Halogen-substituted compounds, processes for their preparation and use

Abstract

The present application relates to a preparation method of halogen-substituted compounds, such as the reaction of piperazine derivatives shown in formula I with halogenated acetyl halide derivatives shown in formula VI to generate halogen-substituted compounds shown in formula II. The present application also relates to a preparation method of pyrazole derivatives prepared from halogen-substituted compounds shown in formula II, such as the reaction of halogen-substituted compounds shown in formula II with methyl hydrazine to generate pyrazole ring to generate halogen-substituted alkyl-1-methyl pyrazole derivatives shown in formula IV; or the reaction of halogen-substituted compounds shown in formula II with methyl hydrazine benzaldehyde hydrazone to generate hydrazone compounds shown in formula III, and under the action of acid, pyrazole ring is closed to generate halogen-substituted alkyl-1-methyl pyrazole derivatives shown in formula IV. The present application also relates to the structure of intermediate compounds. The preparation method of halogen-substituted compounds and pyrazole derivatives of the present application is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to an industrial-scale synthesis method for halogen-substituted compounds, belonging to the field of chemical synthesis technology. Background Technology

[0002] Halogen-substituted pyrazole derivatives, especially fluroxypyrazole derivatives, are intermediates in many pharmaceuticals and pesticides. Among these fluroxypyrazole derivatives, 3-difluoromethyl-1-methylpyrazole-4-carboxylic acid is an important pesticide intermediate, playing a crucial role in many new pesticide varieties. Examples include Bixafen, a cereal fungicide from Bayer Crop Science; Fluxapyroxad, a new fungicide from BASF; Isopyrazam, a pyrazole fungicide from Syngenta; and Sedaxane, a fluroxypyr fungicide.

[0003] .

[0004] International patent WO1992 / 12970 discloses 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid and its use as a fungicide. The method involves converting 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid to the corresponding acyl chloride, and then using a suitable amine to convert it to the corresponding amide, thereby producing an amide-based fungicide.

[0005] Since 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is a key intermediate in the synthesis of the above-mentioned novel amide bactericides, its synthesis process has sparked extensive research among chemists. Existing preparation methods can be categorized as follows: The first method, Claisen condensation, is mainly reported in patents by BASF and Syngenta. Starting with ethyl difluoroacetate, a Claisen condensation reaction yields ethyl difluoroacetoacetate, which is then condensed with triethyl orthoformate to give ethyl 4,4-difluoro-2-(ethoxymethylene)-3-oxobutyrate. After cyclization with methylhydrazine, it generates ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (DFMMP). Hydrolysis with sodium hydroxide and acidification with hydrochloric acid yields 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (DFPA). Due to its high cost, this route is generally no longer used in new synthetic method research, except for existing production lines.

[0006] Second, the dimethylaminoacrylate method, as described in Bayer patent WO2009043444, and similarly, BASF WO2009133178, which replaces the dimethylamino group with a piperidinyl group. This method involves passing difluoroacetyl fluoride gas into dimethylaminoacrylate, and the resulting intermediate directly undergoes cyclization with methylhydrazine to form ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate (DFMMP). After hydrolysis with sodium hydroxide and acidification with hydrochloric acid, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (DFPA) is obtained. The difluoroacetyl fluoride gas is obtained through high-temperature cracking of tetrafluoroethyl ether. This route is ingeniously designed, featuring short steps and high yield, and is currently a relatively low-cost method. The disadvantages include high equipment requirements, the generation of large amounts of volatile dimethylamine, environmental impact, and the lack of a solution to the selectivity problem in the cyclization synthesis of the pyrazole ring from methylhydrazine.

[0007] Third, the difluorochloroacetyl chloride process, Solvay's patent WO2012025469. This route, developed by Solvay, uses difluorochloroacetyl chloride (CDFAC) as the starting material. After reacting with ketene and quenching with ethanol, ethyl difluorochloroacetoacetate is obtained. Similar to Claysen condensation, ethyl 3-(difluorochloromethyl)-1-methyl-1H-pyrazole-4-carboxylate is obtained. Zinc powder reduction or palladium carbon hydrogenation yields ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate (DFMMP). Hydrolysis with sodium hydroxide and acidification with hydrochloric acid yields 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate (DFPA). The disadvantages of this route are its length, the availability of raw materials, and the final dechlorination process, which increases both cost and waste.

