Method for converting diacylation byproduct of fluxapyroxad into monoacylation product

Abstract

The invention discloses a method for converting a diacylation byproduct of fluxapyroxad into a monoacylation product, and belongs to the field of pesticides and intermediates. According to the method, the fluxapyroxad in the crystallization mother liquor can be effectively recovered, and a diacylation byproduct which is difficult to avoid in the synthesis process is converted into a monoacylation product. The polarity of a diacylation byproduct is close to that of fluxapyroxad, and the diacylation byproduct is difficult to remove through a conventional recrystallization method; the method comprises the following steps: dissolving the diacylation byproduct-containing fluxapyroxad crystallization mother liquor kettle residue into an organic solvent, quantitatively introducing alkali, converting the diacylation byproduct into monoacylation fluxapyroxad, and concentrating, recrystallizing and purifying the reaction liquid to obtain the monoacylation product. According to the method, the diacylation byproduct is converted into the target product, meanwhile, another byproduct with high polarity is generated, separation is very easy through recrystallization, the high-purity target product is obtained, the technological operation is simple, the condition is mild, the separation yield is high, and the method has important significance for reducing three wastes, lowering the cost and improving the product quality.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide intermediate synthesis in fine chemical industry and is a method for converting diacylated by-products into fluopyraclostrobin. Background Art

[0002] Fluxapyroxad (trade name Xemium) is a SDHI fungicide launched by BASF in 2012. It has both preventive and therapeutic effects and excellent systemic activity. In 2015, it successfully surpassed its own developed boscalid to become the largest product in the SDHI fungicide category. Currently, the global sales of fluxapyroxad are close to US$500 million, making it the second largest fungicide of BASF, second only to pyraclostrobin, and the market prospects are very broad.

[0003] The existing literature reports that the mainstream synthesis method of fluopyrabamide is to prepare it by the amidation reaction of difluoromethylpyrazole carboxylic acid and its derivatives with trifluorobenzidine. This synthesis method will inevitably produce diacylated by-products while synthesizing fluopyrabamide. Its chemical structure is This results in lower reaction yields, difficulty in separation and purification, and increased industrial production costs and operational difficulty. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a method for converting the diacylated by-product of fluopyrabamide into a monoacylated product. The method introduces alkali into the fluopyrabamide crystal residue containing the diacylated by-product to promote the dissociation of the diacylated by-product into the fluopyrabamide target product, and obtains the pure fluopyrabamide through concentration and recrystallization separation.

[0005] The method of converting the diacylated byproduct of fluopyraclostrobin into a monoacylated product according to the present invention has a reaction principle represented by the following reaction equation:

[0006] A: When an inorganic base is introduced, the reaction equation is expressed as:

[0007]

[0008] B: When an organic base is introduced, the reaction equation is expressed as:

[0009]

[0010] The technical scheme of the present invention is as follows: the still residue of the mother liquor of the fluopyrabamide crystallization containing the diacylated by-product is dissolved in an organic solvent, a dissociation reaction is carried out in the presence of an alkali, and the reaction liquid is concentrated, dissolved by switching the solvent, crystallized by cooling, filtered, and washed to obtain a pure fluopyrabamide product.

[0011] Preferably, in this step, the organic solvent is selected from one or more of aromatic hydrocarbons, aliphatic hydrocarbons or alcohols.

[0012] Preferably, in this step, the aromatic hydrocarbon is selected from toluene, xylene or chlorobenzene; the aliphatic hydrocarbon is selected from heptane, dichloromethane or dichloroethane; and the alcohol is selected from methanol, ethanol or isopropanol.

[0013] Preferably, in this step, the base is selected from an inorganic base solution or an organic base.

[0014] Preferably, in this step, the concentration of the inorganic alkali solution is 1-20% dilute alkali, and the amount used is 1.0-1.5eq of the diacylated by-product substrate; the amount of the organic alkali used is 1.0-1.5eq of the diacylated by-product substrate.

[0015] Preferably, in this step, the inorganic base solution is selected from sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution or potassium carbonate solution; and the organic base is selected from aliphatic or aromatic amines.

[0016] Preferably, in this step, the organic base is selected from n-butylamine, n-octylamine, benzylamine, liquid ammonia, diethylamine, piperidine, aniline, o-methylaniline, p-phenylenediamine or N-methylaniline.

[0017] Preferably, in this step, the dissociation reaction temperature is 40-100° C. and the dissociation time is 1-2 h.

[0018] Beneficial effects of the present invention

[0019] The present invention dissolves the diacylated byproducts and the still residue of the crystallization of fluopyram contained in the fluopyram synthesized by the amidation method in an organic solvent, quantitatively introduces an alkali, and effectively dissociates the diacylated byproducts into the monoacylated fluopyram target product and difluoropyrazole carboxylate or difluoropyrazole carboxamide, the latter having a strong polarity and having a large difference in polarity from the target product, and is easily separated to obtain a pure fluopyram product by concentrating and switching solvents for recrystallization, thereby effectively improving the yield of the target product. The dissociation method of the present invention is simple and easy to implement, and has important significance and high industrial application value for improving yield, reducing three wastes, reducing costs, and improving product quality. DETAILED DESCRIPTION

[0020] The present invention is further described below with specific examples.

[0021] Example 1

[0022] Add 50g of the acylated crystallization mother liquor containing diacylated byproduct (8% of diacylated byproduct, 89% of flupyracoxadil), 100mL of 1,2-dichloroethane and 5.9g of 5% sodium hydroxide aqueous solution to a 250mL four-necked bottle, stir and react for 1-2h at 60-65℃, take a sample and HPLC to detect that the diacylated byproduct completely disappears, and 5% of difluorobenzidine, a byproduct of flupyracoxad hydrolysis, is detected. After the reaction is completed, the water layer is separated and discarded, the organic layer is concentrated to dryness, 50mL of tetrachloroethylene is added, the temperature is raised to dissolve, and then the system is cooled to 0-5℃ for crystallization and filtration, and an appropriate amount of tetrachloroethylene is used for elution to obtain 37.2g of flupyracoxad with a purity of 99.0% and a recovery rate of 77.8%.

