4-dichlorophenyl-magnesium bromide with Grignard reaction,which was dropped in trimethyl borate,then hydrolyzed to get 3,4-dichlorophenylboronic acid.Then catalysts,bases and solvents in Suzuki coupling reaction were respectively studied.Tetrakis(triphenyl phosphine)palladium was chosen to be catalyzer,potassium phosphate to be alkali and acetonitrile and water as solvent.We got 2-(3,4-dichlorophenyl)-4-fluoroaniline under 80 C for 4h,then deacetylated by sulfoxide chloride with a yield of 98%.The final product was got by chromatography column,yield 66.3%,the intermediate and final products were characterized by HPLC,GC,GC-MS,NMR,It is a new and effective method for the synthesis of diphenyl derivates.As the substrate in decarboxylation coupling is simple and the literature yield in decarboxylation coupling catalyzed by bimetal is high.3-fluoro-benzoicacid were nitrified with fuming nitric acid,then decarboxylation coupled with 1-bromo-3,4-dichlorobenzene,The combination of different metals and catalysts,bases and ligands in the synthesis for 2-(3,4-dichlorophenyl)-4-fluoro nitrobenzene were studied.Since its reaction is strictly anhydrous anaerobic,but in the first step the salt formation reaction of benzoic acid and potassium carbonate can produce water,the effective product is still not got,effective reaction conditions are still under exploration.