Novel synthesis process of pyridaben intermediate dichloropyridazinone

Abstract

The invention relates to a novel method for synthesizing dichloropyridazinone, which is characterized in that the pyridazinone is generated through the reaction of tert-butylhydrazine and furfuryl acid under the condition of a non-water-soluble organic solvent by changing the initial raw materials of the reaction, the reaction product acetic acid can be recycled, and the reaction solvent and the subsequent synthesis of pyridaben are the same solvent, so that the desolvation process and the crystallization process are omitted, and the yield is improved. The method avoids high-temperature decomposition of a heat-sensitive material intermediate dichloropyridazinone, greatly improves the production field environment, effectively improves the comprehensive yield of a finished product, and is more suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticide synthesis, and particularly relates to a new method for synthesizing dichloropyridazinone. Background Art

[0002] Dichloropyridazinone (chemical name: 2-tert-butyl-4,5-dichloro-3(2H)-pyridazinone, CAS: 84956-71-8, molecular formula: C 8 H 10 Cl 2 N 2 O), is the main intermediate for synthesizing the acaricide and insecticide pyridaben, and its chemical structural formula is as follows:

[0003]

[0004] Currently, the main synthesis process routes of dichloropyridazinone are as follows:

[0005] Route 1: React tert-butylhydrazine hydrochloride with liquid alkali to form tert-butylhydrazine, then react with furoic acid chloride to form tert-butyl hydrazone, add the solvent toluene (or pure benzene) and acetic acid, heat and keep warm for reaction, then wash and remove the solvent to obtain dichloropyridazinone, and crystallize and purify.

[0006] Route 2: React tert-butylhydrazine hydrochloride with sodium acetate to form an aqueous solution of tert-butylhydrazine, then react with furoic acid chloride to form tert-butyl hydrazone, add the solvent toluene (or pure benzene), heat and keep warm for reaction, then wash and remove the solvent to obtain dichloropyridazinone, and crystallize and purify.

[0007] Route 3: React tert-butylhydrazine hydrochloride with liquid alkali to form tert-butylhydrazine, first obtain an aqueous solution of tert-butylhydrazine by distillation; then dropwise add the aqueous solution of tert-butylhydrazine into the reaction kettle with the solvent toluene (or pure benzene) and furoic acid chloride to form tert-butyl hydrazone, add acetic acid, heat and keep warm for reaction, then wash and remove the solvent to obtain dichloropyridazinone, and crystallize and purify.

[0008] The solvents for the three routes are pure benzene or toluene. After synthesizing dichloropyridazinone, the solvent needs to be removed, then crystallized and further purified to obtain the intermediate dichloropyridazinone. Since dichloropyridazinone is a heat-sensitive material, a part of it decomposes and deteriorates during the high-temperature solvent removal process, and there will be a part of tarry substances after crystallization. The crystallized dichloropyridazinone needs to be washed and centrifuged for purification again. After purification, it contains water, and since the subsequent processes are water-sensitive, water needs to be removed. A part of dichloropyridazinone is also lost in these three processes. During the process, a large amount of odor, tar, and wastewater are generated. Since dichloropyridazinone is irritating and sensitizing, it causes great harm to the production environment and the working environment of workers. Route 2 uses anhydrous sodium acetate as a raw material, with a relatively high cost; in Route 3, the energy consumption is relatively large for first distilling out the tert-butylhydrazine solution. A large amount of wastewater and waste liquid are generated in the three original processes, with low yield, high energy consumption, high cost, and poor environment.

[0009] Therefore, it is necessary to develop a new method for synthesizing dichloropyridazinone. Summary of the Invention

[0010] The present invention provides a new method for synthesizing dichloropyridazinone. By changing the starting reaction materials and reaction solvents for the reaction of tert-butylhydrazine and furoyl chloride, the technical problems of thermal sensitivity decomposition and irritation of dichloropyridazinone are solved. While simplifying the process, the overall yield of the finished product is effectively improved.

