Formation of para-alkylphenols based on the intermolecular reaction of ethyne with 2-alkylfuran in the presence of gold (I) complexes

Abstract

The invention relates to the synthesis of para-alkylphenols and 2,6-dimethyl-4-alkylphenols from 2-alkylfuran with acetylene in the presence of gold(I) complexes, and to 2,3,6-trimethylhydroquinone.

Description

Technical Field

[0001] This invention relates to the preparation of alkylphenols and 2,3,6-trimethylhydroquinone, and the use of Au(I) complexes in their synthesis. Background Technology

[0002] Alkylphenols represent a very important class of substances in chemistry. The compounds p-isopropylphenol and p-tert-butylphenol are important intermediates in resin synthesis, particularly for phenolic resins, but also for polycarbonates. Alkylphenols possess preservative, disinfectant, bactericidal, and antioxidant properties. Due to these properties, they are widely used as preservatives, disinfectants, bactericides, and antioxidants. In particular, p-cresol is a very important substance because it is extensively used in the synthesis of 2,6-di-tert-butyl-p-cresol (BHT), one of the most important antioxidants in industry. In the fragrance industry, p-cresol is used to obtain p-cresol carboxylic acid esters and p-cresol methyl ether, which is an intermediate of anisaldehyde.

[0003] Historically, cresol was isolated from coal tar. Subsequent synthetic routes for cresol or alkylphenols generally suffer from the following drawbacks: such synthesis yields corresponding ortho (o-), meta (m-), and para (p-) isomers. These isomers are difficult to separate. For example, it is well known that meta and para cresols, in particular, are difficult to separate and costly to do so.

[0004] From an ecological perspective, synthesis based on any renewable raw material is highly attractive because it can significantly reduce the chemical industry's dependence on dwindling fossil oil reserves. Y. Román-Leshkov et al., Nature 2007, 447, 982–985, disclosed the availability of 2-methylfuran from biomass. Therefore, 2-methylfuran is a very interesting structural unit for use in the chemical industry.

[0005] Furthermore, using starting materials from renewable resources helps to provide a better CO2 balance compared to starting materials derived from petroleum.

[0006] WO 2016 / 114668 A1 discloses that furans can react with dienophiles having electron-withdrawing groups to generate phenolic compounds with electron-withdrawing groups. Example 1 discloses the production of p-cresol via a multi-step synthesis of 2-methylfuran and methyl propargylate in the presence of Lewis acid AlCl3, followed by hydrolysis and decarboxylation at 170 °C. However, this method is quite complex and exhibits a very low yield of only 19% (across all three steps).

[0007] WO 2015 / 110654 A1 or WO 2015 / 110655 A1 discloses the use of Au(I) complexes for the synthesis of 2,5-dimethylphenol or 2,3,6-trimethylphenol from 2,5-dimethylfuran and acetylene or propyne, respectively. However, the methyl group in 2,5-dimethylphenol or 2,3,6-trimethylphenol is located in the ortho or meta position of the phenolic hydroxyl group.

[0008] 2,6-Dimethyl-4-alkylphenol, especially trimethylphenol (2,4,6-trimethylphenol), is an important and widely used compound, particularly in the formulation of adhesives for printing or paper repair purposes.

[0009] 2,3,6-Trimethylhydroquinone is a key intermediate in the synthesis of α-tocopherol.

[0010] Synthetic routes based on renewable resources for general p-alkylphenols, as well as for p-cresol, tricresyl, or 2,3,6-trimethylhydroquinone, are in high demand in the market. Summary of the Invention

[0011] Therefore, the problem to be solved by the present invention is to provide a synthesis of p-alkylphenol with high selectivity and yield.

[0012] Surprisingly, the present invention is able to solve this problem. The method of the present invention is very unique because it produces the target p-alkylphenol in a very efficient manner. Furthermore, the starting materials are sustainable, which is very advantageous, considering that 2-methylfuran can be obtained from renewable biomass and that the gold(I) complex is a catalyst that can be recycled and reused.

[0013] Furthermore, it has been found that by using this method, 2,6-dimethyl-4-alkylphenol (especially tricresol) and 2,3,6-trimethylhydroquinone can be obtained from 2-methylfuran (a bio-derived chemical) in a very efficient process, thus providing a very favorable CO2- balance in the synthesis of these substances.

