Synthesis method of pyroxasulfone
By using persulfate and concentrated sulfuric acid as oxidants and catalysts, the synthesis reaction conditions of sulfonylpyrazole were optimized, solving the problems of slow reaction rate and impurity control in the existing technology, and achieving the production of sulfonylpyrazole with high yield and high purity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HEFEI JIUYI AGRI DEV
- Filing Date
- 2024-11-25
- Publication Date
- 2026-05-26
Smart Images
Figure CN122079975A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing sulfonylpyrazole. Background Technology
[0002] Pyroxasulfone (CAS No.: 447399-55-5) is an isoxazole herbicide developed by Japan's Combinatorial Chemicals Co., Ltd., and its chemical structure is shown below:
[0003]
[0004] Sulfonamide is a sulfonylurea herbicide mainly used in the field management of cereal crops (such as wheat, barley, and corn) to control broadleaf weeds and certain grass weeds. It has the following characteristics:
[0005] (1) High efficiency: Sulfonazole has high activity against a variety of broadleaf weeds and some grass weeds. It requires a small amount of dosage and has a significant effect.
[0006] (2) Selectivity: It has good selectivity for cereal crops and will not cause damage to the crops.
[0007] (3) Low toxicity: It has low toxicity to humans and animals and is environmentally friendly.
[0008] (4) Broad spectrum: It can control a variety of annual and perennial weeds, including broadleaf weeds and some grass weeds.
[0009] Currently, in the synthesis of sulfonylpyrazine, the structure shown in Formula 1 is a common intermediate compound:
[0010]
[0011] In existing technologies, methods for preparing sulfonylpyrazine from the compound shown in Formula 1 often employ hydrogen peroxide for oxidation, as shown in the following reaction formula:
[0012]
[0013] For example, the invention patent with publication number CN113831333B discloses a method for synthesizing sulfonylpyrazole, comprising: adding a compound of formula 1 and a catalyst to a solvent, and then adding hydrogen peroxide with a concentration of 27.5-50% dropwise at 20-80°C to carry out an oxidation reaction to obtain sulfonylpyrazole; wherein the solvent is one of methanol, ethanol, acetonitrile, and tetrahydrofuran; and the catalyst is one of sodium tungstate and ammonium molybdate. The sulfonylpyrazole prepared under these reaction conditions has a yield of 95.0-95.3% and a purity of 98.3-98.5%.
[0014] US Patent No. 20120264947 discloses a method for preparing sulfonylpyrazole from the compound shown in Formula 1, comprising: oxidizing the compound shown in Formula 1 at room temperature for 16 hours in the presence of sodium tungstate dihydrate, hydrogen peroxide and acetic acid to obtain sulfonylpyrazole.
[0015] Chinese patent application CN118307533A discloses a method for preparing sulfonylpyrazole from the compound shown in Formula 1, comprising: mixing the compound shown in Formula 1, a solvent, a catalyst, and hydrogen peroxide to carry out an oxidation reaction to obtain sulfonylpyrazole. The solvent is methanol, ethanol, or tetrahydrofuran; the catalyst is sodium tungstate or ammonium molybdate; the mass concentration of the hydrogen peroxide is 30-40%; the mass ratio of the sulfide, catalyst, and hydrogen peroxide is 30-40:0.2-1:40-55; the oxidation reaction is carried out at a temperature of 20-25°C for 0.5-6 hours.
[0016] All of the above methods use hydrogen peroxide for oxidation, which is slow, produces oxygen, and generates harmful byproducts. Furthermore, the yield and purity of the reaction need to be further improved, and the impurity content needs to be further reduced.
[0017]
[0018] During the synthesis of sulfonylpyrazole, the compound shown in Formula 2 is a byproduct with a structure similar to the product sulfonylpyrazole, making it difficult to remove. However, failure to separate the compound shown in Formula 2 may lead to a decrease in the quality of the sulfonylpyrazole formulation and may also cause toxicity to crops. Therefore, controlling the content of the impurity shown in Formula 2 is particularly important.
[0019] Due to the above-mentioned drawbacks, the present invention provides a method for synthesizing sulfopyrazole, which can improve the yield and purity of the product, reduce the content of impurities shown in Formula 2, and facilitate large-scale production. Summary of the Invention
[0020] This invention addresses the problems existing in the prior art by providing a method for synthesizing sulfonylpyrazine, which can improve the yield and purity of the product, reduce the content of impurities and reaction time, and reduce the content of oxide impurities in the product to less than 0.1%, which is beneficial for quality control and large-scale production.
