A selective oxidation method for phenolic compounds

Abstract

The present invention discloses a method for selectively oxidizing phenolic compounds. This method involves subjecting the phenolic compounds to an oxidation reaction in the presence of an oxidant in a catalytic system. By regulating the reaction conditions, benzoquinones and / or aromatic aldehydes are generated. The oxidant is oxygen. The catalytic system comprises 4-R-2,2,6,6-tetramethylpiperidinyl oxide, a nitrite, a protonic acid, and a solvent, wherein the solvent is a combination of water and a polar solvent miscible with water. In formula (i), R represents a hydrogen atom, a hydroxyl group, an amide group, a carboxyl group, an ester group, or a maleimide group. This method can produce the desired product in high yield, and oxygen can be used as the oxidant. The method is low-cost, environmentally friendly, and eliminates the need for a transition metal catalyst, thereby avoiding the use of halogen ions and transition metals. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemical synthesis, and in particular to a method for selectively oxidizing phenolic compounds and efficiently preparing quinone compounds and / or aromatic aldehyde compounds. Background Art

[0002] Lignin is the most abundant aromatic compound resource in nature. Controlled oxidative depolymerization to produce small-molecule aromatic aldehydes or benzoquinones is an important approach for achieving high-value-added utilization of lignin (Nat. Chem. 2021, 13, 1118-1125). Aromatic aldehydes, as important edible and daily fragrances, pharmaceutical intermediates, and bulk chemicals, are currently primarily produced through the petrochemical industry chain (New Sci. 1987, 116, 39–42). Benzoquinones are also a widely distributed class of compounds in nature. They are found in a wide variety of plant, animal, and microbial metabolites. Quinones possess potential pharmacological activities such as antioxidant, anti-inflammatory, antibacterial, and anticancer properties. Their redox activity is also of great biological significance in photosynthesis and respiration. Furthermore, due to their electronic and chemical properties, quinones are often used as precursors or building blocks for the construction of complex drug molecules and have extensive applications in photoelectrochemical and fuel cells. Therefore, the production of aromatic aldehydes and benzoquinones from lignin is a renewable resource with significant research significance and potential for application (J.Am.Coll.Nutr.2001,20,591–598). Notably, this method can also be applied to the production of vanillin from guaiacol. Vanillin, commonly known as vanillin or vanillic aldehyde, is chemically 4-hydroxy-3-methoxybenzaldehyde. It is a natural product originally found in the Mexican vanilla plant and is widely used as a fixative and flavoring agent in foods and cosmetics. It is one of the most produced synthetic fragrances worldwide. Vanillin is also an important chemical synthesis intermediate with extensive applications in pharmaceutical synthesis and electroplating.

[0003] Lignin is an aromatic polymer formed by the cross-linking polymerization of three phenylpropane units: p-hydroxyphenyl (H-), guaiacyl (G-), and syringyl (S-). The corresponding precursors are p-coumarol, coniferyl alcohol, and sinapyl alcohol, respectively. Currently, existing technologies often utilize oxidants such as hydrogen peroxide, oxygen, air, and nitrobenzene, catalyzed by transition metals / noble metals, to oxidatively cleave lignin into aromatic aldehydes. Guaiacol is often used as a raw material for the synthesis of vanillin. A more mainstream approach involves the reaction of glyoxylic acid with guaiacol (J. Chem. Technol. Biotechnol. 1986, 36, 38–46). The two condense in an alkaline environment to produce 3-methoxy-4-hydroxymandelic acid, which is then oxidized with copper hydroxide and air to produce the oxidative decarboxylation product, vanillin. This process is relatively mature and has been industrialized, but the process is complex and lengthy, and the conversion rate of the raw materials during the condensation reaction is low. To date, there is no method that can efficiently oxidize guaiacol to vanillin in a one-step process under transition metal catalysis and a non-strong alkaline oxidizing 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 mostly used as substrates, and quinone compounds are synthesized using oxygen or hydrogen peroxide in the presence of a metal catalyst. However, the above methods cannot avoid the use of precious metals / transition metals, which increases the cost of synthesis and the difficulty of purification, and there is also an unavoidable environmental pollution problem.

