An optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenol
By employing a staged oxidation method and a post-treatment process involving acid dissolution and alkali precipitation, the problems of low product yield and environmental pollution in the synthesis of 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine were solved, achieving efficient and low-cost production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- CHONGQING TECH & BUSINESS UNIV
- Filing Date
- 2026-05-12
- Publication Date
- 2026-07-24
AI Technical Summary
Existing technologies for synthesizing 3,3',5,5'-tetramethyl-2,2'-biphenyldiol suffer from low product yields, complex operations, high costs, and severe environmental pollution, and lack effective means for separating and purifying raw materials and products.
A staged oxidation method is adopted, first using hydrogen peroxide and then sodium persulfate for oxidation, combined with a post-treatment process of acid dissolution and alkali precipitation, to recover raw materials and reduce the generation of waste salt.
It improves product yield, reduces production costs, simplifies operating procedures, reduces environmental pollution, and is suitable for large-scale production.
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Figure CN122444575A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis, specifically to a novel method for the synthesis and post-processing of 3,3',5,5'-tetramethyl-2,2'-biphenyl. Background Technology
[0002] In the field of organic chemistry, biphenols are considered a crucial structural unit, widely found in various natural products and drug molecules. Among various biphenol derivatives, 3,3',5,5'-tetramethyl-2,2'-biphenyldiol has been extensively studied and applied due to its excellent thermal stability. It can be used not only as a modifying monomer for the preparation of high-performance engineering plastics and composite materials, but also as a rubber anti-aging agent, plastic antioxidant, and stabilizer for dye intermediates. Furthermore, it can also be used as an intermediate in the synthesis of various phosphorus-containing ligand catalysts.
[0003] Several methods exist for synthesizing 3,3',5,5'-tetramethyl-2,2'-biphenyl, mainly including photocatalysis, electrochemical catalysis, and oxidative coupling. ACS Catal. 2020, 10, 14615−14623 and Eur. J. Org. Chem. 2022, e202101469, among others, report the preparation of this compound using photocatalysis in an oxygen atmosphere; however, the product yield of this method is low, with a maximum of only 55%. On the other hand, Chem. Eur. J. 2021, 27, 8252−8263 and ACS Appl. Mater. Interfaces 2023, 15, 42, 49595−49610, among others, introduce an electrochemical catalytic synthesis route. Its core principle is based on a dehydrogenation coupling reaction initiated by anodic oxidation. Using 2,4-dimethylphenol as a starting material, C-C bonds are formed on the anode surface through an electron transfer process, thereby obtaining the target product. However, this electrochemical method suffers from problems such as complex operation steps and long reaction time, which reduces atom economy.
[0004] Direct oxidative coupling is the most ideal strategy for constructing biphenol compounds. This strategy mainly relies on the direct oxidative coupling reaction of double C-H bonds to construct C-C bonds. This route has attracted much attention due to its simple steps and high atom economy. Org. Lett. 2018, 20, 4077−4080 reported the preparation of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol in a DCM / TFA solvent system using nitrosium tetrafluoroborate as the terminal oxidant. Although nitrosium salt is a strong single-electron oxidant, the product yield synthesized by this method was only 41%, and the selectivity and product yield of this reaction still need to be further improved. Molecular oxygen is one of the most common and ideal oxidants, and its use for the selective oxidative functionalization of C-H bonds has become one of the key technologies for achieving green synthesis. Eur. J. Org. Chem. 2013, 1861−1866 reported the oxidative coupling preparation of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol from phenolic compounds under an oxygen atmosphere using cobalt(II)-porphyrin T(p-OMe)PPCo as a catalyst. This method is mild, simple to operate, and low in cost, but the product yield is only 46% and it is time-consuming. J. Org. Chem. 2004, 69, 17, 5660−5667 and Chem. Commun. 2017, 53, 9616−9619, among others, reported the preparation of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol using persulfate as an oxidant without any catalyst. Although this method uses inexpensive and readily available raw materials and achieves a yield of over 70%, it easily generates asymmetric biphenyldiol byproducts. Patent CN105272826 discloses an oxidative coupling route using selenium dioxide as the oxidant, but the cost of selenium dioxide is much higher than that of other oxidants. Patent US6077979A reports the preparation of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol under Na2S2O8 / FeSO4 or hydrogen peroxide / FeCl3 oxidation conditions. The raw material conversion rate reaches over 95% under the Na2S2O8 / FeSO4 oxidation system, but the amount of oxidant added is greatly excessive; under the hydrogen peroxide / FeCl3 oxidation conditions, the raw material conversion rate decreases to 80%. Both methods yield brick-red solid crude products, and there is a lack of effective impurity separation methods. Patent CN101155768A improved the Na2S2O8 / FeSO4 oxidation system. The amount of oxidant Na2S2O8 added can be reduced to 0.6 times the molar amount of the raw material 2,4-dimethylphenol. An organic solvent (toluene or petroleum ether) is added to the system to improve the oxidation conditions. However, the yield is reduced to 61%, and the unreacted raw materials are not recovered.
