A kind of preparation method of chlorantraniliprole

Abstract

The invention provides a preparation method of chlorantraniliprole, which comprises the following steps: reacting 3-chloro-2-(3,5-dibromo-1H-pyrazole-1-yl)pyridine, 2-amino-5-chloro-N,3-dimethylbenzamide and CO in the presence of a palladium catalyst to obtain the chlorantraniliprole. The preparation method has the advantages of high reaction yield, simple and easy-to-obtain raw materials, low cost, convenient operation and environmental friendliness, and the preparation method of the invention is more suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of insecticide synthesis, and in particular to a method for preparing chlorantraniliprole. Background Art

[0002] Chlorantraniliprole is a new generation of highly effective and low-toxic insecticide. It exhibits insecticidal effects by inducing insect nicotinic acid receptors to regulate the release of intracellular calcium ions. It is particularly effective against lepidopteran pests, has low toxicity to fish, bees, aquatic organisms and mammals, and is very environmentally friendly. Chlorantraniliprole is used to control lepidopteran pests on rice, fruits and vegetables.

[0003] There are many methods for preparing chlorantraniliprole. For example, DuPont's patent US9173400 discloses that 2,3-dichloropyridine is used as a raw material, and the key intermediate 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid is generated through hydrazine formation, cyclization, bromination, oxidation and hydrolysis, and then reacts with 2-amino-3-methyl-5-chlorobenzoic acid under the conditions of methanesulfonyl chloride and triethylamine to generate 2-[3-bromo-1-(3-chloro-2-pyridyl)- 1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-one, and finally generate chlorantraniliprole under the action of methylamine; DuPont also announced in patent WO2006062978 that the key intermediate 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid and 2-amino-5-chloro-N,3-dimethylbenzamide generate chlorantraniliprole under the action of methanesulfonyl chloride and 3-methylpyridine. Both of the above routes require the use of highly toxic controlled substance methanesulfonyl chloride, and the overall route is lengthy, the operation is cumbersome, and there are many three wastes.

[0004] Patent US20100317864 improves the DuPont patent by first converting the key intermediate 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid into an acid chloride, which is then condensed with 2-amino-5-chloro-N,3-dimethylbenzamide to produce chlorantraniliprole. Although the improved route avoids the use of the highly toxic controlled substance methanesulfonyl chloride, it prolongs the reaction steps and reduces the overall yield.

[0005] In summary, the development of a high-yield, low-cost, simple, safe and environmentally friendly preparation method is of great significance for the industrial production of chlorantraniliprole. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing chlorantraniliprole with high yield, low cost, simple and safe operation and environmental friendliness.

[0007] In order to solve the above problems, the present invention adopts the following technical solutions:

[0008] The invention provides a method for preparing chlorantraniliprole. The method comprises the steps of reacting 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine, 2-amino-5-chloro-N,3-dimethylbenzamide and CO in the presence of a palladium catalyst to obtain the chlorantraniliprole.

[0009] Preferably, the molar ratio of the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine to the 2-amino-5-chloro-N,3-dimethylbenzamide is 1:(1-1.2), for example, 1:1.02, 1:1.05, 1:1.08, 1:1.12, 1:1.16, 1:1.8, etc.

[0010] More preferably, the molar ratio of the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine to the 2-amino-5-chloro-N,3-dimethylbenzamide is 1:(1-1.1).

[0011] Preferably, the palladium catalyst is selected from palladium-containing compounds having a palladium oxidation state of 0 and / or palladium-containing compounds having a palladium oxidation state of 2.

[0012] Preferably, the palladium-containing compound with a palladium oxidation state of 0 is selected from one or more of tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, di(tri-tert-butylphosphine)palladium and metallic palladium supported on an inert carrier; the palladium compound with a palladium oxidation state of 2 is selected from one or more of palladium chloride, palladium acetate, bis(acetonitrile)palladium dichloride, bis(triphenylphosphine)palladium chloride, bis(tricyclohexylphosphine)palladium dichloride, bis(methyldiphenylphosphine)palladium dichloride and benzylbis(triphenylphosphine)palladium chloride.

