Sodium Sulfite → Levoverbenone

Temperature

30 °C

(−)-α-pinene (136.2 g, 1 mole) was oxidised by bubbling in O2 in the presence of cobalt stearate (0.5 g), which is added portionwise, maintaining the temperature at approximately 5-55° C., for at least 50-60 hours. When the reaction was complete, the peroxide index was approximately 27-29%. After cooling to room temperature, the excess of peroxides was decomposed by adding to the reaction mixture an equal quantity of a hot aqueous solution (˜50° C.) of 5% ferrous sulphate and 1% sulphuric acid; the peroxide index was approximately 0 within approximately 2 hours. The organic phase was then separated and washed 2-3 times with water until a pH of 5-6 is obtained. The non-reacted (−)-α-pinene was removed by column distillation at a temperature of approximately 100° C. and at a pressure of 20-25 mmHg (2.6×10−2−3.3×10−2 bar). The distillation residue was constituted by a mixture of terpenes which was characterized by oxygenated functions (alcohol, ketone and aldehyde functions). A Bertagnini reaction was then carried out by adding to the reaction mixture a solution containing sodium sulphite (120 g, 0.954 mole), while maintaining the temperature at 55-60° C. Because the pH of the mixture gradually moved to basic values, a 50% acetic acid solution was added until the pH is neutral. When the pH remained stable at ˜7, the reaction, might be regarded as complete. The organic phase (containing the alcohols PINOCARVEOL, MIRTENOL, VERBENOL) was separated and the aqueous phase was counter-extracted 2-3 times with hexane. The aqueous solution was alkalinised to pH ˜14 and then extracted with hexane, thus obtaining the fraction containing carbonyl products (MIRTENAL AND VERBENONE). The hexane extract, washed 2-3 times with water, was concentrated to obtain a high-boiling oily residue constituted to the extent of more than 80% by VERBENONE. The residue was dissolved with methanol; the methanol solution was cooled to −5 to −1° C. and, while maintaining this temperature, sodium borohydride was added until the MIRTENAL was undetectable (monitoring by TLC). The reduction was then stopped by the addition of a small amount of acetic acid, until the solution was neutral. The methanol solution was concentrated to ⅔ the volume, then diluted with water and extracted with hexane. The hexane solution was evaporated under vacuum and the residue is distilled at 80° C./1.5 mm Hg (1.9×10−3 bar) to give VRBENONE (25 g, yield 16.6%) with [α]D2b=−217° (c=10 in ethanol).

1. customby bubbling in O2 in the presence of cobalt stearate (0.5 g), which
2. additionis added portionwise
3. waitfor at least 50-60 hours
4. temperatureAfter cooling to room temperature
5. additionby adding to the reaction mixture an equal quantity of a hot aqueous solution (˜50° C.) of 5% ferrous sulphate and 1% sulphuric acid
6. customwithin approximately 2 hours
7. customThe organic phase was then separated
8. washwashed 2-3 times with water until a pH of 5-6
9. customis obtained
10. customThe non-reacted (−)-α-pinene was removed by column distillation at a temperature of approximately 100° C. and at a pressure of 20-25 mmHg (2.6×10−2−3.3×10−2 bar)
11. additionThe distillation residue was constituted by a mixture of terpenes which
12. customby oxygenated functions (alcohol, ketone and aldehyde functions)
13. customA Bertagnini reaction
14. additionby adding to the reaction mixture a solution
15. temperaturewhile maintaining the temperature at 55-60° C
16. customthe reaction
17. customwas separated
18. extractionthe aqueous phase was counter-extracted 2-3 times with hexane
19. extractionextracted with hexane
20. customthus obtaining the fraction
21. extractionThe hexane extract
22. washwashed 2-3 times with water
23. concentrationwas concentrated
24. customto obtain a high-boiling oily residue
25. additionwas added until the MIRTENAL
26. concentrationThe methanol solution was concentrated
27. additiondiluted with water
28. extractionextracted with hexane
29. customThe hexane solution was evaporated under vacuum
30. distillationthe residue is distilled at 80° C./1.5 mm Hg (1.9×10−3 bar)
31. customto give

ORD record

ord-89a4c00900e5412c8c750076b9c62aea

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06649658B1