Synthesis method and application of pyroxasulfone

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method and application of pyroxasulfone. The synthesis method comprises the following steps: taking a compound shown as a formula I as a raw material, and reacting with inorganic acid, organic carboxylic acid, hydrogen peroxide and an organic solvent. The invention provides a novel method for oxidative synthesis of pyroxasulfone, and the method has the advantages of low raw material cost, continuous and simple reaction operation, high yield and high content of the product pyroxasulfone, is suitable for large-scale production, and has a good industrial application prospect. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method and application of sulfonepyraclostrobin. Background Art

[0002] Pyroxasulfone is an isoxazole herbicide developed by Kumihiko Chemical Co., Ltd. Its chemical name is 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, and its molecular formula is C 12 H 14 F5N3O4S, molecular weight is 391.32. Sulfonepyraclostrobin can be used as a pre-emergence soil treatment agent in most crop fields. After application, it is absorbed by the young roots and shoots of weeds, inhibiting the early growth of seedlings, destroying meristems and coleoptiles, and is a serious potential inhibitor of VLCFA (very long side chain fatty acids, C20-C30) biosynthesis in plants. The chemical structure of sulfonepyraclostrobin is as follows:

[0003]

[0004] At present, most of the preparation processes of sulfonepyraclostrobin use hydrogen peroxide, inorganic acid and metal catalyst as the oxidation system, or use hydrogen peroxide and metal catalyst as the oxidation system.

[0005] For example, Chinese invention patent publication number CN111393427A discloses a method for synthesizing sulfonepyraclostrobin, comprising the following steps: using compound I as a starting material, synthesizing intermediate II through a cyclization reaction, wherein intermediate II is subjected to a chlorination reaction under the action of a chlorinating agent to obtain intermediate III; intermediate III is reacted with thiourea to obtain hydrochloride intermediate IV; the chlorinating agent is phosphorus pentachloride and / or phosphorus oxychloride; the hydrochloride intermediate IV, compound VI and formaldehyde are reacted to obtain intermediate VII, intermediate VII is subjected to a difluoromethoxylation reaction to obtain intermediate VIII, and finally, in the presence of a catalyst, intermediate VIII is oxidized using hydrogen peroxide to obtain IX; the catalyst is sodium tungstate and acid, and finally the sulfonepyraclostrobin content is greater than 99%, but the above catalyst is difficult to separate and recover, which is not conducive to industrial production.

[0006] Another Chinese invention patent publication number CN113831333A discloses a method for synthesizing sulfonepyraclostrobin, which comprises taking 1-methyl-3-trifluoromethyl-5-hydroxy-1H-pyrazole as a raw material, reacting 1-methyl-3-trifluoromethyl-5-hydroxy-1H-pyrazole with formaldehyde in the presence of an organic solvent and an alkali solution to obtain hydroxypyrazole methanol; etherification reaction of hydroxypyrazole methanol with difluorochloromethane to obtain etherified pyrazole methanol; then condensation reaction of etherified pyrazole methanol with isoxazole thiourea salt and a phase transfer catalyst to obtain thioether; oxidizing the thioether in the presence of a double oxidation and a catalyst, wherein the catalyst is one of sodium tungstate and ammonium molybdate, and the content of the sulfonepyraclostrobin obtained can reach 98.5%, and the yield is above 95.0%.

[0007] In view of this, in order to overcome the technical problems of high cost, large amount of three wastes in the preparation process, low yield and content in the prior art of synthesizing sulfonepyraclostrobin, it is necessary to develop a new method for synthesizing sulfonepyraclostrobin. Summary of the invention

[0008] The invention aims at the problems existing in the prior art and provides a synthesis method and application of sulfonepyraclostrobin. The method has low raw material cost, continuous and simple reaction operation, and high yield and content of the product sulfonepyraclostrobin.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] A method for synthesizing sulfonepyraclostrobin comprises the following steps: using a compound shown in formula I as a raw material, reacting with an inorganic acid, an organic carboxylic acid, hydrogen peroxide and an organic solvent to obtain the product.

[0011] The synthetic route is as follows:

[0012]

[0013] The reaction mechanism is as follows:

[0014] The organic carboxylic acid in the reaction system is oxidized to a peroxy organic acid by hydrogen peroxide under the catalysis of an inorganic acid, and the peroxy organic acid then oxidizes the compound shown in formula I (3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole), first generating an intermediate (whose structural formula is shown below), and then oxidizing to the product sulfonepyraclostrobin.

[0015]

[0016] Preferably, the inorganic acid is sulfuric acid or phosphoric acid.

[0017] Preferably, the organic carboxylic acid is selected from one or more of formic acid, acetic acid, propionic acid and trifluoroacetic acid.

