Synthesis method of 2-methylsulfonyl-4-trifluoromethyl benzoic acid

Abstract

The invention relates to the technical field of synthesis of pesticide intermediates, and particularly discloses a synthesis method of 2-methylsulfonyl-4-trifluoromethyl benzoic acid. The invention relates to a synthesis method of 2-methylsulfonyl-4-trifluoromethyl benzoic acid, which comprises the following steps: 1) 2-nitro-4-trifluoromethyl cyanophenyl is subjected to a methyl vulcanization reaction, and 2-methylthio-4-trifluoromethyl cyanophenyl is prepared; (2) carrying out oxidation reaction on the 2-methylthio-4-(trifluoromethyl) cyanophenyl prepared in the step (1) under the action of a catalyst, so as to prepare 2-methylsulfonyl-4-(trifluoromethyl) cyanophenyl; and 3) carrying out an alkaline hydrolysis reaction on the 2-methylsulfonyl-4-trifluoromethyl cyanophenyl prepared in the step 2), and then carrying out an acidification reaction to prepare the 2-methylsulfonyl-4-trifluoromethyl benzoic acid. The synthesis method provided by the invention has the advantages of high reaction efficiency, few process steps and high yield.

Description

Technical Field

[0001] The present application relates to the technical field of pesticide intermediate synthesis, and more specifically, to a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid. Background Art

[0002] With the continuous development of the pesticide industry, the application of herbicides has become quite popular, and about 85% of crops use herbicides. At the same time, herbicides are also developing towards the general trend of low toxicity, low dosage, high activity and low residue. For this reason, technicians have developed benzoylpyrazole herbicides, such as sulfonylmethane, isoxathiapiprolin, and bispyribac, which are a type of highly active, low-toxic, broad-spectrum herbicides.

[0003] 2-Methylsulfonyl-4-trifluoromethylbenzoic acid is an important intermediate for the synthesis of benzoylpyrazole herbicides. At present, there are many synthetic routes for 2-methylsulfonyl-4-trifluoromethylbenzoic acid, such as using 2-methylthio-4-trifluoromethylbenzonitrile as the initial raw material, firstly undergoing oxidation reaction with hydrogen peroxide under the action of a catalyst to generate 2-methylsulfonyl-4-trifluoromethylbenzonitrile, in which the methylthio group is oxidized to a methylsulfonyl group, and then 2-methylsulfonyl-4-trifluoromethylbenzonitrile is subjected to alkaline hydrolysis and acidification, and the cyano group is converted into a formic acid group to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid, but the oxidation reaction efficiency of this route is low.

[0004] Another example is the preparation of p-trifluoromethylbenzoic acid by hydrolysis of o-nitro-p-trifluoromethylbenzonitrile. In this process, a certain amount of by-products will be generated because the trifluoromethyl group on the benzene ring is unstable in strong acid and high temperature. Another method is to obtain o-nitro-p-trifluoromethylbenzoic acid by nitration and oxidative hydrolysis of p-chlorotrifluorotoluene, and then undergo esterification, thiolation and oxidation to obtain the product. However, the overall process has many reaction steps, low reaction efficiency and high cost. Summary of the invention

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

[0006] In the first aspect, the present application provides a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, using the following technical scheme: A method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid comprises the following steps: 1) subjecting 2-nitro-4-trifluoromethylbenzonitrile to a methylsulfidation reaction to prepare 2-methylthio-4-trifluoromethylbenzonitrile; 2) subjecting the 2-methylthio-4-trifluoromethylbenzonitrile prepared in step 1) to an oxidation reaction under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile; 3) The 2-methylsulfonyl-4-trifluoromethylbenzonitrile prepared in step 2) is first subjected to alkaline hydrolysis reaction, and then subjected to acidification reaction to prepare 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0007] Preferably, the step 1) further includes at least one of the following technical features: 11) The methylsulfidation reaction is carried out in a solvent, and the solvent is one of DMF, DMSO, and DCM; 12) The sulfur source for the methylsulfidation reaction is one of sodium sulfide, potassium sulfide, and sodium methyl mercaptan; 13) The temperature of the methylsulfidation reaction is less than 25°C.

