A method for preparing pyroxasulfone

Abstract

The application discloses a preparation method of metrafenone. The method comprises the following steps: taking an isoxazole compound as a raw material, coupling with SO2 under the action of formate and a nickel catalyst to obtain an intermediate, and then performing a substitution reaction on the intermediate under alkaline conditions to obtain metrafenone. The method has the advantages of mild reaction condition, high yield, less waste, no dangerous reaction such as oxidation, low cost, high safety, and suitability for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of furilazole, in particular to a preparation method of furilazole with simple synthesis process and simple operation, and belongs to the technical field of organic synthesis. BACKGROUND

[0002] Furilazole is developed by Japan Group Chemical Co., Ltd., and its chemical name is: 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl methyl sulfuryl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, and has the following structure:

[0003]

[0004] Furilazole can be used as a pre-emergence soil treatment agent in most crop fields, and after application, it is absorbed by the young roots and young shoots of weeds, inhibits the early growth of seedlings, and destroys the meristem and hypocotyl, which is a serious potential inhibitor in the biosynthesis of VLCFA (very long chain fatty acid) (C20-C30) in plants.

[0005] The preparation method of furilazole has the following prior art reports:

[0006] Patent CN102666503 discloses that it can be synthesized by the following route:

[0007]

[0008] Specifically, the following steps are included: under alkaline conditions, 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol, formaldehyde aqueous solution and 5,5-dimethyl-4,5-dihydroisoxazole sulfamidine hydrochloride are subjected to condensation reaction in water, and then subjected to alkylization with freon to obtain furilazole intermediate 3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl] methyl sulfanyl]-5,5-dimethyl-4H-1,2-oxazole, and then subjected to oxidation with hydrogen peroxide to obtain furilazole 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl methyl sulfuryl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole. However, the synthesis method has the disadvantages of low product yield, existence of sulfur-containing wastewater, difficulty in treatment of three wastes, and use of dangerous process (oxidation reaction).

[0009] Patent CN101213181A reports a method for synthesizing a key intermediate of furilazole by the following route:

[0010]

[0011] The above method occurs substitution reaction under alkaline condition, but due to the substrate activity and poor water system solubility, the reaction yield is very low, less than 70%.

[0012] The patent CN116761802 reports a method of using oxidant hydrogen peroxide for oxidation:

[0013]

[0014] The current literature reports the preparation of metrafenone, which adopts hydrogen peroxide or other oxidants for oxidation reaction. Oxidation reaction belongs to one of the 18 key regulated dangerous processes in China, and has safety risks. SUMMARY

[0015] In view of the deficiencies of the prior art, the present application provides a preparation method of metrafenone. The method uses isoxazole compound of formula (I) as raw material, and couples with SO2 under the action of formate and nickel catalyst to obtain intermediate, and then the intermediate is subjected to substitution reaction with pyrazole compound of formula (II) under alkaline condition to obtain metrafenone. The present application uses a new process route to prepare metrafenone, which has the advantages of mild reaction condition, less waste, low cost, high safety, etc. The innovative use of catalytic coupling reaction avoids the national key regulated dangerous process-oxidation reaction, realizes intrinsic safety, and is suitable for industrial production.

[0016] The specific technical scheme of the present application is as follows:

[0017] A preparation method of metrafenone, which uses a compound of formula (I) as a raw material, and couples with SO2 under the action of formate and nickel catalyst to obtain intermediate A; the intermediate A is subjected to substitution reaction with a compound of formula (II) under alkaline condition to obtain metrafenone; the reaction formula is as follows:

[0018]

[0019] Further, in the above preparation method, in formula (I) and formula (II), X is an easily leaving group, for example halogen, OTf, OMs, OTs, etc., wherein halogen can be fluorine, chlorine, bromine, iodine.

[0020] Further, in the above preparation method, in the structural formula of intermediate A, M comes from the metal ion of formate, which can be sodium, potassium, etc.

[0021] Further, in the above preparation method, the compound of formula (I) couples with SO2 under the action of nickel catalyst, and the compound of formula (I) can be purchased from the market or can be prepared according to the method reported in the prior art.

[0022] Further, 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 nickel dichloride, nickel dibromide, and the like. The nickel salt is used in combination with a phosphine ligand, which can be at least one of 1,2-bis(diphenylphosphino)ethane (DPPE), 1,3-bis(diphenylphosphino)propane (DPPP), 1,4-bis(diphenylphosphino)butane (DPPB), and the like.

[0023] Further, in the above preparation method, the molar ratio of the compound 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%.

