CN112574190B - Method for synthesizing chlorantraniliprole - Google Patents
Method for synthesizing chlorantraniliprole Download PDFInfo
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- CN112574190B CN112574190B CN202011517104.1A CN202011517104A CN112574190B CN 112574190 B CN112574190 B CN 112574190B CN 202011517104 A CN202011517104 A CN 202011517104A CN 112574190 B CN112574190 B CN 112574190B
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- C07—ORGANIC CHEMISTRY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses a synthesis method of chlorantraniliprole, wherein phosgene is dissolved in a solvent to form a material A, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid are used as raw materials, the raw materials are mixed in the presence of alkali and the solvent, the material A is added into the mixture to react, 2- (3-bromo-1- (3-chloro-2-pyridyl) -1H-5-pyrazolyl) -6-chloro-8-methyl-4H-benzo [ d ] [1,3] oxazine-4-one (oxazinone for short) is obtained, and the oxazine is not purified and directly reacts with monomethylamine to synthesize the chlorantraniliprole. The synthesis method has the advantages of low raw material cost, high reaction activity, simple post-treatment process and no residue; the reaction synthesis condition is mild, the generation of three wastes is less, special equipment is not needed, and the industrial production is easy to realize.
Description
Technical Field
The invention relates to the technical field of synthetic processes of pesticides, and particularly relates to a legal method of chlorantraniliprole.
Background
Chlorantraniliprole (Chlorantraniliprole) is a novel low-toxicity and high-efficiency bisamide insecticide developed by dupont in the united states, and has the trade name: kang Kuan. The compound has a brand-new action mechanism, enables a receptor channel to open abnormally for a long time by activating a ryanodine receptor, leads to unlimited calcium ion release, calcium reservoir failure, muscle paralysis and final death, and has the advantages of good activity, long duration and the like. Chlorantraniliprole has a wide insecticidal spectrum, can be used for various crops, has low toxicity and environmental biosafety, is used as the first insecticide in the world with the sale rate of $ 13.65 hundred million in 2016, and is tamped in the lead army position of the global insecticide by the third insecticide for rice.
At present, key intermediates for synthesizing chlorantraniliprole are mainly as follows: 2-amino-5-chloro-3-methylbenzoic acid having an aromatic ring structure and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid having a pyrazole ring structure.
The synthesis method of chlorantraniliprole which can be found mainly comprises 2 methods; the method comprises the following steps: WO2006062978 is characterized in that 2-amino-5-chloro-3-methylbenzoic acid and phosgene are subjected to cyclization reaction to obtain 6-chloro-8-methyl-1H-benzo [ d ] [1,3] oxazine-2,4-diketone, the 6-chloro-8-methyl-1H-benzo [ d ] [1,3] oxazine-2,4-diketone is subjected to ammonolysis in a methylamine aqueous solution to obtain 2-amino-5-chloro-N, 3-dimethylbenzamide, and then the 2-amino-5-chloro-N, 3-dimethylbenzamide is subjected to reaction with 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid under the action of an amidation reagent methanesulfonyl chloride and acid-binding agent 3-methylpyridine to synthesize the chlorantranilide.
The method 2 comprises the following steps: WO2003015519 reacts 2-amino-5-chloro-3-methylbenzoic acid with 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid under the action of a catalytic reagent methanesulfonyl chloride and an acid-binding agent 3-methylpyridine to generate 2- (3-bromo-1- (3-chloro-2-pyridyl) -1H-5-pyrazolyl) -6-chloro-8-methyl-4H-benzo [ d ] [1,3] oxazine-4-ketone, and finally aminolysis is carried out in a methylamine water solution to synthesize chlorantraniliprole.
In the two synthetic methods, the synthetic steps of the method 1 are one more step than those of the method 2, and the reaction yield is slightly low. In both methods, methanesulfonyl chloride and 3-methylpyridine are used for reaction, the using amount is more than 1 time equivalent, methanesulfonyl chloride is expensive, methanesulfonic acid is generated in the reaction process, atom economy is poor, the treatment process after the reaction is complex, and a large amount of three wastes are generated. Therefore, the method has positive significance for seeking a synthetic route of chlorantraniliprole with strong process feasibility and good economy.
