General procedure for the synthesis of 3-(trifluoromethyl)-1H-1,2,4-triazole from ethyl trifluoroacetate and formamidine acetate: first, hydrazine monohydrate (4.8 g, 96 mmol) was dissolved in industrial methanol (160 mL) and the solution was cooled to 0 °C. Subsequently, ethyl trifluoroacetate (14 g, 100 mmol; purchased from Aldrich Chemical Company, Inc., Milwaukee, WI) was slowly added dropwise. The reaction mixture was gradually warmed to room temperature and stirred for 1 hour. Upon completion of the reaction, the solvent was removed under reduced pressure and the residue was redissolved in industrial methanol (100 mL). Next, formamidine acetate (9.9 g, 95 mmol; purchased from Aldrich Chemical Company, Inc., Milwaukee, WI) was added and the reaction mixture was heated to 80 °C and maintained at this temperature for 2.5 hours. At the end of the reaction, the mixture was cooled to room temperature and the solvent was removed under reduced pressure. Aqueous sodium bicarbonate (100 mL) was added to the residue and the product was extracted with ethyl acetate (2 x 100 mL). The organic phase was dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by fast column chromatography (eluent ratio 1:3 hexane/ethyl acetate) to give about 10 g of a light peach-colored oil, which was left to crystallize overnight. The crystalline product was filtered, washed with hexane and dried in an oven overnight to give the final colorless crystals 3-(trifluoromethyl)-1H-1,2,4-triazole (8.73 g, 66% yield). Its 1H NMR (400 MHz, DMSO-d6) data was: δ 8.81 (1H).
