CN116535388A - Preparation method of chlorantraniliprole - Google Patents

Abstract

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

Description

A kind of preparation method of chlorantraniliprole

technical field

The invention relates to the field of insecticide synthesis, in particular to a preparation method of chlorantraniliprole.

Background technique

Chlorantraniliprole is a new generation of new, high-efficiency, and low-toxicity insecticide. It exhibits insecticidal effect by inducing insect ryanodine receptors to regulate the release of intracellular calcium ions. It has special effects on Lepidoptera pests and is effective on fish , bees, aquatic organisms and mammals have low toxicity and are very friendly to the environment. Chlorantraniliprole for Lepidoptera pest control on rice, fruits and vegetables.

There are many preparation methods of chlorantraniliprole, such as DuPont disclosed in patent US9173400 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, and 2-amino-3-methyl-5-chlorobenzoic acid under the conditions of methanesulfonyl chloride and triethylamine Generate 2-[3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine -4-ketone, and finally generate chlorantraniliprole under the action of methylamine; DuPont announced the key intermediate 3-bromo-1-(3-chloro-2-pyridyl)-1H pyrazole in patent WO2006062978 Chlorantraniliprole was produced from 5-formic acid and 2-amino-5-chloro-N,3-dimethylbenzamide under the action of methanesulfonyl chloride and 3-picoline. Both of the above two routes need to use methanesulfonyl chloride, a highly toxic control product, and the overall route is lengthy, cumbersome to operate, and there are many three wastes.

Patent US20100317864 has improved the DuPont patent. First, the key intermediate 3-bromo-1-(3-chloro-2-pyridyl)-1H pyrazole-5-carboxylic acid is made into acid chloride, and then combined with 2-amino-5-chloro -N,3-Dimethylbenzamide is condensed to generate chlorantraniliprole. Although the improved route avoids the use of highly toxic control product methanesulfonyl chloride, the reaction steps are prolonged and the overall yield is reduced.

In summary, it is of great significance for the industrial production of chlorantraniliprole to develop a high-yield, low-cost, easy-to-operate, safe and environmentally friendly preparation method.

Contents of the invention

The purpose of the present invention is to provide a method for preparing chlorantraniliprole with high yield, low cost, simple and safe operation, and environment-friendly.

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

The invention provides a preparation method of chlorantraniliprole, which comprises 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine, 2-amino-5-chloro-N, 3-Dimethylbenzamide and CO are reacted in the presence of a palladium catalyst to obtain the chlorantraniliprole.

Preferably, the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine and the 2-amino-5-chloro-N,3-dimethylbenzamide The molar ratio of feed is 1:(1~1.2), such as 1:1.02, 1:1.05, 1:1.08, 1:1.12, 1:1.16, 1:1.8, etc.

Further preferably, the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine and the 2-amino-5-chloro-N,3-dimethylbenzyl The feed molar ratio of amides is 1:(1~1.1).

Preferably, the palladium catalyst is selected from palladium-containing compounds with palladium oxidation state 0 and/or palladium-containing compounds with palladium oxidation state 2.

Preferably, the palladium-containing compound whose palladium oxidation state is 0 is selected from tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, bis(tri-tert-butylphosphine)palladium and supported on an inert carrier One or more of the metal palladium on the palladium; said palladium oxidation state is 2 palladium compounds selected from palladium chloride, palladium acetate, bis (acetonitrile) palladium dichloride, bis (triphenylphosphine) palladium chloride , one or more of bis(tricyclohexylphosphine)palladium dichloride, bis(methyldiphenylphosphine)palladium dichloride and benzylbis(triphenylphosphine)palladium chloride.

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

According to a specific and preferred embodiment, the palladium-containing compound whose palladium oxidation state is 0 is selected from tris(dibenzylideneacetone)dipalladium, bis(tri-tert-butylphosphine)palladium, tetrakis(triphenylphosphine) ) One or more of palladium.

