Preparation method of pyroxasulfone

Abstract

The invention provides a preparation method of pyroxasulfone, which comprises the following steps: under an acidic condition and in the presence of perborate, taking a compound I as a raw material, and reacting to obtain the pyroxasulfone. According to the preparation method, a rare metal catalyst and high-risk hydrogen peroxide are not needed for oxidation, the prepared pyroxasulfone is high in yield and purity, post-treatment is simple, the production cost is reduced, and the preparation method is environmentally friendly.

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticides, and particularly relates to a preparation method of pyroxasulfone. Background Art

[0002] Pyroxasulfone is an isoxazole herbicide and can be used as a pre-emergence soil treatment agent for most crop fields. It is a potential inhibitor that seriously affects the biosynthesis of VLCFA (very long-chain fatty acids, such as C20-C30 fatty acids) in plants. After application, it is absorbed by the young roots and shoots of weeds, destroys the meristem and coleoptile, and inhibits the early growth of seedlings. It is widely used in fields such as corn, cotton, and beans to control gramineous weeds and broad-leaved weeds.

[0003] WO2021002484A2 discloses a preparation method of pyroxasulfone, using a compound Taking [raw material] as the raw material, pyroxasulfone is prepared by oxidation with hydrogen peroxide under the catalysis of sodium tungstate dihydrate or ammonium molybdate tetrahydrate. This involves the catalysis of rare metal catalysts and the relatively risky hydrogen peroxide oxidation, and the highest product yield can reach 95.9%. However, both tungsten and molybdenum are non-renewable scarce strategic resources. Tungsten alloys are widely used in national defense and military industries (atomic bombs, rockets), aerospace, machining, metallurgy, oil drilling, mining tools, electronic communications, construction and other fields due to their high melting points and high hardness. Major countries such as the United States and Russia have successively established national strategic reserves of tungsten; molybdenum, with its unique electrical and thermal conductivity, is widely used in national defense and military industries, superalloys, iron and steel metallurgy, electrochemistry and aerospace and other fields. Countries such as the United States, Canada, Japan, and South Korea have successively established national strategic reserves of molybdenum. In addition, a research team at the University of Exeter in the UK found that the probability of stroke increases significantly in people with higher tungsten content in the body, and people with higher molybdenum content will develop diseases such as joint swelling, distortion, kidney damage, growth retardation, hair loss, arteriosclerosis, and connective tissue lesions. The "Guidelines for Drinking Water Quality" of the World Health Organization and the "Surface Water Environment Quality Standard" of China stipulate that the emission limit of molybdenum mass concentration is 0.07 mg / L, with extremely high requirements. In the examples of the WO2021002484 patent method, the dosage of the tungsten-based catalyst used is relatively large, reaching 0.03 - 0.05 equivalents (calculated based on the molar amount of the catalytic metal tungsten element in the used catalyst relative to the molar amount of the aforementioned compound raw material, and the following meaning is the same); the dosage of the molybdenum-based catalyst is even higher, reaching 0.07 equivalents; according to the patent report, for example, when synthesizing one ton of technical material, about 26.4 kg of sodium tungstate dihydrate is consumed, and about 32.9 kg of ammonium molybdate tetrahydrate is consumed, with a relatively large dosage. The use of tungsten / molybdenum catalysts, on the one hand, causes waste of scarce strategic metal resources, and on the other hand, there are large amounts of highly toxic tungsten and molybdenum inorganic waste salts in the wastewater after the reaction, with relatively high potential harm to humans and the environment. These inorganic waste salts must be treated harmlessly at a relatively high cost, otherwise industrial production is not sustainable, which undoubtedly increases the cost.

