4-Hydroxybenzaldehyde → 4-(2,2,2-Trifluoroethoxy)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

50 grams (0.41 mol) of 4-hydroxybenzaldehyde, 400 ml of N,N-dimethylformamide (DMF), and 5 grams of 18-crown-6 ether was added into a one-litre four-necked flask with thermometer, mechanical stirrer and reflux condenser, and then the mixture was stirred for 20 minutes. 168 grams (1.22 mol) of potassium carbonate powder was added in batch and stirred another 30 minutes. The reaction mixture was heated to 110° C., and then a solution of 115 gram (0.45 mol) of trifluoroethyl toluene-4-sulfonate in 100 ml DMF was added dropwise within about 1 hour. The reaction mixture was heated to 130° C. for 3-4 hours. The reaction was monitored by TLC. The mixture was cooled to 0° C. and was poured into cooled 600 ml of 3N hydrochloric acid, and was stirred. The mixture was extracted with 1000 ml of ether. The water layer was separated and extracted with ether (3×400 ml). The ether extracts were combined and washed with 400 ml of 3N hydrochloric acid, distilled water, brine in turn. Then it was dried over anhydrous magnesium sulfate. The ether was removed by flash distillation, and the residue was vacuum distilled to give 4-trifluoroethoxybenzaldehyde (95-97° C./10 mmHg) in a yield of 88%. 1H-NMR (ppm) δ: 9.80 (1H, s; —CHO); 7.65 (2H, m; 2,6-ArH); 6.83 (2H, m; 3,5-ArH); 4.56 (2H, q; J3H-F=7.2 Hz; —CH2CF3).

Provenance & Evidence