Preparation method of pyroxasulfone

Abstract

The invention discloses a preparation method of pyroxasulfone, which comprises the following steps: taking an isoxazole compound as a raw material, carrying out coupling reaction on the isoxazole compound and SO2 in the presence of formate and a nickel catalyst to obtain an intermediate, and then carrying out substitution reaction on the intermediate and a pyrazole compound under an alkaline condition to obtain the pyroxasulfone. The method is mild in reaction condition, high in yield, less in three wastes, free of dangerous reactions such as oxidation, low in cost, high in safety and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to a preparation method of sulfonepyraclostrobin, in particular to a preparation method of sulfonepyraclostrobin with simple synthesis process and simple operation, belonging to the technical field of organic synthesis. Background Art

[0002] Sulfonepyrazol was developed by Kumizu Chemical Co., Ltd. of Japan. Its chemical name is: 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, and it has the following structure: 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 the biosynthesis of VLCFA (very long side-chain fatty acids) (C20-C30) in plants.

[0003] The preparation method of sulfonepyraclostrobin is reported in the following prior art: Patent CN102666503 discloses that it can be synthesized by the following route: Specifically, the method comprises the following steps: 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-ol, formaldehyde aqueous solution and 5,5-dimethyl-4,5-dihydroisoxazole sulfamidine hydrochloride are subjected to condensation reaction in water under alkaline conditions, and then alkylated with freon to obtain sulfonepyrazol intermediate 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfanyl]-5,5-dimethyl-4H-1,2-oxazole, and then oxidized with hydrogen peroxide to obtain sulfonepyrazol 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole. However, the synthesis method has the disadvantages of too low product yield, sulfur-containing wastewater, difficulty in treating three wastes, and the use of dangerous processes (oxidation reactions).

[0004] Patent CN101213181A reports the following route for synthesizing the key intermediate of sulfonepyraclostrobin: The above method undergoes a substitution reaction under alkaline conditions, but due to the poor activity of the substrate and the solubility of the water system, the reaction yield is very low, less than 70%.

[0005] Patent CN116761802 reports a method of oxidation using an oxidant, hydrogen peroxide: The routes for preparing sulfonepyraclostrobin reported in the literature all use hydrogen peroxide or other oxidants for oxidation reactions. Oxidation reactions are one of the 18 hazardous processes that are subject to key national supervision and pose safety risks. Summary of the invention

[0006] In view of the shortcomings of the prior art, the present invention provides a method for preparing sulfonepyraclostrobin, which uses an isoxazole compound represented by formula (I) as a raw material, reacts with SO in the presence of a formate and a nickel catalyst, 2 A coupling reaction is performed to obtain an intermediate, and then the intermediate is subjected to a substitution reaction with a pyrazole compound shown in formula (II) under alkaline conditions to obtain sulfonepyraclostrobin. The present invention uses a new process route to prepare sulfonepyraclostrobin, which has the advantages of mild reaction conditions, less three wastes, low cost, high safety, etc., and innovatively uses a catalytic coupling reaction to circumvent the national key supervision dangerous process - oxidation reaction, thereby achieving intrinsic safety and being suitable for industrial production.

[0007] The specific technical solutions of the present invention are as follows: A method for preparing sulfonepyraclostrobin, wherein the compound of the structure shown in formula (I) is used as a raw material, and SO is reacted with the compound in the presence of a formate salt and a nickel catalyst. 2 A coupling reaction occurs to obtain an intermediate A; the intermediate A undergoes a substitution reaction with the compound of the structure shown in formula (II) under alkaline conditions to obtain sulfonepyraclostrobin; the reaction formula is as follows: Furthermore, in the above preparation method, in formula (I) and formula (II), X is a group that is easy to leave, such as halogen, OTf, OMs, OTs, etc., wherein the halogen can be fluorine, chlorine, bromine, or iodine.

[0008] Furthermore, in the above preparation method, in the structural formula of the intermediate A, the M is derived from the metal ion of formate, which may be sodium, potassium, or the like.

[0009] Furthermore, in the above preparation method, the compound represented by the structure of formula (I) is reacted with SO 2 The coupling reaction occurs, and the compound of the structure shown in formula (I) can be purchased from the market, or can be prepared by itself according to the method reported in the prior art.