[0004] In addition, the oxidant specifically used in this patent is hydrogen peroxide, and the usage amount is as high as 2.3 - 6.0 mol equivalents [corresponding to a consumption of 0.59 - 1.54 tons of 35% hydrogen peroxide per ton (the meaning of "ton consumption" is: the amount of raw materials consumed for each ton of pyroxasulfone technical drug production, the same hereinafter)]. Hydrogen peroxide is a carcinogen announced by the World Health Organization and is also a strong explosive oxidant. When it meets organic substances and is heated, it decomposes to release oxygen and water. National standards GB 31570 - 2015 (Discharge Standard of Pollutants for Petroleum Refining Industry) and GB 31571 - 2015 (Discharge Standard of Pollutants for Petrochemical Industry) have relevant regulations on the oxygen content in the tail gas of the petroleum refining and petrochemical industries. In many refinery and petrochemical plants, the oxygen content in the tail gas is controlled at a level less than 2% to ensure that combustible gases do not form an explosive mixture with oxygen. Therefore, the excess hydrogen peroxide after the oxidation reaction using hydrogen peroxide must be properly post - treated. For example, WO2021002484 reports adding a 17% sodium sulfite aqueous solution to the reaction mixture to decompose the excess hydrogen peroxide after the oxidation reaction (the ton consumption of the 17% sodium sulfite aqueous solution is 0.59 tons, corresponding to the generation of 0.11 tons of waste salt), and CN117545741A also reports adding a 20% sodium sulfite aqueous solution to the reaction mixture to decompose the excess hydrogen peroxide after the oxidation reaction (the ton consumption of the 20% sodium sulfite aqueous solution is 0.87 tons, corresponding to the generation of 0.20 tons of waste salt); CN118307533A reports adding a 10% sodium thiosulfate solution to the reaction mixture to decompose the excess hydrogen peroxide after the oxidation reaction (the ton consumption of the 10% sodium thiosulfate aqueous solution is 2.87 tons, corresponding to the generation of 0.56 tons of waste salt), but doing so not only newly increases the types and contents of inorganic waste salts in the wastewater, but also increases the manufacturing cost of pyroxasulfone due to the consumption of sodium sulfite or sodium thiosulfate.

[0005] CN115776978A discloses an improved preparation method of pyroxasulfone. It is an improvement based on the preparation method reported in WO2021002484A2, mainly using carboxylic acid - assisted catalytic oxidation; the catalysts are mainly sodium tungstate and ammonium molybdate, the usage amount of the tungsten - based catalyst used is 0.02 - 0.03 equivalents, and the molybdenum - based catalyst is as high as 0.07 equivalents; the reported usage amount of the oxidant is still as high as 2.5 - 3.0 mol equivalents; it can be seen that CN115776978A still has the problems or defects in the preparation method of WO2021002484A2 described above.

[0006] Similar patents such as CN117794925A, CN117440754A, CN111574511A, and CN114929693A all disclose the preparation methods of pyroxasulfone, but all completely or mostly have the problems or defects existing in the preparation method of WO2021002484A2.

[0007] Therefore, there is an urgent need in the art to develop a preparation method for pyroxasulfone that is suitable for industrial production, which does not use scarce strategic metal resources or hydrogen peroxide, is resource-saving, safe and controllable, eco-friendly, has less waste and less pollution. Summary of the Invention

[0008] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a preparation method for pyroxasulfone. The preparation method does not require the use of rare metal catalysts and hydrogen peroxide with relatively high risks for oxidation. The pyroxasulfone prepared has a high yield, high purity, simple post-treatment, reduced production costs, and is environmentally friendly.

[0009] To achieve this purpose, the present invention adopts the following technical solutions:

[0010] In a first aspect, the present invention provides a preparation method for pyroxasulfone, the preparation method comprising the following steps: in the presence of an acidic condition and a perborate, using compound I as a raw material and reacting to obtain the pyroxasulfone; compound I has the structure shown in formula I: In formula I, R 1 is selected from 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1H-pyrazol-4-yl, and R 2 , R 3 are each independently selected from methyl.

[0011] In the present invention, in the preparation method, under acidic conditions and using a perborate as a catalyst, the pyroxasulfone prepared has a high yield and high purity, does not require the use of rare metal catalysts and hydrogen peroxide with relatively high risks for oxidation, the preparation process is safe and controllable, eco-friendly, has less waste and less pollution, and the post-treatment is simple and the cost is low.

[0012] In the present invention, the structure of the pyroxasulfone is The synthetic route of the preparation method is as follows:

[0013]

[0014] Preferably, the perborate includes any one or a combination of at least two of sodium perborate and its hydrates, potassium perborate and its hydrates, ammonium perborate and its hydrates, magnesium perborate and its hydrates, calcium perborate and its hydrates.

