Process for preparing tocopherol acetate

Abstract

The present invention relates to a process for preparing tocopherol acetate which comprises reacting, in the presence of a bentonite catalyst, 2,3,5-trimethylhydroquinone diacetate with at least one unsaturated compound selected from the compound of formula (IIIa), the compound of formula (IIIb), and the compound of formula (IIIc) wherein Y is selected from OH, halogen, -O-R11, -S-R12 and -SO2-R12, R11 is selected from C1-C4-alkyl, C1-C4-alkanoyl and trifluoroacetyl, R12 is selected from C1-C6-alkyl, trifluoromethyl and phenyl, which phenyl is unsubstituted or substituted with 1, 2, 3, 4 or 5 radicals selected from halogen and methyl, and two of (A) represent a double bond and the remainder of (A) represents single bonds, to obtain tocopherol acetate. The method is devoid of a distinct esterification step.

Description

[0001] BASF SE 1 220279W001

[0002] Process for Preparing Tocopherol Acetate

[0003] The present invention relates to a process for preparing tocopherol acetate, and halogen-free tocopherol acetate.

[0004] Vitamin E is the most important fat-soluble antioxidant in biological systems. The term vitamin E includes all tocol and tocotrienol derivatives having the biological activity of (2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2 / 7-chromen-6-ol , which is the most relevant vitamin E for human health (see for instance W. Bonrath et al., Angew. Chem. Int. ed., 2012, 51, 12960 - 12990; T. Netscher, Vitamins and Hormons, 2007, Elsevier Inc. volume 76, 155).

[0005] Industrially, o-tocopherol is mainly produced in the form of all-racemic o-tocopherol and all-racemic a-tocopherol acetate, which represent equimolar mixtures of eight possible stereoisomers. Typically, all-racemic o-tocopherol is synthesized via the condensation of trimethylhydroquinone with all-racemic isophytol. This condensation reaction involves a Friedel-Crafts alkylation of the trimethylhydroquinone followed by a subsequent ring-closing reaction. The thus obtained all-racemic o-tocopherol is then transformed into the more stable acetate form via esterification, typically with acetic acid anhydride. The other tocopherols, i.e. p-, y- and 5-tocopherol, as well as the corresponding tocotrienols, in particular o-tocotrienol, preferably in the form of their acetates, are generally produced in analogous way.

[0006] Over the last decades, a large number of processes for the production of o-tocopherol have been developed. A key step in many of these processes is the Friedel-Crafts alkylation of the corresponding hydroquinone precursors, as outlined above, which is performed in the presence of a Friedel-Crafts catalyst. In particular, the following Friedel-Crafts catalysts have been suggested: Lewis acids such as ZnCh, AICI3, FeCh, TiCk, BF3 etherates, optionally in combination with strong Bronsted acids and heterogeneous catalysts including zeolites, bentonites, montmorillonites, saponites in acidic ion exchange resins.

[0007] For example, WO 2020 / 035604 suggests preparing all-racemic tocopherol acetate comprising the reaction of 2,3,5-trimethylhydroquinone with isophythol or an isophytol precursor in the presence of an acidic bentonite catalyst followed by reacting the thus obtained vitamin E with an acylating agent, such as acetic anhydride.

[0008] However, the above-mentioned methods for preparing tocopherol acetate, irrespective of the catalyst used, have in common that the crude product obtained after Friedel-Crafts-alkylation and the ring-closing reaction requires a further esterification step for obtaining tocopherol acetate.

[0009] It is an object of the present invention to provide a process for preparing tocopherol acetate comprising as few reaction steps as possible, without the need to apply expensive, corrosive and / or environmentally harmful

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[0011] catalysts and solvents. The process should be simple and applicable in large-scale production. Particularly preferably, the process should be a halogen-free process in order to avoid halogen impurities in the final product.

[0012] The object of the present invention is solved by a process for preparing a compound of formula (I) being tocopherol acetate

[0013]

[0014] the process comprising reacting, in the presence of a bentonite catalyst, a compound of formula (II) being 2,3,5-trimethylhydroquinone diacetate

[0015]

[0016] with at least one unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc)

[0017]

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[0019] wherein

[0020] Y is selected from OH, halogen, -O-R11, -S-R12and -SO2-R12,

[0021] R11is selected from Ci-C4-alkyl, Ci-C4-alkanoyl and trifluoroacetyl,

[0022] R12is selected from Ci-Ce-alkyl, trifluoromethyl and phenyl, which phenyl is unsubstituted or substituted with 1, 2, 3, 4 or 5 radicals selected from halogen and methyl, and

[0023] two of represent a carbon-carbon double bond and the remainder of represents carbon-carbon single bonds,

[0024] to obtain tocopherol acetate of formula (I).

[0025] The present invention further relates to halogen-free tocopherol acetate obtainable by the process described above. In the context of the present invention, the term "halogen-free” denotes a halogen content of less than 5 ppm.

[0026] It has surprisingly been found that 2,3,5-trimethylhydroquinone diacetate (herein also referred to "trimethylhydroquinone diacetate”) consitutes a suitable starting material for efficient, preferably halogen-free, tocopherol acetate synthesis using bentonite catalysts. The process involves hydrolysis of the trimethylhydroquinone diacetate to the corresponding monoacetate in the presence of the bentonite catalyst, followed by Friedel-Crafts-alkylation of the monoacetate with the unsaturated compound as shown above, and condensation yielding tocopherol acetate. Advantageously, the inventive method is devoid of a distinct step of esterifying the crude product obtained after Friedel-Crafts-alkylation and condensation. 2,3,5-trimethylhydroquinone diacetate can be obtained halogen-free allowing for providing a halogen-free process for preparing tocopherol acetate.

[0027] Herein, the term "alkyl” refers to a linear or branched saturated hydrocarbon radical having 1 to 3 (“Ci-Ca-alkyl”), 1 to 4 ("Ci-C4-alkyl”), 1 to 6 (“Ci-Ce-alkyl”) carbon atoms. Ci-Cs-Alkyl is methyl, ethyl, propyl and isopropyl. C1-C4-Alkyl is additionally n-butyl, 1 -methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1,1 -dimethylethyl (tertbutyl). Ci-Ce-Alkyl is additionally also, for example, n-pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, n-hexyl, 1 -methylpentyl, 2-methylpentyl, 3-methy I pentyl, 4-methylpentyl or 1 ,3-dimethylbutyl.

[0028] Herein, the term "Ci-C4-alkanoyl” denotes a Ci-C4-alkyl group, as defined above, attached via a carbonyl [(C=O)] group to the remainder of the molecule. Ci-C4-alkanoyl is methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, 1 -methylpropylcarbonyl, 2-methylpropylcarbonyl or 1,1-dimethylethylcarbonyl.

[0029] The term "halogen” denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine. Halogen as a substituent on phenyl is preferably Cl or Br.

[0030] Due to their structure, the compounds (I) can be present in the form of pure enantiomers or diastereoisomers as well as in the form of enantiomer or diastereoisomer mixtures.

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[0032] The term "stereoisomers” encompasses optical isomers, such as enantiomers or diastereoisomers, the latter existing due to more than one stereogenic centre in the molecule. The invention relates to both, the pure enantiomers or diastereoisomers of compounds of formula (I) as well as to mixtures thereof.

[0033] As outlined above, the inventive process comprises reacting, in the presence of a bentonite catalyst, 2,3,5-trimethylhydroquinone diacetate with at least one unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc) as shown above.

[0034] It was found that the process of the invention involves a partial hydrolysis of one of the acetate groups of 2,3,5-trimethylhydroquinone diacetate (II) which is catalyzed by the bentonite catalyst. Surprisingly, the hydrolysis of the diacatete compound of the formula (II) results in the formation of the monoacetate compound of the formula (Ila), i.e. (4-hydroxy-2,3,6-trimethylphenyl) aceate with high selectivity, while its isomer (4-hydroxy-2,3,5-trimethylphenyl) aceate of the formula (lib) and the fully hydrolyzed 2,3,5-trimethylhydroquinone of the formula (IV) are not formed or only formed in minor amounts.

[0035]

[0036] The reaction of the compound of formula (Ila) with one or more of the unsaturated compounds of the formulae (Illa) - (lllb) yields the target product of formula (I), i.e. tocopherol acetate. The reaction of (Ila) with one ore more of the compounds of the formulae (Illa) - (lllb) typically proceeds under formation of the Friedel-Crafts alkylation product. Since the hydroxyl groups adjacent to the alkylation position in (Ila) is unprotected, the Friedel-Crafts alkylation reaction is accompanied by a ring-closing reaction (intramolecular hydroxyalkylation) to form a condensed six-membered cycle containing an oxygen atom. If desired, the intermediate Friedel-Crafts alkylation product can also be isolated and the ring-closing reaction can be performed in a separate step. However, it is preferable that the Friedel-Crafts-al ky lation and the ring-closing reaction are performed in a single step.

[0037] Hydrolysis and Friedel-Crafts alkylation followed by ring-closure condensation can be carried out in separate reaction steps comprisingin the hydrolysis as a first step and the Friedel-Crafts alkylation reaction and ringclosure as a sectond step. The hydrolysis product can be isolated and the Friedel-Crafts alkylation reaction and ring-closure can be carried out thereafter. However, it preferred to carry out both reaction steps successively in as a one-pot process, i.e. without isolating the hydrolysis product (Ila). Surprisingly, both the hydrolysis of (II) and the the Friedel-Crafts alkylation reaction and ring-closure can be carried out simultaneously.