[0010] Furthermore, in the above preparation method, the nickel catalyst is a combination of a nickel salt and a phosphine ligand, wherein the nickel salt is at least one of halides such as nickel dichloride and nickel dibromide. The nickel salt is used in combination with the phosphine ligand, and the phosphine ligand can be at least one of 1,2-bis(diphenylphosphino)ethane (DPPE), 1,3-bis(diphenylphosphino)propane (DPPP) and 1,4-bis(diphenylphosphino)butane (DPPB).

[0011] Furthermore, in the above preparation method, the molar ratio of the compound of the structure represented by formula (I) to the nickel salt is 1:0.05% to 5%, for example, 1:0.05%, 1:0.06%, 1:0.07%, 1:0.08%, 1:0.09%, 1:0.1%, 1:0.2%, 1:0.3%, 1:0.4%, 1:0.5%, 1:0.6%, 1:0.7%, 1:0.8%, 1:0.9%, 1:1.0%, 1:1.1%, 1:1.2%, 1:1.3%, 1:1.4%, 1:1.5%, 1:1.6%, 1:1.7%, 1:1.8%, 1:1.9% , 1:2.0%, 1:2.1%, 1:2.2%, 1:2.3%, 1:2.4%, 1:2.5%, 1:2.6%, 1:2.7%, 1:2.8%, 1:2.9%, 1:3.0%, 1:3.1%, 1:3.2%, 1:3.3%, 1:3.4%, 1:3.5%, 1:3.6%, 1:3.7%, 1:3.8%, 1:3.9%, 1:4.0%, 1:4.1%, 1:4.2%, 1:4.3%, 1:4.4%, 1:4.5%, 1:4.6%, 1:4.7%, 1:4.8%, 1:4.9%, 1:5.0%.

[0012] Furthermore, in the above preparation method, the molar ratio of the compound of the structure represented by formula (I) to the phosphine ligand is 1:0.05% to 5%, for example, 1:0.05%, 1:0.06%, 1:0.07%, 1:0.08%, 1:0.09%, 1:0.1%, 1:0.2%, 1:0.3%, 1:0.4%, 1:0.5%, 1:0.6%, 1:0.7%, 1:0.8%, 1:0.9%, 1:1.0%, 1:1.1%, 1:1.2%, 1:1.3%, 1:1.4%, 1:1.5%, 1:1.6%, 1:1.7%, 1:1.8%, 1:1.9 %, 1:2.0%, 1:2.1%, 1:2.2%, 1:2.3%, 1:2.4%, 1:2.5%, 1:2.6%, 1:2.7%, 1:2.8%, 1:2.9%, 1:3.0%, 1:3.1%, 1:3.2%, 1:3.3%, 1:3.4%, 1:3.5%, 1:3.6%, 1:3.7%, 1:3.8%, 1:3.9%, 1:4.0%, 1:4.1%, 1:4.2%, 1:4.3%, 1:4.4%, 1:4.5%, 1:4.6%, 1:4.7%, 1:4.8%, 1:4.9%, 1:5.0%.

[0013] Furthermore, in the above preparation method, when the catalyst is a nickel catalyst, the formate used is at least one of sodium formate and potassium formate.

[0014] Furthermore, in the above preparation method, the molar ratio of the compound of the structure represented by formula (I) to the formate is 1:1.05-2.5, for example, 1:1.05, 1:1.10, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0, 1:2.05, 1:2.10, 1:2.15, 1:2.20, 1:2.25, 1:2.30, 1:2.35, 1:2.40, 1:2.45, 1:2.50.

[0015] Furthermore, in the above preparation method, the compound represented by formula (I) and SO 2 The molar ratio is 1:1.05 to 5, for example 1:1.05, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3.0, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, 1:4.0, 1:4.1, 1:4.2, 1:4.3, 1:4.4, 1:4.5, 1:4.6, 1:4.7, 1:4.8, 1:4.9, 1:5.0.

[0016] Furthermore, in the above preparation method, the reaction for preparing the intermediate A is carried out in a solvent, and when the catalyst is a nickel catalyst, the solvent is an alcohol solvent, a nitrile solvent, a ketone solvent, an amide solvent, a sulfone solvent, etc., and examples thereof include methanol, ethanol, acetonitrile, acetone, DMF, DMSO, etc. Among them, alcohol solvents are relatively safe, and the product yield and purity are also higher, so alcohol solvents are preferred, and methanol and ethanol are most preferred.

