Synthesis of dimethylphenol or trimethylphenol from 2, 5-dimethylfuran with platinum catalyst

Abstract

The invention relates to the production of dimethylphenol, in particular 2, 5-dimethylphenol, and trimethylphenol, in particular 2, 3, 6-trimethylphenol, respectively, from 2, 5-dimethylfuran and acetylene and propyne, in particular in the presence of a platinum catalyst, in particular in MAF gas. The present invention provides sustainable synthesis of [beta]-tocopherol and [alpha]-tocopherol.

Description

Technical Field

[0001] The present invention relates to the synthesis of dimethylphenol or trimethylphenol. Background Art

[0002] Trimethylphenols and dimethylphenols are key compounds for the synthesis of tocopherols, particularly α-tocopherol, and especially (all-rac)-α-tocopherol. Several methods for their synthesis have been proposed.

[0003] WO 2015 / 110654 A1 discloses the synthesis of 2,3,6-trimethylphenol from 2,5-dimethylfuran and propyne using a gold catalyst.

[0004] WO 2015 / 110655 A1 discloses the synthesis of 2,5-dimethylphenol from 2,5-dimethylfuran and acetylene using a gold catalyst.

[0005] N. Huguet et al., Chem. Eur. J. 2013, 19, 6581-6585 disclose the formation of phenolic compounds from 2,5-dimethylfuran and certain substituted alkynes in the presence of gold(I) catalysts. A disadvantage is the formation of hydroarylation by-products, which are usually formed in significant amounts.

[0006] Platinum catalysts are typically used on a large scale in industry, particularly in hydrogenation and oxidation reactions. Consequently, the availability of suitable gold catalysts is significantly limited in volume, and consequently, the cost of using gold catalysts is significantly higher than that of platinum catalysts. Therefore, the use of catalysts as alternatives to gold catalysts has a significant impact on costs and is of high economic interest in the production of tocopherols such as 2,5-dimethylphenol and 2,3,6-trimethylphenol.

[0007] In the processes described in the prior art, expensive catalysts with limited selectivity are applied and the processes described require separation methods for product isolation.

[0008] The use of 2,5-dimethylfuran is very interesting since it can be obtained from a renewable source (cellulose) as known in the prior art, for example Y. Román-Leshkov, CJ Barrett, ZY Liu, JA Dumesic, Nature 2007, 447, 982-985.

[0009] The sustainability of chemical processes has become very important among the public and in the market.

[0010] Therefore, there is great interest in the synthesis of 2,5-dimethylphenol and 2,3,6-trimethylphenol from renewable sources. Summary of the Invention

[0011] Therefore, the problem to be solved by the present invention is to provide a method for synthesizing dimethylphenol compounds or trimethylphenol compounds, especially 2,3,6-trimethylphenol, based on a platinum catalyst.

[0012] Surprisingly, it was found that the method according to claim 1 provides a solution to this problem.

[0013] Surprisingly, it has been found that the disadvantages of the prior art processes can be avoided by using platinum-based catalysts in the reaction of 2,5-dimethylfuran with acetylene or propyne, in particular in MAF gas.

[0014] Platinum-based catalysts were found to be useful for this synthesis, although until now platinum catalysts were not known to react 2,5-dimethylfuran and alkynes to dimethylphenols or trimethylphenols with excellent selectivity. Surprisingly, no hydroarylation products were observed, as is often the case in the corresponding gold-catalyzed reactions.

[0015] Therefore, platinum catalysts available in large quantities from various suppliers can be used for this reaction, as they are also known and used for other hydrogenation reactions in the synthesis of α-tocopherol. From a logistical point of view, this is of course more advantageous, as the same catalyst can be used for different steps in the synthesis of vitamin E.

[0016] Another advantage of the present invention is the formation of dimethylphenols or trimethylphenols from 2,5-dimethylfuran in a single step reaction with high yield and selectivity, and thus a very sustainable process for the production of dimethylphenols or trimethylphenols or α-tocopherol, respectively.

