Hydrochloric Acid → 2-Bromo-4-nitrobenzaldehyde

Beteiligte Stoffe

Reaktionsschritte

2-Bromo-4nitrotoluene (6.29 g, 29.1 mmol) was dissolved in a mixture of glacial acetic acid 46 mL, and acetic anhydride 46 mL, and cooled in an ice bath. Concentrated sulfuric acid (6.9 mL) was added dropwise. Chromium trioxide (8.08 g, 80.8 mmol) was added portionwise over 1 h. The reaction mixture was stirred for an additional 15 min then poured onto ice. The precipitate was isolated by filtration and dissolved in 16 mL of 1,4-dioxane. Concentrated hydrochloric acid (3 mL) was added and the solution was refluxed for 2 h. The reaction mixture was diluted with ethyl acetate (150 mL) and washed with water, saturated sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and evaporated to yield 1.09 g of 2-bromo-4-nitrobenzaldehyde. The aldehyde was dissolved in methanol (50 mL) and potassium carbonate (0.82 g, 5.96 mmol) and tosylmethyl isocyanide (1.16 g, 5.96 mmol) was added. The reaction mixture was refluxed for 3 h, cooled to room temperature and concentrated. The residue was dissolved in methylene chloride (200 mL) and the organic layer was washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated to yield 1.53 g. (96%) of 5-(4-nitro-2-bromophenyl)oxazole. 5-(4-Nitro-2-bromophenyl)oxazole (500 mg, 1.86 mmol) was dissolved in a mixture of 10 mL of ethanol and 20 ml of ethyl acetate. Tin dichloride dihydrate 1.74 g (7.72 mmol) was added and the reaction mixture heated to 80° C. for 0.5 h. The reaction mixture was poured into 400 mL of ice/water and neutralized with sodium carbonate. The suspension was extracted with ethyl acetate (3×100 mL), and the combined organic layer was washed with brine, separated and dried over magnesium sulfate, filtered and the solvent removed under reduced pressure to yield 463 mg of 5-(4-amino-2-bromophenyl)oxazole. 93% pure by HPLC method A. Mass spectrum M+H+=240.95, 1H 400 MHz NMR (CD3OD): 8.09 (s, 1H), 7.40 (s, 1H), 7.34 (d, 1H J=8.5 Hz), 6.89 (d, 1H, J=8.5 Hz), 6.60 (m, 1H).

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