Phenyl pyrazole derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of compound synthesis and pesticides, in particular to a phenylpyrazole derivative and a preparation method and application thereof.The phenylpyrazole derivative is mainly based on a phenylpyrazole structure, and the derivative has the excellent control effect on six weeds under 37.5-150 g a.i. / ha, has the good weeding activity on multiple weeds under the low dosage, and has the good application prospect. The compound disclosed by the invention can be developed and used as a potential novel broad-spectrum herbicide in a wheat field, and the derivative is relatively novel in structure, easily available in raw materials and relatively high in overall yield, and has a relatively great application prospect.

Description

Technical Field

[0001] The invention belongs to the field of compound pesticides, and specifically relates to a phenylpyrazole derivative and a preparation method and application thereof. Background Art

[0002] Globally, due to the wide variety of weeds, most weeds have seriously harmed the growth of crops, posing a threat to agricultural production and leading to a decline in food crop yields. Weed control is crucial to crop production, and the use of chemical herbicides to control weeds plays an important role in increasing crop yields. Therefore, the development of new, efficient, low-toxic, and environmentally friendly green herbicides is a major demand in current agricultural production.

[0003] Small molecules containing pyrazole rings are widely used in the fields of medicine, pesticides and materials. In the field of pesticides, herbicides developed based on pyrazoles and already on the market, such as pyraclostrobin, isopyraclostrobin and bispyribac nitrile, etc. In addition, research on pyrazole herbicides has made certain progress in recent years, such as application numbers WO9602515A1, WO 01 / 16112A1, CN1151159A, CN1402979A, US20190069512A1 and CN107518008A disclose the preparation and herbicidal activity of pyrazole herbicides. These compounds have the characteristics of high efficiency, broad spectrum and low residue, especially for broad-leaved weeds, but at the same time, such compounds are more serious for broad-leaved crops, and safety aspects are still to be improved, and there are problems such as high production cost and low overall yield.

[0004] Most existing herbicides not only have high weed control activity against weeds, but also have strong damage to crops, which makes these herbicides not suitable for use in the growth of crops. However, with the emergence of environmental pollution and weed resistance, and in actual production, crop growth has a high demand for weed control. Therefore, it is urgent to develop new, efficient, low-toxic, and environmentally friendly green herbicides.

[0005] In the prior art, although the disclosed compounds have certain similarities with the compounds of the present invention, the compounds represented by the general formula of the present invention have significant differences in structure from the compounds of the prior art. The structure of the present invention is relatively novel and has good herbicidal activity. At the same time, the raw materials are easily available, the overall yield is high, and it has great application prospects. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention provides a phenylpyrazole derivative and a preparation method and application thereof.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] A phenylpyrazole derivative was designed and synthesized, and the general structural formula of the phenylpyrazole derivative is as follows:

[0009]

[0010] In formula (I):

[0011] X is selected from CH 2 ,O,S,COO,NR 7 ;

[0012] Y is selected from (CR 8 R 9 )n;

[0013] Z is selected from O, S, NR 7 ;

[0014] n is selected from 0, 1, 2, 3, and 4 respectively;

[0015] R 1 Selected from C 1 -C 6 Alkyl or C 1 -C 6 Haloalkyl;

[0016] R 2 Selected from OCR 10 R 11 , CR 12 , -CN and halogen;

[0017] R 3 are respectively selected from H, -CN and halogen;

[0018] R 4 , R 5 are selected from H, halogen, -CN, NO 2 NH 2 , C 1 -C 6 The alkyl group (C 1 -C 6 haloalkyl)-O- or (C 1 -C 6 alkyl)-SO 2 -;

[0019] R 6 Selected from H, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 3 -C 6 Alkenyl, C 3 -C 6 Halogenated alkenyl, C3 -C 6 Alkynyl, C 1 -C 4 Alkoxy C 1 -C 6 -alkyl, C 1 -C 4 Halogenated alkoxy C 1 -C 6 alkyl;

[0020] R 7 are selected from H, hydroxyl, C 1 -C 6 Alkyl or C 1 -C 4 Alkoxy;

[0021] R 8 , R 9 , R 10 , R 11 and R 12 are selected from H, halogen, hydroxyl, C 1 -C 6 Alkyl or C 1 -C 6 Halogenated alkyl.

[0022] The phenylpyrazole derivatives are characterized by comprising the following compounds:

[0023] Compound A1: 1-(methoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0024] Compound A2: 1-(ethoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0025] Compound A3: 1-(((ethylthio)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0026] Compound A4: 1-((isopropoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0027] Compound A5: 1-((Propoxy)carbonyl)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0028] Compound A6: 1-((isobutylcarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0029] Compound A7: 1-((Butoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0030] Compound A8: 1-(((but-3-en-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0031] Compound A9: 1-((but-3-yn-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0032] Compound A10: 1-((2-methoxyethoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ester;

[0033] Compound A11: 1-(((cyclopropylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0034] Compound A12: 1-(((cyclobutylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0035] Compound A13: 1-((cyclopentylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0036] Compound A14: 1-((((tetrahydrofuran-2-yl)methoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0037] Compound A15: 1-((cyclohexylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0038] Compound A16: 1-((phenoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0039] Compound A17: 1-(naphthalen-2-ylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0040] Compound A18: 1-((2-ethoxy-2-oxyethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0041] Compound A19: 1-((((1-ethoxy-2-methyl-1-oxopropyl-2-yl)oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0042] Compound A20: (Ethoxycarbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0043] Compound A21: ((isopropoxycarbonyl)oxy)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0044] Compound A22: ((Propyloxy)carbonyl)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0045] Compound A23: ((Cyclopentylmethoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate

[0046] Compound A24: ((phenoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0047] Compound A25: 1-(Ethoxycarbonyl)oxy-ethyl-3-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)benzoate;

[0048] Compound A26: 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chlorobenzoate;

[0049] Compound A27: 1-(ethoxycarbonyl)oxy-2-chloro-5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-4-fluorobenzoate;

[0050] Compound A28: 1-(Ethoxycarbonyl)oxyethyl-5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0051] Compound A29: 1-(Ethoxycarbonyl)oxy-5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0052] Compound A30: (Ethoxycarbonyl)oxymethyl 2-chloro-5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-4-fluorobenzoate;

[0053] Compound A31: (Ethoxycarbonyl)oxymethyl-5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate;

[0054] Compound A32: (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)methyl carbonate;

[0055] Compound A33: 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate;

[0056] Compound A34: 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate;

[0057] Compound A35: isopropyl 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate.

[0058] The present invention also provides a method for preparing the above-mentioned phenylpyrazole derivative, comprising the following steps:

[0059] (1) Preparation of intermediate 1:

[0060] Sodium hydride and dimethyl carbonate are added to toluene in an ice bath in batches and stirred at room temperature. Then 2,4-disubstituted-5-methylacetophenone is dissolved in a constant pressure dropping funnel containing toluene, and the mixed solution is added dropwise to the toluene containing sodium hydride and dimethyl carbonate within 40 minutes. After stirring at room temperature for 10 minutes, the mixture is heated to react. After the reaction is completed, the reaction mixture is cooled to room temperature, glacial acetic acid is added, and the mixture is extracted with water and ethyl acetate. A saturated sodium bicarbonate solution is then added for extraction. After drying and column chromatography, intermediate 1 is obtained.

