Selective oxidation method for phenolic compound

Abstract

Disclosed is a selective oxidation method for a phenolic compound. The method causes the phenolic compound undergo an oxidation reaction in a catalytic system in the presence of an oxidant, and by means of controlling reaction conditions, quinone and / or aromatic aldehyde compounds are generated. The oxidant is oxygen, and the catalytic system comprises a 4-R-2,2,6,6-tetramethylpiperidine oxide as shown in formula (i), a nitrite, a proton acid, and a solvent, the solvent being a combination of water and a polar solvent miscible with water; in formula (i), R is a hydrogen atom, hydroxyl, amide, carboxyl, ester, or maleimide group. The present method can obtain a target product with a high yield, can use oxygen as an oxidant, is low-cost and environmentally friendly, does not require a transition metal catalyst, and avoids the use of halide ions and transition metals.

Description

Selective oxidation method of phenolic compounds TECHNICAL FIELD

[0001] The present application relates to the technical field of fine chemical synthesis, and particularly relates to a selective oxidation method of phenolic compounds, and a high-efficiency preparation method of quinone compounds or / and aromatic aldehyde compounds. BACKGROUND

[0002] Lignin is the most abundant aromatic compound resource in nature, and obtaining small-molecule aromatic aldehyde compounds or quinone compounds through controllable oxidative depolymerization is an important way to realize high-value utilization of lignin (Nat. Chem. 2021, 13, 1118-1125). Aromatic aldehyde is an important edible and daily chemical perfume, pharmaceutical intermediate and bulk chemical, which is currently mainly produced through a petroleum chemical industry chain (New Sci. 1987, 116, 39-42); quinone compounds are also a class of compounds widely distributed in nature. They widely exist in various plant, animal or microbial metabolites. Quinone compounds have potential antioxidant, anti-inflammatory, antibacterial and anticancer pharmacological activities, and their redox activity has important biological significance in photosynthesis and respiration. In addition, quinones are often used as precursors or basic building blocks for constructing complex drug molecules due to their electronic and chemical properties, and also have a wide range of applications in photoelectrochemistry and fuel cells. Therefore, it is of important research significance and application potential to produce aromatic aldehyde compounds and quinone compounds from lignin as raw materials (J. Am. Coll. Nutr. 2001, 20, 591-598). It is worth mentioning that the present method can be applied to generate vanillin from guaiacol. Vanillin, commonly known as vanilla aldehyde or vanillin, is chemically named 4-hydroxy-3-methoxybenzaldehyde, and is originally derived from the natural product component of Mexican vanilla, and is widely used as a fragrance and flavoring agent in food and cosmetics. It is one of the largest synthetic flavor varieties in the world. At the same time, vanillin is also an important chemical synthesis intermediate, and has a wide range of applications in the fields of drug synthesis and electroplating.

[0003] Lignin is an aromatic polymer, which is formed by cross-linking polymerization of three phenylpropane units, namely p-hydroxyphenyl (H-), guaiacyl (G-), and syringyl (S-), corresponding to the precursors p-coumaric acid, coniferyl alcohol and sinapyl alcohol. At present, hydrogen peroxide, oxygen, air, nitrobenzene and other oxidants are often used in the existing public technology to oxidize and crack lignin into aromatic aldehyde compounds under the catalysis of transition metal / gold. Vanillin is often synthesized by using guaiacol as raw material. The mainstream method is to react glyoxylic acid and guaiacol (J. Chem. Technol. Biotechnol. 1986, 36, 38-46) to obtain 3-methoxy-4-hydroxyphenyl glycolic acid in an alkaline environment, and then to obtain vanillin by passing air into the reaction system with copper hydroxide as catalyst. This process is relatively mature and has been industrialized, but the process is complex, the route is long, and the conversion rate of raw materials in the condensation reaction process is low. So far, there is no method for efficiently synthesizing vanillin from guaiacol in one step under the catalysis of transition metal and non-strong base oxidation environment (Chinese patent CN115925524A (202110919954.2); Chinese patent CN115138374A (202210544126.X); Chinese patent CN114988990A (202210680455.7)). As for the preparation of benzoquinone compounds, phenol and hydroquinone compounds are often used as substrates to synthesize quinone compounds in the presence of metal catalysts using oxygen or hydrogen peroxide. However, the above methods cannot avoid the use of noble metals / transition metals, resulting in increased synthesis cost, increased purification difficulty, and unavoidable environmental pollution problems. SUMMARY

