Synthetic method of 3, 3 ', 5, 5-tetramethyl-4, 4'-dihydroxybiphenyl and derivatives thereof

Abstract

The invention discloses a preparation method of 3, 4-difluorobenzene. The invention discloses a synthesis method of 3, 3 ', 5, 5-tetramethyl-4, 4'-dihydroxybiphenyl and a derivative thereof, which comprises the following steps: adding 1 mmol of 4-halogenated aryl phenol compound, 0.1 mmol of metal catalyst and 0.1 mmol of ligand into a reaction container in a nitrogen atmosphere, reacting for 30 minutes at normal temperature, adding a solvent, stirring until the raw materials are dissolved, adding 1 mmol of metal reducing agent into the solution, stirring for 24 hours at room temperature, filtering, washing and drying to obtain the 3, 3 ', 5, 5-tetramethyl-4, 4'-dihydroxybiphenyl and the derivative thereof. The preparation method comprises the following steps: adding 2, 3 ', 5, 5'-tetramethyl-4, 4 '-dihydroxybiphenyl into a reaction kettle, carrying out thin layer chromatography detection reaction, after the reaction is finished, carrying out filtration and rotary evaporation on a reaction solution to obtain a crude product, and carrying out recrystallization or column chromatography on the crude product by using a mixed solvent to obtain a final product 3, 3', 5, 5 '-tetramethyl-4, 4'-dihydroxybiphenyl and the derivative thereof. The method has the advantages of high reaction yield and mild reaction conditions. According to the chemical reaction process, the problems that in a traditional preparation method, much waste water is difficult to solve, a large number of reducing agents are needed and the like are solved, an amplification test is carried out, and good application prospects are achieved.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing 3,3',5,5-tetramethyl-4,4'-dihydroxybiphenyl and its derivatives. Background Art

[0002] Biphenol is a very important class of organic synthesis intermediates, which occupies a certain position in organic synthesis and material synthesis. With the development of the electronic chemical industry, the requirements and demands for electronic packaging materials are constantly increasing. Epoxy resin-based plastic packaging materials are excellent in terms of reliability, production cost, and stability of electronic components after production. 4,4'-Biphenol and its derivatives are one of the important raw materials for synthesizing epoxy resins. Therefore, studying the synthesis methods of 4,4'-biphenol and its derivatives plays an important role in the development of China's electronic technology. 3,3',5,5'-Tetramethyl-4,4'-dihydroxybiphenyl is an organic compound widely used in electronic packaging materials. The stable large Π bond provided after its polymerization and the hyperconjugation effect brought by the methyl groups in the molecule enable it to play an important role in electronic packaging materials. The epoxy resin material synthesized from 3,3',5,5'-tetramethyl-4,4'-dihydroxybiphenyl can effectively protect electronic components from moisture corrosion and other effects, and enhance the stability of electronic components. At present, in the context of the increasing demand for advanced packaging materials in China, synthesizing various 4,4'-biphenol derivatives and studying their performance in epoxy resin packaging materials also has important significance.

[0003] Currently, the mainstream method for synthesizing 3,3',5,5'-tetramethyl-4,4'-dihydroxybiphenyl is the oxidative coupling method, that is, 2,6-dimethylphenol is carried out under the catalysis of transition metals (usually catalysts such as copper, rhodium, ruthenium, etc.) with oxygen as the oxidation source.

[0004] In 2014, Marisa C. Kozlowski et al. found that a catalyst formed by coordinating a Salen ligand with a cadmium salt could, in the presence of oxygen, react at 85 °C for 1-2 days, and then be treated with sodium dithionite to obtain the product with a yield of 67%. The ligand used in this study is relatively complex and the yield is good, but the catalyst requires the use of cadmium with greater environmental hazard as the catalytic center, which is not conducive to environmental protection.

[0005] In 2017, Koichiro Jitsukawa et al. used a noble metal catalyst to conduct an oxidative coupling reaction on 2,6-dimethylphenol under ruthenium catalysis with oxygen, and then used hydrogen to reduce it to obtain the target product with a relatively high yield of 97%. The highlight of this reaction is the synthesis of the target product using a one-pot method, without changing the catalyst during the reduction process, and using hydrogen instead of the commonly used sodium dithionite, which is very significant for research. However, this reaction still has deficiencies such as the need to use high-explosive products like hydrogen and a relatively long reaction time.