[0008] IV. Other Synthetic Methods. 1) EP 2008996 reported a five-step reaction to synthesize 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid from dichloroacetyl chloride, vinyl ether compounds, and methylhydrazine. Although it has certain advantages in cost control, the reaction conditions are quite harsh. Dichloroacetyl chloride and vinyl ether compounds need to react at -40 to -20°C; in the catalytic pressurized carboxylation reaction, the reaction temperature is 150°C, and the pressure inside the reactor needs to be constantly changed, making operation inconvenient, and isomers are not easy to separate; 2) WO2009000442 reported a method using ethyl difluoroacetate as a raw material, reacting with hydrazine hydrate to generate an acylhydrazine, followed by methylation and then cyclization with ethyl propargylate to obtain ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (DFMMP). This method has a low yield, and ethyl propargylate is expensive, making it unsuitable for industrial production. Summary of the Invention

[0009] The technical problem to be solved by the present invention is to provide a halogen-substituted compound suitable for industrial production of pyrazole derivatives, a method for preparing the halogen-substituted compound, and a method and use of the halogen-substituted compound as an intermediate to prepare pyrazole derivatives.

[0010] To address the aforementioned technical problems, this invention proposes a method for preparing a halogen-substituted compound, wherein a piperazine derivative as shown in Formula I reacts with a haloacetyl halide derivative as shown in Formula VI to generate a halogen-substituted compound as shown in Formula II. The preferred reaction solvent is chloroform, and the preferred catalyst is triethylamine. The reaction formula is as follows: , in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 X 2 and X 3 Each can be either chlorine or fluorine. Preferred X 1 X 2 and X 3 It is fluorine, R 4 For hydrogen, R 1 It is OC2H5 or CH3.

[0011] To address the aforementioned technical problems, the present invention proposes a technical solution: a halogen-substituted compound having a structure as shown in Formula II. , in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be either chlorine or fluorine. Preferred X 1 X 2It is fluorine, R 4 For hydrogen, R 1 It is OC2H5 or CH3.

[0012] To address the aforementioned technical problems, this invention proposes a method for preparing pyrazole derivatives from halogen-substituted compounds. The method involves reacting a halogen-substituted compound (as shown in Formula II) with methylhydrazine to close the pyrazole ring, thereby generating a halogen-substituted alkyl-1-methylpyrazole derivative (as shown in Formula IV). The reaction formula is as follows: , in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be either chlorine or fluorine. Preferred X 1 X 2 It is fluorine, R 4 For hydrogen, R 1 It is OC2H5 or CH3; When R 1 OR A When the halogenated alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes a hydrolysis reaction with an alkaline solution, preferably a sodium hydroxide solution, it generates a halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V. 1 For R A When the halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes an oxidation reaction with an oxidant, preferably a sodium hypochlorite solution, a sodium hypobromite solution, or oxygen, a halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V is generated, the reaction formula is as follows: .

[0013] To address the aforementioned technical problems, this invention proposes a method for preparing pyrazole derivatives from halogen-substituted compounds. The method involves reacting a halogen-substituted compound (as shown in Formula II) with methylhydrazine benzaldehyde hydrazone to generate a hydrazone compound (as shown in Formula III), as described in the following reaction formula: , in, R 1OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be either chlorine or fluorine. Preferred X 1 X 2 It is fluorine, R 4 For hydrogen, R 1 It is OC2H5 or CH3; The hydrazone compound shown in Formula III, preferably sulfuric acid, undergoes a reaction in which the pyrazole ring closes to form a halogen-substituted alkyl-1-methylpyrazole derivative shown in Formula IV, as shown in the following reaction formula: , When R 1 OR A When the halogenated alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes a hydrolysis reaction with an alkaline solution, preferably a sodium hydroxide solution, it generates a halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V. 1 For R A When the halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes an oxidation reaction with an oxidant, preferably a sodium hypochlorite solution, a sodium hypobromite solution, or oxygen, a halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V is generated, the reaction formula is as follows: .

