A method for preparing benzoquinone compound and 2-methyl-1,4-naphthoquinone

Abstract

The invention discloses a method for preparing a benzoquinone compound and 2-methyl-1,4-naphthoquinone. The method comprises the steps of: causing a phenol compound to undergo an oxidation reaction in a catalyst system in the presence of an oxidant to generate the benzoquinone compound. The oxidant is oxygen. The catalyst system comprises 4-R-2,2,6,6-tetramethylpiperidinyl oxide, nitrite, a protonic acid and a solvent. R is -H, -OH, -NHAc, -COOH, -COOPh or the protonic acid is at least one selected from trifluoromethanesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, a hydrochloric acid alcohol solution and sulfuric acid. The solvent is at least one selected from methanol, ethanol, propanol, tert-butanol, water and acetonitrile. The method can obtain the benzoquinone compound with a high yield. Oxygen can be used as an oxidant. The method is green and environmentally friendly. No metal catalyst is required. The use of halogen and transition metal can be avoided. The method is conducive to the preparation of high-quality 2-methyl-1,4-naphthoquinone or other benzoquinone compounds.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemical synthesis, and in particular to a method for preparing a benzoquinone compound and 2-methyl-1,4-naphthoquinone. Background Art

[0002] o-Methylbenzoquinone, also known as o-methyl-p-benzoquinone, 2-methyl-p-benzoquinone, and methyl-1,4-benzoquinone, has a molecular formula of C7H6O2. It can be used as a pigment, dye, and other industrial intermediates. Its structural formula is:

[0003]

[0004] Vitamin K3, also known as menadione (2-methyl-1,4-naphthoquinone), is an organic compound that can be derived to produce other K vitamins, such as vitamin K1 and K2. Clinically, vitamin K is a procoagulant used to treat bleeding disorders caused by vitamin K deficiency. It is also used in various foods, beverages, and dietary supplements to aid blood clotting and maintain bone health, playing a vital role in health. Vitamin K3 is the primary K vitamin produced industrially.

[0005] Currently, the prior art discloses a route for synthesizing vitamin K3 using o-methylbenzoquinone as an intermediate, and the synthesis route is:

[0006]

[0007] In this process, o-cresol is oxidized with 50% hydrogen peroxide in a microchannel reactor, followed by a Diels-Alder reaction under pressure. DMSO is then used as both solvent and oxidant to oxidize 2-methyl-1,4-tetrahydronaphthoquinone in the presence of a copper bromide / manganese bromide mixed catalyst system. However, this method uses high concentrations of peroxide to oxidize cresol to produce o-methylbenzoquinone, which not only presents significant safety issues in terms of storage and transportation, but is also expensive to prepare. Summary of the Invention

[0008] The object of the present invention is to overcome one or more deficiencies of the prior art and to provide an improved method for preparing benzoquinone compounds, which can use oxygen as an oxidant, is low-cost, environmentally friendly, and can obtain the target product in high yield, and can be used to produce o-methylbenzoquinone.

[0009] The present invention also provides a method for preparing 2-methyl-1,4-naphthoquinone, which includes the preparation process of the above-mentioned benzoquinone compound (specifically o-methylbenzoquinone).

[0010] To achieve the above object, the present invention adopts a technical solution: a method for preparing a benzoquinone compound, the preparation method comprising:

[0011] The phenol compound represented by formula (a) is oxidized in the presence of a first oxidant in a first catalytic system to generate a benzoquinone compound represented by formula (b). The reaction formula is:

[0012] Among them, R 1 、R 2 、R 3 、R 4 are independently selected from H, C 1-10 Alkyl; or, R 1 、R 2 C 1-10 Alkylene, and R 1 , on the benzene ring and R 1 The carbon atom connected to the 2 , on the benzene ring and R 2 The connected carbon atoms together form an unsaturated 4-8 membered ring, R 3 、R 4 are independently selected from H, C 1-10 alkyl;

[0013] The first oxidant is oxygen;

[0014] The first catalytic system comprises 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), a nitrite, a protonic acid, and a first solvent, wherein the protonic acid is a combination of one or more selected from trifluoromethanesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, an alcoholic solution of hydrogen chloride, and sulfuric acid, and the first solvent is a combination of one or more selected from methanol, ethanol, propanol, tert-butanol, water, and acetonitrile;

[0015] R is -H, -OH, -NHAc, -COOH, -COOPh or

[0016] In some embodiments of the present invention, the alcoholic hydrogen chloride solution may be added in the form of a hydrogen chloride-ethanol solution.

[0017] According to the present invention, in the catalytic system of the present invention, since the first oxidant can be oxygen, which is environmentally friendly and readily available, the first oxidant can be provided, for example, by introducing pure oxygen gas or a gas mixture containing oxygen (e.g., air) into the reaction system. Furthermore, according to the present invention, the purity of the oxygen in the pure oxygen gas is greater than 99%, and the oxygen concentration in the gas mixture containing oxygen is less than 99%.

[0018] According to some preferred aspects of the present invention, the molar ratio of the phenolic compound represented by formula (a), the 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), the nitrite and the protonic acid is 10-200:1:1-4:1-4; further, the molar ratio of the phenolic compound represented by formula (a), the 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), the nitrite and the protonic acid is 10-50:1:1.5-2.5:1.5-2.5.

[0019] According to some preferred aspects of the present invention, the molar ratio of the total amount of 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), the nitrite and the protonic acid to the phenolic compound represented by formula (a) is 0.01-1:1.

[0020] According to some preferred aspects of the present invention, the first solvent is at least one of methanol, tert-butanol, and acetonitrile, the nitrite is potassium nitrite and / or sodium nitrite, and the protonic acid is trifluoromethanesulfonic acid and / or methanesulfonic acid.

[0021] According to some preferred aspects of the present invention, the reaction temperature of the oxidation reaction is 20-80°C. Further, the reaction temperature of the oxidation reaction is 30-50°C.

[0022] According to some preferred aspects of the present invention, the reaction pressure of the oxidation reaction is 0.1-20 MPa. Further, the reaction pressure of the oxidation reaction is 0.2-15 MPa.

[0023] According to some preferred and specific aspects of the present invention, R 1 、R 2 、R 3 、R 4 are independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl or hexyl; or, R 1 、R 2 C 1-10 Alkylene, and R 1 , on the benzene ring and R 1 The carbon atom connected to the 2 , on the benzene ring and R 2 The connected carbon atoms together form an unsaturated 6-membered ring, R 3 、R 4 Each is independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl or hexyl.