[0018] More preferably, the organic carboxylic acid is formic acid, acetic acid or propionic acid.

[0019] Preferably, the mass concentration of the hydrogen peroxide is 25-70%.

[0020] More preferably, the mass concentration of the hydrogen peroxide is 30-40%.

[0021] Preferably, the organic solvent is selected from one or more of toluene, xylene, acetonitrile, butanone and methyltetrahydrofuran.

[0022] More preferably, the organic solvent is toluene or acetonitrile.

[0023] Preferably, the molar ratio of the compound represented by formula I, the inorganic acid, the organic carboxylic acid and hydrogen peroxide is 1:0.1-0.3:0.5-3:2-5.

[0024] More preferably, the molar ratio of the compound represented by formula I, the inorganic acid, the organic carboxylic acid and hydrogen peroxide is 1:0.2-0.3:1-2:2-4.

[0025] Further preferably, the molar ratio of the compound represented by formula I, the inorganic acid, the organic carboxylic acid and the hydrogen peroxide is 1:0.25-0.3:1-1.5:2.5-3.5.

[0026] Preferably, the reaction process comprises first mixing the compound represented by formula I, an inorganic acid, an organic carboxylic acid and an organic solvent, heating the mixture to 30-80° C., then adding hydrogen peroxide, and keeping the mixture warm for 13-17 hours.

[0027] More preferably, the reaction process comprises first mixing the compound represented by formula I, an inorganic acid, an organic carboxylic acid and an organic solvent, heating the mixture to 65-75° C., then adding hydrogen peroxide, and keeping the mixture warm for 13-15 hours.

[0028] Preferably, after the reaction is completed, post-treatment is required, and the post-treatment includes first cooling the reaction solution to 20-25° C., and then adding a sodium sulfite aqueous solution with a mass concentration of 8-12% for oxidation quenching and drying.

[0029] The present invention also provides application of the synthesis method in preparing a herbicide containing sulfonepyraclostrobin.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The invention provides a novel method for oxidatively synthesizing sulfonepyraclostrobin. The method has low raw material cost, continuous and simple reaction operation, high yield and content of the product sulfonepyraclostrobin, is suitable for large-scale production, and has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the liquid chromatogram of the reaction solution when the reaction was continued for 10 h in Example 2.

[0033] Figure 2 This is the liquid chromatogram of the reaction solution when the reaction was continued for 15 h in Example 2. DETAILED DESCRIPTION

[0034] It is worth noting that the raw materials used in the present invention are all common commercially available products.

[0035] HPLC detection conditions:

[0036] Instrument: Shimadzu LC-2010 series;

[0037] Chromatographic column: YMC-Pack ODS-A (5 μm, 12 nm), 150 × 6.0 mm ID;

[0038] Chromatographic column stationary phase: high purity silica gel particles chemically bonded with octadecyl and highly end-capped;

[0039] Detection wavelength: UV 230nm;

[0040] Column temperature: 40°C;

[0041] Flow rate: 1.0 mL / min;

[0042] Sample volume: 5 μL;

[0043] Mobile phase A: acetonitrile;

[0044] Mobile phase B: 0.1% phosphoric acid aqueous solution;

[0045] The elution procedure is shown in Table 1:

[0046] Table 1 Elution program

[0047] Time (min) Acetonitrile (%) 0.1% phosphoric acid aqueous solution (%) 0 45 55 10 45 55 15 80 20 20 80 20

[0048] Preparation of reference solution: Accurately weigh 25 mg of reference solution, place in a 25 mL volumetric flask, dilute to the mark with acetonitrile, and shake well.

[0049] Preparation of test solution: Accurately weigh 25 mg of the test sample, place it in a 25 mL volumetric flask, dilute to the mark with acetonitrile, and shake well.

[0050] Determination method: Accurately pipette 5 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0051] Example 1

[0052] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0053] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) and acetic acid (5.0 g, 0.0833 mol) with a mass concentration of 98% were added to the reaction bottle, the temperature was raised to 70°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition, and the dropwise addition was completed. The reaction was kept warm for 15 hours. The product content in the reaction liquid was 95.5%, the raw material content was 2.5%, and the intermediate content was 0.0% as detected by liquid chromatography.

[0054] After the reaction is completed, the temperature is lowered to 25°C, and a 10% sodium sulfite aqueous solution is added to the reaction solution to quench the oxidation. When the starch potassium iodide paper does not turn blue, the upper toluene is separated and desolventized. The wet product is dried to obtain 27.0 g of the product sulfonepyraclostrobin. The yield of sulfonepyraclostrobin is 96.6% and the content is 97.5% as determined by liquid chromatography.