[0011] The technical solutions adopted to achieve the above invention purposes are as follows:

[0012] A new method for synthesizing dichloropyridazinone, comprising the following steps:

[0013] (1) Neutralize an aqueous sodium hydroxide solution with acetic acid to obtain an aqueous sodium acetate solution;

[0014] (2) React tert-butylhydrazine hydrochloride with the aqueous sodium acetate solution obtained in step (1) to generate a tert-butylhydrazine solution. The reaction formula Ⅰ is as follows:

[0015]

[0016] (3) React furoyl chloride with the tert-butylhydrazine solution obtained in step (2) to generate a tert-butylhydrazone solution. The reaction formula Ⅱ is as follows:

[0017]

[0018] (4) Carry out a heat preservation reaction on the tert-butylhydrazone solution obtained in step (3) under the condition of a water-insoluble organic solvent, and separate the phases to obtain a pyridazinone organic phase. The reaction formula Ⅲ is as follows:

[0019]

[0020] (5) Wash the pyridazinone organic phase obtained in step (4) successively with alkali, acid, and water until it is neutral to obtain a dichloropyridazinone reaction material solution.

[0021] Among them, the concentration of the aqueous sodium hydroxide solution in step (1) is 3 - 50% (g / v).

[0022] Among them, the concentration of the acetic acid in step (1) is 5 - 99.9% (g / v).

[0023] Among them, the temperature of the reaction in step (2) is 0 - 38 °C.

[0024] Among them, the water-insoluble organic solvent in step (4) is selected from at least one of dichloromethane, dichloroethane, chloroform, solvent oil, ether, diphenyl ether, petroleum ether, isopropyl ether, cyclohexane, hexane, n-butane, acetonitrile, methyl acetate, ethyl acetate, and pyridine.

[0025] Among them, the water-insoluble organic solvent described in step (4) is preferably at least one of methylene chloride, dichloroethane, solvent oil, and petroleum ether.

[0026] Among them, the temperature of the heat preservation reaction described in step (4) is 30-50 °C.

[0027] Among them, the aqueous solution separated in the heat preservation reaction in step (4) is used as the acetic acid raw material for the neutralization reaction described in step (1).

[0028] Among them, the base used for alkali washing in step (5) is an aqueous sodium hydroxide solution with a concentration of 3-32% (g / v), and the acid used for acid washing is an aqueous sulfuric acid solution with a concentration of 3-30% (g / v).

[0029] Among them, the reaction material liquid of pyridazinone in step (5) is directly used as the reaction raw material for synthesizing the original drug of pyridaben. The synthesis reaction formula Ⅳ of pyridaben is as follows:

[0030]

[0031] The technical solution of the present invention has at least the following beneficial technical effects:

[0032] 1. Compared with the prior art, in the present invention, acetic acid reacts with liquid alkali to generate sodium acetate solution. The acetic acid can use the recycled acetic acid aqueous solution with a relatively large concentration range, which is beneficial to the comprehensive utilization of chemical enterprises. The acetic acid in the synthesis of pyridazinone does not participate in the reaction, but only provides an acidic environment. The acetic acid content in the separated aqueous solution after the reaction is relatively high, which can be recycled as an acetic acid solution, reducing wastewater discharge and utilizing the remaining acetic acid. It saves costs and reduces emissions compared with using anhydrous sodium acetate;

[0033] 2. The present invention replaces the reaction solvent, and the used solvent can be the same as the solvent for the synthesis of pyridaben in the subsequent process, reducing the solvent removal process, crystallization process, purification process, and water removal process. It avoids the high-temperature decomposition of the heat-sensitive material intermediate dichloropyridazinone and improves the conversion rate of pyridazinone synthesis;

[0034] 3. By changing the starting reaction raw materials and reaction solvents for the reaction of tert-butylhydrazine and furoic acid, the present invention reduces the solvent removal process, crystallization process, purification process, and water removal process, saving energy consumption and labor costs, and reducing the waste liquid and wastewater emissions produced in the above processes. In addition, due to the irritation and sensitization of pyridazinone, the production site environment and the working environment of workers are greatly improved, making it more suitable for industrial production, effectively improving the overall yield of the pyridaben finished product, with the product purity greater than 98.5% and the yield above 94%. Specific embodiments

[0035] The present invention will be further described below in conjunction with specific embodiments. It should be understood that the following embodiments are only used to illustrate the present invention and not to limit the scope of the present invention.

[0036] In the embodiments of the present invention, the content determination of pyridazinone adopts Q / 320700LB 105-2017:

[0037] In the embodiments of the present invention, the content determination is carried out by gas chromatography detection method. Chromatographic conditions: The sample is dissolved in acetone, dimethyl phthalate is used as the internal standard, and a stainless steel column filled with chromosorb W-HP (150-180) μm with 5% OV-225 as the stationary liquid and a hydrogen flame ionization detector are used for gas chromatographic separation and determination of pyridazinone in the sample.