[0015] It should be noted that the "and / or" relationship is meant by the "and its" in the present invention. For example, sodium perborate and its hydrates means that the perborate can be sodium perborate and / or sodium perborate hydrate; the hydrates include monohydrates and / or tetrahydrates of the salt.

[0016] In the present invention, before the reaction, perborate is mixed with Compound I. The mixing method is not particularly limited. The perborate can be slowly added to the system through a solid feeder, or Compound I can be slowly added to the system.

[0017] Preferably, the mixing time is 0 - 3 h (0 h means rapid pouring), for example, it can be 0 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h or 3 h, as well as specific values between the above point values; the mixing time refers to the time when perborate or Compound I is added to the system.

[0018] Preferably, the molar ratio of perborate to Compound I is (2 - 4):1, where the specific values in (2 - 4) can be, for example, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, etc.; more preferably (2.2 - 3):1, and even more preferably (2.4 - 2.8):1.

[0019] Preferably, the acidic condition is derived from an acidic solvent, or a solution formed by an acidic catalyst and a non - acidic solvent.

[0020] Preferably, the acidic solvent includes any one or a combination of at least two of acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid, and is further preferably acetic acid.

[0021] Preferably, the mass ratio of the acidic solvent to Compound I is (2 - 10):1, where the specific values in (2 - 10) can be, for example, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, etc.; more preferably (3 - 8):1, and even more preferably (3 - 6):1.

[0022] Preferably, the acidic catalyst includes any one or a combination of at least two of organic acids, inorganic acids, or compounds that can react with water to form acids.

[0023] Preferably, the organic acid is selected from any one or a combination of at least two of formic acid, acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid.

[0024] Preferably, the inorganic acid is selected from any one or a combination of at least two of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, boric acid, chlorosulfonic acid, and chlorousulfonic acid.

[0025] Preferably, the compound capable of reacting with water to form an acid is selected from any one or a combination of at least two of sulfonyl chloride, thionyl chloride, acetyl chloride, dichloroacetyl chloride, trichloroacetyl chloride, trifluoroacetyl chloride, trifluoroacetyl fluoride, acetic anhydride, trifluoroacetic anhydride, peracetic acid, phosgene, chlorine, and bromine.

[0026] Preferably, the molar ratio of the acidic catalyst to Compound I is (1-4):1, where the specific values in (1-4) can be, for example, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, etc.; more preferably (1.2-3):1, and even more preferably (1.5-2.5):1.

[0027] Preferably, the non-acidic solvent includes any one or a combination of at least two of halogenated aliphatic hydrocarbons, aromatic hydrocarbons, or halogenated aromatic hydrocarbons.

[0028] In the present invention, the non-acidic solvent includes, but is not limited to, any one or a combination of at least two of 1,2-dichloroethane, dichloromethane, chloroform, 1,1,2-trichloroethane, toluene, xylene, mesitylene, chlorobenzene, or dichlorobenzene, etc.

[0029] Preferably, the mass ratio of the non-acidic solvent to Compound I is (2-10):1, where the specific values in (2-10) can be, for example, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, etc.; more preferably (3-8):1, and even more preferably (3-6):1.

[0030] Preferably, the temperature of the reaction is 0-100 °C, for example, 0 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, 100 °C, etc.; more preferably 20-80 °C, and even more preferably 30-60 °C.

[0031] Preferably, the reaction time is 2-12 h, for example, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, 11 h, 12 h, etc.

[0032] Preferably, after the reaction, it further includes a post-treatment step.

[0033] Preferably, the post-treatment includes the steps of first filtration, solvent removal, crystallization, second filtration, washing, and drying in sequence.

[0034] In the present invention, the first filtration is hot filtration, aiming to remove borate salts; the solvent removal is carried out under negative pressure; the crystallization is carried out by adding water; the solvent for washing includes but is not limited to methanol.

[0035] As a preferred technical solution of the present invention, the preparation method includes the following steps:

[0036] Under acidic conditions, compound I is mixed with perborate and reacted at 0 - 100 °C for 2 - 12 h. After the first filtration, solvent removal, crystallization, second filtration, washing and drying, the said pyroxasulfone is obtained; the molar ratio of perborate to compound I is (2 - 4):1; the acidic conditions are derived from an acidic solvent, or a solution formed by an acidic catalyst and a non-acidic solvent, and the mass ratio of the acidic solvent to compound I is (2 - 10):1; the molar ratio of the acidic catalyst to compound I is (1 - 4):1.

