Preparation method of pyroxasulfone

Abstract

The invention discloses a pyroxasulfone preparation method, which comprises: (1) in the presence of a catalyst and a solvent, completely oxidizing a thioether intermediate with hydrogen peroxide, and carrying out post-treatment to obtain a mixture containing pyroxasulfone and a sulfoxide intermediate; (2) in the presence of a catalyst and a solvent, oxidizing the mixture obtained in the step (1) by using hydrogen peroxide to obtain pyroxasulfone; wherein the concentration of the hydrogen peroxide is 15-27.5 wt%, the dosage in the step (1) is 1.1-1.9 times that of the thioether intermediate, and the dosage in the step (2) is 0.2-1.5 times that of the thioether intermediate. According to the step-by-step oxidation method, the effect of oxidizing the thioether intermediate, especially the sulfoxide intermediate, by the hydrogen peroxide can be greatly improved, so that the problem of sulfoxide intermediate residue can be solved by the low-concentration and low-dosage hydrogen peroxide, and the hydrogen peroxide is low in concentration and small in dosage, has higher safety, is simpler in post-treatment and less in three wastes, and is suitable for industrial production. And the method is environment-friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of herbicide preparation, and particularly relates to a method for preparing pyraclostrobin. Background Art

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

[0003] Sulfonepyraclostrobin is a broad-spectrum herbicide that can effectively control a series of annual grass weeds and is suitable for crops such as corn, soybeans, wheat, peanuts, cotton, sunflowers and potatoes. Sulfonepyraclostrobin has the advantages of broad weed control spectrum, high activity, low dosage and good safety.

[0004] At present, the last step of synthesizing sulfonepyraclostrobin is basically to oxidize the sulfide intermediate with hydrogen peroxide to obtain sulfonepyraclostrobin [see Chinese patent documents CN113754647A, CN113754648A, CN113831333A, CN117229273A, CN117417333A, CN117777122A, CN117924265A, etc.], and the reaction formula is as follows: .

[0005] The oxidation reaction will leave a small amount of impurity sulfoxide intermediates in the finished product. The impurity structure is similar to that of sulfonepyraclostrobin and is very difficult to remove, resulting in low purity of the sulfonepyraclostrobin finished product. In particular, the impurity will cause certain phytotoxicity to crops. In order to reduce the content of the impurity sulfoxide intermediate and improve the purity of the sulfonepyraclostrobin finished product, the methods used in the prior art mainly include the following: 1. Increase the amount of hydrogen peroxide and / or use high concentration hydrogen peroxide.

[0006] (1) Increasing the amount of hydrogen peroxide (usually more than 3 times the molar equivalent) not only has limited effect on improving the purity of the product, but also leaves a large amount of hydrogen peroxide residue after the reaction, leading to complicated post-processing. In particular, a large amount of reducing agent (such as sodium thiosulfate) is required to quench the excess hydrogen peroxide, which not only increases costs but also produces more waste, which is not environmentally friendly.

[0007] (2) Although the use of high-concentration hydrogen peroxide [usually above 30%] can achieve a better oxidation effect, the higher the concentration of hydrogen peroxide, the greater the risk of explosion, which poses a greater safety hazard to the reaction.

[0008] 2. Chinese patent document CN117794925A discloses a method for preparing sulfonepyraclostrobin which is substantially free of sulfoxide intermediates, using sodium tungstate or the like as a catalyst, acetic acid or the like as a solvent, and 2.6 to 5 times the molar equivalent of 50% hydrogen peroxide as an oxidant, and finally obtaining sulfonepyraclostrobin with a high purity of more than 99%.

[0009] The shortcomings of this method are: (1) the use of sodium tungstate as a catalyst leads to high production costs and is not suitable for large-scale industrial production; (2) the hydrogen peroxide concentration used in this document is as high as 50%, and the amount of hydrogen peroxide used is also high (2.6 to 5 times the molar equivalent), which also has the first problem mentioned above.

[0010] 3. Chinese patent document CN114716429A discloses a method for synthesizing sulfonepyraclostrobin, which uses a functionalized ionic liquid (sulfonic acid imidazole ionic liquid) and hydrogen peroxide to carry out an oxidation reaction, thereby improving the purity of the product to a maximum of 99.2%.

[0011] The shortcomings of this method are: (1) the functionalized ionic liquid needs to be specially prepared, resulting in higher production costs and is also not suitable for large-scale industrial production; (2) the amount of hydrogen peroxide used in this document is as high as 5 times the molar equivalent, and the concentration of hydrogen peroxide is also high (30%), which also has the first problem mentioned above.