[0004] The purpose of the present application is to overcome one or more deficiencies of the prior art, and to provide an efficient preparation method of quinone compounds or / and aromatic aldehyde compounds using lignin monomers as substrates. The method can efficiently convert the substrates into quinones or / and aldehydes by adjusting the reaction conditions. The present application uses oxygen as an oxidant and does not require transition metal / gold catalyst, which is low in cost, green and environmentally friendly, and can obtain the target product with high yield.

[0005] To achieve the above purpose, the present application studies and invents a selective regulation oxidation method of phenol compounds, which comprises:

[0006] In the presence of a catalyst and oxygen, the phenol compound is subjected to an oxidation reaction in a protic acid and a solvent to selectively generate a quinone compound or / and an aromatic aldehyde compound, and the reaction formula is as follows:

[0007] In the above formula, R' is a C1-C6 alkyl group or a C1-C6 alkoxy group, and R' can represent a plurality of substituents on a benzene ring;

[0008] R1 is a C1-C6 hydrocarbon group or a hydroxy-substituted C1-C6 hydrocarbon group;

[0009] R2 is H, a C1-C5 hydrocarbon group or a hydroxy-substituted C1-C5 hydrocarbon group;

[0010] The catalyst consists of 4-R-2,2,6,6-tetramethylpiperidine oxide represented by formula (i) and a nitrite salt:

[0011] (i), R is -H, -OH, C 1-4 an alkylamide (e.g., -NHAc), -COOH, -COOPh, or

[0012] The solvent is a combination of water and a polar solvent that is miscible with water.

[0013] In the above oxidation reaction, in order to obtain an aromatic aldehyde compound product, there need to be two Hs on the C to which R1 is attached to the benzene ring. Otherwise, the oxidation reaction can only generate a quinone compound, in which case the structure of R1 is R2CH2-. In R2, the hydrocarbon group mentioned can be an alkyl group or an alkenyl group. C1-C5 hydrocarbon groups include C1-C5 alkyl groups or C2-C5 alkenyl groups.

[0014] As a preference, the phenol compound is 2,4,6-trimethylphenol, 2,6-di-tert-butyl-p-cresol, 2,6-di-tert-butyl-4-ethylphenol, 4-sec-butyl-2,6-di-tert-butylphenol, 2,4,6-tri-tert-butylphenol, 4-methylguaiacol, 2,6-dimethoxy-4-methylphenol, 2,6-dimethoxy-4-ethylphenol, 4-hydroxy-3,5-dimethoxyphenol, 4-hydroxymethyl-3,5-dimethoxyphenol, or mustard alcohol.

[0015] As a preference, the protic acid is one or more of trifluoromethanesulfonic acid, methylsulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, benzoic acid, or acetic acid.

[0016] As a preference, the oxygen gas is pure oxygen gas or a gas mixture containing oxygen.

[0017] According to some preferred embodiments of the present application, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) is 5-200:1. Further, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) is 10-100:1. Further, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) is 20-40:1.

[0018] According to some preferred embodiments of the present application, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) to the nitrite salt is 1:0.5-4. Further, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) to the nitrite salt is 1:1-2.

[0019] According to some preferred embodiments of the present application, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinoxide shown as (i) to the protonic acid is 1:0.5-4.

[0020] As preferred, the polar solvent is one or more of C1-C4 alkyl alcohol or acetonitrile. As further preferred, the polar solvent is selected from one or more of methanol, ethanol, propanol, tert-butanol and acetonitrile.

[0021] As preferred, the solvent is a binary mixed solvent of acetonitrile / water, methanol / water, ethanol / water, tert-butanol / water, propanol / water, with a mass ratio of 1-10:1. Further, the solvent is a binary mixed solvent of acetonitrile / water, methanol / water, tert-butanol / water, with a mass ratio of 1-4:1.

