A preparation method of sulfonepyraclostrobin intermediate

Abstract

The present invention relates to a method for preparing a sulfonepyraclostrobin intermediate, comprising the following steps: S1, in a solvent, acetic acid oxime and N-chlorosuccinimide react to obtain a reaction solution containing dichloroformaldehyde oxime; S2, in water, under the action of a catalyst and a base, dichloroformaldehyde oxime and isobutylene in the reaction solution obtained by S1 react, and after the reaction is completed, 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is obtained by post-treatment. The present invention produces 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole at a higher yield on the basis of using acetic acid oxime, with the advantages of reducing reaction temperature, improving reaction yield, effectively controlling side reactions, and realizing greater economic benefits.

Description

Technical Field

[0001] The invention relates to the technical field of organic intermediate synthesis, in particular to a method for preparing a sulfonepyraclostrobin intermediate. Background Art

[0002] Pyroxasulfone, whose English name is Pyroxasulfone and whose chemical name is 3-(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-methylsulfonyl)-4,5-2H-5,5-dimethyl-1,2-oxazole, is a new type of pre-emergence herbicide. The development and application of this compound are of great significance in modern agriculture because it can effectively control the growth of weeds and thus protect the healthy growth of crops. 3-Chloro-5,5-dimethyl-4,5-dihydroisoxazole is a key intermediate of pyroxasulfone, and its synthesis method directly affects the production cost and safety of pyroxasulfone. At present, there are three main methods for the synthesis of 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole.

[0003] The first method is to use ethyl carbamate as the starting material and prepare it through three steps of aminolysis, cyclization and chlorination. However, the raw material cost of this method is relatively high, especially when the chlorination reaction is achieved by phosphorus oxychloride or phosphorus pentachloride, the treatment pressure of the by-product is relatively high. Related literature includes EP0697406A1; and OrgChem, 1990, 55: 2155-2159.

[0004] The second synthesis method is to use methyl butynol as the starting material, and prepare it by cyclization with propyl copper oxime and chlorination with chlorine. Although this method is feasible, the raw material cost is high and it involves the use of dangerous gas chlorine, which increases the safety risk in the production process. Related literature includes Polyhedron, 2000, 19, 1693-1698; Tetrahedron Letters, 1988, 29 (28): 6253-6256; and WO2011063842.

[0005] The third method is to use acetic acid oxime as the starting material, and prepare it by NCS chlorination and subsequent cyclization. The raw material cost of this method is relatively low, but the reaction yield is low, only 38%. Related literature includes Agric Food Chem, 2010, 58, 4356-4360; and US20040110749.

[0006] In view of the problems existing in the above three methods, it is of great economic value to develop a safe and low-cost method for preparing 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. This can not only reduce production costs and improve economic benefits, but also improve the safety of the production process and reduce environmental pollution. Therefore, researchers need to continuously explore and optimize the synthesis process in order to find a better synthesis route and promote the widespread application of sulfonepyraclostrobin in the agricultural field. Summary of the invention

[0007] The problem to be solved by the present invention is to provide a method for preparing a sulfonepyraclostrobin intermediate in view of the above-mentioned deficiencies existing in the prior art. On the basis of using acetic acid oxime, 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is produced in a high yield, and the method has the advantages of reducing the reaction temperature, improving the reaction yield, effectively controlling the side reactions, and achieving greater economic benefits.

[0008] The above-mentioned object of the present invention is achieved through the following technical solutions:

[0009] A method for preparing a sulfonepyraclostrobin intermediate, the route of the preparation method is as follows:

[0010] ;

[0011] The preparation method comprises the following steps:

[0012] S1: in a solvent, acetic acid oxime reacts with N-chlorosuccinimide to obtain a reaction solution containing dichloroformaldehyde oxime;

[0013] S2: In water, under the action of a catalyst and a base, the dichloroformaldehyde oxime in the reaction solution obtained in S1 reacts with isobutylene. After the reaction is completed, post-treatment is performed to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole.

[0014] Furthermore, in S1, the solvent is one or a combination of halogenated alkane solvents, ether solvents, alcohol solvents, ketone solvents, amide solvents, ester solvents, and nitrile solvents.

