A method of converting a by-product of the diacylation of fluoxastrobin into a monoacylated product

Abstract

The application discloses a method for converting diacylated by-product into monoacylated product in the synthesis of fluoxastrobin, and belongs to the field of pesticides and intermediates. The method can effectively recover fluoxastrobin in a crystallization mother liquor and convert diacylated by-product, which is difficult to avoid in the synthesis process, into monoacylated product. The diacylated by-product and fluoxastrobin are close in polarity, and are difficult to remove by a conventional recrystallization method. In the application, the crystallization mother liquor containing the diacylated by-product and fluoxastrobin is dissolved in an organic solvent, a base is quantitatively introduced, the diacylated by-product is converted into monoacylated fluoxastrobin, the reaction solution is concentrated and recrystallized to purify, and the monoacylated product is obtained. In the application, the diacylated by-product is converted into the target product, and another by-product with stronger polarity is generated at the same time, which can be easily separated by recrystallization to obtain the target product with high purity. The process operation is simple, the conditions are mild, the separation yield is high, and the application has important significance for reducing three wastes, reducing cost and improving product quality.

Description

Technical Field

[0001] This invention belongs to the field of pesticide intermediate synthesis technology in fine chemical industry, and is a method for converting diacylation by-products into fluopyram. Background Technology

[0002] Fluxapyroxad (trade name Xemium) is an SDHI fungicide launched by BASF in 2012. It has both preventative and curative effects and exhibits excellent systemic activity. In 2015, it surpassed BASF's own boscalid to become the number one SDHI fungicide. Currently, fluxapyroxad's global sales are close to $500 million, making it BASF's second-largest fungicide after pyraclostrobin, indicating a very promising market prospect.

[0003] Existing literature reports that the mainstream synthetic method for fluopyram involves an amidation reaction of difluoromethylpyrazole carboxylic acid and its derivatives with trifluorobenzidine. This synthetic method inevitably produces a diacylation byproduct during the synthesis of fluopyram, the chemical structure of which is... This leads to a decrease in reaction yield, difficulty in separation and purification, and an increase in industrial production costs and operational complexity. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a method for converting fluopyram diacylation byproducts into monoacylated products. This method involves introducing an alkali into fluopyram crystallization reactor residue containing diacylation byproducts to induce the dissociation of the diacylation byproducts into the target fluopyram product. After concentration and recrystallization separation, pure fluopyram is obtained.

[0005] The method for converting fluopyram diacylation byproducts into monoacylated products according to the present invention is 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 solution of the present invention is as follows: the residue of fluopyram crystallization mother liquor containing diacylation byproduct is dissolved in an organic solvent, and a dissociation reaction is carried out in the presence of alkali. The reaction solution is concentrated, dissolved by switching solvents, cooled and crystallized, filtered and washed to obtain pure fluopyram.

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

[0012] In a preferred embodiment, 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] In a preferred embodiment, the alkali in this step is selected from inorganic alkali solutions or organic alkalis.

[0014] In a preferred embodiment, in this step, the concentration of the inorganic base solution is 1-20% dilute base, and the amount used is 1.0-1.5 eq of the diacytization byproduct substrate; the amount of the organic base used is 1.0-1.5 eq of the diacytization byproduct substrate.

[0015] In a preferred embodiment, the inorganic base solution in this step 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.

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

[0017] In a preferred embodiment, the dissociation reaction temperature in this step is 40-100℃, and the dissociation time is 1-2 hours.

[0018] Beneficial effects of the invention

[0019] This invention dissolves the diacylation byproducts and crystallization residues of fluopyram obtained by amidation synthesis in an organic solvent. A alkali is quantitatively introduced to effectively dissociate the diacylation byproducts into the target product of monoacylated fluopyram and difluoropyrazole carboxylate or difluoropyrazole carboxamide. The latter is more polar and differs significantly in polarity from the target product. Through concentration, solvent switching, and recrystallization, pure fluopyram is easily obtained, thus effectively improving the yield of the target product. This dissociation method is simple and easy to implement, and it is of great significance and high industrial application value for improving yield, reducing waste, lowering costs, and improving product quality. Detailed Implementation

[0020] The present invention will be further described below with reference to specific embodiments.

