Production of 2, 3, 5-trimethylhydroquinone from mixture of 2, 4, 6-tricresol and 2, 3, 6-trimethylphenol

Abstract

The invention relates to a method for producing 2, 3, 5-trimethylhydroquinone from a mixture of 2, 4, 6-tricresol and 2, 3, 6-trimethylphenol (= 2, 3, 6-TMP). The method provides a very interesting and commercially interesting method of producing alpha-tocopherol.

Description

Technical Field

[0001] The present invention relates to the field of producing 2,3,5-trimethylhydroquinone and α-tocopherol. Background Art

[0002] 2,3,5-Trimethylhydroquinone (2,3,5-Trimethylhydroquinone, TMHQ) is a key substance for synthesizing α-tocopherol. It is typically produced by meta-cresol, then methylated to produce 2,3,6-trimethylphenol and oxidized to trimethylquinone (trimethylquinone, TMHQ) and reduced to produce TMHQ, such as disclosed below: W.Bonrath et al.Angew.Chem.Int.Ed.2012,51,12982-12985or Bonrath, W.et al.(2021).Vitamins,4.Vitamin E (Tocopherols, Tocotrienols).In Ullmann'sEncyclopedia of IndustrialChemistry.https: / / doi.org / 10.1002 / 14356007.o27_o07.pub2.

[0003] Traditionally, cresol can be extracted from coal tar. However, this results in a mixture of the isomers o-cresol, m-cresol, and p-cresol. From this mixture, o-cresol is easy to separate, but m-cresol is difficult to separate from the residual mixture of m-cresol and p-cresol. Therefore, in the current industrial production of TMHQ, m-cresol is obtained through other synthetic pathways that specifically lead to the meta-isomer. However, these processes are very complex and expensive, which has a significant impact on the price of m-cresol suitable for this process.

[0004] Given the growing awareness about sustainability in chemical processes, interest in using raw materials from natural resources has increased significantly.

[0005] WO 2015 / 110654 A1 and WO 2015 / 110655 A1 disclose that 2,5-dimethylphenol or 2,3,6-trimethylphenol can be obtained from 2,5-dimethylfuran and acetylene or propyne, respectively, in the presence of an Au(I) complex. However, these methods result in isomeric mixtures of phenols. It is known that, particularly in the case of acetylene, a large amount of 2,4-dimethylphenol is produced as a byproduct during the synthesis of the target 2,5-dimethylphenol.

[0006] A new oxidation process leading to TMHQ has recently been discovered. WO 2021 / 234077 A1 discloses that 2,3,5-trimethylphenol can be photooxidized to 2,3,5-trimethylbenzoquinone.

[0007] WO 2022 / 128852 A1 discloses that 2,4,6-trimethylphenol can be photooxidized to 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one, which can be converted to 2,3,5-trimethylhydroquinone.

[0008] Common to all these prior art documents is that the respective syntheses start from specific isomers of dimethylphenol or trimethylphenol.

[0009] CH 576,928 discloses a process for preparing TMHQ starting from a mixture of 2,3,6-trimethylphenol and 2,4,6-trimethylphenol by sulfonation and separation of the desired isomer from the undesired isomer. However, this process is very disadvantageous because only one isomer (2,3,6) of the trimethylphenol in the isomer mixture is used to synthesize the desired 2,3,5-trimethylhydroquinone, while the other isomer (2,4,6-TMP) present in a significant amount (24%) is a waste product. Summary of the Invention

[0010] Surprisingly, it has been found that, using the process according to claim 1 , 2,3,5-trimethylhydroquinone can be formed from a mixture of 2,4,6-trimethylphenol and 2,3,6-trimethylphenol.

[0011] This provides a new approach to using isomeric mixtures of phenols as starting materials. It eliminates the need to separate the isomers using expensive separation techniques or complex, expensive synthetic pathways that specifically result in only one isomer being used as a starting material. In particular, it has been discovered that m-cresol and p-cresol can be used to produce TMHQ in high yield and selectivity. Furthermore, the present invention increases the attractiveness of using 2,5-dimethylfuran as a sustainable starting material for the synthesis of TMHQ.

[0012] This process is very advantageous because both the isomers 2,4,6-trimethylphenol and 2,3,6-trimethylphenol can be converted into the desired 2,3,5-trimethylhydroquinone.

[0013] Further aspects of the invention are the subject matter of further independent claims. Particularly preferred embodiments are the subject matter of the dependent claims. DETAILED DESCRIPTION

[0014] In a first aspect, the present invention relates to a process for producing 2,3,5-trimethylhydroquinone (TMHQ) of formula (I) from a mixture of 2,4,6-mesitol (=2,4,6-trimethylphenol) of formula (IIa) (=2,4,6-trimethylphenol) (=2,4,6-TMP) and 2,3,6-trimethylphenol of formula (IIb) (=2,3,6-TMP).

[0015]

[0016] The method comprises the consecutive steps of:

[0017] a) providing a mixture of a compound of formula (IIa) and a compound of formula (IIb),

[0018]

[0019] b) oxidizing a mixture of compounds of formula (IIa) and formula (IIb) to form a mixture of compounds of formula (IIIa) and compounds of formula (IIIb),

[0020]

[0021] c) reducing the mixture of the compound of formula (IIIa) and the compound of formula (IIIb) by a reducing agent to obtain a mixture of the compound of formula (IV) and the compound of formula (I),

[0022]

[0023] d) Rearranging the compound of formula (IV) in the mixture of the compound of formula (IV) and the compound of formula (I) by treating the mixture of the compound of formula (IV) and the compound of formula (I) with a basic substance at a temperature of >200°C, preferably >240°C, to obtain a compound of formula (I)

[0024]

[0025] In this document, “C x-y -alkyl" groups are alkyl groups containing x to y carbon atoms, i.e., for example, C 1-3 -Alkyl is an alkyl group containing 1 to 3 carbon atoms. Alkyl groups can be straight or branched. For example, -CH(CH3)-CH2-CH3 is considered a C4-alkyl group.

[0026] Similarly, C x-y Alkanol or C x-y Alkylene glycols are alcohols having one or two OH groups, wherein the alcohol has an alkyl group or an alkylene group having x to y carbon atoms.

[0027] The term "independent of each other" herein means that, in the context of substituents, moieties or groups, the same designated substituents, moieties or groups can occur simultaneously in the same molecule with different meanings.

[0028] In case the same labeled symbol or group is present in several formulae, in this document the definition of said group or symbol given in the context of one specific formula also applies to the other formulae containing the same said symbol.

[0029] The term "inert" as used herein when describing a material means that the material does not undergo any chemical reaction under the reaction conditions.

[0030] The peak wavelength is the wavelength at which the spectrum reaches its highest intensity.

