A method for synthesizing para-substituted phenol derivatives

Abstract

The application discloses a method for synthesizing para-substituted phenol derivatives, which is characterized by the following steps: taking p-methylphenol and its derivatives and beta-phenyl ketonic acid and its derivatives as raw materials, stirring under the conditions of a mixture of anhydrous sodium carbonate, acetonitrile and deionized water, a constant current and an electrode which is easy to obtain, and synthesizing corresponding para-substituted phenol derivatives through one-step electro-synthesis under the conditions of no metal catalyst and stoichiometric amount of redox reagent and at room temperature. The method has the advantages of low price, reaction at room temperature, mild reaction conditions, convenience for the oxidation of p-methylphenol, simple synthesis operation, environmental friendliness, no special protection, wide industrial production prospect, and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of natural product and drug intermediate synthesis, and particularly relates to a method for synthesizing para-substituted phenol derivatives. BACKGROUND

[0002] Phenol derivatives have a wide range of applications in material science, synthetic chemistry and pharmaceutical industry. In particular, para-substituted phenols are key structural motifs of many natural products. For example, Pinocembrin chalcone (2', 4', 6'-Trihydroxychalcone), a pinocembrin chalcone, is an antibacterial compound widely derived from Helichrysum. Pinocembrin chalcone can prevent gastric ulcers in rats, resist T47D cytokines, and be used for treating diseases of immune suppression and other immune deficiencies or autoimmune deficiencies. Parthenocissin A is first isolated from Parthenocissus quinquefolia of grape family, and is a common stilbene oligomer. Stilbene oligomers are a class of natural polyphenols with the strongest anti-tumor activity. A large number of studies have shown that stilbene oligomers have a variety of biological activities, including anti-tumor, anti-oxidation, anti-inflammatory, treatment of some metabolic related diseases (such as abnormal glycolipid metabolism, etc.), certain protection for ischemia-reperfusion injury, neurodegenerative injury and cardiovascular and cerebrovascular diseases, and are expected to be used for preventing excessive obesity and diseases such as diabetes and coronary heart disease caused by excessive obesity. Therefore, the bottom-up assembly of para-substituted phenols has attracted widespread attention.

[0003] C-H / X-H (X = C, N, O, S, etc.) oxidative cross-coupling is considered to be an effective strategy because they do not require further pre-functionalization of substrates. And p-methylphenol is an ideal precursor for approaching para-substituted phenol derivatives through oxidative cross-coupling. However, previous methods for functionalizing C(sp 3 )-H of p-methylphenol through oxidative cross-coupling largely rely on superstoichiometric amounts of oxidants such as copper salts or oxo-ketones, which generate stoichiometric amounts of unwanted chemical waste. In view of the problem of resource saving, it is urgent to develop a green and environmentally friendly synthesis method to meet the production needs. SUMMARY

[0004] In order to overcome the deficiencies of superstoichiometric amounts of oxidants, complicated operation and harsh reaction conditions in the prior art for synthesizing para-substituted phenol derivatives, the present application provides a method for synthesizing para-substituted phenol derivatives. The method is a green synthesis method for synthesizing para-substituted phenol derivatives through electrocatalysis without oxidants. The reaction condition is to carry out the reaction at room temperature, the operation is simple, the condition is mild, no special protection is needed, the yield is high, and the industrial production prospect is broad.

[0005] A method for synthesizing para-substituted phenol derivatives, p-methyl phenol and its derivatives and beta-phenyl ketonic acid and its derivatives The method comprises the following steps: using p-methyl phenol and its derivatives as raw materials, adding an inorganic base under the conditions of no metal catalyst and stoichiometric amount of oxidant, using a mixed solvent of acetonitrile and deionized water as a reaction solvent, and performing one-step electro-synthesis of corresponding para-benzyl-substituted phenol derivatives at room temperature; after the reaction is completed, the reaction solution is dried with anhydrous sodium sulfate, filtered, and the filter cake is washed with dichloromethane; the solvent in the filtrate is removed by distillation under reduced pressure; and finally, the purified product is obtained by column chromatography; wherein R1 is a substituent on the ortho position of methyl phenol and its derivatives; R2 is a substituent on the ortho position of methyl phenol and its derivatives; and R3 is no substituent, or a single substituent or double substituent on the ortho position, the meta position or the para position of the benzene ring of beta-ketonic acid and its derivatives.

[0006] The reaction formula is as follows:

[0007]

[0008] As an improvement, the inorganic base is anhydrous sodium carbonate, and the amount of the inorganic base added is 0.5 equivalents; and the volume ratio of acetonitrile to deionized water in the mixed solvent of acetonitrile and deionized water is 3:1.

