A method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid

Abstract

This application relates to the field of pesticide intermediate synthesis technology, specifically disclosing a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid includes the following steps: 1) subjecting 2-nitro-4-trifluoromethylbenzonitrile to a methylsulfonation reaction to obtain 2-methylthio-4-trifluoromethylbenzonitrile; 2) subjecting the 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1) to an oxidation reaction under the action of a catalyst to obtain 2-methylsulfonyl-4-trifluoromethylbenzonitrile; 3) subjecting the 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) to an alkaline hydrolysis reaction, followed by an acidification reaction to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid. The synthesis method of this application has the advantages of high reaction efficiency, few process steps, and high yield.

Description

Technical Field

[0001] This application relates to the field of pesticide intermediate synthesis technology, and more specifically, it relates to a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid. Background Technology

[0002] With the continuous development of the pesticide industry, the application of herbicides has become quite widespread, with approximately 85% of crops using herbicides. At the same time, herbicides are developing towards a general trend of lower toxicity, lower dosage, higher activity, and lower residues. To this end, technicians have developed benzoylpyrazole herbicides, such as sulfoacetamide, isoxaflutole, and bispyribac-sodium, which are a class of highly active, low-toxicity, and broad-spectrum herbicides.

[0003] 2-Methylsulfonyl-4-trifluoromethylbenzoic acid is an important intermediate in the synthesis of benzoylpyrazole herbicides. Currently, there are many synthetic routes for 2-methylsulfonyl-4-trifluoromethylbenzoic acid. One route uses 2-methylthio-4-trifluoromethylbenzonitrile as the starting material, first reacting it with hydrogen peroxide under a catalyst to produce 2-methylsulfonyl-4-trifluoromethylbenzonitrile. In this oxidation process, the methylthio group is oxidized to the methylsulfonyl group. Then, 2-methylsulfonyl-4-trifluoromethylbenzonitrile undergoes alkaline hydrolysis and acidification, converting the cyano group to the formic acid group to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid. However, this route has a relatively low oxidation reaction efficiency.

[0004] For example, o-nitro-p-trifluoromethylbenzoic acid is prepared by hydrolysis of o-nitro-p-trifluoromethylbenzonitrile. During this process, the trifluoromethyl group on the benzene ring is unstable in strong acids and at high temperatures, generating a certain amount of byproducts. Another method involves obtaining o-nitro-p-trifluoromethylbenzoic acid from p-chlorotrifluorotoluene through nitration, oxidative hydrolysis, and then further processing it through esterification, thiolation, and oxidation. However, this process involves numerous steps, low efficiency, and high cost. Summary of the Invention

[0005] To further improve the synthesis efficiency and yield of 2-methylsulfonyl-4-trifluoromethylbenzoic acid, this application provides a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0006] In a first aspect, this application provides a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, using the following technical solution:

[0007] A method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, comprising the following steps:

[0008] 1) 2-Nitro-4-trifluoromethylbenzonitrile was prepared by methylsulfidation reaction;

[0009] 2) The 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1) is oxidized under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile;

[0010] 3) The 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) is first subjected to an alkaline hydrolysis reaction, and then subjected to an acidification reaction to prepare 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0011] Preferably, step 1) further includes at least one of the following technical features:

[0012] 11) The methyl sulfidation reaction is carried out in a solvent, wherein the solvent is one of DMF, DMSO, and DCM;

[0013] 12) The sulfur source for the methyl sulfide reaction is one of sodium sulfide, potassium sulfide, or sodium methanethiol;

[0014] 13) The temperature of the methyl sulfidation reaction is less than 25°C.

[0015] Preferably, step 2) further includes at least one of the following technical features:

[0016] 21) The catalyst includes a main catalyst and a co-catalyst, wherein the main catalyst is a heteropoly acid;

[0017] 22) The oxidizing agent in the oxidation reaction is hydrogen peroxide;

[0018] 23) The oxidation reaction is carried out at a temperature of 80-85℃ for 5-10 hours.

[0019] Preferably, the heteropolyacid is one of sodium tungstate, potassium tungstate, and cobalt tungstate.