[0031] Providing a mixture of 2,4,6-trimethylphenol (Formula (IIa)) and 2,3,6-TMP (Formula (IIb)) (step a))

[0032] In step a), a mixture of a compound of formula (IIa) (2,4,6-trimethylphenol (=2,4,6-trimethylphenol=2,4,6-TMP)) and a compound of formula (IIb) (2,3,6-trimethylphenol (=2,3,6-TMP)) is provided.

[0033]

[0034] In a first preferred embodiment, the mixture is provided by a methylation step a") of a mixture of m-cresol and p-cresol to a mixture of 2,4,6-trimethylol and 2,3,6-TMP.

[0035] Therefore, preferably, the mixture of compound (IIa) and the compound of formula (IIb) is obtained by reaction step a"),

[0036] a") A mixture of p-cresol of formula (Op) and m-cresol of formula (Om) is methylated to obtain a mixture of compounds of formula (IIa) and compounds of formula (IIb).

[0037]

[0038] The methylation in step a") can be performed by various methods.

[0039] In a preferred manner, p-cresol and m-cresol are methylated with methanol in the presence of lithium hydroxide monohydrate at elevated temperature (e.g. in an autoclave), as disclosed in EP 1 108 705 A1, in particular by way of Example 3, to produce a mixture of 2,4,6-trimethylphenol and 2,4,6-TMP, the entire disclosure of which is incorporated herein by reference.

[0040] In an even more preferred embodiment, the methylation of p-cresol and m-cresol is achieved by gas-phase methylation, in particular by converting a mixture of p-cresol and m-cresol into a mixture of methanol and optionally water in the presence of an oxidizing catalyst in an inert atmosphere at a temperature between 300 and 500° C. to produce a mixture of 2,4,6-trimethylphenol and 2,4,6-TMP. This process produces less waste, allows for a continuous process, and is therefore very advantageous economically and ecologically.

[0041] In a second more preferred embodiment, the mixture of 2,4,6-trimethylphenol and 2,3,6-TMP is provided by methylation step a′) of a mixture of 2,4-dimethylphenol (=2,4-DMP, formula (IIa-1H)) and 2,5-dimethylphenol (=2,5-DMP, formula (IIb-H)).

[0042]

[0043] The methylation in step a') can be performed by various methods.

[0044] In a preferred manner, 2,4-DMP and 2,5-DMP are methylated with methanol (e.g. in an autoclave) in the presence of lithium hydroxide monohydrate at elevated temperature, as disclosed in EP 1 108 705 A1, in particular by way of Example 3, to produce a mixture of 2,4,6-trimethylphenol and 2,4,6-TMP, the entire disclosure of which is incorporated herein by reference.

[0045] In an even more preferred manner, the methylation of 2,4-DMP and 2,5-DMP is achieved by gas phase methylation, in particular by converting a mixture of 2,4-DMP and 2,5-DMP into a mixture of methanol and optionally water in the presence of an oxidizing catalyst in an inert atmosphere at a temperature of 300-500° C. to produce a mixture of 2,4,6-trimethylphenol and 2,4,6-TMP.

[0046] The main advantage of the gas phase methylation process is the high selectivity, which leads to reduced waste formation and allows a continuous process. The use of this process leads to particularly high economic and ecological advantages.

[0047] A mixture of 2,4-DMP (Formula (IIa-1H)) and 2,5-DMP (Formula (IIb-H)) can be obtained by reacting a compound of Formula (V) with acetylene in the presence of a Pt or Au catalyst in the form of a salt or complex.

[0048]

[0049] In a third preferred embodiment, the mixture of 2,4,6-trimethylphenol and 2,3,6-TMP is obtained by reacting the compound of formula (V) and propyne in the presence of a Pt or Au catalyst in the form of a salt or a complex.

[0050] Therefore, in a very preferred embodiment, the mixture of compound (IIa) and a compound of formula (IIb) is obtained by reaction step a0),

[0051] a0) reacting a compound of formula (V) with a compound of formula (VI) in the presence of a Pt catalyst or an Au catalyst in the form of a salt or a complex to form a mixture of a compound of formula (IIa-1) and a compound of formula (II-b),

[0052]

[0053] HC≡CR (VI)

[0054] wherein R represents H or CH3, preferably CH3;

[0055]

[0056] Provided that, in the case where R represents H, a mixture of a compound of formula (IIa-1H) and a compound of formula (IIb-1H) is subjected to reaction step a'),

[0057]

[0058] a') methylating a mixture of a compound of formula (IIa-1H) and a compound of formula (IIb-1H) to obtain a mixture of a compound of formula (IIa) and a compound of formula (IIb),

[0059]

[0060] 2,5-Dimethylfuran reacts with propyne (R = CH3) or acetylene (R = H). Both propyne and acetylene are gases.

[0061] In the case where R represents CH3, propyne can also be mixed with propadiene. A specific mixture comprising propyne and propadiene is referred to by those skilled in the art as MAF gas (MAF=methylacetylene-propadiene fraction). MAF gas is an inexpensive process gas and is commercially available from various suppliers.

[0062] In one embodiment, step a0) is performed in the presence of a gold catalyst.

[0063] This is described in great detail in WO 2015 / 110655 A1 (using acetylene) or WO 2015 / 110654 A1 (using propyne), the entire disclosure of which is incorporated herein by reference.

[0064] In another embodiment, step a0) is performed in the presence of a platinum catalyst.

[0065] The platinum catalyst is preferably in the form of a platinum salt or a platinum complex.

[0066] In one embodiment, the platinum catalyst is preferably a Pt(II) salt, in particular PtCl2.

[0067] In another embodiment, the platinum catalyst is preferably a complex of Pt(II), in particular a complex of Pt(II) having at least one organic ligand comprising at least one phosphorus atom, in particular the ligand being selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

[0068] A particularly preferred Pt catalyst is PtCl2 in the presence of an organic ligand comprising at least one phosphorus atom, in particular a ligand selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

