Synthesis method of pesticide fluopyram

Abstract

The invention discloses a synthesis method of pesticide fluopyram, which comprises the following steps: under protective gas, mixing 2-trifluoromethyl benzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine and alkali, vacuumizing, filling the protective gas, adding an organic solvent, heating and stirring until the reaction is complete, cooling to room temperature, filtering, washing, and drying to obtain the fluopyram. And performing post-treatment to obtain the pesticide fluopyram. According to the synthesis method of the pesticide fluopyram, the target product is directly and efficiently synthesized through one-step reaction, and the yield is good. Compared with existing synthesis routes, the route is short, the atom utilization rate is high, the requirement for equipment is simple, and a foundation is laid for further pilot scale production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and in particular relates to a method for synthesizing the pesticide fluopyram. Background Technology

[0002] Fluopyram is a novel pyridyl ethyl benzamide fungicide with a broad spectrum of control. It can be used to control diseases such as leaf spot, gray mold, powdery mildew, sclerotinia rot, and early blight. It has also been developed globally for use as a nematicide, seed treatment agent, and agricultural product storage and preservation agent.

[0003] There are currently many reported methods for synthesizing fluopyram, with two main routes being...

[0004] 1. Starting with o-trifluoromethylbenzamide, N-hydroxymethyl-2-(trifluoromethyl)benzamide is obtained by hydroxymethylation, followed by esterification with acetyl chloride or acetic anhydride to obtain N-acetoxymethyl-2-(trifluoromethyl)benzamide, which is then condensed with diethyl 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]malonate and hydrolyzed to decarboxylate to obtain fluopyram. This reaction route has five steps, which is relatively long and has low atom utilization.

[0005] 2. Fluopyram is synthesized via an intermediate of 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride and o-trifluoromethylbenzoyl chloride. This route involves a 5-step reaction, including palladium-on-carbon catalytic hydrogenation, requiring a high-pressure reactor and demanding equipment requirements. Furthermore, the palladium-on-carbon catalyst contributes to the high production cost. Summary of the Invention

[0006] In view of this, the present invention aims to provide a method for synthesizing the pesticide fluopyram to solve at least one technical problem in the background art.

[0007] To achieve the above objectives, the technical solution of the present invention is implemented as follows:

[0008] A method for synthesizing the pesticide fluopyram includes the following steps: under a protective gas atmosphere, 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and a base are added sequentially to a reaction vessel. The reaction vessel is evacuated and filled with an inert gas, and this process is repeated three times. Then, under gas protection, an organic solvent is added, and the mixture is heated to a specified temperature and stirred until the reaction is complete.

[0009] After the reaction is complete, the reaction system is cooled to room temperature, and the organic phase is obtained by water washing and extraction. The organic phase is concentrated under reduced pressure to recover the solvent and obtain a mixture. The mixture is recrystallized to obtain the target product, fluopyram.

[0010] The reaction formula is shown below:

[0011]

[0012] Further, the molar ratio of 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and base is 1:(1-2):(0.5-1).

[0013] Furthermore, the molar ratio of 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and the base is 1:1.5:0.5.

[0014] Furthermore, the protective gas is one of nitrogen, helium, neon, argon, or krypton.

[0015] Furthermore, the alkali includes one of sodium hydroxide, potassium hydroxide, and potassium phosphate.

[0016] Furthermore, the mass-to-volume ratio of 2-trifluoromethylbenzamide to the organic solvent is 1:5 to 10.

[0017] Furthermore, the mass-to-volume ratio of 2-trifluoromethylbenzamide to the organic solvent is 1:7.

[0018] Furthermore, the organic solvent includes one or more of N-methylpyrrolidone, dimethyl sulfoxide, and N,N-dimethylacetamide.

[0019] Furthermore, the temperature for heating and stirring is 100–110°C.

[0020] Compared with existing technologies, the method for synthesizing the pesticide fluopyram described in this invention has the following advantages:

[0021] The present invention discloses a method for synthesizing the pesticide fluopyram, which directly and efficiently synthesizes the target product in a one-step reaction with good yield. Compared with existing synthetic routes, this route is shorter, has higher atom utilization, and requires simpler equipment, laying the foundation for further pilot-scale production. Attached Figure Description

[0022] The accompanying drawings, which constitute part of the present invention, are intended to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are intended to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[0023] Figure 1 This is the HPLC chromatogram of fluopyram as described in Example 1 of the present invention. Detailed Implementation

[0024] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0025] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which this invention pertains. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0026] Example 1

[0027] Under nitrogen protection, 1.89 g of 2-trifluoromethylbenzamide, 3.11 g of 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and 0.20 g of sodium hydroxide were added sequentially to a reaction vessel. The reaction vessel was evacuated and purged with nitrogen three times. Then, under nitrogen protection, 13.3 mL of N-methylpyrrolidone was added, followed by heating to 100 °C and stirring until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, washed with water, and extracted with methyl tert-butyl ether to obtain the organic phase. The organic phase was concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a mixture. The mixture was recrystallized from methanol / water to obtain 3.53 g of the target product, fluopyram, with a yield of 89%.

