The general procedure for the synthesis of 3-bromo-4-ethylbenzoic acid from 4-ethylbenzoic acid was as follows: bromine (7 mL, 0.14 mol) was slowly added to a mixed solution of acetic acid (300 mL), nitric acid (65 mL) and water (50 mL) containing 4-ethylbenzoic acid (15.0 g, 0.10 mol). A solution of silver nitrate (17.0 g, 0.10 mmol) in water (50 mL) was added dropwise to the reaction system under vigorous stirring. The reaction mixture was stirred continuously at room temperature overnight, during which a yellow solid precipitated. The precipitate was collected by filtration, washed well with water and extracted several times with chloroform (CHCl3). The organic phases were combined, washed with water and the solvent was removed by distillation under reduced pressure to afford 3-bromo-4-ethylbenzoic acid as a white solid (11.8 g, 52% yield). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3): δ 1.26 ppm (t, 3H, J = 7.8 Hz); 2.83 ppm (q, 2H, J = 7.8 Hz); 7.34 ppm (d, 1H, J = 8.1 Hz); 7.97 ppm (dd, 1H, J = 8.1, 1.8 Hz); 8.27 ppm (d, 1H, J = 1.8 Hz).