[0017] 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

[0018] In a first aspect, the present invention relates to a process for producing a mixture of a compound of formula (Ia) and a compound of formula (Ib),

[0019]

[0020] comprising the step of reacting a compound of formula (II) with a compound of formula (III) in the presence of a Pt catalyst, wherein the Pt catalyst is in the form of a Pt salt or a Pt complex,

[0021]

[0022] wherein R represents H or CH3, preferably CH3.

[0023]

[0024] For the sake of clarity, it is emphasized that, 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 a specific formula also applies to the other formulae containing the same said symbol.

[0025] 2,5-Dimethylfuran reacts with propyne (R = CH3) or acetylene (R = H). Both propyne and acetylene are gases. They are handled differently than liquid alkynes. Dosage and pressure control, in particular, require appropriate attention and knowledge.

[0026] In the case where R represents CH 3 , propyne can also be mixed with propadiene. A specific mixture containing propyne and propadiene is referred to by those skilled in the art as MAF gas (MAF=methylacetylene-allene fraction). MAF gas is an inexpensive process gas and can be commercially obtained from various suppliers.

[0027] In order for the reaction of 2,5-dimethylfuran with propyne or acetylene to occur, the presence of a platinum catalyst is required. The key factor is that the process uses a platinum catalyst rather than a gold catalyst, making it a platinum-based and gold-free process.

[0028] The platinum catalyst is in the form of a platinum salt or a platinum complex.

[0029] In one embodiment, the platinum catalyst is preferably a Pt(II) salt, in particular PtCl2.

[0030] 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.

[0031] A particularly preferred Pt catalyst is PtCl2 in the presence of an organic ligand comprising at least one phosphorus atom, in particular selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

[0032] 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 triphenylphosphinedisulfonate (=TPPDS), and sodium triphenylphosphinemonosulfonate (=TPPMS);

[0033] Where Ph represents phenyl, Ph 5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

[0034] 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 triphenylphosphine trisulfonate (=TPPTS), 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.

[0035] Preferably, the reaction between 2,5-dimethylfuran and propyne or acetylene is carried out in the presence of an ether, in particular a cyclic ether, preferably tetrahydrofuran, or a ketone, in particular acetone or methyl ethyl ketone or diethyl ketone (=3-pentanone), preferably acetone or diethyl ketone, more preferably diethyl ketone.

[0036] It is further preferred that the amount of Pt catalyst is present in an amount of 0.1-25 mol %, in particular 6-12 mol %, relative to the compound of formula (II).

[0037] 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.

[0038] Preferably, the molar ratio of the compound of formula (II) to the compound of formula (III) 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.

[0039] 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.

[0040] The reaction is preferably carried out under pressure at a temperature above the boiling point of the solvent.

[0041] The above process produces a mixture of compounds of formula (Ia) and compounds of formula (Ib).

[0042] However, this is largely irrelevant since only the compound of the formula (Ib) is reactive in the further reaction sequence towards tocopherol.

[0043] Dimethylphenol and trimethylphenol are converted into dimethylhydroquinone or trimethylhydroquinone, and then dimethylhydroquinone or trimethylhydroquinone reacts with isophytol (X) or phytol to produce the corresponding α-tocopherol or β-tocopherol (XI), such as Figure 2 Schematically shown in .

[0044] However, only dimethylphenol or trimethylphenol of formula (Ib) can form the desired hydroquinone of formula (Ib'). Dimethylphenol or trimethylphenol of formula (Ia) has a methyl group at the para position of the phenol group, and therefore cannot directly form the desired hydroquinone.

[0045] Therefore, the dimethylphenol or trimethylphenol of formula (Ia) does not participate in the further reaction steps to form α-tocopherol or β-tocopherol and is removed from α-tocopherol or β-tocopherol, respectively, during the reaction work-up and / or purification.

[0046] In the case where R is H, typically predominantly 2,4-DMP (Ia) is formed. Thus, typically the molar ratio of 2,4-DMP:2,5-DMP is greater than 50:50.

[0047] As indicated above, high levels are preferably formed in 2,5-DMP due to the presence of a methyl group in the para position to the phenolic OH group in 2,4-DMP.

[0048] It has been observed that the molar ratio of compound of formula (Ia) (=2,4-dimethylphenol=2,4-DMP):compound of formula (Ib) (=2,5-dimethylphenol=2,5-DMP) is typically <70:30, in particular <60:40, preferably <50:50.