[0028] Example 2

[0029] Under nitrogen protection, 1.89 g of 2-trifluoromethylbenzamide, 4.15 g of 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and 0.56 g of potassium hydroxide were added sequentially to a reaction vessel. The reaction vessel was evacuated and purged with nitrogen three times. Then, under nitrogen protection, 9.5 mL of dimethyl sulfoxide was added, followed by heating to 110 °C and stirring until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, washed with water, and extracted with methyl tert-butyl ether to obtain the organic phase. The organic phase was concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a mixture. The mixture was recrystallized from methanol / water to obtain 3.37 g of the target product, fluopyram, with a yield of 85%.

[0030] Example 3

[0031] Under nitrogen protection, 1.89 g of 2-trifluoromethylbenzamide, 2.08 g of 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and 1.69 g of potassium phosphate were added sequentially to a reaction vessel. The reaction vessel was evacuated and purged with nitrogen three times. Then, under nitrogen protection, 18.0 mL of N,N-dimethylacetamide was added, and the mixture was heated to 100 °C and stirred until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, washed with water, and extracted with methyl tert-butyl ether to obtain the organic phase. The organic phase was concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a mixture. The mixture was recrystallized from methanol / water to obtain 3.17 g of the target product, fluopyram, with a yield of 80%.

[0032] Example 4

[0033] Under nitrogen protection, 1.89 g of 2-trifluoromethylbenzamide, 2.91 g of 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and 0.28 g of sodium hydroxide were added sequentially to a reaction vessel. The reaction vessel was evacuated and purged with nitrogen three times. Then, under nitrogen protection, 13.2 mL of dimethyl sulfoxide was added, followed by heating to 110 °C and stirring until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, washed with water, and extracted with methyl tert-butyl ether to obtain the organic phase. The organic phase was concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a mixture. The mixture was recrystallized from methanol / water to obtain 3.61 g of the target product, fluopyram, with a yield of 91%.

[0034] Example 5

[0035] Under nitrogen protection, 1.89 g of 2-trifluoromethylbenzamide, 3.11 g of 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and 1.06 g of potassium phosphate were added sequentially to a reaction vessel. The reaction vessel was evacuated and purged with nitrogen three times. Then, under nitrogen protection, 13.2 mL of dimethyl sulfoxide was added, followed by heating to 110 °C and stirring until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, washed with water, and extracted with methyl tert-butyl ether to obtain the organic phase. The organic phase was concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a mixture. The mixture was recrystallized from methanol / water to obtain 3.69 g of the target product, fluopyram, with a yield of 93%.

[0036] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing the pesticide fluopyram, characterized in that: The process includes the following steps: 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and a base are mixed under a protective gas atmosphere, a vacuum is drawn and a protective gas atmosphere is introduced, an organic solvent is added, the mixture is heated and stirred until the reaction is complete, cooled to room temperature, and then post-treated to obtain the pesticide fluopyram.

2. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The molar ratio of 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and base is 1:(1-2):(0.5-1).

3. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The molar ratio of 2-trifluoromethylbenzamide, 3-chloro-5-(trifluoromethyl)-2-vinylpyridine, and the base is 1:1.5:0.

5.

4. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The alkali includes one of sodium hydroxide, potassium hydroxide, and potassium phosphate.

5. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The mass-to-volume ratio of 2-trifluoromethylbenzamide to organic solvent is 1:5 to 10.

6. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The mass-to-volume ratio of 2-trifluoromethylbenzamide to the organic solvent is 1:

7.

7. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: Organic solvents include one or more of N-methylpyrrolidone, dimethyl sulfoxide, and N,N-dimethylacetamide.

8. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: The temperature for heating and stirring is 100-110℃.

9. The method for synthesizing the pesticide fluopyram according to claim 1, characterized in that: Post-processing includes cooling the reaction system to room temperature, washing and extracting with water to obtain an organic phase, concentrating the organic phase under reduced pressure to recover the solvent and obtain a mixture, and recrystallizing the mixture to obtain the pesticide fluopyram.

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