[0022] As preferred, the mass ratio of the phenolic compound to the binary mixed solvent is 1:10-200.

[0023] As preferred, the reaction temperature of the oxidation reaction is 20-80℃, preferably 30-50℃.

[0024] The reaction pressure of the oxidation reaction is 0.1-20MPa, preferably 0.1-10Mpa.

[0025] In the present application, the solvent system and the type of the protonic acid play a key role in the regulation of the selectivity. Generally, under the synergistic effect of the nitrite salt and the protonic acid, when the protonic acid is a strong acid, the main product of the oxidation reaction is a benzoquinone compound, and when the protonic acid is a weak acid, the main product of the oxidation reaction is an aromatic aldehyde compound.

[0026] As a preference, when the protic acid is methylsulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid or nitric acid, and the solvent is acetonitrile / water, the main product of the oxidation reaction is a quinone compound;

[0027] When the protic acid is benzoic acid or acetic acid, and the solvent is acetonitrile / water, the main product of the oxidation reaction is an aromatic aldehyde compound; or,

[0028] When the protic acid is benzoic acid or acetic acid, and the solvent is acetonitrile / water, the main product of the oxidation reaction is an aromatic aldehyde compound; or,

[0029] As a preference, the nitrite salt is sodium nitrite or potassium nitrite.

[0030] In some preferred embodiments of the present application, the oxidation reaction is carried out under stirring, and the stirring speed is not particularly limited, as long as the reaction materials can be mixed sufficiently.

[0031] Compared with the prior art, the present application has the following advantages:

[0032] (1) Through a large number of experimental researches, it is found that the substrate can be converted into a corresponding quinone or / and aldehyde by changing the solvent and protic acid in the reaction system. It is found that, under the synergistic action of a nitrite salt and methylsulfonic acid, in a specific mixed solvent such as acetonitrile / water, using an organic catalyst 4-R-2,2,6,6-tetramethylpiperidine oxide (4-R-TEMPO), the oxygen oxidation of a phenol compound to a benzoquinone compound is realized. Under the synergistic action of a nitrite salt and methylsulfonic acid, in a specific mixed solvent such as acetonitrile / water, using an organic catalyst 4-R-2,2,6,6-tetramethylpiperidine oxide (4-R-TEMPO), the oxygen oxidation of a phenol compound to an aromatic aldehyde compound is realized. In the mixed solvent of acetonitrile / water, with the change of the acidity of the protic acid in the system from strong to weak, the main product is gradually changed from the corresponding quinone to the corresponding aldehyde. Under the synergistic action of a nitrite salt and benzoic acid / acetic acid, in a specific mixed solvent such as acetonitrile / water, using an organic catalyst 4-R-2,2,6,6-tetramethylpiperidine oxide (4-R-TEMPO), the oxygen oxidation of a phenol compound to an aromatic aldehyde compound is realized.

[0033] (2) The substrate involved in the present application, compared with the traditional phenol oxidation, due to the involvement of demethylation, the oxidation difficulty is greatly improved, and the traditional method cannot avoid the application of strong oxidizing agent / metal catalyst. The present application greatly improves the selectivity by adding water, realizes the mild demethylation under the condition of no transition metal. At the same time, the oxidation method proposed in the present application is not only low in cost, green and environmental protection, simple in operation, and the present application does not need to use transition metal catalyst, and can avoid the use of halogen ions and transition metals, which is conducive to improving the quality of quinone compounds and aromatic aldehyde compounds in industrial production. DETAILED DESCRIPTION

[0034] The above scheme will be further described in combination with specific examples; it should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present application, and the present application is not limited in scope by the following examples; the implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0035] In the following examples, all raw materials are from commercial sources or prepared by conventional methods in the art, unless otherwise specified.

[0036] In the following, unless otherwise specified, all reaction conversion rates and yields are determined by gas chromatography (using commercially available raw materials and products to determine standard curves).

