Hydrochloric Acid → 2-(4-Methylthiophenyl)-1-(4-methylphenyl)ethanone

Participants

Reaction Conditions

Reaction Steps

A 1000 mL four-necked round-bottomed flask equipped with mechanical stirrer, reflux condenser, nitrogen inlet, constant pressure addition funnel and thermometer was charged with 3-(4-methylthiophenyl-2-(4-methylphenyl)propenoic acid from Step 1 (25 g, 87.91 mmol), triethylamine (12.9 mL, 92.31 mmol) and toluene (200 mL). The addition funnel was charged with diphenylphosphoryl azide (19 mL, 87.91 mmol) dissolved in toluene (100 mL), and the reaction vessel was cooled to 0° C. Over approximately ten minutes, the diphenylphosphoryl azide solution was added to the reaction flask, keeping the reaction temperature ≥10° C. After holding the reaction temperature at 0° C. for 30 minutes, water (100 mL) was added, and the biphasic solution was transferred to a separatory funnel and extracted with toluene (2×200 mL). The combined organic solution was dried over anhydrous MgSO4 and filtered. Over approximately thirty minutes, the solution was carefully warmed to reflux and held for one hour. Upon removing the heat source, tert-butanol (9 mL, 96.7 mmol) was added, and reflux was continued for an additional thirty minutes. Concentrated HCl (8 mL, 96.8 mmol) was added with extreme caution, producing copious evolution of gas. After continuing reflux for a final twenty minutes, the reaction was cooled to room temperature, and held for 16 hours. The solvent volume was reduced in vacuo, until crystals appeared. Diethyl ether (300 mL) was added, and the suspension was cooled to 0° C., held for 30 minutes, filtered and washed with diethyl ether to provide, after air-drying, pure 2-(4-methylthiophenyl)-1-(4-methylphenyl) ethanone (11.3 g, 50%): mp 120°-121° C. 1H NMR (CDCl3) 300MHz 7.89 (d, J=8.26 Hz, 2H), 7.23-7.15(m, 6H), 4.21(s, 2H), 2.45(s, 3H), 2.40(s, 3H).

Provenance & Evidence