[0069] The organic ligand is preferably selected from triphenyl phosphite (P(OPh)3), diphenyl phosphate ((PhO)2P=O(OH)), triphenyl phosphate ((PhO)3P=O), triethyl phosphate ((EtO)3P=O), dibenzyl phosphite ((PhCH2O)2P=O(H)), methyl diphenyl phosphite ((MeO)P(OPh)2), triphenylphosphine (P(Ph)3), P(Ph 5F )3, bis-(2,2,2-trifluoroethyl)-phosphite ((CF3CH2O)2P=O(H)), triethyl 2-fluoro-2-phosphonoacetate ((CHFCOOEt)(EtO)2P=O), tri(2-methylphenyl) phosphite, ethyl 3-(diethoxyphosphoryl)propionate (=triethyl 3-phosphonopropionate) ((CH2CH2COOEt)(EtO)2P=O), 2-(diphenylphosphino)benzoic acid (P(Ph)2C6H4COOH), 3,9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane (Ultranox 626), P(O-isooctyl)3, P(O-isopropyl)3), P(Oi-PrF6)3, P(On-Bu)3, bis(2,4-di-tert-butylphenoxy)-λ 2-phosphine, CH3P(EtO)2, 1,1'-binaphthyl-2,2'-dihydrogen phosphate (=4-hydroxybinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphane 4-oxide), VAPOL hydrogen phosphate (=18-hydroxy-8,9-diphenyldiphenanthro[4,3-d:3',4'-f][1,3,2]dioxophosphine 18-oxide), methyltriphenoxyphosphine iodide ([CH3P(OPh)3] + I - ), 4-ethyl-2,6,7-trioxa-1-phosphobicyclo[2.2.2]octane ((CH2CH2COOEt)(EtO)2P=O, trimethylolpropane phosphite), trisodium triphenylphosphine trisulfonate (=TPPTS), disodium triphenylphosphine disulfonate (=TPPDS), and sodium triphenylphosphine monosulfonate (=TPPMS);

[0070] Where Ph represents phenyl, Ph 5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

[0071] The organic ligand is more preferably selected from triphenyl phosphite (P(OPh)3), diphenyl phosphate ((PhO)2P=O(OH)), dibenzyl phosphite ((PhCH2O)2P=O(H)), triphenyl phosphate ((PhO)3P=O), methyl diphenyl phosphite ((MeO)P(OPh)2), trisodium triphenylphosphinetrisulfonate (=TPPTS (trisodium triphenylphosphinetrisulfonate)), P(Ph 5F )3, bis-(2,2,2-trifluoroethyl)-phosphite ((CF3CH2O)2P=O(H)), tris(2-methylphenyl) phosphite, ethyl 3-(diethoxyphosphoryl)propionate (=triethyl 3-phosphonopropionate) ((CH2CH2COOEt)(EtO)2P=O), 2-(diphenylphosphino)benzoic acid (P(Ph)2C6H4COOH) and 9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane (Ultranox 626); wherein Ph represents phenyl, Ph represents phenyl. 5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

[0072] Preferably, the reaction between 2,5-dimethylfuran and propyne or acetylene is carried out in the presence of an ether or a ketone, in particular in the presence of a cyclic ether, preferably tetrahydrofuran, or acetone or methyl ethyl ketone or diethyl ketone, preferably acetone.

[0073] It is further preferred that the amount of the Pt catalyst is present in an amount of 0.1-25 mol %, in particular 6-12 mol %, relative to the compound of formula (V).

[0074] It is further preferred that the molar ratio of the above-mentioned organic ligand comprising at least one phosphorus atom to Pt is in the range of 1-2, preferably 0.5-1.5, more preferably 0.4-1.2.

[0075] Preferably, the molar ratio of the compound of formula (V) to the compound of formula (VI) is in the range of 1:1 to 1:8, in particular in the range of 1:1 to 1:8, preferably 1:1 to 1:3.

[0076] It is further preferred that the reaction is carried out at a temperature of 0°C to 80°C, in particular 10°C to 60°C, preferably 20°C to 30°C.

[0077] The reaction is preferably carried out under pressure at a temperature above the boiling point of the solvent.

[0078] The above-described methods produce a mixture of a compound of formula (IIa) and a compound of formula (IIb) or a compound of formula (IIa-1H) and a compound of formula (IIb-1H), respectively.

[0079] In the case where R is H, 2,4-DMP (IIa-1H) is primarily formed. Typically, the molar ratio of 2,4-DMP:2,5-DMP is greater than 50:50.

[0080] Since 2,4-DMP having a methyl group in the para position to the phenolic OH group in 2,4-DMP can also be used to produce the desired 2,3,5-TMHQ in the present process, the formation of a high content of 2,5-DMP is not a disadvantage.

[0081] It has been observed that the molar ratio of compound of formula (IIa-1H) (=2,4-dimethylphenol=2,4-DMP): compound of formula (IIb-1H) (=2,5-dimethylphenol=2,5-DMP) is typically <70:30, in particular <60:40, preferably <50:50.

[0082] If R is CH3, the molar ratio of compound of formula (IIa):compound of formula (IIb) is i≤50:50, in particular <10:90, more in particular <5:95, preferably <3:97, more preferably <2:98.

[0083] Oxidation (step b)

[0084] In step b), a mixture of a compound of 2,4,6-trimethylol (Formula (IIa)) and a compound of 2,3,6-TMP (Formula (IIb)) is oxidized to provide a mixture of a compound of Formula (IIIa) and a compound of Formula (IIIb).

[0085]

[0086] In one embodiment, the oxidation in step b) is a classical chemical oxidation and can be carried out by methods known in principle to a person skilled in the art.

[0087] In particular, it can be carried out by means of molecular oxygen, in particular in the presence of a cobalt complex and / or in the presence of a base, in particular an alkali metal salt, details of which are disclosed in DE 2 314 600 or DE 2 747 497.

[0088] Furthermore, the oxidation of step b) can be carried out by chlorine in a suitable solvent, preferably in the absence of a base, followed by hydrolysis with water, as described in US 4,612,401, the entire disclosure of which is incorporated herein by reference.

[0089] Furthermore, the oxidation of step b) can be carried out by means of hypohalous acids or salts in aqueous medium or in a mixture of water and an organic solvent; details of which are disclosed in EP 0 084 158 A1, the entire disclosure of which is incorporated herein by reference.

[0090] In another more preferred embodiment, the oxidation of step b) is a photochemical oxidation.

[0091] Particularly preferably, the oxidation step b) is carried out in water and at least one C 1-8 Alkanol or at least one C 2-4 Photooxidation using oxygen and a photosensitizer of formula (X) in a solvent mixture of an alkylene glycol; and using a peak wavelength (λ max ) light in the range between 580 and 780 nm,

[0092]

[0093] wherein R8, R8', R8" and R8'" independently represent H or C 1-4 alkyl;

[0094] or

[0095] where R 8 and R 8' and / or R 8” and R 8”' Together with N, it forms a five-membered or six-membered ring;

[0096] The prerequisite is that at least one residue R 8 、R 8' 、R 8” and R 8”' Different from H;

[0097] And X - Indicates anion.

[0098] Further details of the preferred photooxidation can be found in WO 2022 / 128852 A1, the entire disclosure of which is incorporated herein by reference.

[0099] In one embodiment, R8 and R8' and / or R8" and R8'" together form -(CH2)5- or -(CH2)2-NH-(CH2)2- or -(CH2)2-N(C 1-4 alkyl)-(CH2)2- or -(CH2)2-S-(CH2)2- or -(CH2)2-O-(CH2)2-.

