Methods for preparing pyroxasulfone

Abstract

The application discloses a preparation method of metalaxyl-M, which comprises the following steps: ① in the presence of a catalyst and a solvent, a sulfide intermediate is oxidized by hydrogen peroxide to obtain a mixture containing metalaxyl-M and a sulfoxide intermediate; ② in the presence of a catalyst and a solvent, the mixture obtained in the step ① is oxidized by hydrogen peroxide to obtain metalaxyl-M; wherein the concentration of the hydrogen peroxide is 15-27.5 wt%, the dosage of the step ① is 1.1-1.9 times of the sulfide intermediate, and the dosage of the step ② is 0.2-1.5 times of the sulfide intermediate. The step-by-step oxidation method can greatly improve the effect of hydrogen peroxide on the oxidation of the sulfide intermediate, especially the sulfoxide intermediate, so that the problem of the sulfoxide intermediate residue can be solved by using low-concentration and low-dosage hydrogen peroxide, the concentration of the hydrogen peroxide is low, the dosage is small, the safety is higher, the post-treatment is simpler, the three wastes are less, and the environment is more friendly.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of herbicide preparation, and particularly relates to a preparation method of pyroxasulfone. BACKGROUND

[0002] Pyroxasulfone is an isoxazole herbicide, and its chemical name is 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, its molecular formula is C 12 H 14 F5N3O4S, and its molecular weight is 391.32, and its CAS registration number is 447399-55-5.

[0003] Pyroxasulfone is a broad-spectrum herbicide, and can effectively control a series of annual grass weeds, and is suitable for crops such as corn, soybean, wheat, peanut, cotton, sunflower and potato. Pyroxasulfone has excellent characteristics such as wide herbicidal spectrum, high activity, low dosage and good safety.

[0004] At present, the last step of synthesizing pyroxasulfone is basically to oxidize the thioether intermediate by hydrogen peroxide to obtain pyroxasulfone

see Chinese patent documents CN113754647A, CN113754648A, CN113831333A, CN117229273A, CN117417333A, CN117777122A, CN117924265A and the like

[0005] .

[0006] The oxidation reaction will have a small amount of impurity sulfoxide intermediate remaining in the finished product. The impurity structure is similar to that of pyroxasulfone, and it is very difficult to remove, resulting in low purity of pyroxasulfone finished product. Especially, the impurity will cause certain phytotoxicity to crops. In order to reduce the content of impurity sulfoxide intermediate and improve the purity of pyroxasulfone finished product, the methods used in the prior art mainly include the following:

[0007] I. Increase the amount of hydrogen peroxide and / or use high-concentration hydrogen peroxide.

[0008] (1) Increasing the amount of hydrogen peroxide

usually more than 3 molar equivalents

such as sodium thiosulfate

[0009] (2) Using high concentrations of hydrogen peroxide [usually above 30%] can achieve better oxidation effects, but the higher the concentration of hydrogen peroxide, the greater the risk of explosion, which brings greater safety hazards to the reaction.

[0010] II. Chinese patent document CN117794925A discloses a method for preparing sulfonylpyrazole that is basically free of sulfoxide intermediates. It uses sodium tungstate as a catalyst, organic acids such as acetic acid as a solvent, and 2.6 to 5 molar equivalents of 50% hydrogen peroxide as an oxidant, and finally obtains sulfonylpyrazole with a purity of more than 99%.

[0011] The shortcomings of this method are: (1) the use of sodium tungstate as a catalyst results in high production costs and is not suitable for large-scale industrial production; (2) the hydrogen peroxide concentration used in this literature is as high as 50%, and the amount of hydrogen peroxide used is also high (2.6 to 5 times molar equivalent), which also has the same problem as the first one mentioned above.

[0012] III. Chinese patent document CN114716429A discloses a method for synthesizing sulfonylpyrazole, which improves the purity of the product by using a functionalized ionic liquid (sulfonic acid imidazole ionic liquid) in combination with hydrogen peroxide for oxidation reaction, up to 99.2%.

[0013] The shortcomings of this method are: (1) the functionalized ionic liquid needs to be specially made, which leads to higher production costs and is also not suitable for large-scale industrial production; (2) the amount of hydrogen peroxide used in this literature is as high as 5 times the molar equivalent, and the concentration of hydrogen peroxide is also high (30%), which also has the same problem as the first one mentioned above.

