Synthesis method of benzoquinone compound

Abstract

The invention discloses a synthesis method of a benzoquinone compound, which comprises the following steps: adding a compound A, a copper salt catalyst and an initiator AIBN into an organic solvent, introducing oxygen for reaction to obtain a precipitate, then evaporating the solvent to dryness to obtain a crude product, separating the precipitate, washing and drying to obtain a compound B; the raw material cost is low, the synthesis route is simple, the purity of the obtained benzoquinone compound is high by precisely regulating and controlling the reaction conditions, and the strict requirements of most of downstream industrial applications on the purity of the raw materials can be met.

Description

Technical Field

[0001] This invention relates to a method for synthesizing benzoquinone compounds, specifically a method for obtaining p-benzoquinone compounds through an oxidation reaction, belonging to the field of organic synthetic chemistry. Background Technology

[0002] Quinones play a crucial role in various electron transfer processes in nature due to their unique redox properties. For example, ubiquinone (CoQ) 10 As a core component of the mitochondrial electron transport chain, quinones are crucial for aerobic respiration in most eukaryotic cells; vitamin K-like quinones are key cofactors involved in electron transfer during photosynthesis. These naturally occurring or synthetically produced quinone compounds, due to their significant biological activity, have become a hot topic in potential drug research targeting specific physiological processes. Furthermore, the unique electronic structures of quinone derivatives have also attracted widespread interest from researchers in the field of functional materials.

[0003] Currently, the synthesis of quinones mainly relies on a stepwise functionalization and oxidation strategy: typically, substituents are introduced into precursor molecules such as p-phenylenediether and phenol via Friedel-Crafts reactions, free radical reactions, or transition metal-catalyzed coupling, followed by oxidation to convert them into the target quinone structure. Another common route uses simple quinones as starting materials, constructing a 2-cyclohexene-1,4-dione intermediate through nucleophilic addition or cycloaddition reactions, which is then rearranged to generate hydroquinone and finally oxidized to quinone.

[0004] However, the above-mentioned synthesis methods generally have limitations such as cumbersome steps, low overall yield, and high cost. Summary of the Invention

[0005] The purpose of this invention is to propose a mild, efficient, and reproducible new method for the synthesis of benzoquinone compounds. This method uses readily available 1,4-dimethoxybenzene as a starting material and synthesizes benzoquinone compounds efficiently through a Brownian reaction and subsequent oxidation. This synthetic route is not only simple to operate but also exhibits good reproducibility, providing new ideas and strategies for the synthesis of benzoquinone compounds and effectively overcoming the main shortcomings of existing technologies.

[0006] The implementation process of this invention is as follows:

[0007] A method for synthesizing a benzoquinone compound, comprising the following steps:

[0008]

[0009] R1 to R4 are selected from hydrogen, C1 to C10 alkyl, C1 to C10 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 are selected from C1 to C10 alkyl, C1 to C10 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 form a benzene ring.

[0010] (1) Compound A, copper salt catalyst and initiator AIBN are added to an organic solvent and oxygen is introduced to react and precipitate is obtained;

[0011] (2) The solvent was then evaporated to obtain the crude product;

[0012] (3) After separating, washing and drying the precipitate, compound B is obtained.

[0013] In a preferred embodiment, R1 to R4 are selected from hydrogen, C1 to C6 alkyl, C1 to C6 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 are selected from C1 to C6 alkyl, C1 to C6 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 form a benzene ring.

[0014] The copper salt catalyst is selected from copper acetate, copper chloride, copper sulfate, basic copper carbonate, copper bromide, copper nitrate, copper oxide, and copper chromate.

[0015] The organic solvent is selected from tetrahydrofuran, ethyl acetate, tert-butanol, acetonitrile, diethyl ether, and methanol.

[0016] The present invention has the following main advantages:

[0017] (1) Low raw material cost: Phenol is a widely available and stable bulk chemical raw material, which is easy to purchase and store on a large scale, significantly reducing production costs from the source and possessing good industrial economics.

[0018] (2) Simple synthetic route: This method only requires one reaction to complete the conversion of phenol to benzoquinone, avoiding the complex operations and lengthy cycle in traditional multi-step synthesis, and significantly improving the synthesis efficiency.