[0061] (2) Preparation of intermediate 2:

[0062] Take intermediate 1 and methylhydrazine sulfate into ethanol, heat the reaction solution, and after the reaction is completed, pour the reaction solution into water, add ethyl acetate, let stand, and filter to obtain intermediate 2;

[0063] (3) Preparation of intermediate 3:

[0064] Take intermediate 2, cesium carbonate and ethyl difluorobromoacetate / bromopropane / iodomethane and add them to DMF, then slowly heat the mixture, wait for the reaction liquid to cool to room temperature, extract with water and ethyl acetate, dry and column chromatograph to obtain intermediate 3;

[0065] (4) Preparation of intermediate 4:

[0066] Add intermediate 3 and N-bromosuccinimide (NBS) to DMF, condense and reflux under argon protection; after the reaction is completed, cool the reaction solution to room temperature, add ethyl acetate and water for extraction; separate the organic layer, wash with saturated brine, dry, concentrate, and perform column chromatography to obtain intermediate 4;

[0067] (5) Preparation of intermediate 5:

[0068] Take intermediate 4 and dissolve it in glacial acetic acid. Add concentrated H 2 SO 4 and chromium trioxide, react at room temperature. After the reaction is completed, pour the reaction solution into ice water, let stand, filter, wash with water, and recrystallize to obtain intermediate 5;

[0069] (6) Preparation of intermediate 6:

[0070] Take intermediate 4, NBS and benzoyl peroxide (BPO) and add them into a three-necked flask, add dimethyl carbonate, react at 90.3°C under argon protection. After the reaction is completed, cool the reaction to room temperature, concentrate under reduced pressure, then add water and ethyl acetate to extract, dry, concentrate under reduced pressure, and purify by column chromatography to obtain intermediate 6;

[0071] (7) Preparation of intermediate 7:

[0072] Take intermediate 6 and dimethyl sulfoxide and add them to a three-necked flask, add aqueous solution, react at 100°C, and after the reaction is completed, cool the reaction to room temperature, then add water and ethyl acetate to extract, dry, concentrate under reduced pressure, and purify by column chromatography to obtain intermediate 7;

[0073] (8) Preparation of intermediate 8:

[0074] Add alcohol / thiol / amino / oxime and pyridine to dichloromethane, slowly add chloroformic acid-1-chloro substituted ester to react under ice bath conditions, add dichloromethane and water to extract, wash with saturated brine, dry, concentrate, and column chromatography to obtain intermediate 8;

[0075] (9) Preparation of Intermediate 9

[0076] Tetrahydrofuran was placed in a three-necked flask, and sodium hydride and 2,4-disubstituted-5-methylacetophenone were added in batches under argon protection. The mixture was stirred at room temperature, and then ethyl trifluoroacetate was slowly added dropwise to the mixture to react at room temperature. After the reaction was completed, water and ethyl acetate were added for extraction, and the mixture was dried, concentrated under reduced pressure, and purified by column chromatography to obtain intermediate 9.

[0077] (10) Preparation of intermediate 10:

[0078] Intermediate 9 and hydrazine hydrate (80%) were condensed and refluxed in glacial acetic acid. After the reaction was completed, the reaction mixture was cooled to room temperature, extracted with water and ethyl acetate, dried, concentrated under reduced pressure, and purified by column chromatography to obtain intermediate 10;

[0079] (11) Preparation of intermediate 11:

[0080] Take the intermediate 10 and dimethyl sulfate into toluene, condense and reflux, and after the reaction is completed, wait for the reaction to cool to room temperature, pour the reaction solution into ice water, let it stand, precipitate flocs, and filter to obtain the intermediate 11;

[0081] (12) Preparation of intermediate 12:

[0082] Take intermediate 11 and NBS / NCS and add them to glacial acetic acid. Heat the reaction solution. After the reaction is completed, cool the reaction solution to room temperature, add ethyl acetate and water for extraction; separate the organic layer, wash with saturated brine, dry, concentrate, and perform column chromatography to obtain intermediate 12;

[0083] (13) Preparation of intermediate 13:

[0084] Take intermediate 12 and add it to glacial acetic acid, add concentrated H 2 SO 4 and chromium trioxide, react at room temperature. After the reaction is completed, pour the reaction solution into ice water, let stand, filter, wash with water, and recrystallize to obtain intermediate 13;

[0085] (14) Preparation of the target compound phenylpyrazole derivative:

[0086] Take intermediate 5 / 7 / 13 and add it to DMF. Add K 2 CO 3 After stirring, the intermediate 8 is added and the reaction is carried out at room temperature. After the reaction is completed, the system is washed with a saturated sodium chloride solution, extracted with water and ethyl acetate, dried, concentrated under reduced pressure, and purified by column chromatography to obtain a phenylpyrazole derivative.

[0087] In step (1), the molar ratio of the 2,4-disubstituted-5-methylacetophenone, dimethyl carbonate and sodium hydride is: 2,4-disubstituted-5-methylacetophenone: dimethyl carbonate: sodium hydride = 1:4:3; the amount of toluene is controlled by adding 1 mL of toluene per millimole of 2,4-disubstituted-5-methylacetophenone;

[0088] In step (2), the molar ratio of the intermediate 1 and methylhydrazine sulfate is: intermediate 1:methylhydrazine sulfate=1:4; the amount of ethanol is controlled by adding 1 mL of ethanol per millimole of intermediate 1;

[0089] In step (3), the molar ratio of the intermediate 2, cesium carbonate and ethyl difluorobromoacetate / propane bromoacetate / methyl iodide is: intermediate 2: cesium carbonate: ethyl difluorobromoacetate / propane bromoacetate / methyl iodide = 1:1.3:1.5; the amount of DMF is controlled by adding 1 mL of DMF per mmol of the intermediate 2;

[0090] In step (4), the molar ratio of the intermediate 3 and NBS is: intermediate 3:NBS=1:3; the amount of DMF is controlled by adding 1 mL of DMF per millimole of intermediate 3;

[0091] In step (5), the molar ratio of the intermediate 4 to chromium trioxide is: intermediate 4: chromium trioxide = 1:3; the amount of acetic acid is controlled by adding 1 mL of acetic acid per millimole of intermediate 4, and the amount of sulfuric acid is controlled by adding 0.1 mL of sulfuric acid per millimole of intermediate 4;

[0092] In step (6), the molar ratio of the intermediate 4, NBS and BPO is: intermediate 4: NBS: BPO = 1: 1: 0.1; the amount of dimethyl carbonate is controlled by adding 1 mL of dimethyl carbonate per millimole of intermediate 4;

[0093] In step (7), the amount of DMSO is controlled by adding 0.1 mL of DMSO per mmol of intermediate 6, and the amount of water is controlled by adding 1 mL of water per mmol of intermediate 6.