[0014] Of particular surprise, a method has been discovered that can selectively produce only the target compound p-alkylphenol without producing the expected corresponding o-alkylphenol or m-alkylphenol, or a mixture of the corresponding o-alkylphenol and m-alkylphenol, or even a mixture of the corresponding o-alkylphenol, m-alkylphenol, and p-alkylphenol. This method has demonstrated such high selectivity with respect to p-alkylphenol that o-alkylphenol or m-alkylphenol is undetectable by analytical methods.

[0015] Other aspects of the invention are the subject of the other independent claims. Particularly preferred embodiments are the subject of the dependent claims. Invention Details

[0017] In a first aspect, the present invention relates to a method for manufacturing p-alkylphenol of formula (I),

[0018]

[0019] The steps include reacting a compound of formula (II) with acetylene of formula (III) in the presence of at least one Au(I) complex.

[0020]

[0021] And R 1 Representing C 1-6 -alkyl.

[0022] The term "independent of each other" in this article means that, in the context of substituents, segments, or groups, the same designated substituents, segments, or groups can appear simultaneously in the same molecule with different meanings.

[0023] “C x-y The "-alkyl" group is an alkyl group containing x to y carbon atoms, i.e., for example, C 1-3 -Alkyl groups are alkyl groups containing 1 to 3 carbon atoms. Alkyl groups can be straight-chain or branched. For example, -CH(CH3)-CH2-CH3 is considered a C4-alkyl group.

[0024] In cases where the same notation for a symbol or group exists in multiple formulas, the definition of the group or symbol in the context of a particular formula also applies to other formulas containing the same notation.

[0025] The term "preparation process" is synonymous with "preparation method" and the two terms can be used interchangeably.

[0026] The "inert" in "inert organic solvent" means that the solvent does not undergo a chemical reaction under the reaction conditions.

[0027] The term "organic ligand" is known in complex or coordination chemistry. In this paper, "organic ligand" refers to an organic molecule in which the electron pairs present on the atoms of the ligand bind to a central metal atom. Organic ligands are preferably neutral, i.e., uncharged.

[0028] The term "phosphorus-containing ligand" in this paper refers to an organic ligand that contains at least one phosphorus atom in its chemical structure.

[0029] The method described in this paper requires a reaction with acetylene of formula (III). Acetylene, also commonly known as carbide gas, is a gas under ambient pressure and temperature.

[0030] Preferably, R1 It is methyl or ethyl, preferably methyl.

[0031] Therefore, the most preferred compound of formula (I) is 4-methylphenol, also known as p-cresol:

[0032]

[0033] The reaction of acetylene with compounds of formula (II) takes place in the presence of at least one Au(I) complex.

[0034] The gold (I) complex preferably has the formula [Au(I)OL]AN, where OL represents an organic ligand and AN represents a monocharged anion.

[0035] The gold(I) complex preferably has a single-charged anion (AN), selected from [BX4]. - [PX6] - [SbF6] - [ClO4] - CF3COO - Sulfonate (especially sulfonates of formula (AN-II)), tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BAr) F – ), tetraphenylborate and anion of formula (AN-I),

[0036]

[0037] Where X represents a halogen atom, specifically F or Cl;

[0038] And Y 1 Represents phenyl or C 1-8 -alkyl group, which is preferably substituted with at least one halogen atom.

[0039] Preferably, Y 1 Represents the CF3 group. Therefore, preferably, the anion of formula (AN-I) is the anion of formula (AN-Ia), that is, the anion of bis(trifluoromethane)sulfonylimide (also known as trifluoromethanesulfonic acid).

[0040]

[0041] The preferred sulfonate anion is the halo anion of an organic sulfonic acid, particularly the halo anion of trifluoromethanesulfonic acid (also known as trifluoromethanesulfonic acid). Therefore, the preferred sulfonate anion is the trifluoromethanesulfonate anion, also known as trifluoromethanesulfonate.

[0042] In a more preferred embodiment, the anion (AN) is selected from [SbF6]. - [BX4]- Anions of the group consisting of trifluoromethanesulfonate and anions of formula (AN-I). A particularly preferred anion is [SbF6]. - .