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[0039] In a first group of embodiments, the process is carried out in separate reaction steps. Thus, in an embodiment, the process comprises the following steps:

[0040] a) reacting, in the presence of the bentonite catalyst, the compound of formula (II) with water, to obtain a compound of formula (Ila) being 2,3,5-trimethylhydroquinone monoacetate

[0041]

[0042] and, subsequently,

[0043] b) reacting, in the presence of the bentonite catalyst, the compound of formula (Ila) obtained in step a) with the at least one unsaturated compound,

[0044] to obtain tocopherol acetate of formula (I).

[0045] Hydrolysing the compound of formula (II) being 2,3,5-trimethylhydroquinone diacetate requires water. Therefore, in the case that the process of the invention is carried out in separate reaction steps, adding water to step a) is necessary. Thus, in an embodiment, the process comprises adding water to step a). Preferably, the amount of water in step a) is in the range of 1 to 10 mol, per 1 mol of the compound of formula (II). Step b), i.e. reacting, in the presence of the bentonite catalyst, the compound of formula (Ila) obtained in step a) with the at least one unsaturated compound as described above may be carried out as described in, for example, WO 2020 / 035604.

[0046] In the case that the process is carried out in separate reaction steps, the process may comprise directly subjecting the reaction mixture obtained in step a) to step b). This advantageously allows for omitting one or more time- and resource-demanding purification step(s).

[0047] It has surprisingly been found that the process of the invention can also be carried out as a one-pot reaction. Thus, in a second group of embodiments, the process is carried out as a one-pot reaction, i.e. the hydrolysis and Friedel-Crafts alkylation followed by condensation is carried out in one pot. In this case, the step of hydrolysing, in the presence of the bentonite catalyst, 2,3,5-trimethylhydroquinone diacetate to obtain 2,3,5-trimethylhydroquinone monoacetate of formula (Ila) occurs in the same reaction mixture as the step of and reacting 2,3,5-trimethylhydroquinone monoacetate with at least one unsaturated compound as described above. Generally, as outlined above, for hydrolysing 2,3,5-trimethylhydroquinone diacetate to obtain 2,3,5-trimethylhydroquinone monoacetate, adding water is required. In a case where Y is OH in the compound of formula (Illa) or the compound of formula (lllb), water is formed as a by-product during Friedel-Crafts alkylation from the compound of formula (Illa) or the compound of formula (lllb). It has surprisingly been found that the water produced as by-product in the Friedel-Crafts alkylation can be used for hydrolysis. In other words,

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[0049] in the case that the process is carried out as a one-pot reaction, the presence of only catalytic amounts of water is sufficient, and adding external water is not necessary.

[0050] The unsaturated compounds of formula (Illa), (lllb) and / or (lllc) are either commercially available or can be prepared from readily available precursors by processes described in the art, or can be obtained from natural sources.

[0051] For example, the compounds of formula (Illa) and (lllb) in which Y is hydroxyl are readily commercially available or can be obtained from natural sources. Compounds of formula (Illa) and (lllb) in which Y represents a leaving group different from hydroxyl, as defined above, can be produced from the corresponding alcohol precursors via conventional nucleophilic substitution reactions. These nucleophilic reactions can be performed under conventional reaction conditions that are well known to the skilled person.

[0052] Specific examples of the compounds of formula (lllc) as shown above are selected from the following compounds (lllc-1), (lllc-2) and (lllc-3):

[0053]

[0054] (lllc-3)

[0055] As outlined above, the process of the invention is carried out in the presence of a bentonite catalyst. The bentonite catalyst is not particularly limited. Suitable bentonite catalysts are described in, for example, WO 2020 / 035604.

[0056] The term "bentonite” or "bentonite catalyst”, as used herein, can generally comprise all types of silicate clay minerals containing the elements H, C, 0, Si, Al, Mg, Ca, Li, Na, K, Fe, Zn, S, F and all combinations thereof. For example, the "bentonite” or "bentonite catalyst” can comprise pyrophyllite, talc, micas (e.g. muscovite, paragonite, phlogopite, biotite, lepidolite, zinnwaldite, taeniolite, fluor-tetrasilicic mica), brittle micas (margarite, chloritoid, seyberite, clintonite), hydrous micas, illites, chlorites, vermiculites, smectites (montmorillonite, saponite, nontronite, beidellite, sauconite, hectorite, fluorhectorite), kandites, serpentines and / or palygorskites (attapulgite, sepiolite). Preferably, the "bentonite” or "bentonite catalyst” comprises montmorillonites as are

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[0058] described, for example, in Klockmann's textbook of mineralogy, 16th edition, F. Euke Verlag 1978, pages 739 to 765 and in R. M. Barrer Zeolites and Clay Minerals as Sorbents and Molecular Sieves, Academic Press, and in Y. Izumi, K. Urabe, M. Onaka Zeolite, Clay, and Heteropoly Acid in Organic Reactions, VCH.

[0059] Typically, the main component of bentonite is montmorillonite, a clay mineral of the smectite group. Montmorillonite consists of two layers of silicon tetrahedrons with a central layer of one aluminium octahedron between them. It has hydroxyl groups between the layers as well as on the surface.

[0060] Suitable bentonite catalysts may be of natural or synthetic origin, as described in detail in, for example, WO 2020 / 035604. Bentonites can be divided into natural bentonites, i.e untreated bentonites, and treated bentonites (see for example J. Nones et al., Applied Clay Science, 2015, 105-106, 225-230). Suitably, the process of the invention is carried out in the presence of a treated bentonite catalyst.

[0061] The term "treated bentonite”, as used herein, refers to bentonites, where the structure, texture and other properties of the bentonite are modified by chemical treatment and / or heat treatment. Thus, the expression "treated” refers to a chemical treatment and / or heat treatment and the term "treated bentonite”, as used herein, refers to chemically treated and / or heat treated bentonite. Generally, the chemical treatment of the bentonite catalyst comprises acid treatment, alkaline treatment, metal salt treatment (cation exchange) or organic treatment. The bentonites obtained by an acid treatment or alkaline treatment are also called "acid treated bentonites”.

[0062] Processes for the production of acid-activated clay minerals, in particular layered silicates, such as bentonites, are well known in the art. An overview is, for example, provided by EP 0398636 B1 and a detailed process for acid treatment of clay minerals, such as bentonites, can for example be found in DE 10245 198 A1.

[0063] Alkaline treatment of bentonites relates to a treatment of the bentonites with mineral bases, such as NaOH, KOH or sodium carbonate, or organic bases, such as ammonia, trimethylamine or tetraalkylammonium hydroxides. Alkaline activation is typically performed by treatment with sodium carbonate.

[0064] The organic treatment of bentonites relates to a treatment of the bentonites with organic compounds, such as quaternary ammonium cations (e.g. alkylammonium and o-co-dialkylammonium).

[0065] Further organic and inorganic compounds that are exchanged into the above described minerals include: hydrazine, urea, formamide, acetamide, the Li, Na, K, Rb, Cs and NH4 salts of lower fatty acids (acetates, propionates, cyanoacetates), oxalate, glycollate, alaninate, lysinate, lactate, glycerine, acetylacetone, a-methoxyacetylacetone, acetoaceticethylester, nonanetrione-2:5:8, hexanedione-2:5, p:p'-oxydipropionitrile, p-ethoxypropionitril, tetracyanoethylene, 7,7,8,8-tetracyanoquinomethane, bis-(2-ethoxyethyl)-ether, bis-(2-

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[0067] methoxyethyl)-ether, ethyleneglycoldiglycid ether, triethyleneglycol, diethyleneglycol, triethyleneglycoldiacetate, diethylenegylcoldiacetate, hexandiol-1 :6, pentanediol-1 :5, 2:4-hexadiynediol-1:6.

[0068] Further organic bases that are exchanged into the above described minerals are amines like n-propylamine, n-butylamine, n-hexylamine, n-octylamine, benzidine, N,N,N',N'- tetramethylbenzidine, diethylamine, triethylamine, triphenylamine, p-phenylenediamine, N,N'-dimethyl-p-phenylenediamine, N,N,N',N'-tetramethyl-p-phenylenediamine, trans-4,4'-diaminostilbene dihydrochloride, benzylamine, aniline, o-toluidine.

[0069] Further long-chain alkylammonium salts that are exchanged into the above described minerals are 1 -n-alkyl pyridinium bromides and cetyltrimethyl ammonium bromide.

[0070] Preferably, the chemical treatment of the bentonite catalyst comprises metal salt treatment (cation exchange) or an acid treatment.

[0071] In a particular preferred group of embodiments, the process is carried out in the presence of an acid treated bentonite catalyst.

[0072] The term "acid treated bentonite” as used herein refers to bentonites, which are treated with a Bronsted acid, e.g. a mineral acid, such as HCI or H2SO4, H3PO3, HNO3, boric acid, silicic acid, carboxylic acids, such as formic acid or acetic acid, or other organic acids, such as trifluoroacetic acid, methane sulfonic acid, toluene sulfonic acid or trifluoromethane sulfonic acid. Preference is given to HCI and / or H2SO4 or mixtures of HCI and / or H2SO4 with other inorganic or organic acids. Typically, acid-activated bentonites are used on a large scale as bleaching earths for the discoloration of oils.