[0013] Further preferably, the inert carrier is selected from one or more of activated carbon, alumina, barium sulfate or barium carbonate.

[0014] According to a specific and preferred embodiment, the palladium-containing compound having a palladium oxidation state of 0 is selected from one or more of tris(dibenzylideneacetone)dipalladium, di(tri-tert-butylphosphine)palladium, and tetrakis(triphenylphosphine)palladium.

[0015] According to another specific and preferred embodiment, the palladium compound with a palladium oxidation state of 2 is selected from palladium chloride and / or palladium acetate.

[0016] Preferably, the molar ratio of the palladium catalyst to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.002):1, for example, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.001:1, 0.0015:1, etc.

[0017] Further preferably, the molar ratio of the palladium catalyst to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.001):1.

[0018] Preferably, the palladium catalyst cooperates with a ligand to participate in the reaction, and the ligand is selected from one or more of triphenylphosphine, 1,3-bis(diisopropylphosphino)propane, 1,3-bis(diphenylphosphino)propane, 1,3-bis(diphenylphosphino)butane, 1,3-bis(dicyclohexylphosphino)propane, 2,2-dimethyl-1,3-bis(diphenylphosphino)propane and 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, and the molar ratio of the ligand to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.002):1.

[0019] Further preferably, the ligand is selected from one or more of 1,3-bis(diphenylphosphino)propane, triphenylphosphine, 1,3-bis(diisopropylphosphino)propane, 1,3-bis(diphenylphosphino)propane, and 1,3-bis(dicyclohexylphosphino)propane.

[0020] Further preferably, the molar ratio of the ligand to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.001):1, for example, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, etc.

[0021] More preferably, the molar ratio of the ligand to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.0008):1.

[0022] Preferably, the reaction is carried out in the presence of a base, the base is selected from one or more of potassium carbonate, sodium carbonate, sodium acetate, triethylamine, pyridine, 3-methylpyridine, 3,5-lutidine and potassium bicarbonate, and the molar ratio of the base to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (1-2):1.

[0023] Further preferably, the base is selected from one or more of potassium carbonate, sodium acetate, triethylamine and pyridine.

[0024] Further preferably, the molar ratio of the base to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (1-1.5):1, for example, 1.1:1, 1.2:1, 1.3:1, 1.4:1, etc.

[0025] Preferably, the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine and the 2-amino-5-chloro-N,3-dimethylbenzamide are reacted in the presence of a solvent, and the solvent is selected from one or more of N,N-dimethylformamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dichloroethane, toluene, N-methylpyrrolidone and chlorobenzene.

[0026] Further preferably, the solvent is selected from one or more of tetrahydrofuran, ethylene dichloride, toluene and acetonitrile.

[0027] Preferably, the CO pressure is controlled to be 0.5-20 bar, for example, 1 bar, 2 bar, 3 bar, 4 bar, 6 bar, 8 bar, 12 bar, 16 bar, 18 bar, etc.

[0028] Further preferably, the CO pressure is controlled to be 2-4 bar.

[0029] Preferably, the reaction temperature is 90-150°C, for example, 100°C, 110°C, 120°C, 130°C, 140°C, etc.

[0030] More preferably, the reaction temperature is 100-120°C.

[0031] Preferably, the reaction time is 10 to 15 hours, such as 11 hours, 12 hours, 13 hours, 14 hours, etc.

[0032] More preferably, the reaction time is 10 to 12 hours.

[0033] Preferably, the specific steps of the preparation method are: under N2 atmosphere, in an autoclave, the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine, the 2-amino-5-chloro-N,3-dimethylbenzamide, the palladium catalyst, the ligand, the base and the solvent are mixed, stirred and mixed, replaced with N2 3 times and then replaced with CO 3 times, heated to react, and filtered after the reaction to obtain the chlorantraniliprole.

[0034] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0035] The preparation method of the present invention provides a new idea for the synthesis of chlorantraniliprole, and the preparation method has the advantages of high yield, simple and easy to obtain raw materials, significantly reduced cost, green and environmentally friendly reagents, simple and safe operation, simple post-processing, etc. The preparation method provided by the present invention is more suitable for industrial production. DETAILED DESCRIPTION

[0036] The present invention is further described in detail below in conjunction with specific examples. It should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited by the following examples. The implementation conditions adopted in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in routine experiments.