[0020] Preferably, in step 2), the hydrogen peroxide content is 30-35%;

[0021] And / or, the molar ratio of the hydrogen peroxide to the 2-methylthio-4-trifluoromethylbenzonitrile is 1:0.43-0.45;

[0022] And / or, the molar ratio of hydrogen peroxide to the main catalyst is 1:0.006-0.0065.

[0023] Preferably, the co-catalyst is prepared by the following steps:

[0024] S1: Dissolve cyclodextrin and carrageenan in water to prepare a gel base solution, then add p-toluenesulfonyl imidazole to the gel base solution, and react under alkaline conditions to obtain intermediate solution one;

[0025] S2: Melamine is placed in a tube furnace and heated to 550℃ for calcination for 3-5 hours to obtain a block solid. The solid is then ground into powder and dispersed into intermediate liquid one. Ferric nitrate, zinc nitrate and manganese nitrate are added and mixed evenly. The mixture is activated at 60℃ for 2-3 hours to obtain intermediate liquid two.

[0026] S3: Add zirconium chloride, sodium silicate, and triethyl phosphate to intermediate liquid II, mix well, then add acetic acid and silicotungstic acid, stir and react at 110-130℃ for 12-20h, then raise the temperature to 180℃ and continue the reaction for 2-5h, then wash and dry to obtain the final product.

[0027] Preferably, the mass ratio of the cyclodextrin, carrageenan, and water is (0.1-0.2):(0.3-0.35):1;

[0028] And / or, the molar ratio of p-toluenesulfonyl imidazole to cyclodextrin is 0.1-0.25:1;

[0029] And / or, in the second intermediate solution, the amount of zirconium chloride added is 5-10%, the amount of sodium silicate added is 15-20%, and the amount of triethyl phosphate added is 2.5-3.5%;

[0030] And / or, the reaction under alkaline conditions is carried out by adding sodium hydroxide and reacting at a temperature of 20-25°C.

[0031] Preferably, step 3) further includes at least one of the following technical features:

[0032] 31) The base used in the alkaline hydrolysis reaction is one of potassium hydroxide, sodium hydroxide, potassium carbonate, and sodium carbonate;

[0033] 32) The acid used in the acidification reaction is hydrochloric acid or sulfuric acid;

[0034] 33) The temperature of the alkaline hydrolysis reaction is 65-90℃;

[0035] 34) The acidification reaction is carried out at a temperature of 20-35℃;

[0036] 35) An organic base is also added in the alkaline hydrolysis reaction.

[0037] Preferably, the organic base is tetrabutylammonium hydroxide or tetrabutylphosphine hydroxide.

[0038] Preferably, in the alkaline hydrolysis reaction, the molar ratio of the base to the 2-methylsulfonyl-4-trifluoromethylbenzonitrile is 4-4.5:1.

[0039] Secondly, the 2-methylsulfonyl-4-trifluoromethylbenzoic acid prepared by the synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid of this application is used in the synthesis of benzoylpyrazole herbicides.

[0040] Compared with the prior art, this application has the following advantages:

[0041] 1. This application uses 2-nitro-4-trifluoromethylbenzonitrile as the starting material. The nitro group reduces the electron cloud density of the benzene ring, directly introducing the methylthio group and avoiding diazotization. Furthermore, in the subsequent oxidation reaction, a main catalyst combined with a co-catalyst is used. The co-catalyst lowers the activation energy, promoting the formation of hydrogen bonds between oxygen and sulfur atoms by hydrogen peroxide, thus activating the methylthio group. The activated methylthio group then undergoes oxidation with hydrogen peroxide, first converting to a sulfoxide intermediate, and then further oxidizing to a sulfonyl group. Moreover, the co-catalyst in this application can also improve the efficiency of electrophilic attack during the reaction, accelerate the separation and transport of electrons and holes, and accelerate the conversion of the sulfoxide intermediate, thereby improving the purity and yield of the oxidation product, reducing the generation of isomeric impurities, and thus improving the synthesis efficiency and yield of 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0042] 2. In the preparation process of the cocatalyst in this application, a polysaccharide gel system is first constructed, and then p-methylsulfonyl imidazole is grafted into the gel system. Then, it reacts with zirconium chloride, sodium silicate, and triethyl phosphate to form a metal-organic framework and a metal multiphase hydrotalcite-based catalytic structure. After drying at a certain temperature, it forms a rich microporous / mesoporous channel with a large number of active vacancies for coordination atoms such as sulfur, phosphorus, and nitrogen, as well as abundant metal nodes. These nodes can synergistically work with the main catalyst to greatly improve the overall catalytic efficiency and promote the reaction efficiency of the oxidation process.