[0006] In 2019, Gansu Taisheng Chemical Technology Co., Ltd. found that when using copper acetate as a catalyst, sodium dodecyl sulfate as an anionic surfactant, and isopropanol as a solvent, oxidative coupling occurs in the presence of oxygen, and then reduction is carried out with sodium dithionite. The yield of this reaction is relatively high, at 85.3%, but it requires high temperature and oxygen during the reaction, which has certain potential safety hazards.

[0007] In summary, in the previous synthesis routes of 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl, it is usually necessary to use oxygen for oxidative coupling, and the oxidative coupling reaction is difficult to control, so a large amount of quinone by-products will be generated.

[0008] In order to solve the problems in the synthesis of 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl, such as the need for high temperature, the need for reducing agents such as sodium dithionite, and the need for high-explosive gases such as oxygen or hydrogen. The present invention provides a method for preparing 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives using a transition metal-catalyzed coupling reaction under mild conditions. Summary of the Invention

[0009] The object of the present invention is to provide a method for synthesizing 3,3’,5,5-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives. To solve the above problems, the present invention provides a method for synthesizing 3,3’,5,5-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives. The method includes the following steps: Under a nitrogen atmosphere, add 1 mmol of 4-haloaryl phenolic compound as a raw material, 0.1 mmol of a metal catalyst, and 0.1 mmol of a ligand to a reaction vessel, react at room temperature for 30 min, add a solvent and stir until the raw material dissolves, then add 1 mmol of a metal reducing agent to the solution and stir at room temperature for 24 h. Detect the reaction by thin-layer chromatography. After the reaction is completed, filter the reaction solution and perform rotary evaporation to obtain a crude product, and recrystallize or perform column chromatography on the crude product with a mixed solvent to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives; The 4-haloaryl phenol compounds are one or more of 4-chlorophenol, 4-bromophenol, 4-iodophenol, 4-chloro-2-methylphenol, 4-bromo-2-methylphenol, 4-iodo-2-methylphenol, 4-chloro-2,6-dimethylphenol, 4-bromo-2,6-dimethylphenol, 4-iodo-2,6-dimethylphenol, 4-chloro-2,3,6-trimethylphenol, 4-bromo-2,3,6-trimethylphenol, 4-iodo-2,3,6-trimethylphenol, 4-chloro-2,3,5,6-tetramethylphenol, 4-bromo-2,3,5,6-tetramethylphenol, 4-chloro-2-methoxyphenol, 4-bromo-2-methoxyphenol, 4-iodo-2-methoxyphenol, 4-chloro-2,6-dimethoxyphenol, 4-bromo-2,6-dimethoxyphenol, 4-iodo-2,6-dimethoxyphenol, 4-chloro-2,3,6-trimethoxyphenol, 4-bromo-2,3,6-trimethoxyphenol, 4-iodo-2,3,6-trimethoxyphenol, 4-chloro-2,3,5,6-tetramethoxyphenol, 4-bromo-2,3,5,6-tetramethoxyphenol; The metal catalyst is one or more of cobalt chloride, cobalt bromide, cobalt iodide, cobalt sulfate, nickel chloride, nickel bromide, nickel iodide, nickel sulfate; The ligand is one or more of pyridine, imidazole, 4-dimethylaminopyridine, bipyridine, 2,9-dimethyl-1,10-phenanthroline (CAS: 484-11-7), 3,4,7,8-tetramethyl-1,10-phenanthroline (CAS: 1660-93-1), 4,7-diphenyl-1,10-phenanthroline (CAS: 1662-01-7), 5,6-dimethyl-1,10-phenanthroline (CAS: 3002-81-1), 4,7-dimethyl-1,10-phenanthroline (CAS: 3248-05-3), 4,4'-dimethyl-2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine; The metal reducing agent is one or more of magnesium, manganese, zinc, iron; The solvent is one or more of acetonitrile, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, n-pentane, n-hexane, cyclohexane; The mixed solvent is one or more of n-pentane, n-hexane, cyclohexane, petroleum ether, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, chloroform, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, 1,4-dioxane; the method has mild conditions and simple operation, and the yields of the final products 3,3',5,5'-tetramethyl-4,4'-dihydroxybiphenyl and its derivatives are stable and have high purity, having certain industrial production value. Description of the Drawings