[0037] In the present invention, the by-products of the preparation method include sulfoxide, with the structure of The pyroxasulfone obtained by the preparation method provided by the present invention has a purity ≥ 99.0% and a sulfoxide mass percentage content < 0.2%.

[0038] The numerical ranges described in the present invention not only include the above-listed point values, but also any point values between the above numerical ranges not listed. Due to space limitations and for the sake of brevity, the present invention does not exhaustively list the specific point values included in the ranges.

[0039] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0040] The preparation method of pyroxasulfone provided by the present invention does not require the use of metal catalysts such as tungsten and molybdenum, avoiding the use and consumption of non-renewable scarce strategic resources, and greatly reducing the risk of harm to the natural environment and human health. Secondly, the present invention does not require the use of oxidants with higher risks such as hydrogen peroxide, avoiding the explosion risk caused by the accumulation and decomposition of hydrogen peroxide in the reaction system. The pyroxasulfone prepared by the preparation method provided by the present invention has high purity and high yield, and the preparation method is more resource-saving, safe and controllable, eco-friendly, with less three wastes and less pollution, more economical, more feasible for industrialization, and has broad industrial application prospects and social value. Detailed embodiments

[0041] The technical solutions of the present invention will be further described below through specific embodiments. Those skilled in the art should understand that the embodiments are only for helping to understand the present invention and should not be regarded as specific limitations to the present invention.

[0042] In the following examples, the preparation method of pyroxasulfone uses Compound I as the raw material, and under acidic conditions and in the presence of perborate, the pyroxasulfone technical material with high yield, high purity and high quality is prepared. The reaction formula is as follows:

[0043]

[0044] Wherein, R 1 is 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1H-pyrazol-4-yl, and R 2 , R 3 are both methyl.

[0045] In the following specific embodiments of the present invention, all raw materials for which the preparation method is not provided are obtained through market channels; the purity of raw materials and products refers to mass percentage content. The reaction conversion rate is measured by HPLC normalization method, the purity (content) of the product is measured by HPLC external standard method, and the yield is mass yield. The molecular structure of the product is characterized and confirmed by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and / or nuclear magnetic resonance hydrogen spectrum ( 1 1H-NMR).

[0046] Example 1

[0047] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0048] Add 180 g of acetic acid and 36.4 g of Compound I (purity 98.7%, 0.1 mol) to the reaction kettle, start stirring, heat up to 45 °C, and add 44.4 g of sodium perborate tetrahydrate (purity 97%, 0.28 mol) thereto. The addition time is 0.5 h. The molar ratio of sodium perborate tetrahydrate to Compound I is 2.8:1, and the mass ratio of acetic acid to Compound I is 4.95:1; after the addition, keep the reaction at a constant temperature for 8 h. After 8 h, monitor the reaction progress. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.07% (HPLC area normalization, 210 nm); then heat the system to 60 °C, filter to remove borate salts, and remove the solvent under negative pressure (4 kPa) from the filtrate. Control the internal temperature within 60 °C and distill out 159.3 g of acetic acid. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0-5 °C, containing 10% water) by stirring and then filter again, and dry (5 kPa, 60 °C) to obtain 38.7 g of pyroxasulfone technical material (white crystal), with a purity of 99.2% and a yield of 98.1%. No sulfoxide was detected in the product.

[0049] An appropriate amount of the obtained pyroxasulfone technical material was taken for analysis and testing, and the following data were obtained: UHPLC-MS (m / z, ESI): 392.0693 (M+H) + , theoretical value: 392.0698; 1 1H-NMR (DMSO, 400 MHz) δ (ppm): 1.520 (s, 6H, 2CH 3 ), 3.106 (s, 2H, CH 2 ), 3.878 (s, 3H, CH 3 ), 4.602 (s, 2H, CH 2 ), 6.831 (t, J = 72 Hz, 1H, CF 2 H).

