A process for the preparation of 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxydiphenyl

Abstract

The application relates to the technical field of organic synthesis, and provides a preparation method of 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxydiphenyl. 2,3,6-trimethylphenol, alkali, borax, a surfactant, a catalyst, a catalyst ligand, a catalyst aid and a solvent are mixed, a first reaction is carried out under oxygen condition, then hydrogen peroxide is added to carry out a second reaction, a reducing agent is further added to carry out reduction, and the target product is obtained. The alkali and the borax jointly provide a stable alkaline environment, and the borax can be used as a phenolic hydroxyl stabilizer to avoid the generation of impurities quinone; hydrogen peroxide is added after the first reaction to carry out oxidation, and a reducing agent is used to reduce the peroxidation product, so that the product yield and the purity are greatly improved; the cyclodextrin is added as the catalyst aid, and the reaction rate can be accelerated. In conclusion, the preparation method provided by the application is simple in operation, high in product yield and purity, and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl. Background Technology

[0002] 2,2',3,3',5,5'-Hexamethyl-4,4'-dihydroxybiphenyl is an important organic synthesis intermediate widely used in pharmaceutical manufacturing and polymer material production. In the synthesis of polyphenylene ethers, 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl is mainly used as a diphenol monomer. For example, commercially available OPEs series polyphenylene ether products are prepared by polymerizing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl with 2,6-xylenol to obtain low molecular weight bifunctional polyphenylene ethers.

[0003] A related technology provides a method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl, in which oxygen is used as an oxidant and copper catalyst is used to complete the oxidative coupling of trimethylphenol (TMP) to achieve the synthesis of the target product. This process has a clear reaction pathway and uses oxygen as an oxidant, offering a significant cost advantage. However, it still has significant limitations for industrial application: Because the reaction is sensitive to the pH of the solvent system, the products and byproducts generated during the reaction disturb the pH. This process achieves pH control by precisely adding alkali, but this method is only feasible for small-batch production and difficult to use for scale-up production. Secondly, due to the significant decrease in TMP conversion in the later stages of the reaction, the final product yield is only 65-89%, and the residual TMP monomer in the product is large, making it difficult to remove by simple rinsing. This forces the production end to add purification processes such as recrystallization or distillation, resulting in increased process complexity and equipment complexity when applied to actual production.

[0004] In summary, the current methods for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl are complex to operate and have low product yields, making them unsuitable for industrial production. Summary of the Invention

[0005] In view of this, the present invention provides a method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl. The method provided by the present invention is simple to operate, has a high product yield, and contains very little monomer residue in the product, requiring no purification and is suitable for industrial production.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] A method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl includes the following steps:

[0008] 2,3,6-Trimethylphenol, alkali, borax, surfactant, catalyst, catalyst ligand, catalyst promoter, and solvent are mixed and subjected to a first reaction under oxygen conditions to obtain a first reaction solution; the catalyst is a copper salt; the catalyst promoter is cyclodextrin.

[0009] The first reaction solution and hydrogen peroxide are mixed to carry out a second reaction, resulting in a second reaction solution;

[0010] The second reaction solution and the reducing agent are mixed to carry out a reduction reaction to obtain the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl.

[0011] Preferably, the base is an alkali metal hydroxide; the molar amount of the base is 0.005 to 0.05 times the molar amount of 2,3,6-trimethylphenol.

[0012] Preferably, the molar amount of borax is 0.002 to 0.02 times the molar amount of 2,3,6-trimethylphenol.

[0013] Preferably, the surfactant is an anionic surfactant, and the molar amount of the surfactant is 0.0005 to 0.02 times the molar amount of 2,3,6-trimethylphenol.

[0014] Preferably, the cyclodextrin is α-cyclodextrin; the molar amount of the cyclodextrin is 0.0005 to 0.002 times the molar amount of 2,3,6-trimethylphenol.

[0015] The copper salt is copper acetate; the catalyst ligand is acetate; the molar amount of the copper salt is 0.0005 to 0.005 times the molar amount of 2,3,6-trimethylphenol; the molar amount of the catalyst ligand is 0.001 to 0.01 times the molar amount of 2,3,6-trimethylphenol.