[0014] IV. Chinese patent document CN117567452A discloses a method for preparing sulfonylpyrazole. On the one hand, the content of sulfoxide intermediate is controlled by fully carrying out the oxidation reaction under specific conditions (isopropanol solvent + sodium tungstate catalyst). On the other hand, the sulfoxide intermediate is completely removed by specific post-treatment, and finally sulfonylpyrazole with a purity of more than 99% is obtained.

[0015] The shortcomings of this method are: (1) the use of sodium tungstate as a catalyst results in a similarly high production cost and makes it unsuitable for large-scale industrial production; (3) the amount of hydrogen peroxide used (2.5 to 4 times the molar equivalent) and the concentration (28 to 60%) are still relatively high, and the problems of the first method mentioned above still exist. Summary of the Invention

[0016] The purpose of this invention is to solve the above problems and provide a method for preparing sulfopyrazole that not only has a better oxidation effect and higher product purity, but also has lower production cost, simpler post-processing, is more environmentally friendly, safer, and suitable for large-scale industrial production.

[0017] The technical concept of this invention is as follows: After extensive experiments, the applicant discovered that the fundamental reason why the oxidation of sulfide intermediates produces a large amount of sulfoxide intermediates is that the existing technology is a one-pot oxidation process. During the oxidation process, as hydrogen peroxide is consumed, its concentration gradually decreases, which greatly reduces the effect of subsequent oxidation of sulfoxide intermediates, ultimately resulting in a high content of sulfoxide intermediates.

[0018] Through extensive experimentation, the applicant discovered that changing the one-pot oxidation process to a step-by-step oxidation process—that is, first using a portion of hydrogen peroxide (approximately 70%) to oxidize the sulfide intermediate, and then processing it sequentially to obtain the mixture after it has been completely converted into sulfonylpyrazine and sulfoxide intermediates—can solve the problem of poor oxidation of sulfoxide intermediates caused by the decrease in hydrogen peroxide concentration in the later stages of the existing one-pot oxidation process.

[0019] The technical solution to achieve the objective of this invention is: a method for preparing sulfonylpyrazole, comprising the following steps:

[0020] ① In the presence of a catalyst and solvent, the sulfide intermediate is completely oxidized with hydrogen peroxide, and after post-treatment, a mixture containing sulfopyrazole and sulfoxide intermediates is obtained.

[0021] ② In the presence of a catalyst and a solvent, the mixture obtained in step ① is oxidized with hydrogen peroxide to obtain sulfopyrazine.

[0022] In steps ① and ② above, the concentration of hydrogen peroxide is 15 to 27.5 wt%, preferably 27.5 wt% [this concentration is the optimal concentration for industrial hydrogen peroxide].

[0023] In step ① above, the molar amount of hydrogen peroxide is 1.1 to 1.9 times that of the sulfide intermediate, preferably 1.5 times.

[0024] In step ② above, the molar amount of hydrogen peroxide is 0.2 to 1.5 times that of the thioether intermediate in step ①, preferably 0.6 times.

[0025] In steps ① and ② above, the catalyst is an inorganic acid, preferably sulfuric acid.

[0026] In step ① above, the molar amount of the catalyst is 0.5 to 2 times that of the sulfide intermediate, preferably 0.75 times.

[0027] In step ② above, the molar amount of the catalyst is 0.2 to 1.5 times that of the sulfide intermediate in step ①, preferably 0.5 times.

[0028] In steps ① and ② above, the solvent is a mixed solvent; the mixed solvent is acetic acid + alcohol solvent.

[0029] In the mixed solvent, the weight ratio of acetic acid to alcohol solvent is 1:10 to 10:1, preferably 1:1.

[0030] The alcohol solvent is one of methanol, ethanol, isopropanol, and tert-butanol, preferably ethanol.

[0031] In steps ① and ② above, the oxidation reaction temperature is 65–85°C, preferably 75–80°C.

[0032] The positive effects of this invention are:

[0033] (1) The stepwise oxidation method of the present invention can greatly improve the effect of hydrogen peroxide oxidation of sulfide intermediates, especially sulfoxide intermediates, thereby solving the problem of sulfoxide intermediate residue with low concentration and low amount of hydrogen peroxide.

[0034] (2) The stepwise oxidation method of the present invention uses hydrogen peroxide with low concentration and small amount. Compared with the prior art which uses hydrogen peroxide with a concentration of more than 30% and / or more than 3 times the molar equivalent, it not only has higher safety, but also leaves less hydrogen peroxide residue after the reaction, making the post-treatment simpler, with less waste, and is more environmentally friendly.

[0035] (3) The stepwise oxidation method of the present invention only requires conventional inorganic acids such as sulfuric acid as catalysts. Compared with the existing technology that requires sodium tungstate or special catalysts to achieve better oxidation effect, it greatly reduces production costs and is more suitable for large-scale industrial production.