Disclosure of Invention
The invention provides a synthesis method of chlorantraniliprole, which has the advantages of low raw material cost, simple and convenient post-treatment process, mild reaction synthesis conditions and less generation of three wastes.
The technical solution of the invention is as follows:
a synthesis method of chlorantraniliprole comprises the steps of dissolving phosgene in a solvent to form a material A, mixing 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid serving as raw materials in the presence of alkali and the solvent, adding the material A into the mixture to react to obtain 2- (3-bromo-1- (3-chloro-2-pyridyl) -1H-5-pyrazolyl) -6-chloro-8-methyl-4H-benzo [ d ] [1,3] oxazine-4-ketone (oxazinone for short), and directly reacting the oxazine with monomethylamine to synthesize the chlorantraniliprole after the oxazine is not purified.
The method specifically comprises the following steps:
dissolving a compound III in a solvent to form a material A; mixing alkali, a solvent, a compound I and a compound II to form a material B, adding the material A into the material B, and reacting to obtain a chlorantraniliprole precursor (a compound shown in a formula IV); reacting the formula IV with a monomethylamine aqueous solution to synthesize the chlorantraniliprole.
The inventor screens the dropping mode, and finds that the reaction effect obtained by dropping the material A into the material B for mixing reaction is optimal.
The base is an organic base.
The base is selected from one or more of pyridine or picoline, preferably 2-picoline, 3-picoline or 4-picoline.
The solvent is one or more selected from dichloroethane, toluene, xylene, tetrahydrofuran and acetonitrile, preferably acetonitrile.
The reaction temperature of the reaction is-10 to 30 ℃, preferably 0 to 10 ℃, and more preferably 0 to 5 ℃.
The molar ratio of the compound of the formula I to the compound of the formula III is 0.9-2.5: 1, preferably 1 to 2:1, more preferably 1.5:1.
in the process of synthesizing the chlorantraniliprole precursor compound shown in the formula IV, phosgene is used as a ring closing reagent, and the phosgene is decomposed into carbon dioxide in the reaction process and is very easy to discharge out of a reaction system in a gas form; excess phosgene was removed by nitrogen sparging. In the seen patent method for synthesizing chlorantraniliprole, the methanesulfonyl chloride is reacted to generate methanesulfonic acid residue in a post-treated water phase, so that a large amount of acidic wastewater is generated, and the treatment cost of the wastewater is increased; moreover, the molecular weight of the methanesulfonyl chloride is larger than that of phosgene, the market price is several times of that of phosgene, and the methanesulfonyl chloride has no advantage in cost.
The present invention will be further described with reference to the following examples.
Detailed Description
Example 1:
step A Synthesis of 2- (3-bromo-1- (3-chloro-2-pyridinyl) -1H-5-pyrazolyl) -6-chloro-8-methyl-4H-benzo [ d ] [1,3] oxazin-4-one
A condenser tube is arranged in a 100ml three-mouth bottle, 45ml acetonitrile is added, the temperature is reduced to 0 ℃, 10g phosgene is introduced, and the temperature is kept at 0-5 ℃ for standby. Adding 50ml of acetonitrile, 9g of 3-methylpyridine, 15g of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid and 9.2g of 2-amino-5-chloro-3-methylbenzoic acid into a 250ml four-neck flask, cooling to 0 ℃ under stirring, beginning to dropwise add a phosgene acetonitrile solution, controlling the reaction temperature to be 0-5 ℃, keeping the temperature for reaction for 1H at room temperature after 3H dropwise addition is finished to obtain yellow suspension, bubbling for 1H with nitrogen, then carrying out suction filtration to obtain a yellow wet product, and directly using the obtained product for next synthesis after impurity.
Step B, synthesizing chlorantraniliprole
Adding 70ml of acetonitrile, the yellow wet product synthesized in the previous step and 5g of 40% monomethylamine aqueous solution into a 250ml four-mouth bottle, heating to 25-30 ℃ under stirring, reacting for 2 hours, stopping the reaction, carrying out suction filtration, washing with 50ml of water, and drying to obtain 19.5g of a target product, wherein the yield is 81.4% and the purity of liquid chromatography is 96.4%.