[0016] Preferably, the solvent is water; the mass of the solvent is 2 to 10 times the mass of 2,3,6-trimethylphenol.

[0017] Preferably, the initial oxygen pressure of the first reaction is 3~5 MPa, the temperature of the first reaction is 65~95℃, and the time is 1.2~3h.

[0018] Preferably, the second reaction includes: adding hydrogen peroxide to the first reaction solution to carry out the second reaction; the concentration of the hydrogen peroxide is 20~50wt%; the molar amount of hydrogen peroxide in the hydrogen peroxide is 0.02~0.1 times the molar amount of 2,3,6-trimethylphenol; the addition time of the hydrogen peroxide is 20~60min; and the temperature of the second reaction is not higher than 40℃.

[0019] Preferably, the reducing agent is sodium dithionite, and the molar amount of the reducing agent is 0.01 to 0.05 times the molar amount of 2,3,6-trimethylphenol.

[0020] Preferably, the reduction reaction is carried out at a temperature of 10-50°C for 15-60 minutes.

[0021] This invention provides a method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl, comprising the following steps: mixing 2,3,6-trimethylphenol, alkali, borax, surfactant, catalyst, catalyst ligand, catalyst promoter, and solvent, and carrying out a first reaction under oxygen conditions to obtain a first reaction solution; wherein the catalyst is a copper salt; and the catalyst promoter is cyclodextrin; mixing the first reaction solution with hydrogen peroxide to carry out a second reaction to obtain a second reaction solution; and mixing the second reaction solution with a reducing agent to carry out a reduction reaction to obtain the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl. This invention utilizes an alkali and borax to form a borate buffer system, providing a stable alkaline environment. During the reaction, there is no need to continuously add alkali water to maintain the pH value, simplifying the operation. Furthermore, borax acts as a phenolic hydroxyl stabilizer (forming borate ester complexes), preventing the formation of quinone impurities. After the first reaction, hydrogen peroxide is added to drive the final conversion, followed by the reduction of the peroxidation product using a reducing agent, significantly increasing the product yield. Simultaneously, the obtained product contains very little monomer residue, eliminating the need for purification. Adding cyclodextrin as a catalyst enhances solubility, accelerates the reaction rate, and improves reaction efficiency and monomer conversion. In summary, the preparation method provided by this invention is simple to operate, yields a high product, contains very little monomer residue, requires no purification, and is suitable for industrial production. Detailed Implementation

[0022] This invention provides a method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl, comprising the following steps:

[0023] 2,3,6-Trimethylphenol, alkali, borax, surfactant, catalyst, catalyst ligand, catalyst promoter and solvent are mixed and subjected to a first reaction under oxygen conditions to obtain a first reaction solution; the catalyst is a copper salt and the catalyst promoter is cyclodextrin;

[0024] The first reaction solution and hydrogen peroxide are mixed to carry out a second reaction, resulting in a second reaction solution;

[0025] The second reaction solution and the reducing agent are mixed to carry out a reduction reaction to obtain the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl.

[0026] This invention involves mixing 2,3,6-trimethylphenol, an alkali, borax, a surfactant, a catalyst, a catalyst ligand, a catalyst promoter, and a solvent, and carrying out a first reaction under oxygen conditions to obtain a first reaction solution. In this invention, the alkali is preferably an alkali metal hydroxide, preferably one or both of potassium hydroxide and sodium hydroxide, more preferably sodium hydroxide; the molar amount of the alkali is preferably 0.005 to 0.05 times the molar amount of 2,3,6-trimethylphenol, specifically 0.005, 0.02, or 0.05 times. The role of the alkali is to react with 2,3,6-trimethylphenol, converting it into sodium phenolate, thereby increasing the nucleophilicity and solubility of the phenolic substrate, thus enhancing its activity in subsequent oxidative coupling reactions. Simultaneously, maintaining an alkaline environment can lower the energy barrier of the oxidation reaction, promoting the oxidative coupling process; furthermore, the addition of the alkali can inhibit the formation of acidic byproducts, reduce side reactions, and help improve the purity and yield of the product.