[0094] In step (8), the molar ratio of the alcohol / mercapto / amino / oxime, 1-chloro substituted chloroformate and pyridine is: alcohol / mercapto / amino / oxime: 1-chloro substituted chloroformate: pyridine = 2:1:1.5; the amount of dichloromethane is controlled by adding 1 mL of dichloromethane per millimole of 1-chloro substituted chloroformate;

[0095] In step (9), the molar ratio of the 2,4-disubstituted-5-methylacetophenone, ethyl trifluoroacetate and sodium hydride is: 2,4-disubstituted-5-methylacetophenone:ethyl trifluoroacetate:sodium hydride=1:4:3; the amount of tetrahydrofuran is controlled by adding 1 mL of tetrahydrofuran per millimole of 2,4-disubstituted-5-methylacetophenone;

[0096] In step (10), the molar ratio of the intermediate 9 to the hydrazine hydrate is: intermediate 9: hydrazine hydrate = 1:2; the amount of glacial acetic acid is controlled by adding 1 mL of glacial acetic acid per millimole of the intermediate 9;

[0097] In step (11), the molar ratio of the intermediate 10 to dimethyl sulfate is: intermediate 10: dimethyl sulfate = 1:3; the amount of toluene is controlled by adding 1 mL of toluene per millimole of the intermediate 10;

[0098] In step (12), the molar ratio of the intermediate 11 to NBS / NCS is: intermediate 11:NBS / NCS=1:3; the amount of acetic acid is controlled by adding 1 mL of acetic acid per millimole of the intermediate 11;

[0099] In step (13), the molar ratio of the intermediate 12 to chromium trioxide is: intermediate 12:chromium trioxide = 1:3; the amount of glacial acetic acid is controlled by adding 1 mL of glacial acetic acid per millimole of the intermediate 12, and the amount of sulfuric acid is controlled by adding 0.1 mL of sulfuric acid per millimole of the intermediate 12.

[0100] In step (14), the intermediates 5 / 7 / 13, intermediate 8 and K 2 CO 3 The dosage is calculated in molar ratio as follows: Intermediate 5 / 7 / 13: Intermediate 8: K 2 CO 3 =1:1.2:1.4; the amount of DMF is controlled by adding 1 mL of DMF per 5 / 7 / 13 mmol of the intermediate.

[0101] The preparation route of the phenylpyrazole derivative is any one of the following:

[0102] Route 1:

[0103]

[0104] Route 2:

[0105]

[0106] At the same time, the purpose of the present invention is to use the phenylpyrazole derivatives in the preparation of herbicides and weed growth enzyme inhibitors.

[0107] Specifically, the weeds are crabgrass, barnyard grass, ramie, Amaranthus retroflexus, ryegrass, purslane, Solanum nigrum, dandelion, clover, Goosegrass, Setaria, Duckweed, Nepeta tenuifolia, oats, bluegrass, Sudan grass, Cassia seed, hairy vetch, alfalfa, snake pea, plantain, astragalus, licorice, marigold, morning glory, zinnia, Amaranthus gracilis, cloud leaf grass, and horse hoof tendon.

[0108] Beneficial effects:

[0109] The present invention is based on the phenylpyrazole structure, and optimizes and derives to create phenylpyrazole herbicide small molecules with relatively stable physicochemical properties and excellent drugability; such derivatives have significant post-emergence inhibitory effects on barnyard grass, crabgrass, foxtail grass, ramie, Amaranthus retroflexus and purslane.

[0110] The results of systematic post-emergence herbicidal activity tests showed that most of the phenylpyrazole compounds had excellent herbicidal activity against barnyard grass, crabgrass, Setaria viridis, velvet, Amaranthus retroflexus and Portulaca oleracea at a dosage of 150 g a.i. / ha. The weeds completely withered and their growth was severely inhibited, with the inhibition rate reaching 100%, which was better than the positive control pyraclostrobin and equivalent to the positive control isopyraclostrobin. At a dosage of 75 g ai / ha, compounds A2, A4, A8, A14, A16, A18, A20, A21, A22, A33 and A35 had excellent herbicidal activity against barnyard grass, crabgrass, Setaria viridis, velvet, Amaranthus retroflexus and Portulaca oleracea, with the inhibition rate reaching 100%, showing good post-emergence herbicidal effect.

[0111] The phenylpyrazole derivative designed and synthesized by the invention has a simple structure, a simple preparation process and is non-toxic and harmless. BRIEF DESCRIPTION OF THE DRAWINGS

[0112] Figure 1 and Figure 2 The preparation route of phenylpyrazole derivatives in Examples 1 to 35 is shown in FIG. DETAILED DESCRIPTION

[0113] The specific embodiments of the present invention are further described in detail below, but the present invention is not limited to these embodiments, and any improvement or substitution based on the basic spirit of the present embodiment still falls within the scope of protection required by the claims of the present invention.

[0114] Example 1: A method for preparing 1-(methoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A1), comprising the following steps:

[0115] (1) Preparation of methyl-3-(2-fluoro-4-chloro-5-methylphenyl)-3-oxopropanoate:

[0116] Sodium hydride (12.86 g, 535.88 mmol) and dimethyl carbonate (36.20 g, 401.91 mmol) were added to toluene (300 mL) in an ice bath in batches and stirred at room temperature for 10 minutes. Then, 2-fluoro-4-chloro-5-methylacetophenone (25.00 g, 133.97 mmol) was dissolved in a constant pressure dropping funnel containing toluene (100 mL), and the mixed solution was added dropwise to the toluene containing sodium hydride and dimethyl carbonate within 40 minutes. After stirring at room temperature for 10 minutes, the mixture was reacted at 110.6°C for 1 hour. After the reaction was completed, glacial acetic acid (100 mL) was added, and the mixture was extracted with ethyl acetate (300 mL) and water (300 mL). Saturated sodium bicarbonate (100 mL) was added, and the mixture was dried. After column chromatography, 13.10 g of methyl-3-(2-fluoro-4-chloro-5-methylphenyl)-3-oxopropanoate intermediate was obtained, with a yield of 52.41%.

[0117] (2) Preparation of 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-1H-pyrazole-5-ol:

[0118] Take methyl-3-(2-fluoro-4-chloro-5-methylphenyl)-3-oxopropanoate (13.10 g, 53.55 mmol) and methylhydrazine sulfate (30.87 g, 214.19 mmol) and add them to a three-necked flask containing ethanol (300 mL), and condense and reflux the reaction mixture at 78.4°C for 4 hours. After the reaction is completed, pour the reaction solution into water (100 mL), add ethyl acetate (100 mL) and let stand for 30 minutes, and filter to obtain 5.14 g of 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-1H-pyrazole-5-ol intermediate, with a yield of 39.85%;

[0119] (3) Preparation of 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole:

[0120] 3-(2-Fluoro-4-chloro-5-methylphenyl)-1-methyl-1H-pyrazole-5-ol (5.14 g, 21.36 mmol), cesium carbonate (6.05 g, 27.77 mmol) and ethyl difluorobromoacetate (6.50 g, 32.04 mmol) were dissolved in DMF, and the temperature was raised to 90 °C for 3 hours. After the reaction was completed, the mixture was cooled to room temperature, and ethyl acetate (200 mL) and H2O were added to the solution. 2 O (200 mL), the organic layer was separated and 2 O (100 mL) and saturated NaCl solution (100 mL), and then washed with anhydrous Na 2 SO 4 The product was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 2.12 g of 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole intermediate with a yield of 34.21%.