[0073] The treatment with mineral acid is also known to impart surface acidity of the clay, which improves its catalytic properties (P. Komandel, Applied Clay Science, 2016, 131, 84-99; D. A. DAmico et al. Applied Clay Science, 2014, 99, 254-260). Without wishing to be bound to theory, it is believed that during acid treatment, the edges of the silicate sheets of the clay minerals in the bentonite are opened and the Al3+and Mg2+cations of the octahedral sheet become soluble. The chemistry of this activation process, where an acidic hydrogen ion, e.g. an acidic hydrogen ion from sulfuric acid, opens the sheet structure of the clay minerals in the bentonite and forms acid sites, is, for example, illustrated in J. Amorim et al. Hydrocarbon Engineering 2016, 21, 11, 83-88. The final acid treated bentonites contain amorphous, porous, protonated and hydrated silica with a three-dimensional cross-linked structure (P. Komandel Applied Clay Science, 2016, 131, 84-99).

[0074] Furthermore, glycine and its peptides, a variety of other amino-acids and ligands that are exchanged into the above described minerals are described in R. M. Barrer Zeolites and Clay Minerals as Sorbents and Molecular Sieves, Academic Press and references cited therein.

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[0076] Preferably, the "acid treated bentonite catalyst” is selected from bentonites treated with mineral acids as well as from bentonites treated with strong organic acids. In particular, the "acid treated bentonite catalyst” is selected from bentonites treated with mineral acids.

[0077] Advantageously, these bentonite catalysts do not cause corrosion problems for the reaction apparatus or a contamination of waste water with metal ions or inorganic acids and are sufficiently acidic to carry out the process of the invention in reasonable to high reaction rates.

[0078] Acid treated bentonites are either commercially available or they can be prepared using processes that are well described in the art, as illustrated above.

[0079] Commercially available acid treated bentonites (e.g also known as acid leached bentonites having the CAS-No.

[0080] 70131-50-9) that can be applied as catalysts in the process of the invention are for example:

[0081] - montmorillonite K 10, montmorillonite K 30, montmorillonite (Aluminum pillared clay) (CAS 139264-88-3), montmorillonite-KSF (CAS 1318-93-0), obtainable e.g. from Sigma-Aldrich,

[0082] - TONSIL™ catalysts from the company Clariant Produkte (Deutschland) GmbH.

[0083] Typically, the acid treated bentonite catalyst has a BET surface area in the range of 50 to 800 m2 / g, preferably 100 to 600 m2 / g, more preferably 120 to 500 m2 / g, most preferably 150 to 400 m2 / g. The expression "BET surface area” as used herein refers to the well-known Brunauer-Emmett-Teller method of determining surface area. The BET surface area values given in the present application are determined via nitrogen adsorption by the BET method by largely following DIN 66131 (1973), as described in detail below.

[0084] Typically, the acid treated bentonite catalyst has a residual acidity, measured as mg KOH I g bentonite by titration with potentiometric indication, in the range of 3 to 70, preferably 5 to 50, more preferably 10 to 45, most preferably 15 to 40. The residual acidity (mg KOH / g bentonite) is determined according to standard procedures, as described in the experimental section below.

[0085] In brief, the determination of the residual acidity of the acid treated bentonite catalyst is conducted in such a way that first an aqueous suspension with a certain amount of bentonite catalyst is prepared. An aqueous NaOH solution with a defined concentration is then titrated to this aqueous bentonite suspension until the pH value of the bentonite suspension switches to the alkaline range (pH > 7.0), which represents to the end-point of the titration. The pH value is determined potentiometrically by means of a previously calibrated KCI-pH electrode (potentiometric indication). Then, the amount of NaOH that was necessary to reach the end-point of the titration (in milligrams) per gram of the bentonite catalyst applied in the aqueous suspension is calculated. This calculated value corresponds to the residual acidity in mg KOH I g bentonite.

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[0087] Typically, the amount of free moisture in the bentonite catalyst, in particular in the acid-treated bentonite, is at most 30 wt.-%, preferably at most 25 wt.-%, more preferably at most 20 wt.-%. The amount of free moisture in the treated bentonite is determined by weighing the individual bentonite against an anhydrous sample of the same bentonite. The anhydrous sample is obtained by drying in a vacuum oven at a temperature in the range of 100 to 200 °C, optionally under reduced pressure of below 200 mbar, preferably at a temperature in the range of 100 to 150 °C and under reduced pressure of below 10 mbar, in particular of below 1 mbar, until constant weight.

[0088] Generally, the amount of the bentonite catalyst, in particular of the acid-treated bentonite, is in the range of of 5 to 750, preferably in the range of of 10 to 500, more preferably in the range of of 20 to 250, most preferably in the range of 25 to 200 or in the range of 30 to 150 g per 1 mol of the unsaturated compound of formulae (Illa), (lllb) and / or (lllc).

[0089] Typically, the weight ratio of the bentonite catalyst, in particular of the acid-treated bentonite, to the compound (II) is in the range of 0.01 : 1 to 0.85 : 1, preferably in the range of 0.05 : 1 to 0.60 : 1.

[0090] The porous structure of bentonite can further be altered by means of hydration and dehydration processes, as it is the case with heat activation, for example (L. A. Shah et al. Applied Clay Science, 2018, 162, 155-164).

[0091] In a particularly preferred embodiment, the process comprises subjecting the bentonite catalyst, preferably the the acid treated bentonite catalyst, to a drying step to obtain the bentonite catalyst to be applied in the process of the invention. The drying step is usually carried out at a temperature in the range of 50 to 200 °C, preferably in the range of 70 to 170 °C, more preferably in the range of 80 to 150 °C, most preferably in the range of 100 to 120 °C. The drying step can generally be performed at ambient pressure or at reduced pressure. It is preferable that the drying step is carried out at reduced pressure. Preferably, the drying step is carried out at a pressure in the range of 0.1 to 500 mbar, more preferably 1 to 200 mbar. The drying time of the bentonite catalyst depends on the temperature and pressure applied in the drying step and can vary over a broad range. Typically, the drying time of the treated bentonite catalyst is in the range of several minutes to several days but is preferably in the range of 30 minutes to 2 days.

[0092] In an embodiment, the process comprises separating the used bentonite catalyst after completion of the process and reusing the separated bentonite catalyst. In other words, the bentonite catalyst is preferably recyclable. The recycling of the bentonite catalysts is described in furhter detail below.

[0093] As outlined above, the process of the invention can be carried out as a one-pot reaction or in separate reaction steps.

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[0095] In the case that the process of the invention is carried out in separate reaction steps, i.e. step a) and step b), step a) and step b) can be carried out at the same or at different temperatures, and at the same or at different pressures. For example, step a) can be carried out at a temperature in the range of 80 to 140 °C, preferably in the range of 100 to 120 °C and step b) can be carried out at a temperature in the range of 80 to 160 °C, preferably in the range of 100 to 140 °C. Alternatively, steps a) and b) can both be carried out at a temperature in the range of 50 to 200 °C, preferably in the range of 70 to 170 °C, more preferably in the range of 80 to 150 °C.

[0096] In the case that the process of the invention is carried out as a one-pot reaction, the process is usually carried out at a temperature in the range of 50 to 200 °C, preferably in the range of 70 to 170 C, more preferably in the range of 80 to 150 °C, and at ambient pressure, elevated pressure or reduced pressure, preferably at ambient pressure.

[0097] Irrespective of whether steps a) and b) are carried out in a single step or in separate steps a) and b), the reaction of these steps mey be carried out at ambient pressure, elevated pressure or reduced pressure, preferably at ambient pressure, e.g. at a pressure in the range of 500 mbar to 2 bar.

[0098] The process of the invention can take place in the absence of or in the presence of an inert gas. The expression "inert gas” as used herein generally means a gas, which under the prevailing reaction conditions does not enter into any reactions with the starting materials, reagents, or solvents participating in the reaction, or with the resultant products. It is preferable that the process of the invention takes place in the presence of an inert gas, preferably in the presence of argon or nitrogen, in particular in the presence of nitrogen.

[0099] The process of the invention is typically carried out in the presence of an aprotic solvent. The aprotic solvents may be polar aprotic organic solvents or non-polar aprotic organic solvents.

[0100] Suitable polar aprotic organic solvents (AS) are in particular selected from the following groups of polar aprotic organic solvents:

[0101] AS.1 organic carbonates, i.e. linear and cyclic carbonates, such as for example ethylene carbonate (243 °C), propylene carbonate, butylene carbonate, 2,3-propylene carbonate, isobutylene carbonate, dimethyl carbonate (90 °C), diethyl carbonate (128 °C) and di-n-propyl carbonate,

[0102] AS.2 ketones, such as for example diethylketone (102 °C) or methylisobutylketone (116 °C),

[0103] AS.3 lactones, such as for example y-butyrolactone (204 to 206 C),

[0104] ASA lactams, such as for example N-methy l-2-py rrolidone (NMP, 203 °C),

[0105] AS.5 nitriles, such as for example acetonitrile (82 °C) and valeronitrile (117 °C),

[0106] AS.6 nitro compounds, such as for example nitromethan (101 °C),

[0107] AS.7 tertiary carboxamides, such as for example dimethylformamide (153 °C),

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[0109] AS.8 urea derivatives, such as for example tetramethylurea (177 °C) and dimethylpropyleneurea (DMPU, 247 °C),

[0110] AS.9 sulfoxides, such as for example dimethylsulfoxide (DMSO, 189 °C),

[0111] AS.10 sulfones, such as for example sulfolane (285 °C),

[0112] AS.11 alicyclic ethers, such as for example 1,4-dioxane (101 °C),

[0113] AS.12 glycol ethers, such as for example alkylene glycol dialkyl ethers, dialkylene glycol dialkyl ethers and polyalkylene glycol dialkyl ethers,

[0114] and mixtures thereof.