[0027] In this invention, the molar amount of borax is 0.002 to 0.02 times the molar amount of 2,3,6-trimethylphenol, specifically 0.002, 0.005, 0.01, or 0.02 times. The role of borax is to form a borate buffer system with the alkali to maintain the pH value of the system. The alkaline environment is conducive to the oxidative coupling reaction of phenolic compounds, which can promote the formation of phenolate ions and thus enhance their reactivity. In addition, borax also acts as a co-catalyst to form a reversible borate intermediate with the phenolic substrate, which helps to stabilize the reaction intermediate, improve the oxidation selectivity, reduce the occurrence of excessive oxidation side reactions, and improve the reaction yield and product purity.

[0028] In this invention, the surfactant is preferably anionic, and the anionic surfactant is preferably sodium dodecyl sulfate; the molar amount of the surfactant is preferably 0.0005 to 0.02 times the molar amount of 2,3,6-trimethylphenol, specifically 0.001 times. The surfactant in the reaction system can effectively disperse the hydrophobic 2,3,6-trimethylphenol substrate into the aqueous phase, increasing the contact area between reactants and ensuring that dissolved oxygen, catalyst, and phenolic substrate can contact fully and uniformly, thereby improving the reaction rate of the oxidative coupling reaction. Simultaneously, uniform dispersion can also enhance the heat transfer efficiency of the reaction process, reduce the formation of by-products, and help obtain high-purity products.

[0029] In this invention, the catalyst promoter is cyclodextrin, preferably α-cyclodextrin; the molar amount of cyclodextrin is preferably 0.0005 to 0.002 times that of 2,3,6-trimethylphenol, specifically 0.001 times. Cyclodextrin is a cyclic oligosaccharide with a cone-shaped cyclic cavity structure and hydroxyl groups distributed on its exterior, exhibiting internal hydrophobicity and external hydrophilicity. This special structure allows cyclodextrin to encapsulate hydrophobic guest molecules within the cavity to form inclusion complexes, and further form micellar aggregates. In this invention, the role of cyclodextrin is mainly reflected in two aspects: first, by binding to the substrate TMP, it enhances its solubility, alleviating the rate reduction caused by the heterogeneous phase system; second, it enriches the substrate, providing a local high-concentration environment for the reaction, enabling the reaction to maintain high conversion efficiency even in the later stages.

[0030] In this invention, the catalyst is a copper salt, preferably copper acetate, specifically copper acetate monohydrate; the molar amount of the copper salt is preferably 0.0005 to 0.005 times the molar amount of 2,3,6-trimethylphenol, specifically 0.0005, 0.002, or 0.005 times; the catalyst ligand is an acetate, preferably sodium acetate, specifically sodium acetate trihydrate; the molar amount of the catalyst ligand is preferably 0.001 to 0.01 times the molar amount of 2,3,6-trimethylphenol, specifically 0.001, 0.004, or 0.01 times. In a specific embodiment of this invention, it is preferable to prepare a catalyst solution from the catalyst and catalyst ligand, and then add the catalyst solution to the system. This helps to uniformly disperse the catalyst and avoids catalyst deactivation or copper salt precipitation caused by excessively high local concentrations.

[0031] In this invention, the solvent is water; the mass of the solvent is preferably 2 to 10 times the mass of 2,3,6-trimethylphenol, specifically 4 times.

[0032] In this invention, the initial oxygen pressure of the first reaction is preferably 3-5 MPa, specifically 3.5 MPa; the temperature of the first reaction is preferably 65-95°C, specifically 67°C, 75°C, 85°C or 95°C; and the time of the first reaction is preferably 1.2-3 h, specifically 1.2, 1.5, 2 or 3 h.

[0033] In a specific embodiment of the present invention, it is preferable to first mix 2,3,6-trimethylphenol, alkali, borax, surfactant, catalyst aid and solvent, then introduce oxygen into the reaction vessel and heat the system to the temperature of the first reaction, then add the catalyst solution (a mixture of catalyst and catalyst ligand) into the system to carry out the reaction, and stop the reaction when the pressure in the reaction vessel no longer decreases; the solvent of the catalyst solution is preferably water.