[0121] (4) Preparation of 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole:

[0122] Take 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole (2.12 g, 7.29 mmol) and add it to 200 mL of DMF. Under argon protection, add NBS (1.24 g, 21.88 mmol) to the solution, and heat the reaction to 80°C for 3 hours. After the reaction is completed, the reaction is cooled to room temperature, and water (100 mL) and ethyl acetate (200 mL) are added to the solution for extraction. The organic layer is separated, washed with saturated brine, dried, concentrated, and column chromatography is performed to obtain 2.31 g of 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole intermediate, with a yield of 85.44%.

[0123] (5) Preparation of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid:

[0124] Take 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole (2.31 g, 625.43 μmol) and dissolve it in glacial acetic acid (100 mL). Add concentrated H 2 SO 4(20 mL) and chromium trioxide (1.88 g, 18.75 mmol), react at room temperature for 6 hours. After the reaction is completed, the reaction solution is poured into 50 mL of ice water, allowed to stand for 30 minutes, filtered, washed with water (100 mL), and recrystallized to obtain 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid intermediate;

[0125] (6) Preparation of 1-chloroethyl methyl carbonate:

[0126] Methanol (67.24 mg, 2.10 mmol) and pyridine (124.49 mg, 1.57 mmol) were added to 15 mL of dichloromethane, and 1-chloroethyl chloroformate (150 mg, 1.05 mmol) was slowly added to react under ice bath conditions. After the reaction was completed, dichloromethane (20 mL) and water (20 mL) were added for extraction, washed with saturated brine (10 mL), and washed with anhydrous Na 2 SO 4 Dry, concentrate under reduced pressure, and obtain 1-chloroethyl methyl carbonate by column chromatography; (7) Preparation of 1-(methoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0127] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl methyl carbonate (121.37 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.13 g of 1-(methoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate with a yield of 42.24%.

[0128] Example 2: A method for preparing 1-(ethoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A2) comprising the following steps:

[0129] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0130] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol;

[0131] (7) Preparation of 1-(ethoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0132] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then 1-chloroethyl carbonate (133.65 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.13 g of 1-(ethoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate with a yield of 40.31%.

[0133] Example 3: A method for preparing 1-((ethylthio)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A3) comprising the following steps:

[0134] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0135] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethyl mercaptan;

[0136] (7) Preparation of 1-((ethylthio)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0137] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3(103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then O-(1-chloroethyl)-S-carbonyl acid ethyl ester (83.46 mg, 801.73 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.15 g of 1-((ethylthio)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 44.33%.

[0138] Example 4: A method for preparing 1-((isopropoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A4), comprising the following steps:

[0139] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0140] Step (6): Referring to step (6) of Example 1, methanol is replaced by isopropanol;

[0141] (7) Preparation of 1-((isopropoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0142] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl isopropyl carbonate (83.46 mg, 801.73 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.13 g of 1-((isopropoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 38.44%.

[0143] Example 5: A method for preparing 1-((propoxy)carbonyl)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A5) comprising the following steps:

[0144] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0145] Step (6): Referring to step (6) of Example 1, methanol is replaced by propanol;

[0146] (7) Preparation of 1-((propoxy)carbonyl)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0147] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then ethyl chloropropyl carbonate (145.94 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.13 g of 1-((propoxy)carbonyl)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 40.13%.

[0148] Example 6: A method for preparing 1-((isobutylcarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A6) comprising the following steps:

[0149] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0150] Step (6): Referring to step (6) of Example 1, methanol is replaced by isobutanol;

[0151] (7) Preparation of 1-((isobutylcarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0152] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then chloroethyl isobutyl carbonate (145.94 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.13 g of 1-((isobutylcarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 51.52%.

[0153] Example 7: A method for preparing 1-((butoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A7) comprising the following steps:

[0154] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0155] Step (6): Referring to step (6) of Example 1, methanol is replaced by butanol;

[0156] (7) Preparation of 1-((butoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0157] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (130 mg, 801.73 μmol) was stirred at room temperature for 30 min, then (1-chloroethyl) butyl carbonate (83.46 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.23 g of 1-((butoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 39.88%.

[0158] Example 8: A method for preparing 1-((but-3-ene-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A8) comprising the following steps:

[0159] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0160] Step (6): refer to step (6) of Example 1, except that methanol is replaced by but-3-en-1-ol;

[0161] (7) Preparation of 1-((but-3-ene-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0162] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (130 mg, 801.73 μmol) was stirred at room temperature for 30 min, then but-3-en-1-yl (1-chloroethyl) carbonate (83.46 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.14 g of 1-((but-3-ene-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 43.66%.

[0163] Example 9: A method for preparing 1-((but-3-yn-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A9) comprising the following steps:

[0164] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0165] Step (6): refer to step (6) of Example 1, except that methanol is replaced by but-3-yn-1-ol;

[0166] (7) Preparation of 1-((but-3-yn-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0167] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then but-3-yn-1-yl (1-chloroethyl) carbonate (154.70 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.14 g of 1-((but-3-yn-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 41.26%.

[0168] Example 10: A method for preparing 1-((2-methoxyethoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ester (i.e., Compound A10) comprising the following steps:

[0169] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0170] Step (6): refer to step (6) of Example 1, except that methanol is replaced by 2-methoxyethane-1-ol;

[0171] (7) Preparation of 1-((2-methoxyethoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ester:

[0172] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3(103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (2-methoxyethyl) carbonate (159.96 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.16 g of 1-((2-methoxyethoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ester in a yield of 46.35%.

[0173] Example 11: A method for preparing 1-((cyclopropylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A11, comprising the following steps:

[0174] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0175] Step (6): Referring to step (6) of Example 1, methanol is replaced by cyclopropylmethanol;

[0176] (7) Preparation of 1-((cyclopropylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0177] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (cyclopropylmethyl) carbonate (156.46 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.14 g of 1-((cyclopropylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 42.15%.

[0178] Example 12: A method for preparing 1-((cyclobutylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A12, comprising the following steps:

[0179] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0180] Step (6): Referring to step (6) of Example 1, methanol is replaced by cyclobutylmethanol;

[0181] (7) Preparation of 1-((cyclobutylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0182] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (cyclobutylmethyl) carbonate (168.75 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.15 g of 1-((cyclobutylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 43.34%.

[0183] Example 13: A method for preparing 1-((cyclopentylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A13, comprising the following steps:

[0184] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0185] Step (6): Referring to step (6) of Example 1, methanol is replaced by cyclopentylmethanol;

[0186] (7) Preparation of 1-((cyclopentylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0187] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (cyclopentylmethyl) (181.04 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.12 g of 1-((cyclopentylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 33.85%.