[0115] More preferably, the polar aprotic organic solvent is selected from the groups AS.1, AS.3, ASA, AS.7, AS.8, AS.9, AS.10 and AS.12, even more preferably from AS.1, AS.7, AS.8 and AS.12, even more preferably from AS.1 and AS.12, in particular from AS.1. In other words, in a preferred embodiment, the aprotic solvent is selected from an organic carbonate.

[0116] Specifically, the polar aprotic organic solvent is selected from cyclic and linear carbonates of the general formula AS.I.a and AS.I.b, with particular preference given to cyclic carbonates,

[0117]

[0118] (AS.I.a) (AS.I.b)

[0119] wherein

[0120] R15, R16and R17independently of each other are selected from hydrogen, methyl and ethyl, in particular from hydrogen and methyl,

[0121] is selected from hydrogen, phenyl and Ci-Ci5-alkyl, where Ci-Ci5-alkyl is unsubstituted or substituted with 1, 2, or 3 radicals, selected from Ci-Ca-alkoxy, polyalkyleneoxide, phenyl and phenoxy, in particular from hydrogen, phenyl, Ci-Cs-alkyl and benzyl, and independently of each other are selected from Ci-C4-alkyl, in particular from ethyl and n- propyl.

[0122] More preferably, the carbonate solvent is selected from cyclic and linear carbonates of the general formula AS.I.a and AS.I.b, wherein

[0123] R15, R16and R17independently of each other are selected from hydrogen and methyl,

[0124] R18 is selected from hydrogen, methyl, ethyl, phenyl and benzyl, and

[0125] R19 independently of each other are selected from ethyl and n-propyl.

[0126] M / BASFTR-4204-PCBASF SE 13 220279W001

[0127] Among the above-mentioned carbonate solvents, cyclic carbonates are especially preferred.

[0128] Amongst these carbonate solvents, those carbonate solvents are preferred which have a boiling point of at least 100 °C, more preferably at least 120 °C, most preferably at least 140 °C.

[0129] Specifically, the carbonate solvent is selected from ethylene carbonate, propylene carbonate, butylene carbonate, 2,3-propylene carbonate, isobutylene carbonate, diethyl carbonate and di-n-propyl carbonate. Specific preference is given to propylene carbonate.

[0130] These cyclic and acyclic carbonates do not give rise to any toxicological concerns. Furthermore, these solvents are well biodegradable.

[0131] The aprotic solvent may also be a non-polar aprotic organic solvent, in particular a hydrocarbon solvent (HS). The hydrocarbon solvent may be selected from the following groups:

[0132] HS.1 linear and branched alkanes having 5 to 15 carbon atoms, such as for example pentane, hexanes, heptanes, octanes, nonanes, decanes, ligroin and petrol ether,

[0133] HS.2 cycloalkanes having 5 to 10 carbon atoms, such as for example cyclohexane,

[0134] HS.3 aromatic hydrocarbon solvents having 6 to 12 carbon atoms, such as for example benzene, toluene, xylenes, ethylbenzene and tetralin,

[0135] and mixtures thereof.

[0136] Preferably, the hydrocarbon solvent is an aromatic hydrocarbon solvent, i.e. HS.3.

[0137] The process of the invention may be carried out in a mixture of the solvents ("solvent mixture”) as defined above, in particular a mixture of at least one solvent AS and at least one solvent HS. For example, the content of the AS in such a solvent mixture may be in the range of 35 to 99 wt.-%, preferably 50 to 99 wt.-%, in particular 50 to 90 wt.-%, based on the total weight of the solvent mixture.

[0138] Accordingly, the weight ratio of AS to HS may be in the range of 1:3 to 100:1, preferably 1:1 to 100:1, in particular 1:1 to 10:1.

[0139] In the case that the process is carried out in separate reaction steps, i.e. steps a) and b) as outlined above, the process may comprise carrying out step a) and step b) in identical or different solvents. For example, the process may comprise carrying out step a) in a solvent as mentioned above, and step b) in a solvent as mentioned above other than the solvent used in step a). Alternatively, the process may comprise carrying out step a) in a solvent as mentioned above, and step b) in the solvent used in step a).

[0140] M / BASFTR-4204-PCBASF SE 14 220279W001

[0141] The process preferably comprises carrying out step b) in the solvent used in step a). In other words, the solvent can be separated off and exchanged. However, it is preferable to continue working in the same solvent in steps a) and b).

[0142] Suitably, the concentration of the compound of formula (II), i.e. of 2,3,5-trimethylhydroquinone diacetate, in the solvent or the solvent mixture is in the range of 200 to 2000 g / L, preferably in the range of 400 to 1500 g / L.

[0143] Suitably, the concentration of the unsaturated compound, i.e. the compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc), in the solvent or the solvent mixture is in the range of 300 to 1000 g / L, preferably in the range of 400 to 900 g / L.

[0144] The molar ratio of the compound of formula (II) to the compound(s) of formula (Illa), (lllb) and / or (lllc) is typically in the range of 1:1.2 to 10:1, preferably in the range of 1:1.1 to 5:1, more preferably in the range of 1:1 to 4:1.

[0145] In a preferred embodiment, the process of the invention comprises a distillative removal of at least one portion of the water formed during the reaction. The distillative removal of the water formed during the reaction can be facilitated by using an entraining agent, e.g. hydrocarbon solvent HS, such as cyclohexane, heptane, octane or toluene, in addition to the aprotic polar organic solvent AS, since hydrocarbon solvents often form azeotropic mixtures with water. To this end, a vapor is removed from the reaction system and condensed. In case the vapor consists of an azeotropic mixture of water with the applied solvent and / or another component of the reaction mixture, or the water comprises significant amounts of product or starting material, the resultant condensate is typically subjected to phase separation to give an aqueous phase and an organic phase. For this, the condensate is typically passed into a phase separator (decanter) where mechanical settling causes it to break down into two phases which can be extracted separately. If necessary, a water immiscible organic solvent, preferably the applied organic solvent, is added to the condensate before passing the condensate into a phase separator. The aqueous phase is removed and discarded and the organic phase is at least to some extent returned to the reaction system. "Return to the reaction system” means that the organic phase is at least partially recycled to the process of the invention.

[0146] Any of the suitable condensers can be used for the condensation or partial condensation of the vapor. These can be cooled by any desired coolants. Preference is given to condensers with air cooling and / or water cooling, particular preference being given to air cooling.

[0147] The process of the invention can be performed either batch wise (discontinuous mode), as described above, or in continuous mode. Preference is given to performing the process of the invention in continuous mode.

[0148] If the process of the invention is conducted batch wise (discontinuous mode), the reactants and the catalyst are typically placed in a suitable reaction vessel, e.g. a stirred vessel or loop reactor, at the temperatures indicated

[0149] M / BASFTR-4204-PCBASF SE 15 220279W001

[0150] above until the desired conversion is reached. The reaction time can be 0.5 to 30 h, preferably 1 to 20 h, depending on the amount of catalyst added.

[0151] Preferably, the process of the invention is conducted in such a way that first a solvent, preferably the aprotic solvent as mentioned above, and the bentonite catalyst are placed into a suitable reaction vessel, e.g. a stirred vessel or loop reactor, and heated to reaction temperature. Optionally, the resulting suspension is kept at reaction temperature for several minutes, e.g. for 1, 2, 5, 10, 15 or 20 min before the suspension is cooled to 80 °C. During these pretreatment steps, an inert gas, preferably argon or nitrogen, is introduced into the apparatus to ensure that the apparatus is oxygen-free. Afterwards, compound of formula (II) is added in one portion to the preheated solvent / cataly st suspension and the resulting mixture is heated to reaction temperature. Following this, the unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc) is added to the reaction mixture, optionally dissolved in a hydrocarbon solvent. Typically, the unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc) is added stepwise to the reaction mixture, comprising the solvent, the bentonite catalyst and the compound of formula (II), in several portions, e.g. in 2, 3, 4, 5, 10, 15 or 20 portions, or is metered in continuously. Preferably, the unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc) is metered in continuously. The addition rate of the unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc) to the reaction mixture is typically in the range of 0.2 to 5 vol.-% I min, preferably 0.3 to 3 vol.-% I min, in particular 0.5 to 2 vol.-% I min, based on the total volume of the unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc).

[0152] Depending on whether an aprotic solvent (AS) alone or a mixture of an aprotic solvent and a hydrocarbon solvent (HS) is applied as solvent in the process of the invention, the desired reaction product is separated from the obtained reaction mixture by phase separation and / or extraction with a hydrocarbon solvent. In this way, two phases are obtained, i.e. an AS-phase, comprising mainly the bentonite catalyst and eventually unreacted compound of formula (II), and a HS-phase, comprising mainly the desired reaction product and eventually unreacted unsaturated compound. After phase separation and / or extraction, the reaction product can be purified by chromatographic methods, distillation and / or crystallization, preferably by distillation.

[0153] For the separation of the bentonite catalyst from the reaction mixture or the AS-phase, generally all processes known to the skilled person that are suitable for separating solids from liquid mixtures can be used. Preferably, the bentonite catalyst is removed from the obtained reaction mixture by filtration. After separation, the bentonite catalyst is suitably dried in an inert gas stream, preferably in a nitrogen stream. The drying time of the bentonite catalyst in the inert gas stream can vary over a broad range, depending on the nature of the solvent applied in the reaction in the process of the invention. The drying time of the bentonite catalyst in the inert gas stream is

[0154] M / BASFTR-4204-PCBASF SE 16 220279W001

[0155] typically in the range of a few minutes to several days, i.e. 5 min to 5 d. The drying time of the bentonite catalyst in the inert gas stream can for example be 10 min, 30 min, 1 h, 5 h, 12 h, 1 d, 3 d or 5 d.