[0009] As an improvement, R1 is one of CH3, OMe, C(CH3)3, or Br, R2 is one of CH3, OMe, C(CH3)3, or Br, and R3 is H, an alkyl group, a halogen, an alkoxy group, or a naphthalene ring.

[0010] As an improvement, the molar ratio of p-methyl phenol and its derivatives to beta-phenyl ketonic acid and its derivatives is 1:1-3.

[0011] As a further improvement, the molar ratio of p-methyl phenol and its derivatives to beta-phenyl ketonic acid and its derivatives is 1:2.

[0012] As an improvement, the electrode device used for one-step electro-synthesis is a platinum sheet electrode (15 mm x 15 mm x 0.1 mm) and a carbon rod electrode (15 mm x 15 mm x 0.2 mm).

[0013] As an improvement, the constant current for one-step electro-synthesis is 3 mA.

[0014] As an improvement, the stirring speed is 300 r / min.

[0015] As an improvement, the room temperature is 25°C.

[0016] Beneficial effects:

[0017] Compared with the prior art, the method for synthesizing para-substituted phenol derivatives has the following advantages:

[0018] 1. Compared with the prior art, the safety of the synthesis process is low, and the advantages of the present application are very obvious, that is, the reaction equipment is simple, only an electrocatalytic device, a carbon electrode and a platinum sheet electrode, a stirring magnet and a three-necked flask can be used for reaction, the reaction time is short, and the process is easy to enlarge;

[0019] 2. The reaction conditions are mild, and the reaction can be carried out at room temperature and in an atmospheric environment, without heating and inert gas protection, thereby reducing the production cost;

[0020] 3. The present application selects acetonitrile and deionized water as the reaction solvent, without additional catalyst and oxidant, which is environmentally friendly, the by-product is less during the reaction process, the reaction product is easy to purify, the yield is high, and it is green and economic;

[0021] 4. The yield of the target compound is high, reaching 50-77%. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 It is the nuclear magnetic hydrogen spectrum of the target product of example 1;

[0023] Figure 2 It is the nuclear magnetic carbon spectrum of the target product of example 1;

[0024] Figure 3 It is the nuclear magnetic hydrogen spectrum of the target product of example 2;

[0025] Figure 4 It is the nuclear magnetic carbon spectrum of the target product of example 2;

[0026] Figure 5 It is the nuclear magnetic hydrogen spectrum of the target product of example 3;

[0027] Figure 6 It is the nuclear magnetic carbon spectrum of the target product of example 3;

[0028] Figure 7 It is the nuclear magnetic hydrogen spectrum of the target product of example 4;

[0029] Figure 8 It is the nuclear magnetic carbon spectrum of the target product of example 4;

[0030] Figure 9 It is the nuclear magnetic hydrogen spectrum of the target product of example 5;

[0031] Figure 10 It is the nuclear magnetic carbon spectrum of the target product of example 5;

[0032] Figure 11NMR of hydrogen spectrum of the target product of Example 6;

[0033] Figure 12 NMR of carbon spectrum of the target product of Example 6;

[0034] Figure 13 NMR of hydrogen spectrum of the target product of Example 7;

[0035] Figure 14 NMR of carbon spectrum of the target product of Example 7;

[0036] Figure 15 NMR of hydrogen spectrum of the target product of Example 8;

[0037] Figure 16 NMR of carbon spectrum of the target product of Example 8. DETAILED DESCRIPTION

[0038] The technical solutions of the present application are described in detail below in combination with examples, which do not mean limitation of the present application. All reagents below are commercially available, and the required acetonitrile, 2,4,6-trimethylphenol, 2,6-dibromo-4-methylphenol, 2,6-di-tert-butyl-4-methylphenol, 2,6-dimethoxy-4-methylphenol, tetrahydrofuran, substituted methyl ketone, dimethyl carbonate and other reagents are purchased from companies such as Anjie, Aladdin, Leyan, Titan Science and Technology, etc.

[0039] The β-phenyl ketonic acid can be synthesized by substituting the methyl ketone with the corresponding commercial reagent dimethyl carbonate (J. Am. Chem. Soc, 2007, 129, 11583)

[0040] Example 1

[0041]

[0042] Electrocatalysis was carried out in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as the anode and a platinum sheet (15 mm x 15 mm x 0.1 mm) as the cathode. 2,4,6-Trimethylphenol 1a (54.48 mg, 0.4 mmol), 3-oxo-3-phenylpropanoic acid 2a (131.33 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H2O (3 mL / 1 mL). Constant current electrolysis was carried out at room temperature for 4 hours at a constant current of 3.0 mA. Then the electrodes were washed with DCM, and the combined solvent was dried with anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, followed by column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain the product 3aa 71 mg

[0043] para-substituted phenol derivative 3aa: yellow oily liquid, yield 70%.