[0037] In the following, 4-OH-2,2,6,6-tetramethylpiperidinoxide: 4-COOH-2,2,6,6-tetramethylpiperidinoxide: 4-NHAc-2,2,6,6-tetramethylpiperidinoxide: 2,2,6,6-tetramethylpiperidinoxide: 4-Maleimide(4-maleimide)-2,2,6,6-tetramethylpiperidinoxide:

[0038] Example 1

[0039] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which adopts the following synthesis route:

[0040] The method comprises: adding 1 mmol 2,4,6-trimethylphenol, 0.1 mmol 4-OH-TEMPO, 0.2 mmol sodium nitrite, 0.3 mmol methyl sulfonic acid, 0.4 g H2O and 1.6 g acetonitrile in a 20 mL reaction bottle, adding a magnetic stirrer, vacuumizing and then introducing oxygen, the pressure is 0.2 MPa, reacting for 24 hours at 40 DEG C under stirring at 800 rpm, the reaction conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 83.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%; after the solvent is removed from the reaction solution, the reaction solution is dissolved in 10 mL ethyl acetate, washed twice with 2 mL sodium hydroxide aqueous solution, washed three times with 5 mL saturated brine, the organic phase is dried with anhydrous sodium sulfate and then rotary evaporated to obtain 0.11 g of purified 2,6-dimethylbenzoquinone, the separation yield is 80.8%, and the purity is 99%.

[0041] Example 2

[0042] The example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, and the method adopts the following synthesis route:

[0043] The method comprises: adding 1 mmol 2,4,6-trimethylphenol, 0.1 mmol 4-OH-TEMPO, 0.2 mmol sodium nitrite, 0.3 mmol methyl sulfonic acid, 0.4 g H2O and 1.6 g acetonitrile in a 20 mL reaction bottle, adding a magnetic stirrer, vacuumizing and then introducing oxygen, the pressure is 0.2 MPa, reacting for 24 hours at 40 DEG C under stirring at 800 rpm, the reaction conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 83.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%; after the solvent is removed from the reaction solution, the reaction solution is dissolved in 10 mL ethyl acetate, washed twice with 2 mL sodium hydroxide aqueous solution, washed three times with 5 mL saturated brine, the organic phase is dried with anhydrous sodium sulfate and then rotary evaporated to obtain 0.11 g of purified 2,6-dimethylbenzoquinone, the separation yield is 80.8%, and the purity is 99%.

[0044] Example 3

[0045] The example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, and the method adopts the following synthesis route:

[0046] The method comprises: adding 1 mmol 2,4,6-trimethylphenol, 0.1 mmol 4-OH-TEMPO, 0.2 mmol sodium nitrite, 0.3 mmol benzoic acid, 0.4 g H2O and 1.6 g acetonitrile in a 20 mL reaction bottle, adding a magnetic stirrer, vacuumizing and then introducing oxygen, the pressure is 0.2 MPa, reacting for 48 hours at 40 DEG C under stirring at 800 rpm, the conversion rate is 100%, the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 94.3%, and the yield of 2,6-dimethylbenzoquinone is only 1%; after the solvent of the reaction solution is removed, the reaction solution is dissolved in 10 mL ethyl acetate, washed twice with 2 mL sodium hydroxide aqueous solution, washed three times with 5 mL saturated brine, the organic phase is dried with anhydrous sodium sulfate and then rotary evaporated to obtain 0.14 g of purified 3,5-dimethyl-4-hydroxybenzaldehyde, the separation yield is 93.2%, and the purity is 99%.

[0047] Example 4

[0048] The example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, which is different from example 2 in that 1.6 g of methanol is adjusted to 1.6 g of tert-butyl alcohol, and the rest is completely same as example 2, the conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 92.5%.

[0049] Example 5

[0050] The example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, which is different from example 2 in that 1.6 g of methanol is adjusted to 1.6 g of ethanol, and the rest is completely same as example 2, the conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 87.2%.

[0051] Example 6

[0052] The example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, which is different from example 2 in that 1.6 g of methanol is adjusted to 1.6 g of propyl alcohol, and the rest is completely same as example 2, the conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 85.4%.

