Hydrogen Peroxide → 4-Hydroxy-α,α,4-trimethyl-2-cyclohexene-1-methanol

Temperature

0 °C

131 mg methyl trioxorhenium was dissolved in 30% aqueous hydrogen peroxide (23.6 ml) and cooled to 0° C. internal in a 21, 3-necked flask. A solution was separately prepared from 1,3-dioxolane (100 ml), (+)-2-carene (13.6 g, 0.1 mol), and pyridine (12 ml). This was also cooled to 0° C. internal. While stirring the cold aqueous solution vigorously, the cold dioxolane solution was added over 70 minutes, keeping the exothermic reaction at 0-5° C. After three hours (when TLC indicated disappearance of (+)-2-carene), the mixture was poured in to a separating funnel and the layers were separated. Saturated NaCl solution (20 ml) was added to the aqueous layer and more separation occurred. The layers were separated again. The aqueous layer was extracted once more with dioxolane (10 ml). The organics were combined. Aqueous pH 5.8 buffer solution (304 ml) was added and stirred vigorously at room temperature until (+)-2-carene epoxide had disappeared by TLC and HPLC (4 hours). The reaction was transferred to a separating funnel and washed once with heptane (75 ml). NaCl (45 g) was added to the aqueous layer and this was extracted with ethyl acetate (3×125 ml, 1×100 ml). The ethyl acetate extracts were combined, dried over Na2SO4, and concentrated in vacuo to ˜150 ml. 200 ml heptane was added and the solution was concentrated to ˜150 ml. 5-10 ml of EtOAc was added to dissolve the solid. It was allowed to cool with stirring and then cooled to 0° C. The solid was collected by vacuum filtration and washed twice with cold 5% EtOAc/heptane. After drying under vacuum, 11.857 g of (+)-p-menth-2-ene-1,8-diol (69.8% yield from (+)-2-carene) was obtained. NMR showed some residual heptane. Elemental Analysis: 70.6% C, 10.6% H.

1. temperatureThis was also cooled to 0° C. internal
2. customthe exothermic reaction at 0-5° C
3. additionthe mixture was poured in to a separating funnel
4. customthe layers were separated
5. additionSaturated NaCl solution (20 ml) was added to the aqueous layer and more separation
6. customThe layers were separated again
7. extractionThe aqueous layer was extracted once more with dioxolane (10 ml)
8. additionAqueous pH 5.8 buffer solution (304 ml) was added
9. stirringstirred vigorously at room temperature until (+)-2-carene epoxide
10. customhad disappeared by TLC and HPLC (4 hours)
11. customThe reaction was transferred to a separating funnel
12. washwashed once with heptane (75 ml)
13. additionNaCl (45 g) was added to the aqueous layer
14. extractionthis was extracted with ethyl acetate (3×125 ml, 1×100 ml)
15. dry with materialdried over Na2SO4
16. concentrationconcentrated in vacuo to ˜150 ml
17. addition200 ml heptane was added
18. concentrationthe solution was concentrated to ˜150 ml
19. addition5-10 ml of EtOAc was added
20. dissolutionto dissolve the solid
21. temperatureto cool
22. stirringwith stirring
23. temperaturecooled to 0° C
24. filtrationThe solid was collected by vacuum filtration
25. washwashed twice with cold 5% EtOAc/heptane
26. customAfter drying under vacuum

ORD record

ord-e8db63f94b804bd3b1d189b60efa975e

Source dataset

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06867335B2