Process for the preparation of limonene-4-ol

Abstract

The present invention relates to a process for the preparation of limonene-4-ol by an epoxide ring opening isomerization of terpinolene epoxide.

Claims

1. A process for the preparation of limonene-4-ol of formula (II) ##STR00003## comprising subjecting a selective epoxide ring opening isomerization to a terpinolene epoxide of formula (I) ##STR00004## in the presence of a sulfonic acid and an organic base as a catalyst.

2. The process of claim 1, wherein the sulfonic acid is selected from the group consisting of (C.sub.1-C.sub.14)-alkylsulfonic acids, halo-(C.sub.1-C.sub.6)-alkylsulfonic acids, (C.sub.1-C.sub.6)-alkyl-(C.sub.6-C.sub.10)-arylsulfonic acids, camphorsulfonic acid and any mixture thereof.

3. The process of claim 1, wherein the sulfonic acid is selected from the group consisting of methane sulfonic acid, dodecyl sulfonic acid, trifluoromethane sulfonic acid, p-toluene sulfonic acid, 2-naphthalene sulfonic acid, camphorsulfonic acid and any mixture thereof.

4. The process of claim 1, wherein the base is selected from the group consisting of tertiary amines, pyridine, substituted pyridines, bicyclic amines and any mixture thereof.

5. The process of claim 1, wherein the base is selected from the group consisting of trimethylamine, triethylamine, tributylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, N-methyl imidazole, pyridine, collidine, lutidine, picoline, N,N-dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-en, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,4-diazabicyclo[2.2.2]octan.

6. The process of claim 1, wherein the base is selected from the group consisting of triethylamine and N,N-dimethylaminopyridine.

7. The process of claim 1, wherein the base is used in the form of a free base or in the form of a salt with a sulfonic acid that may be the same or different to the sulfonic acid used as the catalyst.

8. The process of claim 7, wherein the base is used in the form of a salt with methanesulfonic acid or p-toluene sulfonic acid.

9. The process of claim 1, wherein the molar ratio of the sulfonic acid used as the catalyst to terpinolene epoxide is from 0.01:1 to 0.5:1.

10. The process of claim 1, wherein the molar ratio of the sulfonic acid used as the catalyst to the organic base calculated as a free base is from 4:1 to 1.01:1.

11. The process of claim 1, wherein the isomerization is carried out in an inert organic solvent.

12. The process of claim 11, wherein the solvent is selected from the group consisting of aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated aromatic hydrocarbons, carboxylic acid esters, ethers, ketones and nitriles.

13. The process of claim 1, wherein the isomerization is carried out at 10 to 60 C.

14. The process of claim 1, wherein limonene-4-ol is further reduced to give terpinene-4-ol.

15. The process of claim 1, wherein terpinolene epoxide of formula (I) is prepared via epoxidation of terpinolene.

16. 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 limonene-4-ol of formula (II) in accordance with claim 1.

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

(1) Isomerization with Dimethylaminopyridinium Mesylate (DMAP Mesylate) and Methanesulfonic Acid as Catalysts.

(2) 2 g (0.012 mol) terpinolene epoxide and 80 g (0.94 mol) dichloromethane were charged into the reaction vessel. 0.26 g (0.0012 mol) DMAP mesylate and 0.06 g (0.0006 mol) methanesulfonic acid were added. The mixture was stirred for 3 h at 25 C. Then, 50 ml water was added and the mixture was stirred for 2 minutes. Phases were separated and the organic phase was washed with 50 ml saturated aqueous NaCl-solution. After drying with sodium sulfate the solvent was distilled off at reduced pressure. The distillation residue contained 57% of limonene-4-ol, which corresponds to a yield of 63%.

EXAMPLE 2

(3) Isomerization with Triethylammonium Mesylate and Methanesulfonic Acid as Catalysts

(4) 10 g (0.06 mol) terpinolene epoxide and 200 g (2.36 mol) dichloromethane were charged into the reaction vessel. 1.2 g (0.006 mol) triethylammonium mesylate and 0.3 g (0.003 mol) methanesulfonic acid were added. The mixture was stirred for 3 h at room temperature. Then 50 ml water was added and the mixture was stirred for 2 minutes. Phases were separated and the organic phase was washed with 50 ml saturated aqueous NaCl-solution. After drying with sodium sulfate the solvent was distilled off at reduced pressure. The distillation residue contained 61% of limonene-4-ol, which corresponds to a yield of 62.5%.

EXAMPLE 3

(5) Isomerization with 4-Dimethylaminopyridine and Methanesulfonic Acid as Catalysts

(6) 1.1 g (0.009 mol) 4-dimethylaminopyridine and 357 g dichloromethane were charged into the reaction vessel. 1.3 g (0.014 mol) methanesulfonic acid was added. The mixture was stirred for 30 minutes. Then 250 g dichloromethane and 15 g (0.09 mol) terpinolene epoxide were added. The mixture was stirred for 4.5 h at room temperature. The dichloromethane solution was washed with 200 ml water and then with 200 ml saturated aqueous NaCl-solution. After drying with sodium sulfate the solvent was distilled off at reduced pressure. The distillation residue contained 58% of limonene-4-ol, which corresponds to a yield of 62%.

