阅读说明：本技术 一种氯虫苯甲酰胺的制备方法 (Preparation method of chlorantraniliprole ) 是由 蒋信义 刘汝章 徐军 张敏华 于 2019-09-05 设计创作，主要内容包括：本发明涉及一种杀虫剂的合成工艺技术领域,且公开了一种氯虫苯甲酰胺的制备方法,包括以下步骤：1)向单颈瓶中加入顺丁稀二酸酐4-8份和甲醇4-8份搅拌升温至50℃保温反应0.5-1.5h,制得马来酸单甲酯；2)将溴化氢-冰醋酸溶液80-120份降温至0℃后滴加马来酸单甲酯3-5份,加毕保温搅拌,3-7min后出现大量黄色黏稠物质,可制得3-溴马来酸单甲酯。该氯虫苯甲酰胺的制备方法,通过以顺丁烯二酸酐、2,3-二氯吡啶和2-氨基-3-甲基苯甲酸为起始原料经过汇聚式反应合成了目标物氯虫苯甲胺,通过HNMR确定了其结构,该路线反应条件温和,操作分离简便,原料易得,无需特殊设备,易于实现工业化生产,而且作用机理新颖独特,具有广阔的应用开发前景。(The invention relates to the technical field of synthetic processes of pesticides, and discloses a preparation method of chlorantraniliprole, which comprises the following steps: 1) adding 4-8 parts of maleic anhydride and 4-8 parts of methanol into a single-necked bottle, stirring, heating to 50 ℃, keeping the temperature, and reacting for 0.5-1.5h to obtain monomethyl maleate; 2) and (3) cooling 80-120 parts of hydrogen bromide-glacial acetic acid solution to 0 ℃, then dropwise adding 3-5 parts of monomethyl maleate, keeping the temperature and stirring, and obtaining a large amount of yellow sticky substances after 3-7min, thus obtaining the monomethyl 3-bromomaleate. According to the preparation method of chlorantraniliprole, maleic anhydride, 2, 3-dichloropyridine and 2-amino-3-methylbenzoic acid are used as initial raw materials to synthesize the target chlorantraniliprole through a convergent reaction, the structure of the chlorantraniliprole is determined through HNMR, the reaction condition of the route is mild, the operation and the separation are simple and convenient, the raw materials are easy to obtain, special equipment is not needed, the industrial production is easy to realize, the action mechanism is novel and unique, and the preparation method has a wide application and development prospect.)

1. The preparation method of chlorantraniliprole is characterized by comprising the following steps:

1) adding 4-8 parts of maleic anhydride and 4-8 parts of methanol into a single-necked bottle, stirring, heating to 50 ℃, keeping the temperature, and reacting for 0.5-1.5h to obtain monomethyl maleate;

2) cooling 80-120 parts of hydrogen bromide-glacial acetic acid solution to 0 ℃, then dropwise adding 3-5 parts of monomethyl maleate, keeping the temperature and stirring, and obtaining a large amount of yellow sticky substances after 3-7min to obtain 3-monomethyl bromomaleate;

3) dissolving 3-bromomaleic acid monomethyl ester in 10-15 parts of dichloromethane, then dripping 4-6 drops of DMF, dripping 2-4 parts of thionyl chloride in dichloromethane solution within 10-20min to prepare 3-bromomaleic acid monomethyl ester acyl chloride;

4) adding 18-24 parts of 2, 3-dichloropyridine and 26-30 parts of ethylene glycol into a single-neck bottle to prepare 3-chloro-2-hydrazinopyridine;

5) adding 4-6 parts of 3-chloro-2-hydrazinopyridine, 30-50 parts of sodium bicarbonate and 30-50 parts of acetonitrile into a three-necked bottle provided with a drying tube and an ice bath, cooling to 0 ℃, dropwise adding 6-8 parts of 3-bromomaleic acid monomethyl ester acyl chloride solution dissolved in acetonitrile, naturally heating to room temperature for reaction for 2-4h after dropwise adding, pouring the reaction solution into a proper amount of water, adjusting the pH value to 6 with acetic acid, extracting with ethyl acetate, drying, concentrating to obtain a brownish red oily substance, and recrystallizing with ethanol to obtain a light yellow solid 2- (3-chloropyridine-2-pyridyl) -5-oxopyrazole-3-methyl formate;