[0043] Preferably, the gold(I) complex has an organic ligand (OL), and the organic ligand (OL) is

[0044] - At least one phosphorus-containing ligand, particularly a phosphorus-containing ligand selected from the group consisting of formulas (P1), (P2), (P3), (P4), (P5), (P6), (P7) and (P8);

[0045] or

[0046] - At least one imidazole-2-subunit ligand, particularly 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazole-2-subunit (= compounds of formula (IM);

[0047] or

[0048] - At least one 1H-1,2,3-triazole ligand, particularly 1H-1,2,3-triazole ligands of formula (TR-1) or (TR-2) or (TR-3), more particularly 1H-1,2,3-triazole ligands of formula (TR-3);

[0049]

[0050]

[0051]

[0052] Where R 10 and R 11 H can be represented independently, either linearly or branched, by C. 1-10 -alkyl or C 4-10 -cycloalkyl;

[0053] and

[0054] Where R 12 R 13 R 14 and R 15 H can be represented independently, either linearly or branched, by C. 1-6 -alkyl;

[0055] n represents an integer from 1 to 6, and n' represents 0, 1, or 2.

[0056] The organic ligand (OL) of formula (P4) is also called CyJohnPhos.

[0057] The synthesis of these organic ligands (OL) is known to those skilled in the art.

[0058] Preferably, the Au(I) complex contains at least one phosphorus-containing ligand.

[0059] Furthermore, it is preferred that the Au(I) complex contains at least 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-yl group (a compound of formula (IM)) as a ligand.

[0060] In itself, the Au(I) complex can be added directly to one or a mixture of the starting materials of the compounds of formula (II) and / or formula (III), i.e., in particular in the form of the gold(I) complex of formula [Au(I)OL]AN, or the Au(I) complex can be formed in situ in one of the starting materials or reaction mixtures (before or after the start of the reaction).

[0061] Specifically, the gold(I) complex is prepared from a gold(I) chloride complex and a silver(I) salt. The silver(I) salt is preferably Ag(I)AN. In this case, the organic ligand is present in the reaction mixture of the gold(I) chloride complex and the silver(I) salt, or is part of the gold(I) complex. The desired gold(I) complex, preferably [Au(I)OL]AN, is prepared by this reaction. The precipitate AgCl formed by this reaction does not adversely interfere with the reaction preparing the compound of formula (I).

[0062] Therefore, the gold(I) complex preferably has the formula [Au(I)OL]AN, where OL represents an organic ligand and AN represents a monocharged anion. The gold(I) complex is prepared by the reaction of Au(I)OLCl and silver AN.

[0063] In a further embodiment, the step of reacting the compound of formula (II) with the acetylene of formula (III) is carried out in the presence of at least one Au(I) complex and at least one Ag(I) salt or a combination of Ag(I) complexes.

[0064] The at least one Ag(I) salt or Ag(I) complex is preferably AgSbF6.

[0065] Preferred Au(I) complexes of the formula [Au(I)OL]AN are selected from the group consisting of:

[0066]

[0067] and [Au(I)P6]AN-Ia, where P6 is an organic ligand of formula (P6) and AN-Ia is an anion of formula (AN-Ia).

[0068] In another preferred embodiment, the gold(I) complex preferably has the formula [Au(I)OL]AN, where OL represents an organic ligand and AN represents a monocharged anion, and the gold(I) complex is prepared by the reaction of Au(I)OLCl and NaAN. If AN is [BAr F 4] – In this case, this reaction is particularly preferred.

[0069] In a more preferred embodiment, the Au(I) complex is chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] gold(I).

[0070] When the step of reacting the compound of formula (II) with the acetylene of formula (III) is carried out in the presence of at least one Au(I) complex and at least one Ag(I) salt or Ag(I) complex, the molar ratio of the Au(I) complex to the Ag(I) salt or Ag(I) complex is preferably in the range of 0.4:1 to 3:1, particularly in the range of 0.75:1 to 1.25:1, and preferably in the range of 0.9:1 to 1.1:1.

[0071] The molar ratio of the compound of formula (II) to acetylene of formula (III) is preferably in the range of 1:1 to 1:20, especially 1:2 to 1:10.