According to another specific and preferred embodiment, the palladium compound whose palladium oxidation state is 2 is selected from palladium chloride and/or palladium acetate.

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.

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.

Preferably, the palladium catalyst is coordinated with a ligand to participate in the reaction, and the ligand is selected from triphenylphosphine, 1,3-bis(diisopropylphosphono)propane, 1,3-bis(diisopropylphosphono)propane, Phenylphosphino)propane, 1,3-bis(diphenylphosphino)butane, 1,3-bis(dicyclohexylphosphino)propane, 2,2-dimethyl-1,3-bis( One or more of diphenylphosphino)propane and 2-bicyclohexylphosphine-2,6-dimethoxybiphenyl, the ligand and the 3-chloro-2-(3,5- The feeding molar ratio of dibromo-1H-pyrazol-1-yl)pyridine is (0.0001～0.002):1.

Further preferably, the ligand is selected from 1,3-bis(diphenylphosphino)propane, triphenylphosphine, 1,3-bis(diisopropylphosphono)propane, 1,3-bis( One or more of diphenylphosphino)propane and 1,3-bis(dicyclohexylphosphino)propane.

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.

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

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

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

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.

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

Further preferably, the solvent is selected from one or more of tetrahydrofuran, dichloroethane, toluene and acetonitrile.

Preferably, the CO pressure is controlled to be 0.5-20 bar, such as 1 bar, 2 bar, 3 bar, 4 bar, 6 bar, 8 bar, 12 bar, 16 bar, 18 bar and so on.

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

Preferably, the reaction temperature is 90-150°C, such as 100°C, 110°C, 120°C, 130°C, 140°C, etc.

Further preferably, the reaction temperature is 100-120°C.

Preferably, the duration of the reaction is 10-15 hours, such as 11 hours, 12 hours, 13 hours, 14 hours, etc.

Further preferably, the duration of the reaction is 10-12 hours.

Preferably, the specific steps of the preparation method are: under _N2 atmosphere, the 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine, the The 2-amino-5-chloro-N,3-dimethylbenzamide, the palladium catalyst, the ligand, the base, and the solvent are mixed, stirred and mixed, and replaced by N for ₃ times and then replaced with CO for 3 times. Heating the reaction, and filtering to obtain the chlorantraniliprole after the reaction.

Due to the use of the above-mentioned technical solutions, the present invention has the following advantages compared with the prior art:

The preparation method described in the present invention provides a new idea for the synthesis of chlorantraniliprole. The preparation method has the advantages of high yield, simple and easy-to-obtain raw materials, significantly reduced cost, environmentally friendly reagents, simple and safe operation and post-treatment Simple and other advantages, the preparation method provided by the invention is more suitable for industrial production.

Detailed ways

The present invention will be described in further 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 used in the examples can be further adjusted according to specific requirements, and the unspecified implementation conditions are usually the conditions in routine experiments.

The present invention is to make 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 2-amino-5-chloro-N,3-dimethylbenzamide (K2) and CO react 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), palladium catalyst, ligand, base and solvent are mixed, after mixing, the reaction system is replaced by CO after _N2 replacement, the temperature rises for reaction, and after the reaction is completed, it is filtered to obtain chlorantraniliprole.

The preparation route of the present invention is as follows:

Through the above 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-processing and environmental friendliness, and is suitable for industrialization. Production overcomes the problems of cumbersome operation, complicated post-treatment, low reaction yield, high cost and many wastes in the prior art.

The scheme of the present application is further discussed below.

Example 1

Preparation of Chlorantraniliprole (KK)

Add 10g ( _29.6mmol ) 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 6.5g (32.7mmol) 2-amino -5-chloro-N,3-dimethylbenzamide (K2), 13.6mg (0.0148mmol) three (dibenzylideneacetone) dipalladium, 3.9mg (0.0148mmol) triphenylphosphine, 4.9g ( 35.5mmol) of potassium carbonate and 30g of tetrahydrofuran, start stirring, replace the system with _N2 three times and then replace it with CO three times, control the pressure of CO at 5bar, then raise the temperature to 130°C for 13h, cool down to room temperature after the reaction, and filter to obtain chlorine The crude product of chlorantraniliprole was beaten with water, filtered and dried to obtain 13.8 g of chlorantraniliprole, with a yield of 96.5%.

