The Synthesis Of 3-(Trifluoromethyl)-aniline And Its Derivatives

3-(trifluoromethyl)-aniline is an important pharmaceutical and chemical intermediates. The amino-group has the strong reactivity thus it can synthesize a series of compounds. 3-(trifluoromethyl)-aniline was prepared using trifluorotoluene as original material, mixed acid as nitrating agent, Bi2O3/C as catalyst and hydrazine hydrate as reductant. Bi2O3/C catalysts were prepared by hydrothermal method using Bi(NO3)3 and NaOH as raw materials and activated carbon as carrier. The catalysts were characterized by X-ray diffraction (XRD). The XRD patterns indicated that bismuth oxide existed in Bi2O3/C catalyst with 8-form. The effect of various reaction parameters for the reduction reaction of 1-Nitro-3-(trifluoromethyl) benzene compounds with hydrazine hydrate to 3-(trifluoromethyl)-aniline, including the category of catalysts, the amount of catalysts, material ratio, solvents and reaction temperature, was investigated in detail and the orthogonal test was carried out. The results revealed that 0.002M Bi2O3/C showed excellent catalytic activity; in reflux of ethanol, the catalytic activity was maintained after 9 runs; the optimal reaction conditions were confirmed as follows:in 25 mL ethanol, the amount of 0.002M Bi2O3/C catalyst was 0.1 g, the reaction temperature 70℃ and the molar ratio of hydrazine hydrate and 1-Nitro-3-(trifluoromethyl) benzene 2:1. The XPS spectra showed that Bismuth doesn’t loss and the valence of Bi didn’t change in 0.002M Bi2O3/C unused and reused. The presence of azobenzene and azoxybenzene compounds detected in the reaction solution further validated the recognized reaction mechanism.Flutamide is a kind of anti-androgen drugs and can be used to treat prostate cancer. Flutamide was prepared using 3-(trifluoromethyl)-aniline as raw material, amidating with isobutyric anhydride, then nitration with mixed acid. The effect of various reaction parameters for the amidating reaction and nitration reaction was investigated in detail and the orthogonal test was carried out. In the amidating reaction, the optimal material ratio of 3-(trifluoromethyl)-aniline and isobutyric anhydride is 1:1 and the optimal solvent is hexane. In the nitration reaction, the volume ratio of nitric acid and sulfuric acid of 1:10, the reaction temperature is-5 ℃, the molar ratio of nitric acid and 2-methyl-N-[3-(trifluoromethyl)phenyl]-propionamide is 1.1:1. The recrystallization of Flutamide used ethanol and petroleum ether as solvents, which avoided the use of benzene and toluene banned or limited in the Chinese Pharmacopoeia, achieving high purity.Semicarbazone compounds have good biological activity after cooperation with metal compounds, and also have promising application in magnetic materials, molecular recognition, optical materials, catalytes and so on. N-[3-(trifluoromethyl) phenyl]-hydrazinecarboxamide was prepared with 3-(trifluoromethyl)-aniline as raw materials, and respectively by the isocyanate two-step method, isocyanate one-pot method, carbamic acid ester sonication method and carbamic acid ester reflux method. Then 2-Thiophenecarboxaldehyde-N(4)-3-(trifluoromethyl)-phenylsemicarbazone and 2-Pyridine carboxaldehyde-N(4)-3-(trifluoro-methyl)-phenylsemicarbazone were prepared by reaction of 2-thiophenecarboxaldehyde and 2-Pyridinecarboxaldehyde. The results revealed that the high yield and environmental friendly method of synthesizing N-[3-(trifluoromethyl) phenyl]-hydrazinecarboxamide is arbamic acid ester sonication method, and 2-Thiophenecarboxaldehyde is easier than 2-Pyridine-carboxalde-hyde to react with N-[3-(trifluoromethyl) phenyl]-hydrazinecarboxamide to generate semicarbazone.