[0017] Furthermore, in the above preparation method, when the catalyst is a nickel catalyst, the reaction temperature is 5°C to 45°C, for example, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, preferably 15 to 25°C. At this reaction temperature, the compound represented by the structure of formula (I) reacts with SO in the presence of a nickel salt, a phosphine ligand, and a formate. 2 The reaction can occur rapidly, and the reaction time is less than 6 hours, such as 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 5.5 hours, and any range value therebetween.

[0018] Furthermore, in the above preparation method, the compound of formula (I), formate, nickel salt, phosphine ligand and solvent are first mixed, and then SO 2 There is no special requirement for the order of adding the compound represented by formula (I), formate, nickel salt, phosphine ligand and solvent. Preferably, formate, nickel salt and phosphine ligand are added under the protection of an inert atmosphere such as nitrogen or argon. After the reaction is completed, the reaction liquid is filtered, and the obtained mother liquor containing intermediate A can be directly used for the next reaction.

[0019] Furthermore, intermediate A undergoes a substitution reaction with the compound of the structure shown in formula (II) under alkaline conditions to obtain sulfonepyraclostrobin, wherein the alkaline conditions are provided by an alkaline substance, and the alkaline substance is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate or potassium carbonate.

[0020] Furthermore, in the above preparation method, the molar ratio of intermediate A to alkaline substance is 1:0.5-1.5, for example, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5.

[0021] Furthermore, in the above preparation method, the molar ratio of intermediate A to the compound of the structure represented by formula (II) is 1:1.05 to 1.5, for example, 1:1.05, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5.

[0022] Furthermore, in the above preparation method, the reaction temperature is 5 to 45° C., for example, 5° C., 10° C., 15° C., 20° C., 25° C., 30° C., 35° C., 40° C., 45° C., preferably 15 to 25° C. At this reaction temperature, the intermediate A and the compound of the structure represented by formula (II) can react rapidly under alkaline conditions, and the reaction time is ≤ 4 hours, for example, 1 hour, 2 hours, 3 hours, 4 hours, and any range value therebetween.

[0023] Furthermore, in the above preparation method, the reaction between the intermediate A and the compound of the structure shown in formula (II) is carried out in the presence of a solvent, and the solvent used is the same as the solvent used to prepare the intermediate A. The reaction solution of the intermediate A can be directly reacted with the compound of the structure shown in formula (II) after filtration. After the reaction is completed, the filtrate is filtered and then the filtrate is cooled and crystallized by adding water, and the obtained crystals are dried to obtain the final product. The present invention has simple post-processing, is easy to operate, and has high purity and high yield of the obtained product.

[0024] The present invention provides a new method for preparing sulfonepyraclostrobin, wherein a compound of the structure shown in formula (I) reacts with SO in the presence of formate and nickel catalyst.2 The intermediate A is prepared by reaction, and the intermediate A reacts with the compound of the structure shown in formula (II) to obtain sulfonepyraclostrobin in one step. Compared with the existing preparation method, the present invention has the following advantages: (1) The reaction conditions of the present invention are mild and the equipment requirements are not high; (2) The present invention has fewer reaction steps, faster reaction speed and simpler synthesis process. By selecting the process conditions, the reaction selectivity is high, the reaction yield is high and the product purity is high. It has been verified that under the preferred process conditions, the product yield is above 83% (based on compound (I)) and the product purity can reach above 97%; (3) The product obtained by the present invention is easy to separate, and the post-treatment is simple and extensive, which is suitable for large-scale production; (4) The three wastes generated in the synthesis process of the present invention are small, easy to handle, and environmentally friendly; (5) The present invention innovatively uses a coupling reaction with a catalyst in the preparation process of sulfonepyraclostrobin, avoiding the oxidation reaction of eighteen dangerous processes and achieving intrinsic safety. DETAILED DESCRIPTION

[0025] The technical scheme of the present invention is further described below in conjunction with specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the raw materials used in the present invention can be purchased on the market. Alternatively, they can be prepared by themselves according to the methods reported in the prior art.

[0026] Unless otherwise specified, the following percentages are by mass.