[0049] When R is CH 3 , 2,3,6-TMP (Ib) is typically formed predominantly. Thus, the molar ratio of 2,4,6-TMP:2,3,6-TMP is typically less than 50:50. Thus, the molar ratio of compound of formula (Ia) (=2,4,6-trimethylphenol=2,4,6-TMP): compound of formula (Ib) (=2,3,6-trimethylphenol=2,3,6-TMP) is preferably ≤50:50, in particular <10:90, more in particular <5:95, preferably <3:97, and more preferably <2:98.

[0050] This finding is particularly interesting in the context of the formation of 2,3,6-trimethylphenol or α-tocopherol, which is the most important embodiment of the present invention, mainly because the volume of 2,3,6-trimethylphenol or α-tocopherol produced worldwide is several orders of magnitude larger than the volume of 2,5-dimethylphenol (2,5-DMP) or β-tocopherol.

[0051] It is therefore very advantageous to minimize losses due to the formation of unreactive 2,4,6-trimethylphenol or 2,4-dimethylphenol.

[0052] Therefore, it is preferred to use propyne rather than acetylene in the above method. In addition, it is also advantageous to use MAF as the propyne source.

[0053] As described above, a mixture of 2,4,6-trimethylphenol (=2,4,6-TMP, compound of formula (Ia)) and 2,3,6-trimethylphenol (=2,3,6-TMP, compound of formula (Ib)) can be prepared from 2,5-dimethylfuran (formula (II)) and propyne or MAF gas (compound of formula (III) where R=methyl), e.g. Figure 1 As indicated in step a0).

[0054] In another embodiment, a mixture of 2,4,6-trimethylphenol (=2,4,6-TMP, compound of formula (Ia)) and 2,3,6-trimethylphenol (=2,3,6-TMP, compound of formula (Ib)) can be prepared by methylating a mixture of 2,4-dimethylphenol (=2,4-DMP, compound of formula (Ia-1H)) and 2,5-dimethylphenol (=2,5-DMP, compound of formula (Ib-1H)), such as Figure 1 The mixture of 2,4-dimethylphenol (=2,4-DMP, compound of formula (Ia-1H)) and 2,5-dimethylphenol (=2,5-DMP, compound of formula (Ib-1H)) can be prepared as described above from 2,5-dimethylfuran (formula (II)) and acetylene (compound of formula (III), wherein R=H), such as Figure 1 As indicated in step a0').

[0055] The methylation in step a') can be performed by different methods.

[0056] 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 Example 3, to produce a mixture of 2,4,6-trimethylphenol and 2,3,6-TMP, the entire disclosure of which is incorporated herein by reference.

[0057] 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 2,3,6-TMP.

[0058] The method generates less waste, allows for a continuous process and is therefore very advantageous economically and ecologically.

[0059] In another aspect, the present invention relates to a process for producing tocopherol of formula (XI),

[0060]

[0061] The following steps are involved:

[0062] a) preparing a mixture of a compound of formula (Ia) and a compound of formula (Ib) by the process discussed in detail above,

[0063]

[0064] b) converting the compound of formula (Ib) into a hydroquinone of formula (Ib')

[0065]

[0066] c) condensing the hydroquinone of formula (Ib') of step b) with a compound of formula (XA) or a compound of formula (XB) to obtain α-tocopherol of formula (XI),

[0067]

[0068]

[0069] wherein R represents H or CH3, preferably CH3;

[0070] and 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);

[0071] And any wavy line therein represents a carbon-carbon bond, which is in the Z configuration or the E configuration when connected to a carbon-carbon double bond.

[0072] In case Q represents a halide ion, preferably Q represents Cl.

[0073] In case Q represents an acyloxy group, the acyloxy group is preferably a group of the formula,

[0074]

[0075] 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.

[0076] Preferably, R 10 Indicates C 1-6 -alkyl or phenyl.

[0077] More preferably, R 10 represents a methyl group or a phenyl group, preferably a methyl group.

