Synthesis method of 2-(3-chloro-5-(trifluoromethyl) pyridine-2-yl) acetonitrile

Abstract

The invention discloses a synthesis method of 2-(3-chloro-5-(trifluoromethyl) pyridine-2-yl) acetonitrile, which comprises the following steps: mixing 3-chloro-2-(chloromethyl)-5-(trifluoromethyl) pyridine, cyanide and an additive, under the protection of inert gas, adding an organic solvent, carrying out heating reaction, and after the reaction is finished, cooling to room temperature to obtain the 2-(3-chloro-5-(trifluoromethyl) pyridine-2-yl) acetonitrile. And carrying out post-treatment to obtain the target product 2-(3-chloro-5-(trifluoromethyl) pyridine-2-yl) acetonitrile. According to the reaction method, the reaction conditions are mild, the target compound can be rapidly and efficiently synthesized, the technological operation is simple, convenient and safe, the yield is good, the reaction solvent can be recycled and reused, a foundation is laid for further amplification, and a new method is provided for synthesizing the 2-(3-chloro-5-(trifluoromethyl) pyridine-2-yl) acetonitrile.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile. Background Art

[0002] 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile is an intermediate of the novel succinate dehydrogenase inhibitor (SDHI), fluopyram. Fluopyram has a broad spectrum of activity and can be used to control diseases such as leaf spot, leaf spot, gray mold, powdery mildew, sclerotinia, and early blight. It can also be used to control various nematodes on a variety of crops. It is a highly effective, green, and low-toxic nematicide.

[0003] Currently, the method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile is: 2,3-dichloro-5-trifluoromethylpyridine is first reacted with ethyl cyanoacetate, and then hydrolyzed and decarboxylated in two steps to obtain 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile. This method uses concentrated hydrochloric acid at 120°C for hydrolysis and decarboxylation, which produces a large amount of acid gas, corrodes equipment, and produces a large amount of acidic wastewater after the reaction, which is not conducive to environmental protection. Invention content In view of this, the present invention aims to provide a method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile to solve at least one technical problem in the background technology.

[0004] To achieve the above object, the technical solution created by the present invention is implemented as follows: A method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile comprises the following steps: 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine, cyanide, and additives are mixed, and under the protection of inert gas, an organic solvent is added. The temperature is raised to react, and after post-treatment, the target product 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile is obtained.

[0005] The above reaction route is: .

[0006] Furthermore, the cyanide includes one or more of cuprous cyanide, potassium ferrocyanide, and potassium ferrocyanide.

[0007] Furthermore, the additive includes one or both of sodium iodide and potassium iodide.

[0008] Furthermore, the organic solvent includes one or more of butyl acetate, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0009] Furthermore, the molar ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine:cyanide:additive is 1:(0.2-2):(0.2-0.5).

[0010] Furthermore, the mass volume ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine to the organic solvent is 1:(5-10).

[0011] Furthermore, the temperature of the temperature-raising reaction is 70-80°C.

[0012] Furthermore, the method further comprises sequentially adding 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine, cyanide, and an additive into a dry reaction vessel, and repeatedly evacuating the reaction vessel and filling it with an inert gas multiple times; And / or, the reaction vessel is evacuated and filled with inert gas repeatedly for at least 3 times.

[0013] Furthermore, the inert gas includes one or both of argon and nitrogen.

[0014] Furthermore, post-treatment includes cooling the reaction system to room temperature, filtering and collecting the filtrate, concentrating the filtrate under reduced pressure to recover the solvent to obtain a mixture, and washing the mixture with water, concentrating, and crystallizing to obtain the target product 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile.