[0010] Figure 1 For the product of Preparation Example 4 1 HNMR Nuclear Magnetic Resonance Hydrogen Spectrum; Figure 2 For the product of Preparation Example 4 13 CNMR Nuclear Magnetic Resonance Carbon Spectrum. Detailed Embodiments

[0011] The following examples are intended to further illustrate the content of the present invention, rather than limiting the scope of protection required by the present invention.

[0012] Nuclear Magnetic Resonance Hydrogen Spectrum 1 H NMR (400 MHz), Nuclear Magnetic Resonance Carbon Spectrum 13 C NMR (101 MHz) detection was obtained by testing with a Bruker spectrometer.

[0013] In the condition exploration experiment, 4-bromo-2,6-dimethylphenol was used as the reaction raw material to synthesize the target 3,3',5,5'-tetramethyl-4,4'-dihydroxybiphenyl and its derivative compounds, and various aspects of the reaction ligands, solvents, and reducing agents were explored.

[0014]

[0015] The specific method for condition screening is as follows: Ligand Screening Scheme 1: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese to a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h and monitor the progress of the reaction by thin-layer chromatography. When the reaction is complete, quench the reaction mixture with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and evaporate the solvent to obtain the crude product. Purify the crude product by column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 95%.

[0016] Ligand screening protocol two: Add 0.108 g (0.5 mmol) of 4,4'-dimethoxy-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese to a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h and monitor the progress of the reaction by thin-layer chromatography. It is found that no product can be obtained under this condition.

[0017] Ligand screening protocol three: Add 0.134 g (0.5 mmol) of 4,4'-di-tert-butyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese to a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h and monitor the progress of the reaction by thin-layer chromatography. When the reaction is complete, quench the reaction mixture with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and evaporate the solvent to obtain the crude product. Purify the crude product by column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 42%.

[0018] Ligand screening protocol four: Add 0.92 g (0.5 mmol) of 5,5'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, quench the reaction solution with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and then rotary evaporate the organic phase to obtain the crude product. The crude product is subjected to column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 33%.

[0019] Ligand screening protocol five: Add 0.092 g (0.5 mmol) of 6,6'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, quench the reaction solution with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and then rotary evaporate the organic phase to obtain the crude product. The crude product is subjected to column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 20%.

[0020] Ligand screening protocol six: Add 0.09 g (0.5 mmol) of 1,10-phenanthroline, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylformamide into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. It is found that no product can be obtained with this protocol.

[0021]

[0022] Solvent screening protocol one: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of dimethyl sulfoxide as the solvent. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, quench the reaction mixture with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and evaporate it to dryness to obtain the crude product. The crude product is purified by column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 97%.

[0023] Solvent screening protocol two: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of N,N-dimethylformamide as the solvent. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, quench the reaction mixture with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and evaporate it to dryness to obtain the crude product. The crude product is purified by column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 95%.

[0024] Solvent screening protocol three: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of tetrahydrofuran as the solvent. React for 24 h and monitor the reaction progress by thin-layer chromatography. It is found that no product can be obtained with this protocol.

[0025] Solvent screening protocol four: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent N,N-dimethylacetamide into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, quench the reaction solution with 1 M hydrochloric acid, then extract with 50 mL of ethyl acetate and separate the layers. Dry the organic phase and rotary evaporate it to obtain the crude product. The crude product is subjected to column chromatography using a mixed solvent of n-hexane:ethyl acetate = 5:1 to obtain the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 63%.

[0026] Solvent screening scheme five: Add 0.092 g (0.5 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 0.065 g (0.5 mmol) of cobalt chloride, and 0.56 g of metallic manganese into a 50 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 1.05 g (5 mmol) of 2,3-dimethyl-4-bromophenol and 5 mL of the solvent DCM into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. It is found that no product can be obtained with this scheme.