[0100] More preferably, R 8 =R 8” and / or R 8' =R 8”' More preferably, R 8 =R 8' =R 8” =R 8”' .

[0101] More preferably, the substituent R 8 、R 8' 、R 8” and R 8”' Representative C 1-4 Alkyl, even more preferably R 8 =R 8' =R 8” =R 8”' = methyl or ethyl.

[0102] Most preferably, R 8 =R 8' =R 8” =R 8”' =CH3.

[0103] In formula (X), X - The anion is an ion that balances the charge of the cation. The cation is represented by the portion within the brackets ([)(]) in the above formula. Therefore, in principle, any anion can be used.

[0104] Preferably, X - represents a halide ion, most preferably a chloride ion.

[0105] Preferably, the compound of formula (X) is methylene blue. Further preferred is the compound of formula (X) in the form of a double salt with zinc chloride or a hydrate, the double salt form being in particular a double salt of methylene blue with zinc chloride, and the hydrate being preferably methylene blue hydrate (CAS: 122965-43-9).

[0106] For the above-mentioned photooxidation, it is important to use the peak wavelength (λ max ) light in the range between 580 and 780 nm.

[0107] In a preferred embodiment, the peak wavelength (λ max ) Light in the range between 585 and 625 nm. This corresponds to light perceived as orange.

[0108] In another more preferred embodiment, the peak wavelength (λ max ) Light in the range between 625 and 740 nm. This corresponds to light perceived as red.

[0109] This light is primarily in the high wavelength range of the visible spectrum.

[0110] In another preferred embodiment, the light used is characterized in that more than 80% of the light has a wavelength between 525 and 780 nm, preferably more than 80% of the light has a wavelength between 525 and 700 nm, more preferably more than 65% of the emitted light has a wavelength between 550 and 650 nm.

[0111] In an even more preferred embodiment, the light used is characterized in that more than 80% of the light has a wavelength between 550 and 780 nm, preferably more than 80% of the light has a wavelength between 600 and 760 nm, more preferably more than 65% of the emitted light has a wavelength between 625 and 700 nm, and most preferably more than 85% of the emitted light has a wavelength between 625 and 700 nm.

[0112] Therefore, it is important that the light used does not have significant amounts of light with wavelengths below 580 nm in its spectrum.Importantly, it has been found that green, blue and violet light or light with significant amounts of green, blue and violet in its spectrum is not suitable for the above-described photooxidation.

[0113] In one embodiment, light for photooxidation can be achieved by filtering undesirable wavelengths of light from the light source. For example, a light source with polychromatic or white emission can be filtered through a filter that blocks undesirable wavelengths.

[0114] There are different possibilities for such filters known and commercially available using different physical methods for filtering light, for example absorption, dichroic, monochromatic, bandpass, short-pass or wedge-shaped filters.

[0115] Particularly useful are absorption or cut-off filters.

[0116] It is particularly preferred that the light source is a white LED lamp in combination with a filter blocking wavelengths below 500 nm, most particularly below 625 nm.

[0117] In another embodiment, the light used for photooxidation can be generated by a corresponding light source emitting light of the desired wavelength. The light source is preferably orange or red light, more preferably an orange or red LED, to use the peak wavelength (λ max ) provides light in the range between 580 and 780 nm.

[0118] Specific examples of light sources for this embodiment are red LEDs or red or orange lasers, preferably red or orange LED lamps. Red and orange LED lamps are widely commercially available. Red and orange LEDs can provide high-intensity red or orange light. In a preferred embodiment, the flexible strip has a plurality of individual LEDs incorporated into the strip. This allows for ensuring radial orientation of the LEDs around a curved surface (e.g., a transparent tube), for example by simply wrapping the strip (preferably in a spiral) around the tube.

[0119] Red LED lamps are the most preferred light source for light.

[0120] Photooxidation in water and at least one C 1-8 Alkanol or at least one C 2-4 The method is carried out in a solvent mixture of alkylene glycol.

[0121] C 1-8 The alkanol is preferably selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, heptanol and hexanol, more preferably selected from the group consisting of methanol, ethanol and isopropanol.

[0122] C 2-4 The alkylene glycol is preferably selected from the group consisting of ethane-1,2-diol, propane-1,2-diol, propane-1,3-diol, butane-1,3-diol, butane-1,4-diol, butane-1,2-diol and butane-2,3-diol, preferably from the group consisting of ethane-1,2-diol, propane-1,2-diol and propane-1,3-diol.

[0123] Preferably, the solvent mixture is water and at least one C 1-8 Alkanol or at least one C2-4 mixture of alkylene glycols to form a homogeneous mixture.

[0124] Preferably, the solvent mixture is water and at least one C 1-8 Alkanol or at least one C 2-4 More preferably, the solvent mixture is water and C 1-8 A mixture of alkanols.

[0125] Even more preferably, the solvent mixture is water and C 1-6 A mixture of alkanols.

[0126] More preferably, the solvent mixture is a mixture of water and methanol and / or ethanol and / or isopropanol.Most preferably, the solvent mixture is a mixture of water and methanol and / or ethanol.

[0127] Preferably, water and C 1-8 Alkanol and C 2-4 The volume ratio of the sum of the alkylene glycols is in the range between 1:10 and 1:1, in particular between 1:5 and 1:2.

[0128] In a very preferred embodiment, the solvent mixture is a mixture of water and methanol, preferably the volume ratio of water to methanol is in the range between 1:20 and 1:2, preferably in the range between 1:10 and 1:2, more preferably in the range between 1:6 and 1:3, most preferably 1:4.

[0129] A key advantage is that photooxidation is carried out in a system consisting of water and at least one C 1-8 Alkanol or at least one C 2-4 The process is carried out in a solvent mixture consisting of alkylene glycols, which are very favorable solvents in terms of ecology and ecotoxicology, and are also economically favorable. Therefore, it is very advantageous that the process is carried out in the absence of any chlorinated solvents.

[0130] Preferably, the concentration of the mixture of compounds of formula (IIa) and (IIb) at the start of the photooxidation is in the range from 0.002 to 2.0 mol / l, preferably from 0.01 to 0.2 mol / l.

[0131] It is further preferred that the ratio of the compound of formula (X) to the compounds of formulae (IIa) and (IIb) is in the range between 0.005 and 20 mol %, preferably between 0.05 and 20 mol %, more preferably between 0.2 and 10 mol %.

[0132] The mixture of compounds of the formula (IIIa) and (IIIb) is produced by photochemical reaction of a mixture of compounds (IIIa) and (IIIb) with oxygen, in particular in a gas mixture comprising at least 15% by volume of oxygen.

