Synthesis method of 2, 3-dichloro-5-trifluoromethylpyridine

Abstract

The invention discloses a synthesis method of 2, 3-dichloro-5-trifluoromethylpyridine, which comprises the following steps: mixing a copper catalyst, a ligand and alkali, then adding an organic solvent, 5-bromo-2, 3-dichloropyridine and trifluoromethyltrimethylsilane under the protection of inert gas, then heating and stirring until the reaction is complete, and after the reaction is complete, carrying out post-treatment to obtain the 2, 3-dichloro-5-trifluoromethylpyridine. The catalyst is 2, 3-dichloro-5-trifluoromethylpyridine. The method has the beneficial effects that the copper catalyst used in the method is cheap and easy to obtain, the raw materials are easy to obtain non-toxic substances, the process 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-dichloro-5-trifluoromethylpyridine.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine. Background Art

[0002] 2,3-Dichloro-5-trifluoromethylpyridine is an important intermediate of fluorinated pyridine pesticides. It can be used to synthesize fungicides such as fluopyram, fluazinam, and fluopyram, insecticides such as chlorpyrifos, pyrimidine, and triflumizone, and herbicides such as haloxyfop-P-ethyl and fluazifop-P-ethyl. This type of pesticide has the advantages of broad spectrum, high efficiency, low toxicity, and low pollution, and has become a hot topic of concern in the industry.

[0003] At present, there are mainly two methods for synthesizing 2,3-dichloro-5-trifluoromethylpyridine:

[0004] 1. Using 2,3-dichloro-5-trichloromethylpyridine as raw material, react at 170°C, and obtain 2,3-dichloro-5-trifluoromethylpyridine through fluorination with hydrogen fluoride gas.

[0005] 2. Using 2-chloro-5-trifluoromethylpyridine as raw material, 2,3-dichloro-5-trifluoromethylpyridine was obtained by chlorination with chlorine gas at a high temperature of 150-170°C.

[0006] The above methods all involve the use of highly toxic gases to participate in the reaction and the reaction temperature is high, which places high demands on the reaction equipment required for production, and has high requirements on process control and safety. In addition, the reaction process contains many isomerized impurities and requires multiple distillation separations to recover and reuse the by-products. Invention content

[0007] In view of this, the present invention aims to provide a method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine to solve at least one technical problem in the background technology.

[0008] To achieve the above object, the technical solution created by the present invention is implemented as follows:

[0009] A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine comprises the following steps: sequentially adding a copper catalyst, a ligand, and a base into a dry reaction container, evacuating the reaction container and filling it with an inert gas (argon or nitrogen) for three times, then adding an organic solvent, 5-bromo-2,3-dichloropyridine and trifluoromethyltrimethylsilane under the protection of the inert gas, and then heating to a specified temperature and stirring until the reaction is complete. After the reaction is complete, the reaction system is cooled to room temperature, the filtrate is filtered and collected, the filtrate is concentrated under reduced pressure to recover the solvent to obtain a mixture, and the target product 2,3-dichloro-5-trifluoromethylpyridine is obtained after the mixture is rectified.

[0010] The above reaction route is:

[0011]

[0012] Furthermore, the usage ratio of the copper catalyst: ligand: base: 5-bromo-2,3-dichloropyridine: trifluoromethyltrimethylsilane is mol: mol: mol: mol: mol = (0.05-0.2): (0.05-0.2): (1-2): 1: (1-2).

[0013] Furthermore, the usage ratio of the 5-bromo-2,3-dichloropyridine to the organic solvent is mass (g): volume (mL) = 1: (5-10).

[0014] Furthermore, the usage ratio of the copper catalyst: ligand: base: 5-bromo-2,3-dichloropyridine: trifluoromethyltrimethylsilane is mol: mol: mol: mol: mol = 0.2: 0.2: 2: 1: 2.

[0015] Further, the amount of 5-bromo-2,3-dichloropyridine and the organic solvent is mass (g): volume (mL) = 1:8

[0016] Furthermore, the copper catalyst is any one of cuprous iodide, cuprous bromide and cuprous chloride.

[0017] Furthermore, the ligand is any one of 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, and 6,6'-dimethyl-2,2'-bipyridine.

[0018] Furthermore, the base is any one of potassium fluoride, potassium tert-butoxide, and lithium methoxide.

[0019] Furthermore, the organic solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide and acetonitrile.

[0020] Furthermore, the specified temperature is 50-60°C.