Example 2

Preparation of Chlorantraniliprole (KK)

Add 30g ( _88.9mmol ) 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 21.0g (105.7mmol) 2-amino -5-Chloro-N,3-dimethylbenzamide (K2), 9.1mg (0.0178mmol) bis(tri-tert-butylphosphine) palladium, 4.9mg (0.0178mmol) 1,3-bis(diisopropyl Phosphono)propane, 8g (97.7mmol) sodium acetate and 75g acetonitrile, start stirring, replace the system with N ₂ three times and then replace it with CO three times, control the CO pressure at 10bar, then raise the temperature to 120°C for 15h, and the reaction is over After cooling down to room temperature, the crude product of chlorantraniliprole was obtained by filtration, and the crude product was beaten with water, filtered and dried to obtain 41.5 g of chlorantraniliprole with a yield of 96.7%.

Example 3

Preparation of Chlorantraniliprole (KK)

Add 50g ( _148.2mmol ) 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 30.9g (155.6mmol) 2-amino -5-Chloro-N,3-dimethylbenzamide (K2), 17.1mg (0.0148mmol) tetrakis(triphenylphosphine) palladium, 6.1mg (0.0148mmol) 1,3-bis(diphenylphosphine) Base) propane, 15g (148.2mmol) triethylamine and 100g toluene, start stirring, replace the system with N ₂ three times and then replace it with CO three times, control the CO pressure at 4bar, then raise the temperature to 100°C for 12h, after the reaction Cool down to room temperature, filter and dry to obtain 70.7 g of chlorantraniliprole, with a yield of 98.7%.

Example 4

Preparation of Chlorantraniliprole (KK)

Add 60g ( _177.8mmol ) 3-chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 37g (186.3mmol) 2-amino- 5-chloro-N,3-dimethylbenzamide (K2), 3.1mg (0.0178mmol) palladium chloride, 7.3mg (0.0178mmol) 1,3-bis(diphenylphosphino)propane, 18g ( 177.8mmol) of triethylamine and 180g of toluene, start stirring, replace the system with N ₂ three times and then replace it with CO three times, control the pressure of CO at 2bar, then raise the temperature to 120°C for 10h, cool down to room temperature after the reaction, filter and dry 84.6 g of chlorantraniliprole was obtained by drying, and the yield was 98.5%.

Example 5

Preparation of Chlorantraniliprole (KK)

Add 100g (296mmol) ₃ -chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 65g (327mmol) 2-amino-5- Chloro-N,3-dimethylbenzamide (K2), 19.9mg (0.0888mmol) palladium acetate, 38.8mg (0.0888mmol) 1,3-bis(dicyclohexylphosphino)propane, 24.6g (310.8mmol ) pyridine and 200g dichloroethane, start stirring, replace the system with _N2 for three times and then replace it with CO three times, control the pressure of CO at 4bar, then raise the temperature to 150°C for 11h, cool down to room temperature after the reaction, and filter to obtain chlorine Chlorantraniliprole was crude product, and the crude product was beaten with water, filtered and dried to obtain 137.4 g of chlorantraniliprole, with a yield of 96.1%.

