Procedure for the synthesis of 4-(trifluoromethyl)-1H-imidazole: 3-bromo-1,1,1-trifluoropropan-2-one (25.0 g, 131 mmol, Aldrich Item No. 374059) and formamide (104 mL, 2.62 mol) were sequentially added to a 500 mL round bottom flask. The reaction mixture was slowly heated to reflux temperature (about 140 °C) and kept at reflux for 2.5 hours of reaction. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 200 mL of 10% aqueous K2CO3 solution and subsequently extracted with ether (5 x 200 mL). The organic phases were combined, washed sequentially with 10% aqueous K2CO3 (2 x 100 mL) and deionized water (2 x 100 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give a brown solid. The resulting solid was washed with dichloromethane (DCM) to finalize 4-(trifluoromethyl)-1H-imidazole (4.0 g, 22% yield) as a brown solid. The structure of the product was confirmed by 1H NMR (CD3OD): δ 7.82 (s, 1H), 7.60 (s, 1H).