[0004] Lignin monomer:

[0005]

[0006] Aromatic units:

[0007] Summary of the Invention

[0008] The present invention aims to overcome one or more deficiencies of the prior art by providing a highly efficient method for preparing quinone compounds and / or aromatic aldehyde compounds using lignin monomer as a substrate. This method allows for efficient conversion of the substrate into quinones and / or aldehydes by regulating reaction conditions. The present invention utilizes oxygen as an oxidant and does not require transition metal or noble metal catalysis, resulting in a low-cost, environmentally friendly method and the ability to obtain the desired product in high yield.

[0009] To achieve the above-mentioned object, the present invention has studied and invented a method for selectively regulating the oxidation of phenolic compounds, which comprises:

[0010] In the presence of a catalyst and oxygen, phenol compounds undergo oxidation reaction in protonic acid and solvent to selectively generate quinone compounds and / or aromatic aldehyde compounds. The reaction formula is:

[0011]

[0012] In the above formula, R' is a C1-C6 alkyl group or a C1-C6 alkoxy group, and R' may represent multiple substituents on the benzene ring;

[0013] R1 is a C1-C6 hydrocarbon group or a C1-C6 hydrocarbon group substituted by a hydroxyl group;

[0014] R2 is H, C1-C5 hydrocarbon group or C1-C5 hydrocarbon group substituted by hydroxyl group;

[0015] The catalyst is composed of 4-R-2,2,6,6-tetramethylpiperidinyl oxide and nitrite as shown in formula (i):

[0016] R is -H, -OH, C 1-4 Alkylamide (e.g., -NHAc), -COOH, -COOPh, or

[0017] The solvent is a combination of water and a polar solvent miscible with water.

[0018] In the above oxidation reaction, in order to obtain aromatic aldehyde compound products, there must be two H on the C where R1 is connected to the benzene ring, otherwise the oxidation reaction can only produce quinone compounds. At this time, the structure of R1 is R2CH2-, and in R2, the hydrocarbon group mentioned can be an alkyl group or an alkenyl group, and the C1~C5 hydrocarbon group includes a C1~C5 alkyl group or a C2~C5 alkenyl group.

[0019] Preferably, 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 sinapyl alcohol.

[0020] Preferably, the protonic acid is one or more of trifluoromethanesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, benzoic acid or acetic acid.

[0021] Preferably, the oxygen is pure oxygen gas or a gas mixture containing oxygen.

[0022] According to some preferred embodiments of the present invention, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) is 5 to 200:1. Furthermore, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) is 10 to 100:1. Furthermore, the molar ratio of the phenolic compound to the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) is 20 to 40:1.

[0023] According to some preferred embodiments of the present invention, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) to the nitrite is 1:0.5 to 4. Furthermore, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) to the nitrite is 1:1 to 2.

[0024] According to some preferred embodiments of the present invention, the molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinyl oxide shown in (i) to the protonic acid is 1:0.5-4.

[0025] Preferably, the polar solvent is one or more of C1-C4 alkyl alcohol or acetonitrile. Further preferably, the polar solvent is one or more of methanol, ethanol, propanol, tert-butanol and acetonitrile.

[0026] Preferably, the solvent is a binary mixed solvent of acetonitrile / water, methanol / water, ethanol / water, tert-butanol / water, or propanol / water, and the mass ratio thereof is 1 to 10:1; further, the solvent is a binary mixed solvent of acetonitrile / water, methanol / water, or tert-butanol / water, and the mass ratio thereof is 1 to 4:1.

[0027] Preferably, the mass ratio of the phenol compound to the binary mixed solvent is 1:10-200.