[0043] 3. The synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid of this application can synthesize 2-methylsulfonyl-4-trifluoromethylbenzoic acid in a high-efficiency and environmentally friendly manner, with high yield and purity of the product. Attached Figure Description

[0044] Figure 1 These are XRD patterns of the cocatalysts in Examples 2 and 3 of this application.

[0045] Figure 2 This is a schematic diagram of the oxidation reaction efficiency of 2-methylthio-4-trifluoromethylbenzonitrile in step 2) of Examples 1-3 of this application.

[0046] Figure 3 This is a SEM image of the cocatalyst of Example 3 of this application. Detailed Implementation

[0047] The present application will be further described in detail below with reference to the embodiments.

[0048] Through extensive experimental research, the inventors of this application have provided a novel method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, which has the advantages of high yield, low cost, simple route, and economic and environmental benefits.

[0049] This application specifically discloses a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, comprising the following steps:

[0050] 1) 2-Nitro-4-trifluoromethylbenzonitrile was prepared by methylsulfidation reaction;

[0051] 2) The 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1) is oxidized under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile;

[0052] 3) The 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) is first subjected to an alkaline hydrolysis reaction, and then subjected to an acidification reaction to prepare 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0053] In some embodiments of this application, in step 1), the methyl sulfidation reaction is carried out in a solvent environment, and the solvent is one of DMF, DMSO, and DCM. For example, it can be DMF, DMSO, or DCM. Generally, a better effect can be obtained in a DMF solvent environment. Typically, the sulfur source for the methyl sulfidation reaction is one of sodium sulfide, potassium sulfide, or sodium methanethiol. Sodium methanethiol is preferred. The temperature of the methyl sulfidation reaction is less than 25°C. For example, the temperature of the methyl sulfidation reaction is 0-5°C, 5-10°C, 10-15°C, 15-20°C, or 20-25°C. More specifically, the temperature of the methyl sulfidation reaction can be 5°C, 10°C, 15°C, 20°C, or 25°C. Generally, a better reaction effect can be obtained at temperatures below 20°C.

[0054] In some embodiments of this application, in step 2), the catalyst includes a main catalyst and a co-catalyst, wherein the main catalyst is a heteropoly acid. For example, the heteropoly acid is selected from sodium tungstate, potassium tungstate, and cobalt tungstate. Generally, sodium tungstate yields better results. The oxidation reaction reagent is hydrogen peroxide, and the hydrogen peroxide content is 30-35%. For example, it can be 30-32%, 32-34%, or 34-35%. Typically, the oxidation reaction temperature is 80-85°C. The oxidation reaction temperature can also be 80-82°C or 82-85°C. More specifically, the reaction time can be 5-6.5h, 6.5-7.5h, 7.5-8.5h, 8.5-9h, or 9-10h. Generally, a good effect can be obtained when the oxidation reaction temperature is 82°C and the oxidation reaction time is 8h.

[0055] In some embodiments of this application, the molar ratio of hydrogen peroxide to 2-methylthio-4-trifluoromethylbenzonitrile can be 1:0.43, 1:0.44, or 1:0.45. The molar ratio of hydrogen peroxide to the main catalyst is 1:0.006-0.0065. Preferably, it is 1:0.0062-0.0065, and more preferably, it can be 1:0.0063, 1:0.00635, or 1:0.0064.

[0056] In some embodiments of this application, the co-catalyst is prepared by the following steps:

[0057] S1: Dissolve cyclodextrin and carrageenan in water to prepare a gel base solution, then add p-toluenesulfonyl imidazole to the gel base solution, and react under alkaline conditions to obtain intermediate solution one;

[0058] S2: Melamine is placed in a tube furnace and heated to 550℃ for calcination for 3-5 hours to obtain a block solid. The solid is then ground into powder and dispersed into intermediate liquid one. Ferric nitrate, zinc nitrate and manganese nitrate are added and mixed evenly. The mixture is activated at 60℃ for 2-3 hours to obtain intermediate liquid two.