[0044] 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (dd, J = 8.4, 1.3 Hz, 2H), 7.61 - 7.52 (m, 1H), 7.46 (t, J = 7.5 Hz, 2H), 6.87 (s, 2H), 4.62 (s, 1H), 3.30 - 3.22 (m, 2H), 2.98 - 2.90 (m, 2H), 2.23 (s, 6H).

[0045] 13 C NMR (101 MHz, Chloroform-d) δ 199.72, 150.64, 137.03, 133.16, 132.96, 128.72, 128.64, 128.20, 123.19, 41.08, 29.43, 16.05.

[0046] Example 2

[0047]

[0048] Electrocatalysis was carried out in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2,4,6-Trimethylphenol la (54.48 mg, 0.4 mmol), 3-(4-methoxyphenyl)-3-oxopropanoic acid 2a (131.33 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were dissolved in acetonitrile / H2O (3 mL / 1 mL) in a 10 mL three-necked flask. The constant current electrolysis was carried out at room temperature for 4 hours at 3.0 mA. Then the electrodes were washed with DCM and the combined solvent was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the product 3ab 85 mg was obtained by column chromatography (petroleum ether: ethyl acetate = 10: 1).

[0049] para-substituted phenol derivative 3ab: yellow oily liquid, yield 75%.

[0050] 1 H NMR (400 MHz, Chloroform-d) δ 7.95 (d, J = 9.0 Hz, H), 6.93 (d, J = 8.9 Hz, 2H), 6.86 (s, 2H), 4.62 (s, 1H), 3.87 (s, 3H), 3.24 - 3.16 (m, 2H), 2.96 - 2.88 (m, 2H), 2.23 (s, 6H).

[0051] 13 C NMR (101 MHz, Chloroform-d) δ 198.33, 163.54, 150.61, 133.12, 130.47, 130.13, 128.63, 123.18, 113.83, 55.60, 40.76, 29.64, 16.06.

[0052] Example 3

[0053]

[0054] Electrocatalysis was carried out in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. The p-methyl phenol derivative la (54.48 mg, 0.4 mmol), β-phenyl ketonic acid 2a (142.45 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H20 (3 mL / 1 mL). The constant current of 3.0 mA was applied at room temperature for 4 hours. Then the electrodes were washed with DCM and the combined solvent was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and then column chromatography (petroleum ether: ethyl acetate = 10:1) to give the product 3ac 75 mg.

[0055] p-Substituted phenol derivative 3ac: yellow oily liquid, yield 70%.

[0056] 1 H NMR (400 MHz, Chloroform-d) δ 7.61 (dd, J = 8.0, 1.4 Hz, 1H), 7.36 (td, J = 7.5, 1.4 Hz, 1H), 7.24 (d, J = 5.0 Hz, 2H), 6.83 (s, 2H), 4.55 (s, 1H), 3.23 - 3.13 (t, 2H), 2.94 - 2.86 (t, 2H), 2.47 (s, 3H), 2.22 (s, 6H).

[0057] 13 C NMR (101 MHz, Chloroform-d) δ 203.98, 150.61, 138.18, 138.09, 132.81, 132.06, 131.33, 128.62, 128.53, 125.77, 123.16, 43.87, 29.64, 21.37, 16.04.

[0058] Example 4

[0059]

[0060] Electrocatalysis was performed in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2,4,6-Trimethylphenol la (54.48 mg, 0.4 mmol), 3-oxo-3-(p-tolyl)propanoic acid 2a (142.45 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H2O (3 mL / 1 mL). The electrolysis was performed at room temperature with a constant current of 3.0 mA for 4 h. Then the electrodes were washed with DCM and the combined solvents were dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and then column chromatography (petroleum ether: ethyl acetate = 10:1) was performed to give the product 3ad 75 mg.

[0061] para-substituted phenol derivative 3ad: yellow oily liquid, yield 70%.

[0062] 1 H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 8.3 Hz, 2H), 7.27 (s, 1H), 7.25 (s, 1H), 6.87 (s, 2H), 4.75 (s, 1H), 3.28 - 3.19 (m, 2H), 2.97 - 2.89 (m, 2H), 2.42 (s, 3H), 2.24 (s, 6H).

