阅读说明：本技术 一种用于合成丙炔氟草胺的农药中间体的合成方法 (Synthetic method of pesticide intermediate for synthesizing flumioxazin ) 是由 易克炎 杨江宇 吴文良 尹凯 顾旻旻 严泽华 张政 于 2019-10-23 设计创作，主要内容包括：本发明提供了一种用于合成丙炔氟草胺的农药中间体的合成方法,属于农药合成领域。解决了现有合成7-氟-6-胺基-2H-1,4-苯并噁嗪-3(4H)-酮收率不高等问题。一种用于合成丙炔氟草胺的农药中间体的合成方法,合成路线如下：<Image he="322" wi="700" file="DDA0002244680250000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明收率高。(The invention provides a synthesis method of a pesticide intermediate for synthesizing flumioxazin, belonging to the field of pesticide synthesis. Solves the problems of low yield and the like of the existing synthesis of 7-fluoro-6-amido-2H-1, 4-benzoxazine-3 (4H) -ketone. A synthetic method of a pesticide intermediate for synthesizing flumioxazin comprises the following synthetic route: the invention has high yield.)

1. A synthetic method of a pesticide intermediate for synthesizing flumioxazin is characterized by comprising the following steps:

s01: m-dichlorobenzene is taken as a raw material, 70 percent nitric acid is taken as a nitration reagent, dichloroethane is taken as a solvent for reaction, and 1, 3-dichloro-4, 6-dinitrobenzene is obtained through reaction; fluorinating the 1, 3-dichloro-4, 6-dinitrobenzene to obtain 1, 5-difluoro-2, 4-dinitrobenzene;

s02: adding dimethylformamide, isopropyl chloroacetate and potassium hydroxide into 1, 5-difluoro-2, 4-dinitrobenzene, stirring and heating to 90-150 ℃, keeping the temperature for reaction for 3-4 hours, performing suction filtration after the reaction is finished, and performing reduced pressure distillation on the filtrate to obtain a product, namely isopropyl 3-fluoro-4, 6-dinitrophenoxy acetate;

s03: adding 3-fluoro-4, 6-dinitrophenoxy isopropyl acetate into a reaction kettle, adding a nickel-based catalyst modified by dimethylformamide and cerium, sealing the reaction kettle, replacing air with nitrogen, replacing nitrogen with hydrogen, finally filling hydrogen to 0.9-1.1MPa, starting stirring, heating to 95-105 ℃, adding hydrogen to 0.9-1.1MPa when the pressure in the kettle is lower than 0.6MPa, reacting for 3-4 hours, taking supernatant liquid after the reaction is finished, carrying out reduced pressure distillation, adding methanol into residues after the reduced pressure distillation, heating to reflux, keeping the temperature for 30-40min, cooling, filtering and drying to obtain 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone solid.

2. The method for synthesizing an intermediate of agricultural chemicals for the synthesis of flumioxazin as claimed in claim 1, wherein in step S02, the temperature is raised to 120 ℃ with stirring.

3. The method for synthesizing an intermediate of agricultural chemicals for the synthesis of flumioxazin as claimed in claim 1, wherein in step S02, the reaction is maintained for 3 hours.

4. The method for synthesizing an agricultural chemical intermediate for flumioxazin according to claim 1, wherein in step S02, the filtrate is distilled under reduced pressure to recover dimethylformamide, and the recovered product is isopropyl 3-fluoro-4, 6-dinitrophenoxyacetate.

5. The method for synthesizing an agricultural chemical intermediate for synthesizing flumioxazin according to claim 1, wherein in step S02, the vacuum degree of reduced pressure distillation is-0.09 MPa and the temperature is less than 120 ℃.

6. The method for synthesizing an agricultural chemical intermediate for synthesizing flumioxazin according to claim 1, wherein in step S02, salt residue is removed by suction filtration, the salt residue is rinsed with dimethylformamide, and the rinse and the liquid after suction filtration are combined into a filtrate.

7. The method for synthesizing an agricultural chemical intermediate for synthesis of flumioxazin as claimed in claim 1, wherein in step S03, after replacing air with nitrogen three times, nitrogen is replaced with hydrogen three times.

8. The method for synthesizing an agricultural chemical intermediate used in the synthesis of flumioxazin as claimed in claim 1, wherein in step S03, after replacing nitrogen with hydrogen, filling hydrogen to 1.0MPa, starting stirring, raising the temperature to 100 ℃, and when the pressure in the kettle is lower than 0.6MPa, filling hydrogen to 1.0 MPa.

9. The method for synthesizing an intermediate of pesticides for the synthesis of flumioxazin as claimed in claim 1, wherein in step S03, the vacuum degree of the reduced pressure distillation is-0.09 Mpa, and the temperature is 90-120 ℃.

10. The method for synthesizing an agricultural chemical intermediate for flumioxazin according to claim 1, wherein in step S03, the supernatant is distilled under reduced pressure to recover dimethylformamide, methanol is added to the residue after distillation under reduced pressure, the temperature is raised to reflux, the temperature is kept for 30min, and the mixture is cooled to room temperature.

Technical Field

The invention belongs to the field of pesticide synthesis, and particularly relates to a synthesis method of a pesticide intermediate for synthesizing flumioxazin.

Background

Flumioxazin is an N-phenylphthalimide herbicide marketed by Sumitomo chemical industry, Japan in 1993, and is mainly used for preventing and killing gramineous weeds and broadleaf weeds on crops such as soybeans, sugarcane, cotton and the like. In the synthesis of flumioxazin, an intermediate of pesticide is often synthesized first, and then the flumioxazin is synthesized. The 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone is an important intermediate for synthesizing flumioxazin.