[0008] Preferably, the step 2) further includes at least one of the following technical features: 21) The catalyst comprises a main catalyst and a co-catalyst, and the main catalyst is a heteropoly acid; 22) The oxidizing agent of the oxidation reaction is hydrogen peroxide; 23) The temperature of the oxidation reaction is 80-85°C and the reaction time is 5-10h.

[0009] Preferably, the heteropoly acid is one of sodium tungstate, potassium tungstate and cobalt tungstate.

[0010] Preferably, in step 2), the content of hydrogen peroxide 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 the hydrogen peroxide to the main catalyst is 1:0.006-0.0065.

[0011] Preferably, the co-catalyst is prepared by the following steps: S1: dissolving cyclodextrin and carrageenan in water to prepare a gel base liquid, then adding p-toluenesulfonyl imidazole to the gel base liquid, and reacting under alkaline conditions to obtain an intermediate liquid 1; S2: Place melamine in a tube furnace, heat to 550°C and calcine for 3-5 hours to obtain a block solid, grind it into powder, and then disperse the powder into intermediate solution 1, add iron nitrate, zinc nitrate and manganese nitrate and mix well, activate at 60°C for 2-3 hours to obtain intermediate solution 2; S3: Add zirconium chloride, sodium silicate and triethyl phosphate to the intermediate solution 2, mix well and then add acetic acid and silicotungstic acid, stir and react at 110-130°C for 12-20h, then heat to 180°C and continue to react for 2-5h, wash and dry to obtain.

[0012] Preferably, 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 intermediate solution 2, 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 to add sodium hydroxide and react at a temperature of 20-25°C.

[0013] Preferably, the 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°C; 34) The temperature of the acidification reaction is 20-35°C; 35) An organic base is also added in the alkaline hydrolysis reaction.

[0014] Preferably, the organic base is tetrabutylammonium hydroxide or tetrabutylphosphine hydroxide.

[0015] Preferably, in the alkaline hydrolysis reaction, the molar ratio of the base to the 2-methylsulfonyl-4-trifluoromethylbenzonitrile is 4-4.5:1.

[0016] In a second aspect, 2-methylsulfonyl-4-trifluoromethylbenzoic acid prepared by the synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid of the present application is used for the synthesis of benzoylpyrazole herbicides.

[0017] Compared with the prior art, this application has the following beneficial effects: 1. The present application uses 2-nitro-4-trifluoromethylbenzonitrile as the starting material, reduces the benzene ring electron cloud density by nitro, thereby directly introducing methylthio, avoiding diazotization reaction. And in the subsequent oxidation reaction, the main catalyst is compounded with a cocatalyst, and the reaction activation energy is reduced by a cocatalyst, promoting hydrogen peroxide to form a hydrogen bond between an oxygen atom and a sulfur atom first, so that the methylthio becomes activated, and then the activated methyl sulfide is oxidized based on hydrogen peroxide, first converted into a sulfoxide intermediate state, and then further oxidized to a sulfonyl group. In addition, the cocatalyst of the present application can also improve the efficiency of electrophilic attack during the reaction, accelerate the separation and transmission of electrons and holes, accelerate the conversion of sulfoxide intermediate states, thereby improving the purity and yield of the oxidation reaction product, reducing the generation of isomeric impurities, thereby improving the synthesis efficiency and yield of 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0018] 2. In the preparation process of the co-catalyst in the present application, a polysaccharide gel system is first constructed, and then methylsulfonyl imidazole is grafted into the gel system, and then reacted 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, abundant microporous / mesoporous channels are formed, and there are a large number of active vacancies of coordination atoms such as sulfur, phosphorus, and nitrogen. At the same time, there are also abundant metal nodes, which can cooperate with the main catalyst to greatly improve the overall catalytic efficiency and promote the reaction efficiency of the oxidation reaction process.