[0053] Example 7

[0054] This example provides a method for efficient preparation of 2,6-di-tert-butyl-p-benzoquinone and 3,5-di-tert-butyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,6-di-tert-butyl-p-cresol. Compared with Example 1, the difference is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-p-cresol, and the rest is exactly the same as Example 1. The reaction conversion rate is 92%, the yield of 2,6-di-tert-butyl-p-benzoquinone is 51.3%, and the yield of 3,5-di-tert-butyl-4-hydroxybenzaldehyde is 23.4%.

[0055] Example 8

[0056] This example provides a method for efficient preparation of 2,6-di-tert-butyl-p-benzoquinone and 3,5-di-tert-butyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,6-di-tert-butyl-p-cresol. Compared with Example 3, the difference is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-p-cresol, and the rest is exactly the same as Example 3. The reaction conversion rate is 89%, the yield of 2,6-di-tert-butyl-p-benzoquinone is 24.3%, and the yield of 3,5-di-tert-butyl-4-hydroxybenzaldehyde is 61.4%.

[0057] Example 9

[0058] This example provides a method for efficient preparation of 2,6-di-tert-butyl-p-benzoquinone and 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone by oxygen oxidation of 2,6-di-tert-butyl-4-ethylphenol. Compared with Example 1, the difference is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-4-ethylphenol, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, the yield of 2,6-di-tert-butyl-p-benzoquinone is 46.3%, and the yield of 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone is 19.8%.

[0059] Example 10

[0060] This example provides a method for efficient preparation of 2,6-di-tert-butyl-p-benzoquinone and 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone by oxygen oxidation of 2,6-di-tert-butyl-4-ethylphenol. Compared with Example 3, the difference is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-4-ethylphenol, and the rest is exactly the same as Example 3. The reaction conversion rate is 100%, the yield of 2,6-di-tert-butyl-p-benzoquinone is 16.9%, and the yield of 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone is 64.8%.

[0061] Example 11

[0062] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone by oxygen oxidation of 4-sec-butyl-2,6-di-tert-butylphenol. The difference between this example and Example 1 is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 4-sec-butyl-2,6-di-tert-butylphenol, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-di-tert-butyl-p-benzoquinone is 61.4%.

[0063] Example 12

[0064] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone by oxygen oxidation of 2,4,6-tri-tert-butylphenol. The difference between this example and Example 1 is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,4,6-tri-tert-butylphenol, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-di-tert-butyl-p-benzoquinone is 82.6%.

[0065] Example 13

[0066] This example provides a method for preparing 2,6-dimethoxy-p-benzoquinone by oxygen oxidation of 2,6-dimethoxy-4-ethylphenol. The difference between this example and Example 1 is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-dimethoxy-4-ethylphenol, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-dimethoxy-p-benzoquinone is 42.3%.

[0067] Example 14

[0068] This example provides a method for preparing 2,6-dimethoxy-p-benzoquinone by oxygen oxidation of 4-hydroxy-3,5-dimethoxyphenol. The difference between this example and Example 1 is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 4-hydroxy-3,5-dimethoxyphenol, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-dimethoxy-p-benzoquinone is 98.5%.

[0069] Example 15

[0070] This example provides a method for preparing 3,5-dimethoxy-4-hydroxybenzaldehyde by oxygen oxidation of 4-hydroxymethyl-3,5-dimethoxyphenol. The difference between this example and Example 3 is that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 4-hydroxymethyl-3,5-dimethoxyphenol, and the rest is exactly the same as Example 3. The reaction conversion rate is 100%, and the yield of 3,5-dimethoxy-4-hydroxybenzaldehyde is 70.5%. The yield of 2,6-dimethoxy-p-benzoquinone is only 10.5%.

[0071] Example 16

[0072] This example provides a method for the preparation of 2,6-dimethoxy-p-benzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of erucin, and the rest is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-dimethoxy-p-benzoquinone is 68.3%.

[0073] Example 17

[0074] This example provides a method for the efficient preparation of 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 3 in that 0.3 mmol of benzoic acid is adjusted to 0.3 mmol of acetic acid, and the reaction time is extended from 48 hours to 60 hours, and the rest is exactly the same as Example 1. The conversion rate is 100%, the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 95.4%, and no 2,6-dimethylbenzoquinone is observed.