[0012] 4. Chinese patent document CN117567452A discloses a method for preparing sulfonepyraclostrobin. On the one hand, the oxidation reaction is fully carried out under specific conditions (isopropanol solvent + sodium tungstate catalyst) to control the content of sulfoxide intermediates. On the other hand, the sulfoxide intermediates are completely removed through specific post-treatment to finally obtain sulfonepyraclostrobin with a high purity of more than 99%.

[0013] The shortcomings of this method are: (1) the use of sodium tungstate as a catalyst leads to high production costs and is also not suitable 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 high, and the first problem mentioned above still exists. Summary of the invention

[0014] The object of the present invention is to solve the above problems and provide a method for preparing sulfonepyraclostrobin which has not only good oxidation effect and high product purity, but also low production cost, simple post-treatment, better environmental friendliness, higher safety and is suitable for large-scale industrial production.

[0015] The technical concept of the present invention is as follows: The applicant has found through a large number of experiments that the fundamental reason why the oxidation of thioether intermediates produces a large amount of sulfoxide intermediates is that the existing technologies all use a one-pot oxidation process. During the oxidation process, as hydrogen peroxide is consumed, its concentration gradually decreases, resulting in a significant reduction in the effect of subsequent oxidation of the sulfoxide intermediate, ultimately leading to a high content of the sulfoxide intermediate.

[0016] After a large number of experiments, the applicant found that: by changing the one-pot oxidation to a step-by-step oxidation, that is, first using a portion of hydrogen peroxide (about 70%) to oxidize the thioether intermediate, and after it is completely converted into sulfonepyraclostrobin and sulfoxide intermediates, the mixture is treated in sequence, and then the mixture is oxidized with the remaining 30% of hydrogen peroxide. In this way, the problem of poor oxidation effect of sulfoxide intermediates caused by the reduction of hydrogen peroxide concentration in the later stage of the existing one-pot oxidation can be solved.

[0017] The technical solution for achieving the purpose of the present invention is: a method for preparing sulfonepyraclostrobin, comprising the following steps: ① In the presence of a catalyst and a solvent, the sulfide intermediate is completely oxidized with hydrogen peroxide, and a mixture containing sulfonepyraclostrobin and sulfoxide intermediate is obtained through post-treatment; ② In the presence of a catalyst and a solvent, the mixture obtained in step ① is oxidized with hydrogen peroxide to obtain sulfonepyraclostrobin.

[0018] In the above steps ① and ②, the concentration of the hydrogen peroxide is 15-27.5wt%, preferably 27.5wt% [this concentration is the optimal concentration of industrial hydrogen peroxide].

[0019] In the above step ①, the molar amount of the hydrogen peroxide is 1.1 to 1.9 times that of the thioether intermediate, preferably 1.5 times.

[0020] In the above step ②, the molar amount of the hydrogen peroxide is 0.2 to 1.5 times, preferably 0.6 times, of the thioether intermediate in step ①.

[0021] In the above steps ① and ②, the catalyst is an inorganic acid, preferably sulfuric acid.

[0022] In the above step ①, the molar amount of the catalyst is 0.5 to 2 times, preferably 0.75 times, of the thioether intermediate.

[0023] In the above step ②, the molar amount of the catalyst is 0.2 to 1.5 times, preferably 0.5 times, of the sulfide intermediate in step ①.

[0024] In the above steps ① and ②, the solvent is a mixed solvent; the mixed solvent is acetic acid + alcohol solvent.

[0025] In the mixed solvent, the weight ratio of acetic acid to alcohol solvent is 1:10 to 10:1, preferably 1:1.

[0026] The alcohol solvent is one of methanol, ethanol, isopropanol and tert-butanol, preferably ethanol.

[0027] In the above steps ① and ②, the oxidation reaction temperature is 65 to 85°C, preferably 75 to 80°C.

[0028] The present invention has the positive effects: (1) The stepwise oxidation method of the present invention can greatly improve the effect of hydrogen peroxide on the oxidation of sulfide intermediates, especially sulfoxide intermediates, thereby solving the problem of residual sulfoxide intermediates with low concentration and low dosage of hydrogen peroxide.

[0029] (2) The step-by-step oxidation method of the present invention uses a low concentration of hydrogen peroxide and a small amount of hydrogen peroxide. Compared with the prior art using a concentration of more than 30% and / or more than 3 times the molar equivalent of hydrogen peroxide, it is not only safer, but also has less residual hydrogen peroxide after the reaction, simpler post-treatment, less waste, and more environmentally friendly.