[0019] 3. The synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid of the present application can efficiently and environmentally friendly synthesize 2-methylsulfonyl-4-trifluoromethylbenzoic acid, and the yield and purity of the product are high. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is the XRD diagram of the co-catalyst of Example 2 and Example 3 of the present application.

[0021] Figure 2 It is a schematic diagram of the oxidation reaction efficiency of 2-methylthio-4-trifluoromethylbenzonitrile in step 2) of Example 1-3 of the present application.

[0022] Figure 3 This is a SEM image of the co-catalyst of Example 3 of the present application. DETAILED DESCRIPTION

[0023] The present application is further described in detail below in conjunction with embodiments.

[0024] After extensive experimental research, the inventors of the present application have provided a new method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, which has the advantages of high yield, low cost, simple route, economy and environmental protection.

[0025] The present application specifically discloses a method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, comprising the following steps: 1) subjecting 2-nitro-4-trifluoromethylbenzonitrile to a methylsulfidation reaction to prepare 2-methylthio-4-trifluoromethylbenzonitrile; 2) subjecting the 2-methylthio-4-trifluoromethylbenzonitrile prepared in step 1) to an oxidation reaction under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile; 3) The 2-methylsulfonyl-4-trifluoromethylbenzonitrile prepared in step 2) is first subjected to alkaline hydrolysis reaction, and then subjected to acidification reaction to prepare 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0026] In some embodiments of the present 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, and DCM. Usually, a better effect can be achieved in a DMF solvent environment. Usually, the sulfur source of the methyl sulfidation reaction is one of sodium sulfide, potassium sulfide, and sodium methyl mercaptan. Preferably, it is sodium methyl mercaptan. 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, and 20-25°C. For example, the temperature of the methyl sulfidation reaction can be 5°C, 10°C, 15°C, 20°C, and 25°C. Usually, a better reaction effect can be achieved at a temperature below 20°C.

[0027] In some embodiments of the present application, in step 2), the catalyst includes a main catalyst and a co-catalyst, and the main catalyst is a heteropoly acid. For example, the heteropoly acid is selected from one of sodium tungstate, potassium tungstate, and cobalt tungstate. Generally, sodium tungstate can achieve better results. The oxidation reaction reagent is hydrogen peroxide, and the content of hydrogen peroxide is 30-35%. For example, it can be 30-32%, 32-34%, and 34-35%. Generally, the temperature of the oxidation reaction is 80-85°C. The oxidation reaction temperature can also be 80-82°C, 82-85°C. For example, the reaction time can be 5-6.5h, 6.5-7.5h, 7.5-8.5h, 8.5-9h, 9-10h, etc. Generally, when the oxidation reaction temperature is 82°C and the oxidation reaction time is 8h, better results can be achieved.

[0028] In some embodiments of the present application, the molar ratio of the hydrogen peroxide to the 2-methylthio-4-trifluoromethylbenzonitrile can be 1:0.43, 1:0.44, 1:0.45. The molar ratio of the 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, 1:0.0064.

[0029] In some embodiments of the present application, the co-catalyst is prepared by the following steps: S1: dissolving cyclodextrin and carrageenan in water to prepare a gel base liquid, then adding p-toluenesulfonyl imidazole to the gel base liquid, and reacting under alkaline conditions to obtain an intermediate liquid 1; S2: Place melamine in a tube furnace, heat to 550°C and calcine for 3-5 hours to obtain a block solid, grind it into powder, and then disperse the powder into intermediate solution 1, add iron nitrate, zinc nitrate and manganese nitrate and mix well, activate at 60°C for 2-3 hours to obtain intermediate solution 2; S3: Add zirconium chloride, sodium silicate and triethyl phosphate to the intermediate solution 2, mix well and then add acetic acid and silicotungstic acid, stir and react at 110-130°C for 12-20h, then heat to 180°C and continue to react for 2-5h, wash and dry to obtain.