[0133] In one embodiment, the oxygen is used in the form of a mixture comprising oxygen and an inert gas. Preferably, the amount of oxygen in this mixture comprising oxygen and an inert gas is at least 15% by volume, in particular at least 20% by volume. Such a mixture may be, for example, a binary mixture, such as an oxygen / nitrogen or oxygen / argon mixture. The mixture may consist of or contain two or more inert gases. Particularly preferably, air is used as the mixture comprising oxygen and an inert gas.

[0134] In a preferred embodiment, oxygen is used in substantially pure form, ie the amount of oxygen in the gas is 90% to 100%, more preferably 95% to 100%, even more preferably 99% to 100%.

[0135] The photooxidation can be carried out at ambient pressure or under pressure. Preferably, the oxidation is carried out under pressure, in particular at a pressure of greater than 2 bar, preferably greater than 3 bar, more preferably at a pressure of 2-20 bar.

[0136] The photooxidation is carried out in a suitable photoreactor. Preferred photoreactors are flow reactors, in particular spiral flow reactors.

[0137] The individual components can be introduced into the photoreactor individually or as a mixture. Preferably, the reaction mixture is prepared before entering the photoreactor.

[0138] The reaction is preferably carried out in such a way that the pressure of the oxygen is controlled by suitable valves and mass flow controllers.Such process control devices and methods for photoreactions using liquids and gases are known to those skilled in the art.

[0139] It is preferred that the photooxidation be carried out in a reactor that allows for a continuous process, as it is preferred that the process be a continuous process.

[0140] It was observed that a mixture of a compound of formula (IIIa) (4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one) and a compound of formula (IIIb) can be obtained by this photooxidation process (step b) in very high yields, preferably greater than 95%, even more preferably greater than 98%, and with very high selectivity.

[0141] Reduction (step c)

[0142] In step c), the mixture of the compound of formula (IIIa) and the compound of formula (IIIb) is reduced by a reducing agent to obtain a mixture of the compound of formula (IV) and the compound of formula (I).

[0143] For the reduction in step c) several reducing agents can be used.

[0144] Suitable reducing agents may be thiosulfates, tertiary phosphines, hydrogen, dithionates, dithionites, sulfites, trialkylphosphites, iodides, metals or dialkylsulfides.

[0145] The reducing agent is preferably selected from the group consisting of Na2S2O3 (sodium thiosulfate), PPh3 (triphenylphosphine), H2 / PdC, Na2S2O4 (sodium dithionite), Na2SO3 (sodium sulfite), P(OEt)3 (triethyl phosphite), NaI (sodium iodide), Zn (and / or other metals) and DMS (dimethyl sulfide).

[0146] Preferred reducing agents are thiosulfates, especially sodium thiosulfate.

[0147] Preferably, the reducing agent is used in significant molecular excess, most preferably in an amount of 2 to 10 equivalents relative to the compound of formula (I). Further preferred is that the reduction is carried out in aqueous alcoholic solution, in particular at room temperature.

[0148] The reduction can be performed on a quantitative scale and in very high yields.

[0149] The reduction in step c) can be carried out in a batch process or in a continuous process.

[0150] Preferably, step c) is performed in a continuous manner.

[0151] Rearrangement (step d)

[0152] In step d), the compound of formula (IV) in the mixture of the compound of formula (IV) and the compound of formula (I) is rearranged by treating the mixture of the compound of formula (IV) and the compound of formula (I) with a basic substance at a temperature of >200°C, preferably >240°C, to obtain the compound of formula (I).

[0153] Examples of such alkaline substances include alkali metals such as sodium, potassium, lithium, rubidium, and cesium; alkaline earth metals such as calcium, magnesium, barium, and strontium; and alkaline compounds containing at least one of these metals in their molecular structure. As examples of such alkaline substances, the following compounds are mentioned:

[0154] A. alkali metal or alkaline earth metal hydroxides, such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, and barium hydroxide; and

[0155] B. Alkali or alkaline earth metal carbonates and bicarbonates, such as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, barium carbonate, and magnesium carbonate; and

[0156] C. Alkaline earth metal oxides such as calcium oxide, magnesium oxide, and barium oxide; and

[0157] D. Alkali metal or alkaline earth metal-containing compounds hitherto used as buffers, for example, suitable mixtures of alkali metal dihydrogen phosphates (such as potassium dihydrogen phosphate) and dialkali metal monohydrogen phosphates (such as dipotassium monohydrogen phosphate), or alkali metal salts of organic carboxylic acids (such as boric acid, citric acid, lactic acid, tartaric acid and acetic acid); and

[0158] E. Metal oxides, especially iron oxides.

[0159] Preferably, step d) is carried out in the presence of water. Further preferably, in step c), in addition to water, at least one water-soluble alcohol is present, preferably methanol and / or ethanol and / or isopropanol.

[0160] Step d) is preferably carried out in the presence of a basic substance so that the pH is not less than 6.5, and preferably not less than 7. The most preferred pH of the reaction mixture is 7-14.

[0161] Preferably, step d) is carried out under reducing conditions or under an inert atmosphere, in particular under nitrogen or argon.

[0162] Preferably, the alkaline reaction mixture is neutralized with an acid at the end of the reaction.

[0163] Preferably, the rearrangement step d) is performed as disclosed in US 3,957,887, in particular as described in Example 12 thereof, or as described in FR 2 200 225 or DE 2 345 062, the entire disclosures of which are incorporated herein by reference.

[0164] The reaction of step d) can be carried out in a batch process or in a continuous process.

[0165] Preferably, step d) is performed in a continuous manner.

[0166] Reduction / rearrangement (step c / d)

[0167] In a preferred embodiment, the reduction step c) and the rearrangement step d) are performed as a combined single step c / d):

[0168] c / d) Reduction / rearrangement of the mixture of compounds of formula (IIIa) and (IIIb) by treating them with a basic substance in the presence of a reducing agent at a temperature >200°C, preferably >240°C, to give compounds of formula (I).

[0169] The details of the reduction and rearrangement have been described above for step c) or step d), respectively.

[0170] The present invention demonstrates that 2,3,5-trimethylhydroquinone can be obtained in high yield and selectivity from a mixture of 2,4,6-TMP and 2,3,6-TMP, which can be obtained in particular from 2,5-dimethylfuran obtained from renewable sources or from a mixture of m-cresol and p-cresol, which are readily and inexpensively available in large quantities from commercial suppliers. Particularly surprising is that in each respective reaction step, both components of the respective mixture can be reacted under identical conditions and without interfering with each other.

[0171] As mentioned above, 2,3,5-trimethylhydroquinone is the key component for the synthesis of α-tocopherol.

