(19)
(11)EP 3 294 700 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
29.01.2020 Bulletin 2020/05

(21)Application number: 16718330.0

(22)Date of filing:  22.04.2016
(51)Int. Cl.: 
C07C 29/17  (2006.01)
C07C 35/18  (2006.01)
C07C 29/56  (2006.01)
C07D 493/08  (2006.01)
(86)International application number:
PCT/EP2016/058963
(87)International publication number:
WO 2016/180614 (17.11.2016 Gazette  2016/46)

(54)

A PROCESS FOR THE PREPARATION OF LIMONENE-4-OL

VERFAHREN ZUR HERSTELLUNG VON LIMONEN-4-OL

PROCÉDÉ DE PRÉPARATION DE LIMONÈNE-4-OL


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 08.05.2015 IN 1291DE2015
30.06.2015 EP 15174608

(43)Date of publication of application:
21.03.2018 Bulletin 2018/12

(73)Proprietor: BASF Agro B.V.
6835 EA Arnhem (NL)

(72)Inventors:
  • WOLF, Bernd
    67150 Niederkirchen (DE)
  • RACK, Michael
    69214 Eppelheim (DE)
  • BENSON, Stefan
    64625 Bensheim (DE)
  • KRAUS, Helmut
    67160 Wissembourg (FR)
  • GOETZ, Roland
    68809 Neulussheim (DE)
  • NARAYANAN, Sukunath
    Mumbai 400076 (IN)
  • RISHINARADAMANGALAM, Chidambaram
    Hosur 635126 (IN)

(74)Representative: BASF IP Association 
BASF SE G-FLP-C006
67056 Ludwigshafen
67056 Ludwigshafen (DE)


(56)References cited: : 
CN-A- 101 602 770
  
  • GURUDUTT K N: "Acid-catalyzd rearrangement of terpinolene oxide", INDIAN JOURNAL OF CHEMISTRY. SECTION B, COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH (C S I R), IN, vol. 24, 1985, pages 820-823, XP009186175, ISSN: 0376-4699
  
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description


[0001] This invention relates to a process for the preparation of limonene-4-ol of formula (II) by an epoxide ring opening isomerization of terpinolene epoxide of formula (I)



[0002] Limonene-4-ol is a valuable intermediate in the synthesis of terpinene-4-ol - an unsaturated tertiary terpene alcohol that occurs naturally in a number of essential oils. Terpinene-4-ol finds use as a component in synthetic essential oils which are compounded for use as flavors or perfumes. Because of high costs and uncertainty of supply of the natural product, synthetic routes to terpinene-4-ol have been developed, e.g. via epoxidation route that includes the step of epoxidation of terpinolene followed by the epoxide ring opening of the resulting terpinolene epoxide. Nevertheless, there is still room for improvement with regard to the step of the epoxide ring opening.

[0003] US 3, 676, 504 describes a process for the preparation of limonene-4-ol from terpinolene epoxide, wherein the epoxide ring is opened by the reaction with an aqueous amine leading to N,N-dimethylaminohydrin. In the next step, N,N-dimethylaminohydrin is oxidized with hydrogen peroxide followed by pyrolysis of the resulting N-oxide giving limonene-4-ol in relatively low overall yield. The multistep route, low yield of the final product and long overall reaction time makes this process not suitable for an industrial scale preparation.

[0004] GB 1 307 053 describes a process for the preparation of limonene-4-ol by an epoxide ring opening isomerization of terpinolene epoxide in the presence of a p-toluene sulfonic acid as an isomerizing agent (catalyst). The reaction is carried out without a base. After the reaction is finished, a base is added in order to convert the p-toluene sulfonic acid into a salt. This process, however, suffers from relatively long reaction times.

[0005] Gurudutt K N et al. "Acid-catalyzed Rearrangement of Terpinolene Oxide", Indian Journal of Chemistry, Vol. 24B, August 1985, pages 820-823 describes the preparation of limonene-4-ol from terpinolene oxide with para-toluene sulphonic acid in the absence of a base.

[0006] It was accordingly an object of the present invention to provide an industrially simple process for the preparation of limonene-4-ol in good yields. Another object of the present invention was to reduce the reaction time.