[0050] Example 2

[0051] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0052] 150 g of acetic acid and 36.4 g of Compound I (purity 98.7%, 0.1 mol) were added to the reaction kettle. Stirring was started, and the temperature was raised to 60 °C. Then 41.2 g of sodium perborate tetrahydrate (purity 97%, 0.26 mol) was added thereto over 2.5 h. The molar ratio of sodium perborate tetrahydrate to Compound I was 2.6:1, and the mass ratio of acetic acid to Compound I was 4.12:1. After addition, the mixture was kept warm and reacted for 6 h. After 6 h, the in-process control showed that the remaining Compound I was 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide was 0.23% (HPLC area normalization, 210 nm). The system was kept warm at 60 °C, and the borate salt was removed by filtration. The filtrate was stripped under negative pressure (4 kPa), and 129.1 g of acetic acid was distilled out while controlling the internal temperature within 60 °C. Then 150 g of water was added, and the temperature was lowered to below 5 °C for crystallization for 30 min. A large amount of solid was precipitated. After filtration, the filter cake was stirred and washed with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) and then filtered again. After drying (5 kPa, 60 °C), 38.6 g of pyroxasulfone technical material (white crystals) was obtained, with a purity of 99.3% and a yield of 98.0%. The sulfoxide content in the product was 0.05%.

[0053] Example 3

[0054] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0055] Add 250 g of acetic acid and 39.7 g of sodium perborate tetrahydrate (purity 97%, 0.25 mol) to the reaction kettle. Start stirring and heat up to 40 °C. Then add 36.4 g of Compound I (purity 98.7%, 0.1 mol) over 1 h. The molar ratio of sodium perborate tetrahydrate to Compound I is 2.5:1, and the mass ratio of acetic acid to Compound I is 6.87:1. After addition, keep the reaction at a constant temperature for 12 h. After 12 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.32% (HPLC area normalization, 210 nm). Heat the system to 60 °C, filter to remove borate salts, and remove the solvent under negative pressure (4 kPa) from the filtrate. Control the internal temperature within 60 °C and distill out 229.6 g of acetic acid. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring, filter again, and dry (5 kPa, 60 °C) to obtain 38.6 g of the original pyroxasulfone drug (white crystal), with a purity of 99.1% and a yield of 97.8%. The sulfoxide content in the product is 0.16%.

[0056] Example 4

[0057] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0058] Add 180 g of trifluoroacetic acid and 36.4 g of Compound I (purity 98.7%, 0.1 mol) to the reaction kettle. Start stirring and heat up to 45 °C. Then add 38.1 g of sodium perborate tetrahydrate (purity 97%, 0.24 mol) over 1 h. The molar ratio of sodium perborate tetrahydrate to Compound I is 2.4:1, and the mass ratio of trifluoroacetic acid to Compound I is 4.95:1. After addition, keep the reaction at a constant temperature for 6 h. After 6 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.05% (HPLC area normalization, 210 nm). Heat the system to 60 °C, filter to remove borate salts, and remove the solvent under negative pressure (4 kPa) from the filtrate. Control the internal temperature within 60 °C and distill out 161.2 g of trifluoroacetic acid. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring, filter again, and dry (5 kPa, 60 °C) to obtain 38.7 g of the original pyroxasulfone drug (white crystal), with a purity of 99.2% and a yield of 98.1%. No sulfoxide is detected in the product.

[0059] Example 5

[0060] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0061] Add 150 g of trifluoroacetic acid and 36.4 g of Compound I (purity 98.7%, 0.1 mol) to the reaction kettle. Start stirring and pour in 36.5 g of sodium perborate tetrahydrate (purity 97%, 0.23 mol). The molar ratio of sodium perborate tetrahydrate to Compound I is 2.3:1, and the mass ratio of trifluoroacetic acid to Compound I is 4.12:1. Heat up to 50 °C and keep the reaction for 8 h. After 8 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.36% (HPLC area normalization, 210 nm). Heat up the system to 60 °C, filter to remove borate salts, and carry out solvent stripping under negative pressure (4 kPa) for the filtrate. Control the internal temperature within 60 °C and distill out 130.2 g of trifluoroacetic acid. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring and then filter again. Dry (5 kPa, 60 °C) to obtain 38.6 g of the original pyroxasulfone drug (white crystal), with a purity of 99.0% and a yield of 97.7%. The sulfoxide in the product is 0.17%.