[0072] The gold (I) complex is typically used in a molar ratio of the compound of formula (II) to the Au(I) complex in the range of 10000:1–5:1, particularly 500:1–5:1, preferably 100:1–5:1, and more preferably 20:1–10:1.

[0073] The compounds of formula (II) are readily available. In particular, 2-methylfuran can be obtained from biomass, especially as disclosed by Y. Román-Leshkov et al., Nature 2007, 447, 982–985. Therefore, 2-methylfuran is a very popular bio-based starting material that can be used for the sustainable synthesis of any corresponding target end product and is an important factor in achieving low CO2 balance in chemical synthesis.

[0074] The reaction is preferably carried out at atmospheric pressure (i.e., 10¹³ mbar). The reaction temperature is particularly between 0°C and 140°C, more particularly between 10°C and 80°C, and preferably between 15°C and 35°C. It is very advantageous that the reaction can be carried out at low temperatures, especially at room temperature.

[0075] The reaction of a compound of formula (II) with acetylene of formula (III) in the presence of at least one Au(I) complex is preferably carried out in an inert organic non-nucleophilic solvent or a mixture of inert organic non-nucleophilic solvents. Preferred solvents are halogenated solvents, particularly dichloromethane, 1,2-dichloroethane, chloroform or 2,2,2-trifluoroethanol; or toluene, ethyl acetate or cyclohexanone.

[0076] It has been observed that, in particular, a mixture of dichloromethane and 2,2,2-trifluoroethanol is highly suitable for obtaining high selectivity for compounds of formula (I), preferably with an excess of dichloromethane, and more preferably with a mixture of dichloromethane and 5% by volume of 2,2,2-trifluoroethanol, which is highly suitable for obtaining high selectivity for compounds of formula (I).

[0077] Preferably, the organic solvent is a hydrocarbon or a chlorinated hydrocarbon, and dichloromethane is preferred.

[0078] It has been observed that the reaction described herein surprisingly produces p-alkylphenol of formula (I), rather than the corresponding m-alkylphenol or o-alkylphenol as would be expected by a person skilled in the art from the disclosures in prior art documents WO 2015 / 110654 A1 or WO 2015 / 110655 A1.

[0079]

[0080] The reaction proceeds smoothly, particularly with high yield and selectivity of the desired product (i.e., p-alkylphenol of formula (I)). Yields greater than 75%, preferably greater than 80%, and even more preferably greater than 83% can be achieved. Even higher yields can be obtained by optimizing the reaction conditions.

[0081] In another aspect, the present invention relates to a composition comprising

[0082] a) at least one compound of formula (II)

[0083]

[0084] Where R 1 Representing C 1-6 -alkyl;

[0085] b) Acetylene of formula (III);

[0086]

[0087] c) at least one Au(I) complex; and

[0088] d) Optionally at least one Ag(I) salt or Ag(I) complex.

[0089] As described above, the composition reacts to give the compound of formula (I).

[0090] As shown above, Au(I) complexes can be used to synthesize compounds of formula (I). Therefore, another aspect of the invention is the use of Au(I) complexes in compounds of formula (I). Preferred embodiments are those already mentioned above.

[0091] In another aspect, the present invention relates to a method for manufacturing 2,6-dimethyl-4-alkylphenol of formula (IV), comprising a combination of the following steps, which includes

[0092] i) To produce p-alkylphenols of formula (I), as discussed in detail above.

[0093]

[0094] Then

[0095] ii) Methylating the compound of formula (I) to generate the compound of formula (IV).

[0096]

[0097] Where R 1 Representing C 1-6 -alkyl.

[0098] This method specifically yields trimethylphenol (2,4,6-trimethylphenol), i.e., formula (IV), wherein R 1 It is a methyl group.

[0099] As disclosed in EP 1 108 705 A1, and particularly in Example 3, the compound of formula (I) can be methylated with methanol in a high-temperature autoclave in the presence of lithium hydroxide monohydrate, for example, to produce the compound of formula (IV).

[0100] It has been found that the methylation of compounds of formula (I) to form compounds of formula (IV) can be achieved, particularly by gas-phase methylation, especially by reacting compounds of formula (I) with a mixture of methanol and water in an inert atmosphere in the presence of an oxidizing catalyst at a temperature of 300 to 500 °C.

