General procedure for the synthesis of 4-bromo-2-methyl-1-nitrobenzene from 2-methyl-4-bromoaniline:
Step 1: Synthesis of 4-bromo-2-methyl-1-nitrobenzene (193)
H2O2 (3.95 mL, 64±5 mmol) was dissolved in DCM (320 mL) at 0°C, cooled and TFAA (10.93 mL, 77 mmol) was added and the mixture was stirred for 5 min at this temperature. The ice bath was then removed, a reflux condenser was installed, and a solution of 4-bromo-2-methylaniline (3 g, 16.12 mmol) in DCM (6.4 mL) was added slowly and dropwise over about 30 minutes. The reaction mixture was heated to reflux for 1 h. After cooling, the reaction mixture was washed sequentially with 30 mL of water and 30 mL of saturated NaHCO3 solution, and the organic layer was dried with MgSO4 and concentrated in vacuum. The crude product was purified by flash column chromatography to give 193 (2.57 g, 11.9 mmol, 74% yield).
1H NMR (CDCl3) δ (ppm): 7.88 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 2.2 Hz, 1H), 7.49 (dd, J = 8.6, 2.2 Hz, 1H), 2.60 (s, 3H).