[0078] Specific examples of the compound of formula (XA) are isophytol, isophytyl chloride, isophytyl bromide, isophytyl iodide, isophytyl acetate, isophytyl methanesulfonate, isophytylethanesulfonate, isophytyl benzenesulfonate, and isophytyl toluenesulfonate.

[0079] Specific examples of the compound of formula (XB) are phytol, phytyl chloride, phytyl bromide, phytyl iodide, phytyl acetate, phytyl methanesulfonate, phytyl ethanesulfonate, phytyl benzenesulfonate and phytyl toluenesulfonate.

[0080] The compounds of formula (XB) 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.

[0081] Q preferably represents OH or Cl.

[0082] Therefore, as the compound of formula (XA) or (XB), preferably phytol, isophytol, phytyl chloride or isophytyl chloride, more preferably phytol or isophytol. Most preferably isophytol.

[0083] The use of compounds of formula (XA) is preferred over compounds of formula (XB).

[0084] The details of step a) and its preferred embodiments, amount ratios and conditions have been discussed in detail above.

[0085] Steps b) and c) are known in principle to the person skilled in the art, for example from 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.

[0086] In step b), the compound of formula (Ib) is oxidized to the corresponding quinone and then reduced to the hydroquinone of formula (Ib').

[0087] The method for the tocopherol of this synthetic formula (XI) has very sustainable advantage.Aromatic moiety can obtain from formula (Ib) compound as discussed in detail above.Also based on the situation of renewable source at the building block (i.e. isophytol) of side chain, the whole method of synthesizing described tocopherol is highly sustainable.

[0088] Since the combination of 2,5-dimethylfuran and acetylene or propyne in the presence of a platinum catalyst results in the production of a mixture of compounds of formula (Ia) and compounds of formula (Ib), in another aspect, the present invention relates to a composition comprising

[0089] - a compound of formula (II);

[0090] - a compound of formula (III); and

[0091] - Pt catalysts in the form of Pt salts or Pt complexes;

[0092]

[0093] wherein R represents H or CH3, preferably CH3.

[0094] All ingredients and their preferred embodiments as well as amounts and ratios have been discussed above in detail.

[0095] The compound of formula (Ib) represents a key intermediate in a new synthetic route to α-tocopherol and β-tocopherol.

[0096] Example

[0097] The present invention is further illustrated by the following experiments.

[0098] First experimental series (Examples 1-26): Reaction of 2,5-dimethylfuran with acetylene

[0099] 2,5-Dimethylfuran was reacted with acetylene (2 wt %) in an organic solvent as shown in Table 1 and a platinum catalyst.

[0100] 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.

[0101] 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.

[0102] All examples in Table 1 produced mixtures of 2,4DMP and 2,5DMP.

[0103]

[0104]

[0105] Table 1 Reaction of 2,5-dimethylfuran with acetylene in different solvents and catalysts

[0106] 1 Acetylene 2% in the mentioned organic solvent

[0107] 2 Relative to 2,5-dimethylfuran

[0108] 3Combined yield of 2,4-DMP and 2,5-DMP

[0109] 4 2,4:2,5: Ratio 2,4-DMP:2,5-DMP (area %)

[0110] 5 Molar ratio of acetylene:2,5-DMF=2:1

[0111] 6 Molar ratio of acetylene:2,5-DMF=3:1

[0112] 6 Molar ratio of acetylene:2,5-DMF=5:1

[0113] 7 nd: Undetermined

[0114] Second experimental series (Examples 27-36): Reaction of 2,5-dimethylfuran with propyne

[0115] 2,5-Dimethylfuran was reacted with propyne (2 wt %) in an organic solvent as shown in Table 2 and a platinum catalyst.

[0116] 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.

[0117]

[0118] Table 2 Reaction of 2,5-dimethylfuran with propyne in different solvents and catalysts

[0119] 1 Propylene 2% in the mentioned organic solvent

[0120] 2 Relative to 2,5-dimethylfuran

[0121] 3 Combined yield of 2,4,6-TMP and 2,3,6-TMP

[0122] 42,4,6:2,3,6: Ratio of 2,4,6-TMP to 2,3,6-TMP (area %)

[0123] Third Experimental Series (Examples 37-43): Reaction of 2,5-Dimethylfuran with MAF

[0124] 2,5-Dimethylfuran was reacted with MAF gas (2 wt %) in an organic solvent as shown in Table 2 and a platinum catalyst.