[0014] The present invention provides a technical solution to solve the above-mentioned technical problems: a method for preparing pesticides, comprising the above-mentioned method for preparing halogen-substituted compounds or pyrazole derivatives. The pesticide is an amide fungicide, preferably bifenthrin, fluopyram, pyraclostrobin, or fluopyram. The method for preparing the pesticide involves converting a halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid, preferably by converting a carboxylic acid halide into an activated halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid, and then reacting the activated halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid with an amine, preferably aniline, to obtain an amide fungicide. For specific preparation methods, refer to international patent WO1992 / 12970.

[0015] The present invention proposes a technical solution to solve the above-mentioned technical problems: the application of the halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid obtained by the above preparation method as an intermediate in the preparation of pesticides. The pesticide is an amide fungicide, preferably bifenthrin, fluopyram, pyraclostrobin, or fluopyram.

[0016] This invention has positive effects: (1) This invention optimizes the structure of halogen-substituted compounds. The two nitrogen atoms in the halogen-substituted compounds form piperazines, giving the halogen-substituted compounds a centrosymmetric structure. When synthesizing pyrazole derivatives using halogen-substituted compounds with this structure, fewer reaction byproducts are produced. The reaction route of this invention is shorter, the reaction conditions are more common, requiring only 40% aqueous solution of alkyl hydrazine compounds. The yields of each step are high, the intermediates are easy to purify, and the product quality is high. Compared with the 3-piperidine ring acrylate structure, this symmetrical diamine structure has higher atom economy, and the symmetrical diamine has a higher boiling point, making it easier to recycle.

[0017] (2) The halogen-substituted compounds prepared in this invention are easy to prepare with the raw material compounds and haloacetyl halide derivatives, which can be directly purchased and have low raw material costs.

[0018] (3) When preparing pyrazole derivatives in this invention, a halogen-substituted compound can be reacted with methylhydrazine benzaldehyde hydrazone first, and then the pyrazole ring can be closed under the action of acid. The advantage is that the formation of methylhydrazine benzaldehyde hydrazone with hydrazone protection group can be carried out in one reaction vessel, which further ensures that the ring-closed product without isomers is obtained. Detailed Implementation

[0019] The present invention will be specifically described below through embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above description.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art. For example: C1–C8 alkyl refers to alkyl groups with carbon chains of 1–8, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, etc. C3–C8 cycloalkyl refers to cycloalkyl groups with carbon chains of 3–8, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc. C3–C8 cycloalkyl groups with substituents, such as 2-methylcyclopropyl, 1-methylcyclopentyl, 4-methylcyclohexyl, etc. Aryl refers to a monovalent group in an aromatic hydrocarbon with a carbon chain of 6–18, such as phenyl, naphthyl, anthracene, etc. Aryl groups with substituents, such as 3-methylphenyl (m-tolyl), 2,4-di-tert-butylphenyl, 4-chlorophenyl, etc. Heteroaryl groups, such as furanyl, pyrroleyl, indolyl, carbazoyl, imidazoyl, etc. Substituent-containing heteroaryl groups refer to groups in which one or more hydrogen atoms of the heteroaryl group are replaced by substituents.

[0021] The embodiments of the present invention take difluoroacetyl fluoride, a haloacetyl halide derivative of formula VI, as an example. , As shown in Formula VI, for haloacetyl halide derivatives, when X 1 X 2 and X 3 It is fluorine, R 4 When it is hydrogen, it is difluoroacetyl fluoride.

[0022] Difluoroacetyl fluoride gas can be produced by high-temperature cracking of tetrafluoroethyl ether. The cracking reaction temperature is 200℃~400℃, and the catalyst is aluminum oxide.