[0027] The present invention will be further described below in conjunction with specific preparation examples Preparation example 1:

[0028] Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g (100 mol) of metallic manganese into a 500 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 17.3 g (100 mol) of p-bromophenol and 200 mL of the solvent N,N-dimethylformamide into the flask. React for 24 h and monitor the reaction progress by thin-layer chromatography. After the reaction is completed, filter the reaction solution through diatomaceous earth and wash the filter cake with ethyl acetate. The obtained solution is rotary evaporated to remove the solvent to obtain the crude product. The crude product is first washed with water and filtered, and the filter cake is recrystallized using a mixed solvent of n-hexane:ethyl acetate = 2:1. Finally, the final product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives are obtained in a yield of 95%.

[0029] Nuclear magnetic resonance data: 1 HNMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 7.7 Hz, 4H), 7.63 (d, J = 7.8 Hz, 4H), 1.36 (s, 24H) ppm.; 13 CNMR (101 MHz, CDCl3) δ 143.66, 135.26, 126.52, 83.85, 24.88 ppm..

[0030] Preparation Example 2:

[0031] Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g of metallic manganese to a 500 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 18.7 g of 2-methyl-4-bromophenol and 200 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h and monitor the progress of the reaction by thin-layer chromatography. After the reaction is completed, filter the reaction solution through diatomaceous earth and wash the filter cake with ethyl acetate. Remove the solvent from the resulting solution by rotary evaporation to obtain a crude product. Wash the crude product with water and filter it. Recrystallize the filter cake from a mixed solvent of n-hexane:ethyl acetate = 4:1 to finally obtain the end product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 92%.

[0032] Nuclear magnetic resonance data: 1 HNMR (400 MHz, Chloroform- d ) δ 7.32 (s, 2H), 7.26 (s, 2H), 6.83 (d, J = 8.2 Hz, 2H), 2.33 (s, 6H) ppm.; 13 CNMR (101 MHz, Chloroform- d ) δ 152.9, 134.1, 129.4, 125.4, 122.4, 115.2, 77.4, 77.0, 76.7, 15.9 ppm..

[0033] Preparation Example 3:

[0034] Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g of metallic manganese to a 500 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 20.1 g of 2,3-dimethyl-4-bromophenol and 200 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h, and monitor the progress of the reaction by thin-layer chromatography. After the reaction is complete, filter the reaction solution through diatomaceous earth, and wash the filter cake with ethyl acetate. Remove the solvent from the resulting solution by rotary evaporation to obtain a crude product. Wash the crude product with water and filter it. Recrystallize the filter cake from a mixed solvent of n-hexane:ethyl acetate = 5:1 to finally obtain the end product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 97%.

[0035] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 7.28 (s, 4H), 7.17 (s, 4H), 4.62 (s,2H), 2.32 (s, 12H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 151.3, 133.3, 127.0, 123.1, 16.1ppm.

[0036] Preparation Example 4:

[0037] Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g of metallic manganese to a 500 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 21.5 g of 2,3,5-trimethyl-4-bromophenol and 200 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h, and monitor the progress of the reaction by thin-layer chromatography. After the reaction is complete, filter the reaction solution through diatomaceous earth, and wash the filter cake with ethyl acetate. Remove the solvent from the resulting solution by rotary evaporation to obtain a crude product. Wash the crude product with water and filter it. Recrystallize the filter cake from a mixed solvent of n-hexane:ethyl acetate = 5:1 to finally obtain the end product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 71%.

[0038] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 6.73 (s, 2H), 4.60 (s, 2H), 2.23 (d, J = 4.6 Hz, 12H), 1.94 (s, 6H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 150.8, 134.8, 133.9, 129.5, 121.7,119.6, 17.0, 16.0, 12.4 ppm.。

[0039] 1H NMR of the product of Preparation Example 4 1 1H NMR is as Figure 1 shown; 13C NMR of the product of Preparation Example 4 13 13C NMR is as Figure 2 shown.

[0040] Preparation Example 5:

[0041] The synthesis method of this compound is as shown in Preparation Example 1: Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g of metallic manganese into a 500 mL round-bottom flask. Evacuate and fill the flask with nitrogen three times. Then add 18.8 g of 2-methyl-4-bromophenol and 200 mL of the solvent N,N-dimethylformamide into the flask. React for 24 h, and monitor the progress of the reaction by thin-layer chromatography. After the reaction is completed, filter the reaction solution through diatomaceous earth, and wash the filter cake with ethyl acetate. Remove the solvent from the obtained solution by rotary evaporation to obtain the crude product. Wash the crude product with water and filter it. Recrystallize the filter cake with ethyl acetate to finally obtain the end product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 77%.