[0038] Example 1 Synthesis of pyridazinone

[0039] Add 120 g (content 30%, 0.6 mol) of recycled acetic acid to a four-necked flask, slowly dropwise add 80 g (content 30%, 0.6 mol) of sodium hydroxide aqueous solution. After the addition is completed, keep warm for 10 minutes, cool down to 10 °C, slowly add 78 g (content 95%, 0.59 mol) of tert-butylhydrazine hydrochloride, keep warm for 10 minutes, slowly add 88 g (content 98%, 0.51 mol) of furoyl chloride, keep warm for 30 minutes, maintain the temperature at 10 °C, add 465 g (4.7 mol) of dichloroethane, slowly heat up to 48 °C, keep warm for 240 minutes, then let it stand for stratification. Wash the lower layer of the liquid with 13 g (content 10-30%) of sodium hydroxide aqueous solution, then wash it with 10 g (content 5-10%) of sulfuric acid aqueous solution, and then wash it with 20 g of water to obtain 568 g of pyridazinone dichloroethane solution with a content of 18.1% and a yield of 91.2%

[0040] Example 2 Synthesis of pyridaben

[0041] Add 568 g (content 18.1% in Example 1, 0.465 mol) of dichloropyridazinone dichloroethane solution to a four-necked flask, slowly add 90 g (content 96%, 0.48 mol) of p-tert-butylbenzyl mercaptan, cool down to 10 °C, and slowly and uniformly add 67 g (content 30%, 0.5 mol) of sodium hydroxide aqueous solution. Keep warm for 30 minutes. Wash the lower layer of the liquid with 13 g (content 10-30%) of sodium hydroxide aqueous solution, then wash it with 100 g (content 5-10%) of sulfuric acid aqueous solution, and then wash it with 100 g of water until the pH = 7. Evaporate 400 g of dichloroethane solvent, cool down to 0 °C for crystallization, and then filter by suction to obtain wet pyridaben powder. After drying, 159 g of pyridaben is obtained with a content of 98.8% and a yield of 94.8%; the total yield based on furoyl chloride is 84.4%

[0042] Example 3 Synthesis of pyridazinone

[0043] Add 360 g (content 10%, 0.6 mol) of recycled acetic acid into a four-necked flask, slowly dropwise add 80 g (content 30%, 0.6 mol) of aqueous sodium hydroxide solution. After the addition is completed, keep warm for 10 minutes, cool down to 10 °C, slowly add 78 g (content 95%, 0.59 mol) of tert-butylhydrazine hydrochloride, keep warm for 10 minutes, slowly add 88 g (content 98%, 0.51 mol) of furoyl chloride, keep warm for 30 minutes, maintain the temperature at 10 °C, add 465 g (5.5 mol) of petroleum ether, slowly heat up to 48 °C, keep warm for 240 minutes, then let it stand for stratification. Wash the upper layer of the liquid with 13 g (content 10 - 30%) of aqueous sodium hydroxide solution, then wash with 10 g (content 5 - 10%) of aqueous sulfuric acid solution, and then wash with 20 g of water to obtain 570 g of pyridazinone petroleum ether solution with a content of 18.4% and a yield of 93.0%

[0044] Synthesis of pyridaben in Example 4

[0045] Add 570 g (content 18.4% in Example 2, 0.47 mol) of dichloropyridazinone petroleum ether solution into a four-necked flask, slowly add 92 g (content 96%, 0.49 mol) of p-tert-butylbenzyl mercaptan, cool down to 10 °C, uniformly and slowly add 68 g (content 30%, 0.51 mol) of aqueous sodium hydroxide solution, keep warm for 30 minutes. Wash the upper layer of the liquid with 13 g (content 10 - 30%) of aqueous sodium hydroxide solution, then wash with 100 g (content 5 - 10%) of aqueous sulfuric acid solution, and then wash with 100 g of water until the pH = 7. Remove 400 g of petroleum ether solvent, cool down to 0 °C for crystallization, then filter by suction to obtain wet pyridaben powder. After drying, 167 g of pyridaben is obtained with a content of 99.1% and a yield of 95.6%; the total yield based on furoyl chloride is 88.9%