[0036] (4) The stepwise oxidation method of the present invention uses a combination of solvents to achieve better reaction results and more complete reaction. Detailed Implementation

[0037] (Example 1)

[0038] The specific preparation method of sulfonylpyrazole in this embodiment is as follows:

[0039] ① Add 35.9 g of thioether intermediate (0.1 mol), 50 g of acetic acid, 50 g of ethanol and 7.5 g of sulfuric acid (0.075 mol, 0.75 eq) to a four-necked reaction flask, stir and heat to 75-80℃, and add 18.5 g of 27.5 wt% hydrogen peroxide (0.15 mol, 1.5 eq) dropwise under controlled temperature. After the addition is complete, maintain the reaction at 75-80℃ until HPLC monitoring shows that the thioether intermediate has been completely converted.

[0040] After the reaction was completed, 75g of water was added dropwise at a controlled temperature of 75-80℃. After the addition was completed, the mixture was stirred at 75-80℃ for 10 minutes, and then cooled to 5-10℃. The solid precipitated and was filtered to obtain a mixture containing sulfoxide intermediate and sulfonylpyrazole (no drying required, it can be used directly in the next step). The sulfoxide intermediate content in the mixture was 50.4%, and the sulfonylpyrazole content was 48.8%.

[0041] ② Add the mixture obtained in step ① to another four-necked reaction flask, then add 50g of acetic acid and 50g of ethanol. Next, add 5g of sulfuric acid (0.05mol, 0.5eq) dropwise while stirring. After the addition is complete, raise the temperature to 75-80℃ and add 7.4g of 27.5wt% hydrogen peroxide (0.06mol, 0.6eq) dropwise while controlling the temperature. After the addition is complete, keep the reaction at 75-80℃ until HPLC monitoring shows that the sulfoxide intermediate has been completely converted (reaction time is about 1 hour).

[0042] After the reaction was completed, 90g of water was added dropwise at a controlled temperature of 75-80℃. After the addition was completed, the mixture was stirred at 75-80℃ for 10 minutes, and then cooled to 5-10℃. The solid precipitated, was filtered, and the filter cake was washed with 60g of water and dried to obtain 37.8g of sulfonylpyrazine, with a yield of 96.7% and an HPLC purity of 99.4%. No sulfoxide intermediate was detected.

[0043] (Example 2 to Example 3)

[0044] The preparation methods of sulfopyrazole in each embodiment are basically the same as those in Example 1, and the differences are shown in Table 1.

[0045] Table 1

[0046] Example 1 Example 2 Example 3 Step 1 hydrogen peroxide concentration 27.5% 20% 15% Step 1 hydrogen peroxide amount 18.5g 25.5g 34g Step 1 hydrogen peroxide molar equivalents 1.5 eq 1.5 eq 1.5 eq Mixture sulfoxide intermediate content 50.4% 53.7% 55.0% Mixture metrafenone content 48.8% 45.0% 43.5% Step 2 hydrogen peroxide concentration 27.5% 20% 15% Step 2 hydrogen peroxide amount 7.4g 10.2g 13.6g Step 2 hydrogen peroxide molar equivalents 0.6 eq 0.6 eq 0.6 eq Metrafenone 37.8g 34.2g 31.7g Yield 96.7% 87.5% 81.1% Purity 99.4% 98.3% 98.0%

[0047] (Examples 4-5)

[0048] The preparation methods of sulfopyrazole in each embodiment are basically the same as those in Example 1, with the differences shown in Table 2.

[0049] Table 2

[0050] Example 1 Example 4 Example 5 Acetic acid 50g 50g 50g Alcoholic solvent 50 g ethanol 50 g isopropanol 50 g t-butanol Mixture sulfoxide intermediate content 50.4% 52.5% 54.0% Mixture metrafenone content 48.8% 46.3% 44.1% Metrafenone 37.8g 36.2g 35.5g Yield 96.7% 92.6% 90.8% Purity 99.4% 98.7% 98.3%

[0051] (Comparative Example 1)

[0052] The specific preparation method of sulfonylpyrazole in this comparative example is as follows:

[0053] 35.9 g of thioether intermediate (0.1 mol), 50 g of acetic acid, 50 g of ethanol and 12.5 g of sulfuric acid (0.125 mol, 1.25 eq) were added to a four-necked reaction flask. The mixture was stirred and heated to 75–80 °C. 26.0 g of 27.5 wt% hydrogen peroxide (0.21 mol, 2.1 eq) was added dropwise under controlled temperature. After the addition was complete, the reaction was maintained at 75–80 °C until complete. HPLC monitoring showed that 10.7% of the sulfoxide intermediate remained.