[0007] Surprisingly we have found that these and further objects are, in part or in whole, achieved by the process of the present invention wherein terpinolene epoxide is subjected to an epoxide ring opening isomerization in the presence of a sulfonic acid and an organic base as a catalyst.

[0008] Accordingly, said process for the preparation of limonene-4-ol is a subject matter of the present invention.

[0009] The process according to the present invention entails a series of advantages and overcomes drawbacks of the prior art processes. It is a simple one-step synthesis leading to limonene-4-ol in very good yields. The reaction time is short and the process provides for a very good regiose-lectivity. Undesired side reactions leading to unwanted by-products are minimized. Sometimes, the product can be employed in the next reaction step without purification. These advantages make the process industrially simple and environmentally friendly.

[0010] Further embodiments of the invention are evident from the claims, the description and the examples. It is to be understood that the single features of the subject matter of the invention described herein can be applied not only in the combination given in each particular case but also in other combinations, without leaving the scope of the invention.

[0011] The ring opening isomerization according to the present invention is carried out in the presence of a sulfonic acid and an organic base as a catalyst.

[0012] The term "sulfonic acid" as used herein refers to a compound having an -SO3H group bonded to a carbon atom.

[0013] Preferably, the sulfonic acid according to the present invention is selected from (C1-C14)-alkylsulfonic acids, halo-(C1-C6)-alkylsulfonic acids, (C1-C6)-alkyl-(C6-C10)-arylsulfonic acids, camphorsulfonic acid and any mixture thereof.

[0014] In a preferred embodiment of the present invention, the sulfonic acid is selected from (C1-C14)-alkylsulfonic acids, preferably from (C1-C6)-alkylsulfonic acids, most preferably from (C1-C4)-alkylsulfonic acids. Suitable examples are methane sulfonic acid, dodecyl sulfonic acid and the like. Preference is given to methane sulfonic acid.

[0015] In another equally preferred embodiment of the present invention, the sulfonic acid is selected from halo-(C1-C6)-alkylsulfonic acids, preferably from halo-(C1-C4)-alkylsulfonic acids. Suitable example is trifluoromethane sulfonic acid and the like.

[0016] In another equally preferred embodiment of the present invention, the sulfonic acid is selected from (C1-C6)-alkyl-(C6-C10)-arylsulfonic acids, preferably from (C1-C4)-alkylphenylsulfonic acids. Suitable examples are p-toluene sulfonic acid and 2-naphthalene sulfonic acid. Preference is given to p-toluene sulfonic acid.

[0017] In yet another equally preferred embodiment of the present invention, the sulfonic acid is camphorsulfonic acid.

[0018] Alkyl chains of the alkyl radicals can be straight or branched. The prefix Cn-Cm denotes in each case the possible number of carbon atoms in the group.

[0019] Examples of such radicals are:
  • C1-C4-alkyl: for example methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl (sec-butyl), isobutyl, tert-butyl;
  • C1-C6-alkyl: C1-C4-alkyl as mentioned above, and also, for example, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-ethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl; preferably methyl, ethyl, n-propyl, i-propyl, n-butyl and the like;
  • C1-C14-alkyl: C1-C4-alkyl as mentioned above, and also, for example, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, 6-methylheptyl, 7-methyloctyl, 8-methylnonyl, 9-methyldecyl, 10-methylundecyl, 11-methyldodecyl, 12-methyltridecyl, 13-methyltetradecyl and the like.
  • C1-C4-haloalkyl: C1-C4-alkyl as mentioned above which are partially or fully substituted by fluorine, chlorine, bromine and/or iodine, for example, chloromethyl, di-chloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloro-fluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, bromomethyl, iodomethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3 trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, nonafluorobutyl, 1,1,2,2,-tetrafluoroethyl, 1-trifluoromethyl-1,2,2,2-tetrafluoroethyl and the like;
  • C1-C6-haloalkyl: C1-C4-haloalkyl and also, for example, 5-fluoropentyl, 5-chloropentyl, 5-bromopentyl, 5-iodopentyl, undecafluoropentyl, 6-fluorohexyl, 6-chlorohexyl, 6-bromohexyl, 6-iodohexyl, dodecafluorohexyl and the like;
  • C6-C10-aryl: aromatic mono- or bi-cyclic ring having 6 to 10 carbon atoms, for example phenyl, naphthyl and the like;