[0021] Example 1

[0022] To a 250 mL four-necked flask, 50 g of concentrate residue from the mother liquor containing acylation byproducts (8% acylation byproducts, 89% fluopyram), 100 mL of 1,2-dichloroethane, and 5.9 g of 5% sodium hydroxide aqueous solution were added sequentially. The mixture was heated to 60–65 °C and stirred for 1–2 h. HPLC analysis showed complete disappearance of the acylation byproducts, with the presence of 5% fluopyram hydrolysis byproduct difluorobenzidine. After the reaction was complete, the aqueous layer was separated and discarded, and the organic layer was concentrated to dryness. 50 mL of tetrachloroethylene was added, and the mixture was heated until dissolved. The system was then cooled to 0–5 °C for crystallization and filtration. After rinsing with an appropriate amount of tetrachloroethylene, 37.2 g of fluopyram was obtained with a purity of 99.0% and a recovery rate of 77.8%.

[0023] Example 2

[0024] Add 50g of concentrated mother liquor containing acylation byproduct (8% acylation byproduct, 89% fluopyram), 100mL of xylene, and 8.8g of 15% potassium carbonate aqueous solution to a 250mL four-necked flask. Heat to 40–45℃ and stir for 1–2 hours. HPLC analysis shows complete disappearance of the acylation byproduct, with 3% of difluorobenzidine, a hydrolysis byproduct of fluopyram, detected. After the reaction is complete, separate and discard the aqueous layer, concentrate the organic layer to dryness, add 50mL of tetrachloroethylene, heat until dissolved, then cool to 0–5℃ for crystallization and filtration. Elute with an appropriate amount of tetrachloroethylene 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 concentrated mother liquor containing acylation byproduct (8% acylation byproduct, 89% fluopyram), 100mL of isopropanol, and 0.6g of diethylamine sequentially to a 250mL four-necked flask. Heat to 90–95℃ and stir for 1–2 hours. HPLC analysis shows complete disappearance of the acylation byproduct. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol mixed solvent, heat until completely dissolved, then cool to 0–5℃ for crystallization and filtration. Elute with a suitable amount of mixed solvent to 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 concentrated mother liquor containing acylation byproduct (8% acylation byproduct, 89% fluopyram), 100mL of 1,2-dichloroethane, and 1.1g of n-octylamine sequentially to a 250mL four-necked flask. Heat to 80–85℃ and stir for 1–2 hours. HPLC analysis confirms complete disappearance of the acylation byproduct. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol mixed solvent, heat until completely dissolved, then cool to 0–5℃ for crystallization and filtration. Elute with a suitable amount of mixed solvent to obtain 47.6g of fluopyram with a purity of 98.5% and a recovery rate of 99.1%.

[0029] Example 5

[0030] Add 50g of concentrated mother liquor containing acylation byproduct (8% acylation byproduct, 89% fluopyram), 100mL of toluene, and 1.0g of o-methylaniline to a 250mL four-necked flask. Adjust the system temperature to 80–85℃ and stir for 1–2 hours. HPLC analysis shows complete disappearance of the acylation byproduct. Concentrate the reaction system to dryness, add 40mL of tetrachloroethylene and 10mL of isopropanol, heat until completely dissolved, then cool to 0–5℃ for crystallization and filtration. Elute with a suitable amount of mixed solvent to 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 to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the present invention. Various changes and modifications can be made to the present invention without departing from its principles, and all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A method for converting fluopyram diacylation byproducts into monoacylated products, characterized in that, Includes the following steps: The residual mother liquor containing the diacylated byproduct of fluopyram crystallization was dissolved in an organic solvent, and a dissociation reaction was carried out in the presence of an alkali. The reaction solution was concentrated, dissolved in a different solvent, cooled for crystallization, filtered, and washed to obtain pure fluopyram. The structure of the diacylated byproduct is as follows: .

2. The method for converting fluopyram diacylation byproducts into monoacylated products 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 fluopyram diacylation byproducts into monoacylated products 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 fluopyram diacylation byproducts into monoacylated products according to claim 1, characterized in that: The alkali is selected from inorganic alkali solutions or organic alkalis.

5. The method for converting fluopyram diacylation byproducts into monoacylated products according to claim 4, characterized in that: The inorganic base solution concentration is 1-20% dilute base, and the amount used is 1.0-1.5 eq of the diacylated by-product substrate; the amount of organic base used is 1.0-1.5 eq of the diacylated by-product substrate.

6. The method for converting fluopyram diacylation byproducts into monoacylated products according to claim 4, characterized in that: The inorganic alkaline 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. The method for converting fluopyram diacylation byproducts into monoacylated products 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 fluopyram diacylation byproducts into monoacylated products according to claim 1, characterized in that: The dissociation reaction temperature is 40–100℃; the dissociation time is 1–2 hours.

9. The method for converting fluopyram diacylation byproducts into monoacylated products according to claim 1, characterized in that: The recrystallization solvent is tetrachloroethylene or a mixture of tetrachloroethylene and isopropanol.

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