[0023] Example 1 The preparation method of the pyrazole derivative in this embodiment includes the following steps: 28.2 g (0.1 mol) of piperazine N,N'-bisacrylate (as shown in Formula I, where R...) was added to the reaction flask. 1 The reaction mixture consisted of 200g of chloroform (OC2H5), 22.2g (0.22mol) of triethylamine, and 21.5g (0.22mol) of difluoroacetyl fluoride (DFAF) was introduced at a controlled temperature of 10℃~30℃. After the purging was completed, the reaction was continued at this temperature for 5 hours. The solvent was concentrated under reduced pressure, and the residue was mixed with 100g of water. The mixture was stirred for 30 minutes, filtered, and dried to obtain 42.9g of the corresponding halogenated compound (as shown in Formula II), with a yield of 98%.

[0024] 39 g (0.0889 mol) of the halogenated compound product was suspended in 200 g of chloroform, stirred and cooled to -25 °C, and 20.5 g (0.178 mol) of 40% methylhydrazine (MMH) was slowly added dropwise. After the addition was complete, the reaction was continued at this temperature for 30 minutes, then heated to room temperature. The aqueous layer and organic layer were separated, and the mixture was concentrated to dryness. The residue was recrystallized in petroleum ether to give 30.8 g of ethyl 3-fluoroalkyl-1-methylpyrazole-4-carboxylate (EDFMPA) (as shown in Formula IV), with a yield of 85%.

[0025] 30.8 g (0.151 mol) of ethyl 3-fluoroalkyl-1-methylpyrazole-4-carboxylic acid (EDFMPA) was added to a reaction flask, along with 100 g of water and 6.7 g of sodium hydroxide. The mixture was stirred at 70 °C for 2 hours. After the reaction was complete, hydrochloric acid was added dropwise to neutralize the pH to 2. The mixture was then cooled to 10 °C, filtered, washed with a small amount of cold water, and dried to obtain 25.2 g of 3-fluoroalkyl-1-methyl-1H-pyrazole-4-carboxylic acid (DFMPA) (as shown in Formula V), with a yield of 95%. The purity was determined to be 99% by high performance liquid chromatography.

[0026] Example 2 The preparation method of the pyrazole derivative in this embodiment includes the following steps: 28.2 g (0.1 mol) of piperazine N,N'-bisacrylate (as shown in Formula I, where R...) was added to the reaction flask. 1 The reaction mixture consisted of 200g of chloroform (OC2H5), 22.2g (0.22 mol) of triethylamine, and 21.5g (0.22 mol) of difluoroacetyl fluoride (DFAF) was introduced while maintaining the temperature between 10℃ and 30℃. After the purging was completed, the reaction was continued at this temperature for 5 hours. After the reaction was completed, 26.8g (0.2 mol) of methylhydrazine benzaldehyde hydrazone (BzH) was added dropwise. The temperature was raised to 50℃ and the reaction was maintained at this temperature for 3 hours. The solvent was removed by vacuum evaporation, and the residue was treated by adding 200g of chloroform and 5g of sulfuric acid. The reaction was carried out at room temperature for 8 hours. 50g of water was added, and the organic layer was separated. The temperature was raised to 60℃, and 90g of a 10% sodium hydroxide solution was added dropwise. After the addition was complete, the reaction continued for 3 hours. After the reaction was complete, the aqueous layer was separated, and hydrochloric acid was added to neutralize it to a pH of 2. The mixture was cooled to 10°C, filtered, washed with water, and dried to obtain 26 g of 3-fluoroalkyl-1-methyl-1H-pyrazole-4-carboxylic acid (DFMPA) (as shown in Formula V). The total yield was 73.8%, and the purity was 99% as determined by high performance liquid chromatography.

[0027] Example 3 The preparation method of the pyrazole derivative in this embodiment includes the following steps: In the reaction flask, 22.2 g (0.1 mol) of N,N'-bisvinylmethylketopiperazine (as shown in Formula I, where R...) was added. 1The following mixture was prepared: 200 g of chloroform (CH3) and 22.2 g (0.22 mol) of triethylamine. The mixture was heated to 10°C–30°C, and 21.5 g (0.22 mol) of difluoroacetyl fluoride (DFAF) was introduced. After the purging was complete, the reaction was continued at this temperature for 5 hours. Then, 26.8 g (0.2 mol) of methylhydrazine benzaldehyde hydrazone (BzH) was added dropwise. The temperature was raised to 50°C, and the reaction was continued at this temperature for 3 hours. The solvent was removed by vacuum distillation. The residue was then treated with 200 g of chloroform and 5 g of sulfuric acid. The reaction was continued at room temperature for 8 hours. 50 g of water was added, and the organic layer was separated. The organic layer was concentrated to dryness, recrystallized with petroleum ether, filtered, and dried to obtain 27.2 g of a 3-trifluoromethyl-1-methyl-4-acetylpyrazole derivative (as shown in Formula IV), with a yield of 78%.