[0020] The term "halogen" as used herein refers to fluorine, chlorine, bromine or iodine. Particular preference is given to fluorine and chlorine. Halogenated radical can be partially or fully halogenated, i.e. 1, 2, 3, 4 or 5 or all of the hydrogen atoms of a given radical can be replaced by a halogen atom. A partially or fully halogenated radical is termed below also "halo-radical". For example, partially or fully halogenated alkyl is termed as "haloalkyl".

[0021] Preferably, the sulfonic acid of the present invention is selected from methane sulfonic acid, dodecyl sulfonic acid, trifluoromethane sulfonic acid, p-toluene sulfonic acid, 2-naphthalene sulfonic acid, camphorsulfonic acid and any mixture thereof.

[0022] More preferably, the sulfonic acid of the present invention is selected from methane sulfonic acid, dodecyl sulfonic acid, p-toluene sulfonic acid, camphorsulfonic acid and any mixture thereof.

[0023] Most preferably, the sulfonic acid of the present invention is selected from methane sulfonic acid, p-toluene sulfonic acid and any mixture thereof.

[0024] The molar ratio of the sulfonic acid used as the catalyst to terpinolene epoxide can vary and is generally from 0.01:1 to 0.5:1, preferably from 0.02:1 to 0.4:1, more preferably from 0.03:1 to 0.3:1and most preferably from 0.04:1 to 0.2:1.

[0025] The base according to the present invention is preferably selected from tertiary amines, pyridine, substituted pyridines, bicyclic amines and any mixture thereof.

[0026] In a preferred embodiment of the present invention, the base is selected from tertiary amines. Examples of suitable tertiary amines are tri-(C1-C6)-alkylamines such as trimethylamine, triethylamine, tributylamine and N,N-diisopropylethylamine; di-(C1-C6)-alkyl-phenylamines such as N,N-dimethylaniline and N,N-diethylaniline; N-methyl imidazole, N,N-dimethylaminopyridine and the like. Preference is given to triethylamine and N,N-dimethylaminopyridine. Particular preference is given to triethylamine.

[0027] In another equally preferred embodiment of the present invention, the base is selected from pyridine and substituted pyridines. Examples of suitable substituted pyridines are collidine, lutidine, picoline, N,N-dimethylaminopyridine and the like. Preference is given to pyridine and N,N-dimethylaminopyridine. Particular preference is given to N,N-dimethylaminopyridine.

[0028] In another equally preferred embodiment of the present invention, the base is selected from bi-cyclic amines. Examples of suitable bicyclic amines are 1,8-diazabicyclo[5.4.0]undec-7-en, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane and the like.

[0029] Preferably, the base of the present invention the is selected from tri-(C1-C6)-alkylamines such as trimethylamine, triethylamine, tributhylamine and N,N-diisopropylethylamine; di-(C1-C6)-alkyl-phenylamines such as N,N-dimethylaniline and 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, 1,4-diazabicyclo[2.2.2]octane and any mixture thereof.

[0030] More preferably, the base of the present invention the is selected from tri-(C1-C6)-alkylamines such as trimethylamine, triethylamine, tributylamine and N,N-diisopropylethylamine; di-(C1-C6)-alkyl-phenylamines such as N,N-dimethylaniline and N,N-diethylaniline; N-methyl imidazole, pyridine, collidine, lutidine, picoline, N,N-dimethylaminopyridine, and any mixture thereof.

[0031] Most preferably, the base of the present invention is selected from tri-(C1-C6)-alkylamines such as trimethylamine, triethylamine, tributylamine and N,N-diisopropylethylamine; pyridine, collidine, lutidine, picoline, N,N-dimethylaminopyridine, and any mixture thereof.

[0032] Particularly preferred base is selected from trimethylamine and N,N-dimethylaminopyridine.

[0033] In one preferred embodiment of the present invention, the base is used in the form of a free base. In this case said the base may form a salt with the sulfonic acid used as a catalyst after both of them are added to the reaction mixture.