[0156] The reaction in process of the invention can be performed either in batch wise or continuous mode. Preference is given to performing the reaction in process of the invention in continuous mode.

[0157] For carrying out the reaction in continuous mode, the reaction is generally carried out in at least one reactor, e.g. 1, 2, 3, 4 or 5 reactors, preferably in one reactor. Preferably, the reactor comprises the treated bentonite catalyst in the form of a fixed bed or moving bed, preferably in the form of a fixed bed, into which, for example, a mixture of the solvent with the compound of formula (II) and the unsaturated compound as mentioned above are fed. In the preferred fixed-bed operation mode, the reactor can be operated in sump operation mode, i.e. the reaction mixture is guided from bottom to top, or in the trickle operation mode, i.e. the reaction mixture is guided through the reactor from top to bottom. The water formed during the reaction may be removed by drawing off a vapor from the top of the reactor, which is condensed and separated into an organic phase, eventually comprising the solvent and minor amounts of unreacted compound of formula (II) and / or reaction product, and a water phase, as described above. The organic phase is optionally returned to the at least one reactor. A stream of the reaction mixture, comprising the solvent, the reaction product and eventually unreacted compound of formula (II) is drawn off from the bottom of the reactor. Depending on whether an aprotic solvent alone or a mixture of an aprotic solvent and a hydrocarbon solvent is used as solvent, the desired reaction product is separated from the obtained reaction mixture by phase separation and / or by extraction with a hydrocarbon solvent. The reaction product can then be purified as described above.

[0158] The catalyst hourly space velocity is preferably in the range of 0.1 to 50 kg of unsaturated compound per kg of catalyst and hour, in particular 0.2 to 30 kg of unsaturated compound per kg of catalyst and hour.

[0159] The at least one reactor may be selected from any desired reactors which are suitable for carrying out heterogeneously catalyzed chemical reactions in liquid phase. Suitable reactors are non-back-mixed reactors, such as tubular reactors or dwell-time containers provided with internals, preferably back-mixed reactors such as stirred-tank reactors or loop reactors. However, it is also possible to use combinations of successive back-mixed reactors and non-back-mixed reactors. Optionally, several reactors can also be combined in a multistage apparatus. Such reactors are, for example, loop reactors with incorporated sieve trays, cascaded containers, tubular reactors with interim feed point or stirred columns.

[0160] The process of the invention provides the compound of formula (I) in high yield and selectivity. The compound of formula (I) may be further purified by recrystallization, distillation, if applicable, or by using chromatographic methods. Generally, only minor amounts of by-products are obtained. Common by-products are for example diene compounds which may be formed from the unsaturated compound via unwanted elimination reactions.

[0161] M / BASFTR-4204-PCBASF SE 17 220279W001

[0162] 2,3,5-Trimethylhydroquinone diacetate of formula (II) is commercially available or can be prepared from readily available precursors by processes described in the art.

[0163] For example, 2,3,5-trimethylhydroquinone diacetate of formula (II) may be prepared by reacting 2,3,5-trimethylhydroquinone of the formula (IV)

[0164]

[0165] with acetic anhydride, to obtain the compound of formula (II).

[0166] The step of reacting the compound of formula (IV) with acetic anhydride, to obtain the compound of formula (II) can be carried out by standard acylating procedures as, e.g., disclosed in Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin 1988, chapter 7.1.4.1. pp. 402-406.

[0167] Reacting the compound of formula (IV) with acetic anhydride may be catalyzed, e.g. by an acidic catalyst. Suitable acidic catalysts are e.g. sulfuric acid, and organic sulfone! acids, such as p-toluenesulfonic acid or methanesulfonic acid.

[0168] 2,3,5-Trimethylhydroquinone (IV) itself may be obtained starting from m-cresol of the formula (IVa) comprising a catalytical methylation of m-cresol (Va)

[0169]

[0170] to obtain 2,3,6-trimethylphenol of the formula (IVb)

[0171]

[0172] (IVb);

[0173] M / BASFTR-4204-PCBASF SE 18 220279W001

[0174] subseqent oxidization of the compound of formula (IVb) with an oxidizing agent, to obtain 2,3,5-trimethyl-p-benzoquinone (IVc)

[0175]

[0176] and

[0177] reduction of 2,3,5-trimethyl-p-benzoquinone (IVc) with a reducing agent, to obtain 2,3,5-trimethylhydroquinone of formula (IV).

[0178] Catalytic methylation of m-cresol (IVa) is typically carried out with methanol or dimethylether as the alkylating agent in the presence of a metal oxide catalyst, such as aluminium oxide, silicon oxide, magnesium oxide, calcium oxide, barium oxide, iron oxide, chromium oxide, zinc oxide, manganese oxide, zirconium oxide, thorium oxide, and the like, as well as mixed metal oxide catalysts. The individual reaction conditions for the catalytic methylation of phenols, such as m-cresol, are well known to the skilled person.

[0179] The oxidation of the thus obtained 2,3,6-trimethylphenol (IVb) can be conducted according to standard procedures that are well known to the skilled person. Typically, the oxidation is carried out in the presence of an oxidizing agent, optionally with the help of a metal salt or noble metal catalyst. In principle, all oxidizing agents known to the skilled person to be capable to oxidize phenols to quinones can be used in the oxidation.

[0180] For example, the oxidizing agent may be selected from

[0181] - hydrogen peroxide, oxygen or an oxygen containing gas in the presence of catalytic amounts of a metal salt, such as Mg(ll)-, Ca(ll)-, Ba(ll)-, Cu(ll)-, Fe(ll)-, Cr(ll)-, Mn(ll)-, Co(ll)-, Ni(ll)-, Zn(ll)-, sulfates or chlorides, as well as mixtures of these metal salts, or a noble metal catalyst, such as a ruthenium, rhodium, platinum or palladium catalyst,

[0182] - mineral acids, such as nitric acid, sulfuric acid, chloric acid, hypochloric acid, perchloric acid, iodic acid or periodic acid, and

[0183] - organic peroxy acids, such as perbenzoic acid or meta-chloroperbenzoic acid.

[0184] Suitable reaction conditions for this oxidation reaction are well known to the skilled person.

[0185] The reduction of the thus obtained 2,3,5-trimethyl-p-benzoquinone (IVc) with a reducing agent (herein also referred to as "reducing means”) can be conducted according to standard procedures that are well known to the skilled person. For example, the reducing means may be a metal in combination with an acid. Metals that will react with acids to form hydrogen are employed. Typical metals of this type are zinc, iron, magnesium,

[0186] M / BASFTR-4204-PCBASF SE 19 220279W001

[0187] aluminium, calcium, manganese, cadmium, and the like. The most preferred metals are zinc and iron. Suitable acids are those having a sufficient acidity to react with the metal employed. Preferred acids are mineral acids, such as hydrochloric acid, sulphuric acid, phosphoric acid, and the like. The most preferred acid is hydrochloric acid. When hydrochloric acid is employed in the reducing step, excellent yields of hydroquinone are obtained.

[0188] As alternative reducing means, metal hydrides, such as sodium hydride, sodium aluminium hydride, sodium borohydride, and the like, can be employed.

[0189] The reducing step may also be a step of catalytic hydrogenation. In this variant, the benzoquinone is usually dissolved in an inert solvent and contacted with hydrogen and a hydrogenation catalyst. Any solvents that are inert, i.e. any solvents that do not react with the starting materials, intermediates and reagents applied in the reducing step or with the obtained products, can be employed. Suitable solvents are selected from alcohols such as methanol, ethanol, propanol and isopropanol; aromatic and substituted aromatic hydrocarbons such as benzene, chlorobenzene, dichlorobenzenes, toluene, xylene; and aliphatic hydrocarbons such as pentane, hexanes, cyclohexane, heptanes, octanes, nonanes, decanes, ligroin and petrol ether, halogenated aliphatic hydrocarbons, such as dichloromethane, trichloromethane and tetrachloromethane, ethers, such as dibutyl ether, tetrahydrofurane (THF), 1,4-dioxane, 1,2-dimethoxyethane; and mixtures thereof.

[0190] Suitable hydrogenation catalysts are those commonly used in the art to catalyse the hydrogenation of organic compounds. Some examples of these include palladium chloride on charcoal, activated nickel, nickel-nickel oxide, platinum-platinum oxide, platinum black, platinum on charcoal, copper chromite, Raney nickel, palladium, palladium black, palladium on charcoal, palladium sponge, nickel, copper impregnated alumina, activated alumina, Raney copper, chromium, vanadium, molybdenum, and the like.

[0191] Preferably the hydrogenation catalyst is a heterogeneous hydrogenation catalyst, more preferably a supported metal catalyst.

[0192] Suitable supports are carbon, carbon black, active charcoal, graphite, aluminium oxide, silicon oxide, titanium dioxide, zirconium dioxide, cerium dioxide, lanthanium(l ll)-oxide, zinc oxide, silicates, asbestos, silicon carbide, calcium carbonate, magnesium carbonate, magnesium sulfate, barium carbonate, barium sulfate, zeolites, diatomaceous earth, and mixtures thereof.

[0193] More preferably, the hydrogenation catalyst is a carbon supported catalyst. In particular, the hydrogenation catalyst is a carbon supported noble metal catalyst, i.e. a noble metal catalyst comprising a support material based on carbon (C), for example activated carbon.