EXAMPLE 4

(7) Isomerization with Dimethylaminopyridinium Tosylate (DMAP Tosylate) and Methanesulfonic Acid as Catalysts

(8) 2 g (0.012 mol) terpinolene epoxide and 80 g (0.94 mol) dichloromethane were charged into the reaction vessel. 0.38 g (0.0012 mol) DMAP tosylate and 0.06 g (0.0006 mol) methanesulfonic acid were added. The mixture was stirred for 6 h at room temperature. Then 50 ml water was added and the mixture was stirred for 2 minutes. Phases were separated and the organic phase was washed with 30 ml saturated aqueous NaCl-solution. After drying with sodium sulfate the solvent was distilled off at reduced pressure. The distillation residue contained 56% of limonene-4-ol, which corresponds to a yield of 59%.

COMPARATIVE EXAMPLE 1

(9) Isomerization in Toluene/Acetone with P-Toluenesulfonic Acid as Catalyst

(10) 50 g (0.30 mol) terpinolene epoxide (92.2%) and 217.5 g (2.36 mol) toluene were charged into the reaction vessel. A solution of 1 g (0.005 mol) p-toluenesulfonic acid (monohydrate) in 13.2 g (0.23 mol) acetone was added. The mixture was stirred for 47 h at room temperature. 36 g sodium bicarbonate solution (5%) was added and the mixture was stirred for 45 minutes. Water was removed by azeotropic distillation. Precipitated salt was filtered off and washed with toluene. Filtrate and wash toluene were combined and toluene was distilled off with a 30 cm column. The distillation residue contained 51% of limonene-4-ol, which corresponds to a yield of 58%.

EXAMPLE 5

(11) Isomerization in Acetone (Dried) with Triethylammonium Tosylate and P-Toluenesulfonic Acid as Catalysts

(12) 3.2 g (20 mmol) terpinolene epoxide (95%) and 30 mL (23.7 g) acetone (dried) were charged into the reaction vessel. The mixture was cooled to 5-10 C. and treated with 170 mg (1 mmol) of p-toluenesulfonic acid and 274 mg (1 mmol) of triethylammonium tosylate. The mixture was stirred for 1 h at room temperature (25 C.). The mixture was extracted with methyl tert-butyl ether and water, washed with sodium bicarbonate solution, dried and evaporated. The residue contained 45% of limonene-4-ol (quantified), which corresponds to a yield of 51%.

COMPARATIVE EXAMPLE 2

(13) Isomerization in Acetone (Dried) with P-Toluenesulfonic Acid as Catalyst

(14) 3.2 g (20 mmol) terpinolene epoxide (95%) and 30 mL (23.7 g) acetone (dried) were charged into the reaction vessel. The mixture was cooled to 5-10 C. and treated with 170 mg (1 mmol) of p-toluenesulfonic acid. The mixture was stirred for 1 h at room temperature (25 C.). The mixture was extracted with methyl tert-butyl ether and water, washed with sodium bicarbonate solution, dried and evaporated. The residue contained 38% of limonene-4-ol (quantified), which corresponds to a yield of 43%.

EXAMPLE 6

(15) Isomerization in Acetone (Not Dried) with Triethylammonium Tosylate and P-Toluenesulfonic Acid as Catalysts

(16) 3.2 g (20 mmol) terpinolene epoxide (95%) and 30 mL (23.7 g) acetone (not dried) were charged into the reaction vessel. The mixture was cooled to 5-10 C. and treated with 170 mg (1 mmol) of p-toluenesulfonic acid and 274 mg (1 mmol) of triethylammonium tosylate. The mixture was stirred for 1 h at room temperature (25 C.). The mixture was extracted with methyl tert-butyl ether and water, washed with sodium bicarbonate solution, dried and evaporated. The residue contained 26.2% of limonene-4-ol (quantified), which corresponds to a yield of 28.4%.

COMPARATIVE EXAMPLE 3

(17) Isomerization in Acetone (Not Dried) with P-Toluenesulfonic Acid as Catalyst

(18) 3.2 g (20 mmol) terpinolene epoxide (95%) and 30 mL (23.7 g) acetone (not dried) were charged into the reaction vessel. The mixture was cooled to 5-10 C. and treated with 170 mg (1 mmol) of p-toluenesulfonic acid. The mixture was stirred for 1 h at room temperature (25 C.). The mixture was extracted with methyl tert-butyl ether and water, washed with sodium bicarbonate solution, dried and evaporated. The residue contained 13.3% of limonene-4-ol (quantified), which corresponds to a yield of 14.4%.