Preparation method of pesticide fluopyram

Abstract

The invention discloses a preparation method of a pesticide fluopyram, which comprises the following steps: mixing a metal palladium catalyst, a ligand, 2-[3-chloro-5-(trifluoromethane) pyridine-2-methylethylamine hydrochloride, o-halogen trifluorotoluene, alkali and an organic solvent under protective gas, increasing the pressure in a kettle, heating and stirring, and carrying out post-treatment to obtain the pesticide fluopyram. The target product is directly and efficiently synthesized through one-step reaction, and the yield is good. Compared with the existing synthesis route, the route has the advantages that the raw materials are easy to obtain, the route is shortened, the reaction conditions are not harsh, and a foundation is laid for further pilot scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for preparing the pesticide fluopyram. Background Art

[0002] Fluopyram is a new type of succinate dehydrogenase inhibitor (SDHI) with a broad spectrum of control. It can be used to control diseases such as leaf spot, leaf spot, gray mold, powdery mildew, sclerotinia, and early blight. It can also be registered for the control of various nematodes on a variety of crops. It is also a highly effective, green, and low-toxic nematicide.

[0003] Currently, there are many reported methods for synthesizing fluopyram. The mainstream route involves synthesizing fluopyram via 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride] and o-trifluoromethylbenzoyl chloride as intermediates. o-Trifluoromethylbenzoyl chloride is synthesized from o-xylene through hazardous processes such as chlorination, fluorination, and oxidation. These processes are risky and costly, which also increases the cost of industrializing fluopyram. Summary of the Invention

[0004] In view of this, the present invention aims to provide a method for preparing the pesticide fluopyram to solve at least one technical problem in the background technology.

[0005] To achieve the above object, the technical solution of the present invention is achieved as follows: A method for preparing the pesticide fluopyram comprises the following steps: under protective gas, sequentially adding a metal palladium catalyst, a ligand, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride, o-halotrifluorotoluene, a base and an organic solvent into an autoclave; replacing the gas in the autoclave with carbon monoxide; subsequently increasing the pressure in the autoclave with carbon monoxide; heating and stirring; and post-processing to obtain the pesticide fluopyram.

[0006] The synthetic route is as follows: ; Furthermore, the protective gas is an inert gas, and the inert gas includes one of argon and nitrogen.

[0007] Furthermore, the metal palladium catalyst includes one or more of bis(dibenzylideneacetone)palladium, palladium acetate, and bis(acetylacetonate)palladium.

[0008] Furthermore, the ligand includes one or more of tricyclohexylphosphine tetrafluoroborate, bis(2-diphenylphosphinophenyl) ether, and bis(diphenylphosphino) propane.

[0009] Furthermore, the base includes one or more of potassium carbonate, potassium acetate, and potassium phosphate.

[0010] Furthermore, the organic solvent includes one or more of N,N-dimethylformamide, N-methylpyrrolidone, and 1,4-dioxane.

[0011] Furthermore, the molar ratio of the metal palladium catalyst, the ligand, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride, o-halotrifluorotoluene, and the base is (0.01-0.05):(0.01-0.1):1:(1-1.5):(2-3), preferably, the molar ratio is 0.02:0.02:1:1.2:2.5.

[0012] Furthermore, the ratio of the 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride to the organic solvent is 1 g: 5-10 mL; Preferably, the ratio of 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride to the organic solvent is 1 g:8 mL.

[0013] Furthermore, the elevated pressure is increased to 2-3 MPa, and the reaction temperature is increased to 70-80°C with stirring; The gas in the autoclave was replaced with carbon monoxide three times.

[0014] Furthermore, the post-treatment to obtain the pesticide fluopyram includes filtering out insoluble matter, recovering the organic solvent under reduced pressure, and then recrystallizing to obtain the pesticide fluopyram.

[0015] Compared with the prior art, the preparation method of the pesticide fluopyram described in the present invention has the following advantages: The present invention describes a method for synthesizing the pesticide fluopyram, using a palladium catalyst to directly and efficiently synthesize the target product in a single step with good yield. Compared to existing synthetic routes, this route offers readily available raw materials, a shorter route, and less stringent reaction conditions, laying the foundation for further pilot production. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The accompanying drawings, which constitute part of the present invention, are provided to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are provided to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings: Figure 1 This is the HPLC chart of fluopyram described in Example 1 of 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 may be combined with each other.

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

[0019] Example 1 Under nitrogen gas, bis(dibenzylideneacetone)palladium (0.057 g), bis(2-diphenylphosphinophenyl) ether (0.054 g), 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride (1.305 g), o-iodotrifluorotoluene (1.632 g), potassium carbonate (1.727 g) and N,N-dimethylformamide (10.4 mL) were added to an autoclave in sequence. The gas in the autoclave was then replaced with carbon monoxide three times, and the pressure in the autoclave was subsequently increased to 2.5 MPa with carbon monoxide. The temperature was raised to 80°C and the reaction was stirred until the reaction was complete. The insoluble matter was removed by filtration, and N,N-dimethylformamide was recovered under reduced pressure and recrystallized from methanol to obtain 1.706 g of fluopyram (yield 86%).