[0024] Further, in the above preparation method, the molar ratio of the compound 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%.

[0025] Further, in the above preparation method, when the catalyst is a nickel catalyst, the formate salt used is at least one of sodium formate and potassium formate.

[0026] Further, in the above preparation method, the molar ratio of the compound represented by formula (I) to the formate salt is 1 : 1.05 to 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.

[0027] Further, in the above preparation method, the molar ratio of the compound having the structure shown in formula (I) to SO2 is 1:1.05-5, 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.

[0028] Further, 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, the alcohol solvent is relatively safe, and the product yield and purity are also higher, and thus the alcohol solvent is preferred, and methanol or ethanol is most preferred.

[0029] Further, in the above preparation method, when the catalyst is a nickel catalyst, the reaction temperature is 5-45°C, for example, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, and preferably 15-25°C. Under this reaction temperature, the compound having the structure shown in formula (I) can rapidly react with SO2 in the presence of a nickel salt, a phosphine ligand, and a formate salt, and the reaction time is <6 hours, for example, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 5.5 hours, and any range value between them.

[0030] Further, in the above preparation method, the compound having the structure shown in formula (I), the formate salt, the nickel salt, the phosphine ligand, and the solvent are mixed first, and then SO2 is introduced for reaction. Among them, there is no special requirement for the order of adding the compound having the structure shown in formula (I), the formate salt, the nickel salt, the phosphine ligand, and the solvent, and preferably, the formate salt, the nickel salt, and the phosphine ligand are added under the protection of an inert gas such as nitrogen or argon. After the reaction is completed, the reaction liquid is filtered, and the mother liquor containing the intermediate A obtained can be directly used for the next reaction.

[0031] Further, the intermediate A and the compound having the structure shown in formula (II) are subjected to a substitution reaction under basic conditions to obtain metamifop, and the basic conditions are provided by a basic substance, and the basic substance is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, or potassium carbonate.

[0032] Further, in the above preparation method, the molar ratio of intermediate A to the basic 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.

[0033] Further, in the above preparation method, the molar ratio of intermediate A to the compound of formula (II) is 1:1.05-1.5, for example, 1:1.05, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5.

[0034] Further, in the above preparation method, the reaction temperature is 5-45℃, for example, 5℃, 10℃, 15℃, 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, preferably 15-25℃. At this reaction temperature, intermediate A can rapidly react with the compound of formula (II) under alkaline conditions, and the reaction time is ≤4 hours, for example, 1 hour, 2 hours, 3 hours, 4 hours, and any range value between them.

[0035] Further, in the above preparation method, the reaction of intermediate A with the compound of formula (II) is carried out in the presence of a solvent, and the solvent used is the same as that used in the preparation of intermediate A. The reaction solution of intermediate A can be directly reacted with the compound of formula (II) after filtration. After the reaction is completed, the filtrate is filtered, then the filtrate is cooled by adding water to precipitate crystals, and the obtained crystals are dried to obtain the final product. The post-treatment of the present application is simple and easy to operate, and the obtained product has high purity and high yield.

[0036] The present application provides a new method for preparing metrafenone, which utilizes the compound of formula (I) to react with SO2 under the catalysis of formate and nickel to prepare intermediate A, and then intermediate A is directly reacted with the compound of formula (II) to obtain metrafenone. Compared with the existing preparation method, the present application has the following advantages:

[0037] (1) The reaction condition of the present application is mild, and the requirement for equipment is not high;

[0038] (2) The present application has fewer reaction steps, fast reaction speed, and simple synthesis process. Through the selection of process conditions, the reaction has high selectivity, high reaction yield, and high product purity. It has been verified that under the optimal process conditions, the product yield is more than 83% (calculated based on compound (I)), and the product purity is more than 97%;

[0039] (3) The product obtained by the present application is easy to separate, the post-treatment is simple and extensive, and it is suitable for large-scale production;

[0040] (4) The three wastes generated in the synthesis process are less, easy to handle, and good in environmental protection;

[0041] (5) The innovation of the application is that a coupling reaction using a catalyst is used in the preparation process of the metalaxyl-M, which avoids 18 dangerous oxidation reactions, and achieves intrinsic safety. DETAILED DESCRIPTION

[0042] The technical solutions of the application will be further described below in combination with specific examples, but the application is not limited to the following examples. If not specifically stated, the raw materials used in the application can be purchased in the market. Or they can be prepared by themselves according to the methods reported in the prior art.

[0043] Unless otherwise specified, the percentages below are mass percentages.

