Synthesis
The general procedure for the synthesis of 2-trifluoromethyl-4-chlorophenol from 2-amino-5-chlorobenzotrifluoride was as follows: an aqueous solution (2 mL) of NaNO2 (0.458 g, 6.63 mmol) was slowly added to a cooled mixture of 4-chloro-2-trifluoromethylaniline (1.08 g, 5.52 mmol) dissolved in 33% H2SO4 (40 mL) at 0 °C in a cooled mixture of 33% H2SO4 (40 mL). After 3 hours of reaction, urea (0.100 g, 1.67 mmol) was added and stirring was continued for 10 minutes. Subsequently, the reaction mixture was poured into 100 mL of preheated 33% H2SO4 and heated to reflux for 1 hour and then cooled to room temperature. The reaction mixture was extracted with EtOAc, the organic phase was washed sequentially with water and saturated NaCl solution, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel column chromatography with 20% EtOAc/hexane as eluent gave 4-chloro-2-trifluoromethylphenol (0.245 g, 23% yield). The product was detected by mass spectrometry (ion spray) showing m/z = 195 (M-1) and 1H NMR (CDCl3) data as follows: δ 7.49 (d, 1H), 7.38 (dd, 1H), 6.91 (d, 1H), 5.44 (brs, 1H).