[0034] In another preferred embodiment of the present invention, the base is used 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. Preference is given to salts of the base with methanesulfonic acid or p-toluene sulfonic acid.

[0035] The sulfonic acid is usually used in excess with respect to the base. The molar ratio of the sulfonic acid used as the catalyst to the organic base calculated as a free base can vary and is generally from 4:1 to 1.01:1, preferably from 3:1 to 1.05:1, more preferably from 2.5:1 to 1.1:1 and most preferably from 1.8:1 to 1.2:1.

[0036] The epoxide ring opening isomerization according to the present invention is preferably carried out in an inert organic solvent.

[0037] The solvent is preferably selected from aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated aromatic hydrocarbons, carboxylic acid esters, ethers, ketones or nitriles.

[0038] Suitable aliphatic hydrocarbons contain 5 to 10 carbon atoms, for example, n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n-decane and their isomers, petroleum ethers, cyclohexane, methylcyclohexane, any mixture thereof and the like.

[0039] Examples of suitable halogenated aliphatic hydrocarbons, are methylene chloride, chloroform, 1,2-dichloroethane, any mixture thereof and the like.

[0040] Examples of suitable aromatic hydrocarbons are benzene, toluene, ethylbenzene, cymene, xylenes, mesitylene, any mixture thereof and the like.

[0041] Examples of suitable halogenated aromatic hydrocarbons are chlorobenzene, dichlorobenzene, any mixture thereof and the like.

[0042] Examples of suitable carboxylic acid ethers are ethyl acetate and the like.

[0043] Examples of suitable ethers are dioxane, anisole, tetrahydrofurane, methyltetrahydrofurane, methyl-tert-butylether, cyclopentylmethylether, any mixture thereof and the like.

[0044] Examples of suitable ketones are acetone, methyl ethyl ketone, diethyl ketone, t-butyl methyl ketone, methylisopropylketone, any mixture thereof and the like.

[0045] Examples of suitable ketones are acetonitrile, propionitrile, any mixture thereof and the like.

[0046] In one embodiment of the present invention, terpinolene epoxide and the solvent are pre-charged in the reaction vessel and then the sulfonic acid and the base are added.

[0047] In another embodiment of the present invention the sulfonic acid, the base and the solvent are pre-charged in the reaction vessel and then terpinolene epoxide is added.

[0048] The process according to the present invention can be carried out under atmospheric pressure or under slightly elevated or reduced pressure. Typically, the atmospheric pressure is employed.

[0049] The ring opening isomerization according to the present invention is usually effected at -10 to 60°C, preferably at 0 to 40°C and more preferably at 10 to 30°C.

[0050] The starting materials according to the present invention are known compounds that are commercially available or can be prepared in a known manner.

[0051] Terpinolene epoxide of formula (I) can be prepared, for example, as described in US 3, 676, 504.

[0052] Limonene-4-ol may be further subjected to a conventional hydrogenation to give terpinene-4-ol, as described, for example in GB 1 307 053.

[0053] Terpinene-4-ol can in turn be used as a starting material for the synthesis of oxabicycloalkane herbicides, in particular of (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane as described, for example in US 4,487,945 or US 4,542,244.

[0054] (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane (herein also referred to as the "exo-(±)- isomers", CAS RN 87818-31-3)

is the racemic mixture containing equal parts of the two enantiomers (+)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane (herein also referred to as the "exo-(+)-isomer", CAS RN 87818-61-9) and (-)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane (herein also referred to as the "exo-(-)- isomer", CAS RN 87819-60-1). The exo-(±)-isomers, the exo-(+)-isomer and the exo-(-)-isomer including their preparation and herbicidal properties are disclosed in EP 0 081 893 A2 (see Examples 29, 34, 35 and 62). Further preparation methods of these compounds are described in US 4,487,945 (see Embodiments 46 and 48). The racemic mixture (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane is also described in the The Pesticide Manual, Fourteenth Edition, Editor: C.D.S. Tomlin, British Crop Production Council, 2006, entry 157, pages 195-196 with its common name cinmethylin, its IUPAC name (1RS,2SR,4SR)-1,4-epoxy-p-menth-2-yl 2-methylbenzyl ether and its Chemical Abstracts name exo-(±)-1-methyl-4-(1-methylethyl)-2-[(2-methylphenyl)methoxy]-7-oxabicyclo[2.2.1]heptane.