[0075] Example 18

[0076] This example provides a method for the efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.1 mmol of 4-NHAc-2,2,6,6-tetramethylpiperidinoxide, and the rest is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 79.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%.

[0077] Example 19

[0078] This example provides a method for the efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.1 mmol of 4-COOH-2,2,6,6-tetramethylpiperidinoxide, and the rest is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 76.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 6.8%.

[0079] Example 20

[0080] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.1 mmol of 4-maleimide(2,2,6,6-tetramethylpiperidinooxy), and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 77.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 8.4%.

[0081] Example 21 This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.1 mmol of 2,2,6,6-tetramethylpiperidinooxy, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 81.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 3.9%.

[0082] Example 22

[0083] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.05 mmol 4-OH-TEMPO, 0.3 mmol of methyl sulfonic acid is adjusted to 0.15 mmol of methyl sulfonic acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 77.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 6.7%.

[0084] Example 23

[0085] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.075 mmol 4-OH-TEMPO, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 89.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 9.4%.

[0086] Example 24

[0087] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.2 mmol of sodium nitrite is adjusted to 0.1 mmol of sodium nitrite, and the rest is exactly the same as Example 1, the conversion rate is 89%, the yield of 2,6-dimethylbenzoquinone is 77.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 4.8%.

[0088] Example 25

[0089] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.3 mmol of methyl sulfonic acid is adjusted to 0.4 mmol of methyl sulfonic acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 91.6%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 1.2%.

[0090] Example 26

[0091] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.3 mmol of methyl sulfonic acid is adjusted to 0.05 mmol of methyl sulfonic acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 54.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 37.3%.

[0092] Example 27

[0093] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.3 mmol of methyl sulfonic acid is adjusted to 0.3 mmol of triflic acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 80.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.3%.

[0094] Example 28

[0095] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.3 mmol of methyl sulfonic acid is adjusted to 0.3 mmol of p-toluenesulfonic acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 85.1%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 12.3%.

[0096] Example 29

[0097] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.3 mmol of methanesulfonic acid is adjusted to 0.3 mmol of nitric acid, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 80.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 11.2%.

[0098] Example 30

[0099] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.4 g of H2O is adjusted to 0.2 g of H2O, and 1.6 g of acetonitrile is adjusted to 1.8 g of acetonitrile, and the rest is exactly the same as Example 1, the conversion rate is 87%, the yield of 2,6-dimethylbenzoquinone is 62.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 32.6%.

[0100] Example 31

[0101] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.4 g of H2O is adjusted to 0.6 g of H2O, and 1.6 g of acetonitrile is adjusted to 1.4 g of acetonitrile, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 87.2%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 13.2%.

[0102] Example 32

[0103] This example provides a method for efficient preparation of 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol, which is different from Example 1 in that 0.4 g of H2O is adjusted to 1.0 g of H2O, and 1.6 g of acetonitrile is adjusted to 1.0 g of acetonitrile, and the rest is exactly the same as Example 1, the conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 90.5%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 8.7%.

[0104] Example 33

[0105] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol. Compared with Example 1, the difference is that the reaction temperature is 20°C and the pressure is 20 MPa, and the rest is the same as Example 1. The conversion rate is 94.2%, the yield of 2,6-dimethylbenzoquinone is 84.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%.

[0106] Example 34

[0107] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol. Compared with Example 1, the difference is that the reaction temperature is 20°C and the pressure is 20 MPa, and the rest is the same as Example 1. The conversion rate is 94.2%, the yield of 2,6-dimethylbenzoquinone is 84.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%.

[0108] Example 35

[0109] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxygen oxidation of 2,4,6-trimethylphenol. Compared with Example 1, the difference is that the reaction temperature is 20°C and the pressure is 20 MPa, and the rest is the same as Example 1. The conversion rate is 94.2%, the yield of 2,6-dimethylbenzoquinone is 84.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%.

[0110] Comparative Example 1

[0111] This example is compared with Example 1, the difference is that the mixed solvent of acetonitrile and water used in the reaction is replaced by pure acetonitrile, and the rest is the same as Example 1. The conversion rate is 77%, the yield of 2,6-dimethylbenzoquinone is 6.2%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 1.2%.