[0034] After obtaining the first reaction solution, the present invention mixes the first reaction solution with hydrogen peroxide to carry out a second reaction to obtain a second reaction solution. In the present invention, the second reaction preferably includes: adding hydrogen peroxide to the first reaction solution to carry out the second reaction; the concentration of the hydrogen peroxide is preferably 20-50 wt%, specifically 40 wt%; the molar amount of hydrogen peroxide in the hydrogen peroxide is 0.02-0.1 times the molar amount of 2,3,6-trimethylphenol; the addition time of the hydrogen peroxide is preferably 20-60 min; the temperature of the second reaction is preferably not higher than 40°C, specifically 5-35°C, and the time of the second reaction is based on the addition time of the hydrogen peroxide.

[0035] In a specific embodiment of the present invention, after the first reaction is completed, the heater in the reactor is turned off, and the temperature of the material inside the reactor is lowered to 5-35°C. The pressure inside the reactor is released, and hydrogen peroxide is added to the reactor at a uniform rate. During the addition, stirring is maintained, and the temperature of the material inside the reactor is controlled not to exceed 40°C. The second reaction is considered complete after the hydrogen peroxide has been added. In the present invention, the second reaction is used to oxidize colored impurities and unreacted substrates or intermediates. Hydrogen peroxide can generate active oxygen species in an alkaline residual environment, further completing the reaction and increasing the reaction conversion rate. By controlling the addition rate of hydrogen peroxide, the present invention can avoid violent exothermic reactions or decomposition of hydrogen peroxide, thereby ensuring operational safety and oxidation efficiency.

[0036] After obtaining the second reaction solution, the present invention mixes the second reaction solution with a reducing agent to carry out a reduction reaction to obtain the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl. In the present invention, the reducing agent is preferably sodium dithionite, and the molar amount of the reducing agent is preferably 0.01 to 0.05 times the molar amount of 2,3,6-trimethylphenol, specifically 0.01, 0.03, or 0.05 times; the temperature of the reduction reaction is preferably 10 to 50°C, more preferably 35 to 40°C, and the time is preferably 15 to 60 minutes; in the present invention, sodium dithionite, as a strong reducing agent, can convert the generated dibenzoquinone structural byproduct into the product through the reduction reaction, increasing the reaction yield; at the same time, the reduction step can convert other impurities into substances that are easier to remove, and a high-purity product can be obtained by combining with simple rinsing.

[0037] After the reduction reaction, the present invention preferably performs post-treatment on the obtained product solution; the post-treatment preferably includes: acidifying the product solution to precipitate the product, followed by filtration, washing and drying to obtain 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl; the acid used for acidification preferably includes one or more of hydrochloric acid, sulfuric acid, nitric acid, and acetic acid, more preferably hydrochloric acid; the pH value of the acidification is preferably 4.5~5.5, specifically 5; during the acidification process, the product changes from a sodium phenolate structure to a phenolic structure, and in water... The solubility decreases, resulting in significant precipitation; the filtration is preferably vacuum filtration; the washing is preferably performed sequentially with hot water and an organic solvent, or with cold water rinsing, wherein the organic solvent is preferably one or more of toluene, methanol, and ethanol, more preferably toluene; the present invention removes residual water-soluble and organic impurities from the material through washing; the drying is preferably vacuum drying, the drying temperature is preferably 60~90℃, and the drying is preferably performed until the moisture content of the material is less than 0.1%; the drying is carried out at a low temperature to avoid thermal decomposition or oxidation of the product.