[0024] In some embodiments of the present invention, the phenolic compound represented by formula (a) is a combination of one or more selected from o-cresol, m-cresol, 2,6-dimethylphenol, 2,3,6-trimethylphenol, 2,5-dimethylphenol, 2-methyl-5-isopropylphenol, 2-isopropyl-5-methylphenol, 2-ethylphenol, 2-isopropylphenol, 2-tert-butylphenol and 2-methylnaphthol.

[0025] In some preferred embodiments of the present invention, the oxidation reaction is carried out under stirring conditions.

[0026] In some embodiments of the present invention, the method for preparing benzoquinone compounds includes adding a phenolic compound represented by formula (a), 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), a nitrite, a protonic acid and a first solvent to a reactor, introducing oxygen, and reacting under stirring conditions.

[0027] Another technical solution provided by the present invention is a method for preparing 2-methyl-1,4-naphthoquinone, which adopts the following synthetic route:

[0028]

[0029] The method comprises the following steps: (1) using a phenolic compound represented by formula (a) as a substrate to prepare a benzoquinone compound represented by formula (b), wherein the phenolic compound represented by formula (a) is o-cresol and / or m-cresol, and the benzoquinone compound represented by formula (b) is o-methylbenzoquinone; (2) using o-methylbenzoquinone and 1,3-butadiene as substrates to prepare 2-methyl-1,4-tetrahydronaphthoquinone; (3) using 2-methyl-1,4-tetrahydronaphthoquinone as a substrate to prepare 2-methyl-1,4-naphthoquinone; wherein: step (1) is carried out using the above-mentioned method for preparing benzoquinone compounds.

[0030] In some embodiments of the present invention, step (2) can be performed using conventional methods.

[0031] Preferably, in step (2), 2-methyl-1,4-tetrahydronaphthoquinone is prepared by the following method:

[0032] o-Methylbenzoquinone and 1,3-butadiene undergo addition reaction under the catalysis of the metal chelate ionic liquid represented by formula (ii) to generate 2-methyl-1,4-tetrahydronaphthoquinone. The reaction formula is:

[0033]

[0034] in, a, b, c, and d are each independently 0, 1, or 2. In the present invention, the metal chelate ionic liquid represented by formula (ii) acts as a Lewis acid to catalyze the Diels-Alder reaction of o-methylbenzoquinone and 1,3-butadiene, achieving significant results. Furthermore, the metal chelate ionic liquid exhibits excellent thermal stability and excellent solubility in conventional organic solvents and water. Therefore, the catalyst can be reused by distillation or by water washing and separation.

[0035] According to some preferred and specific aspects of the present invention, the values ​​of a, b, c and d are the same.

[0036] According to a specific aspect of the present invention, the structure of the metal chelate ionic liquid (Chelate-Cu-IL) represented by formula (ii) is as follows:

[0037]

[0038] According to some preferred aspects of the present invention, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methylbenzoquinone is 1:5-5000.

[0039] Furthermore, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methylbenzoquinone is 1:5-2500.

[0040] Furthermore, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methylbenzoquinone is 1:5-2000.

[0041] Furthermore, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methylbenzoquinone is 1:5-1000.

[0042] In some preferred and specific embodiments of the present invention, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methylbenzoquinone is 1:5-500.

[0043] In some embodiments of the present invention, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methyl benzoquinone is 1:10-5000. Further, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methyl benzoquinone is 1:10-2500. Still further, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methyl benzoquinone is 1:10-2000. Still further, the molar ratio of the metal chelate ionic liquid represented by formula (ii) to the o-methyl benzoquinone is 1:10-1000.

[0044] According to the present invention, under the catalysis of the metal chelate ionic liquid of the present invention, the addition reaction can be carried out at a relatively low temperature; in some embodiments of the present invention, the reaction temperature of the addition reaction is 0-80°C, and further, can be carried out at 0-70°C.

[0045] According to the present invention, under the catalytic action of the metal chelate ionic liquid of the present invention, the reaction pressure of the addition reaction can be normal pressure, and no pressure treatment is required. The ideal product yield can be obtained by carrying out the reaction under normal pressure.

[0046] According to the present invention, under the catalysis of the metal chelate ionic liquid of the present invention, the molar ratio of o-methyl benzoquinone to 1,3-butadiene can be 1:0.95-1.05. According to a specific aspect of the present invention, the molar ratio of o-methyl benzoquinone to 1,3-butadiene can be 1:1.

[0047] According to some preferred aspects of the present invention, the method for preparing the metal chelate ionic liquid represented by formula (ii) comprises:

[0048] The compound represented by formula (iii) is reacted with the compound represented by formula (iv) in a second solvent to prepare a metal chelate ionic liquid represented by formula (ii):

[0049] , the definitions of a, b, c, and d are the same as before.

[0050] According to some preferred and specific aspects of the present invention, the second solvent comprises acetone. In some embodiments of the present invention, the second solvent is acetone.

[0051] According to some preferred and specific aspects of the present invention, the reaction is carried out at 10-40°C.

[0052] According to some preferred aspects of the present invention, the compound represented by formula (iii) is synthesized using the following route:

[0053]

[0054] Among them, 2,6-dimethylaniline is reacted with 2,6-pyridinedicarbonyl chloride to produce the compound represented by formula (v), and the compound represented by formula (v) is reacted with copper chloride and methanol to produce the compound represented by formula (iii).

[0055] According to some preferred aspects of the present invention, during the preparation of the compound represented by formula (v), the reaction is carried out in an alkaline environment, wherein the alkaline environment is formed by adding an alkaline reagent, and the alkaline reagent comprises triethylamine.

[0056] According to some preferred aspects of the present invention, in the process of preparing the compound represented by formula (v), the reaction is carried out at 10-40° C. in a third solvent, wherein the third solvent comprises a halogenated C1-C3 alkyl group. In some embodiments of the present invention, the halogen in the halogenated C1-C3 alkyl group is one or more selected from fluorine, chlorine and bromine. Furthermore, the halogenated C1-C3 alkyl group can be dichloromethane, dichloroethane, etc.

[0057] According to some preferred aspects of the present invention, in the process of preparing the compound represented by formula (iii), the reaction of the compound represented by formula (iii) with copper chloride and methanol is carried out at 10-40° C. in the presence of an alkali metal methoxide, wherein the alkali metal methoxide is a combination of one or more selected from sodium methoxide, potassium methoxide and lithium methoxide.

[0058] In some embodiments of the present invention, step (3) can be performed using conventional methods.

