Process for the preparation of terpinolene epoxide

Abstract

The present invention relates to a process for the preparation of terpinolene epoxide by epoxidation of terpinolene.

Claims

1. A process for the preparation of terpinolene epoxide of formula (I) ##STR00003## comprising reacting terpinolene with an oxidizing agent comprising hydrogen peroxide in the presence of a halogenated ketone selected from halogenated di-(C.sub.1-C.sub.6)-alkyl ketones as catalyst and the reaction is carried out in a non-halogenated inert organic solvent and in the absence of a halogenated organic solvent except halogenated di-(C.sub.1-C.sub.6)-alkyl ketones.

2. The process according to claim 1, wherein the halogenated ketone is selected from hexafluoroacetone, hexachloroacetone, perfluoromethyl isopropyl ketone, perfluoromethyl ethyl ketone and any mixture thereof.

3. The process according to claim 1, wherein the halogenated ketone is hexachloroacetone.

4. The process according to claim 1, wherein the non-halogenated inert organic solvent is selected from non-halogenated aliphatic hydrocarbons, non-halogenated aromatic hydrocarbons and any mixture thereof.

5. The process according to claim 1, wherein the non-halogenated inert organic solvent is selected from non-halogenated aromatic hydrocarbons and any mixtures thereof.

6. The process according to claim 1, wherein the epoxidation is carried out in the presence of an organic base.

7. The process according to claim 6, wherein the base is selected from tertiary amines, pyridine, substituted pyridines, bicyclic amines and any mixture thereof.

8. The process according to claim 6, wherein the base is pyridine or substituted pyridines.

9. The process according to claim 6, wherein the pH of the reaction mixture is from 3 to 6.

10. The process according to claim 1, wherein the molar ratio of the halogenated ketone to terpinolene is from 0.05:1 to 1:1.

11. The process according to claim 1, wherein the molar ratio of hydrogen peroxide to terpinolene is from 1:1 to 2:1.

12. The process according to claim 1, wherein the epoxidation is carried out at 5 to 40 C.

13. The process according to claim 1, wherein the terpinolene epoxide of formula (I) is further subjected to an epoxide ring opening isomerization leading to limonene-4-ol.

14. The process according to claim 13, wherein limonene-4-ol is further reduced to give terpinene-4-ol.

15. A process for preparing ()-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane, any of its individual enantiomers or any non-racemic mixture thereof, comprising preparing the terpinolene epoxide of formula (I) in accordance with claim 1.

16. The process of claim 15, further comprising subjecting terpinolene epoxide of formula (I) to an epoxide ring opening isomerization to give limonene-4-ol.

17. The process of claim 16, further comprising hydrogenating limonene-4-ol to afford terpinene-4-ol.

18. The process of claim 17, further comprising treating terpinene-4-ol successively or concurrently with an oxidizing agent and an acid in an inert solvent to effect epoxidation and cyclization to give ()-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane.

19. The process of claim 18, further comprising reacting ()-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane with a compound of the formula WCH.sub.2L wherein W is 2-methylphenyl and L is a leaving group to afford ()-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane, any of its individual enantiomers or any non-racemic mixture thereof.

Description

EXAMPLE 1: EPOXIDATION IN TOLUENE (0.10 EQ. HEXACHLOROACETONE)

(1) 400.0 g (90%; 2.64 mol) terpinolene, 70.0 g (0.26 mol) hexachloroacetone, 8.26 g (0.11 mol) pyridine and 700 g (2.88 mol) toluene were placed in a 2000 mL glass reactor and 287.6 g (50%; 1.6 mol) H.sub.2O.sub.2 was added within 5 h. The resulting mixture was stirred overnight at room temperature. Thereafter, aqueous Na.sub.2SO.sub.3-solution 1620 g (10%) was added. After stirring and phase split the solvent of the organic phase was evaporated. The distillation residue contained 58% of terpinolene epoxide, which corresponds to a yield of 81.5%.

EXAMPLE 2: EPOXIDATION IN TOLUENE (0.15 EQ. HEXACHLOROACETONE)

(2) 772.8 g (90.6%; 5.14 mol) terpinolene, 473.4 g (5.14 mol) toluene, 206.2 g (0.77 mol) hexachloroacetone and 16.4 g (0.21 mol) pyridine were placed in a 2500 mL glass reactor. 559.2 g (50%; 8.22 mol) H.sub.2O.sub.2 was dosed continuously over 2 h at 20-22 C. to the reaction mixture under vigorous stirring. The reaction mixture was stirred for further 6.5 h at 22 C.

(3) Then phases were separated and water phase was collected in a bottle. To the organic phase in the reactor was added 474.9 g (0.57 mol) sodium sulfite solution (15% in water) in portions and the mixture was stirred for 30 minutes. Phases were separated. To the organic phase in the reactor was added 463 g sodium hydroxide solution (10% in water). After stirring and phase split the organic phase was washed three times with 342 g water in each case.

(4) The solvent of the organic phase was distilled off at reduced pressure. The distillation residue (924 g) contained 68.2% of terpinolene epoxide (quantitative GC with internal standard), which corresponds to a yield of 80.5%.