[0030] In the preparation method of the co-catalyst provided in the present application, the mass ratio of the 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, 0.2:0.32:1. In the intermediate solution 2, 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, in the intermediate solution, 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 effect is relatively good. The reaction under alkaline conditions is to add sodium hydroxide and react at a temperature of 20-25°C, more preferably, react at a temperature of 25°C for 3-5h.

[0031] In some specific embodiments, in step 3), the base used in the alkaline hydrolysis reaction is one of potassium hydroxide, sodium hydroxide, potassium carbonate, and sodium carbonate. For example, under normal circumstances, the effect of using sodium hydroxide in the alkaline hydrolysis reaction is better. The acid used in the acidification reaction is hydrochloric acid or sulfuric acid. The temperature of the alkaline hydrolysis reaction is 65-90°C, for example, it can be 65-70°C, 75-80°C, 85-90°C. The temperature of the acidification reaction is 20-35°C, for example, it can be 20°C, 25°C, 30°C, 35°C.

[0032] 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, tetramethylphosphonium hydroxide, tetrapropylphosphonium hydroxide, tetraethylphosphonium hydroxide, and tetrabutylphosphonium hydroxide. Under normal circumstances, the organic base is tetrabutylammonium hydroxide or tetrabutylphosphonium hydroxide, which can achieve better results. In the alkaline hydrolysis reaction, the molar ratio of the base to the 2-methylsulfonyl-4-trifluoromethylbenzonitrile is 4-4.5:1.

[0033] Unless otherwise specified, the raw materials used in the examples and comparative examples of the present application are all commercially available. Example

[0034] The synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment comprises the following steps: 1) Add 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile 43.75 g and 60 g DMF into a three-necked flask equipped with a stirrer, a thermometer and a dropping funnel, and slowly drop 75.75 g (0.216 mol) of 20% sodium methyl mercaptan solution at 20°C to carry out methyl sulfidation reaction. After reacting for 4 hours, cool in an ice bath to 0-5°C to precipitate a yellow solid product. After washing and drying, 41.22 g of 2-methylthio-4-trifluoromethylbenzonitrile was prepared, with a yield of 98.9% and a purity of 99.2%. 1 H NMR (600 MHz, CDCl 3 )δ: 2.61 (s, 3H, SCH 3 ), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH); 2) In a 250 mL four-necked flask equipped with a stirrer, a thermometer, a water separator and a condenser, 0.45 mol of 2-methylthio-4-trifluoromethylbenzonitrile (97.75 g), 6 g of glacial acetic acid, 0.0065 mol of sodium tungstate (catalyst), and 150 mL of toluene were added. The reaction system was then heated to 85° C. and 110 g of 35% hydrogen peroxide solution was added dropwise within 3.5 h. The oxidation reaction was continued for 6 h, and then the water in the system was azeotropically removed. The product was cooled to obtain a yellow solid, which was washed and dried to obtain 107.1 g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile with a purity of 98.1% and a yield of 95.5%. 1 H NMR (600 MHz, CDCl 3 )δ: 3.33 (s, 3H, S0 2 CH 3 ), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH); 3) In a four-necked flask equipped with an electric stirrer, a thermometer, and a dropping funnel, 0.15 mol of 2-methylsulfonyl-4-trifluoromethylbenzonitrile (37.38 g) prepared in step 2) was added, and then 0.65 mol of sodium hydroxide (26 g) and 150 g of glycerol were added. The temperature was raised to 85° C. for alkaline hydrolysis reaction. After reacting for 5 hours, the mixture was cooled to 25° C., and then 30% hydrochloric acid was added for acidification reaction. The pH value of the system was adjusted to 2-3, filtered, and washed with deionized water to obtain an off-white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid was prepared with a yield of 97.1% and a purity of 98.6%. 1 H NMR (600 MHz, CDCl 3 )δ: 3.46 (s, 3H, S0 2 CH 3 ), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H). Example