[0194] In principle, suitable carbon-based support materials are all carbon materials known to the person skilled in the art for such uses. Suitable carbon-based support materials are for example carbon, carbon black, active

[0195] M / BASFTR-4204-PCBASF SE 20 220279W001

[0196] charcoal and graphite. The support materials may preferably be used in the form of shaped bodies, granules, strands, pellets, spall, tablets or prills. The BET surface area of the support materials (25 °C) is typically in the range of 1 to 10000 m2 / g, preferably 10 to 5000 m2 / g.

[0197] Suitable noble metals are for example selected from Pt, Pd, Ru, Rh and Ir.

[0198] Specifically, the hydrogenation catalyst is selected from a carbon supported Pd catalyst, more specifically from Pd on charcoal.

[0199] The metal content of the supported metal catalyst is typically in the range of 0.1 to 20 wt.-%, preferably 1 to 15 wt.-%, based on the total weight of the carbon supported noble metal catalyst.

[0200] Typically, the amount of the hydrogenation catalyst is in the range of 0.05 to 20 wt.-%, preferably 0.1 to 10 wt.-%, more preferably 0.2 to 5 wt.-%, based on the amount of quinone present in the reaction mixture.

[0201] Catalytic hydrogenation may be carried out at atmospheric pressure or at elevated pressures. Higher pressures usually result in faster hydrogenation rates. Suitable hydrogenation pressures are typically in the range of 1 to 100 bar, preferably 1 to 50 bar, more preferably 2 to 30 bar.

[0202] Suitable hydrogenation temperatures are in the range of 20 to 150 °C, preferably 30 to 120 °C, more preferably 40 to 100 °C.

[0203] The catalytic hydrogenation can be carried out in a variety of reactors known for this purpose, such as a serial loop reactor as described in US 5,756,856, but also in simpler reactors, as described for example in DE 2008128. Preference is given to fixed bed reactors, in particular to trickle bed reactors.

[0204] The obtained compound of formula (IVc) is typically worked up by filtering off the hydrogenation catalyst. The thus obtained reaction mixture is preferably directly used in the reaction to obtain the compound of formula (II).

[0205] If desired, the obtained reaction mixture can be further purified in a conventional way, e.g. by mixing with water, separating the phases and, where appropriate, purifying the crude products by using chromatographic methods, by distillation, or by recrystallization.

[0206] M / BASFTR-4204-PCBASF SE 21 220279W001

[0207] 2,3,5-trimethylhydroquinone diacetate of formula (II) may be prepared by reacting 4-oxoisophorone of formula (V)

[0208]

[0209] with acetic anhydride, to obtain the compound of formula (II). Reacting the compound of 4-oxoisophorone (V) with acetic anhydride to obtain the compound of formula (II) involves a rearrangement of the hydrocarbon skeleton of 4-oxoisophorone (V).

[0210] The reaction of 4-oxoisophorone (V) with acetic anhydride, to obtain the compound of formula (II) is, e.g., disclosed in DE 2 149 159 A1, DE 19805690 A1, EPO 916642 A1, EP 0952 137 A1, EP 1 028 103 A1 and EP 1 094062 A1.

[0211] The rearrangement is suitably carried out in the presence of a catalyst. The catalyst may be an acid-acting solid which is stable under the reaction conditions. Examples of such substances are crystalline and / or amorphous aluminosilicates, clay minerals or Pillard clays that are used in each case in the H-form, mineral acids on suitable supports, for example sulfuric acid on ZrC>2 or SnC>2, or phosphoric acid on Si O2, ion exchange resins with acidic groups, in particular based on fluorinated resins such as Nafion-H (duPont) or Amberlyst (Rohm and Haas), as well as polysiloxanes with acidiyc groups, for example Deloxan ASP (Degussa-Huls AG). SO3 groups in particular serve as acidic groups.

[0212] Particularly suitable are acidic, large pore zeolites, in partiuclar those with 12 annular pores, having pore diameters in the range of 0.5 to 0.8 nm. Examples include Y-zeolites, beta-zeolites, dealuminated zeolites or mordenites. These are described in particular in "Atlas of Zeolite Structure Types” (W. M. Meier et al., 4th Revised Edition, Elsevier, 1996). In principle, acidic zeolite types having the above or larger pore diameters are suitable. Also suitable are medium pore (with 10 annular pores) zeolites, for example of the ZSM-5 type.

[0213] The modulus, i.e. the SIO2 / AI2O3 molar ratio of a zeolite, which is an important measure of its acid capacity, may vary within wide limits. The modulus of a given zeolite type may be determined basically by the composition of the synthesis gel from which it is crystallized. In the case of the Y-zeolites this can also be adjusted in a wide range by the subsequent dealumination, for example by reaction with steam or SiCU. Conventional zeolite syntheses, as are described, for example, in "Handbook of Molecular Sieves” (R. Szostak, Van Nostrand Reinhold, 1992) and literature cited therein, yield the zeolites generally in the catalytically inactive Na-form. In order to convert them into the catalytically active H-form, an ion exchange may be carried out with acids, for example hydrochloric acid or sulfuric acid, or with ammonium salts, for example NH4CI, (NH4)2SO4 or NH4-acetate, followed by calcination.

[0214] M / BASFTR-4204-PCBASF SE 22 220279W001

[0215] Especially suitable are H-Y-zeolites with a modulus in the range of 7.5 to 200, in particular in the range of 25 to 120, H-beta-zeolites with a modulus in the range of 13 to 60, in particular in the range of 18 to 30, and Flmordenites with a modulus in the range of 5 to 100, in particular in the range of 10 to 30.

[0216] Also suitable are aluminosilicates having a regular mesopore structure, for example MCM-41 or MCM-48. The mesopores with pore diameters in the range of 2.0 to 10.0 nm permit a rapid diffusion of the reactants to the catalytically active centers.

[0217] The zeolites or aluminosilicates with regular mesopore structure may be used in shaped or unshaped form. The unshaped materials are obtained directly after the synthesis and a possible ion exchange. The shaping may be carried out directly after the synthesis, by known methods such as granulation for example by spray drying, fluidized bed-spray granulation drying, or plate granulation, extrusion as well as tabletting. Examples of possible binders that may be added in the shaping step are silicon dioxide, aluminum oxide, titanium dioxide and clay minerals.

[0218] The materials used as catalysts generally lose their catalytic activity during the reaction. The reason for this is in particular the deposition of high molecular weight secondary products or by-products in the pore system. In order to restore the original activity, these products must be removed by suitable methods. This can be achieved in the case of inorganic materials for example by calcination in a muffle furnace, a rotating cylinder or any other suitable equipment, at a temperature in the range of 250 to 800 °C, preferably in the range of 400 to 650 °C. The calcination is generally carried out in an air or inert gas atmosphere.

[0219] It is particularly advantageous to carry out the calcination in a nitrogen atmosphere and afterwards in air. The calcination duration can easily be matched to the specific conditions, a duration of 2 h generally being sufficient. The heating rate may vary within a wide range. If no or only slight amounts of high molecular weight products have been formed, the regeneration may also be carried out by means of an extraction using suitable solvents. Suitable solvents for this purpose are esters such as ethyl acetate; ketones such as acetone; organic acids, acetic acid; acid anhydrides, such as acetic anhydride, or alcohols. In this case, the catalyst to be regenerated is stirred with the corresponding solvent at room temperature or elevated temperature. The solid is then separated, for example by filtration or centrifugation, if necessary dried, calcined, and returned to the process.

[0220] The amount of catalyst may be in the range of 5 to 150 wt-%, preferably in the range of 20 to 60 wt-%, based on the compound of formula (V).

[0221] The rearrangement may be carried out at a temperature in the range of 0 to 140 °C, preferably in the range of 20 to 100 °C.

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[0223] The molar ratio of acetic anhydride to the compound of formula (V) may be in the range of 3:1 to 10:1, preferably in the range of 3:1 to 5:1.

[0224] The rearrangement may be carried out in an organic solvent. Suitable organic solvents are aliphatic and cyclic esters such as ethyl acetate, propyl acetate, isopropyl acetate, isobutyl acetate and y-butyrolactone; hydrocarbons such as hexane, heptane, toluene, and xylene; and ketones such as isobutyl methyl ketone, diethyl ketone and isophorone.

[0225] 4-Oxoisophorone (V) can be prepared starting from isophorone (o-isophorone) of the formula (Va). The preparation of 4-oxoisophorone (V) typically comprises reacting isophorone of formula (Va)

[0226] with a catalyst, to obtain p-isophorone of formul

[0227]

[0228]

[0229] and

[0230] oxidation of p-isophorone of formula (Vb) with an oxidation catalyst, to obtain 4-oxoisophorone of formula (V).

[0231] The isomerization step of reacting isophorone (Va) with a catalyst, to obtain p-isophorone of formula (Vb) is, e.g., disclosed in US 4845303 A and US 5276 197 A.

[0232] The catalyst for reacting isophorone (Va) to obtain p-isophorone (Vb) may be a heterogeneous catalyst. The heterogeneous catalyst may be an oxide or a mixed oxide, preferably of the elements Mg, Al, Si and Ni. Aluminum silicate can be used as the catalyst, whereby this should be considered as being a mixed oxide of aluminium and silicon oxides.

[0233] The catalyst can be present in pure form, can be mixed with an inert carrier material, preferably with an inert carrier material having a little porosity, or can be fixed on an inert, formed carrier material, e.g. ceramic, glass or gamma-aluminum oxide.

[0234] Nickel oxide itself or nickel oxide, optionally calcinated, on an inert, formed carrier material (for example ceramic, glass as well as gamma-aluminium oxide) is a preferred catalyst. Nickel oxide on a ceramic carrier material is

[0235] M / BASFTR-4204-PCBASF SE 24 220279W001

[0236] especially preferred. A further especially preferred catalyst is nickel oxide, calcinated at a temperature of > 1000 °C, on a gamma-aluminium oxide carrier.