[0028] Preferably, the reaction temperature of the oxidation reaction is 20 to 80°C, preferably 30 to 50°C;

[0029] The reaction pressure of the oxidation reaction is 0.1-20 MPa, preferably 0.1-10 MPa.

[0030] In the present invention, the solvent system and the type of protonic acid play a key role in regulating selectivity. Generally speaking, under the synergistic action of the nitrite and the protonic acid, when the solvent is an acetonitrile / water mixture, 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.

[0031] Preferably, when the protonic acid is methanesulfonic 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;

[0032] When the protonic 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

[0033] Under the action of the nitrite and the protonic acid, when 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.

[0034] Preferably, the nitrite is sodium nitrite or potassium nitrite.

[0035] In some preferred embodiments of the present invention, the oxidation reaction is carried out under stirring conditions. There is no particular strict limit on the stirring speed, as long as the reaction raw materials can be fully mixed.

[0036] Compared with the prior art, the beneficial effects of the present invention are embodied in:

[0037] (1) After extensive experimental studies, the present invention has found that the substrate can be regulated to generate the corresponding quinone or / and aldehyde by changing the solvent and proton acid in the reaction system. It was found that under the synergistic effect of nitrite and methanesulfonic acid, in a specific mixed solvent such as acetonitrile / water, the use of the organic catalyst 4-R-2,2,6,6-tetramethylpiperidinyl oxide (4-R-TEMPO) can achieve the oxygen oxidation of phenolic compounds to benzoquinone compounds. Under the synergistic effect of nitrite and methanesulfonic acid, in a specific mixed solvent such as methanol / water, ethanol / water, tert-butanol / water, and propanol / water, the use of the organic catalyst 4-R-2,2,6,6-tetramethylpiperidinyl oxide (4-R-TEMPO) can achieve the oxygen oxidation of phenolic compounds to aromatic aldehyde compounds. In the acetonitrile / water mixed solvent, as the acidity of the proton acid in the system changes from strong to weak, the main product gradually changes from the corresponding quinone to the corresponding aldehyde. Under the synergistic action of nitrite and benzoic acid / acetic acid, the oxygen oxidation of phenolic compounds to aromatic aldehydes was achieved using the organic catalyst 4-R-2,2,6,6-tetramethylpiperidinyl oxide (4-R-TEMPO) in a specific mixed solvent such as acetonitrile / water.

[0038] (2) Compared with traditional phenol oxidation, the substrate involved in the present invention is much more difficult to oxidize because it involves demethylation. Traditional methods cannot avoid the use of strong oxidants / metal catalysts. The present invention greatly improves the selectivity by adding water, and achieves mild demethylation under transition metal-free conditions. At the same time, the oxidation method proposed in the present invention is not only low-cost, environmentally friendly, and simple to operate, but also does not require the use of transition metal catalysts and can avoid the use of halide ions and transition metals, which is beneficial to improving the quality of quinone compounds and aromatic aldehyde compounds during industrial production. DETAILED DESCRIPTION

[0039] 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.

[0040] Unless otherwise specified in the following examples, all raw materials were purchased from commercial sources or prepared by conventional methods in the art.

[0041] In the following, unless otherwise specified, all reaction conversions and yields were determined by gas chromatography (using commercially available raw materials and products to determine the standard curve).

[0042] In the following, 4-OH-2,2,6,6-tetramethylpiperidinyl oxide: 4-COOH-2,2,6,6-Tetramethylpiperidinyloxide: 4-NHAc-2,2,6,6-tetramethylpiperidinyloxide: 2,2,6,6-Tetramethylpiperidinyloxide: 4-Maleimide (maleimide)-2,2,6,6-tetramethylpiperidinoxide:

[0043] Example 1

[0044] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. The method adopts the following synthetic route:

[0045]

