Synthesis process of 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidine ethyl formate

Abstract

The invention relates to a method for preparing 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidine ethyl formate, which comprises the following steps: firstly adding 3-chloro-2-hydrazinopyridine under a nitrogen reaction condition, then simultaneously adding a sodium ethoxide alcoholic solution and diethyl maleate to carry out cyclization reaction, and finally adding water to cool, acidify and crystallize to obtain a finished product. The synthesis process of the 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidine ethyl formate is optimized, the yield and content of finished products in the process are high, and the process is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and particularly relates to a synthesis process of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate. Background Art

[0002] Chlorantraniliprole is a nicotinic acid receptor activator. Its chemical name is: 3-bromo-N-{4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl}-1-(3-chloro-2-pyridinyl)-1H-pyridine-5-carboxamide. Its CAS registration number is: 500008-45-7. It is a new type of highly effective and low-toxic o-formylaminobenzamide insecticide developed by DuPont in the United States in 2000. It has excellent preventive effects on lepidopteran pests in crops such as rice, and is safe for mammals and environmentally friendly. 2-(3-chloropyridin-2-yl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester is the most important intermediate in the synthesis of chlorantraniliprole. Its chemical name is 2-(3-chloropyridin-2-yl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester. Its CAS registration number is: 500011-88-1. Its chemical structure is as follows:

[0003]

[0004] At present, the commonly used synthesis process route of 2-(3-chloropyridin-2-yl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester is to put 3-chloro-2-hydrazine pyridine, ethanol and sodium ethoxide into a reaction kettle, add diethyl maleate dropwise at a high temperature, reflux and keep warm after the dropwise addition, evaporate the ethanol under reduced pressure after the reaction is completed, add water to acidify, cool and crystallize, and centrifuge and dry to obtain the product. There are three main by-products in the synthesis process: diethyl 2-ethoxysuccinate, 3-chloro-2-aminopyridine, (E)-4-(2-(3-chloropyridin-2-yl)hydrazine)-4-oxo-2-butenoate, and it is found that the unreacted raw material 3-chloro-2-hydrazine pyridine forms acetate with acetic acid during the post-treatment process, and the formation of by-products has a significant impact on the appearance, quality and yield of 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester. The finished product of the current process is reddish brown in color, has a low yield and low content. Summary of the invention

[0005] The invention provides a synthesis process of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate. By changing the feeding sequence of 3-chloro-2-hydrazinopyridine and diethyl maleate for cyclization reaction and combining with an acidification post-treatment process, the reaction yield and content are higher, and industrial production is easily realized.

[0006] The technical solution adopted to achieve the above invention object is:

[0007] A method for preparing ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate comprises the following steps:

[0008] 1) dissolving 3-chloro-2-hydrazinopyridine in ethanol to obtain a 3-chloro-2-hydrazinopyridine alcohol solution;

[0009] 2) adding sodium ethanol alcohol solution and diethyl maleate to the 3-chloro-2-hydrazinopyridinol solution of step 1) to carry out a cyclization reaction to obtain a crude product of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate;

[0010] 3) Add water to the crude product of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate described in step 2), cool it, acidify it and crystallize it to obtain the finished product.

[0011] The above cyclization reaction is as follows:

[0012]

[0013] Wherein, the order of adding materials for the cyclization reaction in step 2) is: first add 3-chloro-2-hydrazinopyridine, and then add sodium ethanol alcohol solution and diethyl maleate at the same time.

[0014] Wherein, the cyclization reaction in step 2) is carried out under nitrogen conditions.

[0015] Wherein, the mass concentration of the sodium ethanol solution in step 2) is 20% to 30%.

[0016] Wherein, the dropping temperature in step 2) is 45°C to 50°C.

[0017] Wherein, the dropping time in step 2) is 0.5 hour to 1 hour.

[0018] Wherein, the cyclization reaction temperature in step 2) is 45°C to 65°C.

[0019] Wherein, the acidification in step 3) is carried out by directly adding water and cooling the temperature without removing ethanol.

[0020] Wherein, the acid in step 3) is glacial acetic acid.

[0021] Wherein, the acidification in step 3) has a pH value of 6-8.

[0022] Wherein, the temperature of step 3) is lowered to 20°C to 25°C.