[0044] Example 1

[0045] 1. Under room temperature, 40 ml of ethanol, 16.69 g of the compound of formula (I) (wherein X is chlorine, content 80%) were added into a reaction bottle and stirred uniformly; under the condition of nitrogen protection, 8.16 g of sodium formate, 0.013 g of NiCl2 and 0.079 g of 1,2-bis(diphenylphosphino)ethane (DPPE) were added into the reaction bottle, then 7.68 g of sulfur dioxide was introduced, and the stirring reaction was continued for 4 hr; after the reaction was completed by HPLC detection, the reaction was filtered first, and the mother liquor was collected to obtain an ethanol solution of intermediate A for standby.

[0046] 2. Under room temperature, 3.68 g of sodium hydroxide solid and 29.75 g of the compound of formula (II) (wherein X is chlorine, content 90%) were added into the ethanol solution of intermediate A and stirred for 4 hr; after the reaction was completed by HPLC control, the filtrate was collected, 60 g of water was added, and the solution was cooled at 5 ℃ for crystallization; after 2 hr of heat preservation, the solid was collected by filtration and dried to obtain 34.86 g of white solid, the purity of which was 98.1% by HPLC detection, and the yield was 87.4% based on the compound of formula (I).

[0047] Example 2

[0048] 1. Under room temperature, 40 ml of ethanol, 16.69 g of the compound of formula (I) (wherein X is chlorine, content 80%) were added into a reaction bottle and stirred uniformly; under the condition of nitrogen protection, 8.16 g of sodium formate, 0.013 g of NiCl2 and 0.079 g of 1,2-bis(diphenylphosphino)ethane (DPPE) were added into the reaction bottle, then 7.68 g of sulfur dioxide was introduced, and the stirring reaction was continued for 4 hr; after the reaction was completed by HPLC detection, the reaction was filtered first, and the mother liquor was collected to obtain an ethanol solution of intermediate A for standby.

[0049] 2. To the solution of intermediate A in ethanol, add sodium hydroxide 3.68 g solid, 29.75 g of compound of formula (II) (wherein X is bromine, content 90%) at room temperature, stir for 4 hr, control the reaction by HPLC, after the reaction is completed, collect the filtrate, add 60 g of water, cool at 5 °C, crystallize, after 2 hr of incubation, filter to obtain the product 35.2 g, which has a purity of 98.2% by HPLC detection, the yield is 88.3% based on the compound of formula (I).

[0050] Example 3

[0051] 1. To the reaction bottle, add 30 ml of acetonitrile, 16.69 g of compound of formula (I) (wherein X is chlorine, content 80%) at 40 °C, stir until uniform; under the protection of nitrogen, add 8.16 g of sodium formate, 0.013 g of NiCl2, 0.079 g of 1,2-bis(diphenylphosphino)ethane (DPPE) to the reaction bottle, then pass in 7.68 g of sulfur dioxide, continue to stir for 4 hr, after the reaction is completed by HPLC detection, first filter the reaction, collect the mother liquor to obtain the acetonitrile solution of intermediate A for standby.

[0052] 2. To the solution of intermediate A in ethanol, add sodium hydroxide 3.68 g solid, 29.75 g of compound of formula (II) (wherein X is chlorine, content 90%) at 30 °C, stir for 4 hr, control the reaction by HPLC, after the reaction is completed, collect the filtrate, add 60 g of water, cool at 5 °C, crystallize, after 2 hr of incubation, filter to collect the solid, dry to obtain white solid 33.83 g, which has a purity of 97.9% by HPLC detection, the yield is 84.6% based on the compound of formula (I).

[0053] Example 4

[0054] Prepare mesotrione according to the method of Example 1, except that in step 1, replace the solvent ethanol with an equal volume of DMF, and replace sodium formate with an equal molar amount of potassium formate; in step 2, replace sodium hydroxide with an equal molar amount of potassium hydroxide, and the rest of the steps and conditions remain unchanged. After detection, the purity of the final product is 97.5%, and the yield is 83.5% based on the compound of formula (I).

[0055] Example 5

[0056] The preparation of pyroxasulfone was carried out according to the method of Example 1, except that: in Step 1, the solvent ethanol was replaced with equal volume of acetone, sodium formate was replaced with equal molar amount of potassium formate, and 1,2-bis(diphenylphosphino)ethane (DPPE) was replaced with equal molar amount of 1,4-bis(diphenylphosphino)butane (DPPB); in Step 2, sodium hydroxide was replaced with equal molar amount of potassium hydroxide, and the rest of the steps and conditions were unchanged. The purity of the final product was detected to be 97.7%, and the yield was 84.5% based on the compound of Formula (I).