[0172] Therefore, the present invention also relates to a method for producing α-tocopherol, comprising the following steps:

[0173] i) providing 2,3,5-trimethylhydroquinone produced from a mixture of 2,4,6-trimethylphenol (Formula (IIa)) and 2,3,6-TMP (Formula (IIb)) by the process already discussed in detail above;

[0174] ii) condensing the 2,3,5-trimethylhydroquinone from step i) with a compound of formula (VII-A) or a compound of formula (VII-B) to obtain α-tocopherol of formula (VIII),

[0175]

[0176] wherein Q is a substituent selected from the group consisting of OH, a halide, an acyloxy group, in particular an acetoxy group or a benzoyloxy group, a methanesulfonyloxy group (=methylsulfonyloxy), an ethanesulfonyloxy group, a benzenesulfonyloxy group and a toluenesulfonyloxy group (=toluenesulfonyloxy);

[0177] Any wavy line represents a carbon-carbon bond, which is in the Z configuration or the E configuration when connected to a carbon-carbon double bond.

[0178] In case Q represents a halide ion, preferably Q represents Cl.

[0179] In the case where Q represents an acyloxy group, the acyloxy group is preferably a group of the formula

[0180]

[0181] where R 10 Indicates C 1-6 -alkyl or aryl, which is optionally substituted, in particular by at least one C 1-6 -alkyl substitution.

[0182] Preferably, R 10 Indicates C 1-6 -alkyl or phenyl.

[0183] More preferably, R 10 represents a methyl group or a phenyl group, preferably a methyl group.

[0184] Specific examples of the compound of formula (VII-A) are isophytol, isophytyl chloride, isophytyl bromide, isophytyl iodide, isophytyl acetate, isophytyl methanesulfonate, isophytylethanesulfonate, isophytyl benzenesulfonate, and isophytyl toluenesulfonate.

[0185] Specific examples of the compound of formula (VII-B) are phytol, phytyl chloride, phytyl bromide, phytyl iodide, phytyl acetate, phytyl methanesulfonate, phytyl ethanesulfonate, phytyl benzenesulfonate, and phytyl toluenesulfonate.

[0186] The compounds of formula (VII-B) can be used as E / Z mixtures as well as in pure E or pure Z form. Preferably, they are used as E / Z mixtures.

[0187] Q preferably represents OH or Cl.

[0188] Therefore, as the compound of formula (VII-A) or (VII-B), preferably phytol, isophytol, phytyl chloride or isophytyl chloride, more preferably phytol or isophytol.Most preferably isophytol.

[0189] The use of compounds of formula (VII-A) is preferred over compounds of formula (VII-B).

[0190] The condensation step ii) is schematically shown in Figure 3 middle.

[0191] It has been found that the condensation reaction of step ii) can be carried out in the manner described, for example, in W. Bonrath et al. Angew. Chem. Int. Ed. 2012, 51, 12982-12985 or Bonrath, W. et al. (2021). Vitamins, 4. Vitamin E (Tocopherols, Tocotrienols). In Ullmann's Encyclopedia of Industrial Chemistry. https: / / doi.org / 10.1002 / 14356007.o27_o07.pub2.

[0192] The condensation reaction (step ii)) is preferably carried out using a Lewis acid or a Bronsted acid.

[0193] The Lewis acids or Bronsted acids are in particular those mentioned in EP 0949255 A1 and Bonrath et al., Adv. Synth. Catal. 2002, 344, 37-39.

[0194] Figure 1 Schematically illustrated are different preferred synthetic routes for the process for producing 2,3,5-trimethylhydroquinone of formula (I) from a mixture of 2,4,6-trimethylphenol (Formula IIa) and 2,3,6-TMP (Formula IIb) as discussed in great detail above.

[0195] Figure 2 Different preferred synthetic routes to the mixture of 2,4,6-trimethylphenol (Formula IIa) and 2,3,6-TMP (Formula IIb) as discussed in greater detail above are schematically shown.

[0196] Figure 3 The production of α-tocopherol (Formula (VIII)) from 2,3,5-trimethylhydroquinone of Formula (I) is schematically shown.

[0197] Example

[0198] The present invention is further illustrated by the following experiments.

[0199] First experimental series (Examples 1-26): Reaction of 2,5-dimethylfuran with acetylene: Step a0)

[0200] 2,5-Dimethylfuran was reacted with acetylene (2 wt %) in an organic solvent as shown in Table 1 and a platinum catalyst.

[0201] To this end, under an argon atmosphere, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and acetylene (1.0 equivalent) dissolved (2 wt %) in the corresponding organic solvent were added to a 10 mL vial with a magnetic stirring bar. The vial was then sealed with a lid and the mixture was stirred in an aluminum block at 23 ° C for the time shown in Table 1. The reaction mixture was then filtered to remove the catalyst and ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed in vacuo at 50 ° C / <30 mbar to obtain an oily residue. The amount of 2,4-dimethylphenol and 2,5-dimethylphenol was determined by GC (gas chromatography). The ratio and yield are shown in Table 1.

[0202] The results in Table 1 show that, in particular, ligands with aromatic substituents are suitable as part of the platinum catalyst. 5F )3(tris(pentafluorophenyl)phosphine) is one of the most suitable ligands. In addition, Table 1 shows that acetone and 3-pentanone are particularly suitable as organic solvents.

[0203] All examples in Table 1 produced mixtures of 2,4DMP and 2,5DMP.

[0204]

[0205]

[0206] Table 1 Reaction of 2,5-dimethylfuran with acetylene in different solvents and catalysts

[0207] 1 Acetylene 2% in the mentioned organic solvent

[0208] 2 Relative to 2,5-dimethylfuran

[0209] 3 Combined yield of 2,4-DMP and 2,5-DMP

[0210] 4 2,4:2,5: Ratio 2,4-DMP:2,5-DMP (area %)

[0211] 5 Molar ratio of acetylene:2,5-DMF=2:1

[0212] 6 Molar ratio of acetylene:2,5-DMF=3:1

[0213] 6 Molar ratio of acetylene:2,5-DMF=5:1

[0214] 7 nd: Undetermined

[0215] Second experimental series (Examples 27-37): Reaction of 2,5-dimethylfuran with propyne: Step a0)

[0216] 2,5-Dimethylfuran was reacted with propyne (2 wt %) in an organic solvent as shown in Table 2 and a platinum catalyst.

[0217] To this end, under an argon atmosphere, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and propyne (1.0 equivalent) dissolved (2 wt %) in the corresponding organic solvent were added to a 10 mL vial with a magnetic stirring bar. The vial was then sealed with a lid and the mixture was stirred in an aluminum block at 23 ° C for the time shown in Table 2. The reaction mixture was then filtered to remove the catalyst and ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed in vacuo at 50 ° C / <30 mbar to obtain an oily residue. The amount of 2,4,6-TMP and 2,3,6-TMP was determined by GC (gas chromatography). The ratios and yields are shown in Table 2.