[0023] The technical solution of the present invention has at least the following beneficial technical effects:

[0024] 1. Compared with the prior art, the present invention replaces the original solid sodium ethoxide with a sodium ethoxide ethanol solution. The original solid sodium ethoxide was directly put into the kettle, and then diethyl maleate was added dropwise. Now, sodium ethoxide and diethyl maleate are added dropwise at the same time, and the drops are finished at the same time. The original reaction was qualified and ethanol was removed. Now, water is directly added to cool down and acidification is performed without removing ethanol, which improves the appearance of the finished product and effectively increases the content and yield;

[0025] 2. The synthesis process of the present invention simplifies the production process, and the yield of the target product can reach more than 90%, and the content is higher than 95%. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific examples. It should be understood that the following examples are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0027] In the embodiments of the present invention, the content of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate is determined by high performance liquid chromatography detection method, the chromatographic conditions are: octadecylsilane bonded silica gel is used as filler, acetonitrile: water = (25:75) is used as mobile phase, the detection wavelength is 251.2nm, and the content is determined in accordance with the "High Performance Liquid Chromatography" and calculated by external standard method.

[0028] Example 1

[0029] Under nitrogen protection, 260 kg of ethanol and 270 kg of 3-chloro-2-hydrazinopyridine were added into the reactor, and the temperature was raised to 45 degrees. At 45-50 degrees, 720 kg of liquid sodium ethoxide and 400 kg of diethyl maleate were added dropwise at the same time. The dripping was completed in 30 minutes. After the dripping was completed, the temperature was kept at 58 degrees for 30 minutes. The central control conversion rate was ≥98%, which was qualified. 1500 kg of water was added to the material, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH = 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 456 kg of product.

[0030] The mother liquor is sent to the still for atmospheric distillation (no liquid is produced as the end point), the crude ethanol is sent to the distillation tower for distillation, the ethanol is collected, and the waste water is treated.

[0031] The product content was determined to be 95.1%, the yield was 90%, and the product appearance was light yellow crystals.

[0032] Example 2

[0033] Under nitrogen protection, 260 kg of ethanol and 270 kg of 3-chloro-2-hydrazinopyridine were added into the reactor, and the temperature was raised to 45 degrees. At 45-50 degrees, 720 kg of liquid sodium ethoxide and 400 kg of diethyl maleate were added dropwise for 30 minutes. After the addition, the temperature was kept at 58 degrees for 30 minutes. The conversion rate was ≥98%, which was qualified. 1500 kg of water was added to the material, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH value of 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 457 kg of product.

[0034] The mother liquor is sent to the still for atmospheric distillation (no liquid is produced as the end point), the crude ethanol is sent to the distillation tower for distillation, the ethanol is collected, and the waste water is treated.

[0035] The product content was determined to be 95.3%, the yield was 90.5%, and the product appearance was light yellow crystals.

[0036] Example 3

[0037] Under nitrogen protection, 260 kg of ethanol and 270 kg of 3-chloro-2-hydrazinopyridine were added into the reactor, and the temperature was raised to 45 degrees. At 45-50 degrees, 720 kg of liquid sodium ethoxide and 400 kg of diethyl maleate were added dropwise at the same time. The dripping was completed in 30 minutes. After the dripping was completed, the temperature was kept at 58 degrees for 30 minutes. The central control conversion rate was ≥98%, which was qualified. 1500 kg of water was added to the material, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH = 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 458 kg of product.

[0038] The mother liquor is sent to the still for atmospheric distillation (no liquid is produced as the end point), the crude ethanol is sent to the distillation tower for distillation, the ethanol is collected, and the waste water is treated.

[0039] The product content was determined to be 95.2%, the yield was 90.5%, and the product appearance was light yellow crystals.

[0040] Comparative Example 1

[0041] Under nitrogen protection, 600 kg of ethanol and 144 kg of solid sodium ethoxide were added into the reactor. After stirring and dissolving, 270 kg of 3-chloro-2-hydrazinopyridine was added, and diethyl maleate was added dropwise at 20-25 degrees. After the addition was completed, the temperature was raised to 83 degrees and refluxed for 2 hours. The conversion rate was controlled to be ≥98%, which was qualified. The material was transferred to the crystallization kettle. After the ethanol was removed at normal pressure, 1500 kg of water was added, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH value of 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 376.7 kg of product.

[0042] Centrifuge the wastewater for treatment.

[0043] The product content was determined to be 90.0%, the yield was 70.0%, and the product appearance was a reddish brown solid.

