Synthetic method of benzamide compound

Abstract

The invention discloses a synthesis method of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide. The synthesis method comprises the steps: taking ethyl cyanoacetate and 2,3-dichloro-5-(trifluoromethyl)pyridine as as raw materials, firstly supplementing N,N-dimethylformamide with the pH value of 2-5 to reaction mother liquor under the action of a catalyst and an alkali, carrying out reflux to obtain 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, and then carrying out catalytic hydrogenation reduction to obtain 3-chloro-5-(trifluoromethyl)-2-ethylaminopyridine; and finally, carrying out condensation on the 3-chloro-5-(trifluoromethyl)-2-ethylaminopyridine and 2-(trifluoromethyl)benzoyl chloride under the participation of a water phase to obtain the target compound N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide. The synthesis method provided by the invention reduces reaction steps, is simple to operate, mild in condition, less in three wastes and high in yield, and is a synthesis method of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide.

Description

technical field

[0001] The invention belongs to the field of pesticide synthesis, in particular to N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide synthetic method. Background technique

[0002] N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide is an important agricultural fungicide, common name It is fluopyram (EP1674455A1 and Liu Anchang et al., Synthesis of new fungicide fluopyram, "Pesticides", 2015, 54(7): 485-486). For the report of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide synthetic method is less, the market is Bayer Corporate monopoly. According to reports in the literature, the synthetic route of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide mainly contains the following Two: Route 1: Use o-trifluoromethylbenzoic acid as raw material to obtain N-methylol-2-trifluoromethylbenzamide through acylation, amidation and hydr...

Examples

Embodiment 1

[0049] Step (1): Add 11.8g of ethyl cyanoacetate, 30ml of N,N-dimethylformamide and 5% triethylbenzyl ammonium chloride into a 100ml reaction flask, and add 5.6g of carbonic acid in batches under uniform stirring Potassium, then stir at 25°C for 0.5h, then slowly add 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine dropwise, after the drop is complete, raise the temperature to 70°C for 1h, stop the reaction, and filter out the insoluble After adding 10ml N,N-dimethylformamide, use 10% hydrochloric acid to adjust the pH value of the reaction mother liquor to 2, and solids will precipitate out, and the temperature will be raised to reflux for 3 hours, and the reaction will be stopped. After collecting and recovering the solvent under the conditions, 19 g of a reddish-brown residue was obtained, with a content of 98% and a yield of 85%, which was 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, which was directly used without purification react in the next step.

[0050] ...

Embodiment 2

[0057] Step (1): Add 11.3g of ethyl cyanoacetate, 30ml of methanol and 5% potassium iodide into a 100ml reaction flask, add 5.6g of sodium methoxide in batches under uniform stirring, then stir at 25°C for 0.5h and slowly drop Add 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine, after dropping, raise the temperature to 70°C for 1h, stop the reaction, filter out insoluble matter, add 40ml of N,N-dimethylformamide Use 10% hydrochloric acid to adjust the pH value of the reaction mother liquor to 2, solids precipitate out, raise the temperature to reflux for 3 hours, stop the reaction, distill under reduced pressure, collect and recover the solvent under the condition of 110°C / 133-266Pa, and obtain a reddish-brown residue 19g, The content is 98%, and the yield is 85%. It is 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, which is directly used in the next step without purification.

[0058] Step (2): Add 19g of 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, 30ml of ...