[0062] Example 6

[0063] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0064] Add 200 g of trifluoroacetic acid and 36.4 g of Compound I (purity 98.7%, 0.1 mol) to the reaction kettle. Start stirring and heat up to 45 °C. Add 22.9 g of sodium perborate monohydrate (purity 96%, 0.22 mol) thereto, and the addition time is 1 h. The molar ratio of sodium perborate monohydrate to Compound I is 2.2:1, and the mass ratio of trifluoroacetic acid to Compound I is 5.49:1. After the addition, keep the reaction for 6 h. After 6 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.27% (HPLC area normalization, 210 nm). Heat up the system to 60 °C, filter to remove borate salts, and carry out solvent stripping under negative pressure (4 kPa) for the filtrate. Control the internal temperature within 60 °C and distill out 182.3 g of trifluoroacetic acid. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring and then filter again. Dry (5 kPa, 60 °C) to obtain 38.7 g of the original pyroxasulfone drug (white crystal), with a purity of 99.1% and a yield of 98.0%. The sulfoxide in the product is 0.11%.

[0065] Example 7

[0066] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0067] Add 220 g of toluene, 36.4 g of Compound I (purity 98.7%, 0.1 mol), and 21.8 g of acetic acid (purity 99%, 0.36 mol) into the reaction kettle. Start stirring and heat up to 60 °C. Then add 55.5 g of sodium perborate tetrahydrate (purity 97%, 0.35 mol) thereto over 1 h. The molar ratio of sodium perborate tetrahydrate to Compound I is 3.5:1, the mass ratio of toluene to Compound I is 6.04:1, and the molar ratio of acetic acid to Compound I is 3.6:1. After addition, keep the reaction at a constant temperature for 8 h. After 8 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.31% (HPLC area normalization, 210 nm). Keep the system at 60 °C, filter to remove borate salts, and conduct solvent stripping under negative pressure (4 kPa) for the filtrate. Control the internal temperature within 60 °C to distill out 218.5 g of low-boiling substances. Then add 150 g of water and cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring and then filter again. Dry (5 kPa, 60 °C) to obtain 38.3 g of the original pyroxasulfone drug (white crystal), with a purity of 99.1% and a yield of 97.0%. The sulfoxide content in the product is 0.09%.

[0068] Example 8

[0069] This example provides a preparation method of pyroxasulfone, which specifically includes the following steps:

[0070] Add 300 g of dichloroethane, 36.4 g of Compound I (purity 98.7%, 0.1 mol), and 18 g of sulfuric acid (purity 98%, 0.18 mol) into the reaction kettle. Start stirring and heat up to 65 °C. Then add 57.1 g of sodium perborate tetrahydrate (purity 97%, 0.36 mol) thereto over 1 h. The molar ratio of sodium perborate tetrahydrate to Compound I is 3.6:1, the mass ratio of dichloroethane to Compound I is 8.24:1, and the molar ratio of sulfuric acid to Compound I is 1.8:1. After addition, keep the reaction at a constant temperature for 8 h. After 8 h, conduct in-process control. The remaining Compound I is 0% (HPLC area normalization, 210 nm), and the remaining sulfoxide is 0.21% (HPLC area normalization, 210 nm). Keep the system at 65 °C, filter to remove borate salts, add 150 g of water to the filtrate, and conduct solvent stripping under negative pressure (26 kPa). Control the internal temperature within 60 °C to distill out 320 g of low-boiling substances. Then cool down to below 5 °C for crystallization for 30 min. A large amount of solid precipitates. Filter, wash the filter cake with 30 g of 90% ice methanol (0 - 5 °C, containing 10% water) by stirring and then filter again. Dry (5 kPa, 60 °C) to obtain 38.3 g of the original pyroxasulfone drug (white crystal), with a purity of 99.2% and a yield of 97.1%. The sulfoxide content in the product is 0.02%.

[0071] Example 9

[0072] This example provides a preparation method of pyroxasulfone, which is only different from Example 1 in that the amount of sodium perborate tetrahydrate is adjusted so that the molar ratio of sodium perborate tetrahydrate to Compound I is 1.5:1, and the other step parameters are the same as those in Example 1; the purity of the obtained pyroxasulfone is 41.3%, the yield is 40.2%, and the sulfoxide in the product is 57.9%.