[0055] Limonene-4-ol and terpinene-4-ol are valuable intermediates in the preparation of (±)-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.

[0056] Limonene-4-ol and terpinene-4-ol may be further converted into (±)-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. Further conversion into (±)-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 can be accomplished by methods known in the art such as, for example, those described in EP 0 081 893 A2 and US 4,487,945.

[0057] Thus, in a further aspect of the present invention, there is provided 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 the steps of:
  1. (i) preparing limonene-4-ol (preferably terpinene-4-ol) as described herein, and
  2. (ii) converting limonene-4-ol (preferably terpinene-4-ol) into (±)-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.


[0058] The invention is illustrated by the following examples without being limited thereto or thereby.

Example 1:


Isomerization with dimethylaminopyridinium mesylate (DMAP mesylate) and methanesulfonic acid as catalysts.



[0059] 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 NaCI-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:


Isomerization with triethylammonium mesylate and methanesulfonic acid as catalysts



[0060] 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 NaCI-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:


Isomerization with 4-dimethylaminopyridine and methanesulfonic acid as catalysts



[0061] 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 NaCI-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:


Isomerization with dimethylaminopyridinium tosylate (DMAP tosylate) and methanesulfonic acid as catalysts



[0062] 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 NaCI-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:


Isomerization in toluene/acetone with p-toluenesulfonic acid as catalyst



[0063] 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:


Isomerization in acetone (dried) with triethylammonium tosylate and p-toluenesulfonic acid as catalysts



[0064] 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 (1mmol) 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:


Isomerization in acetone (dried) with p-toluenesulfonic acid as catalyst



[0065] 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:


Isomerization in acetone (not dried) with triethylammonium tosylate and p-toluenesulfonic acid as catalysts



[0066] 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:


Isomerization in acetone (not dried) with p-toluenesulfonic acid as catalyst



[0067] 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).

[0068] 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%.


Claims

1. A process for the preparation of limonene-4-ol of formula (II)

wherein terpinolene epoxide of formula (I)

is subjected to a selective epoxide ring opening isomerization in the presence of a sulfonic acid and an organic base as a catalyst.
 
2. The process according to claim 1, wherein the sulfonic acid is selected from (C1-C14)-alkylsulfonic acids, halo-(C1-C6)-alkylsulfonic acids, (C1-C6)-alkyl-(C6-C10)-arylsulfonic acids, camphorsulfonic acid and any mixture thereof.
 
3. The process according to claim 1 or 2, wherein the sulfonic acid is selected from 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 according to any one of claims 1 to 3, wherein the base is selected from tertiary amines, pyridine, substituted pyridines, bicyclic amines and any mixture thereof.
 
5. The process according to any one of claims 1 to 4, wherein the base is selected from 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 according to any one of claims 1 to 5, wherein the base is selected from triethylamine and N,N-dimethylaminopyridine.
 
7. The process according to any one of claims 1 to 6, 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 according to claim 7, wherein the base is used in the form of a salt with methanesulfonic acid or p-toluene sulfonic acid.
 
9. The process according to any one of claims 1 to 8, 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 according to any one of claims 1 to 9, 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 according to any one of claims 1 to 10, wherein the isomerization is carried out in an inert organic solvent.
 
12. The process according to claim 11, wherein the solvent is selected from aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated aromatic hydrocarbons, carboxylic acid esters, ethers, ketones or nitriles.
 
13. The process according to any one of claims 1 to 12, wherein the isomerization is carried out at -10 to 60°C.
 
14. The process according any one of claims 1 to 13, wherein limonene-4-ol is further reduced to give terpinene-4-ol.
 
15. The process according to any one of claims 1 to 14, wherein terpinolene epoxide of formula (I) is prepared via epoxidation of terpinolene.
 
16. The process according to any one of claims 1 to 15, wherein the limonene-4-ol or terpinene-4-ol is further converted into (±)-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.
 