[0059] Preferably, in step (3), 2-methyl-1,4-naphthoquinone is prepared by the following method:

[0060] 2-methyl-1,4-tetrahydronaphthoquinone is subjected to an oxidative dehydrogenation reaction in the second catalytic system in the presence of a second oxidant to generate 2-methyl-1,4-naphthoquinone. The reaction formula is:

[0061]

[0062] The second catalytic system comprises a heterogeneous nitrogen-doped carbon material supported cobalt catalyst and a fourth solvent;

[0063] The preparation method of the heterogeneous nitrogen-doped carbon material loaded cobalt catalyst comprises: preparing glucosamine hydrochloride (molecular formula: C6H 13 NO5·HCl (molecular weight 215.63), melamine, and cobalt acetate are mixed and sintered under an inert atmosphere; the mass ratio of glucosamine hydrochloride to melamine is 1:25-45, and the molar ratio of glucosamine hydrochloride to cobalt acetate is 1:0.01-0.75. The heterogeneous nitrogen-doped carbon material-supported cobalt catalyst prepared by the method of the present invention can efficiently and selectively prepare 2-methyl-1,4-naphthoquinone by oxidative dehydrogenation of 2-methyl-1,4-tetrahydronaphthoquinone. This process is both environmentally friendly and the catalyst is easily recyclable, which helps reduce costs.

[0064] According to the present invention, in the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst prepared by the method of the present invention, the nitrogen-doped carbon material is used as a carrier, and the cobalt element obtained by sintering is coated with the carrier nitrogen-doped carbon material as an active component.

[0065] In some embodiments of the present invention, the inert atmosphere can be formed by introducing nitrogen, argon, etc.

[0066] According to some preferred aspects of the present invention, the mass ratio of the glucosamine hydrochloride to the melamine is 1:30-40. Further, the mass ratio of the glucosamine hydrochloride to the melamine is 1:32-38.

[0067] According to some preferred aspects of the present invention, the molar ratio of the glucosamine hydrochloride to the cobalt acetate is 1:0.02-0.70. Further, the molar ratio of the glucosamine hydrochloride to the cobalt acetate is 1:0.025-0.45.

[0068] In some preferred embodiments of the present invention, the molar ratio of the glucosamine hydrochloride to the cobalt acetate is 1:0.1-0.2.

[0069] According to some preferred aspects of the present invention, the sintering is performed at 550-850°C.

[0070] Furthermore, the sintering is carried out in the following manner: sintering at 550-650°C for a sintering time of t1; then heating to 750-850°C at a heating rate of 1.5-3.5°C / min and sintering for a sintering time of t2, where t1 and t2 are 0.5-2h respectively.

[0071] In some preferred embodiments of the present invention, the embodiment of preparing the heterogeneous nitrogen-doped carbon material-loaded cobalt catalyst includes: dispersing glucosamine hydrochloride, melamine and cobalt acetate in deionized water, stirring under heating conditions until the deionized water is completely evaporated, and then sintering the dried mixture under an inert atmosphere to prepare the heterogeneous nitrogen-doped carbon material-loaded cobalt catalyst.

[0072] According to some preferred aspects of the present invention, the added mass of the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst is greater than 0.1% of the added mass of the 2-methyl-1,4-tetrahydronaphthoquinone, calculated as a percentage by mass.

[0073] Furthermore, the added mass of the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst is 0.5%-10% of the added mass of the 2-methyl-1,4-tetrahydronaphthoquinone, calculated as a percentage by mass. Furthermore, the added mass of the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst is 0.5%-6% of the added mass of the 2-methyl-1,4-tetrahydronaphthoquinone, calculated as a percentage by mass. Still further, the added mass of the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst is 0.8%-5% of the added mass of the 2-methyl-1,4-tetrahydronaphthoquinone, calculated as a percentage by mass.

[0074] According to the present invention, under the catalytic system of the present invention, the oxidative dehydrogenation reaction can be carried out at a relatively low temperature. According to some preferred and specific aspects of the present invention, the reaction temperature of the oxidative dehydrogenation reaction is 0-40°C.

[0075] In some embodiments of the present invention, the reaction time of the oxidative dehydrogenation reaction is 0.5-5 h.

[0076] In some embodiments of the present invention, the reaction pressure of the oxidative dehydrogenation reaction is 0.01-0.15 MPa.

[0077] According to some preferred aspects of the present invention, the fourth solvent is an alcohol solvent and / or a nitrile solvent.

[0078] According to some preferred aspects of the present invention, the alcohol solvent is a C1-C6 alkyl alcohol. In the present invention, "C1-C6 alkyl alcohol" refers to an alkyl alcohol having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0079] Furthermore, the alcohol solvent is a combination of one or more selected from methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, n-pentanol and isopentanol.

[0080] According to some preferred aspects of the present invention, the nitrile solvent comprises acetonitrile.

[0081] According to the present invention, in the catalytic system of the present invention, the second oxidant can be oxygen, which is environmentally friendly and low-cost. The first oxidant can be provided by introducing pure oxygen gas or a gas mixture containing oxygen (e.g., air) into the reaction system. According to the present invention, the purity of the oxygen in the pure oxygen gas is greater than 99%, and the oxygen concentration in the gas mixture containing oxygen is less than 99%.

[0082] In some preferred embodiments of the present invention, the oxidative dehydrogenation reaction is carried out as follows: 2-methyl-1,4-tetrahydronaphthoquinone, a heterogeneous nitrogen-doped carbon material-loaded cobalt catalyst, and a fourth solvent are uniformly mixed, and then pure oxygen gas or air with a purity greater than 99% is introduced, and the reaction temperature is controlled to be 0-40°C and the reaction pressure is controlled to be 0.01-0.15MPa to carry out an oxidative dehydrogenation reaction to generate 2-methyl-1,4-naphthoquinone.

[0083] In the present invention, the cobalt acetate may contain crystalline water or may be treated to not contain crystalline water.

[0084] In the present invention, the descriptions of "first", "second", "third" and "fourth" are only for distinguishing the catalytic systems or solvents used in each reaction, which is convenient for description and not easy to be confused. They do not represent a sequence relationship, nor do they mean the same or different.