[0021] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0022] In a first aspect, the present invention provides a method for synthesizing sulfonylpyrazole, comprising the following steps:
[0023] The compound shown in Formula 1 undergoes an oxidation reaction under the action of an oxidizing agent and a catalyst to give sulfonylpyrazol:
[0024]
[0025] The oxidant is selected from persulfates.
[0026] The persulfate is a commonly used type of persulfate. Preferably, the persulfate is selected from ammonium persulfate, sodium persulfate, potassium persulfate, or potassium peroxymonosulfate, and more preferably, ammonium persulfate or potassium persulfate.
[0027] The catalyst is preferably concentrated sulfuric acid, and the molar ratio of the catalyst, oxidant, and compound shown in Formula 1 is 0.1-0.5:2.5-3.0:1, preferably 0.1-0.5:3.0:1, and more preferably 0.1:3.0:1. In one embodiment, the compound shown in Formula 1 undergoes an oxidation reaction under the action of an oxidant and a catalyst to obtain sulfonylpyrazol; the oxidant is ammonium persulfate; the catalyst is concentrated sulfuric acid; the oxidation reaction further includes a solvent, the solvent being methanol; the molar ratio of concentrated sulfuric acid, ammonium persulfate, and compound shown in Formula 1 is 0.1-0.5:2.5-3.0:1, preferably 0.1-0.5:3.0:1, and more preferably 0.1:3.0:1.
[0028] The oxidation reaction is carried out at a temperature of 30-100℃, preferably 60-75℃, and more preferably 60-65℃.
[0029] The oxidation reaction takes 0.5-10 hours, preferably 0.5-5 hours, and more preferably 2 hours.
[0030] The oxidation reaction further includes a solvent, which includes commonly used solvent types for oxidation reactions. The solvent does not participate in the oxidation reaction but serves as the reaction medium in the system. The solvent is selected from alcohol solvents or nitrile solvents. Preferably, the alcohol solvent is selected from methanol, ethanol, isopropanol, or tert-butanol, more preferably methanol or ethanol, and most preferably methanol. The nitrile solvent is preferably acetonitrile.
[0031] In one embodiment, the compound shown in Formula 1 undergoes an oxidation reaction under the action of an oxidant and a catalyst to obtain sulfonylpyrazol; the oxidant is ammonium persulfate; the catalyst is concentrated sulfuric acid; the oxidation reaction further includes a solvent, the solvent being methanol; the molar ratio of concentrated sulfuric acid, ammonium persulfate, and the compound shown in Formula 1 is 0.1-0.5:2.5-3.0:1, preferably 0.1-0.5:3.0:1, more preferably 0.1:3.0:1; the oxidation reaction temperature is 30-100℃, preferably 60-75℃, more preferably 60-65℃.
[0032] In one embodiment, the compound shown in Formula 1 undergoes an oxidation reaction under the action of an oxidant and a catalyst to yield sulfonylpyrazol; the oxidant is ammonium persulfate; the catalyst is concentrated sulfuric acid; the oxidation reaction further includes a solvent, the solvent being methanol; the molar ratio of concentrated sulfuric acid, ammonium persulfate, and the compound shown in Formula 1 is 0.1-0.5:2.5-3.0:1, preferably 0.1-0.5:3.0:1, more preferably 0.1:3.0:1; the oxidation reaction temperature is 30-100℃, preferably 60-75℃, more preferably 60-65℃. The oxidation reaction time is preferably 2 hours.
[0033] Compared with the prior art, the present invention has the following beneficial effects:
[0034] In the synthesis method of sulfonylpyrazole provided by the present invention, persulfate is used as an oxidant, and the prepared sulfonylpyrazole has higher yield and purity, reduces the content of impurities and reaction time, and the content of monoxide impurities in the product is less than 0.1%, which is beneficial to quality control and large-scale production. Detailed Implementation
[0035] It is worth noting that, unless otherwise specified, the raw materials used in this invention are all commercially available products, and their sources are not specifically limited.