[0188] Example 14: A method for preparing 1-((((tetrahydrofuran-2-yl)methoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A14, comprising the following steps:

[0189] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0190] Step (6): refer to step (6) of Example 1, except that methanol is replaced by (tetrahydrofuran-2-yl)methanol;

[0191] (7) Preparation of 1-((((tetrahydrofuran-2-yl)methoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0192] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl ((tetrahydrofuran-2-yl) methyl) carbonate (182.76 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO4 The residue was dried and concentrated under reduced pressure. 0.16 g of 1-((((tetrahydrofuran-2-yl)methoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 45.22%.

[0193] Example 15: A method for preparing 1-((cyclohexylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A15), comprising the following steps:

[0194] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0195] Step (6): Referring to step (6) of Example 1, methanol is replaced by cyclohexylmethanol;

[0196] (7) Preparation of 1-((cyclohexylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0197] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (cyclohexylmethyl) (193.32 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.11 g of 1-((cyclohexylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 30.15%.

[0198] Example 16: A method for preparing 1-((phenoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A16) comprising the following steps:

[0199] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0200] Step (6): Referring to step (6) of Example 1, methanol is replaced by benzyl alcohol;

[0201] (7) Preparation of 1-((phenoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0202] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then 1-chloroethyl carbonate (188.03 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.21 g of 1-((phenoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 58.12%.

[0203] Example 17: A method for preparing 1-(naphthalen-2-ylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A17, comprising the following steps:

[0204] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0205] Step (6): Referring to step (6) of Example 1, methanol is replaced by naphthalene-2-ylmethanol;

[0206] (7) Preparation of 1-(naphthalen-2-ylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0207] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3(103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, and then 1-chloroethyl (naphthalene-2-methyl) carbonate (231.88 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.24 g of 1-((naphthalen-2-ylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 61.33%.

[0208] Example 18: A method for preparing 1-((2-ethoxy-2-oxyethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A18, comprising the following steps:

[0209] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0210] Step (6): Referring to step (6) of Example 1, methanol was replaced with ethyl 2-hydroxyacetate;

[0211] (7) Preparation of 1-((2-ethoxy-2-oxyethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0212] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 The mixture was stirred at room temperature for 30 min, and then ethyl 2-((1-chloroethoxy)carbonyl)oxyacetate (184.49 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.18 g of 1-(((2-ethoxy-2-oxyethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 49.27%.

[0213] Example 19: A method for preparing 1-((((1-ethoxy-2-methyl-1-oxopropyl-2-yl)oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A19, comprising the following steps:

[0214] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0215] Step (6): Referring to step (6) of Example 1, methanol was replaced by ethyl 2-hydroxy-2-methylpropionate;

[0216] (7) Preparation of 1-((((1-ethoxy-2-methyl-1-oxopropyl-2-yl)oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0217] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then ethyl-2-((1-chloroethoxy)carbonyl)-2-methylpropanoate (209.07 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The reaction mixture was dried and concentrated under reduced pressure. 0.19 g of 1-((((1-ethoxy-2-methyl-1-oxopropyl-2-yl)oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 51.08%.

[0218] Example 20: A method for preparing (ethoxycarbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A20) comprising the following steps:

[0219] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0220] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0221] (7) Preparation of (ethoxycarbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0222] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (121.37 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.16 g of (ethoxycarbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 52.14%.

[0223] Example 21: A method for preparing ((isopropoxycarbonyl)oxy)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A21, comprising the following steps:

[0224] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0225] Step (6): Referring to step (6) of Example 1, methanol is replaced by isopropanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0226] (7) Preparation of ((isopropoxycarbonyl)oxy)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0227] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3(103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then chloromethyl isopropyl carbonate (133.65 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.13 g of ((isopropoxycarbonyl)oxy)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 40.23%.

[0228] Example 22: A method for preparing ((propoxy)carbonyl)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A22, comprising the following steps:

[0229] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0230] Step (6): Referring to step (6) of Example 1, methanol is replaced by propanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0231] (7) Preparation of ((propoxy)carbonyl)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0232] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then chloromethyl propyl carbonate (133.65 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried and concentrated under reduced pressure. 0.18 g of ((propoxy)carbonyl)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate was obtained by column chromatography. The yield was 54.87%.

[0233] Example 23: The preparation method of ((cyclopentylmethoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A23) comprises the following steps:

[0234] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0235] Step (6): Referring to step (6) of Example 1, methanol is replaced by cyclopentylmethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0236] (7) Preparation of ((cyclopentylmethoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0237] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then chloromethyl carbonate (cyclopentylmethyl) (168.75 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.15 g of ((cyclopentylmethoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 44.42%.

[0238] Example 24: The preparation method of ((phenoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A24) comprises the following steps:

[0239] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0240] Step (6): referring to step (6) of Example 1, methanol was replaced by benzyl alcohol, and 1-chloroethyl chloroformate was replaced by chloromethyl chloroformate;

[0241] (7) Preparation of ((phenoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0242] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then (chloromethyl) benzyl carbonate (175.74 mg, 875.99 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.22 g of ((phenoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 62.48%.

[0243] Example 25: A method for preparing 1-(ethoxycarbonyl)oxy-ethyl-3-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)benzoate (i.e., Compound A25, comprising the following steps:

[0244] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0245] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol;

[0246] (7) Preparation of 1-(ethoxycarbonyl)oxy-ethyl-3-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)benzoate:

[0247] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then 1-chloroethyl carbonate (153.84 mg, 1.01 mmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.12 g of 1-(ethoxycarbonyl)oxy-ethyl-3-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)benzoate with a yield of 35.57%.

[0248] Example 26: A method for preparing 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chlorobenzoate (i.e., Compound A26, comprising the following steps:

[0249] Steps (1) to (5): the same as steps (1) to (5) of Example 1;

[0250] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol;

[0251] (7) Preparation of 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chlorobenzoate:

[0252] Take 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 625.71 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.77 mg, 750.85 μmol) was stirred at room temperature for 30 min, then 1-chloroethyl carbonate (139.95 mg, 917.29 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.16 g of 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chlorobenzoate in a yield of 49.78%.

[0253] Example 27: A method for preparing 1-(ethoxycarbonyl)oxy-2-chloro-5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-4-fluorobenzoate (i.e., Compound A27) comprising the following steps:

[0254] Steps (1)-(3): same as steps (1)-(3) of Example 1;

[0255] Step (4): refer to step (5) of Example 1

[0256] Step (5): Referring to step (6) of Example 1, methanol is replaced by ethanol;

[0257] (6) Preparation of 1-(ethoxycarbonyl)oxy-5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0258] Take 5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 779.66 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (129.30 mg, 935.59 μmol) was stirred at room temperature for 30 min, then 1-chloroethyl carbonate (166.54 mg, 1.09 mmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.16 g of 1-(ethoxycarbonyl)oxy-5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 48.26%.