[0112] Comparative Example 1 illustrates that the addition of water in the present application plays a decisive role in improving the selectivity of oxygen oxidation of 2,4,6-trimethylphenol.

[0113] Comparative Example 2

[0114] This example is compared with Example 1, the difference is that 0.4 g of H2O and 1.6 g of acetonitrile used in the reaction are replaced by 0.4 g of H2O and 1.6 g of perfluoro-tert-butanol, and the rest is the same as Example 1. The conversion rate is 99%, the yield of 2,6-dimethylbenzoquinone is 5.1%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 9.1%.

[0115] Comparative Example 3

[0116] The difference between this example and Example 1 is that 0.4 g of H2O and 1.6 g of acetonitrile used in the reaction are replaced by 2.0 g of hexafluoroisopropanol, and the rest is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 4.6%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 0.6%.

[0117] Comparative Example 4

[0118] The difference between this example and Example 1 is that 0.4 g of H2O and 1.6 g of acetonitrile used in the reaction are replaced by 2.0 g of acetic acid, and the rest is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 3.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 47%.

[0119] Comparative Examples 2-4 show that the specific solvent system of the present application plays a decisive role in the yield of oxygen oxidation of 2,4,6-trimethylphenol.

[0120] Comparative Example 5

[0121] The difference between this example and Example 1 is that no methyl sulfonic acid is added during the reaction, and the rest is exactly the same as Example 1. The substrate is not converted.

[0122] Comparative Example 6

[0123] The difference between this example and Example 1 is that 0.3 mmol of methyl sulfonic acid is adjusted to 0.3 mmol of cesium carbonate, and the rest is exactly the same as Example 1. The substrate is not converted.

[0124] Comparative Examples 5 and 6 show that the protonic acid is the key to the catalysis of the TEMPO catalyst, and the selectivity can be controlled by adjusting the strength and amount of the acid. In the absence of acid or the use of base to disperse TEMPO, the reaction cannot occur.

[0125] Comparative Example 7

[0126] The difference between this example and Example 1 is that no TEMPO catalyst is added during the reaction, and the rest is exactly the same as Example 1. The substrate is not converted. This comparative example shows that the TEMPO catalyst plays a key role in activating 2,4,6-trimethylphenol and converting it to 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde.

[0127] Comparative Example 8

[0128] The example is compared with example 1, the difference is that in step (1) no NaNO2 is added, the rest is exactly the same as example 1, the reaction conversion rate is 10.5%, the yield of 2,6-dimethylbenzoquinone is 3.5%, and 3,5-dimethyl-4-hydroxybenzaldehyde is not observed. This example shows that sodium nitrite plays a role in recycling TEMPO catalyst, thereby completely converting the substrate.

[0129] Comparative example 9

[0130] The example is compared with example 1, the difference is that in step (1) no oxygen is passed, the reaction system is protected with nitrogen, the rest is exactly the same as example 1, the reaction conversion rate is 9.4%, the yield of 2,6-dimethylbenzoquinone is 3.3%, and 3,5-dimethyl-4-hydroxybenzaldehyde is not observed. This example shows that oxygen is an indispensable oxidant.

[0131] Comparative example 10

[0132] The example is compared with example 1, the difference is that 0.2 mmol of CuCl2 is used instead of 0.2 mmol of NaNO2 during the reaction, the rest is exactly the same as example 1, the reaction conversion rate is 20.5%, the yield of 2,6-dimethylbenzoquinone is 9.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 1.5%.

[0133] Comparative example 10 shows that compared with using transition metal salts as cocatalysts, the catalytic system of the present application works better.

[0134] The above examples are only for illustrating the technical concept and characteristics of the present application, the purpose is to enable those skilled in the art to understand the content of the present application and to implement it, and it cannot limit the protection scope of the present application. Any equivalent changes or modifications made in accordance with the spirit and essence of the present application should be covered within the protection scope of the present application.