[0038] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0039] Example 1

[0040] Add 10.9 kg (1 eq, 80 mol, 136.2 Da) of 2,3,6-trimethylphenol, 64.0 g (0.02 eq, 1.6 mol, 40 Da) of sodium hydroxide, 153 g (0.005 eq, 0.4 mol, 381.4 Da) of borax, 23.1 g (0.001 eq, 0.08 mol, 288.4 Da) of sodium dodecyl sulfate, 77.8 g (0.001 eq, 0.08 mol, 972 Da) of α-cyclodextrin, and 43.6 kg of pure water to a stainless steel reactor. Turn on the stirring and heating functions of the reactor, heat the materials inside to 65°C, and dissolve and mix them under stirring. Close the reactor and check that the sealing performance is good. Replace the atmosphere inside the reactor with oxygen and then fill the reactor with oxygen until the pressure inside the reactor reaches 3.5 MPa. The reaction system temperature was raised from 65℃ to 85℃. 31.9 g (0.002 eq, 0.16 mol, 199.6 Da) of copper acetate monohydrate and 43.6 g (0.004 eq, 0.32 mol, 136.1 Da) of sodium acetate trihydrate were dissolved in 150 g of hot water to prepare a catalyst solution. This catalyst solution was added to the reactor through a constant pressure feeder, and the reaction was continued at this temperature. The reaction was maintained at this temperature for 1.5 h, during which the pressure inside the reactor continuously decreased to below 0.25 MPa and stopped decreasing. The reactor heater was then turned off, and the temperature of the material inside the reactor was lowered to 35℃. The pressure inside the reactor was released, and 340 g (0.05 eq, 4 mol, 34 Da, 40 wt%) of hydrogen peroxide was uniformly added to the reactor over 30 min, while stirring was maintained and the temperature of the material inside the reactor was controlled to not exceed 40℃. After oxidation, 418 g (0.03 eq, 2.4 mol, 174 Da) of sodium dithionite was added to the reactor, and the reaction was continued with stirring for 15 min. A 35% hydrochloric acid solution was slowly added to the material while continuously stirring, adjusting the pH of the solution to 5. The material was filtered using a vacuum filtration device to obtain a solid crude product. The solid filter cake was rinsed with cold water and then dried in a vacuum dryer at 80℃ until the moisture content was below 0.1%, yielding 10.18 kg of white powder. Samples of the product were taken and analyzed according to the specifications in GB / T 16631-2019. High-performance liquid chromatography (HPLC) was used to quantitatively analyze the content of 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl and other impurities using the external standard method, and the yield was calculated. The data showed that the product purity was 99.2%, the impurity hexamethylbiphenylquinone content was 0.02%, and the reaction yield was 93.4%.

[0041] Examples 2-4

[0042] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same scheme as in Example 1. During the feeding stage into the reactor, the amount of borax added was changed from 153 g (0.005 eq, 0.4 mol, 381.4 Da) in Example 1 to 305 g (0.01 eq, 0.8 mol, 381.4 Da) in Example 2, 610 g (0.02 eq, 1.6 mol, 381.4 Da) in Example 3, and 61 g (0.002 eq, 0.16 mol, 381.4 Da) in Example 4, respectively. Except for the change in the amount of borax added, the amounts of other raw materials and the operating steps of each process remained consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same scheme as in Example 1.

[0043] Examples 5-6

[0044] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same scheme as in Example 1. During the feeding stage into the reactor, the amount of sodium hydroxide added was changed from 64.0 g (0.02 eq, 1.6 mol, 40 Da) in Example 1 to 16 g (0.005 eq, 0.4 mol, 40 Da) in Example 5 and 160 g (0.05 eq, 4 mol, 40 Da) in Example 6. Except for the change in the amount of sodium hydroxide added, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same scheme as in Example 1.

[0045] Examples 7-8

[0046] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same scheme as in Example 1. After the materials in the reactor were heated and dissolved, the amounts of copper acetate monohydrate and sodium acetate trihydrate added to the copper acetate monohydrate solution were adjusted from 31.9 g (0.002 eq, 0.16 mol, 199.6 Da) of copper acetate monohydrate and 43.6 g (0.004 eq, 0.32 mol, 136.1 Da) of sodium acetate trihydrate in Example 1. The amounts of copper acetate monohydrate and sodium acetate trihydrate were changed to 8.0 g (0.0005 eq, 0.04 mol, 199.6 Da) and 10.9 g (0.001 eq, 0.08 mol, 136.1 Da) respectively in Example 7, and 79.8 g (0.005 eq, 0.4 mol, 199.6 Da) and 108.9 g (0.01 eq, 0.8 mol, 136.1 Da) respectively in Example 8. Except for the change in the amount of catalyst, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same scheme as in Example 1.