[0015] Furthermore, in S1, the solvent is one or a combination of toluene, chlorobenzene, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, and ethylene glycol dimethyl ether.

[0016] Furthermore, in the S1, the usage ratio of the solvent, acetic acid oxime and N-chlorosuccinimide is 200-2000 mL: 1 mol: 1.50-2.50 mol.

[0017] Furthermore, in S1, acetic acid oxime is first dissolved in a solvent and heated to 50-100° C., and then N-chlorosuccinimide is added in multiple portions within 1 hour, and then the reaction is kept warm for 0.5-1.5 hours to obtain a reaction solution containing dichloroformaldehyde oxime.

[0018] Furthermore, in S2, the catalyst is a Lewis acid catalyst.

[0019] Furthermore, in S2, the catalyst is one or a combination of copper sulfate, cuprous sulfate, cupric chloride, cuprous chloride, zinc chloride, ferric chloride, and ferrous chloride.

[0020] Furthermore, in S2, the base is an inorganic base and an organic base or a combination of several thereof.

[0021] Furthermore, in S2, the alkali is one or a combination of sodium carbonate, sodium bicarbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate.

[0022] Furthermore, in S2, the usage ratio of water, catalyst, base, dichloroformaldehyde oxime and isobutylene is 40-60 g: 0.01-0.40 mol: 0.40-16.00 mol: 1 mol: 1.50-2.50 mol.

[0023] Furthermore, in S2, the reaction solution obtained in S1 is first cooled to -10~10°C, and then water, a catalyst, and a base are added, stirred and mixed for 20~40min, and then isobutylene is added, and the reaction is carried out at room temperature for 4~6h. After the reaction is completed, water is added to separate the layers, and the aqueous phase is extracted with petroleum ether for multiple times. The organic phase obtained by separation is washed several times with a saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole.

[0024] In summary, the beneficial technical effects of the present invention are:

[0025] 1. By optimizing the reaction conditions, the high-yield synthesis of 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole was achieved, which effectively increased the yield of the target product and reduced the production cost;

[0026] 2. The reaction conditions adopted by the present invention are mild and the reaction temperature is low, which reduces the occurrence of side reactions and improves the selectivity of the reaction, thereby improving the purity of the product;

[0027] 3. The solvent and catalyst system used in the present invention are environmentally friendly, reduce environmental pollution, and conform to the development trend of green chemistry;

[0028] 4. The present invention provides an efficient, environmentally friendly and economical method for preparing a sulfonepyraclostrobin intermediate, which not only solves the problems existing in the prior art, but also has high industrial application value. Through the implementation of the present invention, a new synthetic route can be provided for related fields, promoting the development of related industries. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the NMR spectrum of 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole of Example 2 of the present invention. DETAILED DESCRIPTION

[0030] In order to make the technical means, creative features, objectives and functions achieved by the present invention clearer and easier to understand, the present invention is further explained below in conjunction with the accompanying drawings and specific implementation methods.

[0031] Example 1: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention. The route of the preparation method is as follows:

[0032] ;

[0033] The preparation method comprises the following steps:

[0034] S1: in a solvent, acetic acid oxime reacts with N-chlorosuccinimide to obtain a reaction solution containing dichloroformaldehyde oxime;

[0035] S2 reacts dichloroformaldehyde oxime and isobutylene in the reaction solution obtained by S1 in water under the action of a catalyst and a base. After the reaction is completed, 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is obtained through post-treatment.

[0036] Example 2: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 1 in that it comprises the following steps:

[0037] S1: First, 1 mol of acetic acid oxime was dissolved in 890 mL of ethylene glycol dimethyl ether (solvent), and heated to 70°C. Then, a total of 2.00 mol of N-chlorosuccinimide was added in several portions within 1 hour, and then the reaction was kept warm for 1.0 hour. According to gas phase detection, acetic acid oxime was completely converted into dichloroformaldehyde oxime, and a reaction solution containing dichloroformaldehyde oxime was obtained.

