反应详情

A freshly prepared mixture of 30% H2O2 (3.9 g), formic acid (11 mL), and concentrated sulfuric acid (3 drops) was maintained for 1 hour at room temperature. The mixture was then cooled to 5° C. and treated with a solution of 5-bromo-2,3-dimethoxybenzaldehyde (4.15 g) in formic acid (25 mL). The mixture was maintained for 4 hours at 5° C. then placed in the 4° C. freezer overnight. Reaction mixture was then treated with a solution of Na2SO3 (3.4 g) in water (100 mL), stirred, and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with 50 mL water followed by 50 mL brine and then organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was dissolved in diethyl ether (20 mL) and after addition of 25% aqueous KOH (220 mL) was vigorously stirred under nitrogen. The organic layer was separated, the aqueous phase acidified to a pH of 3 with 2 N HCl and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under vacuum to yield an oily residue which was purified by chromatography on silica in 3:1 hexane/ethyl acetate to provide 2,3-dimethoxy-5-bromophenol in 50% yield. 1H NMR (400 MHz) (CDCl3) δ 3.87 (s, 3H), 3.89 (s, 3H), 5.84 (s, 1H), 6.64 (d, J=4.0 Hz, 1H), 6.80 (d, J=4.0 Hz, 1H).

1. temperatureThe mixture was then cooled to 5° C.
2. temperatureThe mixture was maintained for 4 hours at 5° C.
3. customthen placed in the 4° C. freezer overnight
4. customReaction mixture
5. extractionextracted with ethyl acetate (3×50 mL)
6. washThe combined extracts were washed with 50 mL water
7. dry with materialorganic layer was dried over sodium sulfate
8. concentrationconcentrated under vacuum
9. dissolutionThe residue was dissolved in diethyl ether (20 mL)
10. additionafter addition of 25% aqueous KOH (220 mL)
11. stirringwas vigorously stirred under nitrogen
12. customThe organic layer was separated
13. extractionextracted with ethyl acetate (3×100 mL)
14. washThe combined organic layers were washed with brine
15. dry with materialdried over sodium sulfate
16. concentrationconcentrated under vacuum
17. customto yield an oily residue which
18. customwas purified by chromatography on silica in 3:1 hexane/ethyl acetate