[0044] Comparative Example 2

[0045] Under nitrogen protection, 600 kg of ethanol and 144 kg of solid sodium ethoxide were added into the reactor. After stirring and dissolving, 270 kg of 3-chloro-2-hydrazinopyridine was added, and diethyl maleate was added dropwise at 20-25 degrees. After the addition was completed, the temperature was raised to 83 degrees and refluxed for 2 hours. The conversion rate was controlled to be ≥98%, which was qualified. The material was transferred to the crystallization kettle. After the ethanol was removed at normal pressure, 1500 kg of water was added, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH value of 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 377.1 kg of product.

[0046] Centrifuge the wastewater for treatment.

[0047] The product content was determined to be 90.1%, the yield was 70.5%, and the product appearance was a reddish brown solid.

[0048] Comparative Example 3

[0049] Under nitrogen protection, 600 kg of ethanol and 144 kg of solid sodium ethoxide were added into the reactor. After stirring and dissolving, 270 kg of 3-chloro-2-hydrazinopyridine was added. Diethyl maleate was added dropwise at 20-25 degrees. After the addition was completed, the temperature was raised to 83 degrees and refluxed for 2 hours. The conversion rate was controlled to be ≥98%, which was qualified. The material was transferred to the crystallization kettle. After the ethanol was removed at normal pressure, 1500 kg of water was added, the temperature was lowered by 20-25 degrees, 150 kg of glacial acetic acid was added dropwise to measure the pH value of 6-7, and the temperature was kept for half an hour. The temperature was lowered to below 10, the material was discharged, centrifuged, and dried (drying temperature 80 degrees) to obtain 376.8 kg of product.

[0050] Centrifuge the wastewater for treatment.

[0051] The product content was determined to be 90.4%, the yield was 70.3%, and the product appearance was a reddish brown solid.

[0052] Examples and comparative examples results

[0053] Table 1 Indices and yields of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate obtained in Examples 1, 2, 3 and Comparative Examples 1 to 3

[0054] Examples and Comparative Examples Appearance content(%) Yield (%) Example 1 Pale yellow crystal 95.1 90 Example 2 Pale yellow crystal 95.3 90.5 Example 3 Pale yellow crystal 95.2 90.5 Comparative Example 1 Reddish brown solid 90.0 70.0 Comparative Example 2 Reddish brown solid 90.1 70.5 Comparative Example 3 Reddish brown solid 90.4 70.3

[0055] As can be seen from Table 1, the present invention changes the order of adding 3-chloro-2-hydrazinopyridine and diethyl maleate for the cyclization reaction, and combines the post-treatment process of acidification without deethanolation, so that the appearance of the obtained 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester is light yellow crystals, which not only improves the appearance but also effectively increases the content and yield.

Claims

1. A method for preparing ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate, comprising the following steps: 1) dissolving 3-chloro-2-hydrazinopyridine in ethanol to obtain a 3-chloro-2-hydrazinopyridine alcohol solution; 2) adding sodium ethanol alcohol solution and diethyl maleate to the 3-chloro-2-hydrazinopyridinol solution of step 1) to carry out a cyclization reaction to obtain a crude product of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate; 3) Add water to the crude product of ethyl 2-(3-chloro-2-pyridyl)-5-oxo-3-pyrazolidinecarboxylate described in step 2), cool it, acidify it and crystallize it to obtain the finished product.

2. The method according to claim 1, characterized in that Step 2) The order of adding materials for the cyclization reaction is: first add 3-chloro-2-hydrazinopyridine, and then add sodium ethoxide solution and diethyl maleate at the same time.

3. The method according to claim 1, characterized in that Step 2) The cyclization reaction is carried out under nitrogen conditions.

4. The method according to claim 1, characterized in that Step 2) The mass concentration of the sodium ethanol solution is 20% to 30%.

5. The method according to claim 1, characterized in that Step 2) the dropping temperature is 45°C to 50°C.

6. The method according to claim 1, characterized in that The dropping time of step 2) is 0.5 hour to 1 hour.

7. The method according to claim 1, characterized in that Step 2) the cyclization reaction temperature is 45°C to 65°C.

8. The method according to claim 1, characterized in that Step 3) The acidification is carried out by directly adding water and cooling the temperature without removing the ethanol.

9. The method according to claim 1, characterized in that Step 3) The acid is glacial acetic acid, and the pH value is acidified to 6-8.

10. The method according to claim 1, characterized in that Step 3) the temperature is lowered to 20°C to 25°C.

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