[0038] S2 first cools the reaction solution obtained in S1 to 0°C, then adds 45g of water, 0.10mol of copper chloride (catalyst), and 4.00mol of potassium bicarbonate (base), stirs and mixes for 30min, then adds 2.00mol of isobutylene, and reacts at room temperature for 5.0h. After the reaction is completed, add 200mL of water to separate the layers, and extract the aqueous phase once with 500mL of petroleum ether. The organic phase obtained by separation is washed once with 200mL of saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled. Figure 1 The NMR was verified to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole as a colorless liquid with an overall yield of 65% (GC purity > 98%).

[0039] Example 3: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 1 in that it comprises the following steps:

[0040] S1: First, dissolve 1 mol of acetic acid oxime in 200 mL of ethylene glycol dimethyl ether (solvent) and heat to 50°C. Then, add a total of 1.50 mol of N-chlorosuccinimide in several times within 1 hour. Then, keep the temperature and react for 0.5 hour. According to gas phase detection, acetic acid oxime is completely converted into dichloroformaldehyde oxime to obtain a reaction solution containing dichloroformaldehyde oxime.

[0041] S2 first cools the reaction solution obtained in S1 to -10°C, then adds 40g of water, 0.01mol of copper chloride (catalyst), and 0.40mol of potassium bicarbonate (base), stirs and mixes for 20min, then adds 1.50mol of isobutylene, and reacts at room temperature for 4.0h. After the reaction is completed, 200mL of water is added to separate the layers, and the aqueous phase is extracted once with 500mL of petroleum ether. The organic phase obtained by separation is washed once with 200mL of saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, a colorless liquid with a total yield of 48% (GC purity>98%).

[0042] Example 4: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 1 in that it comprises the following steps:

[0043] S1: First, dissolve 1 mol of acetic acid oxime in 500 mL of ethylene glycol dimethyl ether (solvent) and heat to 60°C. Then, add a total of 1.75 mol of N-chlorosuccinimide in several times within 1 hour. Then, keep the temperature and react for 0.8 hours. According to gas phase detection, acetic acid oxime is completely converted into dichloroformaldehyde oxime to obtain a reaction solution containing dichloroformaldehyde oxime.

[0044] S2 first cools the reaction solution obtained in S1 to -5°C, then adds 50g of water, 0.05mol of copper chloride (catalyst), and 2.00mol of potassium bicarbonate (base), stirs and mixes for 25min, then adds 1.75mol of isobutylene, and reacts at room temperature for 4.5h. After the reaction is completed, 200mL of water is added to separate the layers, and the aqueous phase is extracted once with 500mL of petroleum ether. The organic phase obtained by separation is washed once with 200mL of saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, a colorless liquid with a total yield of 57% (GC purity>98%).

[0045] Example 5: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 1 in that it comprises the following steps:

[0046] S1: First, dissolve 1 mol of acetic acid oxime in 1500 mL of ethylene glycol dimethyl ether (solvent), and heat to 80°C. Then, add 2.25 mol of N-chlorosuccinimide in several times within 1 hour, and then keep the temperature to react for 1.2 hours. According to gas phase detection, acetic acid oxime is completely converted into dichloroformaldehyde oxime, and a reaction solution containing dichloroformaldehyde oxime is obtained.

[0047] S2 first cools the reaction solution obtained in S1 to 5°C, then adds 55g of water, 0.20mol of copper chloride (catalyst), and 8.00mol of potassium bicarbonate (base), and stirs and mixes for 35min, then adds 2.25mol of isobutylene, and reacts at room temperature for 5.5h. After the reaction is completed, 200mL of water is added to separate the layers, and the aqueous phase is extracted once with 500mL of petroleum ether. The organic phase obtained by separation is washed once with 200mL of saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, a colorless liquid with a total yield of 61% (GC purity>98%).

[0048] Example 6: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 1 in that it comprises the following steps:

[0049] S1: First, dissolve 1 mol of acetic acid oxime in 2000 mL of ethylene glycol dimethyl ether (solvent), and heat to 100°C. Then, add a total of 2.50 mol of N-chlorosuccinimide in several portions within 1 hour, and then keep the temperature to react for 1.5 hours. According to gas phase detection, acetic acid oxime is completely converted into dichloroformaldehyde oxime, and a reaction solution containing dichloroformaldehyde oxime is obtained.