Ansprüche

1. Verfahren zur Herstellung von Limonen-4-ol der Formel (II)

wobei Terpinolenepoxid der Formel (I)

einer selektiven Isomerisierung, bei der eine Epoxidringöffnung stattfindet, in Gegenwart einer Sulfonsäure und einer organischen Base als Katalysator unterzogen wird.
 
2. Verfahren nach Anspruch 1, wobei die Sulfonsäure aus (C1-C14) -Alkylsulfonsäuren, Halogen- (C1-C6) - alkylsulfonsäuren, (C1-C6) -Alkyl- (C6-C10) - Arylsulfonsäuren, Camphersulfonsäure und einer Mischung davon ausgewählt wird.
 
3. Verfahren nach Anspruch 1 oder 2, wobei die Sulfonsäure aus Methansulfonsäure, Dodecylsulfonsäure, Trifluormethansulfonsäure, p-Toluolsulfonsäure, 2-Naphthalinsulfonsäure, Camphersulfonsäure und einer Mischung davon ausgewählt wird.
 
4. Verfahren nach einem der Ansprüche 1 bis 3, wobei die Base aus tertiären Aminen, Pyridin, substituierten Pyridinen, bicyclischen Aminen und einer Mischung davon ausgewählt wird.
 
5. Verfahren nach einem der Ansprüche 1 bis 4, wobei die Base aus Trimethylamin, Triethylamin, Tributylamin, N,N-Diisopropylethylamin, N,N-Dimethylanilin, N,N-Diethylanilin, N-Methylimidazol, Pyridin, Collidin, Lutidin, Picolin, N,N-Dimethylaminopyridin, 1,8-Diazabicyclo[5.4.0]undec-7-en, 1,5-Diazabicyclo[4.3.0]non-5-en und 1,4-Diazabicyclo[2.2.2]octan ausgewählt wird.
 
6. Verfahren nach einem der Ansprüche 1 bis 5, wobei die Base aus Triethylamin und N,N-Dimethylaminopyridin ausgewählt wird.
 
7. Verfahren nach einem der Ansprüche 1 bis 6, wobei die Base in Form einer freien Base oder in Form eines Salzes mit einer Sulfonsäure, die mit der als Katalysator verwendeten Sulfonsäure identisch oder davon verschieden sein kann, verwendet wird.
 
8. Verfahren nach Anspruch 7, wobei die Base in Form eines Salzes mit Methansulfonsäure oder p-Toluolsulfonsäure verwendet wird.
 
9. Verfahren nach einem der Ansprüche 1 bis 8, wobei das Molverhältnis der als Katalysator verwendeten Sulfonsäure zu Terpinolenepoxid 0,01:1 bis 0,5:1 beträgt.
 
10. Verfahren nach einem der Ansprüche 1 bis 9, wobei das Molverhältnis der als Katalysator verwendeten Sulfonsäure zur organischen Base, bezogen auf freie Base, 4:1 bis 1,01:1 beträgt.
 
11. Verfahren nach einem der Ansprüche 1 bis 10, wobei die Isomerisierung in einem inerten organischen Lösungsmittel durchgeführt wird.
 
12. Verfahren nach Anspruch 11, wobei das Lösungsmittel aus aliphatischen Kohlenwasserstoffen, halogenierten aliphatischen Kohlenwasserstoffen, aromatischen Kohlenwasserstoffen, halogenierten aromatischen Kohlenwasserstoffen, Carbonsäureestern, Ethern, Ketonen oder Nitrilen ausgewählt wird.
 
13. Verfahren nach einem der Ansprüche 1 bis 12, wobei die Isomerisierung bei -10 bis 60 °C durchgeführt wird.
 
14. Verfahren nach einem der Ansprüche 1 bis 13, wobei Limonen-4-ol ferner zu Terpinen-4-ol reduziert wird.
 
15. Verfahren nach einem der Ansprüche 1 bis 14, wobei Terpinolenepoxid der Formel (I) durch Epoxidation von Terpinolen hergestellt wird.
 
16. Verfahren nach einem der Ansprüche 1 bis 15, wobei das Limonen-4-ol oder Terpinen-4-ol ferner in (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptan, eine seiner enantiomerreinen Formen oder ein nichtracemisches Gemisch davon umgewandelt wird.
 