[0101] In another aspect, the present invention relates to a method for manufacturing 2,3,6-trimethylhydroquinone of formula (VI), comprising the following steps

[0102] i) To manufacture compounds of formula (I), as discussed in detail above.

[0103]

[0104] Then

[0105] ii) Methylating the compound of formula (I) to generate the compound of formula (IV).

[0106]

[0107] Then

[0108] iii) Oxidate the compound of formula (IV) to produce the compound of formula (V).

[0109]

[0110] iv) Rearrange the compound of formula (V) to generate the compound of formula (VI).

[0111]

[0112] Where R 1 Represents methyl.

[0113] The conversion of tricresyl to 2,3,6-trimethylhydroquinone is well known to those skilled in the art, for example from Ullmann’s Encyclopedia of Industrial Chemistry, 2012 edition, “Vitamins”, Vol. 38, p. 204 (DOI: 10.1002 / 14356007.o27_o07).

[0114] The methylation in step ii) has been discussed in great detail above.

[0115] The oxidation in step iii) can be carried out by methods well known to those skilled in the art.

[0116] In particular, it can be carried out by molecular oxygen, especially in the presence of cobalt complexes and / or in the presence of alkali, particularly alkali metal salts, details of which are disclosed in DE 2 314 600 or DE 2 747 497.

[0117] Furthermore, the oxidation in step iii) can be carried out in a suitable solvent by chlorine, preferably in the absence of a base, followed by hydrolysis with water as described in US 4,612,401.

[0118] Furthermore, the oxidation in step iii) can be carried out in an aqueous medium or a mixture of water and an organic solvent by means of a hypohalogenous acid or a salt; details of which are disclosed in EP 0 084 158 A1.

[0119] The rearrangement in step iv) can be performed using methods well known to those skilled in the art.

[0120] In particular, it can be carried out by heating, preferably by heating the compound of formula (V) to a temperature of about 95°C, preferably in the presence of a base (e.g., sodium hydroxide), as disclosed in DE 2 314 600.

[0121] Furthermore, the rearrangement in step iv) can be performed by heating the compound of formula (V) to a temperature of at least 100°C in a non-acidic liquid medium and an aqueous medium, details of which are disclosed in FR 2 200 225 or DE 2 345 062, wherein the non-acidic liquid medium is selected from methanol and the aqueous medium is selected from water and aqueous solutions of water-soluble organic solvents.

[0122] The method described in this paper can be used to successfully obtain 2,3,6-trimethylhydroquinone of formula (VI). Example

[0123] The invention is further illustrated by the following experiments.

[0124] Synthesis of p-cresol

[0125] In a 10 mL glass septum equipped with a magnetic stir bar, 38.0 mg of chloro[1,3-bis(2,6-diisopropylphenyl)imidazolium-2-ylidene]gold(I) (60 μmol, 0.06 equivalents) and 21.0 mg of silver hexafluoroantimonate (60 μmol, 0.06 equivalents) were dissolved in 2000 μL of dichloromethane under argon atmosphere. Additionally, 90.8 μL of 2-methylfuran (1 mmol, 1 equivalent) was added. Acetylene was generated in an acetylene generator, and 130.0 mg of acetylene (5 mmol, 5 equivalents) was bubbled into the reaction mixture over two hours at 23 °C. GC was then performed after the reaction. After the 2-methylfuran was consumed, the catalyst was filtered off, dichloromethane was removed under reduced pressure, and the product was analyzed by GC / MS and NMR. Analysis showed that p-cresol was in 84% yield. o-cresol and m-cresol were not detected by GC / MS. NMR analysis confirmed the structure of p-cresol.

[0126] The same reaction was carried out without the gold (I) complex, i.e., using silver hexafluoroantimonate alone or with other metal salts or complexes, such as Au(III) (such as AuCl3) or ZnCl2, CuCl, AuCl, AgBF4, Cu(OTf)2 (or Cu(OSO2CF3)2) or AgNO3, without the formation of any desired product.