[0020] Example 2 Under nitrogen gas, palladium acetate (0.056 g), tricyclohexylphosphine tetrafluoroborate (0.184 g), 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride (1.305 g), o-iodotrifluorotoluene (2.040 g), potassium acetate (1.472 g) and N-methylpyrrolidone (13.1 mL) were added to the autoclave in sequence, and the gas in the autoclave was replaced with carbon monoxide three times. Subsequently, the pressure in the autoclave was increased to 3 MPa with carbon monoxide, the temperature was raised to 80°C, and the reaction was stirred until the reaction was complete. The insoluble matter was removed by filtration, and N-methylpyrrolidone was recovered under reduced pressure. The product was then recrystallized from methanol to obtain 1.607 g of fluopyram with a yield of 81%.

[0021] Example 3 Under nitrogen gas, di(acetylacetonate)palladium (0.046 g), bis(diphenylphosphine)propane (0.062 g), 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride (1.305 g), o-bromotrifluorotoluene (1.238 g), potassium phosphate (2.122 g) and 1,4-dioxane (7.8 mL) were added to the autoclave in sequence, and the gas in the autoclave was replaced with carbon monoxide three times. Subsequently, the pressure in the autoclave was increased to 2 MPa with carbon monoxide, the temperature was raised to 70°C, and the reaction was stirred until the reaction was complete. The insoluble matter was removed by filtration, and 1,4-dioxane was recovered under reduced pressure and recrystallized from methanol to obtain 1.468 g of fluopyram with a yield of 74%.

[0022] Comparative Example 1 The difference from Example 1 is that the molar ratio of bis(dibenzylideneacetone)palladium, bis(2-diphenylphosphinophenyl)ether, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine] hydrochloride, o-iodobenzotrifluoride, and potassium carbonate is 0.06:0.02:1:1.2:2.5. The yield of fluopyram is 82%.

[0023] Comparative Example 2 The difference from Example 1 is that the molar ratios of bis(dibenzylideneacetone)palladium, bis(2-diphenylphosphinophenyl)ether, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine] hydrochloride, o-iodobenzotrifluoride, and potassium carbonate are 0.02:0.15:1:1.2:2.5. The yield of fluopyram is 65%.

[0024] Comparative Example 3 The difference from Example 1 is that the molar ratio of bis(dibenzylideneacetone)palladium, bis(2-diphenylphosphinophenyl)ether, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride, o-iodotrifluorotoluene, and potassium carbonate is 0.02:0.02:1:2:2.5.

[0025] The yield of fluopyram was 85%.

[0026] Comparative Example 4 The difference from Example 1 is that the molar ratio of bis(dibenzylideneacetone)palladium, bis(2-diphenylphosphinophenyl)ether, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride, o-iodotrifluorotoluene, and potassium carbonate is 0.02:0.02:1:1.2:3.5.

[0027] The yield of fluopyram was 83%.

[0028] 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 preparing the pesticide fluopyram, characterized in that: The method comprises the following steps: mixing a metal palladium catalyst, a ligand, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride, o-halogenotrifluorotoluene, a base and an organic solvent under a protective gas, increasing the pressure in the kettle, heating and stirring, and obtaining the pesticide fluopyram after post-treatment.

2. The method for preparing the pesticide fluopyram according to claim 1, wherein: The shielding gas is an inert gas, which includes argon or nitrogen.

3. The method for preparing the pesticide fluopyram according to claim 1, wherein: The metal palladium catalyst includes one or more of bis(dibenzylideneacetone)palladium, palladium acetate, and bis(acetylacetonate)palladium.

4. The method for preparing the pesticide fluopyram according to claim 1, wherein: The ligand includes one or more of tricyclohexylphosphine tetrafluoroborate, bis(2-diphenylphosphinophenyl) ether, and bis(diphenylphosphino) propane.

5. The method for preparing the pesticide fluopyram according to claim 1, wherein: The base includes one or more of potassium carbonate, potassium acetate, and potassium phosphate.

6. The method for preparing the pesticide fluopyram according to claim 1, wherein: The organic solvent includes one or more of N,N-dimethylformamide, N-methylpyrrolidone, and 1,4-dioxane.

7. The method for preparing the pesticide fluopyram according to claim 1, wherein: The molar ratio of the metal palladium catalyst, the ligand, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride, the o-halotrifluorotoluene, and the base is (0.01-0.05):(0.01-0.1):1:(1-1.5):(2-3), and preferably, the molar ratio is 0.02:0.02:1:1.2:2.

5.

8. The method for preparing the pesticide fluopyram according to claim 1, wherein: The ratio of 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride to the organic solvent is 1 g: 5-10 mL; Preferably, the ratio of 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethanamine hydrochloride to the organic solvent is 1 g:8 mL.

9. The method for preparing the pesticide fluopyram according to claim 1, wherein: The elevated pressure is raised to 2-3 MPa, and the reaction temperature is raised to 70-80°C with stirring; and / or, under protective gas, sequentially adding a metal palladium catalyst, a ligand, 2-[3-chloro-5-(trifluoromethane)pyridine-2-methylethylamine hydrochloride, o-halotrifluorotoluene, a base, and an organic solvent into an autoclave, then replacing the gas in the autoclave with carbon monoxide, and subsequently increasing the pressure in the autoclave with carbon monoxide; And / or, the gas in the autoclave was replaced with carbon monoxide three times.

10. The method for preparing the pesticide fluopyram according to claim 1, wherein: The post-processing to obtain the pesticide fluopyram includes filtering to remove insoluble matter, recovering the organic solvent under reduced pressure, and then recrystallizing to obtain the pesticide fluopyram.

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