[0005] The literature and patents mentioned above, apart from column chromatography, mostly lack effective methods for separating and purifying raw materials and products. In the preparation of 3,3',5,5'-tetramethyl-2,2'-biphenyl, the product obtained after the reaction is a brick-red solid containing Fe. 3+ Unreacted 2,4-dimethylphenol is difficult to remove. When hydrogen peroxide oxidizes monophenols alone, the oxidation conversion rate is low; when using Na2S2O8 for oxidative coupling, the large molecular weight of sodium persulfate requires a large amount of oxidant, and sodium persulfate is expensive, resulting in high preparation costs; furthermore, after oxidative coupling with sodium persulfate, the sodium persulfate is reduced to sodium sulfate, generating excessive amounts of waste salt. This invention employs a staged oxidation process, first using hydrogen peroxide followed by sodium persulfate oxidation. This method requires only half the amount of sodium persulfate used in other patents, and the resulting product can be purified, allowing for raw material recovery. This not only saves costs but also avoids high-temperature recrystallization, improving both overall yield and product quality. Furthermore, the mixed oxidation mode significantly reduces waste salt generation, greatly minimizing environmental pollution. Summary of the Invention
[0006] The technical problem to be solved by this invention is to provide an optimized synthesis process for 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine. This synthesis method is simple to operate, achieves complete oxidation, and the post-processing can recover raw materials, reducing material costs. It is also simple and easy to implement.
[0007] An optimized synthetic process for 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine, the synthetic route of which is shown in the figure below, is characterized by comprising the following steps:
[0008]
[0009] (1) 2,4-Dimethylphenol, FeCl3, sulfuric acid and hydrogen peroxide are placed in water to carry out the first stage of oxidation reaction, and then sodium persulfate is added to the reaction solution to carry out the second stage of oxidation reaction.
[0010] (2) After the reaction is completed, the solid and liquid phases are separated by filtration, and the aqueous phase is extracted with a low-boiling-point organic solvent to recover the monophenols in the aqueous phase.
[0011] (3) Adjust the pH of the solid phase to alkaline to dissolve the sodium diphenolate, and then react the Fe complexed with the phenol. 3+ It is converted into Fe(OH)3 precipitate, filtered, and liquid phase 1 is taken. The liquid phase is 3,3',5,5'-tetramethyl-2,2'-biphenyl sodium salt.
[0012] (4) First add ethanol to liquid phase 1, then adjust the pH to acidic so that 3,3',5,5'-tetramethyl-2,2'-biphenyldiphenol is in a precipitate state and the monophenol is in a dissolved state. Filter, and the solid is 3,3',5,5'-tetramethyl-2,2'-biphenyldiphenol.
[0013] (5) Remove ethanol from the ethanol-water solution of monophenol by vacuum distillation, and then extract with a low-boiling organic solvent to recover monophenol from the aqueous phase.