[0035] The synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment comprises the following steps: 1) Add 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile 43.75 g and 60 g DMF into a three-necked flask equipped with a stirrer, a thermometer and a dropping funnel, and slowly drop 75.75 g (0.216 mol) of 20% sodium methyl mercaptan solution at 20°C to carry out methyl sulfidation reaction. After reacting for 4 hours, cool in an ice bath to 0-5°C to precipitate a yellow solid product. After washing and drying, 41.3 g of 2-methylthio-4-trifluoromethylbenzonitrile was prepared, with a yield of 99.1% and a purity of 99.4%. 1H NMR (600 MHz, CDCl 3 )δ: 2.61 (s, 3H, SCH 3 ), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH); 2) In a 250 mL four-necked flask equipped with a stirrer, a thermometer, a water separator and a condenser, 0.45 mol of 2-methylthio-4-trifluoromethylbenzonitrile (97.75 g), 6 g of glacial acetic acid, 0.0065 mol of sodium tungstate (catalyst), 1.2 g of a co-catalyst and 150 mL of toluene were added, and then the reaction system was heated to 85° C., 110 g of a 35% hydrogen peroxide solution was added dropwise, and the addition was completed within 3.5 h. The oxidation reaction was continued for 6 h, and then the water in the system was azeotropically removed. The product was cooled to obtain a yellow solid, which was washed and dried to obtain 108.5 g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile with a purity of 99.3% and a yield of 99.5%. 1 H NMR (600 MHz, CDCl 3 )δ: 3.33 (s, 3H, S0 2 CH 3 ), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH); 3) In a four-necked flask equipped with an electric stirrer, a thermometer, and a dropping funnel, 0.15 mol of 2-methylsulfonyl-4-trifluoromethylbenzonitrile (37.38 g) prepared in step 2) was added, and then 0.65 mol of sodium hydroxide (26 g) and 150 g of glycerol were added. The temperature was raised to 85° C. for alkaline hydrolysis reaction. After reacting for 5 hours, the mixture was cooled to 25° C., and then 30% hydrochloric acid was added for acidification reaction. The pH value of the system was adjusted to 2-3, filtered, and washed with deionized water to obtain an off-white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid was prepared with a yield of 99.2% and a purity of 99.3%. 1 H NMR (600 MHz, CDCl 3 )δ: 3.46 (s, 3H, S0 2 CH 3 ), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H).

[0036] The co-catalyst of this embodiment is prepared by the following preparation method: S1: Add 15 g of cyclodextrin, 32 g of carrageenan, and 100 g of distilled water into a four-necked flask equipped with a stirrer, a thermometer, and a dropping funnel, mix them evenly to form a gel base liquid, then slowly add 3 g of p-toluenesulfonyl imidazole to the gel base liquid, add sodium hydroxide, and react under alkaline conditions for 8 hours to obtain an intermediate solution 1; S2: 5 g of melamine was placed in a tube furnace, heated to 550°C and calcined for 3.5 h to obtain a block solid, which was ground into powder. The powder was then dispersed into 150 mL of intermediate solution 1, 10 mmol of ferric nitrate, 10 mmol of zinc nitrate and 10 mmol of manganese nitrate were added and mixed evenly, ammonia water was added to adjust the pH value to 10, and the mixture was activated at 60°C for 2-3 h to obtain intermediate solution 2; S3: Add 6.5g zirconium chloride and 3g triethyl phosphate to 100g intermediate solution 2 respectively, mix well, add 10g acetic acid and 0.5g phosphotungstic acid, stir and react at 120°C for 15h, then heat to 180°C and continue to react for 3h, wash and dry to obtain. Example