[0047] Examples 9-10

[0048] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same scheme as in Example 1. After the reaction was completed and the pressure in the reactor was released, the amount of hydrogen peroxide added was changed from 340 g (0.05 eq, 4 mol, 34 Da, 40%) in Example 1 to 680 g (0.1 eq, 8 mol, 34 Da, 40%) in Example 9 and 136 g (0.02 eq, 1.6 mol, 34 Da, 40%) in Example 10. Except for the change in the amount of hydrogen peroxide added, the amounts of other raw materials and the operating steps of each process were consistent with those in Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain solid products. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same scheme as in Example 1.

[0049] Examples 11-12

[0050] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same scheme as in Example 1. After adding hydrogen peroxide, the amount of sodium dithionite to be added was changed from 418 g (0.03 eq, 2.4 mol, 174 Da) in Example 1 to 696 g (0.05 eq, 4 mol, 174 Da) in Example 11 and 139.2 g (0.01 eq, 0.8 mol, 174 Da) in Example 12. Except for the change in the amount of sodium dithionite, the amounts of other raw materials and the operating steps of each process were consistent with those in Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain solid products. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same scheme as in Example 1.

[0051] Examples 13-15

[0052] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. After the materials were dissolved, the temperature inside the reactor was raised to the reaction temperature, which was changed from 85°C in Example 1 to 95°C in Example 13, 75°C in Example 14, and 65°C in Example 15, respectively. Except for the change in reaction temperature, the feeding and operation steps were consistent with those in Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain solid products. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0053] Examples 16-18

[0054] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. The reaction started after the addition of copper acetate solution. The reaction time was changed from 1.5 h in Example 1 to 2 h in Example 16, 3 h in Example 17, and 1.2 h in Example 18, respectively. Except for the change in reaction time, the feeding and operation steps were consistent with those in Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain solid products. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0055] Comparative Example 1

[0056] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. During the feeding stage into the reactor, the amount of borax added was changed from 153 g (0.005 eq, 0.4 mol, 381.4 Da) in Example 1 to 0 in Comparative Example 1, i.e., no borax was added. Except for the change in the amount of borax added, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0057] Comparative Example 2

[0058] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. During the feeding stage into the reactor, the amount of sodium hydroxide added was changed from 64.0 g (0.02 eq, 1.6 mol, 40 Da) in Example 1 to 0 in Comparative Example 2, i.e., no sodium hydroxide was added. Except for the change in the amount of sodium hydroxide added, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0059] Comparative Example 3

[0060] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. After the reaction was completed and the pressure in the reactor was released, the amount of hydrogen peroxide added was changed from 340 g (0.05 eq, 4 mol, 34 Da, 40%) in Example 1 to 0 in Comparative Example 3, i.e., no hydrogen peroxide was added. Except for the change in the amount of hydrogen peroxide, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain solid products. Samples of the copolymer products obtained in each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0061] Comparative Example 4

[0062] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. After adding hydrogen peroxide, the amount of sodium dithionite to be added was changed from 418 g (0.03 eq, 2.4 mol, 174 Da) in Example 1 to 0 in Comparative Example 4, i.e., no sodium dithionite was added. Except for the change in the amount of sodium dithionite, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0063] Comparative Example 5

[0064] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. After the reaction was completed and the pressure in the reactor was released, hydrogen peroxide and sodium dithionite were not added before proceeding with post-processing. Except for the omission of hydrogen peroxide and sodium dithionite, the amounts of other raw materials and the operational steps of each process were consistent with those in Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0065] Comparative Example 6

[0066] 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl was prepared according to the same procedure as in Example 1. During the feeding stage into the reactor, the amount of α-cyclodextrin was changed from 77.8 g (0.001 eq, 0.08 mol, 972 Da) in Example 1 to 0 in Comparative Example 1, i.e., no α-cyclodextrin was added. Except for the change in the amount of α-cyclodextrin during feeding, the amounts of other raw materials and the operating steps of each process were consistent with Example 1. After the reaction was completed, each example underwent post-processing in the same manner as in Example 1 to obtain a solid product. Samples of the copolymer products obtained from each example were taken, and the purity of the products was tested and the reaction yield was calculated according to the same procedure as in Example 1.

