A method for synthesizing picoxystrobin

Abstract

This invention relates to a method for synthesizing azoxystrobin, belonging to the field of organic synthesis technology. The method uses 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 2-hydroxy-6-trifluoromethylpyridine as raw materials, condensing them under alkaline conditions to obtain an etherified intermediate, which is then directly hydrolyzed and esterified with methanol under acidic conditions to obtain azoxystrobin. This method avoids the use of expensive 3-isochloroketone as a raw material, using inexpensive 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile prepared from o-methylphenylacetonitrile as the key fragment, further reducing the cost of azoxystrobin raw materials. Furthermore, the process route is simple, the yield is high, and it is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing pyridoxine. Background Technology

[0002] Azoxystrobin is a methoxyacrylate fungicide developed by Syngenta. It is a broad-spectrum, highly systemic, and efficient fungicide with low toxicity. It is widely used in crops such as soybeans, corn, wheat, rice, sunflowers, and rapeseed. It exhibits good control effects against various diseases in wheat crops, including powdery mildew, leaf blight, and brown spot, and has a promising market prospect. The chemical structure of azoxystrobin is as follows:

[0003] ;

[0004] Currently, domestic and international literature reports methods for synthesizing azoxystrobin, such as CN104250213 and US5663370, which use 3-isochromone as a starting material, followed by formylation, methylation, chlorination ring-opening, and finally etherification with 2-hydroxy-6-trifluoromethylpyridine. The synthetic route is as follows:

[0005] ;

[0006] The high cost of raw materials for this synthesis method, due to the high price of the raw material 3-isochromone, the long synthetic route, and the complex reaction process, results in a high cost of raw materials for the product.

[0007] Another synthetic method, as described in EP0854866, uses 3-isochromone as a starting material. Under alkaline conditions, it is first etherified with 2-chloro-6-trifluoromethylpyridine, followed by esterification, formylation, and methylation to obtain pyridoxine. The synthetic route is as follows:

[0008] .

[0009] This synthetic method is not suitable for large-scale production due to its long synthetic route, complex reaction process, and expensive raw materials.

[0010] Therefore, finding a clean, efficient, low-cost synthesis method for azoxystrobin suitable for industrial-scale production is a key focus of research in this field. Summary of the Invention

[0011] This invention provides a method for synthesizing pyraclostrobin, which solves the problems mentioned in the background art. The raw materials used in this synthesis method are inexpensive, the process is simple, the reaction conditions are mild, the yield is high, the atom economy is high, and it has high industrial application value.

[0012] The present invention provides the following solution to the above-mentioned technical problems: a method for synthesizing pyraclostrobin, characterized in that the synthesis method includes the following steps: Step 1, adding 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 2-hydroxy-6-trifluoromethylpyridine and a solvent, wherein the solvent is dichloroethane, and then adding an alkali, wherein the alkali is sodium hydroxide or potassium hydroxide, and maintaining the reaction temperature at 15-20°C for 6-7 hours;

[0013] Step 2: After the reaction is completed, the mixture is filtered and concentrated to obtain an etherified intermediate. Methanol and acid water (70-85% dilute sulfuric acid) are added to the etherified intermediate. After the addition is complete, the reaction is kept at a temperature of 50-60°C for 5-6 hours.

[0014] Step 3: After the reaction is complete, cool to 0-5℃ and filter to obtain azoxystrobin;

[0015] The synthesis process route is as follows:

[0016] .

[0017] Based on the above technical solution, the present invention can be further improved as follows.

[0018] Furthermore, the molar ratio of 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 2-hydroxy-6-trifluoromethylpyridine is 1:1.0-1.2;

[0019] The molar ratio of 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile to alkali is 1:1.0-1.2. This molar ratio range can ensure that the raw materials react fully, avoid waste caused by excessive feeding, maximize the conversion rate of etherification reaction, reduce the generation of by-products, and thus improve the yield and purity of the target product.

[0020] Furthermore, the solvent mentioned in Step 2 is a mixed solvent composed of one or more solvents such as dichloroethane, toluene, xylene, dichloromethane, dichloroethane, tetrahydrofuran, 2-methyltetrahydrofuran, methanol, ethanol, n-propanol, isopropanol, DMF, NMP, acetonitrile, acetone, and butanone. This solvent selection range broadens the adaptability of the process, allowing for flexible selection based on actual production conditions and costs. At the same time, the mixed solvent system can improve the solubility and mass transfer effect of the reactants, promote the further conversion of the etherification intermediate, and improve the reaction efficiency.

[0021] Furthermore, the acidic solution is hydrochloric acid or dilute phosphoric acid. Replacing part of the dilute sulfuric acid with hydrochloric acid or dilute phosphoric acid can avoid the corrosion of equipment by sulfate ions or interference with subsequent separation. At the same time, different acidic media can adjust the pH environment of the reaction system, so that the cyclization or hydrolysis steps can be carried out under milder conditions, reducing side reactions and improving the crystal purity of azoxystrobin.