[0037] The synthesis method of 2-methylsulfonyl-4-trifluoromethylbenzoic acid in this embodiment comprises the following steps: 1) Add 0.2 mol 2-nitro-4-trifluoromethylbenzonitrile 43.75 g and 60 g DMF into a three-necked flask equipped with a stirrer, a thermometer and a dropping funnel, and slowly drop 75.75 g (0.216 mol) of 20% sodium methyl mercaptan solution at 20°C to carry out methyl sulfidation reaction. After reacting for 4 hours, cool in an ice bath to 0-5°C to precipitate a yellow solid product. After washing and drying, 41.27 g of 2-methylthio-4-trifluoromethylbenzonitrile was prepared, with a yield of 99% and a purity of 99.3%. 1 H NMR (600 MHz, CDCl 3 )δ: 2.61 (s, 3H, SCH 3 ), 7.72 (d, 1H, ArH), 7.46 (d, 1H, ArH), 7.48 (s, 1H, ArH); 2) In a 250 mL four-necked flask equipped with a stirrer, a thermometer, a water separator and a condenser, 0.45 mol of 2-methylthio-4-trifluoromethylbenzonitrile (97.75 g), 6 g of glacial acetic acid, 0.0065 mol of sodium tungstate (catalyst), 1.2 g of a co-catalyst and 150 mL of toluene were added, and then the reaction system was heated to 85° C., 110 g of a 35% hydrogen peroxide solution was added dropwise, and the addition was completed within 3.5 h. The oxidation reaction was continued for 6 h, and then the water in the system was azeotropically removed. The product was cooled to obtain a yellow solid, which was washed and dried to obtain 109.56 g of 2-methylsulfonyl-4-trifluoromethylbenzonitrile with a purity of 99.5% and a yield of 99.6%. 1H NMR (600 MHz, CDCl 3 )δ: 3.33 (s, 3H, S0 2 CH 3 ), 8.09 (d, 1H, ArH), 8.06 (d, 1H, ArH), 8.46 (s, 1H, ArH); 3) In a four-necked flask equipped with an electric stirrer, a thermometer, and a dropping funnel, 0.15 mol of 2-methylsulfonyl-4-trifluoromethylbenzonitrile (37.38 g) prepared in step 2) was added, followed by 0.65 mol of sodium hydroxide (26 g), 0.05 mol of tetrabutylphosphonium hydroxide (13.8 g), and 150 g of glycerol. The temperature was raised to 85° C. for alkaline hydrolysis reaction. After reacting for 5 h, the mixture was cooled to 25° C., and then 30% hydrochloric acid was added for acidification reaction. The pH value of the system was adjusted to 2-3, filtered, and washed with deionized water to obtain an off-white solid product. After drying, 2-methylsulfonyl-4-trifluoromethylbenzoic acid was obtained with a yield of 99.6% and a purity of 99.5%. 1 H NMR (600 MHz, CDCl 3 )δ: 3.46 (s, 3H, S0 2 CH 3 ), 7.88 (d, 1H, ArH), 8.21 (d, 1H, ArH), 8.23 ​​(s, 1H, ArH), 14.2 (s, 1H).

[0038] The co-catalyst of this embodiment is prepared by the following preparation method: S1: Add 15 g of cyclodextrin, 32 g of carrageenan, and 100 g of distilled water into a four-necked flask equipped with a stirrer, a thermometer, and a dropping funnel, mix them evenly to form a gel base liquid, then slowly add 3 g of p-toluenesulfonyl imidazole to the gel base liquid, add sodium hydroxide, and react under alkaline conditions for 8 hours to obtain an intermediate solution 1; S2: 5 g of melamine was placed in a tube furnace, heated to 550°C and calcined for 3.5 h to obtain a block solid, which was ground into powder. The powder was then dispersed into 150 mL of intermediate solution 1, 10 mmol of ferric nitrate, 10 mmol of zinc nitrate and 10 mmol of manganese nitrate were added and mixed evenly, ammonia water was added to adjust the pH value to 10, and the mixture was activated at 60°C for 2-3 h to obtain intermediate solution 2; S3: Add 6.5g zirconium chloride, 20g sodium silicate, 0.5g silicotungstic acid and 3g triethyl phosphate to 100g intermediate solution 2 respectively, mix well, add 10g acetic acid and 0.5g silicotungstic acid, stir and react at 120℃ for 15h, then heat to 180℃ and continue to react for 3h, wash and dry to obtain.