Embodiment 3

[0061] Step (1): Add 13.6g of ethyl cyanoacetate, 30ml of ethyl acetate and 5% 18-crown-6 into a 100ml reaction flask, add 20.7g of potassium carbonate in batches under uniform stirring, and then control the temperature at 25°C After stirring for 0.5h, 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine was slowly added dropwise. After the drop was completed, the temperature was raised to 70°C for 1h, and the reaction was stopped. The insoluble matter was filtered off, and 30ml of N,N- After dimethylformamide, use 10% hydrochloric acid to adjust the pH value of the reaction mother liquid to 2, and solids will precipitate out, raise the temperature to reflux for 3 hours, stop the reaction, distill under reduced pressure, and collect and recover the solvent under the condition of 70°C / 133~266Pa to obtain Reddish-brown residue 19.3g, content 98%, yield 86%, namely 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, directly used in the next step without purification,

[0062] Ste...

technical field

[0001] The invention belongs to the field of pesticide synthesis, in particular to N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide synthetic method. Background technique

[0002] N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide is an important agricultural fungicide, common name It is fluopyram (EP1674455A1 and Liu Anchang et al., Synthesis of new fungicide fluopyram, "Pesticides", 2015, 54(7): 485-486). For the report of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide synthetic method is less, the market is Bayer Corporate monopoly. According to reports in the literature, the synthetic route of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl]-2-(trifluoromethyl)benzamide mainly contains the following Two: Route 1: Use o-trifluoromethylbenzoic acid as raw material to obtain N-methylol-2-trifluoromethylbenzamide through acylation, amidation and hydr...

Examples

Embodiment 1

[0049] Step (1): Add 11.8g of ethyl cyanoacetate, 30ml of N,N-dimethylformamide and 5% triethylbenzyl ammonium chloride into a 100ml reaction flask, and add 5.6g of carbonic acid in batches under uniform stirring Potassium, then stir at 25°C for 0.5h, then slowly add 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine dropwise, after the drop is complete, raise the temperature to 70°C for 1h, stop the reaction, and filter out the insoluble After adding 10ml N,N-dimethylformamide, use 10% hydrochloric acid to adjust the pH value of the reaction mother liquor to 2, and solids will precipitate out, and the temperature will be raised to reflux for 3 hours, and the reaction will be stopped. After collecting and recovering the solvent under the conditions, 19 g of a reddish-brown residue was obtained, with a content of 98% and a yield of 85%, which was 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, which was directly used without purification react in the next step.

[0050] ...

Embodiment 2

[0057] Step (1): Add 11.3g of ethyl cyanoacetate, 30ml of methanol and 5% potassium iodide into a 100ml reaction flask, add 5.6g of sodium methoxide in batches under uniform stirring, then stir at 25°C for 0.5h and slowly drop Add 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine, after dropping, raise the temperature to 70°C for 1h, stop the reaction, filter out insoluble matter, add 40ml of N,N-dimethylformamide Use 10% hydrochloric acid to adjust the pH value of the reaction mother liquor to 2, solids precipitate out, raise the temperature to reflux for 3 hours, stop the reaction, distill under reduced pressure, collect and recover the solvent under the condition of 110°C / 133-266Pa, and obtain a reddish-brown residue 19g, The content is 98%, and the yield is 85%. It is 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, which is directly used in the next step without purification.

[0058] Step (2): Add 19g of 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, 30ml of ...

Embodiment 3

[0061] Step (1): Add 13.6g of ethyl cyanoacetate, 30ml of ethyl acetate and 5% 18-crown-6 into a 100ml reaction flask, add 20.7g of potassium carbonate in batches under uniform stirring, and then control the temperature at 25°C After stirring for 0.5h, 21.5g of 2,3-dichloro-5-(trifluoromethyl)pyridine was slowly added dropwise. After the drop was completed, the temperature was raised to 70°C for 1h, and the reaction was stopped. The insoluble matter was filtered off, and 30ml of N,N- After dimethylformamide, use 10% hydrochloric acid to adjust the pH value of the reaction mother liquid to 2, and solids will precipitate out, raise the temperature to reflux for 3 hours, stop the reaction, distill under reduced pressure, and collect and recover the solvent under the condition of 70°C / 133~266Pa to obtain Reddish-brown residue 19.3g, content 98%, yield 86%, namely 3-chloro-5-(trifluoromethyl)-2-acetonitrile pyridine, directly used in the next step without purification,

[0062] Ste...

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