[0085] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0086] After extensive experimental research, the present invention has found that under the synergistic effect of nitrite and specific protonic acids, the use of the organic catalyst 4-R-2,2,6,6-tetramethylpiperidinyl oxide (4-R-TEMPO) in specific solvents such as methanol, ethanol, propanol, or acetonitrile can achieve oxygen oxidation of o-cresol to o-methylbenzoquinone. This is low-cost, environmentally friendly, and can also achieve excellent yields in the process of preparing the target product o-methylbenzoquinone. Furthermore, the present invention does not require the use of metal catalysts and can avoid the use of halide ions and transition metals, which is beneficial to industrial production and improves the quality of vitamin K3 drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 Electrospray ionization high-resolution mass spectrometry and atomic absorption characterization spectra of the cations in the copper chelate ionic liquid Chelate-Cu-IL prepared in Example 32 of the present invention;

[0088] Figure 2 Electrospray ionization high-resolution mass spectrometry and atomic absorption characterization spectra of anions in the copper chelate ionic liquid Chelate-Cu-IL prepared in Example 32 of the present invention;

[0089] Figure 3 : X-ray diffraction spectra of Co@CN catalysts with different cobalt contents. Example 32 uses 1Co@CN catalyst, Example 42 uses 0.25Co@CN, Example 44 uses 2Co@CN, and Example 45 uses 4Co@CN catalyst;

[0090] Figure 4 The X-ray photoelectron spectrum (oxygen 1s electron) of the 1Co@CN catalyst and CN in Example 32 of the present invention is shown;

[0091] Figure 5 X-ray photoelectron spectrum (nitrogen 1s electron) of 1Co@CN catalyst and CN in Example 32 of the present invention;

[0092] Figure 6 X-ray photoelectron spectra (cobalt 2p electrons) of the 1Co@CN catalyst at different binding energies in Example 32 of the present invention;

[0093] Figure 7 These are the X-ray diffraction spectra of the 1Co@CN catalyst of Example 32 and the Co / AC catalyst of Comparative Example 15 in the examples of the present invention. DETAILED DESCRIPTION

[0094] The above scheme is further described below in conjunction with specific examples; it should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited to the scope of the following examples; the implementation conditions adopted in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are generally the conditions in routine experiments.

[0095] Unless otherwise specified in the following examples, all raw materials were purchased from commercial sources or prepared by conventional methods in the art.

[0096] In the following, all reaction conversions and yields were determined by gas chromatography (using commercially available starting materials and products as standard curves).

[0097] In the following, the structural formula of 4-OH-TEMPO is: The structural formula of 4-COOH-2,2,6,6-tetramethylpiperidinyl oxide is: The structural formula of 4-COOPh-2,2,6,6-tetramethylpiperidinyl oxide is: The structural formula of 4-NHAc-2,2,6,6-tetramethylpiperidinyl oxide is: The structural formula of 2,2,6,6-tetramethylpiperidinyl oxide is: The structural formula of 4-Maleimide (maleimide)-2,2,6,6-tetramethylpiperidinyl oxide is: The structural formula of 4-NH2-2,2,6,6-tetramethylpiperidinyl oxide is:

[0098] In the following, trifluoromethanesulfonic acid, p-toluenesulfonic acid, and methanesulfonic acid are respectively commercially available products with a purity of 99%; acetic acid is commercially available and has a purity of 99.5%; nitric acid is an analytically pure reagent with a mass concentration of 98% fuming nitric acid; sulfuric acid is a commercially available product with a purity of AR (Shanghai test) of 95.0 to 98.0%; hydrogen chloride is a commercially available hydrogen chloride-ethanol solution with a concentration of 2 mol / L; the charging amount of each acid is converted according to the required molar weight.

[0099] Example 1

[0100] This example provides a method for preparing o-methylbenzoquinone, which adopts the following synthetic route:

[0101]

[0102] The method comprises the following steps: adding 1 mmol of o-cresol, 0.05 mmol of 4-OH-TEMPO, 0.1 mmol of sodium nitrite, 0.1 mmol of trifluoromethanesulfonic acid and 2 mL of methanol into a 20 mL reaction bottle, adding a magnet, passing oxygen (pure oxygen gas with a purity greater than 99%) at a pressure of 0.5 MPa, reacting for 18 hours at 30° C. and 800 rpm under stirring, wherein the reaction conversion rate is 100% and the o-methyl benzoquinone yield is 92.7%; after removing the solvent from the reaction solution by rotary vortexing, dissolving the solution in 10 mL of ethyl acetate, washing the solution twice with 2 mL of sodium hydroxide aqueous solution, extracting the solution three times with 5 mL of saturated saline, drying the organic phase with anhydrous sodium sulfate and then rotary drying the solution to obtain purified o-methyl benzoquinone with a purity of 99%.

[0103] Example 2

[0104] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of m-cresol. The rest is exactly the same as Example 1. The reaction conversion rate is 98.2%, the o-methyl benzoquinone yield is 87.9%, and the purity is 97%.

[0105] Example 3

[0106] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2,6-dimethylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 97.1%, and the purity is 99%.

[0107] Example 4

[0108] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2,3,6-trimethylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2,3,6-trimethylbenzoquinone is 98.5%, and the purity is 99%.

[0109] Example 5

[0110] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-methyl-5-isopropylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-methyl-5-isopropylbenzoquinone is 94.3%, and the purity is 98%.

[0111] Example 6

[0112] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2,5-dimethylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2,5-dimethylbenzoquinone is 89.3%, and the purity is 96%.

[0113] Example 7

[0114] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-isopropyl-5-methylphenol. The rest of the reaction is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-isopropyl-5-methylbenzoquinone is 88.2%, and the purity is 97%.

[0115] Example 8

[0116] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-ethylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-ethylbenzoquinone is 90.3%, and the purity is 98%.

[0117] Example 9

[0118] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-isopropylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-isopropylbenzoquinone is 85.6%, and the purity is 96%.

[0119] Example 10

[0120] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-tert-butylphenol. The rest of the reaction is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-tert-butylbenzoquinone is 83.2%, and the purity is 94%.

[0121] Example 11

[0122] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the substrate o-cresol is adjusted to 1 mmol of 2-methylnaphthol. The rest is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2-methylnaphthoquinone is 90.4%, and the purity is 93%.

[0123] Example 12

[0124] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.005 mmol 4-NHAc-2,2,6,6-tetramethylpiperidinoxide, 0.01 mmol trifluoromethanesulfonic acid, and 0.01 mmol NaNO2. The rest is exactly the same as Example 1. The reaction conversion rate is 89.4%, the o-methylbenzoquinone yield is 80.1%, and the purity is 95%.

[0125] Example 13

[0126] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.1 mmol 4-NHAc-2,2,6,6-tetramethylpiperidinoxide, 0.2 mmol trifluoromethanesulfonic acid, and 0.2 mmol NaNO2. The rest is exactly the same as Example 1. The reaction conversion rate is 100%, the o-methylbenzoquinone yield is 92.4%, and the purity is 98%.

