反应详情

A mixture of gramine (120.0 g., 0.69 mole), 2-nitropropane (443 ml.), and NaOH (28.8 g., 0.72 mole) was stirred and gradually heated to reflux under N2. After a 6.5 hour reflux period, the reaction mixture was allowed to stand at room temperature overnight, and then diluted with 600 ml. of 10% aqueous AcOH. The mixture was extracted with 1.5 l of Et2O, and the organic layer washed with H2O (4×500 ml.). Concentration of the Et2O solution in vacuum gave an oil which was dissolved in 500 ml. of 95% EtOH. This solution was diluted with 300 ml. of H2O. (Seeding and scratching early in the dilution kept the product from oiling out). After cooling, the yellow solid was collected on a filter to give 105 g. (70%) of nitro intermediate, m.p. 72°-74°. The nitro compound was dissolved in 1.3 l of 95% EtOH, and Raney nickel (70 g., EtOH-washed) and added. The mixture was heated to reflux, and a solution of 85% hydrazine hydrate (116 g., 2.3 mole) in 95% EtOH (110 ml.) was added dropwise at a rate to maintain gentle reflux. The mixture was then heated at reflux for an additional 1.5 hours, cooled, and filtered. Concentration of the filtrate gave crude product as a solid. A solution of the solid in 400 ml. of EtOAC was diluted with 500 ml. of (i-Pr)2O and cooled. The white, cottony solid which separated was collected on a filter to give 91 g., (100%) of product, m.p. 122°-126°. It was used in Procedure 26A without further purification.

1. temperaturegradually heated
2. temperatureto reflux under N2
3. temperatureAfter a 6.5 hour reflux period
4. additiondiluted with 600 ml
5. extractionThe mixture was extracted with 1.5 l of Et2O
6. washthe organic layer washed with H2O (4×500 ml.)
7. customConcentration of the Et2O solution in vacuum gave an oil which
8. dissolutionwas dissolved in 500 ml
9. additionThis solution was diluted with 300 ml
10. temperatureAfter cooling
11. customthe yellow solid was collected on
12. filtrationa filter
13. customto give 105 g
14. temperatureThe mixture was heated
15. temperatureto reflux
16. temperatureto maintain gentle reflux
17. temperatureThe mixture was then heated
18. temperatureat reflux for an additional 1.5 hours
19. temperaturecooled
20. filtrationfiltered
21. customConcentration of the filtrate gave crude product as a solid
22. additionof EtOAC was diluted with 500 ml
23. customThe white, cottony solid which separated
24. customwas collected on
25. filtrationa filter
26. customto give 91 g
27. customIt was used in Procedure 26A without further purification