[0028] 25 g (0.14 mol) of 3-trifluoromethyl-1-methyl-4-acetylpyrazole derivative, 80 g of acetic acid, 1 g of manganese nitrate, and 1 g of ferric nitrate were added to a reaction flask. The mixture was heated to 80 °C, and oxygen was introduced to react for 20 hours. The acetic acid was removed by vacuum distillation. 80 g of water was added to the residue, and the mixture was stirred and heated to 80 °C. The mixture was then cooled to 10 °C, filtered, and dried to obtain 24 g of 3-fluoroalkyl-1-methyl-1H-pyrazole-4-carboxylic acid (DFMPA) (as shown in Formula V), with a yield of 95%. The purity was determined to be 99% by high performance liquid chromatography.

[0029] Obviously, the above embodiments are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, these obvious variations or modifications derived from the spirit of the present invention are still within the scope of protection of the present invention.

Claims

1. A halogen-substituted compound, characterized in that: It has a structure as shown in Formula II. ， in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be chlorine or fluorine, respectively.

2. A method for preparing the halogen-substituted compound as described in claim 1, characterized in that: The piperazine derivative shown in Formula I reacts with the haloacetyl halide derivative shown in Formula VI to generate the halogenated compound shown in Formula II, as shown in the following reaction formula: ， in, R 1 OR A or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 X 2 and X 3 Each can be chlorine or fluorine, respectively.

3. A method for preparing pyrazole derivatives using the halogen-substituted compound as described in claim 1, characterized in that: The halogen-substituted compound shown in Formula II reacts with methylhydrazine to close the pyrazole ring and generate a halogen-substituted alkyl-1-methylpyrazole derivative shown in Formula IV, as shown in the following reaction formula: ， in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be chlorine or fluorine, respectively.

4. The method for preparing pyrazole derivatives from halogen-substituted compounds according to claim 3, characterized in that: Where R 1 OR A The halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes a hydrolysis reaction to generate the halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V, as follows: 。 5. The method for preparing pyrazole derivatives from halogen-substituted compounds according to claim 3, characterized in that: Where R 1 For R A The halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes an oxidation reaction to generate the halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V, as follows: 。 6. A method for preparing pyrazole derivatives using the halogen-substituted compound as described in claim 1, characterized in that: The halogen-substituted compound shown in Formula II reacts with methylhydrazine benzaldehyde hydrazone to produce the hydrazone compound shown in Formula III, as shown in the following reaction formula: ， in, R 1 OR A Or R A , where R A It can be a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkyl group with substituents, an aryl group, an aryl group with substituents, a heteroaryl group, or a heteroaryl group with substituents. R 4 It is hydrogen, chlorine, fluorine, or a C1-C8 alkyl group. X 1 and X 2 Each can be either chlorine or fluorine; The hydrazone compound shown in Formula III, under the action of acid, closes the pyrazole ring to generate a halogen-substituted alkyl-1-methylpyrazole derivative shown in Formula IV, as shown in the following reaction formula: 。 7. The method for preparing pyrazole derivatives from halogen-substituted compounds according to claim 6, characterized in that: Where R 1 OR A The halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes a hydrolysis reaction to generate the halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V, as follows: 。 8. The method for preparing pyrazole derivatives from halogen-substituted compounds according to claim 6, characterized in that: Where R 1 For R A The halogen-substituted alkyl-1-methylpyrazole derivative as shown in Formula IV undergoes an oxidation reaction to generate the halogen-substituted alkyl-1-methyl-1H-pyrazole-4-carboxylic acid as shown in Formula V, as follows: 。 9. A method for preparing pesticides, characterized in that: The preparation method includes any one of claims 2, 3, and 6.

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