General procedure for the synthesis of 1-chloro-3-fluoro-5-nitrobenzene from 3-chloro-5-fluoroaniline:
(a) Sodium perborate tetrahydrate (7.69 g, 50.0 mmol) was suspended in 30 mL of acetic acid and the suspension was heated to 55 °C. 3-Chloro-5-fluoroaniline (1.46 g, 10 mmol) was dissolved in 20 mL of acetic acid and slowly added to the above suspension over a period of 1 hour. The reaction mixture was stirred at 55 °C for 1 h and then cooled to room temperature. To the reaction mixture was added 300 mL of tert-butyl methyl ether (TBME) and the solid was separated by filtration. The organic layer was washed sequentially with saturated saline, 20 mL of aqueous sodium thiosulfate and saturated saline. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (40 g SiO; eluent: cyclohexane) to afford 1-chloro-3-fluoro-5-nitrobenzene as a solid (320 mg, 18% yield).
1H-NMR (400 MHz; DMSO-d6): δ 8.20 (s, 1H), 8.18 (d, 1H), 8.07 (d, 1H).
