Process for making perillyl alcohol
View Patent ↗A process for making perillyl alcohol is disclosed. The process comprises isomerizing a starting material comprising trans-isocarveol at a temperature within the range of 100° C. to 220° C. in the presence of a Group 5 metal catalyst to produce perillyl alcohol. We surprisingly found that trans-isocarveol, which can be selectively produced from a commercially available mixture of cis- and trans-LMO, can be isomerized directly to perillyl alcohol. Yields of perillyl alcohol are improved when the isomerization is performed under an inert atmosphere and/or in the presence of a phenolic antioxidant. Performing the isomerization in the presence of a high-boiling alcohol and/or distilling the perillyl alcohol product from the reaction mixture in the presence of a high-boiling alcohol, enhances yields and maximizes catalyst use. The resulting distillation residue, which contains recovered Group 5 metal catalyst, is valuable for catalyzing additional trans-isocarveol isomerizations.
1. A process for making perillyl alcohol, comprising isomerizing a starting material comprising trans-isocarveol at a temperature within the range of 100° C. to 220° C. in the presence of a Group 5 metal catalyst to produce perillyl alcohol.
2. The process of claim 1 wherein the isomerization is performed at a temperature within the range of 130° C. to 190° C.
3. The process of claim 1 wherein the isomerization is performed under an inert atmosphere.
4. The process of claim 3 wherein the isomerization is performed under nitrogen.
5. The process of claim 1 wherein the isomerization is performed in the presence of a phenolic antioxidant.
6. The process of claim 5 wherein the phenolic antioxidant is 2,6-di-tert-butyl-4-methylphenol or tert-butyl hydroquinone.
7. The process of claim 1 wherein the catalyst is a salt, organic ester, or complex of a Group 5 metal.
8. The process of claim 1 wherein the catalyst comprises vanadium.
9. The process of claim 8 wherein the catalyst is ammonium metavanadate.
10. The process of claim 1 wherein the starting material further comprises cis-isocarveol.
11. The process of claim 1 further comprising recovering the perillyl alcohol by distillation.
12. The process of claim 11 wherein the distillation is performed in the presence of an alcohol having a boiling point greater than 260° C., and the resulting distillation residue is used to catalyze additional trans-isocarveol isomerizations.
13. The process of claim 12 wherein the alcohol is triethylene glycol.
14. The process of claim 1 wherein the perillyl alcohol has a neat optical rotation [α] D 22 of at least 104°.