A process for the preparation of a chlorantraniliprole intermediate

Abstract

This invention discloses a method for preparing a chlorantraniliprole intermediate, comprising: using ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate as a raw material, and N-hydroxyphthalimide as a catalyst, under the action of the catalyst, ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate undergoes an oxidation reaction with an oxidant to obtain ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate. Compared with existing methods, the preparation method of this invention is mild and efficient, simple to operate, environmentally friendly, and has a high product yield.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis of pesticides and relates to a method for preparing an intermediate of chlorantraniliprole, specifically a method for preparing ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate, an intermediate of chlorantraniliprole. Background Technology

[0002] Chlorantraniliprole, with the structural formula shown in Formula A, is a novel, highly effective, and low-toxicity o-formamidobenzamide insecticide. Its chemical name is 3-bromo-N-[4-chloro-2-methyl-6-[(methylcarbamoyl)benzene]-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide. This insecticide is broad-spectrum, highly effective, and environmentally friendly, exhibiting good control effects against Lepidoptera, Coleoptera, Diptera, Hemiptera, and termites. It also demonstrates good safety and has broad application prospects.

[0003]

[0004] Ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate (Formula II) is a key intermediate in the preparation of chlorantraniliprole. Currently, the synthetic route for this key intermediate is as follows:

[0005]

[0006] Compound II is obtained by oxidizing a compound with the structure shown in Formula I (chemical name: ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate) under the action of potassium persulfate and concentrated sulfuric acid. This reaction requires a large amount of potassium persulfate and other sulfates, as well as highly corrosive concentrated sulfuric acid. The reaction generates a large amount of high-salt, high-COD wastewater, which is difficult to treat, and the operation is complex and costly.

[0007] There is an urgent need for a method to prepare chlorantraniliprole intermediates that is mild, efficient, simple to operate, environmentally friendly, and yields high product yield. Summary of the Invention

[0008] The purpose of this invention is to provide a method for preparing ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate (compound II) as an intermediate of chlorantraniliprole. This preparation method is mild and efficient, simple to operate, environmentally friendly, and yields a high product.

[0009] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0010] A method for preparing a chlorantraniliprole intermediate, the synthetic route is as follows:

[0011]

[0012] The process includes: using ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (compound I) as a raw material and N-hydroxyphthalimide (NHPI) as a catalyst, ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate undergoes an oxidation reaction with an oxidant to obtain ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate under the action of the catalyst.

[0013] The reaction solvent is a nitrile compound such as acetonitrile or benzonitrile, preferably acetonitrile.

[0014] The mass ratio of the reaction solvent to ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 1:1 to 10:1, preferably 3:1 to 5:1.

[0015] The inventors made a surprising discovery during their research: NHPI can efficiently catalyze the oxidation of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate to ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate. Generally, a mass ratio of N-hydroxyphthalimide to ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate of 0.0001:1 to 0.1:1, preferably 0.002:1 to 0.02:1, yields satisfactory reaction results. Especially at the preferred dosage, the reaction rate is fast, and the raw materials are almost completely converted to chlorantraniliprole intermediate II. Insufficient NHPI catalyst will lead to a decrease in reaction rate and incomplete conversion of raw materials. While an NHPI dosage exceeding 0.02:1 (i.e., 2%) has little impact on reaction rate and raw material conversion, excessive NHPI use will result in material waste. Therefore, the preferred mass ratio of N-hydroxyphthalimide to ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 0.002:1 to 0.02:1.

[0016] The oxidation reaction is carried out at a temperature of 0–60°C, preferably 20–40°C.

[0017] The oxidant is air or oxygen. Under normal or positive pressure conditions, the oxidant is continuously introduced into the reaction system to react with ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate for oxidation.

[0018] When the oxidant is air, the oxidation reaction is carried out at atmospheric pressure.