[0030] (3) The step-by-step oxidation method of the present invention only requires conventional sulfuric acid or other inorganic acids as catalysts. Compared with the prior art which requires sodium tungstate or special catalysts to achieve better oxidation effects, the production cost is greatly reduced and it is more suitable for large-scale industrial production.

[0031] (4) The step-by-step oxidation method of the present invention uses a combination of solvents to achieve better reaction effects and more complete reactions. DETAILED DESCRIPTION

[0032] (Example 1) The preparation method of sulfonepyraclostrobin in this embodiment is as follows: 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) into a four-necked reaction bottle, stir and heat to 75-80 ° C, control the temperature and add 18.5 g of 27.5 wt% hydrogen peroxide (0.15 mol, 1.5 eq) dropwise, keep the reaction at 75-80 ° C until HPLC monitoring shows that the thioether intermediate has been completely converted.

[0033] After the reaction is completed, 75 g of water is added dropwise at a temperature of 75 to 80 ° C. After the addition, the mixture is stirred at a temperature of 75 to 80 ° C for 10 minutes, and then cooled to 5 to 10 ° C. The solid is precipitated and filtered to obtain a mixture containing a sulfoxide intermediate and sulfonepyraclostrobin (no need to dry, directly used in the next step), the sulfoxide intermediate content in the mixture is 50.4%, and the sulfonepyraclostrobin content is 48.8%.

[0034] ② Add the mixture obtained in step ① into another four-necked reaction bottle, then add 50 g of acetic acid and 50 g of ethanol, then add 5 g of sulfuric acid (0.05 mol, 0.5 eq) dropwise while stirring, raise the temperature to 75-80°C, add 7.4 g of 27.5 wt% hydrogen peroxide (0.06 mol, 0.6 eq) dropwise at a temperature controlled to react at 75-80°C until HPLC monitoring shows that the sulfoxide intermediate has been completely converted (reaction time is about 1 h).

[0035] After the reaction, 90 g of water was added dropwise at a temperature of 75 to 80 ° C. After the addition, the mixture was stirred at 75 to 80 ° C for 10 min, and then cooled to 5 to 10 ° C. The solid was precipitated and filtered. The filter cake was washed with 60 g of water and then dried to obtain 37.8 g of sulfonepyraclostrobin with a yield of 96.7%. The HPLC purity was 99.4%, and no sulfoxide intermediate was detected.

[0036] (Example 2 to Example 3) The preparation methods of sulfonepyraclostrobin in each embodiment are basically the same as that in Example 1, and the differences are shown in Table 1.

[0037] Table 1 Example 1 Example 2 Example 3 Step ① Hydrogen peroxide concentration 27.5% 20% 15% Step ① Amount of hydrogen peroxide 18.5g 25.5g 34g Step ① Hydrogen peroxide molar equivalent 1.5eq 1.5eq 1.5eq Sulfoxide intermediate content of the mixture 50.4% 53.7% 55.0% Content of sulfonepyraclostrobin in mixture 48.8% 45.0% 43.5% Step ② Hydrogen peroxide concentration 27.5% 20% 15% Step ②Amount of hydrogen peroxide 7.4g 10.2g 13.6g Step ② Hydrogen peroxide molar equivalent 0.6eq 0.6eq 0.6eq Sulfonepyraclostrobin 37.8g 34.2g 31.7g Yield 96.7% 87.5% 81.1% purity 99.4% 98.3% 98.0%

[0038] (Example 4 to Example 5) The preparation methods of sulfonepyraclostrobin in each embodiment are basically the same as that in Example 1, and the differences are shown in Table 2.

[0039] Table 2 Example 1 Example 4 Example 5 Acetic acid 50g 50g 50g Alcohol solvents 50g ethanol 50g isopropyl alcohol 50g tert-butyl alcohol Sulfoxide intermediate content of the mixture 50.4% 52.5% 54.0% Content of sulfonepyraclostrobin in mixture 48.8% 46.3% 44.1% Sulfonepyraclostrobin 37.8g 36.2g 35.5g Yield 96.7% 92.6% 90.8% purity 99.4% 98.7% 98.3%

[0040] (Comparative Example 1) The preparation method of sulfonepyraclostrobin in this comparative example is as follows: 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, and the temperature was raised to 75-80°C with stirring. 26.0 g of 27.5 wt% hydrogen peroxide (0.21 mol, 2.1 eq) was added dropwise under temperature control. After the addition was completed, the mixture was kept at 75-80°C for reaction until completion. HPLC monitoring showed that 10.7% of the sulfoxide intermediate remained.