[0046] The method comprises the following steps: adding 1 mmol of 2,4,6-trimethylphenol, 0.1 mmol of 4-OH-TEMPO, 0.2 mmol of sodium nitrite, 0.3 mmol of methanesulfonic acid, 0.4 g of H2O and 1.6 g of acetonitrile into a 20 mL reaction bottle, adding a magnetic bar, evacuating the solution and introducing oxygen at a pressure of 0.2 MPa, reacting at 40°C and stirring at 800 rpm for 24 hours, wherein 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 removing the solvent from the reaction solution, the solution is dissolved in 10 mL of ethyl acetate, washed twice with 2 mL of sodium hydroxide aqueous solution, extracted three times with 5 mL of saturated brine, and the organic phase is dried with anhydrous sodium sulfate and then spin-dried to obtain 0.11 g of purified 2,6-dimethylbenzoquinone with an isolated yield of 80.8% and a purity of 99%.

[0047] Example 2

[0048] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. The method adopts the following synthetic route:

[0049]

[0050] The method comprises the following steps: adding 1 mmol of 2,4,6-trimethylphenol, 0.1 mmol of 4-OH-TEMPO, 0.2 mmol of sodium nitrite, 0.3 mmol of methanesulfonic acid, 0.4 g of H2O and 1.6 g of methanol into a 20 mL reaction bottle, adding a magnetic bar, evacuating the solution and introducing oxygen at a pressure of 0.2 MPa, reacting at 40°C and stirring at 800 rpm for 24 hours, wherein the reaction conversion rate is 100%, the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 92.7%, and the yield of 2,6-dimethylbenzoquinone is only 2%. After removing the solvent from the reaction solution, the reaction solution is dissolved in 10 mL of ethyl acetate, washed twice with 2 mL of sodium hydroxide aqueous solution, extracted three times with 5 mL of saturated brine, and the organic phase is dried with anhydrous sodium sulfate and then spin-dried to obtain 0.13 g of purified 3,5-dimethyl-4-hydroxybenzaldehyde with an isolated yield of 86.6% and a purity of 99%.

[0051] Example 3

[0052] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. The method adopts the following synthetic route:

[0053]

[0054] The method comprises the following steps: adding 1 mmol of 2,4,6-trimethylphenol, 0.1 mmol of 4-OH-TEMPO, 0.2 mmol of sodium nitrite, 0.3 mmol of benzoic acid, 0.4 g of H2O and 1.6 g of acetonitrile into a 20 mL reaction bottle, adding a magnetic bar, evacuating the solution and introducing oxygen at a pressure of 0.2 MPa, reacting at 40°C and 800 rpm for 48 hours, wherein the reaction 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 removing the solvent from the reaction solution, the reaction solution is dissolved in 10 mL of ethyl acetate, washed twice with 2 mL of sodium hydroxide aqueous solution, extracted three times with 5 mL of saturated brine, and the organic phase is dried with anhydrous sodium sulfate and then spin-dried to obtain 0.14 g of purified 3,5-dimethyl-4-hydroxybenzaldehyde with an isolated yield of 93.2% and a purity of 99%.

[0055] Example 4

[0056] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 2, this example differs in that 1.6 g of methanol is adjusted to 1.6 g of tert-butanol. The rest is exactly the same as Example 2. The conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 92.5%.

[0057] Example 5

[0058] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 2, this example differs in that 1.6 g of methanol is adjusted to 1.6 g of ethanol. The rest of the process is exactly the same as Example 2. The conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 87.2%.

[0059] Example 6

[0060] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 2, this example differs in that 1.6 g of methanol is adjusted to 1.6 g of propanol. The rest of the reaction is exactly the same as Example 2. The conversion rate is 100%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is 85.4%.

[0061] Example 7

[0062] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone and 3,5-di-tert-butyl-4-hydroxybenzaldehyde by oxidizing 2,6-di-tert-butyl-p-cresol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-p-cresol. The rest of the process 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%.

[0063] Example 8

[0064] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone and 3,5-di-tert-butyl-4-hydroxybenzaldehyde by oxidizing 2,6-di-tert-butyl-p-cresol with oxygen. Compared with Example 3, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-p-cresol. The rest of the process 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%.

