Preparation method of fluopyram

Abstract

The invention discloses a fluopyram preparation method, which comprises: S1, carrying out a heating reaction on 2-vinyl-3-chloro-5-trifluoromethylpyridine, ammonia water, a catalyst and a solvent, carrying out reduced pressure distillation after the heating reaction to recover the solvent so as to obtain a residue, and adding dichloromethane and triethylamine to the residue so as to obtain a reaction liquid; and S2, dropwise adding o-trifluoromethyl benzoyl chloride into the reaction liquid in an ice bath, then removing the ice bath, stirring at the room temperature, adding water into the reaction liquid obtained in the step S1, extracting an organic layer, drying with anhydrous magnesium sulfate, recovering the solvent under reduced pressure, and performing vacuum drying to obtain the fluopyram. The method has the advantages of high reaction yield, high product purity, recyclable and reusable solvent, simple and mild production process, and suitableness for mass production.

Description

Technical Field

[0001] The present invention belongs to the technical fields of pesticides and organic synthesis, and in particular relates to a preparation method of fluopyram. Background Art

[0002] Fluopyram is a novel pyridyl ethyl benzamide fungicide and nematicide developed by Bayer. The patent CN1319946 in China expired on August 8, 2023. The preparation patent CN101080391 will expire on December 19, 2025.

[0003] Currently, the synthetic methods of fluopyram in the literature mainly focus on the key intermediate 2-aminoethyl-3-chloro-5-trifluoromethylpyridine. The main reported methods are as follows: 1. The route through 2-aminoethyl-3-chloro-5-trifluoromethylpyridine: Using 2,3-dichloro-5-trifluoromethylpyridine and ethyl cyanoacetate as starting materials, the intermediate 2-ethylamino-3-chloro-5-trifluoromethylpyridine hydrochloride is prepared through a reduction reaction, and then reacted with 2-trifluoromethylbenzoyl chloride. Such reported literatures include: patents CN1319946C, CN102276520A, Pesticides, 2015, 54(7): 485-486. Such reaction routes are basically five or six steps, with long steps, large losses, and low efficiency.

[0004] 2. The route without passing through 2-aminoethyl-3-chloro-5-trifluoromethylpyridine: Such routes mainly carry out 4-6 steps of reaction through diethyl malonate and are obtained through classical condensation reactions. Such literatures include: patents CN101080391B, WO0111965. Summary of the Invention

[0005] In view of this, the present invention aims to propose a preparation method of fluopyram to solve at least one technical problem in the background art.

[0006] To achieve the above object, the technical solution of the present invention is realized as follows: A preparation method of fluopyram, comprising the following steps: S1: React 2-vinyl-3-chloro-5-trifluoromethylpyridine, ammonia water, a catalyst, and a solvent by heating. After the heating reaction, the solvent is recovered by vacuum distillation to obtain a residue. Dichloromethane and triethylamine are added to the residue to obtain a reaction solution; S2: Drop 2-trifluoromethylbenzoyl chloride into the reaction solution under an ice bath, then remove the ice bath and stir at room temperature. Water is added to the reaction solution obtained in step S1, the organic layer is extracted, dried with anhydrous magnesium sulfate, the solvent is recovered under reduced pressure, and vacuum drying is carried out to obtain fluopyram.

[0007] The above reaction formula is: 。

[0008] Further, the catalyst in step S1 includes one or more of benzyltriethylammonium chloride, tetrabutylammonium chloride, potassium iodide, ammonium chloride, ammonium bromide, phenyltributylammonium bromide, tetrabutylammonium bromide, propyltrimethylammonium chloride, potassium fluoride, and cetyl dimethylbenzylammonium bromide.

[0009] Further, the mass ratio of the catalyst added in step S1 is 1% - 30% of 2 - vinyl - 3 - chloro - 5 - trifluoromethylpyridine.

[0010] Further, the solvent in step S1 includes one or more of isopropanol, methanol, dichloromethane, ethyl acetate, chloroform, 1,2 - dichloroethane, toluene, dioxane, dimethyl sulfoxide, N,N - dimethylformamide, and water.

[0011] Further, the molar ratio of 2 - vinyl - 3 - chloro - 5 - trifluoromethylpyridine : ammonia water : solvent : dichloromethane : o - trifluoromethylbenzoyl chloride : triethylamine is 1:(3 - 9):(10 - 50):(10 - 20):(1 - 1.02):(1 - 2).