[0259] Example 28: A method for preparing 1-(ethoxycarbonyl)oxyethyl-5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A28, comprising the following steps:

[0260] Steps (1)-(2): the same as steps (1)-(2) of Example 1;

[0261] Step (3): Referring to step (3) of Example 1, ethyl difluorobromoacetate was replaced by iodomethane;

[0262] Steps (4)-(5): refer to steps (4)-(5) of Example 1

[0263] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0264] (7) Preparation of 1-(ethoxycarbonyl)oxyethyl-5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0265] Take 5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 687.63 μmol) and dissolve it in 15 mL DMF.2 CO 3 (114.04 mg, 825.16 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (133.38 mg, 962.68 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.17 g of 1-(ethoxycarbonyl)oxyethyl-5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 52.15%.

[0266] Example 29: A method for preparing 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A29, comprising the following steps:

[0267] Steps (1)-(2): the same as steps (1)-(2) of Example 1;

[0268] Step (3): Referring to step (3) of Example 1, ethyl difluorobromoacetate was replaced by bromopropane;

[0269] Steps (4)-(5): refer to steps (4)-(5) of Example 1

[0270] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0271] (7) Preparation of 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0272] Take 5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 638.37 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (105.87 mg, 766.05 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (123.82 mg, 893.72 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.15 g of 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 49.01%.

[0273] Example 30: A method for preparing (ethoxycarbonyl)oxymethyl 2-chloro-5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-4-fluorobenzoate (i.e., Compound A30) comprising the following steps:

[0274] (1) Preparation of 1-(2-fluoro-4-chloro-5-methylphenyl)-4,4,4-trifluorobutane-1,3-dione intermediate:

[0275] Under argon protection, sodium hydride (3.86 g, 160.76 mmol) and 2-fluoro-4-chloro-5-methylacetophenone (10.00 g, 53.59 mmol) were added to tetrahydrofuran (300 mL) in an ice bath. After stirring at room temperature for 30 minutes, ethyl trifluoroacetate (30.45 g, 214.35 mmol) was slowly added dropwise to the mixture. The mixture was reacted at room temperature for 2 hours. After the reaction was completed, water and ethyl acetate were added for extraction, dried, concentrated under reduced pressure, and purified by column chromatography to obtain 9.45 g of 1-(4-chloro-2-fluoro-5-methylphenyl)-4,4,4-trifluorobutane-1,3-dione intermediate with a yield of 62.44%.

[0276] (2) Preparation of 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(trifluoromethyl)-1H-pyrazole:

[0277] 1-(4-chloro-2-fluoro-5-methylphenyl)-4,4,4-trifluorobutane-1,3-dione (9.45 g, 53.55 mmol) and hydrazine hydrate (80%) (5.02 g, 100.31 mmol) were added to a three-necked flask containing glacial acetic acid (300 mL), and the reaction mixture was condensed and refluxed for 2 hours. After the reaction was completed, the reaction solution was poured into water (200 mL), ethyl acetate (200 mL) was added, and the mixture was allowed to stand for 30 minutes, and then filtered to obtain 5.14 g of 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(trifluoromethyl)-1H-pyrazole, with a yield of 72.42%;

[0278] (3) Preparation of 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole:

[0279] 3-(2-Fluoro-4-chloro-5-methylphenyl)-5-(trifluoromethyl)-1H-pyrazole (5.14 g, 18.45 mmol) and dimethyl sulfate (6.98 g, 55.34 mmol) were added to toluene and refluxed for 3 hours. After the reaction was completed, the mixture was cooled to room temperature and washed with sodium hydroxide. Ethyl acetate (200 mL) and H 2 O (200 mL), washed with saturated NaCl solution (200 mL), the organic layer was separated and washed with anhydrous Na 2 SO 4 The product was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 1.84 g of 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole intermediate with a yield of 34.21%.

[0280] Step (4): referring to step (4) of Example 1, 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole was replaced by 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole, and NBS was replaced by NCS;

[0281] Step (5): Referring to step (5) of Example 1, 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole was replaced with 4-chloro-3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole;

[0282] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0283] (7) Preparation of (ethoxycarbonyl)oxymethyl-5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)2-chloro-4-fluorobenzoate:

[0284] Take 5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)2-chloro-4-fluorobenzoic acid (250 mg, 622.60 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (103.26 mg, 747.12 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (120.76 mg, 871.65 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4The mixture was dried, concentrated under reduced pressure, and column chromatography was performed to obtain 0.15 g of (ethoxycarbonyl)oxymethyl 5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl) 2-chloro-4-fluorobenzoate. The yield was 49.01%.

[0285] Example 31: The preparation method of (ethoxycarbonyl)oxymethyl-5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate (i.e., Compound A31) comprises the following steps:

[0286] Steps (1)-(3): same as steps (1)-(3) of Example 30;

[0287] Step (4): Referring to step (4) of Example 1, 3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole was replaced with 3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole;

[0288] Step (5): Referring to step (5) of Example 1, 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole was replaced with 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole;

[0289] Step (6): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0290] (7) (Ethoxycarbonyl)oxymethyl-5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate:

[0291] Take 5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoic acid (250 mg, 700.11 μmol) and dissolve it in 15 mL DMF. Add K 2 CO 3 (116.11 mg, 840.13 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (135.80 mg, 980.16 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4The residue was dried, concentrated under reduced pressure, and purified by column chromatography to obtain 0.19 g of (ethoxycarbonyl)oxymethyl-5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate in a yield of 59.11%.

[0292] Example 32: A method for preparing methyl (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)carbonate (i.e., Compound A32), comprising the following steps:

[0293] Steps (1)-(4): same as steps (1)-(4) of Example 1;

[0294] (5) Preparation of 4-bromo-3-(5-(bromomethyl)-4-chloro-2-fluorophenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole:

[0295] 4-bromo-3-(2-fluoro-4-chloro-5-methylphenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole (5.00 g, 13.53 mmol), NBS (2.41 g, 13.53 mmol) and BPO (327.72 mg, 1.35 mmol) were added to a three-necked flask, and dimethyl carbonate (100 mL) was added. The mixture was reacted at 90.3° C. under argon protection for 2 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and the reaction solution was concentrated under reduced pressure. Then, water (100 mL) and ethyl acetate (100 mL) were added for extraction, dried, concentrated under reduced pressure, and purified by column chromatography to obtain 4-bromo-3-(5-(bromomethyl)-4-chloro-2-fluorophenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole;

[0296] (6) Preparation of (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol:

[0297] 4-Bromo-3-(5-(bromomethyl)-4-chloro-2-fluorophenyl)-5-(difluoromethoxy)-1-methyl-1H-pyrazole (5 g, 535.88 mmol) and DMSO (100 mL) were added to a three-necked flask, and water (100 mL) was added. The mixture was reacted at 100° C. for 2 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and then water (100 mL) and ethyl acetate (100 mL) were added for extraction. The mixture was dried, concentrated under reduced pressure, and purified by column chromatography to obtain (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol.

[0298] Step (7): Referring to step (6) of Example 1, methanol is replaced by ethanol, and 1-chloroethyl chloroformate is replaced by chloromethyl chloroformate;

[0299] (8) Preparation of (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)methyl carbonate:

[0300] Take (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol (250 mg, 648.40 μmol) and add it to 15 mL DMF to dissolve. 2 CO 3 (107.53 mg, 778.08 μmol) was stirred at room temperature for 30 min, then ethyl chloromethyl carbonate (125.77 mg, 907.76 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.12 g of methyl (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy) carbonate in a yield of 38.95%.