[0014] In step (1), the molar amount of hydrogen peroxide in the hydrogen peroxide solution is 0.25 to 0.3 times the molar amount of 2,4-dimethylphenol.
[0015] Furthermore, in step (1), the molar amount of sodium persulfate is 0.25 to 0.3 times the molar amount of 2,4-dimethylphenol.
[0016] Furthermore, in step (1), the oxidation method is a staged oxidation, first using hydrogen peroxide for the first stage of oxidation, and then using sodium persulfate for the second stage of oxidation.
[0017] Furthermore, the oxidation reaction temperature in step (1) is 25~50 ℃.
[0018] Furthermore, the low-boiling-point organic solvent in steps (2) and (5) is dichloromethane, ethyl acetate, or toluene.
[0019] Furthermore, the final alkaline pH in step (3) is controlled at 12-14.
[0020] Furthermore, the dissolution temperature in step (3) is 45~65 ℃.
[0021] Furthermore, the volume ratio of ethanol to water in step (4) is 1 / 2 to 3 / 2.
[0022] Furthermore, the final pH of the acidity in step (4) is controlled at 3 to 5.
[0023] The beneficial effects of this invention are:
[0024] This invention employs two oxidants in a staged oxidation process, reducing reaction costs compared to traditional synthetic routes. The post-treatment uses acid dissolution and alkali precipitation to avoid high-temperature recrystallization. The entire synthetic route allows for the recycling of raw materials, saving costs and reducing environmental pollution. The entire synthesis and post-treatment process is simple to operate and suitable for large-scale production. Attached Figure Description
[0025] Figure 1 This is a schematic flowchart of an optimized synthesis process for 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to the present invention.
[0026] Figure 2 This is an image of 3,3',5,5'-tetramethyl-2,2'-biphenyl before post-processing.
[0027] Figure 3 This is a post-processed image of 3,3',5,5'-tetramethyl-2,2'-biphenyl.
[0028] Figure 4 2,4-Dimethylphenol as a raw material 1 H NMR.
[0029] Figure 5 The 3,3',5,5'-tetramethyl-2,2'-biphenyl hydroquinone before post-treatment in Example 1 1 H NMR.
[0030] Figure 6 The 3,3',5,5'-tetramethyl-2,2'-biphenyl hydroquinone before post-treatment in Example 1 1 High-field magnified image of H NMR.
[0031] Figure 7 The post-treatment of 3,3',5,5'-tetramethyl-2,2'-biphenyl hydroquinone after Example 1 1 H NMR. Detailed Implementation
[0032] The embodiments of the present invention will now be described in detail with reference to examples.
[0033] Example 1:
[0034] The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine includes the following steps:
[0035] (1) 4.06 g (0.025 mol) FeCl3, 1 L water, 5 g dilute sulfuric acid and 61.08 g (0.5 mol) 2,4-dimethylphenol were added sequentially to a 2 L flask and stirred at 35 °C for 10 minutes. Then, 28.33 g of 15% (0.125 mol) hydrogen peroxide was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for 1 hour, and then sodium persulfate solution (29.76 g sodium persulfate dissolved in 60 mL water) was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for another 17 hours.
[0036] (2) After the reaction was completed, the mixture was filtered to obtain an aqueous phase and a solid. 300 mL of dichloromethane was added to the aqueous phase for extraction to recover 2,4-dimethylphenol from the aqueous phase. 0.92 g of 2,4-dimethylphenol was obtained by vacuum distillation.
[0037] (3) Add the solid to 400 mL of water, adjust the pH to about 12 with NaOH solution, stir at 50°C for 30 minutes, filter out the insoluble matter (including ferric hydroxide and other oxidation byproducts), and take the liquid phase.
[0038] (4) Add 200 mL of ethanol to the liquid phase, and add sulfuric acid dropwise to adjust the pH of the solution to about 3. During this process, precipitate will continuously form. After filtration, the solid is 3,3',5,5'-tetramethyl-2,2'-biphenylhydrophenol, and the liquid phase is an ethanol-water solution of monophenol. Dry the 3,3',5,5'-tetramethyl-2,2'-biphenylhydrophenol to obtain 50.94 g.