[0046] Synthesis of pyridazinone in Example 5

[0047] Add 360 g (content 10%, 0.6 mol) of recycled acetic acid into a four-necked flask, slowly dropwise add 80 g (content 30%, 0.6 mol) of aqueous sodium hydroxide solution. After the addition is completed, keep warm for 10 minutes, cool down to 10 °C, slowly add 78 g (content 95%, 0.59 mol) of tert-butylhydrazine hydrochloride, keep warm for 10 minutes, slowly add 88 g (content 98%, 0.51 mol) of furoyl chloride, keep warm for 30 minutes, maintain the temperature at 10 °C, add 465 g (5.5 mol) of petroleum ether, slowly heat up to 48 °C, keep warm for 240 minutes, then let it stand for stratification. Wash the upper layer of the liquid with 13 g (content 10 - 30%) of aqueous sodium hydroxide solution, then wash with 10 g (content 5 - 10%) of aqueous sulfuric acid solution, and then wash with 20 g of water to obtain 572 g of pyridazinone petroleum ether solution with a content of 18.6% and a yield of 94.3%

[0048] Synthesis of Pyridaben in Example 6

[0049] Add the petroleum ether solution of 572 g (content 18.6% in Example 2, 0.48 mol) of dichloropyridazinone into a four-necked flask, slowly add 94 g (content 96%, 0.50 mol) of p-tert-butylbenzyl mercaptan, cool down to 10 °C, and slowly and uniformly add 92 g (content 30%, 0.26 mol) of aqueous sodium carbonate solution. Keep warm for 30 minutes, wash the upper layer of the liquid with 13 g (content 10 - 30%) of aqueous sodium hydroxide solution, then wash with 100 g (content 5 - 10%) of aqueous sulfuric acid solution, add 100 g of water to wash until pH = 7, remove 400 g of petroleum ether solvent, cool down to 0 °C for crystallization, and then filter by suction to obtain wet pyridaben powder. After drying, 169 g of pyridaben is obtained, with a content of 98.9% and a yield of 95.3%; the total yield based on trichloromaleic acid: 89.8%

[0050] Comparative Example 1

[0051] Synthesis of Pyridazinone

[0052] Put 240 g of water and 78 g (content 95%, 0.59 mol) of tert-butylhydrazine hydrochloride into a four-necked flask, control at 10 °C, slowly add 80 g (content 30%, 0.6 mol) of aqueous sodium hydroxide solution. After the dropping is completed, keep warm for 10 minutes. Keep warm for 10 minutes, slowly add 88 g (content 98%, 0.51 mol) of trichloromaleic acid, keep warm for 30 minutes, maintain the temperature at 10 °C, add 36 g (content 98%, 0.59 mol) of acetic acid and 465 g (4.7 mol) of toluene, slowly heat up to 48 °C, keep warm for 240 minutes, then let it stand for stratification. Wash the upper layer of the liquid with 13 g (content 10 - 30%) of aqueous sodium hydroxide solution, then wash with 10 g (content 5 - 10%) of aqueous sulfuric acid solution, add 20 g of water to wash, heat up to remove the solvent toluene completely, and discharge the material into a bucket for crystallization to obtain 106 g of crude pyridazinone, with a content of 90.9% and a yield of 85.7%. Add the crystallized crude pyridazinone into a four-necked flask, then add 300 g (content 10%, 0.75 mol) of aqueous sodium hydroxide solution and stir for washing, then filter and wash with clear water and dry to obtain 91 g of crude and refined pyridazinone, with a content of 99.3% and a yield of 80.2%

[0053] Synthesis of Pyridaben

[0054] Put 560 g (content 99%, 17.33 mol) of methanol into a four-necked flask, slowly add 91 g (content 99.3%, 0.41 mol) of dichloropyridazinone, then add 79 g (content 96%, 0.42 mol) of p-tert-butylbenzyl mercaptan, control the temperature at 0 - 25°C, dropwise add 87 g (content 28%, 0.45 mol) of sodium methoxide methanol solution. After the addition is completed, keep warm for 30 minutes, cool down to 0°C for crystallization, then filter by suction to obtain the wet powder of pyridaben. Add 100 g of hot water and rinse 3 times, dry to obtain 141.6 g of pyridaben, with a content of 95.7% and a yield of 90.8%.