[0050] S2 first cools the reaction solution obtained in S1 to 10°C, then adds 60g of water, 0.40mol of copper chloride (catalyst), and 16.00mol of potassium bicarbonate (base), stirs and mixes for 40min, then adds 2.50mol of isobutylene, and reacts at room temperature for 6.0h. After the reaction is completed, 200mL of water is added to separate the layers, and the aqueous phase is extracted once with 500mL of petroleum ether. The organic phase obtained by separation is washed once with 200mL of saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, a colorless liquid with a total yield of 62% (GC purity>98%).

[0051] Examples 7 to 11 are methods for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention. The difference from Example 2 is that the solvents are toluene, chlorobenzene, ethyl acetate, tetrahydrofuran, and 2-methyltetrahydrofuran, respectively, and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is finally obtained as a colorless liquid with a total yield of 43 to 57% (GC purity > 98%).

[0052] Examples 12 to 17 are methods for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention. The difference from Example 2 is that the catalysts are copper sulfate, cuprous sulfate, cuprous chloride, zinc chloride, ferric chloride, and ferrous chloride, respectively, and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is finally obtained as a colorless liquid with a total yield of 55 to 61% (GC purity > 98%).

[0053] Examples 18 to 30: A method for preparing a sulfonepyraclostrobin intermediate disclosed in the present invention, which is different from Example 2 in that the bases are sodium carbonate, sodium bicarbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium bicarbonate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate, respectively, and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is finally obtained as a colorless liquid with a total yield of 56 to 63% (GC purity > 98%).

[0054] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for preparing a sulfonepyraclostrobin intermediate, characterized in that: The route of the preparation method is as follows, ； The preparation method comprises the following steps: S1: in a solvent, acetic acid oxime reacts with N-chlorosuccinimide to obtain a reaction solution containing dichloroformaldehyde oxime; S2: reacting the dichloroformaldehyde oxime and isobutylene in the reaction solution obtained in S1 in water under the action of a catalyst and a base, and after the reaction is completed, post-processing is performed to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole; In S2, the catalyst is one or a combination of copper sulfate, cuprous sulfate, cupric chloride, cuprous chloride, zinc chloride, ferric chloride, and ferrous chloride.

2. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In S1, the solvent is one or a combination of halogenated alkane solvents, ether solvents, alcohol solvents, ketone solvents, amide solvents, ester solvents, and nitrile solvents.

3. The method for preparing a sulfonepyraclostrobin intermediate according to claim 2, characterized in that: In S1, the solvent is one or a combination of toluene, chlorobenzene, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, and ethylene glycol dimethyl ether.

4. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In the S1, the usage ratio of the solvent, acetic acid oxime and N-chlorosuccinimide is 200-2000 mL: 1 mol: 1.50-2.50 mol.

5. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In S1, acetic acid oxime is first dissolved in a solvent and heated to 50-100° C., and then N-chlorosuccinimide is added in multiple portions within 1 hour, and then the reaction is kept warm for 0.5-1.5 hours to obtain a reaction solution containing dichloroformaldehyde oxime.

6. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In S2, the base is an inorganic base and an organic base or a combination of several thereof.

7. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In S2, the alkali is one or a combination of sodium carbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate.

8. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In the S2, the usage ratio of water, catalyst, base, dichloroformaldehyde oxime and isobutylene is 40-60 g: 0.01-0.40 mol: 0.40-16.00 mol: 1 mol: 1.50-2.50 mol.

9. The method for preparing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: In the S2, the reaction solution obtained in S1 is first cooled to -10~10°C, and then water, a catalyst, and a base are added, stirred and mixed for 20~40 minutes, and then isobutylene is added, and the reaction is carried out at room temperature for 4~6 hours. After the reaction is completed, water is added to separate the layers, and the aqueous phase is extracted with petroleum ether for multiple times. The organic phase obtained by separation is washed several times with a saturated sodium chloride aqueous solution, dried with sodium sulfate, concentrated, and distilled to obtain 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole.

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