[0055] The synthetic route is as follows:

[0056]

[0057] Example 2

[0058] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0059] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) and acetic acid (10.0 g, 0.167 mol) with a mass concentration of 98% were added to the reaction bottle, the temperature was raised to 70°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition. After the dropwise addition was completed, the reaction was kept warm for 15 hours. The product content in the reaction liquid was 97.8%, the raw material content was 2.2%, and the intermediate content was 0.0% as detected by liquid chromatography.

[0060] After the reaction is completed, the temperature is lowered to 25°C, and a 10% sodium sulfite aqueous solution is added to the reaction solution to quench the oxidation. When the starch potassium iodide paper does not turn blue, the upper toluene is separated and desolventized. The wet product is dried to obtain 27.0 g of the product sulfonepyraclostrobin. The yield of sulfonepyraclostrobin is 98.3% and the content is 99.0% as determined by liquid chromatography.

[0061] When the reaction was kept warm for 10 hours, the reaction solution was detected by liquid chromatography, and the chromatogram was as follows: Figure 1 When the reaction was kept warm for 15 hours, the reaction solution was detected by liquid chromatography, and the chromatogram was as shown in Figure 2 shown.

[0062] Example 3

[0063] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0064] The compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) was used as a raw material. Acetonitrile (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) with a mass concentration of 98% and acetic acid (10.0 g, 0.167 mol) were added to the reaction bottle. The temperature was raised to 70°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition. After the dropwise addition was completed, the reaction was kept warm for 15 hours. The product content in the reaction liquid was 96.8%, the raw material content was 0.0%, and the intermediate (whose chemical structure is as follows) content was 2.5% as detected by liquid chromatography.

[0065]

[0066] After the reaction was completed, the temperature was lowered to 25°C, and a 12% sodium sulfite aqueous solution was added to the reaction solution to quench the oxidation. When the starch potassium iodide paper did not turn blue, a large amount of solid was precipitated. After filtration and drying, 26.6 g of the product sulfonepyraclostrobin was obtained. The yield of sulfonepyraclostrobin was 94.8% and the content was 97.1% as determined by liquid chromatography.

[0067] Example 4

[0068] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0069] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) with a mass concentration of 98% and formic acid (8.0 g, 0.174 mol) were added to the reaction bottle, the temperature was raised to 75°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition, and the dropwise addition was completed. The reaction was kept warm for 15 hours. The product content in the reaction liquid was 95.4%, the raw material content was 0.0%, and the intermediate content was 3.5% as detected by liquid chromatography.

[0070] After the reaction was completed, the temperature was lowered to 20°C, and an aqueous sodium sulfite solution with a mass concentration of 8% was added to the reaction solution to quench the oxidation. When the starch potassium iodide paper did not turn blue, a large amount of solid was precipitated. After filtration and drying, 26.7 g of the product sulfonepyraclostrobin was obtained. The yield of sulfonepyraclostrobin was 94.3% and the content was 96.3% as determined by liquid chromatography.

[0071] Example 5

[0072] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0073] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) with a mass concentration of 98% and propionic acid (14.8 g, 0.20 mol) were added to the reaction bottle, the temperature was raised to 65°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition, and the dropwise addition was completed. The reaction was kept warm for 13 hours. The product content in the reaction liquid was 93.8%, the raw material content was 2.2%, and the intermediate content was 3.1% as detected by liquid chromatography.

[0074] After the reaction was completed, the temperature was lowered to 25°C, and a 12% sodium sulfite aqueous solution was added to the reaction solution to quench the oxidation. When the starch potassium iodide paper did not turn blue, a large amount of solid was precipitated. After filtration and drying, 25.9 g of the product sulfonepyraclostrobin was obtained. The yield of sulfonepyraclostrobin was 89.5% and the content was 94.1% as determined by liquid chromatography.

[0075] Comparative Example 1

[0076] Compared with Example 2, the only difference is that toluene is replaced by ethyl acetate.

[0077] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0078] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, ethyl acetate (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) and acetic acid (10.0 g, 0.167 mol) with a mass concentration of 98% were added to the reaction bottle, the temperature was raised to 70°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition, and the dropwise addition was completed. The reaction was kept warm for 15 hours. The product content in the reaction liquid was 77.0%, the raw material content was 0.0%, and the intermediate content was 18.1% as detected by liquid chromatography.

[0079] After the reaction is completed, the temperature is lowered to 25°C, and a 10% sodium sulfite aqueous solution is added to the reaction solution to quench the oxidation. When the starch potassium iodide paper does not turn blue, the upper toluene is separated and desolventized. The wet product is dried to obtain 25.2 g of the product sulfonepyraclostrobin. The yield of sulfonepyraclostrobin is 72.7% and the content is 78.5% as determined by liquid chromatography.