[0218]

[0219] Table 2 Reaction of 2,5-dimethylfuran with propyne in different solvents and catalysts

[0220] 1 Propylene 2% in the mentioned organic solvent

[0221] 2 Relative to 2,5-dimethylfuran

[0222] 3 Combined yield of 2,4,6-TMP and 2,3,6-TMP

[0223] 4 2,4,6:2,3,6: Ratio of 2,4,6-TMP to 2,3,6-TMP (area %)

[0224] Third Experimental Series (Examples 37-43): Reaction of 2,5-Dimethylfuran with MAF

[0225] 2,5-Dimethylfuran was reacted with MAF gas (2 wt %) in an organic solvent as shown in Table 2 and a platinum catalyst.

[0226] To this end, under an argon atmosphere, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and MAF gas (1.0 equivalent) dissolved (2 wt %) in the corresponding organic solvent were added to a 10 mL vial with a magnetic stirrer bar. The vial was then sealed with a lid and the mixture was stirred in an aluminum block at 23 ° C for the time shown in Table 3. The reaction mixture was then filtered to remove the catalyst and ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed in vacuo at 50 ° C / <30 mbar to obtain an oily residue. The amount of 2,4,6-TMP and 2,3,6-TMP was determined by GC (gas chromatography). The ratios and yields are shown in Table 2.

[0227]

[0228] Table 3 Reaction of 2,5-dimethylfuran with propyne / propadiene (MAF) in different solvents and catalysts

[0229] 1 MAF 2% in the mentioned organic solvents

[0230] 2 Relative to 2,5-dimethylfuran

[0231] 3 Combined yield of 2,4,6-TMP and 2,3,6-TMP

[0232] 4 2,4,6:2,3,6: Ratio of 2,4,6-TMP to 2,3,6-TMP (area %)

[0233] Example 44: Methylation: Step a')

[0234] The gas phase flow reactor was filled with an iron oxide catalyst (13 g). The reactor was closed and heated to 350° C. in the reactor under nitrogen. The feed consisted of a mixture of 2,5-dimethylphenol and 2,4-dimethylphenol (Example 2) in a molar ratio of 0.35:0.65:0.35:1.7 and methanol and water. The mixture was pumped into the gas phase reactor from top to bottom at 0.39 ml / min. After the heating zone, the reaction mixture was cooled to room temperature and collected in a bottle. The bottle was emptied and analyzed every 24 hours for five days.

[0235] The average conversion rate and selectivity over the five days were:

[0236] Conversion rate of 2,5-dimethylphenol: 16%

[0237] Conversion rate of 2,4-dimethylphenol: 32%

[0238] Selectivity to 2,3,6-trimethylphenol: 95%

[0239] Selectivity to 2,4,6-trimethylphenol: 89%

[0240] Example 45: Photooxidation of a mixture of 2,4,6-TMP and 2,3,6-TMP: Step b)

[0241] A solution of a mixture of 2,4,6-TMP (3.3 mmol) and 2,3,6-TMP (1.7 mmol) and methylene blue hydrate ([CAS: 122965-43-9], 14.4 mg, 0.900 mol%) in methanol and water (4:1, v / v, 250 mL) was prepared to give a homogeneous blue solution. The solution was pumped into the photoreactor (tubing system: 0.75 mm ID, 1.58 mm OD, PFA coil) using a high pressure liquid chromatography pump at a constant pressure of 10 bar (liquid flow rate: 0.250-0.023 mL / min, HPLC regulated piston pump).

[0242] Before entering the photoreactor, the solution was enriched with air (air flow rate: 1.350-0.125 mL / min, mass flow controller). Inside the photoreactor, the reaction mixture was exposed to a super red LED light source with a residence time of 40 minutes. The complete conversion was confirmed by thin layer chromatography and QNMR. The photoreactor was maintained at ambient temperature (20°C). After two residence times, the reaction mixture (25 mL) was collected by round bottom. Water (50 mL) was added and the solution was extracted with pentane (2 × 50 mL) and ether (2 × 50 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the organic solvent was removed under reduced pressure (15 mbar) to give a mixture of: 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-diene-1-one (Formula (IIIa)) (conversion: >99%, yield: 99%) and 2,3,5-trimethylbenzoquinone (=2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione, TMQ) (Formula (IIIb)) (conversion: >99%, yield: 71%).

[0243] Example 46: Reaction of 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one and 2,3,5-trimethylbenzoquinone Reduction of the mixture: step c)

[0244] Platinum on carbon (1.0 mol%) was charged to a flame-dried flask and methanol was carefully added to give a dark, heterogeneous solution. A mixture of 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-diene-1-one (Formula (IIIa)) and 2,3,5-trimethylbenzoquinone (=2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione, TMQ) (Formula (IIIb)) (0.25 mmol) was prepared in methanol and water (4:1, v / v) to give a yellow homogeneous solution, which was added to the catalyst solution. The flask was evacuated and then hydrogen was introduced. The reaction mixture was stirred at ambient temperature (20°C) for >1 hour until complete conversion. Water (10 mL) was added and the solution was extracted with diethyl ether (3×5 mL). The combined organic layers were dried over Na2SO4, filtered, and the organic solvent was removed under reduced pressure (15 mbar) to give a mixture of 2,3,5-trimethylhydroquinone (Formula (I)) (conversion: >99%, yield: 99%) and 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one (Formula (IV)) (conversion: >99%, yield: 51%).

[0245] Example 47: Rearrangement of 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one to 2,3,5-trimethylphenylene Diphenols: step d)

[0246] A mixture of 2,3,5-trimethylhydroquinone (Formula (I)) and 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-diene-1-one (Formula (IV)) in aqueous NaOH solution, methanol, and sodium sulfite (6.3 mol % relative to Formula (IV)) was pumped at 10 mL / min through a flow reactor (1.5 mm diameter, 2000 mm length) at 250°C. The solution was neutralized with sulfuric acid at the end of the flow reactor. The reaction mixture was extracted with ethyl acetate, dried over MgSO4, and concentrated in vacuo. 2,3,5-trimethylbenzoquinone (Formula (I)) was obtained in an overall yield of 92%.