[0073] Example 10

[0074] This example provides a preparation method of pyroxasulfone, which is only different from Example 1 in that the amount of acetic acid is adjusted so that the mass ratio of acetic acid to Compound I is 1.5:1, and the other step parameters are the same as those in Example 1; the purity of the obtained pyroxasulfone is 15.5%, the yield is 14.3%, and the sulfoxide in the product is 83.6%.

[0075] Example 11

[0076] This example provides a preparation method of pyroxasulfone, which is only different from Example 7 in that the amount of acetic acid is adjusted so that the molar ratio of acetic acid to Compound I is 0.5:1, and the other step parameters are the same as those in Example 7; the purity of the obtained pyroxasulfone is 31.8%, the yield is 30.7%, and the sulfoxide in the product is 67.3%.

[0077] Comparative Example 1

[0078] Example 6 in CN115776978A provides a preparation method of pyroxasulfone, which has something in common with Example 1 in this technical solution, both using acetic acid as a solvent. The difference is that Example 6 in CN115776978A uses sodium tungstate as a catalyst and hydrogen peroxide for oxidation, and the reported total yield of the reaction solution is 90%. The applicant repeated the experiment of Example 6 in CN115776978A according to the statement, as follows.

[0079] Under nitrogen protection, 36.4 g of compound I (purity 98.7%, 0.1 mol), 108.5 g of acetic acid and 1.0 g of sodium tungstate dihydrate (purity 99%, 0.003 mol) were added to the reaction kettle. Stirring was started, and the internal temperature of the reaction kettle was raised to 50 °C. About 28.3 g of hydrogen peroxide (purity 30%, 0.25 mol) was added dropwise over about 20 min. After the addition was complete, the reaction was carried out under insulation at 50 - 55 °C for 4 h. After 4 h, the intermediate control showed that the remaining compound I was 0% (HPLC area normalization, 210 nm), the remaining sulfoxide was 7.6% (HPLC area normalization, 210 nm), and compound II (i.e., the product pyroxasulfone) was 91.7% (HPLC area normalization, 210 nm). 150 g of acetonitrile was added to the system to form a homogeneous solution, and 320.8 g of a mixed solution containing pyroxasulfone was obtained. The content analyzed by the HPLC external standard method was 11.1%, and the reaction liquid yield was 91.0%.

[0080] Comparative Example 2

[0081] WO2021002484A2 provides another preparation method of pyroxasulfone. The highest yield of pyroxasulfone obtained by the method of Example 2 - 14 was 95.9%. The catalyst used was sodium tungstate dihydrate. Based on compound I, the catalyst dosage was 0.03 mol, the hydrogen peroxide dosage was 2.3 equivalents, the reaction temperature was 75 - 80 °C, and the residual sulfoxide was 0.5% after 5 h of insulation. After post-treatment, the final product yield was 95.9%. The applicant repeated the experiments of Examples 2 - 14 in WO2021002484A2 according to the description, as follows.

[0082] Under nitrogen protection, 88.9 g of an acetonitrile solution of compound I (purity 40.4%, 0.1 mol, the rest is acetonitrile), 10 g of water and 1.0 g of sodium tungstate dihydrate (purity 99%, 0.003 mol) were added to the reaction kettle. Stirring was started, and the internal temperature of the reaction kettle was raised to 75 - 80 °C. 22.4 g of hydrogen peroxide (purity 35%, 0.23 mol) was added dropwise within 1 h. After the addition was completed, the reaction was carried out at 75 - 80 °C for 5 h. After 5 h, the intermediate control showed that the remaining compound I was 0% (HPLC area normalization, 210 nm), the remaining sulfoxide was 26.82% (HPLC area normalization, 210 nm), and compound II (i.e., the product pyroxasulfone) was 72.37% (HPLC area normalization, 210 nm). 22.2 g of an aqueous sodium sulfite solution (content 17%, 0.03 mol) was added to the system, and the mixture was stirred at an internal temperature of 55 - 65 °C for 30 min. After standing and separating the aqueous phase, the organic phase was concentrated under reduced pressure after adding 50 ml of water, and then 80 ml of isopropanol was added for crystallization at room temperature. Then, after filtration, washing with 10 ml of isopropanol, washing with 10 ml of water, and drying (5 kPa, 60 °C), 38.8 g of compound II (white crystals) was obtained, with a purity of 72.5% and a yield of 71.9%. The sulfoxide content in the product was 26.6%.