[0037] The present invention is to react 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 2-amino-5-chloro-N,3-dimethylbenzamide (K2) and CO in the presence of a palladium catalyst to obtain chlorantraniliprole (KK). Specifically, under the protection of N2, 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 2-amino-5-chloro-N,3-dimethylbenzamide (K2), a palladium catalyst, a ligand, a base and a solvent are mixed, after mixing, the reaction system is replaced by N2 and then replaced by CO, the temperature is raised for reaction, and after the reaction is completed, chlorantraniliprole is obtained by filtering.

[0038] The preparation route of the present invention is as follows:

[0039]

[0040] Through the above-mentioned preparation method, the yield of chlorantraniliprole is improved, and the reaction raw materials of the present application are simple and easy to obtain, and the cost is greatly reduced. At the same time, it also has the advantages of simple operation, simple post-treatment and environmental friendliness, and is suitable for industrial production, overcoming the problems of the prior art such as cumbersome operation, complex post-treatment, low reaction yield, high cost and many wastes.

[0041] The solution of this application is further discussed below.

[0042] Example 1

[0043] Preparation of Chlorantraniliprole (KK)

[0044] Under N2 protection, 10 g (29.6 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 6.5 g (32.7 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 13.6 mg (0.0148 mmol) of tri(dibenzylideneacetone)dipalladium, 3.9 mg (0.0148 mmol) of triphenylphosphine, 4.9 g (35.5 mmol) of potassium carbonate and 30 g of tetrahydrofuran were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 5 bar, and then the temperature was raised to 130°C for reaction for 13 h. After the reaction was completed, the temperature was cooled to room temperature and chlorantraniliprole was obtained by filtration. The crude product was then slurried with water, filtered and dried to obtain 13.8 g of chlorantraniliprole with a yield of 96.5%.

[0045] Example 2

[0046] Preparation of Chlorantraniliprole (KK)

[0047] Under N2 protection, 30 g (88.9 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 21.0 g (105.7 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 9.1 mg (0.0178 mmol) of di(tri-tert-butylphosphine)palladium, 4.9 mg (0.0178 mmol) of 1,3-bis(diisopropylphosphonyl)propane, 8 g (97.7 mmol) of sodium acetate and 75 g of acetonitrile were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 10 bar, and then the temperature was raised to 120°C for reaction for 15 h. After the reaction was completed, the temperature was lowered to room temperature and chlorantraniliprole crude product was obtained by filtration. The crude product was then slurried with water, filtered and dried to obtain 41.5 g of chlorantraniliprole with a yield of 96.7%.

[0048] Example 3

[0049] Preparation of Chlorantraniliprole (KK)

[0050] Under N2 protection, 50 g (148.2 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 30.9 g (155.6 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 17.1 mg (0.0148 mmol) of tetrakis(triphenylphosphine)palladium, 6.1 mg (0.0148 mmol) of 1,3-bis(diphenylphosphino)propane, 15 g (148.2 mmol) of triethylamine and 100 g of toluene were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 4 bar, and then the temperature was raised to 100°C for reaction for 12 h. After the reaction was completed, the temperature was lowered to room temperature, and 70.7 g of chlorantraniliprole was obtained by filtration and drying with a yield of 98.7%.

[0051] Example 4

[0052] Preparation of Chlorantraniliprole (KK)

[0053] Under N2 protection, 60 g (177.8 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 37 g (186.3 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 3.1 mg (0.0178 mmol) of palladium chloride, 7.3 mg (0.0178 mmol) of 1,3-bis(diphenylphosphino)propane, 18 g (177.8 mmol) of triethylamine and 180 g of toluene were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 2 bar, and then the temperature was raised to 120°C for reaction for 10 h. After the reaction was completed, the temperature was lowered to room temperature, and 84.6 g of chlorantraniliprole was obtained by filtration and drying. The yield was 98.5%.