[0059] S3: Add zirconium chloride, sodium silicate, and triethyl phosphate to intermediate liquid II, mix well, then add acetic acid and silicotungstic acid, stir and react at 110-130℃ for 12-20h, then raise the temperature to 180℃ and continue the reaction for 2-5h, then wash and dry to obtain the final product.

[0060] In the preparation method of the co-catalyst provided in this application, the mass ratio of cyclodextrin, carrageenan, and water is (0.1-0.2):(0.3-0.35):1. For example, the mass ratio of cyclodextrin, carrageenan, and water can be 0.1:0.3:1, 0.2:0.35:1, 0.1:0.35:1, 0.2:0.3:1, 0.15:0.3:1, 0.15:0.35:1, 0.1:0.32:1, 0.15:0.32:1, or 0.2:0.32:1. In the second intermediate solution, the amount of zirconium chloride added is 5-10%, the amount of sodium silicate added is 15-20%, and the amount of triethyl phosphate added is 2.5-3.5%. Generally, the effect is relatively better when the amount of zirconium oxide added is 6.5%, the amount of sodium silicate added is 20%, and the amount of triethyl phosphate added is 3%. The reaction under alkaline conditions involves adding sodium hydroxide and reacting at a temperature of 20-25°C, more preferably at 25°C for 3-5 hours.

[0061] In some specific embodiments, in step 3), the alkali used in the alkaline hydrolysis reaction is one of potassium hydroxide, sodium hydroxide, potassium carbonate, and sodium carbonate. For example, sodium hydroxide is generally preferred for the alkaline hydrolysis reaction. The acid used in the acidification reaction is hydrochloric acid or sulfuric acid. The temperature of the alkaline hydrolysis reaction is 65-90℃, for example, 65-70℃, 75-80℃, or 85-90℃. The temperature of the acidification reaction is 20-35℃, for example, 20℃, 25℃, 30℃, or 35℃.

[0062] In some specific embodiments, an organic base is also added to the alkaline hydrolysis reaction. The organic base is an alkyl organic base, such as tetramethylammonium hydroxide, tetrapropylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, tetramethylphosphorus hydroxide, tetrapropylphosphorus hydroxide, tetraethylphosphorus hydroxide, and tetrabutylphosphorus hydroxide. Generally, tetrabutylammonium hydroxide or tetrabutylphosphorus hydroxide is preferred for better results. In the alkaline hydrolysis reaction, the molar ratio of the base to the 2-methylsulfonyl-4-trifluoromethylbenzonitrile is 4-4.5:1.

[0063] Unless otherwise specified, the raw materials used in the embodiments and comparative examples of this application are all commercially available. Example

[0064] The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment includes the following steps:

[0065] 1) Add 43.75 g of 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile and 60 g of DMF to a three-necked flask equipped with a stirrer, thermometer, and dropping funnel. Slowly add 75.75 g (0.216 mol) of 20% sodium methanethiol solution at 20 °C to carry out the methyl sulfidation reaction. After reacting for 4 h, cool to 0-5 °C in an ice bath. A yellow solid product precipitates out. After washing and drying, 41.22 g of 2-methylthio-4-trifluoromethylbenzonitrile is obtained with a yield of 98.9% and a purity of 99.2%. 1 H NMR (600MHz, CDCl3) δ: 2.61 (s, 3H, SCH3), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH);

[0066] 2) In a 250mL four-necked flask equipped with a stirrer, thermometer, water separator, and condenser, add 97.75g of 2-methylthio-4-trifluoromethylbenzonitrile (prepared in step 1), 6g of glacial acetic acid, 0.0065mol of sodium tungstate (catalyst), and 150mL of toluene. Then, heat the reaction system to 85℃ and add 110g of 35% hydrogen peroxide solution dropwise over 3.5h. Continue the oxidation reaction for 6h, then remove the water from the system by azeotropic extraction. After cooling, a yellow solid product is obtained. Wash and dry the product to obtain 107.1g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile with a purity of 98.1% and a yield of 95.5%. 1 H NMR (600MHz, CDCl3) δ: 3.33 (s, 3H, S02CH3), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH);