[0027] Example 1 1. At room temperature, add 40 ml of ethanol and 16.69 g of the compound of formula (I) (where X is chlorine, content 80%) to the reaction bottle and stir evenly; under nitrogen protection, add 8.16 g of sodium formate and 0.013 g of NiCl 2 , 0.079 g 1,2-bis(diphenylphosphino)ethane (DPPE), and then 7.68 g sulfur dioxide were introduced, and the reaction was continued with stirring for 4 hours. After the reaction was completed by HPLC detection, the reaction was filtered and the mother liquor was collected to obtain an ethanol solution of intermediate A for use.

[0028] 2. To the ethanol solution of intermediate A, 3.68 g of solid sodium hydroxide and 29.75 g of a compound of formula (II) (wherein X is chlorine, content 90%) were added at room temperature, and the mixture was stirred for 4 hours. The reaction was controlled by HPLC. After the reaction was completed, the filtrate was collected, 60 g of water was added, and the mixture was cooled to 5°C for crystallization. After keeping the temperature for 2 hours, the solid was filtered and collected. After drying, 34.86 g of a white solid was obtained. The purity was 98.1% as determined by HPLC, and the yield was 87.4% based on the compound of formula (I).

[0029] Example 2 1. At room temperature, add 40 ml of methanol and 22.25 g of the compound of formula (I) (where X is bromine, content 80%) to the reaction bottle and stir evenly; under nitrogen protection, add 8.16 g of sodium formate and 0.022 g of NiBr 2 , 0.082 g 1,3-bis(diphenylphosphino)propane (DPPP), and then 7.68 g sulfur dioxide were introduced, and the reaction was continued with stirring for 4 hours. After the reaction was completed by HPLC detection, the reaction was filtered and the mother liquor was collected to obtain an ethanol solution of intermediate A for use.

[0030] 2. To the ethanol solution of intermediate A, 3.68 g of solid sodium hydroxide and 29.75 g of a compound of formula (II) (wherein X is bromine, content 90%) were added at room temperature, and the mixture was stirred for 4 hours. The reaction was controlled by HPLC. After the reaction was completed, the filtrate was collected, 60 g of water was added, and the mixture was cooled to 5°C for crystallization. After keeping the temperature for 2 hours, 35.2 g of the product was obtained by filtration. The purity of the product was 98.2% as determined by HPLC, and the yield was 88.3% based on the compound of formula (I).

[0031] Example 3 1. Add 30 ml of acetonitrile and 16.69 g of the compound of formula (I) (where X is chlorine, content 80%) to the reaction bottle at 40°C and stir evenly; under nitrogen protection, add 8.16 g of sodium formate and 0.013 g of NiCl 2 , 0.079g 1,2-bis(diphenylphosphino)ethane (DPPE), then 7.68g sulfur dioxide was introduced, and the reaction was continued with stirring for 4 hours. After the reaction was completed as detected by HPLC, the reaction was filtered and the mother liquor was collected to obtain an acetonitrile solution of intermediate A for use.

[0032] 2. Add 3.68 g of solid sodium hydroxide and 29.75 g of a compound of formula (II) (wherein X is chlorine, content 90%) to the ethanol solution of intermediate A at 30°C, stir and react for 4 hours, and control the reaction by HPLC. After the reaction is completed, collect the filtrate, add 60 g of water, cool to 5°C for crystallization, keep warm for 2 hours, filter, collect the solid, and dry to obtain 33.83 g of a white solid. The purity of the solid is 97.9% as determined by HPLC, and the yield is 84.6% based on the compound of formula (I).

[0033] Example 4 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that: in step 1, the solvent ethanol was replaced by an equal volume of DMF, and the sodium formate was replaced by an equal molar amount of potassium formate; in step 2, the sodium hydroxide was replaced by an equal molar amount of potassium hydroxide, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 97.5%, and the yield was 83.5% based on the compound of formula (I).

[0034] Example 5 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that: in step 1, the solvent ethanol was replaced by an equal volume of acetone, sodium formate was replaced by an equal molar amount of potassium formate, and 1,2-bis(diphenylphosphino)ethane (DPPE) was replaced by an equal molar amount of 1,4-bis(diphenylphosphino)butane (DPPB); in step 2, sodium hydroxide was replaced by an equal molar amount of potassium hydroxide, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 97.7%, and the yield was 84.5% based on the compound of formula (I).

[0035] Example 6 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that the temperature of the coupling reaction in step 1 was 15°C, sodium formate was replaced by an equimolar amount of potassium formate, and in step 2, sodium hydroxide was replaced by an equimolar amount of potassium bicarbonate, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 98.3%, and the yield was 88.7% based on the compound of formula (I).