[0042] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 7.98 (m, 4H), 7.03 (d, J = 2.0 Hz,2H), 6.88 (m, 2H), 6.83 (d, J = 8.0 Hz, 4H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 145.3, 144.1, 133.5, 117.9, 115.6, 113.6 ppm.

[0043] Preparation Example 6:

[0044] The synthesis method of this compound is as shown in Preparation Example 1: Add 1.56 g (10 mmol) of 4,4'-dimethyl-2,2'-bipyridine, 1.3 g (10 mmol) of cobalt chloride, and 5.6 g of metallic manganese to a 500 mL round-bottom flask. Evacuate and refill the flask with nitrogen three times. Then add 18.8 g of 2-methyl-4-bromophenol and 200 mL of the solvent N,N-dimethylformamide to the flask. React for 24 h, and monitor the progress of the reaction by thin-layer chromatography. After the reaction is completed, filter the reaction solution through diatomaceous earth, and wash the filter cake with ethyl acetate. Remove the solvent from the obtained solution by rotary evaporation to obtain the crude product. Wash the crude product with water and filter it. Recrystallize the filter cake with ethyl acetate to finally obtain the end product 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives in a yield of 63%.

[0045] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 4.46 (m, 4H), 6.54 (d, J = 4.0 Hz, 2H), 6.65 (d, J = 4.1 Hz, 2H), 6.77 (s, 2H), 8.89 (m, 2H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 112.5, 114.2, 114.6, 132.9, 136.6, 142.9 ppm.

[0046] Preparation Example 7:

[0047] The synthesis method of this compound is as shown in Preparation Example 1.

[0048] Nuclear magnetic resonance data: 11H NMR (400 MHz, Chloroform- d ) δ 7.30 (d, J = 2.4 Hz, 2H), 7.27 (m,2H), 6.81 (d, J = 7.8 Hz, 2H), 4.82 (s, 2H), 2.67 (t, J = 7.6 Hz, 4H), 1.77-1.68 (m, 4H), 1.04 (t, J = 7.6 Hz, 6H) ppm. 13 13C NMR (101 MHz, Chloroform- d ): δ 152.5, 133.9, 128.7, 128.6, 125.3,115.5, 32.3, 23.1, 14.1 ppm.。

[0049] Preparation Example 8:

[0050] The synthesis method of this compound is as shown in Preparation Example 1.

[0051] Nuclear magnetic resonance data: 1 1H NMR (400 MHz, Chloroform- d ) δ 6.95 (s, 2H), 6.66 (s, 2H), 4.63 (s,2H), 3.18 (m, 2H), 1.24 (d, J = 7.0 Hz, 6H), 1.23 (d, J = 7.0 Hz, 6H) ppm.; 13 13C NMR (101 MHz, Chloroform- d ) δ 151.5, 134.7, 134.1, 131.3, 128.0,116.4, 26.7, 22.8, 22.7, 19.5 ppm.。

[0052] Preparation Example 9:

[0053] The synthesis method of this compound is as shown in Preparation Example 1.

[0054] Nuclear magnetic resonance data: 1 1H NMR (400 MHz, Chloroform- d) δ 6.68 (s, 4H), 5.51 (s, 2H), 3.96 (s,12H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 147.1, 134.1, 133.2, 104.0, 56.4ppm..

[0055] Preparation Example 10:

[0056] The synthesis method of this compound is as shown in Preparation Example 1.

[0057] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 8.23 (m, 2 H), 7.46 (m, 2 H), 7.34(d, J = 8.2 Hz, 2 H), 7.22 - 7.27 (m, 4 H), 5.18 (s, 2 H), 2.47 (s, 6 H) ppm.; 13 C NMR (101 MHz, Chloroform- d ) δ 148.2, 132.9, 131.1, 130.7, 126.6,125.3, 125.1, 124.2, 121.0, 115.7, 15.6 ppm..