[0065] Example 9

[0066] This example provides a method for efficiently preparing 2,6-di-tert-butyl-4-ethylphenol to 2,6-di-tert-butyl-p-benzoquinone and 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone by oxidizing 2,6-di-tert-butyl-4-ethylphenol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-4-ethylphenol. The rest of the process 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%.

[0067] Example 10

[0068] This example provides a method for efficiently preparing 2,6-di-tert-butyl-4-ethylphenol to 2,6-di-tert-butyl-p-benzoquinone and 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone by oxidizing 2,6-di-tert-butyl-4-ethylphenol with oxygen. Compared with Example 3, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-di-tert-butyl-4-ethylphenol. The rest of the process 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%.

[0069] Example 11

[0070] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone by oxidizing 4-sec-butyl-2,6-di-tert-butylphenol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol 4-sec-butyl-2,6-di-tert-butylphenol. The rest of the process 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%.

[0071] Example 12

[0072] This example provides a method for efficiently preparing 2,6-di-tert-butyl-p-benzoquinone by oxidizing 2,4,6-tri-tert-butylphenol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,4,6-tri-tert-butylphenol. The rest of the process 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%.

[0073] Example 13

[0074] This example provides a method for preparing 2,6-dimethoxy-4-ethylphenol by oxidizing 2,6-dimethoxy-4-ethylphenol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 2,6-dimethoxy-4-ethylphenol. The rest of the process is exactly the same as Example 1. The reaction conversion rate is 100%, and the yield of 2,6-dimethoxy-4-benzoquinone is 42.3%.

[0075] Example 14

[0076] This example provides a method for preparing 2,6-dimethoxy-p-benzoquinone by oxidizing 4-hydroxy-3,5-dimethoxyphenol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of 4-hydroxy-3,5-dimethoxyphenol. The rest of the process 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%.

[0077] Example 15

[0078] This example provides a method for preparing 3,5-dimethoxy-4-hydroxybenzaldehyde by oxidizing 4-hydroxymethyl-3,5-dimethoxyphenol with oxygen. This example differs from Example 3 in that the substrate 2,4,6-trimethylphenol is replaced with 1 mmol of 4-hydroxy-3,5-dimethoxyphenol. The remaining steps are identical to Example 3. The reaction conversion 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%.

[0079] Example 16

[0080] This example provides a method for preparing 2,6-dimethoxy-p-benzoquinone by oxidizing sinapyl alcohol with oxygen. Compared with Example 1, this example differs in that the substrate 2,4,6-trimethylphenol is adjusted to 1 mmol of sinapyl alcohol. 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%.

[0081] Example 17

[0082] This example provides a method for efficiently preparing 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 3, this example differs 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. 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.

[0083] Example 18

[0084] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is replaced with 0.1 mmol of 4-NHAc-2,2,6,6-tetramethylpiperidinyl oxide. 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%.

[0085] Example 19

[0086] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is replaced with 0.1 mmol of 4-COOH-2,2,6,6-tetramethylpiperidinyl oxide. 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%.

[0087] Example 20

[0088] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is replaced with 0.1 mmol of 4-Maleimide (maleimide)-2,2,6,6-tetramethylpiperidinoxide. 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%.

[0089] Example 21 This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, the difference in this example is that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.1 mmol of 2,2,6,6-tetramethylpiperidinyl oxide. 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%.

[0090] Example 22

[0091] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.05 mmol of 4-OH-TEMPO, and 0.3 mmol of methanesulfonic acid is adjusted to 0.15 mmol of methanesulfonic acid. The remaining contents are identical to those in 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%.

[0092] Example 23

[0093] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.075 mmol of 4-OH-TEMPO. The remaining contents are identical to those in 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%.

[0094] Example 24

[0095] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.2 mmol of sodium nitrite is adjusted to 0.1 mmol of sodium nitrite. 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%.