6) adding 2- (3-chloropyridine-2-pyridyl) -5-oxopyrazole-3-methyl formate and 15-35 parts of acetonitrile into a reaction bottle, adding 4-6 parts of phosphorus oxybromide under stirring, heating up, refluxing for reaction for 20-80min, pouring the reaction liquid into a proper amount of water, adjusting the reaction liquid to be neutral by using saturated sodium bicarbonate, extracting by using ethyl acetate, drying and concentrating to obtain black oily 3-bromo-1- (3-chloropyridine-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-methyl formate;

7) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-methyl formate, 30-50 parts of acetonitrile and 10-14 parts of concentrated sulfuric acid into a reaction bottle, stirring at room temperature, adding 14-18 parts of potassium persulfate, heating for reflux reaction for 1-5H, stopping the reaction, and performing suction filtration to obtain yellow solid methyl 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-carboxylate;

8) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-methyl formate into a solution of sodium hydroxide dissolved in 4-8 parts of methanol, stirring at room temperature until the solution is dissolved, stopping reaction after 1H, adding a proper amount of water, adjusting the pH value to 4 by using dilute hydrochloric acid, extracting by using ethyl acetate, drying and concentrating to obtain a yellow solid, namely 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-carboxylic acid;

9) adding 3-methyl-2-aminobenzoic acid and glacial acetic acid into a reaction bottle, dropwise adding 20-24 parts of concentrated hydrochloric acid while stirring, dropwise adding thirty-percent hydrogen peroxide after 5min, reacting at room temperature to obtain a brownish clear solution, dropwise adding water to precipitate a solid, and performing suction filtration and drying to obtain a brownish solid 5-chloro-3-methyl-2-aminobenzoic acid;

10) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-formic acid, 5-chloro-3-methyl-2-aminobenzoic acid and 50-70 parts of acetonitrile into a reaction bottle, cooling to 10 ℃, dropwise adding 26-30 parts of 3-methylpyridine, adding a solution of methylsulfonyl chloride dissolved in acetonitrile after 10-40min, changing the turbid reaction liquid into brown and clarifying, stirring at a constant temperature, heating to room temperature for reaction, stopping the reaction, adding a proper amount of water, and performing suction filtration to obtain a yellow solid, namely 6-chloro-2- (3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazol-5-yl) -8-methyl-4H-3, 1-benzoxazin-4-one;

11) putting 6-chloro-2- (3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazol-5-yl) -8-methyl-4H-3, 1-benzoxazine-4-one and 20-40 parts of acetonitrile into a reaction bottle, dropwise adding twenty-five percent of methylamine water solution to obtain a clear solution, stirring for 10min, and performing suction filtration to obtain an off-white solid.

2. The method for preparing chlorantraniliprole according to claim 1, wherein the monomethyl maleate is prepared by reacting maleic anhydride with methanol to obtain a colorless transparent solution, and evaporating the solvent under reduced pressure to obtain a colorless viscous liquid.

3. The preparation method of chlorantraniliprole according to claim 1, wherein the 3-bromomaleic acid monomethyl ester acyl chloride is subjected to reflux reaction for 1.5h, and then the solvent is evaporated under reduced pressure to obtain yellow liquid which is directly used for the next reaction without treatment.

4. The method for preparing chlorantraniliprole according to claim 1, wherein the hydrogen bromide-glacial acetic acid solution is subjected to heat preservation overnight for reaction according to the proportion of thirty-three percent, the reaction solution is poured into a proper amount of water the next day, and the ethyl acetate is used for extraction, drying and concentration to obtain the 3-bromomaleic acid monomethyl ester as a light yellow oily substance.

5. The preparation method of chlorantraniliprole according to claim 1, wherein the 2, 3-dichloropyridine and the glycol are added with eighty-five percent of hydrazine hydrate under stirring, and the white solid 3-chloro-2-hydrazinopyridine is obtained after reflux reaction for 2-6h, cooling and suction filtration.

Technical Field

The invention relates to the technical field of synthetic processes of insecticides, in particular to a preparation method of chlorantraniliprole.