[0301] Example 33: A method for preparing 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate (i.e., Compound A33), comprising the following steps:

[0302] Steps (1)-(6): same as steps (1)-(6) of Example 32;

[0303] (7) Preparation of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl methyl carbonate:

[0304] Take (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol (250 mg, 648.40 μmol) and add it to 15 mL DMF to dissolve. 2 CO 3 (107.53 mg, 778.08 μmol) was stirred at room temperature for 30 min, then methyl chloroformate (85.78 mg, 907.76 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.15 g of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate methyl ester in a yield of 51.43%.

[0305] Example 34: A method for preparing 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate (i.e., Compound A34) comprising the following steps:

[0306] Steps (1)-(6): same as steps (1)-(6) of Example 32;

[0307] (7) Preparation of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ethyl carbonate:

[0308] Take (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1h-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol (250 mg, 648.40 μmol) and add it to 15 mL DMF to dissolve. Add K 2 CO 3 (107.53 mg, 778.08 μmol) was stirred at room temperature for 30 min, then ethyl chloroformate (98.51 mg, 907.76 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.12 g of ethyl 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate in a yield of 40.88%.

[0309] Example 35: A method for preparing 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl carbonate isopropyl (i.e., Compound A35), comprising the following steps:

[0310] Steps (1)-(6): same as steps (1)-(6) of Example 32;

[0311] (7) Preparation of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl isopropyl carbonate:

[0312] Take (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1h-pyrazol-3-yl)-2-chloro-4-fluorophenyl)methanol (250 mg, 648.40 μmol) and add it to 15 mL DMF to dissolve. Add K 2 CO 3 (107.53 mg, 778.08 μmol) was stirred at room temperature for 30 min, then carbonyl chloride (111.24 mg, 907.76 μmol) was added and reacted at room temperature for 6 hours. After the reaction was completed, it was poured into 20 mL of water, and the mixture was extracted with 20 mL of ethyl acetate. The organic layer was collected and washed with anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and subjected to column chromatography to obtain 0.14 g of 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenyl isopropyl carbonate in a yield of 44.85%.

[0313] The structural formula and molecular formula of the target compound prepared in the above examples are shown in Table 1, and its physicochemical properties and spectral information are shown in Table 1;

[0314] Table 1 Molecular formula and structural formula of the target compound obtained in Examples 1-35

[0315]

[0316]

[0317]

[0318] Table 2 Spectral data of target compounds obtained in Examples 1-35

[0319]

[0320]

[0321]

[0322]

[0323]

[0324]

[0325]

[0326] Post-emergence activity test of target compounds:

[0327] This test adopts the spray method, with a variety of weeds as the test objects. Weed seeds are directly sown and evenly spread in 8x8cm plastic pots filled with two-thirds organic substrate soil and grown in a greenhouse. When both grass weeds and broadleaf weeds grow to the two- to three-leaf stage, they can be used for testing. The compound is dissolved in 100μLDMF and diluted to a dose of 37.5–150g ai / ha with 0.1% Tween-80. All weeds are sprayed with pyraclostrobin and isopyraclostrobin as positive controls and target compounds. After the treated weeds are placed in the greenhouse for 15 days, their herbicidal activity is evaluated by visual inspection against the CK group, and repeated three times.

[0328] Table 3 Post-emergence herbicidal activity of target compounds of Examples 1-35

[0329]

[0330]

[0331]

[0332] It can be seen from Table 3 that at a dosage of 150 g ai / ha, compounds A1-A14, A16, A18-A24, A33 and A35 have excellent herbicidal activity against barnyard grass, crabgrass, Setaria viridis, velvet, Amaranthus retroflexus and Portulaca oleracea, the weeds are completely withered, and their growth is severely inhibited, with the inhibition rate reaching 100%, which is better than the positive control pyraclostrobin and equivalent to the positive control isopyraclostrobin; at a dosage of 75 g ai / ha, compounds A2, A4, A8, A14, A16, A18, A20, A21, A22, A33 and A35 have excellent herbicidal activity against barnyard grass, crabgrass, Setaria viridis, velvet, Amaranthus retroflexus and Portulaca oleracea, with the control rate reaching 100%.

[0333] Table 4 Herbicidal spectrum test of target compounds of Examples 20 and 21 (150 g ai / ha)

[0334]

[0335]

[0336] The herbicidal spectrum of compounds A20 and A21 was evaluated by measuring the herbicidal activity of compounds A20 and A21 against 29 different weeds. As shown in Table 4, compounds A20 and A21 have good herbicidal activity against most dicotyledonous weeds. Compounds A20 and A21 have 100% control effect on 22 weeds including Cassia seed, Hairy vetch, Alfalfa, Arrow snake pea, Echinochloa crusgalli, Setaria viridis, Goosegrass, Digitaria sanguinalis, Abutilon, Amaranthus retroflexus, Purslane, Plantain, Astragalus, Licorice, Marigold, Morning glory, Solanum nigrum, Clover, Zinnia, Amaranthus oleraceus and Horseshoe tendon at 150 g.ai / ha. In addition, it is worth mentioning that the inhibition rate of compounds A20 and A21 on four weeds, Cassia seed, hairy vetch, alfalfa and snake pea, reached 100%, which was significantly better than pyraclostrobin (40%, 60%, 80% and 60%) and isopyraclostrobin (70%, 80%, 70% and 90%). The results showed that compound A20 had the best inhibitory effect and was more broad-spectrum than the positive control drugs pyraclostrobin and isopyraclostrobin, and could be used as a potential PPO inhibitory herbicide.

[0337] Target compound crop safety testing:

[0338] Six crops (wheat, corn, rice, cotton, peanut and soybean) were used as further crop safety tests. The test method was similar to the post-emergence herbicidal activity test. The commercial herbicides pyraclostrobin and isopropylpyraclostrobin were used as control drugs. The crop safety of compounds A20 and A21 at a dosage of 150 g ai / ha was determined. The results are shown in Table 5.

[0339] Table 5 Crop safety test of target compounds of Examples A20 and A21 (150 g ai / ha)

[0340]

[0341] As shown in Table 5, compared with pyraclostrobin and isopyraclostrobin, compounds A20 and A21 cause less damage to crops and have less impact on the growth of the six crops. Compounds A20 and A21 are highly sensitive to peanuts, soybeans and cotton, with damage values ​​of 45-60%. In contrast, compounds A20 and A21 are less sensitive to wheat, corn and rice, with damage values ​​of 20-40%. Among them, compound A20 is the least sensitive to wheat, with only 20% crop damage. Comprehensive crop selectivity analysis shows that compound A20 has good crop selectivity and can be used as a potential herbicide for wheat and rice weed management.

[0342] The present invention also conducted a crop loss rate test on compounds A1-A19 and A22-A35, and found that the damage rates of compounds A1-A19 and A22-A35 to six crops (wheat, corn, rice, cotton, peanuts and soybeans) were all low (no more than 60%), and the target compounds of the present invention have excellent crop safety. Therefore, this series of compounds can be used as a potential new broad-spectrum herbicide for wheat fields, and can be further developed so that it can be applied to more farmlands.