[0127] Example 14

[0128] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that air is passed through. The rest is exactly the same as Example 1. The reaction conversion rate is 100%, the o-methyl benzoquinone yield is 86.4%, and the purity is 97%.

[0129] Example 15

[0130] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the solvent methanol is adjusted to 2 mL of acetonitrile. The rest is exactly the same as Example 1. The conversion rate is 100%, the yield of o-methylbenzoquinone is 89.2%, and the purity is 97%.

[0131] Example 16

[0132] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the solvent methanol is adjusted to 2 mL of tert-butanol. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 92.3%, and the purity is 97%.

[0133] Example 17

[0134] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the solvent methanol is adjusted to 1.6 mL of tert-butanol plus 0.4 mL of acetonitrile. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 94.3%, and the purity is 98%.

[0135] Example 18

[0136] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.05 mmol 4-COOH-2,2,6,6-tetramethylpiperidinyl oxide. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 88.5%, and the purity is 95%.

[0137] Example 19

[0138] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.05 mmol 4-NHAc-2,2,6,6-tetramethylpiperidinyl oxide. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methyl benzoquinone yield is 89.7%, and the purity is 97%.

[0139] Example 20

[0140] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.05 mmol of 2,2,6,6-tetramethylpiperidinyl oxide. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 90.6%, and the purity is 98%.

[0141] Example 21

[0142] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.05 mmol 4-Maleimide (maleimide)-2,2,6,6-tetramethylpiperidinoxide. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 91.6%, and the purity is 99%.

[0143] Example 22

[0144] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the catalyst is 0.05 mmol 4-COOPh-2,2,6,6-tetramethylpiperidinyl oxide. The rest of the process is exactly the same as Example 1. The conversion rate is 100%, the yield of o-methylbenzoquinone is 89.9%, and the purity is 97%.

[0145] Example 23

[0146] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the protonic acid is 0.1 mmol methanesulfonic acid. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 93.1%, and the purity is 99%.

[0147] Example 24

[0148] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the protonic acid is 0.1 mmol H2SO4. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 81.4%, and the purity is 95%.

[0149] Example 25

[0150] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the protonic acid is 0.1 mmol HCl. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 79.4%, and the purity is 96%.

[0151] Example 26

[0152] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that the protonic acid is 0.1 mmol p-toluenesulfonic acid. The rest is exactly the same as Example 1. The conversion rate is 89.2%, the o-methylbenzoquinone yield is 74.1%, and the purity is 98%.

[0153] Example 27

[0154] This example provides a method for preparing o-methylbenzoquinone. Compared with Example 1, this example differs in that trifluoromethanesulfonic acid is 0.2 mmol and NaNO2 is 0.2 mmol. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methylbenzoquinone yield is 84.9%, and the purity is 96%.

[0155] Example 28

[0156] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that trifluoromethanesulfonic acid is 0.05 mmol and NaNO2 is 0.05 mmol. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methyl benzoquinone yield is 79.5%, and the purity is 93%.

[0157] Example 29

[0158] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that the reaction temperature is 20°C and the pressure is 20 MPa. The rest is exactly the same as Example 1. The conversion rate is 95.4%, the o-methyl benzoquinone yield is 84.6%, and the purity is 96%.

[0159] Example 30

[0160] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that the reaction temperature is 80°C and the pressure is 0.1 MPa. The rest is exactly the same as Example 1. The conversion rate is 93.1%, the o-methyl benzoquinone yield is 83.3%, and the purity is 94%.

[0161] Example 31

[0162] This example provides a method for preparing o-methyl benzoquinone. Compared with Example 1, this example differs in that the reaction temperature is 40°C and the pressure is 10 MPa. The rest is exactly the same as Example 1. The conversion rate is 100%, the o-methyl benzoquinone yield is 90.4%, and the purity is 97%.

[0163] Comparative Example 1

[0164] Compared with Example 1, this example differs in that the catalyst is 0.05 mmol 4-NH2-2,2,6,6-tetramethylpiperidinyl oxide, and the rest is exactly the same as Example 1. The conversion rate is 80.9%, the yield of o-methylbenzoquinone is 69.3%, and the purity is 86%.

[0165] Comparative Example 2

[0166] Compared with Example 1, this example differs in that trifluoromethanesulfonic acid is replaced by 0.1 mmol acetic acid. The rest is exactly the same as Example 1. The conversion rate is 50.9%, the yield of o-methylbenzoquinone is 41.4%, and the purity is 90%.

[0167] Comparative Example 3

[0168] Compared with Example 1, this example differs in that trifluoromethanesulfonic acid is replaced by 0.1 mmol nitric acid. The rest is exactly the same as Example 1. The conversion rate is 85.4%, the yield of o-methylbenzoquinone is 50.2%, and the purity is 86%.

[0169] Comparative Example 4

[0170] Compared with Example 1, this example differs in that trifluoromethanesulfonic acid is not added during the reaction. The rest is exactly the same as Example 1. The reaction conversion rate is 13.1%, and the yield of o-methylbenzoquinone is 12.1%.

[0171] Comparative Examples 2-4 show that trifluoromethanesulfonic acid, methanesulfonic acid, and p-toluenesulfonic acid are proton acids that are the key to the disproportionation of TEMPO catalysts, and are one of the key factors in achieving high yields.

[0172] Comparative Example 5

[0173] Compared with Example 1, this example differs in that the solvent 2 mL of methanol is replaced by 2 mL of dimethyl sulfoxide (DMSO). The rest is exactly the same as Example 1. The reaction conversion rate is 20.8%, and the yield of o-methylbenzoquinone is 2.1%.

[0174] Comparative Example 6

[0175] Compared with Example 1, this example differs in that the solvent 2 mL of methanol is replaced by 2 mL of dichloromethane. The rest is exactly the same as Example 1. The reaction conversion rate is 96.4%, and the yield of o-methylbenzoquinone is 34.3%.

[0176] Comparative Example 7

[0177] Compared with Example 1, this example differs in that the solvent 2 mL of methanol is replaced by 2 mL of chlorobenzene. The rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of o-methylbenzoquinone is 23.1%.

[0178] Comparative Examples 5-7 illustrate that the specific solvent system of the present invention has a decisive effect on the yield of o-methylbenzoquinone.

[0179] Comparative Example 8

[0180] This comparative example differs from Example 1 in that no TEMPO catalyst was added during the reaction. Otherwise, the reaction conversion rate was 0%, and the yield of o-methylbenzoquinone was 0%. This comparative example demonstrates the critical role of TEMPO catalyst in activating o-cresol and converting it to o-methylbenzoquinone.