[0039] (5) The ethanol-water solution of monophenol was subjected to vacuum distillation to remove the ethanol, and then extracted with 150 mL of dichloromethane to recover the monophenol in the aqueous phase. A mixture of 6.33 g of 2,4-dimethylphenol and a small amount of 3,3',5,5'-tetramethyl-2,2'-biphenyl was obtained by vacuum distillation. A total of 7.25 g of raw materials were recovered in two batches (of which 3,3',5,5'-tetramethyl-2,2'-biphenyl was the product and not an impurity. For the convenience of calculation, it was regarded as a raw material).
[0040] according to Figures 4-6 The material balance for Example 1 is as follows:
[0041]
[0042] Where 2.00 is H in 3,3',5,5'-tetramethyl-2,2'-biphenyldiol. i The integral area, 0.30, represents the H in 2,4-dimethylphenol. b The integral area.
[0043]
[0044]
[0045]
[0046] 122.16 and 242.32 are the relative molecular masses of 2,4-dimethylphenol and 3,3',5,5'-tetramethyl-2,2'-biphenyl, respectively.
[0047] After deducting recycled materials,
[0048] Example 2:
[0049] The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine includes the following steps:
[0050] (1) 8.11 g (0.05 mol) FeCl3, 2 L water, 10 g dilute sulfuric acid and 122.16 g (1 mol) 2,4-dimethylphenol were added sequentially to a 5 L flask and stirred at 40 °C for 10 minutes. Then, 68 g of 15% (0.3 mol) hydrogen peroxide was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for 1 hour, and then sodium persulfate solution (47.62 g sodium persulfate dissolved in 100 mL water) was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for another 17 hours.
[0051] (2) After the reaction was completed, the mixture was filtered to obtain an aqueous phase and a solid. 500 mL of ethyl acetate was added to the aqueous phase for extraction to recover 2,4-dimethylphenol from the aqueous phase. 1.75 g of 2,4-dimethylphenol was obtained by vacuum distillation.
[0052] (3) Add the solid to 800 mL of water, adjust the pH to about 13 with NaOH solution, stir at 50°C for 30 minutes, filter out the insoluble matter (including ferric hydroxide and other oxidation byproducts), and take the liquid phase.
[0053] (4) Add 800 mL of ethanol to the liquid phase, and then adjust the pH to about 3.5. During this process, precipitates will continuously form. After filtration, the solid is 3,3',5,5'-tetramethyl-2,2'-biphenyl, and the liquid phase is an ethanol-water solution of monophenol. The 3,3',5,5'-tetramethyl-2,2'-biphenyl is dried to obtain 101.53 g.
[0054] (5) The ethanol-water solution of monophenol was subjected to vacuum distillation to remove the ethanol, and then extracted with 250 mL of ethyl acetate to recover the monophenol in the aqueous phase. A mixture of 12.11 g of 2,4-dimethylphenol and a small amount of 3,3',5,5'-tetramethyl-2,2'-biphenyl was obtained by vacuum distillation. The single-pass yield was calculated to be 83.80%, and the overall yield after deducting the recovered raw materials was 94.61%.
[0055] Example 3:
[0056] The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine includes the following steps:
[0057] (1) 16.22 g (0.1 mol) FeCl3, 4 L water, 20 g dilute sulfuric acid and 242.32 g (2 mol) 2,4-dimethylphenol were added sequentially to a 10 L flask and stirred at 45 °C for 10 minutes. Then, 158.66 g of 15% (0.7 mol) hydrogen peroxide was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for 1 hour, and then sodium persulfate solution (71.43 g sodium persulfate dissolved in 150 mL water) was slowly added dropwise over 3 hours. After the addition was complete, the mixture was stirred for another 17 hours.
