反应详情

Hydrogen peroxide (70 ml, 30%) was added with caution to a solution of formic acid (350 ml, 88%) in a three-necked flask (1 L) cooled with running water. Isosafrole (72 ml) was added drop-wise, by a dropping funnel, to the reaction mixture at a rate to keep the temperature of the reaction mixture below 35° C. After the complete addition of isosafrole, a non-homogeneous solution was obtained. At this point, acetone (200 ml) was added to the reaction mixture at a rate to keep the temperature below 35° C. The reaction was allowed to stand at room temperature overnight. The solvent was removed by a rotary evaporator equipped with a dry-ice acetone cold trap, a high vacuum pump and a water bath with temperature not exceeding 30° C. Ethyl ether (500 ml) was added to the residue. The solution was transferred into a separatory funnel. The organic phase was washed with sodium bicarbonate (0.1 N, 2×500 ml) and water (3×300 ml). The organic phase was transferred into a round bottom flask. The solvent was removed by rotary evaporation. Concentrated sulfuric acid (75 ml) was diluted drop-wise in water (425 ml). Methanol (160 ml) was added to the oily residue, and mixed to obtain a homogeneous solution. The sulfuric acid solution was added to the methanolic reaction mixture. The flask was equipped with a water-cooled reflux condenser and a heating mantel. The reaction mixture was heated to reflux for 4 hours. The heat was removed and crushed ice (150 g) was added to the reaction mixture. The reaction mixture was transferred into a separatory funnel and extracted with ethyl ether (1×350 ml, 1×150 ml and 1×100 ml). The combined organic layers were washed with water (3×150 ml). Sodium hydroxide (40 ml, 0.1 N) was diluted in water (360 ml). The organic phase was washed with diluted sodium hydroxide (2×200 ml, 10 mM) and saturated sodium chloride solution (100 ml). The organic layer was dried with anhydrous sodium sulfate (20 g) overnight. The drying agent was filtered and the cake was washed with ethyl ether (2×10 ml). The solvent was removed by rotary evaporation. The product was distilled at reduced pressure (2-0.5 mmHg). The second fraction distilling at 90-100° C. (˜1 mmHg) contained product. The product was identified by El/MS with the m/z of 182. Infrared spectrum (cm−1) indicated 1714 (C═O) and 2898 (C—H) stretches corresponding to the product.

1. customby a dropping funnel, to the reaction mixture at a rate to keep
2. customthe temperature of the reaction mixture below 35° C
3. customa non-homogeneous solution was obtained
4. customthe temperature below 35° C
5. customThe solvent was removed by a rotary evaporator
6. customequipped with a dry-ice acetone cold trap
7. customexceeding 30° C
8. additionEthyl ether (500 ml) was added to the residue
9. customThe solution was transferred into a separatory funnel
10. washThe organic phase was washed with sodium bicarbonate (0.1 N, 2×500 ml) and water (3×300 ml)
11. customThe organic phase was transferred into a round bottom flask
12. customThe solvent was removed by rotary evaporation
13. additionConcentrated sulfuric acid (75 ml) was diluted drop-wise in water (425 ml)
14. additionMethanol (160 ml) was added to the oily residue
15. additionmixed
16. customto obtain a homogeneous solution
17. temperaturecooled
18. temperaturereflux condenser
19. temperatureThe reaction mixture was heated
20. temperatureto reflux for 4 hours
21. customThe heat was removed
22. customcrushed ice (150 g)
23. additionwas added to the reaction mixture
24. customThe reaction mixture was transferred into a separatory funnel
25. extractionextracted with ethyl ether (1×350 ml, 1×150 ml and 1×100 ml)
26. washThe combined organic layers were washed with water (3×150 ml)
27. additionSodium hydroxide (40 ml, 0.1 N) was diluted in water (360 ml)
28. washThe organic phase was washed with diluted sodium hydroxide (2×200 ml, 10 mM) and saturated sodium chloride solution (100 ml)
29. dry with materialThe organic layer was dried with anhydrous sodium sulfate (20 g) overnight
30. filtrationThe drying agent was filtered
31. washthe cake was washed with ethyl ether (2×10 ml)
32. customThe solvent was removed by rotary evaporation
33. distillationThe product was distilled at reduced pressure (2-0.5 mmHg)
34. distillationThe second fraction distilling at 90-100° C. (˜1 mmHg)