[0054] After the reaction was completed, 100 g of water was added dropwise at a controlled temperature of 75–80 °C. After the addition was completed, the mixture was stirred at 75–80 °C for 10 min, and then cooled to 5–10 °C. The solid precipitated, was filtered, and the filter cake was washed with 60 g of water and dried to obtain 33.3 g of sulfonylpyrazine, with a yield of 85.2% and an HPLC purity of 88.4% (sulfoxide intermediate content was 9.6%).

[0055] (Comparative Example 2)

[0056] The specific preparation method of sulfonylpyrazole in this comparative example is as follows:

[0057] Add 35.9 g of thioether intermediate (0.1 mol), 50 g of acetic acid, 50 g of ethanol and 12.5 g of sulfuric acid (0.125 mol, 1.25 eq) to a four-necked reaction flask, stir and heat to 75-80 °C, and add 30.9 g of 27.5 wt% hydrogen peroxide (0.25 mol, 2.5 eq) dropwise under controlled temperature. After the addition is complete, maintain the reaction at 75-80 °C until complete. HPLC monitoring showed that 2.8% of sulfoxide intermediate remained.

[0058] After the reaction was completed, 100g of water was added dropwise at a controlled temperature of 75-80℃. After the addition was complete, the mixture was stirred at 75-80℃ for 10 minutes, then cooled to 5-10℃, and a solid precipitated. The solid was filtered, and sodium sulfite was added to the filtrate to quench excess hydrogen peroxide. The filter cake was washed with 60g of water and dried to obtain 35.6g of sulfonylpyrazol, with a yield of 91.0% and an HPLC purity of 95.2% (sulfonyl intermediate content was 2.6%).

[0059] (Comparative Examples 3 to 5)

[0060] The preparation methods of sulfonylpyrazole in each comparative example are basically the same as those in comparative examples 1 and 2, with the differences shown in Table 3.

[0061] Table 3

[0062] Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Step 1 hydrogen peroxide concentration 27.5% 27.5% 27.5% 30% 35% Step 1 hydrogen peroxide amount 26.0g 30.9g 37.1g 23.8g 20.4g Step 1 hydrogen peroxide molar equivalents 2.1 eq 2.5 eq 3.0 eq 2.1 eq 2.1 eq Mixture sulfoxide intermediate content 10.7% 2.8% 2.0% 10.2% 10.5% Metrafenone 33.3g 35.6g 37.0g 34.1g 33.8g Yield 85.2% 91.0% 94.6% 87.2% 86.4% Purity 88.4% 95.2% 97.5% 88.5% 87.0% Mixture sulfoxide intermediate content Mixture metrafenone content Metrafenone Yield Purity Finished sulfoxide intermediate content 9.6% 2.6% 1.6% 9.8% 10.0%

Claims

1. A method for preparing a mesotrione, comprising the following steps: ① oxidizing a thioether intermediate with hydrogen peroxide in the presence of a catalyst and a solvent to obtain a mixture containing mesotrione and a sulfoxide intermediate after post-treatment; ② oxidizing the mixture obtained in step ① with hydrogen peroxide in the presence of a catalyst and a solvent to obtain mesotrione. In the above steps ① and ②, the concentration of the hydrogen peroxide is 27.5 wt%. In the above step ①, the molar amount of the hydrogen peroxide is 1.5 times that of the thioether intermediate; in the above step ②, the molar amount of the hydrogen peroxide is 0.6 times that of the thioether intermediate in step ①. In the above steps ① and ②, the catalyst is an inorganic acid. In the above step ①, the molar amount of the catalyst is 0.5-2 times that of the thioether intermediate; in the above step ②, the molar amount of the catalyst is 0.2-1.5 times that of the thioether intermediate in step ①. In the above steps ① and ②, the solvent is a mixed solvent; the mixed solvent is acetic acid + an alcoholic solvent; the alcoholic solvent is one of methanol, ethanol, isopropanol and tert-butanol. In the mixed solvent, the weight ratio of acetic acid to the alcoholic solvent is 1:10-10:

1.

2. The method of preparing metalochlor according to claim 1, characterized in that: In the above steps ① and ②, the reaction temperature for the oxidation is 65-85℃.

3. The method of preparing metalochlor according to claim 2, characterized in that: ​ 4. The method of preparing metalochlor according to claim 1, characterized in that: ​