Copper-catalyzed Pyridine-directed Csp~2-H Halogenation And Triflouromethylation Of Aromatic Amines

Direct functionalization of the C-H bonds in aromatic compounds has always been an efficient way to construct carbon-hetero bonds.In recent years,the transition metal-catalyzed functionalization of the C-H bond of aromatic amines has become an important method for structure modification of aromatic amine compounds and the synthesis of aromatic amine derivatives.In this thesis,the selective halogenation and trifluoromethylation of aromatic amine compounds were achieved by using pyridine guided groups as substrates and copper salts as catalysts,and their applications in drug synthesis were expanded.The thesis was divided into the following three chapters.In the first chapter,the progress of the transition metal-catalyzed bidentate-directed aromatic amine Csp²-H functionalization reaction was reviewed.In the second chapter,the C-X?X=Cl,Br?reaction of aromatic amine catalyzed by copper guided by pyridine under mild conditions was reported.This method used aromatic amine derivatives and halogenated succinimide as the raw materials to selectively synthesized halogenated aromatic amine compounds.This reaction materials were simple and easy to be obtained,with high yield and substrate tolerance.In the third chapter,a simple protocol for the synthesis of2-?trifluoromethyl?aniline derivatives through a coordinating activation strategy was developed,and the recovery of the high yield of the guide group was realized,providing a new effective path for the synthesis of floctafenine.With pyridine aniline compounds and CF₃SO₂Na as the starting materials,and Cu Br as a catalyst,trifluoromethylation was acquired in a medium to good yields,then,2-?trifluoromethyl?aniline was obtained by stripping the guide group through hydrolysis reaction,and then the analgesic floctafenine was obtained through a series of reactions with Meldrum's acid and isatoic anhydride as the raw material.