[0019] (3) Excellent product quality: By precisely controlling the reaction conditions, the obtained benzoquinone compounds have high purity, which can meet the strict requirements of most downstream industrial applications for raw material purity. Detailed Implementation Plan

[0020] To better illustrate the embodiments of the present invention, the following will further describe them in conjunction with specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. Experimental methods not specifically specified in the examples are generally performed under conventional operating conditions or with reference to the recommended conditions provided by the manufacturers of the reagents and instruments used.

[0021] Example 1

[0022]

[0023] Under a nitrogen atmosphere, 2,3,5,6-tetramethylphenol (1 mmol), AIBN (0.1 mmol), and copper acetate (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of ethyl acetate was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500 MHz, Chloroform-d) δ 2.09 (s, 1H). 13 C NMR (125 MHz, Common NMRCDCl3) δ 188.61, 143.95, 12.23. Product yield was 83%.

[0024] Example 2

[0025]

[0026] Under a nitrogen atmosphere, 2-methyl-3,5,6-trimethoxyphenol (1 mmol), AIBN (0.1 mmol), and copper sulfate (0.1 g) were placed in a dry 10 mL round-bottom flask, and 2 mL of tetrahydrofuran was added with stirring. Oxygen was then introduced, and the reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500 MHz, Chloroform-d) δ 3.76 – 3.67 (m, 1H), 2.10 (s, 0H) 13 CNMR (125 MHz, Common NMR CDCl3) δ 176.55, 146.62, 60.35. Yield: 66%.

[0027] Example 3

[0028]

[0029] Under a nitrogen atmosphere, 2-methyl-4-nitrophenol (1 mmol), AIBN (0.1 mmol), and copper chloride (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of diethyl ether was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain the target product. 1 HNMR (500 MHz, Chloroform-d)δ7.41 (s, 1H), 6.98 (s, 1H), 2.19 (s, 3H). 13 C NMR (125 MHz, Common NMR CDCl3) δ 178.73, 175.02, 159.33, 135.94, 124.15, 116.32, 57.65. Yield: 72%.

[0030] Example 4

[0031]

[0032] Under a nitrogen atmosphere, 6-methyl-3-trifluoromethylphenol (1 mmol), AIBN (0.1 mmol), and copper acetate (0.1 g) were placed in a dry 10 mL round-bottom flask, and 2 mL of tert-butanol was added. Oxygen was then introduced, and the reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500 MHz, Chloroform-d)δ7.33 (s, 1H), 6.83 (s, 1H), 2.21 (s, 3H). 13 C NMR (125 MHz, Common NMR CDCl3) δ 185.31, 183.76, 143.66, 137.37, 133.12, 125.71, 121.71, 15.61. Its yield is 81%.

[0033] Example 5

[0034]

[0035] Under a nitrogen atmosphere, 3-ethyl-6-methylphenol (1 mmol), AIBN (0.1 mmol), and basic copper carbonate (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of methanol was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1H NMR (500 MHz, Chloroform-d) δ6.70 (s, 1H), 6.59 (s, 1H), 2.50 (s, 2H), 2.22 (s, 3H), 1.12 (s, 3H). 13 C NMR (125 MHz, Common NMR CDCl3) δ 190.20, 188.40, 148.38, 146.60, 135.04, 134.60, 23.56, 15.76, 13.22. Yield: 74%.

[0036] Example 6

[0037]

[0038] Under a nitrogen atmosphere, 3-tert-butyl-6-methylphenol (1 mmol), AIBN (0.1 mmol), and copper bromide (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of diethyl ether was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 HNMR (500 MHz, Chloroform-d)δ6.81 (s, 1H), 6.76 (s, 1H), 1.29 (s, 9H). 13 C NMR (125 MHz, Common NMR CDCl3) δ 190.51, 189.42, 153.01, 146.43, 136.43, 133.21, 36.80, 30.04, 15.76. Yield 62%.

