Direct Trifluoromethysulfonation And Trifluoromethylation Of Aromatic Hydrocarbons Catalyzed By Copper

In recent years,the success of many fluorinated drugs has made the resear ch of fluorinated compounds,especially fluorinated compounds with biological a ctivity,increasingly attracting attention.The introduction of fluorinated groups in active natural products and drug molecules has improved the biological activity of compounds.The way that attracted the attention of organic chemists.This t opic will explore a reasonable reaction route for the introduction reaction of trif luoromethylsulfinyl and trifluoromethyl in active molecules.In the past,due to t he instability of intermediates in the introduction reaction,it is difficult for the fluorine-containing groups to access specific chemical structures,and the existin g introduction methods of aromatic trifluoromethylation and trifluoromethanesulfo nation are to use Expensive transition metal catalysts and harsh experimental co nditions are realized.The method has a narrow application range of substrates,uncontrollable side reactions,and low yields.Therefore,the development of a method for efficiently introducing trifluoromethylsulfinylation and trifluoromethyl ation is of great significance for the development of medicinal chemistry.This paper innovatively proposes copper-catalyzed synthesis of direct C-H trifluoromethanesulfonation and trifluoromethylation.By optimizing the reaction conditions such as catalyst type,oxidant type,solvent,reaction temperature,etc.,and rationally expanding the reaction substrate,we explored an experimental route with mild reaction conditions,simple operation,wide substrate application range,and good functional group compatibility:First,a new method for the direct trifluoromethanesulfonation of aromatics was systematically studied.Select Langlois reagent(CF3SO2Na)as the best trifluoromethyl reagent,explore the effects of different catalysts and their dosages,different oxidants and their dosages,solvents,reaction temperature and reaction time on the reaction,and then determine the best reaction conditions:Using copper acetate as the catalyst and iodobenzene diacetate as the oxidizing agent,under the condition of acetonitrile solvent,reacting at 85℃ for 1 hour,the orthotrifluoromethanesulfonation product can be obtained in moderate yield,and the functional group compatibility is good.In this project,a new method for the direct trifluoromethylation of aromatic hydrocarbons C-H is studied.Using sodium trifluoromethanesulfonate as the trifluoromethylation reagent,explore the effects of different catalysts and their amounts,different oxidants and their amounts,solvents,reaction temperature and reaction time on the reaction,and finally determine the best reaction conditions as:Cuprous chloride is the catalyst,TBHP is the oxidant for the reaction,and the mixed solution of 2,2,2,trifluoroethanol,dichloromethane and water is the reaction solvent.The reaction can be carried out at 50℃ for 12 hours with higher yield(55%-60%)to obtain the target product.This subject has developed innovatively,copper-catalyzed methods for triflu oromethylation and trifluoromethylsulfinylation of aromatic hydrocarbon C-H.Bo th methods have expanded substrates,the conditions are mild,and the fluorinati on reagents are cheap and easy to use The obtained sodium trifluoromethanesulf inate is green,environmentally friendly and economically feasible.It provides a reference for the synthesis of intermediates in organic synthesis and fine chemic als,and has broad application prospects.