[0012] Further, the temperature of the temperature - rising reaction in step S1 is 30 - 150°C. Preferably, the temperature of the temperature - rising reaction is 85°C.

[0013] Further, the temperature of the ice - bath reaction in step S2 is - 5 - 10°C. Preferably, the temperature of the ice - bath reaction is 0°C.

[0014] Compared with the prior art, the method for preparing fluopyram of the present invention has the following advantages: 1. The present application provides a one - pot method for preparing fluopyram, which has a high reaction yield, high product purity, the solvent used can be recycled, the production process is simple and mild, and is suitable for mass production.

[0015] 2. The present application efficiently introduces an amino group through the nucleophilic substitution reaction of ammonia water and 2 - vinyl - 3 - chloro - 5 - trifluoromethylpyridine, and then condenses with o - trifluoromethylbenzoyl chloride under mild conditions to form an amide bond. The reaction conditions are controllable (temperature gradient rising from ice - bath to room temperature), and the product yield is high; the purification method of combining dichloromethane extraction and drying with anhydrous magnesium sulfate effectively removes impurities, and vacuum distillation and vacuum drying ensure complete removal of the solvent, finally obtaining high - purity fluopyram. The process operation is simple and suitable for large - scale production. Description of the Drawings

[0016] The accompanying drawings, which form a part of the present invention, are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation to the present invention. In the drawings: Figure 1 It is the HPLC chart of fluxapyroxad described in Example 1 of the present invention. Detailed implementation manners

[0017] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other.

[0018] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments.

[0019] Example 1 20.7 g of 2-vinyl-3-chloro-5-trifluoromethylpyridine, 160 g of isopropanol, 156 g of ammonia water, 2 g of benzyltriethylammonium chloride, the solvents are added into a closed reactor, heated to 85 °C and reacted for 15 hours. The solvents are recovered by vacuum distillation under reduced pressure. Then, 150 g of dichloromethane and 15 g of triethylamine are added to the residue under mechanical stirring. The reaction solution is cooled to 0 °C in an ice bath, and 20.9 g of o-trifluoromethylbenzoyl chloride is added dropwise to the reaction solution. After removing the ice bath and stirring at room temperature for 1 hour, 130 ml of water is added to the reaction solution. The dichloromethane layer is taken, and then extracted twice with 50 ml of dichloromethane. It is dried with 15 g of anhydrous magnesium sulfate, filtered, the solvent dichloromethane in the filtrate is recovered by vacuum distillation under reduced pressure, and vacuum dried at 70 °C for 10 hours to obtain 34.4 g of off-white solid fluxapyroxad, with a yield of 86.72%. The liquid phase content is 99.42%, the water content is 0.05%, and there is no acetone-insoluble matter.

[0020] Example 2 20.7 g of 2-vinyl-3-chloro-5-trifluoromethylpyridine, 180 g of ammonia water, 180 g of isopropanol, 2.6 g of benzyltriethylammonium chloride, the solvents are added into a closed reactor, heated to 85 °C and reacted for 15 hours. The solvents are recovered by vacuum distillation under reduced pressure. Then, 160 g of dichloromethane and 15 g of triethylamine are added to the residue under mechanical stirring. The reaction solution is cooled to 0 °C in an ice bath, and 20.9 g of o-trifluoromethylbenzoyl chloride is added dropwise to the reaction solution. After removing the ice bath and stirring at room temperature for 1 hour, 150 ml of water is added to the reaction solution. The dichloromethane layer is taken, and then extracted twice with 50 ml of dichloromethane. It is dried with 20 g of anhydrous magnesium sulfate, filtered, the solvent dichloromethane in the filtrate is recovered by vacuum distillation under reduced pressure, and vacuum dried at 70 °C for 10 hours to obtain 35.1 g of off-white solid fluxapyroxad, with a yield of 88.48%. The liquid phase content is 99.39%, the water content is 0.04%, and there is no acetone-insoluble matter.