Revendications

1. Procédé pour la préparation de limonène-4-ol de formule (II)

un époxyde de terpinolène de formule (I)

étant soumis à une isomérisation avec ouverture de cycle époxyde sélective en présence d'un acide sulfonique et d'une base organique en tant que catalyseur.
 
2. Procédé selon la revendication 1, l'acide sulfonique étant choisi parmi les acides C1-14-alkylsulfoniques, les acides halogéno-C1-6-alkylsulfoniques, les acides C1-6-alkyl-C6-10-arylsulfoniques, l'acide camphosulfonique et un quelconque mélange correspondant.
 
3. Procédé selon la revendication 1 ou 2, l'acide sulfonique étant choisi parmi l'acide méthanesulfonique, l'acide dodécylsulfonique, l'acide trifluorométhanesulfonique, l'acide p-toluènesulfonique, l'acide 2-naphtalènesulfonique, l'acide camphosulfonique et un quelconque mélange correspondant.
 
4. Procédé selon l'une quelconque des revendications 1 à 3, la base étant choisie parmi des amines tertiaires, la pyridine, des pyridines substituées, des amines bicycliques et un quelconque mélange correspondant.
 
5. Procédé selon l'une quelconque des revendications 1 à 4, la base étant choisie parmi la triméthylamine, la triéthylamine, la tributylamine, la N,N-diisopropyléthylamine, la N,N-diméthylaniline, la N,N-diéthylaniline, le N-méthylimidazole, la pyridine, la collidine, la lutidine, la picoline, la N,N-diméthylaminopyridine, le 1,8-diazabicyclo[5.4.0]undéc-7-ène, le 1,5-diazabicyclo[4.3.0]non-5-ène et le 1,4-diazabicyclo[2.2.2]octane.
 
6. Procédé selon l'une quelconque des revendications 1 à 5, la base étant choisie parmi la triéthylamine et la N,N-diméthylaminopyridine.
 
7. Procédé selon l'une quelconque des revendications 1 à 6, la base étant utilisée sous forme d'une base libre ou sous forme d'un sel avec un acide sulfonique qui peut être identique ou différent de l'acide sulfonique utilisé en tant que catalyseur.
 
8. Procédé selon la revendication 7, la base étant utilisée sous forme d'un sel avec l'acide méthanesulfonique ou l'acide p-toluènesulfonique.
 
9. Procédé selon l'une quelconque des revendications 1 à 8, le rapport molaire de l'acide sulfonique utilisé en tant que catalyseur à l'époxyde de terpinolène étant de 0,01:1 à 0,5:1.
 
10. Procédé selon l'une quelconque des revendications 1 à 9, le rapport molaire de l'acide sulfonique utilisé en tant que catalyseur à la base organique calculée en tant que base libre étant de 4:1 à 1,01:1.
 
11. Procédé selon l'une quelconque des revendications 1 à 10, l'isomérisation étant mise en œuvre dans un solvant organique inerte.
 
12. Procédé selon la revendication 11, le solvant étant choisi parmi des hydrocarbures aliphatiques, des hydrocarbures aliphatiques halogénés, des hydrocarbures aromatiques, des hydrocarbures aromatiques halogénés, des esters d'acide carboxylique, des éthers, des cétones ou des nitriles.
 
13. Procédé selon l'une quelconque des revendications 1 à 12, l'isomérisation étant mise en œuvre à une température de -10 à 60 °C.
 
14. Procédé selon l'une quelconque des revendications 1 à 13, un limonène-4-ol étant réduit davantage pour donner un terpinène-4-ol.
 
15. Procédé selon l'une quelconque des revendications 1 à 14, un époxyde de terpinolène de formule (I) étant préparé via époxydation de terpinolène.
 
16. Procédé selon l'une quelconque des revendications 1 à 15, le limonène-4-ol ou terpinène-4-ol étant converti davantage en (±)-2-exo-(2-méthylbenzyloxy)-1-méthyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane, un quelconque de ses énantiomères individuels ou un quelconque mélange non racémique correspondant.
 




REFERENCES CITED IN THE DESCRIPTION



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Patent documents cited in the description




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