[0036] In the product of this invention embodiment, the structure of the oxide impurity is shown in Formula 2:
[0037]
[0038] Examples 1-6
[0039] Synthesis method of sulfonylpyrazole:
[0040]
[0041] At room temperature, using methanol as the solvent, ammonium persulfate (oxidant) and concentrated sulfuric acid (catalyst) were added sequentially to 60 mL of methanol. After heating to the reaction temperature, the compound shown in Formula 1 (3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, purity: 99.0%, 55.1 mmol, 1.0 eq) was added dropwise. The reaction temperature was kept constant, and after 2 hours, the reaction was monitored by HPLC to ensure complete reaction of the compound shown in Formula 1. 40 mL of water was added to the reaction system, and the mixture was slowly cooled to room temperature. The product was filtered out, the precipitate was washed with water and dried to obtain the product sulfonylpyrazol. The purity of the product and the content of monoxide impurities were determined by liquid chromatography.
[0042] The amounts of ammonium sulfate and concentrated sulfuric acid added, reaction temperatures, product yields, product purity, and the content of oxide impurities in the products in Examples 1-6 are shown in Table 1.
[0043] Table 1
[0044]
[0045] Examples 7-10
[0046] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1. In Examples 7-10, the types of solvents were different from those in Example 1. The types of solvents, product yields, product purity, and the content of monoxide impurities in the products are shown in Table 2.
[0047] Table 2
[0048]
[0049]
[0050] Examples 11-13
[0051] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1. In Examples 11-13, the types of oxidants were different from those in Example 1. The types of oxidants, product yields, product purity, and the content of monoxide impurities in the products are shown in Table 3.
[0052] Table 3
[0053]
[0054] Comparative Examples 1-6
[0055] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1. In Comparative Examples 1-6, the amount of ammonium persulfate oxidant and concentrated sulfuric acid catalyst, and the reaction temperature were different from those in Example 1. The amount of ammonium persulfate oxidant and concentrated sulfuric acid catalyst, the reaction temperature, the product yield, the product purity, and the content of monoxide impurities in the product are shown in Table 4.
[0056] Table 4
[0057]
[0058] Comparative Examples 7-10
[0059] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1. In Comparative Examples 7-10, the types of catalysts selected were different from those in Example 1. The types of catalysts, product yields, product purity, and the content of oxide impurities in the products are shown in Table 5.
[0060] Table 5
[0061]
[0062] Comparative Example 11
[0063] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1, except that n-butanol was used as the solvent. The product yield, product purity and the content of monoxide impurities in the product are shown in Table 6.
[0064] Table 6
[0065]
[0066] Comparative Examples 12-19
[0067] Sulfonylpyrazol was synthesized according to the synthesis method of Example 1. In Comparative Examples 12-19, the types of oxidants were different from those in Example 1. The types of oxidants, product yields, product purity, and the content of monoxide impurities in the products are shown in Table 7.
[0068] Table 7
[0069]
[0070]
[0071] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.
Claims
1. A method of synthesizing pyroxasulfone, characterized by, The method comprises the following steps: The compound shown in formula 1 is subjected to oxidation reaction under the action of an oxidant and a catalyst to obtain pyroxasulfone: The oxidant is selected from one of persulfate.
2. The method of claim 1, wherein, The persulfate is selected from ammonium persulfate, sodium persulfate, potassium persulfate or potassium hydrogen persulfate.
3. The method of claim 2, wherein, The persulfate is selected from ammonium persulfate or potassium persulfate.
4. The method of claim 1, wherein, The catalyst is concentrated sulfuric acid.
5. The method of claim 4, wherein, The molar ratio of the catalyst, the oxidant and the compound shown in formula 1 is 0.1-0.5:2.5-3.0:
1.
6. The method of claim 1, wherein, The temperature of the oxidation reaction is 30-100 DEG C.
7. The method of synthesis of claim 6, wherein, The temperature of the oxidation reaction is 60-75 DEG C.
8. The method of claim 1, wherein, The oxidation reaction further comprises a solvent.
9. The method of synthesis of claim 8, wherein, The solvent is selected from an alcohol solvent or a nitrile solvent.
10. The method of synthesis of claim 9, wherein, The alcohol solvent is selected from methanol, ethanol, isopropanol or tert-butanol; and the nitrile solvent is acetonitrile.