[0135] The endpoints of the ranges and any values disclosed herein are not limited to the precise values stated. The ranges or values should be construed to be roughly around the ranges or values. For ranges of values, the endpoints of the ranges are combined with the individual points to form new ranges or values that are within the scope of the present disclosure.

Claims

1. A method for selective oxidation of a phenolic compound, characterized by, In the presence of a catalyst and oxygen, a phenolic compound is oxidized in a protic acid and a solvent to selectively generate a quinone compound or / and an aromatic aldehyde compound, and the reaction formula is: In the above formula, R' is C1-C6 alkyl or C1-C6 alkoxy, and R' can represent multiple substituents on a benzene ring; R1 is C1-C6 alkyl or hydroxyl-substituted C1-C6 alkyl; R2 is H, C1-C5 alkyl or hydroxyl-substituted C1-C5 alkyl; The catalyst is composed of 4-R-2,2,6,6-tetramethylpiperidine oxide represented by formula (I) and nitrite: The solvent is a combination of water and a polar solvent that is miscible with water. R is -H, -OH, C 1-4 alkanoylamido, -COOH, -COOPh or The phenolic compound is 2,4,6-trimethylphenol, 2,6-di-tert-butyl-p-cresol, 2,6-di-tert-butyl-4-ethylphenol, 4-sec-butyl-2,6-di-tert-butylphenol, 2,4,6-tri-tert-butylphenol, 4-methylguaiacol, 2,6-dimethoxy-4-methylphenol, 2,6-dimethoxy-4-ethylphenol, 4-hydroxy-3,5-dimethoxyphenol, 4-hydroxymethyl-3,5-dimethoxyphenol, or mustard alcohol.

2. The method of selective oxidation of phenolic compounds according to claim 1, wherein, The protic acid is one or more of trifluoromethanesulfonic acid, methylsulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, benzoic acid, or acetic acid.

3. The method of selective oxidation of phenolic compounds according to claim 1, wherein, The polar solvent is selected from one or more of methanol, ethanol, propanol, tert-butanol, and acetonitrile.

4. The method of selective oxidation of phenolic compounds according to claim 1, wherein, The oxygen is pure oxygen gas or a gas mixture containing oxygen.

5. The method of selective oxidation of phenolic compounds according to claim 1, wherein: The molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidine oxide represented by formula (I) is 5-200:1; 6. The method of selective oxidation of phenolic compounds according to claim 1, wherein: The molar ratio of the 4-R-2,2,6,6-tetramethylpiperidine oxide represented by formula (I) to the nitrite is 1:0.5-4; The molar ratio of the 4-R-2,2,6,6-tetramethylpiperidine oxide represented by formula (I) to the protic acid is 1:0.5-4. The solvent is a binary mixed solvent of acetonitrile / water, methanol / water, ethanol / water, tert-butanol / water, or propanol / water, with a mass ratio of 1-10:

1.

7. The method of selective oxidation of phenolic compounds according to claim 1, wherein: The mass ratio of the phenolic compound to the binary mixed solvent is 1:4-100.

8. The method of selective oxidation of phenolic compounds according to claim 1 or 7, characterized in that: The reaction temperature of the oxidation reaction is 20-80°C, preferably 30-50°C; 9. The method of selective oxidation of phenolic compounds according to claim 1, wherein: The reaction pressure of the oxidation reaction is 0.1-20 MPa, preferably 0.1-10 MPa.

10. The selective oxidation method of the phenolic compound according to claim 1 or 7, characterized in that: when the protic acid is methylsulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, or nitric acid, and the solvent is acetonitrile / water, the main product of the oxidation reaction is a quinone compound; or, when the protic acid is benzoic acid or acetic acid, and the solvent is acetonitrile / water, the main product of the oxidation reaction is an aromatic aldehyde compound; or, when the nitrite and the protic acid act synergistically, and the solvent is a mixed solvent of methanol / water, ethanol / water, tert-butanol / water, or propanol / water, the main product of the oxidation reaction is an aromatic aldehyde compound. The nitrite is sodium nitrite or potassium nitrite.

11. The method of selective oxidation of phenolic compounds according to claim 1 or 7, characterized in that: ​

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