[0237] The isomerization of (Va) to (Vb) may be carried out in the presence of a diluent gas. Suitably, the diluent gas is an inert gas. Isomerization may be carried out at a pressure of 1 to 200 kPa. In an especially preferred embodiment, the isomerization reaction is carried out at atmospheric pressure. Isomerization may be carried out at a temperature in the range of 300 to 450 °C.

[0238] The oxidation of p-isophorone (Vb) with an oxidation catalyst, to obtain 4-oxoisophorone of formula (Vc) is, e.g., disclosed in US 5874632 A and US 4046813 A.

[0239] The oxidation catalyst may be any salt of lead, vanadium, chromium, manganese, iron or cobalt. In a preferred embodiment, the oxidation catalyst is vanadium, manganese or iron salt. The salts of lead, vanadium, chromium, manganese, iron and cobalt used as the oxidation catalysts can be classified as follows: salts of acids, salts of enols (salts of 1 ,3-diketones), salts of alcohols (alcoholates).

[0240] Any conventional organic or inorganic acid which forms a salt with the above-mentioned metals can be utilized as the oxidation catalyst. Among the preferred acid salts are salts of weak acids, especially weak organic acids such as aroic acids, alkanoic acids and aryl alkanoic acids. Examples of such salts are lead naphthenate, lead acetate, vanadium naphthenate, vanadium acetate, chromium naphthenate, chromium acetate, manganese naphthenate, manganese acetate, iron naphthenate, iron acetate, iron propionate, cobalt acetate, cobalt propionate, preferably vanadium naphthenate, manganese acetate and iron naphthenate. Among the metal salts are metal salts of inorganic acids, especially strong inorganic acids. Among the preferred acids are hydrohalic acids, sulfuric acids, phosphoric acids, etc. Among the inorganic acid salts of these metals are vanadium oxysulfate and the chlorides and sulfates of iron, wherein iron (III) chloride and iron (II) sulfate are especially preferred. Any salt of the above metals with an enol can be utilized to carry out the oxidation of p-isophorone.

[0241] Examples of salts of enols (1 ,3-diketones) are vanadium acetylacetonate, chromium acetylacetonate, manganese acetylacetonate, iron acetylacetonate and cobalt acetylacetonate.

[0242] Any salt of the above metals with an alcohol (alcoholate) can be utilized to carry out the oxidation of p-isophorone (Vb) to 4-oxoisophorone (V). Among the preferred alcohols are those alcohols of the aliphatic saturated hydrocarbons such as the lower alkanols.

[0243] Examples of salts of alcohols (alcoholates) are vanadium isopropylate, vandium n-butylate, manganese butylate, iron propylate and cobalt hexanolate.

[0244] M / BASFTR-4204-PCBASF SE 25 220279W001

[0245] Especially preferred oxidation catalysts are selected from vanadium acetylacetonate, vanadium isopropylate, vanadium oxysulphate, managanse acetylacetonate, manganese acetate and iron (III) acetylacetonate.

[0246] The oxidation of p-isophorone (Vb) to 4-oxoisophorone (V) is preferably carried out in the presence of an organic nitrogen base. Any conventional organic nitrogen base can be utilized. The presence of one or more bases increases the yield of the desired oxidation product and extensively supresses the formation of undesirable byproducts. Among the organic nitrogen bases are the organic amine bases such as the primary, secondary or tertiary amine bases. Preferred bases include cyclic nitrogen bases, especially aromatic nitrogen bases such as pyridine and its homologues (e.g. 2-methyl-4-ethyl-pyridine) and also N-heterocyclic bases (e.g. piperidine and morpholine); aliphatic nitrogen bases which include mono, di or tertiary alkyl or alkanol amines e.g. triethylamine and ethanolamine. Mixtures of cyclic and aliphatic nitrogen bases can also be used.

[0247] The oxidation can be carried out in either the presence or absence of a solvent. If the catalyst used is at least partly soluble in the substrate (e.g. vanadium isopropylate in p-isophorone), the addition of a solvent is superfluous. Furthermore, the base utilized can serve as the solent. In general, it is recommended, however, to add a solvent to the oxidation components. If desired, any conventional inert organic solvent can be utilized. Preferred solvents include alcohols such as methanol, ethanol, isopropanol, butanol, ethyleneglycol and diethyleneglycol; ketones such as acetone and butanone; aromatic hydrocarbons such as benzene and toluene; dimethylformamide, dimethyl sulfoxide and ethylenglycol monomethyl ether; pyridine and its homologues; and the ketoisophorone resulting in the oxidation. Dimethylformamide, ethyleneglycol monomethyl ether, ketoisophorone and pyridine and its homologues are preferred.

[0248] Oxidation of p-isophorone is carried out using an oxidant. Any oxidant capable of oxidizing p-isophorone can be used. Suitable oxidants are selected from oxygen and an oxygen containing gas such as air.

[0249] Oxidation of p-isophorone can be carried out at room temperature and atmospheric pressure. Preferably, oxidation of p-isophorone is carried out at a temperature in the range of -20 °C to 120 °C, preferably 20 to 100 °C.

[0250] Preparing the compound of formula (II) starting from isophorone as starting material may advantageously be realized as a halogen-free process. Thus, this embodiment advantageously allows for preparing tocopherol acetate in a halogen-free process.

[0251] The invention further relates to tocopherol acetate obtainable by the process described above, in particular according to a process comprising preparing the compound of formula (II) starting from 2,3,5-trimethylhydroquinone and / or isophorone as starting material, having a halogen content of less than 5 ppm.

[0252] M / BASFTR-4204-PCBASF SE 26 220279W001

[0253] As outlined above, the process comprising preparing the compound of formula (II) starting from 2,3,5-trimethylhydroquinone and / or isophorone as starting material may advantageously be realized as a halogen-free process. This allows for obtaining tocopherol acetate having the preferred low halogen contents mentioned above.

[0254] The invention is further illustrated by the examples that follow.

[0255] Abbreviations

[0256] The following abbreviations are used in the following:

[0257]

[0258] Materials

[0259] Trimethylhydroquinone diacetate was synthesized according to the following procedure: To a 77 wt.-% solution of 2,3,5-trimethylhydroquinone (100.0 g, 1.0 eq.) in triethylamine was added acetic anhydride (162.7 g, 2.5 eq.) at ambient temperature. The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with methyl-tertbutylether (1 L) followed by addition of water (0.5 L) at 0 °C. The phases were separated and the aqueous phase was further extracted with methyl-tertbutylether (2 x 0.25 L). The combined organic phases were washed with a 5%-HCI aq. solution (2 x 0.25 L) followed by aq. NaHCOa solution (2 x 0.25 L). The organic phase was dried over Na2SO4 and concentrated in vacuo to obtain trimethylhydroquinone diacetate as a yellowish solid (150.7 g, 98% yield).

[0260] Trimethylhydroquinone monoacetate was synthesized according to the following procedure: To a 19 wt.-% solution of 2,3,5-trimethylhydroquinone diacetate (150.7 g, 1.0 eq.) in MeOH was added a 25 wt.-% ammoniumhydroxide solution (67.5 g, 0.8 eq.) at ambient temperature. The reaction mixture was heated under reflux for 3 h. After cooling to ambient temperature, the mixture was concentrated in vacuo. The residue was recrystallized from a mixture of toluene : cyclohexane (250 mL, 1:1, wt.-%) in order to obtain trimethylhydroquinone monoacetate as brownish solid (76.2 g, 61% yield).

[0261] Isophytol was obatined in-house (BASF SE internal material); the isophytol had a purity of 96.5 to 98.5%.

[0262] M / BASFTR-4204-PCBASF SE 27 220279W001

[0263] The bentonite catalysts which can be used in the following examples are acid treated bentonites from BASF SE. Acid treated bentonite catalysts having the specifications as shown in Table 0 can be applied.

[0264] Table 0.

[0265]

[0266] <

[0267] For the preparation of the acid treated bentonite catalyst, Aberdeen clay was used as the natural bentonite starting material. These bentonites are activated using sulfuric acid followed by conversion to the final granular mineral catalysts.

[0268] Propylene carbonate (from Sigma-Aldrich), toluene (from Sigma-Aldrich), ZnBr2 (from Sigma-Aldrich) and HBraq(from Merck) are commercially available.

[0269] Methods

[0270] Gas Chromatography

[0271] The purity of the products was determined by Gas Chromatography. The results are given in area-%. The GC conditions were as follows:

[0272] - GC-system: Agilent 6980N

[0273] - GC-Column: Agilent DB-1 : 30 m (length), 0.25 mm (inner diameter), 0.25 pm (film-thickness)

[0274] - Temperature program: 80 to 350 °C at 10 ° / min, 350 °C for 10 min, total runtime: 37 min.

