Sulfuric Acid → Benzene, 1-bromo-3-fluoro-4-(methylthio)-2-(trifluoromethyl)-

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Reaction Conditions

Reaction Steps

With cooling, 1.12 g (16.3 mmol) of sodium nitrite were introduced carefully into 8.00 ml of concentrated sulfuric acid. At 10-15° C., 4.00 g (15.5 mmol) of 4-bromo-2-fluoro-3-(trifluoromethyl)aniline dissolved in 30 ml of glacial acetic acid were slowly added dropwise to the clear solution, and the mixture was stirred at this temperature for 1.5 hours. 20 mg (0.31 mmol) of copper powder and 1.82 ml (20.2 mmol) of dimethyl disulfide were initially charged in 12 ml of glacial acetic acid and warmed to 45° C. The solution of the diazonium salt prepared beforehand was slowly added dropwise to this solution. After the addition had ended, the reaction mixture was stirred at 70° C. for 4 hours. The solution was then added to about 500 ml of water and extracted with CH2Cl2. The organic phase was washed with water, dilute NaHCO3 solution, dilute HCl solution and saturated NaCl solution. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product obtained was separated by column chromatography (silica gel, gradient heptane/ethyl acetate). 1-Bromo-3-fluoro-4-(methylsulfanyl)-2-(trifluoromethyl)benzene was obtained as a brown solid.

Provenance & Evidence