Examples 2 to 4:
according to the method of A, B in example 1, the different solvents in step A were changed, 45ml of phosgene was dissolved in each solvent, 50ml of mixed organic base, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid were added in each solvent (same solvent as that for the dissolved phosgene), and the reaction conditions and results are shown in Table 1.
TABLE 1 comparison of reaction conditions and results for examples 2-4
Examples 5 to 7:
the reaction temperature, reaction conditions and results in step A were adjusted as in A, B of example 1 and are shown in Table 2, indicating that the best results are obtained at reaction temperatures between 0 ℃ and 5 ℃ and that chlorantraniliprole is obtained in high yield and purity.
TABLE 2 comparison of reaction conditions and results for examples 5-7
Examples 8 to 10:
the molar ratio of phosgene to 2-amino-5-chloro-3-methylbenzoic acid in step A was adjusted according to the method of A, B in example 1, and the reaction conditions and results are shown in Table 3, and it can be seen that the best results were obtained when the molar ratio of phosgene to 2-amino-5-chloro-3-methylbenzoic acid was 2:1, and that the purity and yield of chlorantraniliprole were the highest.
TABLE 3 comparison of reaction conditions and results for examples 8-10
Examples 11 to 13:
the procedure of A, B in example 1 was followed, with the type of base, reaction conditions and results shown in table 4, and the inorganic base was found to be the least effective, preferably 3-picoline followed by pyridine.
TABLE 4 comparison of reaction conditions and results for examples 11-13
Although the embodiments of the present invention have been described, the present invention is not limited to the foregoing specific embodiments. The invention extends to any novel feature or any novel combination of features disclosed in this specification and any novel method or process steps or any novel combination of features disclosed.
Claims (6)
1. A method for synthesizing a chlorantraniliprole precursor is characterized by comprising the following steps: the method comprises the following steps:
dissolving a compound III in a solvent to form a material A; mixing alkali, a solvent, a compound I and a compound II to form a material B; adding the material A into the material B, and mixing and reacting to obtain the compound shown in the formula IV.
2. The method for synthesizing the chlorantraniliprole precursor as claimed in claim 1, wherein the method comprises the following steps: the base is an organic base.
3. The method for synthesizing the chlorantraniliprole precursor as claimed in claim 2, wherein the method comprises the following steps: the organic base is 3-methylpyridine.
4. The method for synthesizing a chlorantraniliprole precursor according to any one of claims 1 to 3, wherein the method comprises the following steps: the solvent is selected from one or more of dichloroethane, toluene, xylene, tetrahydrofuran and acetonitrile.
5. The method for synthesizing the chlorantraniliprole precursor according to any one of claims 1 to 3, which is characterized in that: the reaction temperature of the reaction is-10 to 30 ℃.
6. The method for synthesizing a chlorantraniliprole precursor according to any one of claims 1 to 3, wherein the method comprises the following steps: the molar ratio of the compound III to the compound I is 0.9-2.5: 1.
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| CN114874185A (en) * | 2022-03-18 | 2022-08-09 | 青岛恒宁生物科技有限公司 | Method for preparing o-formamido benzamide compound |
| CN115057843B (en) * | 2022-06-15 | 2024-04-30 | 湖南化工研究院有限公司 | Preparation method of chlorantraniliprole insecticide |
| CN115745959B (en) * | 2022-11-30 | 2024-06-21 | 山东友道化学有限公司 | Industrial production method of chlorantraniliprole |
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| AR036872A1 (en) * | 2001-08-13 | 2004-10-13 | Du Pont | ANTRANILAMIDE COMPOSITE, COMPOSITION THAT INCLUDES IT AND METHOD FOR CONTROLLING AN INVERTEBRATE PEST |
| TWI363756B (en) * | 2004-12-07 | 2012-05-11 | Du Pont | Method for preparing n-phenylpyrazole-1-carboxamides |
| CN107089970B (en) * | 2017-05-26 | 2020-06-16 | 迈克斯(如东)化工有限公司 | Method for preparing N-acyl anthranilamide |
| CN111662269B (en) * | 2019-03-07 | 2021-05-07 | 湖南化工研究院有限公司 | 1-pyridyl pyrazole amide compound and preparation method and application thereof |
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