Trifluoro-p-tolunitrile

Preparation

nitrogen-protected flask, thermometer, and stirrer were installed. 200 mL of acetonitrile, 6.6 g (25 mmol) of triphenylphosphine, and 10 mmol of anhydrous nickel chloride (dried under vacuum at 100 °C with 2.4 g NiCl₂·6H₂O until yellow, requiring approximately 6–9 h) were added. Under nitrogen protection, the mixture was heated to reflux in an oil bath (80–82 °C) and stirred for 10 min until the solution turned dark green. The mixture was cooled to room temperature, and 4.3 g (60 mmol) of zinc powder was added. The reaction proceeded until an orange-yellow precipitate formed. The temperature was then raised to 45 °C, and the reaction proceeded for 0.5 h. 122.4 g (0.68 mol) of p-chlorotrifluorotoluene was added, and the mixture was stirred for 5 min. 44.2 g (0.68 mol) of potassium cyanide was then added, and the solution immediately turned yellow-green. The reaction was continued at this temperature with stirring. Gas chromatography monitoring showed that after 15 h, the conversion rate of p-chlorotrifluorotoluene was 82.7%, the hydrogenated dehalogenated trifluorotoluene was 0.4%, and the biphenyl product 4,4'-ditrifluoromethylbiphenyl was 0.8%. Anhydrous potassium carbonate was added and stirred for 5 min. The mixture was filtered, and the filtrate was an orange-red solution. Vacuum distillation yielded white Trifluoro-p-tolunitrile crystals.

Chemical Properties

white to light yellow crystal powder

Uses

4-(Trifluoromethyl)benzonitrile is used in the synthesis of quinazolines for amidines. Also used in the synthesis of s-transferase p1-1 and cancer cell proliferation.

General Description

4-(Trifluoromethyl)benzonitrile is a key intermediate in the synthesis of fluvoxamine. It participates in nickel-catalyzed arylcyanation reaction of 4-octyne.