[0067] 3) Add 37.38 g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) to a four-necked flask equipped with an electric stirrer, thermometer, and dropping funnel. Then add 26 g of 0.65 mol sodium hydroxide and 150 g of glycerol. Heat to 85 °C for alkaline hydrolysis. After reacting for 5 h, cool to 25 °C and then add 30% hydrochloric acid for acidification. Adjust the pH of the system to 2-3. Filter and wash with deionized water to obtain a white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid is obtained with a yield of 97.1% and a purity of 98.6%. 1 H NMR (600MHz, CDCl3) δ: 3.46 (s, 3H, SO2CH3), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H). Example

[0068] The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment includes the following steps:

[0069] 1) Add 43.75 g of 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile and 60 g of DMF to a three-necked flask equipped with a stirrer, thermometer, and dropping funnel. Slowly add 75.75 g (0.216 mol) of 20% sodium methanethiol solution at 20 °C to carry out the methylthiolation reaction. After reacting for 4 h, cool to 0-5 °C in an ice bath. A yellow solid product precipitates out. After washing and drying, 41.3 g of 2-methylthio-4-trifluoromethylbenzonitrile is obtained with a yield of 99.1% and a purity of 99.4%. 1H NMR (600MHz, CDCl3) δ: 2.61 (s, 3H, SCH3), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH);

[0070] 2) In a 250mL four-necked flask equipped with a stirrer, thermometer, water separator, and condenser, add 97.75g of 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1), 6g of glacial acetic acid, 0.0065mol of sodium tungstate (catalyst), 1.2g of co-catalyst, and 150mL of toluene. Then, heat the reaction system to 85℃ and add 110g of 35% hydrogen peroxide solution dropwise over 3.5h. Continue the oxidation reaction for 6h, then remove the water in the system by azeotropic extraction. After cooling, a yellow solid product is obtained. Wash and dry the product to obtain 108.5g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile with a purity of 99.3% and a yield of 99.5%. 1 H NMR (600MHz, CDCl3) δ: 3.33 (s, 3H, S02CH3), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH);

[0071] 3) Add 37.38 g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) to a four-necked flask equipped with an electric stirrer, thermometer, and dropping funnel. Then add 26 g of 0.65 mol sodium hydroxide and 150 g of glycerol. Heat to 85 °C for alkaline hydrolysis. After reacting for 5 h, cool to 25 °C and then add 30% hydrochloric acid for acidification. Adjust the pH of the system to 2-3. Filter and wash with deionized water to obtain a white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid is obtained with a yield of 99.2% and a purity of 99.3%. 1 H NMR (600MHz, CDCl3) δ: 3.46 (s, 3H, SO2CH3), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H).

[0072] The co-catalyst in this embodiment was prepared using the following method:

[0073] S1: Add 15g cyclodextrin, 32g carrageenan, and 100g distilled water to a four-necked flask equipped with a stirrer, thermometer, and dropping funnel. Mix well to prepare a gel base solution. Then, slowly add 3g p-toluenesulfonyl imidazole to the gel base solution and add sodium hydroxide. After reacting under alkaline conditions for 8 hours, intermediate solution one is obtained.

[0074] S2: Place 5g of melamine in a tube furnace and calcine it at 550℃ for 3.5h to obtain a blocky solid. Grind it into powder and then disperse the powder into 150mL of intermediate liquid one. Add 10mmol of ferric nitrate, 10mmol of zinc nitrate and 10mmol of manganese nitrate and mix well. Add ammonia water to adjust the pH to 10 and activate it at 60℃ for 2-3h to obtain intermediate liquid two.