Claims

1. A method for producing 2,3,5-trimethylhydroquinone, The following steps are involved: a) providing a mixture of a compound of formula (IIa) and a compound of formula (IIb), b) oxidizing a mixture of compounds of formula (IIa) and formula (IIb) to form a mixture of compounds of formula (IIIa) and compounds of formula (IIIb), c) reducing the mixture of the compound of formula (IIIa) and the compound of formula (IIIb) by a reducing agent to obtain a mixture of the compound of formula (IV) and the compound of formula (I), d) Rearranging the compound of formula (IV) in the mixture of the compound of formula (IV) and the compound of formula (I) by treating the mixture of the compound of formula (IV) and the compound of formula (I) with a basic substance at a temperature of >200°C, preferably >240°C, to obtain a compound of formula (I) 2. The method according to claim 1, characterized in that The mixture of compound (IIa) and compound of formula (IIb) is obtained by reaction step a0), a0) reacting a compound of formula (V) with a compound of formula (VI) in the presence of a Pt catalyst or an Au catalyst in the form of a salt or a complex to form a mixture of a compound of formula (IIa-1) and a compound of formula (II-b), wherein R represents H or CH3, preferably CH3; Provided that, in the case where R represents H, a mixture of a compound of formula (IIa-1H) and a compound of formula (IIb-1H) is subjected to reaction step a') a') methylating a mixture of a compound of formula (IIa-1H) and a compound of formula (IIb-1H) to obtain a mixture of a compound of formula (IIa) and a compound of formula (IIb), 3. The method according to claim 2, characterized in that The mixture of step a0) is carried out in the presence of a Pt catalyst in the form of a Pt salt or a Pt complex.

4. The method according to claim 2 or 3, characterized in that In the case where R represents CH3, propyne is used in combination with propadiene in the reaction.

5. The method according to any one of the preceding claims 2 to 4, characterized in that The Pt catalyst is a Pt(II) salt, in particular PtCl2.

6. The method according to any one of the preceding claims 2 to 5, characterized in that The Pt catalyst is a Pt(II) complex having at least one organic ligand comprising at least one phosphorus atom, the ligand being in particular selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

7. The method according to any one of the preceding claims 2 to 6, characterized in that The Pt catalyst is PtCl2 in the presence of an organic ligand comprising at least one phosphorus atom, the ligand being in particular selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

8. The method according to claim 6 or 7, characterized in that The organic ligand is selected from triphenyl phosphite (P(OPh)3), diphenyl phosphate ((PhO)2P=O(OH)), triphenyl phosphate ((PhO)3P=O), triethyl phosphate ((EtO)3P=O), dibenzyl phosphite ((PhCH2O)2P=O(H)), methyl diphenyl phosphite ((MeO)P(OPh)2), triphenylphosphine (P(Ph)3), P(Ph 5F )3, bis-(2,2,2-trifluoroethyl)-phosphite ((CF3CH2O)2P=O(H)), triethyl 2-fluoro-2-phosphonoacetate ((CHFCOOEt)(EtO)2P=O), tri(2-methylphenyl) phosphite, ethyl 3-(diethoxyphosphoryl)propionate (=triethyl 3-phosphonopropionate) ((CH2CH2COOEt)(EtO)2P =O), 2-(diphenylphosphino)benzoic acid (P(Ph)2C6H4COOH), 3,9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane, P(O-isooctyl)3, P(O-isopropyl)3), P(Oi-PrF6)3, P(On-Bu)3, bis(2,4-di-tert-butylphenoxy)-λ 2 -phosphine, CH3P(EtO)2, 1,1'-binaphthyl-2,2'-dihydrogen phosphate (=4-hydroxybinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphane 4-oxide), VAPOL hydrogen phosphate (=18-hydroxy-8,9-diphenyldiphenanthro[4,3-d:3',4'-f][1,3,2]dioxophosphine 18-oxide), methyltriphenoxyphosphine iodide ([CH3P(OPh)3] + I - ), 4-ethyl-2,6,7-trioxa-1-phosphobicyclo[2.2.2]octane ((CH2CH2COOEt)(EtO)2P=O, trimethylolpropane phosphite), trisodium triphenylphosphine trisulfonate (=TPPTS), disodium triphenylphosphine disulfonate (=TPPDS), and sodium triphenylphosphine monosulfonate (=TPPMS); Where Ph represents phenyl, Ph 5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

9. The method according to claim 1, characterized in that The mixture of compound (IIa) and compound of formula (IIb) is obtained by reaction step a"), a″) methylating a mixture of p-cresol of formula (Op) and m-cresol of formula (Om) to obtain a mixture of a compound of formula (IIa) and a compound of formula (IIb), 10. The method according to any one of the preceding claims, characterized in that The oxidation step b) is carried out in water and at least one C 1-8 Alkanol or at least one C 2-4 Photooxidation using oxygen and a photosensitizer of formula (X) in a solvent mixture of an alkylene glycol; and using a peak wavelength (λ max ) light in the range between 580 and 780 nm, where R 8 、R 8' 、R 8” and R 8”' represents H or C independently of each other 1-4 alkyl; or where R 8 and R 8' and / or R 8” and R 8”' Together with N, it forms a five-membered or six-membered ring; The prerequisite is that at least one residue R 8 、R 8' 、R 8” and R 8”' Different from H; And X - Indicates anion.

11. The method according to claim 10, characterized in that The peak wavelength (λ) of the light used in its spectrum max ) in the range between 625 and 740 nm.

12. The method according to claim 10 or 11, characterized in that The light source for the light is a white LED lamp combined with a filter that blocks wavelengths below 500 nm, in particular below 625 nm.

13. Method according to any one of the preceding claims 10 to 11, characterized in that The light source used for the light is a red LED lamp.

14. Method according to any one of the preceding claims 10 to 13, characterized in that The solvent mixture is a mixture of water and methanol and / or ethanol and / or isopropanol.

15. Method according to any one of the preceding claims 10 to 14, characterized in that R 8 =R 8' =R 8” =R 8”' =CH3 and preferably X - It represents a halide ion, especially a chloride ion.

16. The method according to any one of the preceding claims, characterized in that The reduction step c) is carried out in the presence of a reducing agent selected from the group consisting of thiosulfates, tertiary phosphines, hydrogen, dithionates, dithionites, sulfites, trialkylphosphites, iodides, metals and dialkylsulfides.

17. A method for producing α-tocopherol, comprising the following steps: i) providing 2,3,5-trimethylhydroquinone produced from a mixture of 2,4,6-trimethylphenol (Formula (IIa)) and 2,3,6-TMP (Formula (IIb)) by a process according to any one of the preceding claims 1 to 16; ii) condensing the 2,3,5-trimethylhydroquinone from step i) with a compound of formula (VII-A) or a compound of formula (VII-B) to obtain α-tocopherol of formula (VIII), wherein Q is a substituent selected from the group consisting of OH, a halide, an acyloxy group, in particular an acetoxy group or a benzoyloxy group, a methanesulfonyloxy group (=methylsulfonyloxy), an ethanesulfonyloxy group, a benzenesulfonyloxy group and a toluenesulfonyloxy group (=toluenesulfonyloxy); and Any wavy line represents a carbon-carbon bond, which is in the Z configuration or the E configuration when connected to a carbon-carbon double bond.

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