Example 6

Preparation of Chlorantraniliprole (KK)

Add 40g (118.6mmol) ₃ -chloro-2-(3,5-dibromo-1H-pyrazol-1-yl)pyridine (K1), 28.2g (142.0mmol) 2-amino -5-Chloro-N,3-dimethylbenzamide (K2), 179.8mg (0.237mmol) benzyl bis(triphenylphosphine) palladium chloride, 97.3mg (0.237mmol) 2-bicyclohexylphosphine- 2,6-dimethoxybiphenyl, 23.7g (237.2mmol) potassium bicarbonate and 80g chlorobenzene, start stirring, replace the system with _N2 three times and then replace it with CO three times, control the pressure of CO at 20bar, and then raise the temperature React at 150°C for 15 hours, cool down to room temperature after the reaction, and filter to obtain the crude chlorantraniliprole, which is then beaten with water, filtered and dried to obtain 47.0 g of chlorantraniliprole, with a yield of 82.0%.

It can be seen from the above examples that the reaction yield of chlorantraniliprole prepared by the preparation method of the present invention is high, and the yield reaches more than 82%. In particular, the technical solution of Example 3 or Example 4 of the present invention is adopted, so The reaction yield of the obtained product 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-pyrazol-1-yl)pyridine, 2-amino-5-chloro-N,3-dimethylbenzene Formamide and CO are used as raw materials to prepare chlorantraniliprole, which improves the reaction yield. The raw materials are simple and easy to obtain, low in cost, convenient in operation, simple in post-treatment and environmentally friendly. Therefore, the preparation method of the present invention is more suitable for industrial production.

The present invention has been described in detail above, and its purpose is to allow those familiar with this field to understand the content of the present invention and implement it, and can not limit the protection scope of the present invention with this. Effect changes or modifications should be covered within the protection scope of the present invention.

Claims (10)

1. A preparation method of chlorantraniliprole is characterized in that 3-chloro-2- (3, 5-dibromo-1H-pyrazol-1-yl) pyridine, 2-amino-5-chloro-N, 3-dimethylbenzamide and CO are reacted in the presence of a palladium catalyst to obtain the chlorantraniliprole.

2. The preparation method according to claim 1, wherein 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).

3. The preparation method according to claim 1, wherein 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 method of claim 1, wherein 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; and/or the feeding mole ratio of the palladium catalyst to the 3-chloro-2- (3, 5-dibromo-1H-pyrazol-1-yl) pyridine is (0.0001-0.002): 1.

5. the method of claim 4, wherein the palladium-containing compound having a palladium oxidation state of 0 is selected from one or more of tetrakis (triphenylphosphine) palladium, tris (dibenzylideneacetone) dipalladium, bis (tri-t-butylphosphine) palladium, and metallic palladium supported on an inert carrier; the palladium compound with the 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 (methyl diphenylphosphine) palladium dichloride and benzyl bis (triphenylphosphine) palladium chloride.

6. The production method according to claim 1, wherein the palladium catalyst participates in the reaction in cooperation with a ligand selected from one or more of triphenylphosphine, 1, 3-bis (diisopropylphosphino) propane, 1, 3-bis (diphenylphosphino) butane, 1, 3-bis (dicyclohexylphosphino) propane, 2-dimethyl-1, 3-bis (diphenylphosphino) propane and 2-dicyclohexylphosphine-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 to 0.002): 1.

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

8. the production method according to claim 1, wherein 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 selected from one or more of N, N-dimethylformamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetonitrile, dichloroethane, toluene, N-methylpyrrolidone and chlorobenzene.

9. The method according to claim 1, wherein the CO pressure is controlled to be 0.5 to 20bar; and/or, the temperature of the reaction is 90-150 ℃; and/or the duration of the reaction is 10-15 h.

10. The preparation method according to any one of claims 1 to 9, characterized in that the specific steps of the preparation method are: n (N) ₂ The 3-chloro-2- (3, 5-dibromo-1H-pyrazol-1-yl) pyridine, the 2-amino-5-chloro-N, 3-dimethylbenzamide, and the palladium catalyst are reacted in an autoclave under an atmosphereMixing the ligand, alkali and solvent, stirring, and passing through N ₂ 3 times of replacement, 3 times of replacement by the CO, heating reaction, and filtering after the reaction is finished to obtain the chlorantraniliprole.