[0022] The beneficial effects of this invention are: This invention provides a method for synthesizing pyraclostrobin, which has the following advantages:

[0023] 1. To address the technical problems of existing technologies using 3-isochloroketone as a raw material, such as high raw material prices, long synthetic routes, complex reaction processes, high production costs, and difficulty in large-scale production, a novel synthetic route is provided. This method uses 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 2-hydroxy-6-trifluoromethylpyridine as starting materials, and the target product, pyridoxine, can be obtained through two steps of etherification and acid-catalyzed cyclization. The process is simple, easy to operate, and the reaction conditions are mild, avoiding high temperature, high pressure, and harsh reaction conditions, which significantly reduces production energy consumption and equipment requirements.

[0024] 2. The raw materials used are inexpensive and readily available, with high atom economy, high overall yield, and good product purity, effectively overcoming the shortcomings of high costs in existing processes. Specifically, by optimizing the molar ratio of 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile to 2-hydroxy-6-trifluoromethylpyridine and base (1:1.0-1.2), it is possible to ensure sufficient reaction of raw materials, avoid waste caused by excessive feeding, maximize the conversion rate of etherification reaction, reduce the generation of by-products, and thus improve the yield and purity of the target product.

[0025] 3. The process is simple, with high yield and low waste, making it suitable for industrial production.

[0026] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Specific embodiments of the present invention are given in detail in the following examples. Detailed Implementation

[0027] The principles and features of the present invention are described below. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. The invention is described more specifically by way of example in the following paragraphs. The advantages and features of the invention will become clearer from the following description.

[0028] Example 1: Step 1, add 20.7g (0.1mol) 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 16.3g (0.1mol) 2-hydroxy-6-trifluoromethylpyridine and 100.0g of dichloroethane solvent to the reaction flask, add 4.4g of sodium hydroxide in portions, control the temperature at 15-20℃, and keep the reaction at this temperature for 6-7h after the addition is complete;

[0029] Step 2: After the reaction is complete, filter the mixture and concentrate the organic phase to obtain the etherified intermediate. Add 100.0g of methanol and 24.0g of 80% sulfuric acid directly. After the addition is complete, keep the mixture at 50-60℃ for 5-6 hours.

[0030] Step 3: After the reaction is complete, cool to 0-5℃, filter, and dry to obtain 33.2g of azoxystrobin, with a yield of 90.4%.

[0031] LC-MS (ESI+): 368 (M+H) + .

[0032] Example 2: Step 1, add 20.7g (0.1mol) 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 16.3g (0.1mol) 2-hydroxy-6-trifluoromethylpyridine and 100.0g of dichloroethane solvent to the reaction flask, add 4.4g of potassium hydroxide in portions, control the temperature at 15-20℃, and keep the reaction at this temperature for 6-7h after the addition is complete;

[0033] Step 2: After the reaction is complete, filter the mixture and concentrate the organic phase to obtain the etherified intermediate. Add 100.0g of methanol and 24.0g of 80% sulfuric acid directly. After the addition is complete, keep the mixture at 50-60℃ for 5-6 hours.

[0034] Step 3: After the reaction is complete, cool to 0-5℃, filter, and dry to obtain 32.2g of azoxystrobin, with a yield of 87.7%.

[0035] LC-MS (ESI+): 368 (M+H) + .

[0036] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Those skilled in the art can readily implement the present invention based on the above description. However, any modifications, alterations, or variations made by those skilled in the art without departing from the scope of the present invention, utilizing the disclosed technical content, are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, or variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A process for the synthesis of picoxystrobin, characterized in that, The synthesis method includes the following steps: Step 1, 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile and 2-hydroxy-6-trifluoromethylpyridine and a solvent, namely dichloroethane, are added to a reaction flask. Then, a base, namely sodium hydroxide or potassium hydroxide, is added in batches. After the addition is complete, the reaction is kept at a temperature of 15-20°C for 6-7 hours. Step 2: After the reaction is completed, the mixture is filtered and concentrated to obtain an etherified intermediate. Methanol and acid water (70-85% dilute sulfuric acid) are added to the etherified intermediate. After the addition is complete, the reaction is kept at a temperature of 50-60°C for 5-6 hours. Step 3: After the reaction is complete, cool to 0-5℃ and filter to obtain azoxystrobin; The synthesis process route is as follows; 。 2. The method of synthesizing picoxystrobin according to claim 1, wherein, The molar ratio of 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile to 2-hydroxy-6-trifluoromethylpyridine is 1:1.0-1.2; The molar ratio of 2-(2-(chloromethyl)phenyl)-3-methoxyacrylonitrile to the base is 1:1.0-1.

2.

3. The method of synthesizing picoxystrobin according to claim 1, wherein, The solvent mentioned in Step 2 is a mixed solvent composed of one or more solvents such as dichloroethane, toluene, xylene, dichloromethane, dichloroethane, tetrahydrofuran, 2-methyltetrahydrofuran, methanol, ethanol, n-propanol, isopropanol, DMF, NMP, acetonitrile, acetone, and butanone.

4. The method of synthesizing picoxystrobin according to claim 1, wherein, The acidic solution is hydrochloric acid or dilute phosphoric acid.

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