[0021] Compared with the prior art, the synthesis method of 2,3-dichloro-5-trifluoromethylpyridine described in the present invention has the following advantages:

[0022] The invention discloses a method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine. 5-bromo-2,3-dichloropyridine and trifluoromethyltrimethylsilane are used to synthesize 2,3-dichloro-5-trifluoromethylpyridine through a one-pot reaction under the catalysis of a copper catalyst. The reaction method has mild reaction conditions and can efficiently synthesize the target compound. The copper catalyst used in the method is cheap and easily available, the raw materials are easily available and are non-toxic substances, the process operation is simple and safe, the yield is good, and the reaction solvent can be recycled and reused, thus laying a foundation for further amplification and providing a new method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The drawings constituting part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments and descriptions of the present invention are used to explain the present invention and do not constitute an improper limitation on the present invention. In the drawings:

[0024] Figure 1 The liquid chromatogram of 2,3-dichloro-5-trifluoromethylpyridine described in Example 1 is created for the present invention. DETAILED DESCRIPTION

[0025] 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.

[0026] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments.

[0027] Example 1

[0028] Add iodide (0.191g), 2,2'-bipyridine (0.156g), potassium fluoride (0.581g) in a dry reaction container, evacuate the reaction container and fill it with nitrogen, repeat 3 times, then add N,N-dimethylformamide (9.1mL), 5-bromo-2,3-dichloropyridine (1.134g) and trifluoromethyltrimethylsilane (1.422g) under nitrogen protection, then heat to 55°C and stir until the reaction is complete. After the reaction is complete, cool the reaction system to room temperature, filter to remove insoluble matter, and concentrate the filtrate under reduced pressure to recover N,N-dimethylformamide to obtain a mixture. After the mixture is distilled, the target product 2,3-dichloro-5-trifluoromethylpyridine 0.983g is obtained, with a yield of 91%. The liquid chromatogram is as follows Figure 1 shown.

[0029] Example 2

[0030] Add bromoketone (0.072g), 4,4'-di-tert-butyl-2,2'-bipyridine (0.134g), potassium tert-butoxide (0.842g) in a dry reaction vessel, evacuate the reaction vessel and fill it with nitrogen, repeat 3 times, then add N,N-dimethylacetamide (11.3mL), 5-bromo-2,3-dichloropyridine (1.134g) and trifluoromethyltrimethylsilane (1.067g) under nitrogen protection, then heat to 60°C and stir until the reaction is complete. After the reaction is complete, cool the reaction system to room temperature, filter to remove insoluble matter, concentrate the filtrate under reduced pressure to recover N,N-dimethylacetamide, and obtain a mixture. After the mixture is rectified, 0.907g of the target product 2,3-dichloro-5-trifluoromethylpyridine is obtained, with a yield of 84%;

[0031] Example 3

[0032] Add chlorinated ketone (0.049g), 6,6'-dimethyl-2,2'-bipyridine (0.092g), and lithium methoxide (0.190g) in a dry reaction vessel, evacuate the reaction vessel and fill it with nitrogen, repeat 3 times, then add acetonitrile (6.8mL), 5-bromo-2,3-dichloropyridine (1.134g) and trifluoromethyltrimethylsilane (0.853g) under nitrogen protection, then heat to 50°C and stir until the reaction is complete. After the reaction is complete, cool the reaction system to room temperature, filter to remove insoluble matter, concentrate the filtrate under reduced pressure to recover acetonitrile to obtain a mixture, and obtain the target product 2,3-dichloro-5-trifluoromethylpyridine 0.778g after distillation of the mixture, with a yield of 72%;

[0033] 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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine, characterized in that: The method comprises the following steps: mixing a copper catalyst, a ligand and a base, then adding an organic solvent, 5-bromo-2,3-dichloropyridine and trifluoromethyltrimethylsilane under the protection of an inert gas, then heating and stirring until the reaction is complete, and after the reaction is complete, post-treating to obtain 2,3-dichloro-5-trifluoromethylpyridine.

2. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The copper catalyst includes any one or more of cuprous iodide, cuprous bromide, and cuprous chloride.

3. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The ligand includes any one or more of 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, and 6,6'-dimethyl-2,2'-bipyridine.

4. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The base includes any one or more of potassium fluoride, potassium tert-butoxide, and lithium methoxide.

5. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The organic solvent includes any one or more of N,N-dimethylformamide, N,N-dimethylacetamide and acetonitrile.

6. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The molar ratio of the copper catalyst: ligand: base: 5-bromo-2,3-dichloropyridine: trifluoromethyltrimethylsilane is: (0.05-0.2): (0.05-0.2): (1-2): 1: (1-2).

7. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The molar ratio of the copper catalyst: ligand: base: 5-bromo-2,3-dichloropyridine: trifluoromethyltrimethylsilane is 0.2:0.2:2:1:

2.

8. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The usage ratio of 5-bromo-2,3-dichloropyridine to the organic solvent is mass (g): volume (mL) = 1: (5-10), preferably, the usage ratio of 5-bromo-2,3-dichloropyridine to the organic solvent is mass (g): volume (mL) = 1:

8.

9. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: The temperature for heating and stirring is 50~60℃.

10. A method for synthesizing 2,3-dichloro-5-trifluoromethylpyridine according to claim 1, characterized in that: 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 distilling the mixture to obtain the target product 2,3-dichloro-5-trifluoromethylpyridine.

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