[0080] Comparative Example 2

[0081] Compared with Example 2, the only difference is that toluene is replaced by methanol.

[0082] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0083] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, methanol (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g, 0.02 mol) and acetic acid (10.0 g, 0.167 mol) with a mass concentration of 98% were added to the reaction bottle, the temperature was raised to 70°C, and hydrogen peroxide (20.0 g, 0.206 mol) with a mass concentration of 35% was added dropwise. A small amount of gas was generated during the dropwise addition. After the dropwise addition was completed, the reaction was kept warm for 15 hours. The product content in the reaction liquid was 2.2%, the raw material content was 1.1%, and the intermediate content was 95.2% as detected by liquid chromatography.

[0084] Almost all the raw materials were converted into intermediates, and only 2.2% of the product was generated. The reaction effect was very poor, and no post-processing steps were performed.

[0085] Comparative Example 3

[0086] Compared with Example 2, the only difference is that acetic acid is replaced by benzoic acid.

[0087] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0088] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g) with a mass concentration of 98%, and benzoic acid (25.5 g, 0.208 mol) were added to the reaction bottle, the temperature was raised to 70°C, and 35% hydrogen peroxide (20.0 g, 0.206 mol) was added dropwise. A small amount of gas was generated during the dropwise addition. After the dropwise addition was completed, the reaction was kept warm for 15 hours. The product content in the reaction liquid was 45.1%, the raw material content was 18.0%, and the intermediate content was 36.0% as detected by liquid chromatography.

[0089] The intermediate content was 36.0%, the reaction effect was very poor, and no post-treatment step was performed.

[0090] Comparative Example 4

[0091] Compared with Example 2, the only difference is that acetic acid replaces sodium tungstate.

[0092] A method for synthesizing sulfonepyraclostrobin, comprising the following steps:

[0093] Using the compound shown in formula I (i.e., 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole) as raw material, toluene (75.0 g), raw material (25.0 g, 0.0696 mol), sulfuric acid (2.0 g) with a mass concentration of 98%, and metal catalyst sodium tungstate (0.7 g, 0.0125 mol) were added to the reaction bottle, the temperature was raised to 70°C, and 35% hydrogen peroxide (20.0 g, 0.206 mol) was added dropwise. A small amount of gas was generated during the dropwise addition. After the dropwise addition was completed, the reaction was kept warm for 15 hours. The product content in the reaction liquid was 99.6%, the raw material content was 0%, and the intermediate content was 0.08% as detected by liquid chromatography.

[0094] After the reaction is completed, the temperature is lowered to 25°C, and a 10% sodium sulfite aqueous solution is added to the reaction solution to quench the oxidation. When the starch potassium iodide paper does not turn blue, the upper toluene is separated and desolventized. The wet product is dried to obtain 26.2 g of the product sulfonepyraclostrobin. The yield of sulfonepyraclostrobin is 93.0% and the content is 96.7% as determined by liquid chromatography.

[0095] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for synthesizing sulfonepyraclostrobin, characterized in that: The method comprises the following steps: using the compound represented by formula I as a raw material, reacting with an inorganic acid, an organic carboxylic acid, hydrogen peroxide and an organic solvent to obtain:

2. The synthesis method according to claim 1, characterized in that The inorganic acid is sulfuric acid or phosphoric acid.

3. The synthesis method according to claim 1, characterized in that The organic carboxylic acid is selected from one or more of formic acid, acetic acid, propionic acid and trifluoroacetic acid.

4. The synthesis method according to claim 3, characterized in that The organic carboxylic acid is formic acid, acetic acid or propionic acid.

5. The synthesis method according to claim 1, characterized in that The mass concentration of the hydrogen peroxide is 25-70%.

6. The synthesis method according to claim 1, characterized in that The organic solvent is selected from one or more of toluene, xylene, acetonitrile, butanone and methyltetrahydrofuran.

7. The synthesis method according to claim 1, characterized in that The molar ratio of the compound represented by formula I, the inorganic acid, the organic carboxylic acid and the hydrogen peroxide is 1:0.1-0.3:0.5-3:2-5.

8. The synthesis method according to claim 1, characterized in that The reaction process comprises firstly mixing the compound represented by formula I, inorganic acid, organic carboxylic acid and organic solvent, heating to 30-80° C., then adding hydrogen peroxide, and keeping the temperature to react for 13-17 hours.

9. The synthesis method according to claim 8, characterized in that After the reaction is completed, post-treatment is required, which includes first cooling the reaction solution to 20-25° C., then adding a sodium sulfite aqueous solution with a mass concentration of 8-12% for oxidation quenching and drying.

10. Use of the synthesis method according to any one of claims 1 to 9 in the preparation of a herbicide containing sulfonepyraclostrobin.

Images