Bromide ion → (2-Aminophenyl)(3-methylphenyl)methanone

Participants

Reaction Conditions

Reaction Steps

To a 250 mL round-bottomed flask charged with magnesium (0.947 g, 39.0 mmol) and diethyl ether (50.0 ml) was added 2 drops of dibromoethane. The reaction mixture was heated to 60° C. for 5 min and then removed from the heat. Next, 1-bromo-3-methylbenzene (5 g, 29.2 mmol) in diethyl ether (50 ml) was added slowly in portions until reflux was achieved. The remaining bromide was added dropwise to maintain reflux. After the addition, the reaction mixture was refluxed for 3 hrs. Next, 2-aminobenzonitrile (1.151 g, 9.74 mmol) in diethyl ether (50.0 ml) was added slowly over 10 min. The resulting mixture was refluxed overnight. The volume of the reaction mixture was reduced to ⅓ and 100 g of crushed ice and 50 ml of 6N HCl was added while stirring. After 3 hrs at room temperature, the pH was adjusted to pH 8 with 5N NaOH and the reaction was diluted with sat NaHCO3 (50 mL). The two phases were separated and the aqueous layer was extracted with ethyl acetate (2×200 mL). The combined organic layers were dried with MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 70% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 80 g) to provide Intermediate A-23 (1.84 g, 89%). 1H NMR (400 MHz, DMSO-d6) δ 7.44-7.23 (m, 6H), 7.08 (br. s., 2H), 6.86 (d, J=8.1 Hz, 1H), 6.50 (t, J=7.5 Hz, 1H), 2.38 (s, 3H).

Provenance & Evidence