[0275] BET surface area

[0276] BET surface area System:

[0277] - Quantachrome Autosorb Automated Gas Sorption System 6B, serial-#: 10896010901

[0278] - Software: Autosorb for Windows® for AS-3 and AS-6 Version 1.22

[0279] - Sample weight: 0.28 to 0.43 g of solid catalyst (e.g. treated bentonite catalyst)

[0280] - Bath temperature: 77.4 K

[0281] M / BASFTR-4204-PCBASF SE 28 220279W001

[0282] - Run time: 64 to 106.7 min

[0283] - Gas for measuring: nitrogen; purity of gas: nitrogen 5.0

[0284] - Drying before measuring: via rotary vane pump and finally turbo-molecular pump for 16 h at 120 °C, < 1 mbar

[0285] - System Parameters: Cross-Sec Area 16.2 A / molec

[0286] - Multipoint BET: 5 points p / po; 0.05 < p / po < 0.30

[0287] Residual acidity

[0288] The determination of the residual acidity of the solid catalyst (e.g. treated bentonite catalyst) is conducted in such a way that first, an aqueous suspension with a certain amount of the solid catalyst is prepared as follows: 1.0 to 1.5 g of the solid catalyst is suspended in 50 mL of deionized water and stirred for 1 h. A previously calibrated KCI-pH electrode is placed into this suspension. An aqueous NaOH solution with a defined concentration of 0.1 mol / L is then titrated to this aqueous suspension until the pH value of the suspension of the solid catalyst switches to the alkaline range (inflection point), which represents the end-point of the titration. The volume V1 in mL of NaOH solution used to reach the inflection point is recorded.

[0289] Furthermore, a blank determination is carried out in the same way using 50 mL of deionized water. The volume V2 in mL of NaOH solution used is recorded. The residual acidity of the solid catalyst sample (in mg KOH / g solid catalyst), which is determined as total acid value, is then calculated based on the following formula:

[0290]

[0291] wherein

[0292] 56,1 g / mol represents a constant (molar mass of KOH in g / mol);

[0293] ml is the mass, in grams, of the test portion, i.e. the solid catalyst sample;

[0294] V1 is the volume, in milliliters, of NaOH solution used to neutralize the catalyst suspension (volume until inflection point is reached);

[0295] V2 is the volume, in milliliters, of NaOH solution used in the blank determination (volume until inflection point is reached - usually no volume consumed I blank is typically zero);

[0296] C is the concentration, in moles per liter, of the NaOH solution;

[0297] t is the titer of the NaOH solution.

[0298] The determination of the residual acidity is repeated once and thus determined twice.

[0299] Comparative Example 1 (C-1)

[0300] A 35 wt.-% solution of trimethylhydroquinone monoacetate (19.9 g, 1.5 eq.) in propylene carbonate was reacted with isophytol (18.4 g, 1.0 eq., dosage rate 1.4 mL / min) in the presence of the bentonite catalyst as outlined

[0301] M / BASFTR-4204-PCBASF SE 29 220279W001

[0302] above, e.g. betonite catalyst No. 1 of the above Table 0 (4.49 g, 21 wt.-%) as shown in Table 1. The ratio of bentonite catalyst to isophytol was 74 mg / mmol. Samples were taken after reaction times indicated in Table 1. The results are shown in Table 1.

[0303] Table 1.

[0304]

[0305] 1] Area-% determined via GC

[0306] [2] Phytyl-TMH monoacetate

[0307] In comparative example 1 using trimethylhydroquinone monoacetate as starting material, only trace amounts of tocopherol acetate were formed.

[0308] Examples 2 to 6

[0309] In examples 2 to 6, hydrolysis of trimethylhydroquinone diacetate to trimethylhydroquinone monoacetate was investigated. TMH diacetate was reacted in the solvent indicated in Table 2 and in the presence of water and the bentonite catalyst as outlined above, e.g. betonite catalyst No. 1 of the above Table 0. See Table 2.

[0310] Table 2.

[0311]

[0312] 1] Equivalents based on TMH diacetate

[0313] [2] Bentonite catalyst No. 1 of Table 0, wt.-% based on TMH diacetate

[0314] [3] Equivalents based on TMH diacetate

[0315] comparative example

[0316] M / BASFTR-4204-PCBASF SE 30 220279W001

[0317] Samples were taken after reaction times indicated in Table 3. The results are shown in Table 3.

[0318] Table 3.

[0319] <

[0320]

[0321] [1] Area-% determined via GC

[0322] * comparative example

[0323] The desired TMH monoacetate being a compound of formula (Ila) was obtained as the main product in examples 2 through 6.

[0324] Isophytol was added to the obtained reaction mixtures of examples 2 to 6 without further purification to carry out Friedel-Crafts alkylation and condensation. The dosage of isophytol was 0.2 mL / min. Samples were taken at the reaction times indicated in Table 4. The results are shown in Table 4.

[0325] M / BASFTR-4204-PCBASF SE 31 220279W001

[0326] Table 4.

[0327]

[0328] 1] Area-% determined via GC

[0329] [2] Phytyl-TMH monoacetate

[0330] * comparative example

[0331] Example 7

[0332] Analogously to examples 2 to 6, a further example was carried out as shown in Tables 5 and 6.

[0333] Table 5.

[0334]

[0335] 1] Equivalents based on TMH diacetate

[0336] [2] Bentonite catalyst No. 1 of Table 0, wt.-% based on TMH diacetate

[0337] [3] Equivalents based on TMH diacetate

[0338] * comparative example

[0339] Table 6.

[0340]

[0341] 1] Area-% determined via GC

[0342] [2] Phytyl-TMH monoacetate

[0343] * comparative example

[0344] M / BASFTR-4204-PCBASF SE 32 220279W001

[0345] It has been shown that this sequential approach of hydrolysis of TMH diacetate and subsequent reaction with isophytol using the same acidic heterogeneous bentonite catalyst yields the desired tocopherol acetate (a compound of formula (I)) in examples 2 through 7.

[0346] Comparative example 2 (C-2)

[0347] A comparative example using ZnBr2 and HBr as catalytic system known from the prior art was carried out as shown in Tables 7 and 8.

[0348] Table 7.

[0349]

[0350] 1] Equivalents based on TMH diacetate

[0351] [2] wt.-% based on TMH diacetate

[0352] [3] Equivalents based on TMH diacetate

[0353] [4] 48% aq.

[0354] [5] Waterfrom HBr

[0355] * comparative example

[0356] Table 8.

[0357]

[0358] 1] Area-% determined via GC

[0359] [2] Phytyl-TMH monoacetate

[0360] * comparative example

[0361] M / BASFTR-4204-PC

Claims

BASF SE 33 220279WC01Claims1. A process for preparing a compound of formula (I) being tocopherol acetatethe process comprising reacting, in the presence of a bentonite catalyst, a compound of formula (II) being 2,3,5-trimethylhydroquinone diacetatewith at least one unsaturated compound selected from the compound of formula (Illa), the compound of formula (lllb), and the compound of formula (lllc)whereinY is selected from OH, halogen, -O-R11, -S-R12and -SO2-R12,R11is selected from Ci-C4-alkyl, Ci-C4-alkanoyl and trifluoroacetyl,R12is selected from Ci-Ce-alkyl, trifluoromethyl and phenyl, which phenyl is unsubstituted or substituted with 1, 2, 3, 4 or 5 radicals selected from halogen and methyl, and two of represent a double bond and the remainder of represents single bonds, to obtain tocopherol acetate of formula (I).M / BASFTR-4204-PCBASF SE 34 220279W0012. The process according to claim 1, comprising carrying out the process in an aprotic solvent.

3. The process according to claim 2, wherein the aprotic solvent is selected from an organic carbonate, an aromatic hydrocarbon solvent, and a mixture thereof.

4. The process according to any one of the preceding claims, wherein the bentonite catalyst is an acid treated bentonite catalyst.

5. The process according to any claim 4, comprising subjecting the acid treated bentonite catalyst to a drying step to obtain the bentonite catalyst.

6. The process according to any one of the preceding claims, wherein the bentonite catalyst has a BET surface area in the range of 50 to 800 m2 / g, preferably 100 to 600 m2 / g, more preferably 120 to 500 m2 / g.

7. The process according to any one of the preceding claims, wherein the bentonite catalyst has a residual acidity, measured as mg KOH I g bentonite by titration with potentiometric indication, in the range of 3 to 70, preferably 5 to 50, more preferably 10 to 45.

8. The process according to any one of the preceding claims, wherein the amount of free moisture in the bentonite catalyst is at most 30 wt.-%, preferably at most 25 wt.-%, more preferably at most 20 wt.-%.

9. The process according to any one of the preceding claims, wherein the weight ratio of the bentonite catalyst to the compound of formula (II) is in the range of 0.005 : 1 to 0.85 : 1.

10. The process according to any one of the preceding claims, comprising separating the used bentonite catalyst after completion of the process and reusing the separated bentonite catalyst.

11. The process according to any one of the preceding claims, comprising the following steps:a) reacting, in the presence of the bentonite catalyst, the compound of formula (II) with water, to obtain a compound of formula (Ila) being 2,3,5-trimethylhydroquinone monoacetateM / BASFTR-4204-PCBASF SE 35 220279W001and, subsequently,b) reacting, in the presence of the bentonite catalyst, the compound of formula (Ila) obtained in step a) with the at least one unsaturated compound,to obtain tocopherol acetate of formula (I).

12. The process according to claim 11, wherein the amount of water in step a) is in the range of 1 to 10 mol, per 1 mol of the compound of formula (II).

13. The process according to claim 11 or 12, comprising carrying out step b) in the solvent used in step a).

14. The process according to any one of claims 11 to 13, comprising directly subjecting the reaction mixture obtained in step a) to step b).

15. The process according to any one of the preceding claims, comprising reacting a compound of formula (IV) being 2,3,5-trimethylhydroquinonewith acetic anhydride, to obtain the compound of formula (II).

16. The process according to any one of claims 1 to 14, comprisingreacting a compound of formula (V) being 4-oxoisophoronewith acetic anhydride, to obtain the compound of formula (II).

17. Halogen-free tocopherol acetate obtainable by the process according to any one of the preceding claims, in particular according to claim 15 or 16.M / BASFTR-4204-PC

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