[0083] In summary, the preparation method of pyroxasulfone provided by the present invention uses perborate as a catalyst under acidic conditions, and the obtained pyroxasulfone has a high yield (≥97%), high purity (≥99%), and a low content of by-product sulfoxide (≤0.17%); and there is no need to use rare metal catalysts and hydrogen peroxide with high risk for oxidation, avoiding the waste of scarce strategic metal resources. At the same time, the preparation process is safe and controllable, environmentally friendly, with less three wastes and less pollution, and the post-treatment is simple, reducing the production cost.

[0084] The specific embodiments described above have further elaborated on the purpose, technical solutions, and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing pyroxasulfone, characterized in that: The preparation method comprises the following steps: Under acidic conditions and in the presence of perborate, compound I is used as a raw material to react to obtain the pyroxasulfone; The compound I has a structure shown in Formula I: In Formula I, R 1 Selected from 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1H-pyrazol-4-yl, R 2 , R 3 are each independently selected from methyl.

2. The preparation method according to claim 1, characterized in that: The perborate includes any one or a combination of at least two of sodium perborate and its hydrate, potassium perborate and its hydrate, ammonium perborate and its hydrate, magnesium perborate and its hydrate, and calcium perborate and its hydrate; Preferably, the molar ratio of the perborate to compound I is (2-4):1, more preferably (2.2-3):

1.

3. The preparation method according to claim 1 or 2, characterized in that: The acidic condition originates from an acidic solvent, or a solution of an acidic catalyst and a non-acidic solvent.

4. The preparation method according to claim 3, characterized in that: The acidic solvent includes any one of acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid, or a combination of at least two thereof; Preferably, the mass ratio of the acidic solvent to compound I is (2-10):1, more preferably (3-8):1, and more preferably (3-6):

1.

5. The preparation method according to claim 3, characterized in that: The acidic catalyst includes any one or a combination of at least two of an organic acid, an inorganic acid or a compound that can react with water to generate an acid; Preferably, the organic acid is selected from any one of formic acid, acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid, or a combination of at least two thereof; Preferably, the inorganic acid is selected from any one of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, boric acid, chlorosulfonic acid, and chlorosulfonic acid, or a combination of at least two thereof; Preferably, the compound capable of reacting with water to generate an acid is selected from any one of sulfonyl chloride, thionyl chloride, acetyl chloride, dichloroacetyl chloride, trichloroacetyl chloride, trifluoroacetyl chloride, trifluoroacetyl fluoride, acetic anhydride, trifluoroacetic anhydride, peracetic acid, light fixation, chlorine, and bromine, or a combination of at least two thereof; Preferably, the molar ratio of the acidic catalyst to compound I is (1-4):1, more preferably (1.2-3):

1.

6. The preparation method according to claim 3, characterized in that: The non-acidic solvent includes any one or a combination of at least two of halogenated aliphatic hydrocarbons, aromatic hydrocarbons or halogenated aromatic hydrocarbons; Preferably, the mass ratio of the non-acidic solvent to compound I is (2-10):1, more preferably (3-8):1, and more preferably (3-6):

1.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The reaction temperature is 0 to 100°C, more preferably 20 to 80°C, and more preferably 30 to 60°C; Preferably, the reaction time is 2 to 12 hours.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The reaction further includes a post-treatment step.

9. The preparation method according to claim 8, characterized in that: The post-treatment comprises the steps of first filtration, solvent removal, crystallization, second filtration, washing and drying performed in sequence.

10. The preparation method according to any one of claims 1 to 9, characterized in that: The preparation method comprises the following steps: Under acidic conditions, compound I is mixed with perborate, reacted at 0-100°C for 2-12h, and the pyroxil is obtained through first filtration, solvent removal, crystallization, second filtration, washing and drying; the molar ratio of the perborate to compound I is (2-4):1; the acidic conditions are derived from an acidic solvent, or a solution formed by an acidic catalyst and a non-acidic solvent, and the mass ratio of the acidic solvent to compound I is (2-10):1; the molar ratio of the acidic catalyst to compound I is (1-4):1.

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