An electrochemical synthesis method for fully substituted sulfonated pyrazole compounds

Abstract

This invention relates to an electrochemical synthesis method for fully substituted sulfonated pyrazole compounds. The method includes the following steps: mixing acetylacetone, substituted arylsulfonyl hydrazides, and an electrolyte, adding the mixture to a mixed solvent to obtain a mixed solution; subjecting the mixed solution to an electrochemical reaction to obtain a reaction mixture; and separating and purifying the reaction mixture to obtain the fully substituted sulfonated pyrazole compounds. Compared with existing technologies, this invention uses an electrochemical method to prepare fully substituted sulfonated pyrazole compounds. During the reaction, an iodine-containing electrolyte undergoes an oxidation reaction at the anode to generate iodine free radicals. These iodine free radicals then react with arylsulfonyl hydrazides and acetylacetone with different substituents to form the fully substituted sulfonated pyrazole compounds. This method has advantages such as simple preparation, convenient operation, high atom utilization, and mild reaction conditions.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to an electrochemical synthesis method for fully substituted sulfonated pyrazole compounds. Background Technology

[0002] Pyrazole compounds have attracted attention from the pesticide and pharmaceutical industries due to their highly efficient biological activity. Since Knott discovered the analgesic, anti-inflammatory, and antipyretic effects of antipyrine containing a pyrazole ring in 1883, and Thampson reported in 1946 that 2-pyrazole-5-one could inhibit crop growth, numerous patents and literature reports have documented various pyrazole compounds with good biological activity. These compounds play a crucial role in pesticides and pharmaceuticals due to their high efficiency, low toxicity, and structural diversity. In recent years, in particular, new pyrazole compounds have been continuously commercialized, such as chlorpyrifos, fenpyroxine, fenpyroxine, and azoxystrobin.

[0003] Traditionally, pyrazole compounds have been synthesized from hydrazine compounds and 1,3-dicarbonyl compounds or their corresponding 1,3-electrophilic compounds, or through intermolecular cyclization to achieve carbon-nitrogen and carbon-carbon bond connections. However, the use of stoichiometric oxidants and the complexity of the preparation process significantly limit the applicability of this method. Summary of the Invention

[0004] The purpose of this invention is to overcome at least one of the defects of the prior art by providing an electrochemical synthesis method for fully substituted sulfonated pyrazole compounds. This method addresses the shortcomings of existing fully substituted sulfonated pyrazole compound preparation processes, which are complex and require the addition of metal catalysts.

[0005] The objective of this invention can be achieved through the following technical solutions:

[0006] An electrochemical method for the synthesis of fully substituted sulfonated pyrazole compounds, comprising the following steps:

[0007] Acetylacetone, substituted arylsulfonyl hydrazide and electrolyte are mixed and added to a mixed solvent to obtain a mixed solution;

[0008] The mixed solution is subjected to an electrochemical reaction to obtain a reaction mixture; platinum sheet is used as the electrode material.

[0009] After separation and purification, the reaction mixture yielded fully substituted sulfonated pyrazole compounds.

[0010] Furthermore, the substituted aryl sulfonyl hydrazides include p-toluenesulfonyl hydrazide or 2-naphthalenesulfonyl hydrazide; the electrolyte includes an iodine-containing electrolyte.

[0011] Furthermore, the iodine-containing electrolyte includes tetrabutylammonium iodide.

[0012] Furthermore, the molar ratio of acetylacetone, substituted arylsulfonyl hydrazine, and electrolyte is 1:(2-3):(0.08-0.12).

[0013] Furthermore, the molar ratio of acetylacetone, substituted arylsulfonyl hydrazine, and electrolyte is 1:2.5:0.1.

[0014] Furthermore, the mixed solvent includes ethyl acetate and water.

[0015] Furthermore, the volume ratio of ethyl acetate to water is 1:(1.8-2.2), preferably 1:2.

[0016] Furthermore, the current for the electro-reaction is 15-25mA, the reaction temperature is 40-50℃, and the time is 4-6h.

[0017] Furthermore, the current for the electro-reaction is 20mA, the reaction temperature is 45℃, and the reaction time is 5h.

[0018] Furthermore, the separation and purification includes extraction, concentration, or column chromatography. During extraction, ethyl acetate is used as the extractant. Concentration is performed under reduced pressure. Column chromatography is used for separation and purification, with a mixed developing solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1.

[0019] Compared with the prior art, the present invention has the following characteristics:

[0020] (1) The present invention uses an electrochemical method to prepare fully substituted sulfonated pyrazole compounds. During the reaction, an iodine-containing electrolyte is oxidized at the anode to obtain iodine free radicals. Then, the iodine free radicals react with arylsulfonyl hydrazides and acetylacetone with different substituents to obtain fully substituted sulfonated pyrazole compounds. This method has the advantages of simple preparation method, convenient operation, high atom utilization rate and mild reaction conditions.