[0127] Synthesis of 2,4,6-trimethylphenol (methylation of p-cresol)

[0128] A catalyst (13 g) consisting of Fe / Si / Cr / K oxides in a molar ratio of 100 / 2 / 1 / 0.1 was placed in a tubular reactor. The reactor was heated to 440 °C (external temperature measurement) under a nitrogen flow. A mixture of p-cresol, methanol, and water (molar ratio: 1:8:1) was pumped through the reactor at 0.1 ml / min. After the reactor, the material was cooled to room temperature and collected in a flask. The reaction was stopped after 223 / 4 hours. During this time, 121 g of the material (p-cresol, methanol, and water) was pumped through the reactor. Approximately 51 g of the material remained in the reactor and tubing. The product mixture was concentrated under vacuum. The remaining residue (23.4 g) contained 89% 2,4,6-trimethylphenol (yield: 89%).

[0129] Characterization of 2,4,6-trimethylphenol:

[0130] 1 H-NMR (300MHz, CDCl3): δ (ppm) = 2.20 (s, 6H, CH3), 2.21 (s, 3H, CH3), 4.45 (s, 1H, OH), 6.77 (s, 2H, CH);

[0131] 13 C-NMR (75MHz, CDCl3): δ (ppm) = 15.9 (CH3), 20.5 (CH3), 122.9 (C), 129.2 (CH), 129.4 (C), 149.9 (C).

Claims

1. A method for manufacturing p-alkylphenol of formula (I), The steps include reacting a compound of formula (II) with acetylene of formula (III) in the presence of at least one Au(I) complex. And R 1 Representing C 1-6 -alkyl; Its features are, Au(I) complexes have the formula [Au(I)OL]AN, where OL represents an organic ligand and AN represents a monocharged anion, chosen from [BX4]. - [PX6] - [SbF6] - [ClO4] - CF3COO - Sulfonate of formula (AN-II), tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BAr) F – The group consists of tetraphenylborate and anions of formula (AN-I). Where X represents a halogen atom; And Y 1 Represents phenyl or C 1-8 -alkyl; And among them, organic ligands (OL) are - At least one phosphorus-containing ligand, selected from the group consisting of (P1), (P2), (P3), (P4), (P5), (P6), (P7) and (P8); or -At least one imidazole-2-subunit ligand; or -At least one 1H-1,2,3-triazole ligand; 2. The method according to claim 1, characterized in that, Y 1 Represents phenyl or C 1-8 -alkyl group, which is substituted with at least one halogen atom; and The at least one imidazole-2-subunit ligand is 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazole-2-subunit (= compounds of formula (IM)); The at least one 1H-1,2,3-triazole ligand is a 1H-1,2,3-triazole ligand of formula (TR-1), (TR-2), or (TR-3). Where R 10 and R 11 H can be represented independently, either linearly or branched, by C. 1-10 -alkyl or C 4-10 -cycloalkyl; and Where R 12 R 13 R 14 and R 15 H can be represented independently, either linearly or branched, by C. 1-6 -alkyl; n represents an integer from 1 to 6, and n' represents 0, 1, or 2.

3. The method according to claim 1 or 2, characterized in that... R 1 It is methyl or ethyl.

4. The method according to claim 1 or 2, characterized in that... R 1 It is a methyl group.

5. The method according to claim 1 or 2, characterized in that... The Au(I) complex includes at least one phosphorus-containing ligand.

6. The method according to claim 1 or 2, characterized in that... The Au(I) complex contains at least a 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-subunit as a ligand.

7. The method according to claim 1 or 2, characterized in that... Having a style The Au(I) complex of [Au(I)OL]AN is prepared by the reaction of Au(I)OLCl and AgAN.

8. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) is carried out in the presence of at least one Au(I) complex and at least one Ag(I) salt or Ag(I) complex combination.

9. The method according to claim 8, characterized in that... The Ag(I) salt or Ag(I) complex is AgSbF6.

10. The method according to claim 8, characterized in that... The molar ratio of Au(I) complex to Ag(I) salt or Ag(I) complex is in the range of 0.4:1 to 3:

1.

11. The method according to claim 8, characterized in that... The molar ratio of Au(I) complex to Ag(I) salt or Ag(I) complex is in the range of 0.75:1 to 1.25:

1.

12. The method according to claim 8, characterized in that... The molar ratio of Au(I) complex to Ag(I) salt or Ag(I) complex is in the range of 0.9:1 to 1.1:

1.