[0019] When the oxidant is oxygen, the oxidation reaction pressure is 0.2–10 MPa. Studies have found that when the reaction pressure exceeds 0.5 MPa, the increase in pressure has little effect on the reaction result; at the same time, excessively high reaction pressure increases safety risks and places high demands on equipment. Therefore, the preferred oxidation reaction pressure is 0.2–0.5 MPa.

[0020] The oxidation reaction takes 2 to 14 hours. When the oxidation reaction takes more than 10 hours, the yield increase is not significant; therefore, the preferred oxidation reaction time is 2 to 10 hours.

[0021] Specifically, a method for preparing a chlorantraniliprole intermediate includes: adding a reaction solvent to a reaction apparatus, adding ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and N-hydroxyphthalimide under stirring, introducing air, and carrying out an oxidation reaction at atmospheric pressure, or continuously introducing oxygen and maintaining the reaction pressure to carry out an oxidation reaction until the reaction pressure no longer decreases.

[0022] As a further preferred embodiment of the method for preparing the chlorantraniliprole intermediate described in this invention, the method further includes: removing part of the solvent from the reaction solution until a solid precipitates, then crystallizing at room temperature (20-25°C), filtering, and obtaining ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate, and reusing the filtrate.

[0023] Beneficial effects of the present invention

[0024] Compared with existing methods, this invention uses N-hydroxyphthalimide as a catalyst to catalyze the oxidation reaction of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate with an oxidant to obtain ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate. The reaction is mild and efficient, simple to operate, environmentally friendly, and has a high product yield (>97%). Detailed Implementation

[0025] The technical solution of the present invention is further described below with reference to specific implementation examples, but the present invention is not limited to the following embodiments.

[0026] The implementation conditions used in the examples can be further adjusted according to specific requirements. Implementation conditions not specified are usually those in routine experiments.

[0027] Example 1

[0028] 300g of acetonitrile was added to a round-bottom flask, followed by stirring. Then, 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (compound I) and 1g of N-hydroxyphthalimide (NHPI) were added. Air was introduced at 20°C, and the mixture was kept at atmospheric pressure for about 6 hours until the reaction was complete. The reaction was then stopped, and samples were taken for testing. The yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was 98.6%.

[0029] The reaction solution was partially solvent-removed until a solid precipitated, and then crystallized at room temperature. After filtration, ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was obtained. The filtrate (containing the catalyst) was reused.

[0030] Example 2

[0031] Add 300g of acetonitrile to a round-bottom flask, then add 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 1g of NHPI while stirring. Purge air at 40°C and maintain the temperature at atmospheric pressure for approximately 2 hours, at which point the reaction is complete. Stop the reaction, take a sample for analysis, and the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 98.2%.

[0032] Example 3

[0033] Add 300g of acetonitrile to a round-bottom flask, then add 60g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 1g of NHPI while stirring. Purge air at 30°C and maintain the temperature at atmospheric pressure for approximately 3 hours, at which point the reaction is complete. Stop the reaction, take a sample for analysis, and the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 98.9%.

[0034] Example 4

[0035] Add 300g of acetonitrile to a round-bottom flask, then add 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 0.2g of NHPI while stirring. Air is bubbled through the mixture at 20°C, and the mixture is kept at atmospheric pressure for approximately 14 hours, at which point the reaction is complete. Stop the reaction, take a sample for analysis, and the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 97.2%.

[0036] Example 5

[0037] Add 300g of acetonitrile to a round-bottom flask, then add 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 5g of NHPI while stirring. Purge air at 20°C and maintain the temperature at atmospheric pressure for approximately 5 hours, at which point the reaction is complete. Stop the reaction, take a sample for analysis, and the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate is 98.8%.

[0038] Example 6

[0039] 300g of acetonitrile was added to an autoclave, followed by stirring and the addition of 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 0.5g of NHPI. Oxygen was introduced at 30°C until the pressure inside the autoclave reached 0.5MPa. The reaction consumed oxygen as it proceeded. When the pressure dropped to 0.4MPa, oxygen was added to maintain the reaction pressure at 0.4–0.5MPa. The reaction was stopped when no further pressure drop was observed (approximately 5 hours). Sampling and analysis showed that the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was 98.6%.