[0063] 13 C NMR (101 MHz, Chloroform-d) δ 199.47, 150.63, 143.92, 134.50, 132.99, 129.38, 128.60, 128.31, 123.22, 40.96, 29.51, 21.74, 16.06.

[0064] Example 5

[0065]

[0066] Electrocatalysis was performed in an undivided cell with carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2,4,6-Trimethylphenol la (54.48 mg, 0.4 mmol), 3-oxo-3-phenylpropanoic acid 2a (171.25 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H20 (3 mL / 1 mL). The electrolysis was performed at room temperature with a constant current of 3.0 mA for 4 h. Then the electrodes were washed with DCM and the combined solvents were dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and then column chromatography (petroleum ether: ethyl acetate = 10: 1) was performed to obtain the product 3ae 73 mg.

[0067] Para-substituted phenol derivative 3aa: yellow oily liquid, yield 60%.

[0068] 1 HNMR (400 MHz, Chloroform-d) δ 8.47 (s, 1H), 8.05 (dd, J = 8.6, 1.8 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 7.91 - 7.85 (m, 2H), 7.64 - 7.51 (m, 2H), 6.91 (s, 2H), 4.75 (s, 1H), 3.44 - 3.35 (m, 2H), 3.05 - 2.96 (m, 2H), 2.25 (s, 6H).

[0069] 13 C NMR (101 MHz, Chloroform-d) δ 199.70, 150.69, 135.66, 134.29, 132.94, 132.62, 129.86, 129.65, 128.64, 128.54, 127.88, 126.86, 123.98, 123.27, 41.18, 29.56, 16.08. Example 6

[0070]

[0071] Electrocatalysis was performed in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2,6-Dimethoxy-4-methylphenol la (67.23 mg, 0.4 mmol), 3-oxo-3-phenylpropanoic acid 2a (131.33 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were dissolved in acetonitrile / H20 (3 mL / 1 mL) in a 10 mL three-necked flask. The electrolysis was performed at room temperature with a constant current of 3.0 mA for 4 h. Then the electrodes were washed with DCM and the combined solvents were dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and then column chromatography (petroleum ether: ethyl acetate = 10: 1) was performed to give the product 3af 74 mg.

[0072] para-Substituted phenol derivative 3af: yellow oily liquid, yield 65%.

[0073] 1 H NMR (400 MHz, Chloroform-d) δ 7.95 (dd, J = 8.5, 1.4 Hz, 2H), 7.58 - 7.53 (m, 1H), 7.45 (t, J = 7.6 Hz, 2H), 6.46 (s, 2H), 5.43 (s, 1H), 3.86 (s, 6H), 3.31 - 3.24 (m, 2H), 3.00 (d, J = 8.0 Hz, 2H).

[0074] 13 C NMR (101 MHz, Chloroform-d) δ 199.56, 147.08, 136.97, 133.21, 133.08, 132.50, 128.72, 128.13, 105.10, 56.35, 40.95, 30.54.

[0075] Example 7

[0076]

[0077] Electrocatalysis was performed in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2-tert-Butyl-4,6-dimethylphenol la (71.26 mg, 0.4 mmol), 3-oxo-3-phenylpropanoic acid 2a (131.33 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H20 (3 mL / 1 mL). The electrolysis was performed at room temperature with a constant current of 3.0 mA for 4 h. Then the electrodes were washed with DCM and the combined solvents were dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and then column chromatography (petroleum ether: ethyl acetate = 10: 1) was performed to obtain the product 3ag 71 mg.

[0078] Para-substituted phenol derivative 3ag: yellow oily liquid, yield 60%.

[0079] 1 H NMR (400 MHz, Chloroform-d) δ 7.98 (dd, J = 8.4, 1.4 Hz, 2H), 7.59 - 7.54 (m, 1H), 7.47 (tt, J = 6.7, 1.4 Hz, 2H), 7.02 (d, J = 2.3 Hz, 1H), 6.91 (d, J = 2.1 Hz, 1H), 4.79 (s, 1H), 3.31 - 3.26 (m, 2H), 3.01 - 2.96 (m, 2H), 2.25 (s, 3H), 1.42 (s, 9H).

[0080] 13 C NMR (101 MHz, Chloroform-d) δ 199.93, 151.13, 137.03, 135.85, 133.13, 132.42, 128.69, 128.57 - 128.31 (m), 128.20, 125.41 - 124.93 (m), 123.26, 41.16, 34.62, 29.90, 29.87, 16.15.