[0054] Example 5

[0055] Preparation of Chlorantraniliprole (KK)

[0056] Under N2 protection, 100 g (296 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 65 g (327 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 19.9 mg (0.0888 mmol) of palladium acetate, 38.8 mg (0.0888 mmol) of 1,3-bis(dicyclohexylphosphino)propane, 24.6 g (310.8 mmol) of pyridine and 200 g of dichloroethane were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 4 bar, and then the temperature was raised to 150°C for reaction for 11 h. After the reaction was completed, the temperature was lowered to room temperature and filtrated to obtain crude chlorantraniliprole. The crude product was then slurried with water, filtered and dried to obtain 137.4 g of chlorantraniliprole with a yield of 96.1%.

[0057] Example 6

[0058] Preparation of Chlorantraniliprole (KK)

[0059] Under N2 protection, 40 g (118.6 mmol) of 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 28.2 g (142.0 mmol) of 2-amino-5-chloro-N,3-dimethylbenzamide (K2), 179.8 mg (0.237 mmol) of benzylbis(triphenylphosphine)palladium chloride, 97.3 mg (0.237 mmol) of 2-dicyclohexylphosphine-2,6-dimethoxybiphenyl, 23.7 g (237.2 mmol) of potassium bicarbonate and 80 g of chlorobenzene were added to the autoclave, and stirring was started. The system was replaced with N2 three times and then with CO three times. The CO pressure was controlled at 20 bar, and then the temperature was raised to 150°C for reaction for 15 h. After the reaction was completed, the temperature was lowered to room temperature and chlorantraniliprole crude product was obtained by filtration. The crude product was then slurried with water, filtered and dried to obtain 47.0 g of chlorantraniliprole with a yield of 82.0%.

[0060] As can be seen from the above examples, the reaction yield of chlorantraniliprole obtained by the preparation method of the present invention is high, and the yield reaches more than 82%, especially, using the technical scheme of the embodiment 3 or embodiment 4 of the present invention, the obtained product reaction yield is more than 98%, and the reaction yield has been significantly improved. The preparation method provided by the present invention, by using 3-chloro-2-(3,5-dibromo-1H-pyrazole-1-yl)pyridine, 2-amino-5-chloro-N,3-dimethylbenzamide and CO as raw materials to prepare chlorantraniliprole, improves the reaction yield, the raw material is simple and easy to obtain, the cost is low, the operation is convenient, and the post-processing is simple and environmentally friendly. Therefore, the preparation method of the present invention is more suitable for industrial production.

[0061] The above detailed description of the present invention is intended to enable persons familiar with the art to understand the contents of the present invention and implement them. It does not limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing chlorantraniliprole, characterized in that: Under N2 atmosphere, 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine, 2-amino-5-chloro-N,3-dimethylbenzamide, a palladium catalyst, a ligand, a base and a solvent are mixed in an autoclave, stirred and mixed, replaced with N2 three times and then replaced with CO three times, heated to react, and filtered after the reaction to obtain the chlorantraniliprole. The palladium catalyst is tetrakis(triphenylphosphine)palladium or palladium chloride, the ligand is 1,3-bis(diphenylphosphino)propane, the solvent is toluene, the CO pressure is 2-4 bar, the reaction temperature is 100-120° C., The molar ratio of the palladium catalyst to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.002): 1, The feeding molar ratio of the ligand to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (0.0001-0.002):

1.

2. The preparation method according to claim 1, characterized in that: The feeding molar ratio of the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine to the 2-amino-5-chloro-N,3-dimethylbenzamide is 1:(1-1.2).

3. The preparation method according to claim 1, characterized in that: The molar ratio of the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine to the 2-amino-5-chloro-N,3-dimethylbenzamide is 1:(1-1.1).

4. The preparation method according to claim 1, characterized in that: The reaction is carried out in the presence of a base, the base is selected from one or more of potassium carbonate, sodium carbonate, sodium acetate, triethylamine, pyridine, 3-methylpyridine, 3,5-lutidine and potassium bicarbonate, and the molar ratio of the base to the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine is (1-2):

1.

5. The preparation method according to claim 1, characterized in that: The reaction time is 10 to 15 hours.

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