Bromochloromethane → 2-(Chloromethoxy)-1,3-dimethylbenzene

Participants

Reaction Conditions

Reaction Steps

3-([2,6-Dimethylphenoxy]methylthio)propanoic acid 29 was prepared by reaction of 2-(chloromethoxy)-1,3-dimethylbenzene with methyl 3-mercaptopropanoate followed by hydrolysis of the ester. 2-(Chloromethoxy)-1,3-dimethylbenzene: A three-necked, 500-mL flask equipped with thermometer, reflux condenser, argon inlet, and a magnetic stirring bar was charged with 6.12 g (0.05 mol) of 2,6-dimethylphenol, 100 mL dry tetrahydrofuran, and 4.0 g (0.1 mol) sodium hydroxide powder. The mixture was heated at 66° C. for 1 hour. The mixture was cooled to room temperature, and 98 mL (1.5 mol) of bromochloromethane was added. The suspension that formed was cooled to room temperature, filtered through CELITE, and the solvent was removed under reduced pressure. The oily residue was purified by vacuum distillation (1-1.5 torr, b.p., 66° C.) to afford an overall yield of 6.50 g (76%) of 2-(chloromethoxy)-1,3-dimethylbenzene. 1H NMR (400 MHz, CDCl3): 2.33 (s, 6H), 5.80 (s, 2H), 6.99-7.06 (m, 3H).

Provenance & Evidence