[0039] Example 7

[0040]

[0041] Under a nitrogen atmosphere, 3-hydroxy-6-methylphenol (1 mmol), AIBN (0.1 mmol), and copper nitrate (0.1 g) were placed in a dry 10 mL round-bottom flask, and 2 mL of tetrahydrofuran was added with stirring. Oxygen was then introduced, and the reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500 MHz, Chloroform-d)δ9.68 (s, 1H), 6.99 (s, 1H), 6.26 (s, 1H). 13CNMR (125 MHz, Common NMR CDCl3) δ 188.49, 181.69, 161.29, 144.68, 135.02, 107.43, 15.68. Yield: 74%.

[0042] Example 8

[0043]

[0044] Under a nitrogen atmosphere, 2-methyl-1-naphthol (1 mmol), AIBN (0.1 mmol), and copper oxide (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of ethyl acetate was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500 MHz, Chloroform-d) δ8.06–8.00 (m, 1H), 7.98–7.93 (m, 1H), 7.76–7.68 (m,2H), 6.86 (s, 1H). 13 C10 NMR (125 MHz, Common NMR CDCl3) δ 188.24, 184.39, 146.30, 136.38, 135.24, 134.76, 134.37, 133.87, 128.91, 128.20, 16.33. Yield: 63%.

[0045] Example 9

[0046]

[0047] Under a nitrogen atmosphere, 3-fluoro-6-methylphenol (1 mmol), AIBN (0.1 mmol), and copper chromate (0.1 g) were placed in a dry 10 mL round-bottom flask, and 2 mL of tert-butanol was added. Oxygen was then introduced, and the reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR(500 MHz, Chloroform-d)δ6.91 (s, 1H), 6.79 (s, 1H). 13 C NMR (125 MHz, CommonNMR CDCl3) δ 189.26, 180.60, 152.45, 144.81, 137.16, 113.88, 15.68. Yield 55%.

[0048] Example 10

[0049]

[0050] Under a nitrogen atmosphere, 9-anthraphenol (1 mmol), AIBN (0.1 mmol), and copper acetate (0.1 g) were placed in a dry 10 mL round-bottom flask, 2 mL of ethyl acetate was added, and the mixture was stirred while oxygen was introduced. The reaction mixture was stirred at room temperature for 48 hours. After the reaction was complete, the mixture was evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography to finally obtain the target product. 1 H NMR (500MHz, Chloroform-d)δ8.19 (dd, 1H), 7.82 (dd, 1H). 13 C NMR (125 MHz, Common NMR, CDCl3) δ 185.26, 137.20, 135.62, 128.89. Yield: 82%.

[0051] Example 11

[0052] Referring to the preparation methods of Examples 1-10, the R1-R4 substituents of the present invention can be selected in various ways, and the target product can be obtained in all of them (as shown in Table 1).

[0053]

[0054] Within the scope of this invention, the above-described technical features and the technical features specifically described in the embodiments can be combined with each other to form new or preferred technical solutions. Furthermore, any feature disclosed in the specification can be replaced by an alternative feature capable of achieving the same, equivalent, or similar function.

Claims

1. A method for synthesizing benzoquinone compounds, characterized in that... Includes the following steps: ； R1 to R4 are selected from hydrogen, C1 to C10 alkyl, C1 to C10 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 are selected from C1 to C10 alkyl, C1 to C10 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 form a benzene ring. (1) Compound A, copper salt catalyst and initiator AIBN are added to an organic solvent and oxygen is introduced to react and precipitate is obtained; (2) The solvent was then evaporated to obtain the crude product; (3) After separating, washing and drying the precipitate, compound B is obtained.

2. The method for synthesizing benzoquinone compounds according to claim 1, characterized in that: R1 to R4 are selected from hydrogen, C1 to C6 alkyl, C1 to C6 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 are selected from C1 to C6 alkyl, C1 to C6 alkoxy, nitro, trifluoromethyl, and hydroxyl; or R1 and R2 form a benzene ring, and R3 and R4 form a benzene ring.

3. The method for synthesizing benzoquinone compounds according to claim 1, characterized in that: The copper salt catalyst is selected from copper acetate, copper chloride, copper sulfate, basic copper carbonate, copper bromide, copper nitrate, copper oxide, and copper chromate.

4. The method for synthesizing benzoquinone compounds according to claim 1, characterized in that: The organic solvent is selected from tetrahydrofuran, ethyl acetate, tert-butanol, acetonitrile, diethyl ether, and methanol.

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