[0015] Compared with the prior art, the method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile created by the present invention has the following advantages: The present invention discloses a method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile. 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine and cyanide are used to synthesize 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile through a one-pot reaction. The method has mild reaction conditions, can rapidly and efficiently synthesize the target compound, is simple and safe to operate, has a good yield, and the reaction solvent can be recycled and reused. This method lays a foundation for further scale-up and provides a new method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] 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: Figure 1 A liquid chromatogram of 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile as described in Example 1 was created for the present invention. DETAILED DESCRIPTION

[0017] It should be noted that, in the absence of conflict, the embodiments of 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 To a dry reaction vessel, 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (2.30 g), cuprous cyanide (1.79 g), and sodium iodide (0.74 g) were added sequentially. The reaction vessel was evacuated and filled with nitrogen three times. Then, under nitrogen, N,N-dimethylformamide (16.1 mL) was added. The temperature was then raised to 75°C and stirred until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, and the filtrate was collected by filtration. The filtrate was concentrated under reduced pressure to recover the solvent to obtain a mixture. The mixture was dissolved in methyl tert-butyl ether, washed with water, and the filtrate was concentrated and crystallized to obtain 1.87 g of the desired product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, in an 85% yield.

[0020] Example 2 To a dry reaction vessel, 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (2.30 g), potassium ferricyanide (0.98 g), and sodium iodide (0.60 g) were added sequentially. The reaction vessel was evacuated and filled with nitrogen three times. Then, under nitrogen, N,N-dimethylacetamide (11.5 mL) was added. The temperature was then raised to 70°C and stirred until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, and the filtrate was collected by filtration. The filtrate was concentrated under reduced pressure to recover the solvent to obtain a mixture. The mixture was dissolved in methyl tert-butyl ether, washed with water, and the filtrate was concentrated and crystallized to obtain 1.83 g of the desired product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, in an 83% yield.

[0021] Example 3 To a dry reaction vessel, 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (2.30 g), potassium ferrocyanide (0.74 g), and potassium iodide (0.33 g) were added sequentially. The reaction vessel was evacuated and filled with nitrogen three times. Then, under nitrogen, butyl acetate (20.7 mL) was added. The temperature was then raised to 80°C and stirred until the reaction was complete. After the reaction was complete, the reaction system was cooled to room temperature, and the filtrate was collected by filtration. The filtrate was concentrated under reduced pressure to recover the solvent to obtain a mixture. The mixture was dissolved in methyl tert-butyl ether, washed with water, and the filtrate was concentrated and crystallized to obtain 1.74 g of the desired product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, in a yield of 79%.

[0022] Comparative Example 1 The difference from Example 1 is that the molar ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine: cuprous cyanide: sodium iodide is 1:2:1. The target product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, is obtained in 80% yield.

[0023] Comparative Example 2 The difference from Example 1 is that the molar ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine: cuprous cyanide: sodium iodide is 1.5:2:0.5. The target product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, is obtained in a 70% yield.

[0024] Comparative Example 3 The difference from Example 1 is that the molar ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine: cuprous cyanide: sodium iodide is 1:2.5:1.5. The target product, 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, is obtained in an 81% yield.

[0025] 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 in the scope of protection of the present invention.

Claims

1. A method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile, characterized in that: The steps include: 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine, cyanide, and additives are mixed, and under the protection of inert gas, an organic solvent is added. The temperature is raised to react, and after post-treatment, the target product 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile is obtained.

2. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The cyanide includes one or more of cuprous cyanide, potassium ferrocyanide, and potassium ferrocyanide.

3. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The additive includes one or both of sodium iodide and potassium iodide.

4. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The organic solvent includes one or more of butyl acetate, N,N-dimethylformamide, and N,N-dimethylacetamide.

5. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The molar ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine:cyanide:additive is 1:(0.2~2):(0.2~0.5).

6. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The mass volume ratio of 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine to the organic solvent is 1:(5~10).

7. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The temperature of the temperature-raising reaction is 70-80°C.

8. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The process further comprises sequentially adding 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine, cyanide, and an additive into a dry reaction vessel, and repeatedly evacuating the reaction vessel and filling it with an inert gas multiple times; And / or, the reaction vessel is evacuated and filled with inert gas repeatedly for at least 3 times.

9. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The inert gas includes one or both of argon and nitrogen.

10. The method for synthesizing 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile according to claim 1, wherein: The post-treatment includes cooling the reaction system to room temperature, filtering and collecting the filtrate, concentrating the filtrate under reduced pressure to recover the solvent to obtain a mixture, and washing the mixture with water, concentrating, and crystallizing to obtain the target product 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)acetonitrile.

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