[0036] Example 7 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that the temperature of the coupling reaction in step 1 was 35°C; the temperature of the substitution reaction in step 2 was 40°C, sodium hydroxide was replaced by an equimolar amount of sodium bicarbonate, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 97.4%, and the yield was 83.2% based on the compound of formula (I).

[0037] Example 8 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that the temperature of the coupling reaction in step 1 was 40°C; the temperature of the substitution reaction in step 2 was 40°C, sodium hydroxide was replaced by an equimolar amount of potassium bicarbonate, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 97.5%, and the yield was 83.4% based on the compound of formula (I).

[0038] Example 9 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that the temperature of the coupling reaction in step 1 was 40°C; the temperature of the substitution reaction in step 2 was 40°C, sodium hydroxide was replaced by an equimolar amount of sodium carbonate, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 97.5%, and the yield was 84.2% based on the compound of formula (I).

[0039] Example 10 The method of Example 1 was used to prepare pyraclostrobin, except that in step 1, the catalyst NiCl 2 The mass was reduced to 0.011 g, and the remaining steps and conditions remained unchanged. After testing, the purity of the final product was 97.8%, and the yield was 87.1% based on the compound of formula (I).

[0040] Embodiment 11 Sulfonepyraclostrobin was prepared according to the method of Example 1, except that in step 1, the mass of the ligand 1,2-bis(diphenylphosphino)ethane (DPPE) was reduced to 0.071 g, and the other steps and conditions remained unchanged. After testing, the purity of the final product was 98.1%, and the yield was 87.2% based on the compound of formula (I).

Claims

1. A method for preparing sulfonepyraclostrobin, characterized in that: The compound of the structure shown in formula (I) is used as a raw material, and a coupling reaction is carried out with SO2 in the presence of a formate and a nickel catalyst to obtain an intermediate A; the intermediate A and the compound of the structure shown in formula (II) undergo a substitution reaction under alkaline conditions to obtain sulfonepyraclostrobin; the reaction formula is as follows: 。 2. The preparation method according to claim 1, characterized in that: In formula (I) and formula (II), X is a group that is easy to leave, preferably halogen, OTf, OMs, Ots; in intermediate A, M is derived from the metal ion of formate.

3. The preparation method according to claim 1, characterized in that: The formate salt is sodium formate and / or potassium formate; the nickel catalyst is a combination of a nickel salt and a phosphine ligand, the nickel salt is nickel dichloride and / or nickel dibromide, and the phosphine ligand is at least one of 1,2-bis(diphenylphosphino)ethane (DPPE), 1,3-bis(diphenylphosphino)propane (DPPP) and 1,4-bis(diphenylphosphino)butane (DPPB).

4. The preparation method according to claim 3, characterized in that: The molar ratio of the compound with the structure shown in formula (I) to the nickel salt is 1:0.05% to 5%, and the molar ratio of the compound with the structure shown in formula (I) to the phosphine ligand is 1:0.05% to 5%.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The molar ratio of the compound of the structure shown in formula (I) to formate is 1:1.05-2.5; the molar ratio of the compound of the structure shown in formula (I) to SO2 is 1:1.05-5.

6. The preparation method according to any one of claims 1 to 4, characterized in that: The temperature of the coupling reaction between the compound represented by formula (I) and SO2 is 5 to 45°C, preferably 15 to 25°C.

7. The preparation method according to any one of claims 1 to 4, characterized in that: The preparation of intermediate A and the preparation of sulfonepyraclostrobin are both carried out in the presence of a solvent, and the solvent is preferably methanol, ethanol, acetonitrile, acetone, DMF or DMSO, more preferably methanol or ethanol.

8. The preparation method according to claim 1, characterized in that: The alkaline condition is provided by an alkaline substance, and the alkaline substance is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate or potassium carbonate; preferably, the molar ratio of intermediate A to the alkaline substance is 1:0.5-1.

5.

9. The preparation method according to claim 1 or 8, characterized in that: The molar ratio of the intermediate A to the compound of the structure represented by formula (II) is 1:1.05-1.

5.

10. The preparation method according to claim 1 or 8, characterized in that: The reaction temperature of the intermediate A and the compound represented by the structure of formula (II) is 5 to 45°C, preferably 15 to 25°C.

Images