Trifluoroethylation Of Aromatic Amines Catalyzed By Metalloporphyrins

Organic molecmm3es containing fluorinated units are privileged structural applicatedinvariousfieldsincludingpharmaceutical,agrochemicaland materials.Aniline derivatives containing electron-withdrawing group such as2,2,2-trifluoroethyl group are more valuable than the parent anilines in medical chemistry for anlines are more easily oxidized.The demand for them promote the development of methods for their synthesis.For example,much advances have been achieved trifluoromethyl reactions.However,the methods of preparing the organic molecmm3es containing N-trifluoroethyl group which are the core units of many drugs,agrochemicals and related candidates are relatively less,therefore the discovery of some drugs and agrochemicals is limited.In this paper,the trifluoroethylation of amine with trifluoroethylamine hydrochloride catalyzed by metalloporphyrin was systematically studied,including the influence factors in the reaction,expansion of reaction system and the mechanism of the metalloporphyrin-catalyzed trifluoroethylation system.The details are summarized as follows:1.FeTPPCl was synthesized and used several other metalloporphyrins and metal salts existing in the laboratory and their catalytic performances for the trifluoroethylation of amine with trifluoroethylamine hydrochloride were investigated.We found when FeTPPCl as catalyst,the catalytic activity was best,the yield up to78%.2.A systematic study on the amine trifluorothylation catalyzed by FeTPPCl was carried out.The effects ofamount of reactant,addition order of reactant,reaction time,reaction tempeture,types of acid were examed.The optimized reaction conditions is shown as follow:the amount of trifluoroethylamine hydrochloride was 81.3 mg,the volume of acetic acid was 36 mm~3,the amount of sodium nitrite was 42 mg,the volume of water was 2 cm~3,the volume of dichloromethane was 2 cm~3,the amount of FeTPPCl was 2 mg,the volume of amine was 28 mm~3,The reaction temperature of the one and two step was at normal temperature.The time of first step of synthesis trifluoromethyl diazomethane was 30 min,the time of second step was 12 h.3.The scope of trifluorothylation of primary amines with trifluoroethylamine hydrochloride catalyzed by FeTPPCl was investigated.The study found that the aromatic ring with electron donating substituents trifluorothylation yield was better than electron-withdrawing substituent.The position and volume of the substituent on the aromatic ring has great influence on the trifluorothylation.4.The organic solvent dichloromethane was replaced with dichloroethane under the same conditions and the temperature of second step was raised to 80℃.The trifluorothylation reaction was carried out with N-methylaniline as substrate,and the yield of trifluorothylation was 72%.5.The scope of trifluorothylation of secondary amine with trifluoroethylamine hydrochloride catalyzed by FeTPPCl was investigated.The study found that the aromatic ring with electron donating substituents trifluorothylation yield was similar good with electron-withdrawing substituent.6.Combining the related literatures with our preliminary research on the role of metalloporphyrin,we proposed a possible mechanism of metalloporphyrin-catalyzed trifluorothylation of amines with trifluoroethylamine hydrochloride,which involved an iron-nitrogen transition state examined by ESR and UV spectrophotometer.