13. The method according to claim 1 or 2, characterized in that... The molar ratio of the compound of formula (II) to acetylene is in the range of 1:1 to 1:

20.

14. The method according to claim 1 or 2, characterized in that The molar ratio of the compound of formula (II) to acetylene is in the range of 1:2 to 1:

10.

15. The method according to claim 1 or 2, characterized in that, The molar ratio of the compound of formula (II) to the Au(I) complex is in the range of 10000:1–5:

1.

16. The method according to claim 1 or 2, characterized in that, The molar ratio of the compound of formula (II) to the Au(I) complex is in the range of 500:1–5:

1.

17. The method according to claim 1 or 2, characterized in that, The molar ratio of the compound of formula (II) to the Au(I) complex is in the range of 100:1–5:

1.

18. The method according to claim 1 or 2, characterized in that, The molar ratio of the compound of formula (II) to the Au(I) complex is in the range of 20:1 to 10:

1.

19. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out in an inert organic non-nucleophilic solvent or a mixture of inert non-nucleophilic organic solvents.

20. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out in a hydrocarbon or chlorinated hydrocarbon.

21. The method according to claim 1 or 2, characterized in that The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out in dichloromethane.

22. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out at a temperature of 0°C to 140°C.

23. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out at a temperature of 10°C to 80°C.

24. The method according to claim 1 or 2, characterized in that... The step of reacting the compound of formula (II) with the acetylene of formula (III) in the presence of at least one Au(I) complex is carried out at a temperature of 15°C to 35°C.

25. A composition comprising: a) at least one compound of formula (II) Where R 1 Representing C 1-6 -alkyl; b) Acetylene of formula (III); HC≡CH (III) c) at least one Au(I) complex; and d) Optionally at least one Ag(I) salt or Ag(I) complex.

26. Uses of Au(I) complexes in compounds of formula (I), Where R 1 Representing C 1-6 -alkyl; The Au(I) complex has the formula [Au(I)OL]AN, where OL represents an organic ligand and AN represents a monocharged anion, chosen from [BX4]. - [PX6] - [SbF6] - [ClO4] - CF3COO - Sulfonate of formula (AN-II), tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BAr) F – The group consists of tetraphenylborate and anions of formula (AN-I). Where X represents a halogen atom; And Y 1 Represents phenyl or C 1-8 -alkyl; And among them, organic ligands (OL) are - At least one phosphorus-containing ligand, selected from the group consisting of (P1), (P2), (P3), (P4), (P5), (P6), (P7) and (P8); or -At least one imidazole-2-subunit ligand; or -At least one 1H-1,2,3-triazole ligand; 27. The use according to claim 26, characterized in that, Y 1 Represents phenyl or C 1-8 -alkyl group, which is substituted with at least one halogen atom; and The at least one imidazole-2-subunit ligand is 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazole-2-subunit (= compounds of formula (IM)); The at least one 1H-1,2,3-triazole ligand is a 1H-1,2,3-triazole ligand of formula (TR-1), (TR-2), or (TR-3); Where R 10 and R 11 H can be represented independently, either linearly or branched, by C. 1-10 -alkyl or C 4-10 -cycloalkyl; and Where R 12 R 13 R 14 and R 15 H can be represented independently, either linearly or branched, by C. 1-6 -alkyl; n represents an integer from 1 to 6, and n' represents 0, 1, or 2.

28. A method for manufacturing 2,6-dimethyl-4-alkylphenol of formula (IV), comprising the following steps: i) To produce p-alkylphenol of formula (I) by any one of claims 1-24. Then ii) Methylating the compound of formula (I) to generate the compound of formula (IV). Where R 1 Representing C 1-6 -alkyl.

29. The method according to claim 28, characterized in that, Formula (IV) is trimethylphenol (2,4,6-trimethylphenol).

30. A method for manufacturing 2,3,6-trimethylhydroquinone of formula (VI), It includes the following steps: i) To manufacture the compound of formula (I) by any one of claims 1-24. Then ii) Methylating the compound of formula (I) to generate the compound of formula (IV). Then iii) Oxidate the compound of formula (IV) to produce the compound of formula (V). iv) Rearrange the compound of formula (V) to generate the compound of formula (VI). Where R 1 Represents methyl.

Images