[0040] Example 7

[0041] 300g of acetonitrile was added to an autoclave, followed by stirring and the addition of 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 0.5g of NHPI. Oxygen was introduced at 60°C until the pressure inside the autoclave reached 0.5MPa. When the pressure dropped to 0.4MPa, oxygen was added to maintain the reaction pressure at 0.4–0.5MPa. The reaction was continued at this temperature until the pressure no longer decreased (approximately 3 hours), at which point the reaction was stopped. Sampling and analysis showed that the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was 98.1%.

[0042] Example 8

[0043] 300 g of acetonitrile was added to an autoclave, followed by 60 g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate and 0.1 g of NHPI. Oxygen was introduced into the autoclave at 40 °C until the pressure reached 0.3 MPa. When the pressure dropped to 0.2 MPa, oxygen was added to maintain the reaction pressure at 0.2–0.3 MPa. The reaction was maintained at this temperature until the pressure no longer decreased (approximately 10 hours), at which point the reaction was stopped. Sampling and analysis showed that the yield of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was 97.8%.

[0044] Comparative Example 1

[0045] Add 300g of acetonitrile to a round-bottom flask, and then add 100g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate while stirring. Purge air at 20°C and maintain the temperature for approximately 6 hours, then stop the reaction. Sample testing revealed that ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate was not detected.

[0046] The present invention has been described in detail above, with the aim of enabling those skilled in the art to understand the content of the present invention and implement it. However, this description should not be construed as limiting the scope of protection of the present invention. Furthermore, the present invention is not limited to the above-described embodiments. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A process for the preparation of a chlorantraniliprole intermediate characterized by: The application relates to a preparation method of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid ethyl ester. The mass ratio of the N-hydroxyphthalimide and the 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester is 0.002:1-0.02:

1. The oxidant is air or oxygen, and the oxidation reaction is carried out under normal pressure or positive pressure. The reaction solvent is a nitrile compound, and the mass ratio of the reaction solvent and the 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester is 1:1-10:

1.

2. The process for the preparation of a chlorantraniliprole intermediate according to claim 1, characterized in that: The reaction solvent is acetonitrile or benzonitrile.

3. A process for the preparation of a chlorantraniliprole intermediate according to claim 1 or 2, characterized in that: The mass ratio of the reaction solvent and the 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester is 3:1-5:

1.

4. The process for the preparation of a chlorantraniliprole intermediate according to claim 2, characterized in that: The temperature of the oxidation reaction is 0-60 DEG C, and the time of the oxidation reaction is 2-14 hours.

5. The process for the preparation of a chlorantraniliprole intermediate according to claim 1, characterized in that: The temperature of the oxidation reaction is 20-40 DEG C, and the time of the oxidation reaction is 2-10 hours.

6. The process for the preparation of a chlorantraniliprole intermediate according to claim 5, characterized in that: When the oxidant is air, the pressure of the oxidation reaction is normal pressure.

7. The process for the preparation of a chlorantraniliprole intermediate according to claim 1, characterized in that: When the oxidant is oxygen, the pressure of the oxidation reaction is 0.2-10 MPa. When the oxidant is oxygen, the pressure of the oxidation reaction is 0.2-0.5 MPa.

8. The process for the preparation of a chlorantraniliprole intermediate according to claim 7, characterized in that: The application relates to a preparation method of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid ethyl ester.

9. The process for the preparation of a chlorantraniliprole intermediate according to claim 1, characterized in that: In a reaction device, a reaction solvent is added, and 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester and N-hydroxyphthalimide are added under stirring, air is inhaled, and the oxidation reaction is carried out under normal pressure or continuous oxygen inhalation and reaction pressure maintenance until the reaction pressure no longer decreases. ​

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