[0058] Preparation Example 11:

[0059] The synthesis method of this compound is as shown in Preparation Example 1.

[0060] Nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform- d ) δ 6.91 (m, 2H), 6.87 (d, J = 2.1 Hz,2H), 5.66 (s, 2H), 3.94 (s, 6H), 2.31 (s, 6H) ppm.; 13 C NMR (101 MHz, Chloroform- d) δ 146.6, 143.0, 133.3, 124.0, 121.9, 107.3, 56.4, 15.9 ppm.

[0061] This method uses 4-haloaryl phenol compounds as raw materials and obtains the required compounds in one step through cobalt catalysis. Using cobalt as a transition metal catalyst avoids the problems of insufficient atom economy and the use of explosive substances in the existing preparation processes. Moreover, this method has mild conditions and simple operations. The yields of the end products 3,3’,5,5’-tetramethyl-4,4’-dihydroxybiphenyl and its derivatives are stable and have high purity, showing certain industrial production value.

[0062] The above are only some embodiments of the present invention. For those of ordinary skill in the art, without departing from the inventive concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 3,3',5,5-tetramethyl-4,4'-dihydroxybiphenyl and its derivatives, characterized in that: Under a nitrogen atmosphere, 1 mmol of a raw material 4-halogenated aromatic phenol compound, 0.1 mmol of a metal catalyst, and 0.1 mmol of a ligand are added to a reaction container, and the mixture is reacted at room temperature for 30 min. After the solvent is added and stirred until the raw material is dissolved, 1 mmol of a metal reducing agent is added to the solution and stirred at room temperature for 24 h. The reaction is detected by thin layer chromatography. After the reaction is completed, the reaction solution is filtered and rotary evaporated to obtain a crude product, and the crude product is recrystallized or column chromatographed with a mixed solvent to obtain the final product 3,3',5,5'-tetramethyl-4,4'-dihydroxybiphenyl and its derivatives; The 4-halogenated aromatic phenol compounds are 4-chlorophenol, 4-bromophenol, 4-iodophenol, 4-chloro-2-methylphenol, 4-bromo-2-methylphenol, 4-iodo-2-methylphenol, 4-chloro-2,6-dimethylphenol, 4-bromo-2,6-dimethylphenol, 4-iodo-2,6-dimethylphenol, 4-chloro-2,3,6-trimethylphenol, 4-bromo-2,3,6-trimethylphenol, 4-iodo-2,3,6-trimethylphenol, 4-chloro-2,3,5,6-tetramethylphenol, 4-bromo-2,3,5,6 -tetramethylphenol, 4-chloro-2-methoxyphenol, 4-bromo-2-methoxyphenol, 4-iodo-2-methoxyphenol, 4-chloro-2,6-dimethoxyphenol, 4-bromo-2,6-dimethoxyphenol, 4-iodo-2,6-dimethoxyphenol, 4-chloro-2,3,6-trimethoxyphenol, 4-bromo-2,3,6-trimethoxyphenol, 4-iodo-2,3,6-trimethoxyphenol, 4-chloro-2,3,5,6-tetramethoxyphenol, 4-bromo-2,3,5,6-tetramethoxyphenol; The metal catalyst is one or more of cobalt chloride, cobalt bromide, cobalt iodide, cobalt sulfate, nickel chloride, nickel bromide, nickel iodide, and nickel sulfate; The ligands are pyridine, imidazole, 4-dimethylaminopyridine, bipyridine, 2,9-dimethyl-1,10-phenanthroline (CAS: 484-11-7), 3,4,7,8-tetramethyl-1,10-phenanthroline (CAS: 1660-93-1), 4,7-diphenyl-1,10-phenanthroline (CAS: 1662-01-7), 5,6-dimethyl-1,10-phenanthroline (CAS: 3002-81-1), 4,7-dimethyl-1,10-phenanthroline (CAS: 3248-05-3), 4,4'-dimethyl-2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine; The metal reducing agent is one or more of magnesium, manganese, zinc and iron; The solvent is one or more of acetonitrile, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, n-pentane, n-hexane, and cyclohexane; The mixed solvent is one or more of n-pentane, n-hexane, cyclohexane, petroleum ether, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, chloroform, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, and 1,4-dioxane.

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