[0021] (2) The present invention carries out the reaction without the use of oxidants or metal catalysts, and makes full use of the anodic oxidation under the condition of electricity to promote the reaction, which meets the relevant requirements of green chemistry and has good development prospects. Detailed Implementation

[0022] The embodiments of the present invention are described in detail below. These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and specific operation processes. However, the scope of protection of the present invention is not limited to the following embodiments.

[0023] An electrochemical synthesis method for fully substituted sulfonated pyrazole compounds, comprising the following steps:

[0024] (1) Acetylacetone, arylsulfonyl hydrazides with different substituents and electrolytes are mixed in a molar ratio of 1:2.5:0.1 and added to a mixed solvent of ethyl acetate and water in a volume ratio of 1:2 to prepare a mixed solution. Then, the solution is subjected to an electrolytic reaction at 45°C in an oil bath with a reaction current of 20mA for 5 hours to obtain a reaction mixture. The electrolyte is an iodine-containing electrolyte. Specifically, the arylsulfonyl hydrazides with different substituents include p-toluenesulfonyl hydrazide and 2-naphthalenesulfonyl hydrazide.

[0025] (2) The reaction mixture was extracted with ethyl acetate. The initial purified product was then concentrated under reduced pressure and separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the developing solvent) to obtain the target product, which forms a pyrazole compound. The specific equation is as follows:

[0026]

[0027] Example 1

[0028] An electrochemical synthesis method for fully substituted sulfonated pyrazole compounds, the specific steps of which are as follows:

[0029] (1) Weigh 1.25 mmol of p-toluenesulfonyl hydrazine, 0.5 mmol of acetylacetone and 0.05 mmol of tetrabutylammonium iodide into a test tube, use a mixture of ethyl acetate and water (1:2) as a solvent, react in an oil bath at 45°C, and pass a reaction current of 20 mA for 5 h to obtain a reaction mixture.

[0030] (2) The reaction mixture was mixed with ethyl acetate and extracted. The supernatant was taken to obtain the initial purified product. The initial purified product was then concentrated under reduced pressure to obtain a concentrate. The concentrate was separated by column chromatography (the developing solvent was a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product 3,5-dimethyl-1,4-bis[(4-methylphenyl)sulfonyl]-1H-pyrazole with a yield of 73%.

[0031] The target products were characterized by nuclear magnetic resonance (NMR), and the results are as follows:

[0032] 1 H NMR (500MHz, Chloroform-d) δ7.91-7.83(m,2H),7.76-7.70(m,2H),7.40-7.26(m,4H),2.85(s,3H),2.48-2.32(m,9H).

[0033] Example 2

[0034] An electrochemical synthesis method for fully substituted sulfonated pyrazole compounds, the specific steps of which are as follows:

[0035] (1) Weigh 1.25 mmol of 2-naphthalenesulfonylhydrazine, 0.5 mmol of acetylacetone and 0.05 mmol of tetrabutylammonium iodide into a test tube, use a mixture of ethyl acetate and water (1:2) as a solvent, react in an oil bath at 45°C, and pass a reaction current of 20 mA for 5 h to obtain a reaction mixture.

[0036] (2) The reaction mixture was mixed with ethyl acetate and extracted. The supernatant was taken to obtain the initial purified product. The initial purified product was then concentrated under reduced pressure to obtain a concentrate. The concentrate was separated by column chromatography (the developing solvent was a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product 3,5-dimethyl-1,4-bis(2-naphthylsulfonyl)-1H-pyrazole with a yield of 61%.

[0037] The target products were characterized by nuclear magnetic resonance (NMR), and the results are as follows:

[0038] 1 H NMR (500MHz, Chloroform-d) δ8.64(s,1H),8.48(s,1H),8.06-7.88(m,7H),7.78-7.60(m,5H),2.98(s,3H),2.42(s,3H).

[0039] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. An electrochemical synthesis method for fully substituted sulfonylpyrazole compounds, characterized in that, The method includes the following steps: Acetylacetone, substituted arylsulfonyl hydrazide and electrolyte are mixed and added to a mixed solvent to obtain a mixed solution; The mixed solution is subjected to an electrolytic reaction to obtain a reaction mixture; After separation and purification, the reaction mixture yielded a fully substituted sulfonated pyrazole compound: 3,5-dimethyl-1,4-bis[(4-methylphenyl)sulfonyl]-1H-pyrazole; The substituted aryl sulfonyl hydrazide is p-toluenesulfonyl hydrazide; the electrolyte is tetrabutylammonium iodide; the mixed solvent is ethyl acetate and water in a volume ratio of 1:

2. The molar ratio of acetylacetone, substituted arylsulfonyl hydrazine, and electrolyte is 1:2.5:0.1; The current for the energized reaction was 20 mA, the reaction temperature was 45 °C, and the reaction time was 5 h. The separation and purification process consists of extraction, concentration, and column chromatography in sequence. The yield of the fully substituted sulfonated pyrazole compounds was 73%.

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