[0023] Example 2

[0024] Add 50g of the acylated crystallization mother liquor containing diacylated byproduct (8% of diacylated byproduct, 89% of fluopyram), 100mL of xylene and 8.8g of 15% potassium carbonate aqueous solution to a 250mL four-necked bottle, stir and react for 1-2h at 40-45°C, take a sample and detect that the diacylated byproduct disappears completely, and 3% of difluorobenzidine, a byproduct of fluopyram hydrolysis, is detected. After the reaction is completed, the water layer is separated and discarded, the organic layer is concentrated to dryness, 50mL of tetrachloroethylene is added, the temperature is raised to dissolve, and then the system is cooled to 0-5°C for crystallization and filtration, and an appropriate amount of tetrachloroethylene is used for elution to obtain 39.4g of fluopyram, with a purity of 99.2% and a recovery rate of 82.5%.

[0025] Example 3

[0026] Add 50g of the acylation crystallization mother liquor containing diacylation byproduct (8% of diacylation byproduct, 89% of fluopyram), 100mL of isopropanol and 0.6g of diethylamine to a 250mL four-necked bottle, stir and react for 1-2h at 90-95°C, and take a sample for HPLC detection to detect that the diacylation byproduct disappears completely. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol mixed solvent, heat the system until all dissolved, then cool to 0-5°C for crystallization and filtration, rinse with an appropriate amount of mixed solvent, and obtain 46.9g of fluopyram, with a purity of 98.8% and a recovery rate of 98.0%.

[0027] Example 4

[0028] Add 50g of the residue of the acylated crystallization mother liquor containing diacylated byproduct (8% of diacylated byproduct, 89% of flupyracoxadil), 100mL of 1,2-dichloroethane and 1.1g of n-octylamine to a 250mL four-necked bottle, stir and react for 1-2h at 80-85°C, and take a sample for HPLC detection to detect that the diacylated byproduct completely disappears. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol mixed solvent, heat the system until all dissolved, then cool to 0-5°C for crystallization and filtration, wash with an appropriate amount of mixed solvent, and obtain 47.6g of flupyracoxadil with a purity of 98.5% and a recovery rate of 99.1%.

[0029] Example 5

[0030] Add 50g of the acylated crystallization mother liquor containing diacylated byproduct (accounting for 8% of diacylated byproduct and 89% of fluopyram), 100mL of toluene and 1.0g of o-methylaniline to a 250mL four-necked bottle, adjust the system to 80-85°C and stir for 1-2h, and take a sample for HPLC to detect that the diacylated byproduct disappears completely. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol mixed solvent, heat the system until all dissolved, then cool to 0-5°C for crystallization and filtration, rinse with an appropriate amount of mixed solvent, and obtain 45.5g of fluopyram with a purity of 99.6% and a recovery rate of 95.8%.

[0031] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for converting a diacylated byproduct of fluopyraclostrobin into a monoacylated product, characterized in that: The following steps are involved: The still residue of the mother liquor of the fluopyrabamide crystallization containing the diacylated by-product is dissolved in an organic solvent, and a dissociation reaction is carried out in the presence of an alkali. The reaction liquid is concentrated, dissolved by a switching solvent, crystallized by cooling, filtered, and washed to obtain a pure fluopyrabamide product.

2. The method for converting the diacylated byproduct of fluopyraclostrobin into a monoacylated product according to claim 1, characterized in that: The organic solvent is selected from one or more of aromatic hydrocarbons, aliphatic hydrocarbons or alcohols.

3. The method for converting the diacylated byproduct of fluopyraclostrobin into a monoacylated product according to claim 2, characterized in that: The aromatic hydrocarbon is selected from toluene, xylene or chlorobenzene; the aliphatic hydrocarbon is selected from heptane, dichloromethane or dichloroethane; and the alcohol is selected from methanol, ethanol or isopropanol.

4. The method for converting the diacylated byproduct of fluopyraclostrobin into a monoacylated product according to claim 1, characterized in that: The base is selected from an inorganic base solution or an organic base.

5. A method for converting diacylated byproduct of fluopyraclostrobin into monoacylated product according to claim 4, characterized in that: The concentration of the inorganic alkali solution is 1-20% of dilute alkali, and the dosage is 1.0-1.5eq of the diacylated by-product substrate; the dosage of the organic alkali is 1.0-1.5eq of the diacylated by-product substrate.

6. A method for converting diacylated byproduct of fluopyraclostrobin into monoacylated product according to claim 4, characterized in that: The inorganic alkali solution is selected from sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution or potassium carbonate solution; the organic base is selected from aliphatic or aromatic amines.

7. A method for converting diacylated byproduct of fluopyraclostrobin into monoacylated product according to claim 4, characterized in that: The organic base is selected from n-butylamine, n-octylamine, benzylamine, liquid ammonia, diethylamine, piperidine, aniline, o-methylaniline, p-phenylenediamine or N-methylaniline.

8. The method for converting the diacylated byproduct of fluopyraclostrobin into a monoacylated product according to claim 1, characterized in that: The dissociation reaction temperature is 40-100°C; the dissociation time is 1-2h.

9. The method for converting diacylated byproduct of fluopyraclostrobin into monoacylated product according to claim 1, characterized in that: The recrystallization solvent is tetrachloroethylene or a mixed solvent of tetrachloroethylene and isopropanol.

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