16618-67-0

18242-39-2

124-41-4

16618-67-0

1. Bromination: 30.0 g of 3,5-dinitrobenzene (0.18 mol) was dissolved in 180 mL of concentrated sulfuric acid and heated to 80°C, maintaining the reaction temperature in the range of 80-90°C. 44.5 g of N-bromosuccinimide (NBS, 0.25 mol) was added in 9 portions. 44.5 g of N-bromosuccinimide (NBS, 0.25 mol) was added in 9 batches. The reaction lasted for 30 min and then cooled to room temperature. The reaction mixture was poured into 600 mL of ice water, a white precipitate was precipitated, which was filtered, washed and dried to give 41.3 g of white solid 3,5-dinitrobromobenzene in 93.7% yield. 2. Methoxylation reaction: 1 g of sodium metal (43.4 mmol) was dissolved in methanol to prepare sodium methanol solution. To this solution, 8.7 g of 3,5-dinitrobromobenzene (35.2 mmol) was added and the reaction was refluxed at 45°C for 2 hours. Upon completion of the reaction, it was cooled to room temperature and neutralized with 50 mL of 1N hydrochloric acid solution, followed by extraction with dichloromethane. The organic phases were combined, washed three times with saturated brine and dried over anhydrous magnesium sulfate. The solvent was filtered and concentrated, purified by column chromatography (petroleum ether:dichloromethane=5:1) to give 4.6 g of white powdery solid 3-methoxy-5-nitrobromobenzene in 56.3% yield. 3. Reduction reaction: 2.32 g of 3-methoxy-5-nitrobromobenzene (10 mmol) was dissolved in 25 mL of methanol, 10 mL of acetone solution and 400 mg of Pd/C catalyst were added. The reaction was carried out for 3 h at room temperature under hydrogen gas. After completion of the reaction, the Pd/C catalyst was removed by filtration and the solvent was evaporated. Purification by column chromatography (petroleum ether:ethyl acetate=4:1) afforded 1.95 g of pale yellow solid 3-bromo-5-nitroanisole in 96.5% yield.