[0096] Example 25

[0097] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.3 mmol of methylsulfonic acid is adjusted to 0.4 mmol of methylsulfonic acid. 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%.

[0098] Example 26

[0099] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.3 mmol of methylsulfonic acid is adjusted to 0.05 mmol of methylsulfonic acid. 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%.

[0100] Example 27

[0101] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.3 mmol of methanesulfonic acid is adjusted to 0.3 mmol of trifluoromethanesulfonic acid. 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%.

[0102] Example 28

[0103] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.3 mmol of methylsulfonic acid is adjusted to 0.3 mmol of p-methylbenzenesulfonic acid. 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%.

[0104] Example 29

[0105] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.3 mmol of methanesulfonic acid is adjusted to 0.3 mmol of nitric acid. 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%.

[0106] Example 30

[0107] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs 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. 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%.

[0108] Example 31

[0109] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs 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. 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%.

[0110] Example 32

[0111] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs 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. 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%.

[0112] Example 33

[0113] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. 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 94.2%, the yield of 2,6-dimethylbenzoquinone is 84.3%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.2%.

[0114] Example 34

[0115] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that the reaction temperature is 80°C and the pressure is 20 MPa. The rest of the process is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 85.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 9.6%.

[0116] Example 35

[0117] This example provides a method for efficiently preparing 2,6-dimethylbenzoquinone by oxidizing 2,4,6-trimethylphenol with oxygen. Compared with Example 1, this example differs in that 0.1 mmol of 4-OH-TEMPO is adjusted to 0.2 mmol of 4-OH-TEMPO, and 0.3 mmol of methylsulfonic acid is adjusted to 0.4 mmol of methylsulfonic acid. The rest of the reaction is exactly the same as Example 1. The conversion rate is 100%, the yield of 2,6-dimethylbenzoquinone is 83.4%, and the yield of 3,5-dimethyl-4-hydroxybenzaldehyde is only 10.1%.

[0118] Comparative Example 1

[0119] Compared with Example 1, this example differs in that the mixed solvent of acetonitrile and water used in the reaction is replaced with pure acetonitrile. The rest is exactly 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%.

[0120] Comparative Example 1 shows that the addition of water in the present invention plays a decisive role in improving the selectivity of oxygen oxidation of 2,4,6-trimethylphenol.

[0121] Comparative Example 2

[0122] Compared with Example 1, this example differs in that 0.4 g H2O and 1.6 g acetonitrile used in the reaction are replaced by 0.4 g H2O and 1.6 g perfluorotert-butanol. The rest is exactly 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%.

[0123] Comparative Example 3

[0124] Compared with Example 1, this example differs in that 0.4 g of H2O and 1.6 g of acetonitrile used in the reaction are replaced by 2.0 g of hexafluoroisopropanol. The rest is exactly the same as in 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%.

[0125] Comparative Example 4

[0126] Compared with Example 1, this example differs in 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. The rest is exactly the same as in 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%.

[0127] Comparative Examples 2 to 4 illustrate that the specific solvent system of the present invention has a decisive effect on the yield of 2,4,6-trimethylphenol by oxygen oxidation.

[0128] Comparative Example 5

[0129] Compared with Example 1, this example differs in that methanesulfonic acid is not added during the reaction. The rest is exactly the same as Example 1, and the substrate is not converted.

[0130] Comparative Example 6

[0131] Compared with Example 1, this example differs in that 0.3 mmol of methanesulfonic acid is adjusted to 0.3 mmol of cesium carbonate. The rest is exactly the same as Example 1, and the substrate is not converted.

[0132] Comparative Examples 5 and 6 show that protonic acid is a catalyst for disproportionation of TEMPO and is the key to its catalytic effect. The selectivity can be controlled by adjusting the strength and amount of the acid. Dedisproportionation of TEMPO without acid or with base is not feasible in the present invention.