[0021] Example 3 20.7 g of 2-vinyl-3-chloro-5-trifluoromethylpyridine, 150 g of ammonia water, 150 g of methanol, 4 g of cetyl dimethyl benzyl ammonium bromide were added to a closed reactor. The temperature was raised to 85 °C and the reaction was carried out for 15 hours. The solvent was recovered by vacuum distillation. Then, 160 g of dichloromethane and 15 g of triethylamine were added to the residue under mechanical stirring. The temperature was lowered to 0 °C in an ice bath, and 20.9 g of o-trifluoromethylbenzoyl chloride was added dropwise to the reaction solution. After removing the ice bath and stirring at room temperature for 1 hour, 150 ml of water was added to the reaction solution. The dichloromethane layer was taken, and the extraction was carried out twice with 50 ml of dichloromethane. It was dried with 20 g of anhydrous magnesium sulfate, filtered, and the solvent dichloromethane in the filtrate was recovered under reduced pressure. It was dried in vacuo at 70 °C for 10 hours to obtain 21.5 g of off-white solid fluxapyroxad, with a yield of 54.20%. The liquid phase content was 98.31%, the water content was 0.06%, and there was no acetone-insoluble matter.

[0022] Example 4 20.7 g of 2-vinyl-3-chloro-5-trifluoromethylpyridine, 150 g of ammonia water, 150 g of ethyl acetate, 5 g of tetrabutyl ammonium bromide were added to a closed reactor. The temperature was raised to 90 °C and the reaction was carried out for 24 hours. The solvent was recovered by vacuum distillation. Then, 160 g of dichloromethane and 15 g of triethylamine were added to the residue under mechanical stirring. The temperature was lowered to 0 °C in an ice bath, and 20.9 g of o-trifluoromethylbenzoyl chloride was added dropwise to the reaction solution. After removing the ice bath and stirring at room temperature for 1 hour, 150 ml of water was added to the reaction solution. The dichloromethane layer was taken, and the extraction was carried out twice with 50 ml of dichloromethane. It was dried with 20 g of anhydrous magnesium sulfate, filtered, and the solvent dichloromethane in the filtrate was recovered under reduced pressure. It was dried in vacuo at 70 °C for 10 hours to obtain 15.3 g of off-white solid fluxapyroxad, with a yield of 38.57%. The liquid phase content was 98.37%, the water content was 0.06%, and there was no acetone-insoluble matter.

[0023] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing fluopyram, characterized in that: The steps include: S1: 2-vinyl-3-chloro-5-trifluoromethylpyridine, ammonia water, a catalyst and a solvent are subjected to a temperature-raising reaction, and after the temperature-raising reaction, the solvent is recovered by distillation under reduced pressure to obtain a residue, and dichloromethane and triethylamine are added to the residue to obtain a reaction solution; S2: Add o-trifluoromethylbenzoyl chloride dropwise to the reaction solution under an ice bath, then remove the ice bath and stir at low temperature, add water to the reaction solution, extract the organic layer, dry it over anhydrous magnesium sulfate, recover the solvent under reduced pressure, and dry it in vacuum to obtain fluopyram.

2. The method for preparing fluopyram according to claim 1, characterized in that: The catalyst in step S1 includes one or more of benzyltriethylammonium chloride, tetrabutylammonium chloride, potassium iodide, ammonium chloride, ammonium bromide, phenyltributylammonium bromide, tetrabutylammonium bromide, propyltrimethylammonium chloride, potassium fluoride, and hexadecyldimethylbenzylammonium bromide.

3. The method for preparing fluopyram according to claim 1, characterized in that: The added mass ratio of the catalyst in step S1 is 1%-30% of 2-vinyl-3-chloro-5-trifluoromethylpyridine.

4. The method for preparing fluopyram according to claim 1, characterized in that: The solvent in step S1 includes one or more of isopropanol, methanol, dichloromethane, ethyl acetate, chloroform, 1,2-dichloroethane, toluene, dioxane, dimethyl sulfoxide, N,N-dimethylformamide, and water.

5. The method for preparing fluopyram according to claim 1, characterized in that: The molar ratio of 2-vinyl-3-chloro-5-trifluoromethylpyridine: ammonia water: solvent: dichloromethane: o-trifluoromethylbenzoyl chloride: triethylamine is 1: (3-9): (10-50): (10-20): (1-1.02): (1-2).

6. The method for preparing fluopyram according to claim 1, characterized in that: The temperature of the temperature-raising reaction in step S1 is 30-150°C.

7. The method for preparing fluopyram according to claim 1, characterized in that: The temperature of the temperature-raising reaction in step S1 is 85°C.

8. The method for preparing fluopyram according to claim 1, characterized in that: The ice bath reaction temperature in step S2 is -5-10°C.

9. The method for preparing fluopyram according to claim 1, characterized in that: The ice bath reaction temperature in step S2 is 0°C.

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