[0181] Comparative Example 9

[0182] This example differs from Example 1 in that no NaNO2 was added in step (1). The remaining steps were identical to Example 1, resulting in a reaction conversion of 8.4% and a yield of 7.1% for o-methylbenzoquinone. This comparative example demonstrates that sodium nitrite acts as a circulating TEMPO catalyst, thereby completely converting the substrate.

[0183] The following describes the preparation of the heterogeneous nitrogen-doped carbon material-supported cobalt catalyst yCo@CN: A mixture of 2 g of GAH, 70 g of melamine, and y mmol of cobalt acetate (since the raw material cobalt acetate is easily deliquescent and carries water, the cobalt acetate can be added in the form of a hydrate, typically tetrahydrate, but can also be added after dehydration; the molar amount of cobalt acetate added need only be controlled) is dissolved in deionized water. The solution is then stirred at 80°C to evaporate the solution. The dried solid is transferred to a tube furnace and calcined at 590°C under nitrogen for 1 hour. The mixture is then heated to 790°C at a ramp rate of 2.5°C / min and held at 790°C for 50 minutes with a nitrogen flow rate of 400 mL / min. The mixture is then cooled naturally to obtain the catalyst, designated yCo@CN.

[0184] Example 32

[0185] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3), which adopts the following synthetic route:

[0186]

[0187] The method includes:

[0188] (1) Preparation of o-methylbenzoquinone: The method of Example 1 was used;

[0189] (2) Preparation of 2-methyl-1,4-tetrahydronaphthoquinone:

[0190] 0.2 mmol Chelate-Cu-IL, 2 mmol o-methylbenzoquinone prepared according to the above method, and 2 mmol 1,3-butadiene were added to a 20 mL reaction flask and reacted at 70°C for 8 hours. The reaction conversion rate was 100%, and the yield of 2-methyl-1,4-tetrahydronaphthoquinone was 95.1%. The reaction solution was vortexed to remove the solvent and dissolved in 10 mL of ethyl acetate. The product was extracted and washed three times with 5 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate and then spin-dried to obtain purified 2-methyl-1,4-tetrahydronaphthoquinone with a purity of 98%.

[0191] Among them, the copper chelate ionic liquid Chelate-Cu-IL is prepared by the following method:

[0192] The reaction formula is as follows:

[0193]

[0194] Specifically: 2,6-dimethylaniline (10 mmol) and triethylamine (26 mmol) were added to a 250 mL round-bottom flask, and a mixture of 2,6-pyridinedicarbonyl chloride (5 mmol) and dichloromethane (20 mL) was slowly added dropwise to the flask at 0°C; after stirring at room temperature for 24 h, the solvent was filtered off, and the filter cake was washed with distilled water and ether for 3-5 times, and dried in vacuo at 40°C to obtain a white powder ligand (the compound represented by formula (v)). The ligand (2.0 mmol), anhydrous copper chloride (2.0 mmol) and MeOH (100 mL) were added to a 250 mL round-bottom flask, and a 0.5 M NaOMe methanol solution (8.0 mL) was added to the mixture; the reaction was stirred at room temperature for 24 h, and an oily solid was obtained by rotary evaporation at 40°C; the solid was dissolved in acetonitrile (20 mL), and toluene (100 mL) was added and allowed to stand for 30 min before filtering. The filtrate was vacuum rotary evaporated at 40°C to obtain a green powder (compound represented by formula (iii)), which was vacuum dried overnight. In a 50 mL round-bottom flask, 2 mmol each of green powder (compound represented by formula (iii)) and trihexyl (tetradecyl) phosphine chloride (compound represented by formula (iv-1)) were added, and 10 mL of acetone was added. The mixture was stirred at room temperature for 12 h, and rotary evaporation was performed to obtain a green liquid, which was then extracted with dichloromethane (3*5 mL). The lower organic phase was again subjected to vacuum rotary evaporation at 40°C to remove the solvent, and then vacuum dried for 24 h to obtain the product: copper chelate ionic liquid Chelate-Cu-IL;

[0195] The elemental analysis table of copper chelate ionic liquid Chelate-Cu-IL is shown in Table 1:

[0196] Table 1

[0197]

[0198] The electrospray high-resolution mass spectrum and atomic absorption characterization spectrum are shown in Figure 1 and Figure 2 As shown;

[0199] (3) Preparation of 2-methyl-1,4-naphthoquinone (vitamin K3):

[0200] In a 20 mL reaction flask, 3 mmol of 2-methyl-1,4-tetrahydronaphthoquinone (prepared according to the above method), 0.01 g of 1Co@CN, and 4.0 g of methanol were added. A magnetic bar was added and an oxygen bag (0.1 MPa, pure oxygen with a purity greater than 99%) was connected. The reaction was ventilated three times and allowed to react at 25°C for one hour. The catalyst was recovered by filtration and washed three times with solvent. The mother liquors were combined and subjected to upper column distillation to obtain the pure product. The reaction conversion rate was 99.3%, the vitamin K3 yield was 98.1%, and the purity was 98.7%.

[0201] The 1Co@CN catalyst was prepared by dissolving a mixture of 2 g of GAH, 70 g of melamine, and 1 mmol of cobalt acetate in deionized water and then stirring at 80°C to evaporate the solution. The dried solid was transferred to a tube furnace and calcined at 590°C in nitrogen for 1 hour. The mixture was then heated to 790°C at a heating rate of 2.5°C / min and maintained at 790°C for 50 minutes with a nitrogen flow rate of 400 mL / min. The mixture was then cooled naturally to obtain the catalyst, designated 1Co@CN. Its X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) patterns are shown in [1]. Figure 3-Figure 6 .

[0202] Example 33

[0203] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that in step (2), the catalyst is 0.0004 mmol Chelate-Cu-IL, the reaction temperature is 80°C, and the rest is exactly the same as Example 32. The reaction conversion rate is 92.2%, the yield of 2-methyl-1,4-tetrahydronaphthoquinone is 81.5%, and the purity is 91%.

[0204] Example 34

[0205] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that in step (2), the catalyst is 0.002 mmol Chelate-Cu-IL, the reaction temperature is 40°C, and the rest is exactly the same as Example 32. The reaction conversion rate is 100%, the yield of 2-methyl-1,4-tetrahydronaphthoquinone is 92.5%, and the purity is 97%.

[0206] Example 35

[0207] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that in step (2), the catalyst is 0.04 mmol Chelate-Cu-IL, the reaction temperature is 0°C, and the rest is exactly the same as Example 32. The reaction conversion rate is 90.9%, the yield of 2-methyl-1,4-tetrahydronaphthoquinone is 89.4%, and the purity is 95%.