[0081] Example 8

[0082]

[0083] Electrocatalysis was performed in an undivided cell with a carbon rod (15 mm x 15 mm x 0.2 mm) as anode and platinum sheet (15 mm x 15 mm x 0.1 mm) as cathode. 2,4,6-Trimethylphenol la (54.48 mg, 0.4 mmol), 3-(3,4-dimethoxyphenyl)-3-oxopropanoic acid 2a (179.37 mg, 0.8 mmol), anhydrous sodium carbonate (21.2 mg, 0.2 mmol) were placed in a 10 mL three-necked flask and dissolved in acetonitrile / H2O (3 mL / 1 mL). The electrolysis was performed at room temperature with a constant current of 3.0 mA for 4 hours. Then the electrodes were washed with DCM and the combined solvents were dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and then column chromatography (petroleum ether: ethyl acetate = 10:1) was performed to obtain the product 3ah 90 mg para-substituted phenol derivative 3ah: dark yellow oily liquid, yield 77%.

[0084] 1 H NMR (400 MHz, Chloroform-d) δ 7.58 (dd, J = 8.4, 2.0 Hz, 1H), 7.52 (d, J = 2.0 Hz, 1H), 6.87 (s, 1H), 6.86 (s, 2H), 4.57 (s, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.23 - 3.16 (m, 2H), 2.95 - 2.87 (m, 2H), 2.22 (s, 6H).

[0085] 13 C NMR (101 MHz, Chloroform-d) δ 198.36, 153.29, 150.63, 149.09, 133.08, 130.26, 128.63, 123.18, 122.79, 110.22 (d, J = 5.6 Hz), 110.08, 56.14, 40.66, 29.75, 16.06..

[0086] The above description is merely preferred specific embodiments of the application. The scope of the protection of the application is not limited to the specific embodiments described herein, but rather covers any and all alternatives falling within the scope of the application.

Claims

1. A method of synthesizing a para-substituted phenol derivative, characterized by, p-methylphenol and derivatives thereof β-phenyl ketonic acid and derivatives thereof The p-benzyl substituted phenol derivatives are synthesized by one-step electro-synthesis under the conditions of using p-methylphenol and derivatives thereof as raw materials, no metal catalyst and stoichiometric amount of oxidant, adding inorganic base and using mixed solvent of acetonitrile and deionized water as reaction solvent, constant current electrolysis at room temperature, drying with anhydrous sodium sulfate after reaction, suction filtration, washing the filter cake with dichloromethane, removing the solvent from the filtrate by reduced pressure distillation, and finally obtaining the purified product by column chromatography separation and purification; wherein R1 is one of CH3, OMe, C(CH3)3 or Br, R2 is CH3, OMe, C(CH3)3 or Br, and R3 is H, alkyl, halogen or alkoxy, and the reaction formula is shown as follows:

2. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The inorganic base is anhydrous sodium carbonate, and the phenol and its derivatives are 1 equivalent, and the amount of inorganic base added is 0.5 equivalent; the volume ratio of acetonitrile to deionized water in the mixed solvent is 3:

1.

3. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The molar ratio of the p-methylphenol and its derivatives to the β-phenyl ketonic acid and its derivatives is 1:1-3.

4. The method of synthesizing para-substituted phenol derivatives according to claim 3, wherein, The molar ratio of the p-methylphenol and its derivatives to the β-phenyl ketonic acid and its derivatives is 1:

2.

5. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The electrode device for one-step electro-synthesis is a platinum sheet electrode and a carbon rod electrode.

6. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The constant current of one-step electro-synthesis is 3mA.

7. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The reaction is carried out under stirring conditions, and the stirring speed is 300r / min.

8. The method of synthesizing para-substituted phenol derivatives according to claim 1, wherein, The room temperature is 25℃.

9. A method of synthesizing para-substituted phenol derivatives, characterized by, p-methylphenol and derivatives thereof β-phenyl ketonic acid and derivatives thereof The p-methylphenol and derivatives thereof are used as raw materials, inorganic base is added under the conditions of no metal catalyst and stoichiometric amount of oxidant, mixed solvent of acetonitrile and deionized water is used as reaction solvent, corresponding p-benzyl substituted phenol derivatives are synthesized by constant current electrolysis at room temperature, after the reaction is completed, the product is dried with anhydrous sodium sulfate, filtered and washed with dichloromethane, the filtrate is distilled under reduced pressure to remove the solvent, and finally, the purified product is obtained by column chromatography, and the reaction formula is as follows:

Images