Ethanethiol → Phenylacetic Acid

Participants

Reaction Steps

To a solution of methyl 3-aminophenylacetate (102 g, 0.62 mole) in 1N HCl (1600 ml ) cooled in an ice bath was added NaNO2 (42.7 g, 0.62mole) portionwise and the solution stirred for 20 minutes. A solution of potassium ethanethiolate was prepared by adding ethanethiol (202 ml, 2.73 mole) dropwise over 10 minutes to a solution of 87.5% KOH (159 g), 2.48 mole) in water (1.2 1) at 0° C. The diazonium salt solution was then added via cannula to the solution of potassium ethanethiolate and the reaction mixture was stirred 30 minutes in an ice bath. Diethyl ether (~ 1.5 1) was added and the mixture was stirred 1.5 hours at room temperature. The ether layer was separated, the aqueous phase further extracted with diethyl ether (3×700 ml ), and the combined ether solutions concentrated. The residue was eluted from silica gel with ethyl acetate:hexane (1:19) to give a mixture of methyl 3- ethylthiophenylacetate H NMR (DMS-d6, 200 MHz) δ: 1.21 (t, J=7 Hz, 3H, ethyl CH3), 2.95 CH2), 3.60 (s, 3H, OCH3), 3.65 (s, 2H, ArCH2), 7.02-7.44 (mr, Ar) and methyl phenylacetate (85.9 g). The esters (84 g) were hydrolyzed in a solution of methanol (500 ml) and 6.25 N NaOH(100 ml) stirred overnight at room temperature. The solution was concentrated in vacuo to remove the methanol the remaining solution acidified with concentrated HCl and the resulting solid was extracted into diethyl ether. The ether solution was washed with brine (3×100 ml), dried (Na2SO4) and concentrated. Vacuum distillation (0.5 mm Hg) gave a distillate (100-115° C.) of phenylacetic acid and a residue of 3-ethylthiophenylacetic acid. The residue in the flask solidified upon cooling to give 3-ethylthiophenylacetic acid (49.8 g). Mp=49-51° C. 1H NMR (DMSO-d6, 200 MHz) δ: 1.21 (t, J=7 Hz, 3H, CH3), 2.95 (q, J=7 Hz, 2H, SCH2), 3.54 (s, 2H, ArCH), 7.01-7.28 (m, 4H, Ar), 12.33 (br s, 1H, CO2H). Mass spectrum (CI--CH4): 197 (M+1, 100%).

Provenance & Evidence