[0067] The test data of the above embodiments were compiled and statistically analyzed, and the results are shown in Table 1:

[0068] Table 1 Test Results

[0069]

[0070] As can be seen from the results in Table 1, the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl prepared in the embodiments of the present invention has a high yield, low content of impurities quinone and TMP monomer, and high purity. In Comparative Example 1, the use of borax was omitted, and in Comparative Example 2, the use of sodium hydroxide was omitted, which prevented the formation of a borate buffer system. The pH value fluctuated greatly during the reaction, resulting in a decrease in the yield and purity of the obtained product, and an increase in the residual amount of impurities quinone and TMP monomer. In Comparative Example 3, the step of adding hydrogen peroxide for the second oxidation was omitted, in Comparative Example 4, the step of using sodium dithionite for reduction was omitted, and in Comparative Example 5, the step of adding hydrogen peroxide was omitted in order to use sodium dithionite for reduction. The yield and purity of the obtained product decreased, especially the residual amount of TMP monomer increased. In Comparative Example 6, the use of cyclodextrin was omitted, and under the same reaction time, the yield and purity of the product decreased significantly.

[0071] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl, characterized in that, Includes the following steps: 2,3,6-Trimethylphenol, alkali, borax, surfactant, catalyst, catalyst ligand, catalyst promoter, and solvent are mixed and subjected to a first reaction under oxygen conditions to obtain a first reaction solution; the catalyst is a copper salt; the catalyst promoter is cyclodextrin; the alkali is an alkali metal hydroxide; the surfactant is an anionic surfactant; the copper salt is copper acetate; the catalyst ligand is sodium acetate; the temperature of the first reaction is 65~95℃, and the time is 1.2~3h; The first reaction solution and hydrogen peroxide are mixed to carry out a second reaction to obtain a second reaction solution; the temperature of the second reaction is not higher than 40°C. The second reaction solution and the reducing agent are mixed to carry out a reduction reaction to obtain the 2,2',3,3',5,5'-hexamethyl-4,4'-dihydroxybiphenyl; the reducing agent is sodium dithionite.

2. The preparation method according to claim 1, characterized in that, The molar amount of the base is 0.005 to 0.05 times the molar amount of 2,3,6-trimethylphenol.

3. The preparation method according to claim 1, characterized in that, The molar amount of borax is 0.002 to 0.02 times the molar amount of 2,3,6-trimethylphenol.

4. The preparation method according to claim 1, characterized in that, The molar amount of the surfactant is 0.0005 to 0.02 times the molar amount of 2,3,6-trimethylphenol.

5. The preparation method according to claim 1, characterized in that, The cyclodextrin is α-cyclodextrin; the molar amount of the cyclodextrin is 0.0005 to 0.002 times the molar amount of 2,3,6-trimethylphenol; The molar amount of the copper salt is 0.0005 to 0.005 times the molar amount of 2,3,6-trimethylphenol; the molar amount of the catalyst ligand is 0.001 to 0.01 times the molar amount of 2,3,6-trimethylphenol.

6. The preparation method according to claim 1, characterized in that, The solvent is water; the mass of the solvent is 2 to 10 times the mass of 2,3,6-trimethylphenol.

7. The preparation method according to claim 1, characterized in that, The initial oxygen pressure for the first reaction is 3-5 MPa.

8. The preparation method according to claim 1, characterized in that, The second reaction includes: adding hydrogen peroxide at a constant rate to the first reaction solution to carry out the second reaction; the concentration of the hydrogen peroxide is 20~50wt%; the molar amount of hydrogen peroxide in the hydrogen peroxide is 0.02~0.1 times the molar amount of 2,3,6-trimethylphenol; and the addition time of the hydrogen peroxide is 20~60min.

9. The preparation method according to claim 1, characterized in that, The molar amount of the reducing agent is 0.01 to 0.05 times the molar amount of 2,3,6-trimethylphenol.

10. The preparation method according to claim 1, characterized in that, The reduction reaction is carried out at a temperature of 10~50℃ for a time of 15min~60min.

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