[0075] S3: Add 6.5g of zirconium chloride and 3g of triethyl phosphate to 100g of intermediate liquid II, mix well, then add 10g of acetic acid and 0.5g of phosphotungstic acid, stir and react at 120℃ for 15h, then raise the temperature to 180℃ and continue to react for 3h, then wash and dry to obtain the final product. Example

[0076] The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment includes the following steps:

[0077] 1) Add 43.75 g of 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile and 60 g of DMF to a three-necked flask equipped with a stirrer, thermometer, and dropping funnel. Slowly add 75.75 g (0.216 mol) of 20% sodium methanethiol solution at 20 °C to carry out the methylthiolation reaction. After reacting for 4 h, cool to 0-5 °C in an ice bath. A yellow solid product precipitates out. After washing and drying, 41.27 g of 2-methylthio-4-trifluoromethylbenzonitrile is obtained with a yield of 99% and a purity of 99.3%. 1 H NMR (600MHz, CDCl3) δ: 2.61 (s, 3H, SCH3), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH);

[0078] 2) In a 250mL four-necked flask equipped with a stirrer, thermometer, water separator, and condenser, add 97.75g of 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1), 6g of glacial acetic acid, 0.0065mol of sodium tungstate (catalyst), 1.2g of co-catalyst, and 150mL of toluene. Then, heat the reaction system to 85℃ and add 110g of 35% hydrogen peroxide solution dropwise over 3.5h. Continue the oxidation reaction for 6h, then remove the water in the system by azeotropic extraction. After cooling, a yellow solid product is obtained. After washing and drying, 109.56g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile is obtained with a purity of 99.5% and a yield of 99.6%. 1 H NMR (600MHz, CDCl3) δ: 3.33 (s, 3H, S02CH3), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH);

[0079] 3) Add 37.38 g of 0.15 mol of 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) to a four-necked flask equipped with an electric stirrer, thermometer, and dropping funnel. Then add 26 g of 0.65 mol sodium hydroxide, 13.8 g of 0.05 mol tetrabutylphosphine hydroxide, and 150 g of glycerol. Heat to 85 °C for alkaline hydrolysis reaction. After reacting for 5 h, cool to 25 °C and then add 30% hydrochloric acid for acidification reaction. Adjust the pH of the system to 2-3. Filter and wash with deionized water to obtain a white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid is obtained with a yield of 99.6% and a purity of 99.5%. 1 H NMR (600MHz, CDCl3) δ: 3.46 (s, 3H, SO2CH3), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H).

[0080] The co-catalyst in this embodiment was prepared using the following method:

[0081] S1: Add 15g cyclodextrin, 32g carrageenan, and 100g distilled water to a four-necked flask equipped with a stirrer, thermometer, and dropping funnel. Mix well to prepare a gel base solution. Then, slowly add 3g p-toluenesulfonyl imidazole to the gel base solution and add sodium hydroxide. After reacting under alkaline conditions for 8 hours, intermediate solution one is obtained.

[0082] S2: Place 5g of melamine in a tube furnace and calcine it at 550℃ for 3.5h to obtain a blocky solid. Grind it into powder and then disperse the powder into 150mL of intermediate liquid one. Add 10mmol of ferric nitrate, 10mmol of zinc nitrate and 10mmol of manganese nitrate and mix well. Add ammonia water to adjust the pH to 10 and activate it at 60℃ for 2-3h to obtain intermediate liquid two.

[0083] S3: Add 6.5g zirconium chloride, 20g sodium silicate, 0.5g silicotungstic acid, and 3g triethyl phosphate to 100g intermediate liquid II. After mixing evenly, add 10g acetic acid and 0.5g silicotungstic acid. Stir and react at 120℃ for 15h, then raise the temperature to 180℃ and continue the reaction for 3h. After washing and drying, the product is obtained.

[0084] Performance testing

[0085] The cocatalysts from Examples 2-3 were subjected to XRD tests, and the test results are as follows: Figure 1 As shown.

[0086] The concentration of the raw material 2-methylthio-4-trifluoromethylbenzonitrile in step 2) of Examples 1-3 was detected by high performance liquid chromatography. The effect of the co-catalyst on the oxidation reaction efficiency was investigated by plotting the reaction time (h) on the x-axis and the total molar amount of 2-methylthio-4-trifluoromethylbenzonitrile (mol) on the y-axis. Specific test results are shown below. Figure 2 As shown.