[0208] Example 36

[0209] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the catalyst in step (3) is 0.004 g 1Co@CN, and the rest is exactly the same as Example 14. The reaction conversion rate is 92.8%, the vitamin K3 yield is 89.4%, and the purity is 96.1%.

[0210] Example 37

[0211] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the catalyst in step (3) is 0.02 g 1Co@CN, and the rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 98.7%, and the purity is 99.3%.

[0212] Example 38

[0213] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the catalyst in step (3) is 0.005 g 1Co@CN, and the rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 94.2%, and the purity is 98.9%.

[0214] Example 39

[0215] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the solvent methanol is replaced with propanol in step (3). The rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 96.4%, and the purity is 99%.

[0216] Example 40

[0217] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the reaction temperature in step (3) is 0°C, and the rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 91.1%, and the purity is 96.8%.

[0218] Example 41

[0219] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the reaction temperature in step (3) is 40°C, and the rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 92.6%, and the purity is 98.7%.

[0220] Example 42

[0221] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the amount of cobalt acetate added during the preparation of the catalyst in step (3) is 0.25 mmol, and the prepared catalyst is recorded as 0.25Co@CN. The X-ray diffraction spectrum (XRD) is shown in FIG. Figure 3 , the rest are exactly the same as Example 32, the reaction conversion rate is 92.2%, the vitamin K3 yield is 90.6%, and the purity is 97.7%.

[0222] Example 43

[0223] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the amount of cobalt acetate added during the preparation of the catalyst in step (3) is 1.5 mmol. The rest is exactly the same as Example 32. The reaction conversion rate is 100%, the vitamin K3 yield is 98.9%, and the purity is 99%.

[0224] Example 44

[0225] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the amount of cobalt acetate added during the preparation of the catalyst in step (3) is 2 mmol. The prepared catalyst is denoted as 2Co@CN, and the X-ray diffraction spectrum (XRD) is shown in FIG. Figure 3 , the rest are exactly the same as Example 32, the reaction conversion rate is 96.3%, the vitamin K3 yield is 92.7%, and the purity is 97.8%.

[0226] Example 45

[0227] This example provides a method for preparing 2-methyl-1,4-naphthoquinone (vitamin K3). Compared with Example 32, this example differs in that the amount of cobalt acetate added during the preparation of Co@CN in step (3) is 4 mmol, the catalyst is denoted as 4Co@CN, and the X-ray diffraction spectrum (XRD) is shown in FIG. Figure 3 , the rest are exactly the same as Example 32, the reaction conversion rate is 94%, the vitamin K3 yield is 90%, and the purity is 97.5%.

[0228] Example 46 Catalyst Recovery and Application Experiment

[0229] To recover and reuse the catalyst, we conducted a scaled-up experiment for the oxidation reaction of 2-methyl-1,4-tetrahydronaphthoquinone. The specific steps were as follows: 30 mmol of 2-methyl-1,4-tetrahydronaphthoquinone, 0.1 g of 1Co@CN, and 40 g of methanol were added to a 100 mL reaction flask. A magnetic bar was added, and an oxygen bag (0.1 MPa, pure oxygen with a purity greater than 99%) was connected. The reaction was vented three times and allowed to react at 25°C for one hour. The catalyst was recovered by filtration and washed three times with solvent. The combined mother liquors were then subjected to upper column distillation to obtain the pure product. The reaction conversion was 100%, and the vitamin K3 yield was 98.5% with a purity of 99%, indicating that a 10-fold scale-up had no significant impact on the yield and product purity.

[0230] Catalyst Co@CN recovery method: filter the reaction liquid to separate the Co@CN catalyst, soak the Co@CN catalyst three times with appropriate amounts of acetone and methanol respectively, filter, and then place it in a vacuum drying oven at 60°C for 8 hours before applying it.

[0231] Compared to Example 32, the difference was that the 1Co@CN catalyst used was a recycled catalyst. All other aspects were identical to Example 32, with a reaction conversion of 99.0%, a vitamin K3 yield of 97.2%, and a purity of 99.1%. The yield did not decrease significantly, demonstrating the good stability of the 1Co@CN catalyst. Furthermore, we repeated the experiment a third time, achieving a reaction conversion of 98.4%, a vitamin K3 yield of 96.3%, and a purity of 98.1%. The slight decrease in conversion and yield was likely due to the reduction in catalyst mass caused by filtration and washing during the recovery process.

[0232] Comparative Example 10

[0233] Compared with Example 32, Comparative Example 10 differs in that, in step (2), the copper chelate ionic liquid Chelate-Cu-IL is replaced by "Chelate-Cu-MeOH", and the rest is exactly the same as Example 32. The reaction conversion rate is 63.5%, the yield of 2-methyl-1,4-tetrahydronaphthoquinone is 55.7%, and the purity is 82%.

[0234]

[0235] Comparative Example 11

[0236] Compared with Example 32, Comparative Example 11 differs in that, in step (2), the copper chelating ionic liquid Chelate-Cu-IL is not added, and the rest is exactly the same as Example 32. The reaction conversion rate is 36.9%, the yield of o-methylbenzoquinone is 30.1%, and the purity is 76%.

[0237] Comparative Example 12

[0238] Comparative Example 12 differs from Example 32 in that cobalt nitrate (with six crystal waters, i.e., zinc nitrate hexahydrate) is used instead of cobalt acetate in the preparation of 1Co@CN in step (3), and the amount of cobalt nitrate added is 1 mmol. All other aspects are identical to those of Example 32. The reaction conversion rate is 62.1%, the vitamin K3 yield is 54.1%, and the purity is 83.6%. This indicates that different cobalt salts have a significant effect on catalytic performance.

[0239] Comparative Example 13

[0240] Comparative Example 13 differs from Example 32 in that the catalyst in step (3) is Co3O4. The remaining steps are identical to those in Example 32, resulting in a reaction conversion of 0% and a vitamin K3 yield of 0%. This comparative example demonstrates that Co@CN plays a key role in substrate activation and cannot be replaced by Co3O4.

[0241] Comparative Example 14

[0242] Comparative Example 14 differs from Example 32 in that the catalyst in step (3) is Co2O3. The remaining steps are identical to those in Example 32, resulting in a reaction conversion of 0% and a vitamin K3 yield of 0%. This comparative example further demonstrates that Co@CN plays a key role in substrate activation and cannot be replaced by common cobalt oxides.