[0133] Comparative Example 7

[0134] This example differs from Example 1 in that no TEMPO catalyst was added during the reaction. The reaction was otherwise identical to Example 1, resulting in no conversion of the substrate. This comparative example demonstrates the critical role of TEMPO catalyst in activating 2,4,6-trimethylphenol and converting it into 2,6-dimethylbenzoquinone and 3,5-dimethyl-4-hydroxybenzaldehyde.

[0135] Comparative Example 8

[0136] This example differs from Example 1 in that no NaNO2 was added in step (1). The remaining reaction conditions were identical to those in Example 1. The reaction conversion was 10.5%, the yield of 2,6-dimethylbenzoquinone was 3.5%, and no 3,5-dimethyl-4-hydroxybenzaldehyde was observed. This comparative example demonstrates that sodium nitrite acts as a circulating TEMPO catalyst, thereby completely converting the substrate.

[0137] Comparative Example 9

[0138] This example differs from Example 1 in that oxygen was not introduced in step (1), and the reaction system was protected with nitrogen. The remaining reaction conditions were identical to those in Example 1. The reaction conversion was 9.4%, the yield of 2,6-dimethylbenzoquinone was 3.3%, and no 3,5-dimethyl-4-hydroxybenzaldehyde was observed. This comparative example demonstrates that oxygen is an indispensable oxidant.

[0139] Comparative Example 10

[0140] Compared with Example 1, this example differs in 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%.

[0141] Comparative Example 10 shows that compared with using transition metal salts as co-catalysts, the catalytic system of the present invention has better effects.

[0142] 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.

[0143] 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 selective oxidation of phenolic compounds, characterized in that: In the presence of a catalyst and oxygen, phenol compounds undergo oxidation reaction in protonic acid and solvent to selectively generate quinone compounds and / or aromatic aldehyde compounds. The reaction formula is: ； In the above formula, R' is a C1~C6 alkyl group or a C1~C6 alkoxy group, and R' can represent multiple substituents on the benzene ring; R1 is a C1~C6 hydrocarbon group or a C1~C6 hydrocarbon group substituted by a hydroxyl group; R2 is H, C1~C5 hydrocarbon group or C1~C5 hydrocarbon group substituted by hydroxyl group; The catalyst is composed of 4-R-2,2,6,6-tetramethylpiperidinyl oxide and nitrite represented by formula (i) composition: (i), R is -OH; The main product of the oxidation reaction is an aromatic aldehyde compound; The protonic acid is benzoic acid or acetic acid, and the solvent is acetonitrile / water; or, under the synergistic effect of the nitrite and the protonic acid, the solvent is a mixed solvent of methanol / water, ethanol / water, tert-butanol / water, or propanol / water, and in this case, the protonic acid is methanesulfonic acid.

2. The selective oxidation method of phenolic compounds according to claim 1, wherein 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 sinapyl alcohol.

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

4. The selective oxidation method of phenolic compounds according to claim 1, wherein: The molar ratio of the phenol compound to the 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by the formula (i) is 5 to 200:1; The molar ratio of 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by the formula (i) to the nitrite is 1:0.5-4; The molar ratio of the 4-R-2,2,6,6-tetramethylpiperidinyl oxide represented by the formula (i) to the protonic acid is 1:0.5-4.

5. The selective oxidation method of phenolic compounds according to claim 1, wherein: 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 to 10:

1.

6. The selective oxidation method of phenolic compounds according to claim 1 or 5, characterized in that: The mass ratio of the phenol compound to the binary mixed solvent is 1:4-100.

7. The selective oxidation method of phenolic compounds according to claim 1, wherein: The reaction temperature of the oxidation reaction is 20-80°C; The reaction pressure of the oxidation reaction is 0.1~20MPa.

8. The selective oxidation method of phenolic compounds according to claim 7, wherein: The reaction temperature of the oxidation reaction is 30-50°C; The reaction pressure of the oxidation reaction is 0.1~10Mpa.

9. The selective oxidation method of phenolic compounds according to claim 1 or 5, characterized in that: The nitrite is sodium nitrite or potassium nitrite.

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