[0125] 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.

[0126]

[0127] Table 3 2,5-dimethylfuran and propyne / propadiene (MAF) in different solvents and different

[0128] Reactions in catalysts

[0129] 1 MAF 2% in the mentioned organic solvents

[0130] 2 Relative to 2,5-dimethylfuran

[0131] 3 Combined yield of 2,4,6-TMP and 2,3,6-TMP

[0132] 4 2,4,6:2,3,6: Ratio of 2,4,6-TMP to 2,3,6-TMP (area %)

[0133] Example 44: Methylation: Step a')

[0134] 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) and methanol and water in a molar ratio of 0.35:0.65:30:1.7. 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 bottles were emptied and analyzed every 24 hours for five days.

[0135] The average conversion rate and selectivity over the five days were:

[0136] Conversion rate of 2,5-dimethylphenol: 16%

[0137] Conversion rate of 2,4-dimethylphenol: 32%

[0138] Selectivity to 2,3,6-trimethylphenol: 95%

[0139] Selectivity to 2,4,6-trimethylphenol: 89%

Claims

1. A process for producing a mixture of a compound of formula (Ia) and a compound of formula (Ib), comprising the step of reacting a compound of formula (II) with a compound of formula (III) in the presence of a Pt catalyst, wherein the Pt catalyst is in the form of a Pt salt or a Pt complex, wherein R represents H or CH3, preferably CH3.

2. The method according to claim 1, characterized in that In the case where R represents CH3, propyne is used in the reaction in combination with propadiene, in particular in combination with propadiene in the form of MAF gas.

3. The method according to claim 1 or 2, characterized in that The Pt catalyst is a Pt(II) salt, in particular PtCl2.

4. The method according to claim 1 or 2, characterized in that The Pt catalyst is a Pt(II) complex having at least one organic ligand containing at least one phosphorus atom, in particular a ligand selected from the group consisting of phosphite, phosphate, phosphonate and phosphine ligands.

5. The method according to any one of the preceding claims, characterized in that The 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.

6. The method according to claim 4 or 5, 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.

7. The method according to any one of the preceding claims, characterized in that The reaction is carried out in the presence of an ether, in particular a cyclic ether, preferably tetrahydrofuran, or a ketone, in particular acetone or methyl ethyl ketone or diethyl ketone, preferably acetone or diethyl ketone, more preferably diethyl ketone.

8. The method according to any one of the preceding claims, characterized in that The amount of the Pt catalyst is in the range of 0.1-25 mol %, particularly 6-12 mol %, relative to the compound of formula (II).

9. The method according to any one of the preceding claims, characterized in that In case R is H, the molar ratio of compound of formula (Ia):compound of formula (Ib) is <70:30, in particular <60:40, preferably <50:

50.

10. The method according to any one of the preceding claims, characterized in that In the case where R is CH3, the molar ratio of compound of formula (Ia):compound of formula (Ib) is ≤50:50, particularly <10:90, more particularly <5:95, preferably <3:97, more preferably <2:

98.

11. The method according to any one of the preceding claims, characterized in that The molar ratio of the compound of formula (II) to the compound of formula (III) 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.

12. The method according to any one of the preceding claims, characterized in that The reaction is carried out at a temperature of 0°C to 80°C, particularly 10°C to 60°C, preferably 20°C to 30°C.

13. A composition comprising: - a compound of formula (II); - a compound of formula (III); and - Pt catalyst in the form of a Pt salt or a Pt complex; wherein R represents H or CH3, preferably CH3.

14. A method for producing α-tocopherol of formula (XI), The following steps are involved: a) producing a mixture of a compound of formula (Ia) and a compound of formula (Ib) by a process according to any one of the preceding claims 1 to 12, b) converting the compound of formula (Ib) into a hydroquinone of formula (Ib') c) condensing the hydroquinone of formula (Ib') of step b) with a compound of formula (XA) or a compound of formula (XB) to obtain α-tocopherol of formula (XI), wherein R represents H or CH3, preferably CH3; and 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 therein 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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