[0243] Comparative Example 15

[0244] Comparative Example 15 is different from Example 32 in that in step (3), 1Co@CN is replaced by a cobalt-supported activated carbon catalyst Co / AC, and the rest is identical to Example 32.

[0245] The cobalt-supported activated carbon catalyst, Co / AC, was prepared by the following method: 2.11 g of cobalt acetate tetrahydrate was weighed and dissolved in appropriate amounts of ethanol and water. Then, 10 g of activated carbon was added, mixed thoroughly, and allowed to stand for 8 hours. The solvent was then evaporated in an 80°C water bath using a glass rod for stirring. The mixture was then dried overnight in a drying oven at 100°C. The mixture was removed, ground in a mortar, and calcined in a tube furnace at 550°C for 3 hours (heating rate 5°C / min) under a nitrogen atmosphere. The mixture was then cooled to room temperature under a nitrogen atmosphere to yield the Co / AC catalyst.

[0246] Comparison of XRD patterns of Co / AC and 1Co@CN catalysts ( Figure 7 ), although the cobalt contents of the two are similar (the cobalt content is determined by ICP detection), we can find that the XRD diffraction peak of the supported Co / AC catalyst is sharper, indicating that the cobalt particles are larger, which may be due to metal agglomeration, while the XRD diffraction peak intensity of 1Co@CN is weaker, indicating that the metal is better dispersed.

[0247] The reaction conversion rate was 2%, and the vitamin K3 yield was 1.3%. By comparison, it can be seen that the performance of the 1Co@CN catalyst prepared by the method of the present invention is significantly better than that of the supported catalyst Co / AC.

[0248] Comparative Example 16

[0249] Compared with Example 32, this example differs in that the amount of cobalt acetate added during the catalyst preparation process is 9 mmol, and the rest is exactly the same as Example 32. The reaction conversion rate is 85.8%, the vitamin K3 yield is 90.7%, and the purity is 97.4%.

[0250] The above embodiments are intended only to illustrate the technical concepts and features of the present invention. Their purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made in accordance with the spirit of the present invention are intended to be covered by the scope of protection of the present invention.

[0251] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

Claims

1. A method for preparing a benzoquinone compound, characterized in that: The preparation method comprises: The phenol compound represented by formula (a) is oxidized in the first catalytic system in the presence of a first oxidant to generate a benzoquinone compound represented by formula (b), and the reaction formula is: Among them, R 1 , R 2 , R 3 , R 4 are independently selected from H, C 1-10 Alkyl; or, R 1 , R 2 C 1-10 Alkylene, and R 1 , benzene ring and R 1 The carbon atom connected, R 2 , benzene ring and R 2 The connected carbon atoms together form an unsaturated 4-8 membered ring, R 3 , R 4 are independently selected from H, C 1-10 alkyl; The first oxidant is oxygen; The first catalytic system comprises 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), nitrite, protonic acid and a first solvent, wherein the protonic acid is a combination of one or more selected from trifluoromethanesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, alcoholic hydrochloric acid solution and sulfuric acid, and the first solvent is a combination of one or more selected from methanol, ethanol, propanol, tert-butanol and acetonitrile; R is -H, -OH, -NHAc, -COOH, -COOPh or 2. The method for preparing benzoquinone compounds according to claim 1, characterized in that: During the oxidation reaction, the first oxidant is provided by introducing pure oxygen gas or a gas mixture containing oxygen into the reaction system.

3. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The molar ratio of the phenolic compound represented by formula (a), the 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), the nitrite and the protonic acid is 10-200:1:1-4:1-4.

4. The method for preparing benzoquinone compounds according to claim 3, characterized in that: The molar ratio of the phenolic compound represented by formula (a), the 4-R-2,2,6,6-tetramethylpiperidinoxide represented by formula (i), the nitrite and the protonic acid is 10-50:1:1.5-2.5:1.5-2.

5.

5. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The molar ratio of the total amount of 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by the formula (i), the nitrite and the protonic acid to the phenolic compound represented by the formula (a) is 0.01-1:

1.

6. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The first solvent is at least one of methanol, tert-butanol and acetonitrile, the nitrite is potassium nitrite and / or sodium nitrite, and the protonic acid is trifluoromethanesulfonic acid and / or methanesulfonic acid.

7. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The reaction temperature of the oxidation reaction is 20-80°C.

8. The method for preparing benzoquinone compounds according to claim 7, characterized in that: The reaction temperature of the oxidation reaction is 30-50°C.

9. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The reaction pressure of the oxidation reaction is 0.1-20 MPa.

10. The method for preparing benzoquinone compounds according to claim 9, characterized in that: The reaction pressure of the oxidation reaction is 0.2-15 MPa.

11. The method for preparing benzoquinone compounds according to claim 1, characterized in that: R 1 , R 2 , R 3 , R 4 are independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl or hexyl; or, R 1 , R 2 C 1-10 Alkylene, and R 1 , benzene ring and R 1 The carbon atom connected, R 2 , benzene ring and R 2 The connected carbon atoms together form an unsaturated 6-membered ring, R 3 , R 4 Each is independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl or hexyl.

12. The method for preparing benzoquinone compounds according to claim 1 or 11, characterized in that: The phenolic compound represented by formula (a) is a combination of one or more selected from o-cresol, m-cresol, 2,6-dimethylphenol, 2,3,6-trimethylphenol, 2,5-dimethylphenol, 2-methyl-5-isopropylphenol, 2-isopropyl-5-methylphenol, 2-ethylphenol, 2-isopropylphenol, 2-tert-butylphenol and 2-methylnaphthol.

13. The method for preparing benzoquinone compounds according to claim 1, characterized in that: The implementation method for preparing benzoquinone compounds includes: adding a phenolic compound represented by formula (a), 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by formula (i), nitrite, protonic acid and a first solvent into a reactor, introducing oxygen, and reacting under stirring conditions.

14. A method for preparing 2-methyl-1,4-naphthoquinone, the method adopts the following synthetic route: The method comprises the following steps: (1) using a phenolic compound represented by formula (a) as a substrate to prepare a benzoquinone compound represented by formula (b), wherein the phenolic compound represented by formula (a) is o-cresol and / or m-cresol, and the benzoquinone compound represented by formula (b) is o-methylbenzoquinone; (2) using o-methylbenzoquinone and 1,3-butadiene as substrates to prepare 2-methyl-1,4-tetrahydronaphthoquinone; (3) using 2-methyl-1,4-tetrahydronaphthoquinone as a substrate to prepare 2-methyl-1,4-naphthoquinone; characterized in that: Step (1) is carried out using the preparation method described in any one of claims 1 to 13.

Images