[0041] After the reaction, 100 ml of water was added dropwise at a temperature of 75-80°C, and the mixture was stirred at 75-80°C for 10 min. The mixture was then cooled to 5-10°C, and a solid was precipitated. The solid was filtered and the filter cake was washed with 60 g of water and dried to obtain 33.3 g of sulfonepyraclostrobin with a yield of 85.2% and a HPLC purity of 88.4% (the sulfoxide intermediate content was 9.6%).

[0042] (Comparative Example 2) The preparation method of sulfonepyraclostrobin in this comparative example is as follows: 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, and the temperature was raised to 75-80°C with stirring. 30.9 g of 27.5 wt% hydrogen peroxide (0.25 mol, 2.5 eq) was added dropwise under temperature control. After the addition was completed, the mixture was kept at 75-80°C for reaction until completion. HPLC monitoring showed that 2.8% of the sulfoxide intermediate remained.

[0043] After the reaction, 100 g of water was added dropwise at a temperature of 75 to 80 ° C. After the addition, the mixture was stirred at 75 to 80 ° C for 10 min, then cooled to 5 to 10 ° C., solids were precipitated, filtered, and sodium sulfite was added to the filtrate to quench excess hydrogen peroxide. The filter cake was washed with 60 g of water and then dried to obtain 35.6 g of sulfonepyraclostrobin with a yield of 91.0% and an HPLC purity of 95.2% (the content of sulfoxide intermediate was 2.6%).

[0044] (Comparative Example 3 to Comparative Example 5) The preparation methods of sulfonepyraclostrobin in each comparative example are basically the same as those in comparative examples 1 and 2, and the differences are shown in Table 3.

[0045] Table 3 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 Amount of hydrogen peroxide 26.0g 30.9g 37.1g 23.8g 20.4g Step ① Hydrogen peroxide molar equivalent 2.1eq 2.5eq 3.0eq 2.1eq 2.1eq Control the content of sulfoxide intermediates 10.7% 2.8% 2.0% 10.2% 10.5% Sulfonepyraclostrobin 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% Content of sulfoxide intermediate in finished product 9.6% 2.6% 1.6% 9.8% 10.0%

Claims

1. A method for preparing sulfonepyraclostrobin, comprising the following steps: ① In the presence of a catalyst and a solvent, the sulfide intermediate is completely oxidized with hydrogen peroxide, and a mixture containing sulfonepyraclostrobin and sulfoxide intermediate is obtained through post-treatment; ② In the presence of a catalyst and a solvent, the mixture obtained in step ① is oxidized with hydrogen peroxide to obtain sulfonepyraclostrobin.

2. The method for preparing sulfonepyraclostrobin according to claim 1, characterized in that: In the above steps ① and ②, the concentration of the hydrogen peroxide is 15 to 27.5 wt %.

3. The method for preparing sulfonepyraclostrobin according to claim 2, characterized in that: In the above steps ① and ②, the concentration of the hydrogen peroxide is 27.5wt%.

4. The method for preparing sulfonepyraclostrobin according to claim 1, characterized in that: In the above step ①, the molar amount of the hydrogen peroxide is 1.1 to 1.9 times that of the thioether intermediate; in the above step ②, the molar amount of the hydrogen peroxide is 0.2 to 1.5 times that of the thioether intermediate in step ①.

5. The method for preparing sulfonepyraclostrobin according to claim 4, characterized in that: 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.

6. The method for preparing sulfonepyraclostrobin according to any one of claims 1 to 5, characterized in that: In the above steps ① and ②, the catalyst is an inorganic acid.

7. The method for preparing sulfonepyraclostrobin according to claim 6, characterized in that: In the above step ①, the molar amount of the catalyst is 0.5 to 2 times that of the sulfide intermediate; in the above step ②, the molar amount of the catalyst is 0.2 to 1.5 times that of the sulfide intermediate in step ①.

8. The method for preparing sulfonepyraclostrobin according to any one of claims 1 to 5, characterized in that: In the above steps ① and ②, the solvent is a mixed solvent; the mixed solvent is acetic acid + alcohol solvent; the alcohol solvent is one of methanol, ethanol, isopropanol, and tert-butanol.

9. The method for preparing sulfonepyraclostrobin according to claim 8, characterized in that: In the mixed solvent, the weight ratio of acetic acid to alcohol solvent is 1:10 to 10:

1.

10. The method for preparing sulfonepyraclostrobin according to any one of claims 1 to 5, characterized in that: In the above steps ① and ②, the oxidation reaction temperature is 65-85°C.