[0055] Total yield calculated based on trichloromaleic acid: 72.8%

[0056] Comparative Example 2

[0057] Synthesis of pyridazinone

[0058] Put 240 g of water and 78 g (content 95%, 0.59 mol) of tert-butylhydrazine hydrochloride into a four-necked flask, control the temperature at 10°C, slowly add 50 g (content 98%, 0.60 mol) of anhydrous sodium acetate. After the addition is completed, keep warm for 10 minutes, slowly add 88 g (content 98%, 0.51 mol) of trichloromaleic acid, keep warm for 30 minutes, maintain the temperature at 10°C, add 465 g (4.7 mol) of toluene, slowly heat up to 48°C, keep warm for 240 minutes, then let it stand for layer separation. Add the upper layer of the liquid to 13 g (content 10 - 30%) of sodium hydroxide aqueous solution for washing, then wash with 10 g (content 5 - 10%) of sulfuric acid aqueous solution, then add 20 g of water for washing, heat up to remove the solvent toluene completely, discharge the material into a bucket for crystallization to obtain 108 g of crude pyridazinone, with a content of 91.1% and a yield of 87.1%. Put the crystallized crude pyridazinone into a four-necked flask, then add 300 g (content 10%, 0.75 mol) of sodium hydroxide aqueous solution for stirring and washing, then filter and rinse with clear water and dry to obtain 94 g of crude and refined pyridazinone, with a content of 99.5% and a yield of 82.8%.

[0059] Synthesis of pyridaben

[0060] Put 560 g (content 99%, 17.33 mol) of methanol into a four-necked flask, slowly add 94 g (content 99.5%, 0.42 mol) of dichloropyridazinone, then add 82 g (content 96%, 0.44 mol) of p-tert-butylbenzyl mercaptan, control the temperature at 0 - 25°C, dropwise add 89 g (content 28%, 0.46 mol) of sodium methoxide methanol solution. After the addition is completed, keep warm for 30 minutes, cool down to 0°C for crystallization, then filter by suction to obtain the wet powder of pyridaben. Add 100 g of hot water and rinse 3 times, dry to obtain 147 g of pyridaben, with a content of 95.9% and a yield of 91.3%.

[0061] Total yield calculated based on trichloromaleic acid: 75.7%.

Claims

1. A new method for synthesizing dichloropyridazinone, comprising the following steps: (1) Neutralize an aqueous sodium hydroxide solution with acetic acid to obtain an aqueous sodium acetate solution; (2) React tert-butylhydrazine hydrochloride with the aqueous sodium acetate solution obtained in step (1) to generate a tert-butylhydrazine solution; (3) React furoyl chloride with the tert-butylhydrazine solution obtained in step (2) to generate a tert-butylhydrazone solution; (4) Heat and keep the temperature of the tert-butylhydrazone solution obtained in step (3) under the condition of a water-insoluble organic solvent, and separate the phases to obtain an organic phase of pyridazinone; (5) Wash the organic phase of pyridazinone obtained in step (4) successively with alkali, acid, and water until it is neutral to obtain a reaction material solution of dichloropyridazinone.

2. According to the method described in claim 1, wherein the concentration of the aqueous sodium hydroxide solution in step (1) is 3-50%.

3. According to the method described in claim 1, wherein the concentration of the acetic acid in step (1) is 5-99.9%.

4. According to the method described in claim 1, wherein the temperature of the reaction in step (2) is 0-38 °C.

5. According to the method described in claim 1, wherein the water-insoluble organic solvent in step (4) is selected from at least one of dichloromethane, dichloroethane, chloroform, solvent oil, ether, diphenyl ether, petroleum ether, isopropyl ether, cyclohexane, hexane, n-butane, acetonitrile, methyl acetate, ethyl acetate, and pyridine.

6. According to the method described in claim 5, wherein the water-insoluble organic solvent is selected from at least one of dichloromethane, dichloroethane, solvent oil, and petroleum ether.

7. According to the method described in claim 1, wherein the temperature of the heat preservation reaction in step (4) is 30-50 °C.

8. According to the method described in claim 1, wherein the aqueous solution separated in the heat preservation reaction in step (4) is used as the acetic acid raw material for the neutralization reaction described in step (1).

9. According to the method described in claim 1, wherein the alkali used for alkali washing in step (5) is an aqueous sodium hydroxide solution with a concentration of 3-32%, and the acid used for acid washing is an aqueous sulfuric acid solution with a concentration of 3-30%.

10. According to the method described in claim 1, wherein the reaction material solution of dichloropyridazinone in step (5) is directly used as the reaction raw material for synthesizing pyridaben technical material.

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