[0058] (2) After the reaction was completed, the mixture was filtered to obtain an aqueous phase and a solid. 800 mL of toluene was added to the aqueous phase for extraction to recover 2,4-dimethylphenol from the aqueous phase. 3.35 g of 2,4-dimethylphenol was obtained by vacuum distillation.
[0059] (3) Add the solid to 1500 mL of water, adjust the pH to about 14 with NaOH solution, stir at 50°C for 30 minutes, filter out the insoluble matter (including ferric hydroxide and other oxidation byproducts), and take the liquid phase.
[0060] (4) Add 1000 mL of ethanol to the liquid phase, and then adjust the pH to about 4. During this process, precipitates will continuously form. After filtration, the solid is 3,3',5,5'-tetramethyl-2,2'-biphenylhydrophenol, and the liquid phase is an ethanol-water solution of monophenol. The 3,3',5,5'-tetramethyl-2,2'-biphenylhydrophenol is dried to obtain 202.16 g.
[0061] (5) The ethanol-water solution of monophenol was subjected to vacuum distillation to remove the ethanol, followed by extraction with 400 mL of toluene to recover the monophenol from the aqueous phase. A mixture of 23.47 g of 2,4-dimethylphenol and a small amount of 3,3',5,5'-tetramethyl-2,2'-biphenyl was obtained by vacuum distillation. The calculated single-pass yield was 83.43%, and the overall yield after deducting the recovered raw materials was 93.71%.
[0062] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Those skilled in the art will recognize various modifications and variations of the embodiments of the present invention. Any modifications, equivalent substitutions, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. An optimized synthetic process for 3,3',5,5'-tetramethyl-2,2'-biphenylhydrazine, characterized in that, Includes the following steps: (1) 2,4-Dimethylphenol, FeCl3, sulfuric acid and hydrogen peroxide are placed in water to carry out the first stage of oxidation reaction, and then sodium persulfate is added to the reaction solution to carry out the second stage of oxidation reaction. (2) After the reaction is completed, the solid and liquid phases are separated by filtration, and the aqueous phase is extracted with a low-boiling-point organic solvent to recover the monophenols in the aqueous phase. (3) Adjust the pH of the solid phase to alkaline to dissolve the sodium diphenolate, and then react the Fe complexed with the phenol. 3+ It is converted into Fe(OH)3 precipitate, filtered, and liquid phase 1 is taken. The liquid phase is 3,3',5,5'-tetramethyl-2,2'-biphenyl sodium salt. (4) First add ethanol to liquid phase 1, then adjust the pH to acidic so that 3,3',5,5'-tetramethyl-2,2'-biphenyldiphenol is in a precipitate state and the monophenol is in a dissolved state. Filter, and the solid is 3,3',5,5'-tetramethyl-2,2'-biphenyldiphenol. (5) Remove ethanol from the ethanol-water solution of monophenol by vacuum distillation, and then extract with a low-boiling organic solvent to recover monophenol from the aqueous phase.
2. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... In step (1), the molar amount of hydrogen peroxide in the hydrogen peroxide solution is 0.25 to 0.3 times the molar amount of 2,4-dimethylphenol.
3. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The molar amount of sodium persulfate in step (1) is 0.25 to 0.3 times the molar amount of 2,4-dimethylphenol.
4. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The oxidation method in step (1) is a staged oxidation, first using hydrogen peroxide for the first stage of oxidation, and then using sodium persulfate for the second stage of oxidation.
5. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The oxidation reaction temperature in step (1) is 25~50℃.
6. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The low-boiling-point organic solvents in steps (2) and (5) are dichloromethane, ethyl acetate, or toluene.
7. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The final alkaline pH in step (3) is controlled at 12-14.
8. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The dissolution temperature in step (3) is 45~65 ℃.
9. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The volume ratio of ethanol to water in step (4) is 1 / 2 to 3 / 2.
10. The optimized synthesis process of 3,3',5,5'-tetramethyl-2,2'-biphenyldiol according to claim 1, characterized in that... The final acid pH in step (4) is controlled at 3-5.