[0057] Example 6

[0058] The preparation of pyroxasulfone was carried out according to the method of Example 1, except that: the temperature of the coupling reaction in Step 1 was 15°C, and sodium formate was replaced with equal molar amount of potassium formate; in Step 2, sodium hydroxide was replaced with equal molar amount of potassium bicarbonate, and the rest of the steps and conditions were unchanged. The purity of the final product was detected to be 98.3%, and the yield was 88.7% based on the compound of Formula (I).

[0059] Example 7

[0060] The preparation of pyroxasulfone was carried out 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, and sodium hydroxide was replaced with equal molar amount of sodium bicarbonate, and the rest of the steps and conditions were unchanged. The purity of the final product was detected to be 97.4%, and the yield was 83.2% based on the compound of Formula (I).

[0061] Example 8

[0062] The preparation of pyroxasulfone was carried out 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, and sodium hydroxide was replaced with equal molar amount of potassium bicarbonate, and the rest of the steps and conditions were unchanged. The purity of the final product was detected to be 97.5%, and the yield was 83.4% based on the compound of Formula (I).

[0063] Example 9

[0064] The preparation of pyroxasulfone was carried out 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, and sodium hydroxide was replaced with equal molar amount of sodium carbonate, and the rest of the steps and conditions were unchanged. The purity of the final product was detected to be 97.5%, and the yield was 84.2% based on the compound of Formula (I).

[0065] Example 10

[0066] Prepare mesotrione according to the method of Example 1, except that in Step 1, the mass of catalyst NiCl2is reduced to 0.011 g, and the remaining steps and conditions are unchanged. The purity of the final product is determined to be 97.8%, and the yield is 87.1% based on the compound of formula (I).

[0067] Example 11

[0068] Prepare mesotrione according to the method of Example 1, except that in Step 1, the mass of ligand 1,2-bis(diphenylphosphino)ethane (DPPE) is reduced to 0.071 g, and the remaining steps and conditions are unchanged. The purity of the final product is determined to be 98.1%, and the yield is 87.2% based on the compound of formula (I).

Claims

1. A method for preparing sulfonylpyrazole, characterized in that: Using the compound with the structure shown in formula (I) as a starting material, a coupling reaction is carried out with SO2 in the presence of formate and nickel catalyst to obtain intermediate A; intermediate A undergoes a substitution reaction with the compound with the structure shown in formula (II) under alkaline conditions to obtain sulfonylpyrazol; the reaction formula is as follows: ； In formulas (I) and (II), X is a departing group; in intermediate A, M is derived from a metal ion of a formate; the nickel catalyst is a combination of a nickel salt and a phosphine ligand, wherein the nickel salt is nickel dichloride and / or nickel dibromide, and the phosphine ligand is at least one of 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, and 1,4-bis(diphenylphosphine)butane.

2. The preparation method according to claim 1, characterized in that: In formulas (I) and (II), X is a halogen, OTf, OMs or OTs.

3. The preparation method according to claim 1, characterized in that: The formate is sodium formate and / or potassium formate.

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

6. The preparation method according to any one of claims 1-4, characterized in that: The coupling reaction temperature of the compound with SO2 shown in formula (I) is 5–45 °C.

7. The preparation method according to claim 6, characterized in that: The coupling reaction of the compound with SO2 shown in formula (I) takes place at a temperature of 15–25 °C.

8. The preparation method according to any one of claims 1-4, characterized in that: The preparation of intermediate A and sulfopyrazole were both carried out in the presence of a solvent.

9. The preparation method according to claim 8, characterized in that: The solvent is methanol, ethanol, acetonitrile, acetone, DMF, or DMSO.

10. The preparation method according to claim 8, characterized in that: The solvent is methanol or ethanol.

11. The preparation method according to claim 1, characterized in that: The alkaline conditions are provided by an alkaline substance, which is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, or potassium carbonate.

12. The preparation method according to claim 11, characterized in that: The molar ratio of intermediate A to the alkaline substance is 1:0.5 to 1.

5.

13. The preparation method according to claim 1 or 11, characterized in that: The molar ratio of intermediate A to the compound with the structure shown in formula (II) is 1:1.05 to 1.

5.

14. The preparation method according to claim 1 or 11, characterized in that: The reaction temperature of intermediate A with the compound with the structure shown in formula (II) is 5–45 °C.

15. The preparation method according to claim 14, characterized in that: The reaction temperature of intermediate A with the compound with the structure shown in formula (II) is 15–25 °C.

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