[0087] The co-catalyst from Example 3 was subjected to scanning electron microscopy (SEM) testing, and the results are as follows: Figure 3 As shown

[0088] It can be seen that using a combination of a main catalyst and a co-catalyst can greatly increase the rate of oxidation reaction, accelerate the reaction process, and improve product yield.

[0089] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, characterized in that, Includes the following steps: 1) 2-Nitro-4-trifluoromethylbenzonitrile was prepared by methylsulfidation reaction; 2) The 2-methylthio-4-trifluoromethylbenzonitrile obtained in step 1) is oxidized under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile; the catalyst includes a main catalyst and a co-catalyst, wherein the main catalyst is a heteropoly acid; the co-catalyst is prepared by the following steps: S1: Dissolve cyclodextrin and carrageenan in water to prepare a gel base solution, then add p-toluenesulfonyl imidazole to the gel base solution, and react under alkaline conditions to obtain intermediate solution one; S2: Melamine is placed in a tube furnace and heated to 550℃ for calcination for 3-5 hours to obtain a block solid. The solid is then ground into powder and dispersed into intermediate liquid one. Ferric nitrate, zinc nitrate and manganese nitrate are added and mixed evenly. The mixture is then activated at 60℃ for 2-3 hours to obtain intermediate liquid two. S3: Add zirconium chloride, sodium silicate, and triethyl phosphate to intermediate liquid II, mix well, then add acetic acid and silicotungstic acid, stir and react at 110-130℃ for 12-20h, then raise the temperature to 180℃ and continue the reaction for 2-5h, and then wash and dry to obtain the product. 3) The 2-methylsulfonyl-4-trifluoromethylbenzonitrile obtained in step 2) is first subjected to an alkaline hydrolysis reaction, and then subjected to an acidification reaction to prepare 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

2. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 1, characterized in that, Step 1) further includes at least one of the following technical features: 11) The methyl sulfidation reaction is carried out in a solvent, wherein the solvent is one of DMF, DMSO, and DCM; 12) The sulfur source for the methyl sulfide reaction is one of sodium sulfide, potassium sulfide, or sodium methanethiol; 13) The temperature of the methyl sulfidation reaction is less than 25°C.

3. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 1, characterized in that, Step 2) further includes at least one of the following technical features: 21) The oxidizing agent in the oxidation reaction is hydrogen peroxide; 22) The oxidation reaction is carried out at a temperature of 80-85℃ for 5-10 hours.

4. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 3, characterized in that, The heteropolyacid is one of sodium tungstate, potassium tungstate, and cobalt tungstate.

5. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 3, characterized in that, In step 2), the hydrogen peroxide content is 30-35%; And / or, the molar ratio of the hydrogen peroxide to the 2-methylthio-4-trifluoromethylbenzonitrile is 1:0.43-0.45; And / or, the molar ratio of hydrogen peroxide to the main catalyst is 1:0.006-0.0065.

6. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 1, characterized in that, The mass ratio of cyclodextrin, carrageenan, and water is (0.1-0.2):(0.3-0.35):1; And / or, the molar ratio of p-toluenesulfonyl imidazole to cyclodextrin is 0.1-0.25:1; And / or, in the second intermediate solution, the amount of zirconium chloride added is 5-10%, the amount of sodium silicate added is 15-20%, and the amount of triethyl phosphate added is 2.5-3.5%; And / or, the reaction under alkaline conditions is carried out by adding sodium hydroxide and reacting at a temperature of 20-25°C.

7. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 1, characterized in that, Step 3) further includes at least one of the following technical features: 31) The base used in the alkaline hydrolysis reaction is one of potassium hydroxide, sodium hydroxide, potassium carbonate, and sodium carbonate; 32) The acid used in the acidification reaction is hydrochloric acid or sulfuric acid; 33) The temperature of the alkaline hydrolysis reaction is 65-90℃; 34) The acidification reaction is carried out at a temperature of 20-35℃; 35) An organic base is also added to the alkaline hydrolysis reaction.

8. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 7, characterized in that, The organic base is tetrabutylammonium hydroxide or tetrabutylphosphine hydroxide.

9. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 7, characterized in that, In the alkaline hydrolysis reaction, the molar ratio of the base to the 2-methylsulfonyl-4-trifluoromethylbenzonitrile is 4-4.5:1.

Images