[0039] Performance testing Take the co-catalyst of Example 2-3 and perform XRD test. The test results are as follows: Figure 1 shown.

[0040] The concentration of the raw material 2-methylthio-4-trifluoromethylbenzonitrile in step 2) of Example 1-3 was detected by high performance liquid chromatography content tracking, with the reaction time (h) as the horizontal axis and the total molar amount of 2-methylthio-4-trifluoromethylbenzonitrile (mol) as the vertical axis to investigate the effect of the co-catalyst on the oxidation reaction efficiency. The specific test results are as follows: Figure 2 shown.

[0041] The co-catalyst of Example 3 was tested by scanning electron microscope. The test results are as follows: Figure 3 Shown It can be seen that the use of a main catalyst in combination with a co-catalyst can greatly increase the rate of the oxidation reaction, accelerate the reaction process and product yield.

[0042] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, characterized in that: The method comprises the following steps: 1) subjecting 2-nitro-4-trifluoromethylbenzonitrile to a methylsulfidation reaction to prepare 2-methylthio-4-trifluoromethylbenzonitrile; 2) subjecting the 2-methylthio-4-trifluoromethylbenzonitrile prepared in step 1) to an oxidation reaction under the action of a catalyst to prepare 2-methylsulfonyl-4-trifluoromethylbenzonitrile; and 3) subjecting the 2-methylsulfonyl-4-trifluoromethylbenzonitrile prepared in step 2) to an alkaline hydrolysis reaction and then 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: The step 1) further includes at least one of the following technical features: 11) the methyl sulfidation reaction is carried out in a solvent, and the solvent is one of DMF, DMSO, and DCM; 12) the sulfur source of the methyl sulfidation reaction is one of sodium sulfide, potassium sulfide, and sodium methyl mercaptan; 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: The step 2) further includes at least one of the following technical features: 21) the catalyst includes a main catalyst and a co-catalyst, and the main catalyst is a heteropolyacid; 22) the oxidizing agent of the oxidation reaction is hydrogen peroxide; 23) the temperature of the oxidation reaction is 80-85°C, and the reaction time is 5-10h.

4. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 3, characterized in that: The heteropoly acid 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 the step 2), the content of hydrogen peroxide 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 the 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 3, characterized in that: The co-catalyst is prepared by the following steps: S1: dissolving cyclodextrin and carrageenan in water to prepare a gel base liquid, then adding p-toluenesulfonyl imidazole to the gel base liquid, and reacting under alkaline conditions to obtain an intermediate liquid one; S2: placing melamine in a tubular furnace, heating it to 550° C. and calcining it for 3-5 hours to obtain a block solid, grinding it into powder, and then dispersing the powder into the intermediate liquid one, adding ferric nitrate, zinc nitrate and manganese nitrate and mixing them evenly, activating it at 60° C. for 2-3 hours, and obtaining an intermediate liquid two; S3: adding zirconium chloride, sodium silicate and triethyl phosphate to the intermediate liquid two, mixing them evenly, adding acetic acid and silicotungstic acid, stirring and reacting at 110-130° C. for 12-20 hours, then heating it to 180° C. and continuing to react for 2-5 hours, washing and drying to obtain the co-catalyst.

7. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 6, 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 intermediate solution 2, the added amount of zirconium chloride is 5-10%, the added amount of sodium silicate is 15-20%, and the added amount of triethyl phosphate is 2.5-3.5%; and / or, the reaction under alkaline conditions is to add sodium hydroxide and react at a temperature of 20-25°C.

8. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 1, characterized in that: The step 3) also 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°C; 34) the temperature of the acidification reaction is 20-35°C; 35) an organic base is also added in the alkaline hydrolysis reaction.

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

10. The method for synthesizing 2-methylsulfonyl-4-trifluoromethylbenzoic acid according to claim 8, 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.

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