Background

Chlorantraniliprole, which is a new high-efficiency and low-toxicity o-formylaminobenzamide pesticide developed by DuPont company in the United states under the Chinese trade name Kangkuan, has good insecticidal activity even under very low concentration, has special effect on lepidoptera insects, and has the chemical name of 3-bromo-N- { 4-chloro-2-methyl-6- [ (methylamino) carbonyl ] phenyl } -1- (3-chloro-2-pyridyl) -1H-pyridine-5-amide.

For example, in the process of synthesizing p-methylindole-2, 3-dione, the method needs to heat the prepared solution to 80 ℃ and stir for 10min, stop the reaction, cool the solution at room temperature, pour the reaction solution onto crushed ice while stirring, stand the solution overnight, and perform suction filtration, and the process has harsh reaction conditions, needs complex equipment, is not easy to control the production process, and is not suitable for industrial production.

Disclosure of Invention

Technical problem to be solved

Aiming at the defects of the prior art, the invention provides a preparation method of chlorantraniliprole, which has the advantages of simple and convenient preparation and the like, and solves the problems that the chlorantraniliprole is harsh in reaction conditions, complex in required equipment, difficult to control in the process of production technology and not suitable for industrial production in the preparation process of the chlorantraniliprole.

(II) technical scheme

In order to realize the purpose of simple and convenient manufacture, the invention provides the following technical scheme: a preparation method of chlorantraniliprole comprises the following steps:

1) adding 4-8 parts of maleic anhydride and 4-8 parts of methanol into a single-necked bottle, stirring, heating to 50 ℃, keeping the temperature, and reacting for 0.5-1.5h to obtain monomethyl maleate;

2) cooling 80-120 parts of hydrogen bromide-glacial acetic acid solution to 0 ℃, then dropwise adding 3-5 parts of monomethyl maleate, keeping the temperature and stirring, and obtaining a large amount of yellow sticky substances after 3-7min to obtain 3-monomethyl bromomaleate;

3) dissolving 3-bromomaleic acid monomethyl ester in 10-15 parts of dichloromethane, then dripping 4-6 drops of DMF, dripping 2-4 parts of thionyl chloride in dichloromethane solution within 10-20min to prepare 3-bromomaleic acid monomethyl ester acyl chloride;

4) adding 18-24 parts of 2, 3-dichloropyridine and 26-30 parts of ethylene glycol into a single-neck bottle to prepare 3-chloro-2-hydrazinopyridine;

5) adding 4-6 parts of 3-chloro-2-hydrazinopyridine, 30-50 parts of sodium bicarbonate and 30-50 parts of acetonitrile into a three-necked bottle provided with a drying tube and an ice bath, cooling to 0 ℃, dropwise adding 6-8 parts of 3-bromomaleic acid monomethyl ester acyl chloride solution dissolved in acetonitrile, naturally heating to room temperature for reaction for 2-4h after dropwise adding, pouring the reaction solution into a proper amount of water, adjusting the pH value to 6 with acetic acid, extracting with ethyl acetate, drying, concentrating to obtain a brownish red oily substance, and recrystallizing with ethanol to obtain a light yellow solid 2- (3-chloropyridine-2-pyridyl) -5-oxopyrazole-3-methyl formate;

6) adding 2- (3-chloropyridine-2-pyridyl) -5-oxopyrazole-3-methyl formate and 15-35 parts of acetonitrile into a reaction bottle, adding 4-6 parts of phosphorus oxybromide under stirring, heating up, refluxing for reaction for 20-80min, pouring the reaction liquid into a proper amount of water, adjusting the reaction liquid to be neutral by using saturated sodium bicarbonate, extracting by using ethyl acetate, drying and concentrating to obtain black oily 3-bromo-1- (3-chloropyridine-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-methyl formate;

7) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-methyl formate, 30-50 parts of acetonitrile and 10-14 parts of concentrated sulfuric acid into a reaction bottle, stirring at room temperature, adding 14-18 parts of potassium persulfate, heating for reflux reaction for 1-5H, stopping the reaction, and performing suction filtration to obtain yellow solid methyl 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-carboxylate;

8) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-methyl formate into a solution of sodium hydroxide dissolved in 4-8 parts of methanol, stirring at room temperature until the solution is dissolved, stopping reaction after 1H, adding a proper amount of water, adjusting the pH value to 4 by using dilute hydrochloric acid, extracting by using ethyl acetate, drying and concentrating to obtain a yellow solid, namely 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-carboxylic acid;

9) adding 3-methyl-2-aminobenzoic acid and glacial acetic acid into a reaction bottle, dropwise adding 20-24 parts of concentrated hydrochloric acid while stirring, dropwise adding thirty-percent hydrogen peroxide after 5min, reacting at room temperature to obtain a brownish clear solution, dropwise adding water to precipitate a solid, and performing suction filtration and drying to obtain a brownish solid 5-chloro-3-methyl-2-aminobenzoic acid;

10) adding 3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazole-5-formic acid, 5-chloro-3-methyl-2-aminobenzoic acid and 50-70 parts of acetonitrile into a reaction bottle, cooling to 10 ℃, dropwise adding 26-30 parts of 3-methylpyridine, adding a solution of methylsulfonyl chloride dissolved in acetonitrile after 10-40min, changing the turbid reaction liquid into brown and clarifying, stirring at a constant temperature, heating to room temperature for reaction, stopping the reaction, adding a proper amount of water, and performing suction filtration to obtain a yellow solid, namely 6-chloro-2- (3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazol-5-yl) -8-methyl-4H-3, 1-benzoxazin-4-one;

11) putting 6-chloro-2- (3-bromo-1- (3-chloropyridine-2-pyridyl) -1H-pyrazol-5-yl) -8-methyl-4H-3, 1-benzoxazine-4-one and 20-40 parts of acetonitrile into a reaction bottle, dropwise adding twenty-five percent of methylamine water solution to obtain a clear solution, stirring for 10min, and performing suction filtration to obtain an off-white solid.

Preferably, the monomethyl maleate is prepared by reacting maleic anhydride and methanol to obtain a colorless transparent solution, and evaporating the solvent under reduced pressure to obtain colorless viscous liquid.

Preferably, the 3-bromomaleic acid monomethyl ester acyl chloride is subjected to reflux reaction for 1.5h, and then the solvent is evaporated under reduced pressure to obtain yellow liquid which is directly used for the next reaction without treatment.

Preferably, the hydrogen bromide-glacial acetic acid solution is subjected to heat preservation overnight reaction according to the proportion of thirty-three percent, and the reaction solution is poured into a proper amount of water the next day, extracted by ethyl acetate, dried and concentrated to obtain a light yellow oily 3-bromomonomethyl maleate.

Preferably, the 2, 3-dichloropyridine and the ethylene glycol are added with eighty-five percent of hydrazine hydrate under stirring, and the white solid 3-chloro-2-hydrazinopyridine is obtained after reflux reaction for 2 to 6 hours, cooling and suction filtration.

(III) advantageous effects

Compared with the prior art, the invention provides a preparation method of chlorantraniliprole, which has the following beneficial effects:

1. the preparation method of chlorantraniliprole synthesizes the target chlorantraniliprole by taking maleic anhydride, 2, 3-dichloropyridine and 2-amino-3-methylbenzoic acid as initial raw materials through a convergent reaction, the structure of the chlorantraniliprole is determined by HNMR, the solution does not need to be heated to an overhigh temperature, and meanwhile, the solution does not need to be processed at a low temperature.

2. The preparation method of chlorantraniliprole has the advantages that 2-amino-3-methylbenzoic acid analogues are used as starting raw materials, target substances are generated under the action of hydrogen peroxide and concentrated hydrochloric acid, liquid bromine and NCS (N-methyl-N-butyl-S) expensive reagents are bypassed, the consumption of the reaction reagents is reduced compared with that of the original method, the consumption of the hydrogen peroxide is reduced, the cost is saved, the reaction time is shortened, the experimental operation is simplified, the method is short in route, easy to operate, capable of reacting at room temperature, simple and convenient to post-treat, the ethyl ester is replaced by the methyl ester, the concept of atom economy is embodied, the reaction activity of a substrate is improved, the raw materials are cheap and easy to obtain, special reagents are not needed, the reaction conditions are mild, the yield is high, and the method is suitable.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.