1-Chloro-4-(chloromethyl)benzene → 3-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-one

Participants

Reaction Conditions

Reaction Steps

A solution of p-chlorobenzyl chloride (80.5 g, 0.5 mol) and ether (150 mL) is slowly added to a vigorously stirred slurry of magnesium turnings (12.15 g, 0.5 mol) and ether (50 mL) over a 45 minute period. After the addition is complete, the reaction mixture is refluxed for 1/2 hour then cooled in an ice bath. The Grignard reagent is then added to a solution of ethyl trifluoroacetate (71.04 g, 0.5 mol) and ether (150 mL) at -60° to -70° C. (acetone-dry ice bath) over a 45 minute period. The cooling bath is removed and the reaction mixture is allowed to warm to -10° C. The reaction mixture is then quenched with saturated ammonium chloride solution and then acidified with 10% hydrochloric acid solution. The organic layer is separated, washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a liquid. Vacuum distillation of the liquid gives the title product as a clear liquid (52.8 g, bp 72°-74° C./34 mm, 47%).

Provenance & Evidence