The existing method for synthesizing 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone has low yield, which leads to high cost for synthesizing 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone. Therefore, a new synthetic route and method are imperative to be found.

Disclosure of Invention

The invention aims to solve the problems in the prior art and provides a synthetic method of a pesticide intermediate for synthesizing flumioxazin.

The purpose of the invention can be realized by the following technical scheme: a synthetic method of a pesticide intermediate for synthesizing flumioxazin is characterized by comprising the following steps:

s01: m-dichlorobenzene is taken as a raw material, 70 percent nitric acid is taken as a nitration reagent, dichloroethane is taken as a solvent for reaction, and 1, 3-dichloro-4, 6-dinitrobenzene is obtained through reaction; fluorinating the 1, 3-dichloro-4, 6-dinitrobenzene to obtain 1, 5-difluoro-2, 4-dinitrobenzene;

s02: adding dimethylformamide, isopropyl chloroacetate and potassium hydroxide into 1, 5-difluoro-2, 4-dinitrobenzene, stirring and heating to 90-150 ℃, keeping the temperature for reaction for 3-4 hours, performing suction filtration after the reaction is finished, and performing reduced pressure distillation on the filtrate to obtain a product, namely isopropyl 3-fluoro-4, 6-dinitrophenoxy acetate;

s03: adding 3-fluoro-4, 6-dinitrophenoxy isopropyl acetate into a reaction kettle, adding a nickel-based catalyst modified by dimethylformamide and cerium, sealing the reaction kettle, replacing air with nitrogen, replacing nitrogen with hydrogen, finally filling hydrogen to 0.9-1.1MPa, starting stirring, heating to 95-105 ℃, adding hydrogen to 0.9-1.1MPa when the pressure in the kettle is lower than 0.6MPa, reacting for 3-4 hours, taking supernatant liquid after the reaction is finished, carrying out reduced pressure distillation, adding methanol into residues after the reduced pressure distillation, heating to reflux, keeping the temperature for 30-40min, cooling, filtering and drying to obtain 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone solid.

Preferably, in step S02, the temperature is raised to 120 ℃ by stirring, and the reaction is maintained for 3 hours.

Preferably, in step S02, the filtrate is distilled under reduced pressure to recover dimethylformamide, and the recovered product, namely 3-fluoro-4, 6-dinitrophenoxyacetic acid isopropyl ester, is obtained, wherein the vacuum degree of the reduced pressure distillation is-0.09 MPa, and the temperature is less than 120 ℃.

Preferably, in step S02, the salt residue is removed by suction filtration, the salt residue is rinsed with dimethylformamide, and the rinse solution and the liquid after suction filtration are combined to obtain a filtrate.

Preferably, in step S03, after replacing air with nitrogen for three times, replacing nitrogen with hydrogen for three times, finally filling hydrogen to 1.0MPa, starting stirring, raising the temperature to 100 ℃, and when the pressure in the kettle is lower than 0.6MPa, filling hydrogen to 1.0 MPa.

Preferably, in step S03, the vacuum degree of the reduced pressure distillation is-0.09 Mpa, the temperature is between 90 ℃ and 120 ℃, the supernatant is subjected to reduced pressure distillation, dimethylformamide is recovered, methanol is added to the residue after the reduced pressure distillation, the temperature is increased to reflux, the temperature is kept for 30min, and the mixture is cooled to room temperature.

The working principle of the invention is as follows: the synthetic method of the invention has the following synthetic route,

the 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H) -ketone is synthesized by taking m-dichlorobenzene which is cheap and easy to obtain as an initial raw material through reactions such as nitration, fluorination, etherification, hydrogenation reduction ring closing and the like.

Compared with the prior art, the invention has the following advantages:

1. the method adopts m-dichlorobenzene as a raw material, 70% nitric acid as a nitration reagent and Dichloroethane (DCE) as a solvent to react, and the nitration reaction has good selectivity and high yield. In the traditional nitration reaction, a mixed acid system of concentrated nitric acid and concentrated sulfuric acid is adopted, a large amount of waste acid which is difficult to treat is generated, and the environmental protection pressure is higher. The invention has less waste acid amount and small environmental protection pressure.

2. The etherification reaction of the invention adopts isopropyl chloroacetate as an etherification reagent, DMF (dimethyl formamide) as a solvent, and potassium hydroxide as an alkali, so that the selectivity is very high. In the traditional process, the method of hydrolyzing, etherifying and nitrifying the 2, 4-difluoronitrobenzene is adopted, so that the selectivity is poor and the byproducts are more during etherification. The invention has good selectivity and few byproducts.

3. The hydrogenation reduction ring closing of the invention adopts the cerium modified nickel-based catalyst (CN201710109138.9), can be completed in one step, and has less side reaction and higher product purity. And the traditional process adopts a method of firstly closing the ring and then nitrifying and then reducing, so that the route is long, the yield is low, and the defluorination phenomenon is obvious.

4. The yield of the reaction steps is high and can reach 92 percent, and the cost is greatly reduced. And the purity can reach 98 percent and is high.

5. The invention uses hydrogen to replace iron powder for hydrogenation reduction, thereby avoiding the generation of a large amount of iron mud which is difficult to treat and reducing solid waste.

Detailed Description

The following are specific examples of the present invention and further describe the technical solutions of the present invention, but the present invention is not limited to these examples.