[0343] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention without departing from the technical solution of the present invention still falls within the scope of the technical solution of the present invention.

Claims

1. A phenylpyrazole derivative, characterized in that: The general structural formula of the derivative is as follows: In formula (I): X is selected from CH2, O, S, COO, NR 7 ; Y is selected from (CR 8 R 9 )n; Z is selected from O, S, NR 7 ; n is selected from 0, 1, 2, 3, and 4 respectively; R 1 are respectively selected from C1-C6 alkyl or C1-C6 haloalkyl; R 2 Selected from OCR 10 R 11 , CR 12 , -CN and halogen; R 3 are respectively selected from H, -CN and halogen; R 4 , R 5 are selected from H, halogen, -CN, NO2, NH2, C1-C6 alkyl, (C1-C6 haloalkyl)-O- or (C1-C6 alkyl)-SO2-; R 6 are respectively selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C4 alkoxy C1-C6-alkyl, C1-C4 haloalkoxy C1-C6 alkyl; R 7 are respectively selected from H, hydroxyl, C1-C6 alkyl or C1-C4 alkoxy; R 8 , R 9 , R 10 , R 11 and R 12 They are respectively selected from H, halogen, hydroxy, C1-C6 alkyl or C1-C6 haloalkyl.

2. The phenylpyrazole derivative according to claim 1, characterized in that Includes the following compounds: Compound A1: 1-(methoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A2: 1-(ethoxycarbonyl)-oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A3: 1-(((ethylthio)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A4: 1-((isopropoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A5: 1-((Propoxy)carbonyl)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A6: 1-((isobutylcarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A7: 1-((Butoxycarbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A8: 1-(((but-3-en-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A9: 1-((but-3-yn-1-oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A10: 1-((2-methoxyethoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl ester; Compound A11: 1-(((cyclopropylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A12: 1-(((cyclobutylmethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A13: 1-((cyclopentylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A14: 1-((((tetrahydrofuran-2-yl)methoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A15: 1-((cyclohexylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A16: 1-((phenoxy)carbonyl)oxyethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A17: 1-(naphthalen-2-ylmethoxy)carbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A18: 1-((2-ethoxy-2-oxyethoxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A19: 1-((((1-ethoxy-2-methyl-1-oxopropyl-2-yl)oxy)carbonyl)oxy)ethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A20: (Ethoxycarbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A21: ((isopropoxycarbonyl)oxy)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A22: ((Propyloxy)carbonyl)methyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A23: ((Cyclopentylmethoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate Compound A24: ((phenoxy)carbonyl)oxymethyl-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A25: 1-(Ethoxycarbonyl)oxy-ethyl-3-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)benzoate; Compound A26: 1-(ethoxycarbonyl)oxy-5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chlorobenzoate; Compound A27: 1-(ethoxycarbonyl)oxy-2-chloro-5-(5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-4-fluorobenzoate; Compound A28: 1-(Ethoxycarbonyl)oxyethyl-5-(4-bromo-5-methoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A29: 1-(Ethoxycarbonyl)oxy-5-(4-bromo-5-isopropoxy-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A30: (Ethoxycarbonyl)oxymethyl 2-chloro-5-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-4-fluorobenzoate; Compound A31: (Ethoxycarbonyl)oxymethyl-5-(4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzoate; Compound A32: (5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorophenoxy)methyl carbonate; Compound A33: 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate; Compound A34: 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate; Compound A35: isopropyl 5-(4-bromo-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl)-2-chloro-4-fluorobenzyl carbonate.

3. The method for preparing a phenylpyrazole derivative according to any one of claims 1 to 2, characterized in that: The steps include: (1) Preparation of intermediate 1: Sodium hydride and dimethyl carbonate are added to toluene in an ice bath in batches and stirred at room temperature. Then 2,4-disubstituted-5-methylacetophenone is dissolved in a constant pressure dropping funnel containing toluene, and the mixed solution is added dropwise to the toluene containing sodium hydride and dimethyl carbonate within 40 minutes. After stirring at room temperature for 10 minutes, the mixture is heated to react. After the reaction is completed, the reaction mixture is cooled to room temperature, glacial acetic acid is added, and the mixture is extracted with water and ethyl acetate. A saturated sodium bicarbonate solution is then added for extraction. After drying and column chromatography, intermediate 1 is obtained. (2) Preparation of intermediate 2: Take intermediate 1 and methylhydrazine sulfate into ethanol, heat the reaction solution, and after the reaction is completed, pour the reaction solution into water, add ethyl acetate, let stand, and filter to obtain intermediate 2; (3) Preparation of intermediate 3: Take intermediate 2, cesium carbonate and ethyl difluorobromoacetate / bromopropane / iodomethane and add them to DMF, then slowly heat the mixture, wait for the reaction liquid to cool to room temperature, extract with water and ethyl acetate, dry and column chromatograph to obtain intermediate 3; (4) Preparation of intermediate 4: Add intermediate 3 and N-bromosuccinimide to DMF, condense and reflux under argon protection; after the reaction is completed, cool the reaction solution to room temperature, add ethyl acetate and water for extraction; separate the organic layer, wash with saturated brine, dry, concentrate, and perform column chromatography to obtain intermediate 4; (5) Preparation of intermediate 5: Take intermediate 4 and dissolve it in glacial acetic acid, add concentrated H2SO4 and chromium trioxide, react at room temperature, after the reaction is completed, pour the reaction solution into ice water, let it stand, filter it with suction, wash it with water, and recrystallize it to obtain intermediate 5; (6) Preparation of intermediate 6: Take intermediate 4, NBS and benzoyl peroxide and add them into a three-necked flask, add dimethyl carbonate, react at 90.3°C under argon protection. After the reaction is completed, cool the reaction to room temperature, concentrate under reduced pressure, then add water and ethyl acetate to extract, dry, concentrate under reduced pressure, and purify by column chromatography to obtain intermediate 6; (7) Preparation of intermediate 7: Take intermediate 6 and dimethyl sulfoxide and add them into a three-necked flask, add a small amount of water to participate in the reaction, and after the reaction is completed, wait for the reaction to cool to room temperature, then add water and ethyl acetate to extract, dry, concentrate under reduced pressure, and purify by column chromatography to obtain intermediate 7; (8) Preparation of intermediate 8: Add alcohol / thiol / amino / oxime and pyridine to dichloromethane, slowly add chloroformic acid-1-chloro substituted ester to react under ice bath conditions, add dichloromethane and water to extract, wash with saturated brine, dry, concentrate, and column chromatography to obtain intermediate 8; (9) Preparation of Intermediate 9 Tetrahydrofuran was placed in a three-necked flask, and sodium hydride and 2,4-disubstituted-5-methylacetophenone were added in batches under argon protection. The mixture was stirred at room temperature, and then ethyl trifluoroacetate was slowly added dropwise to the mixture to react at room temperature. After the reaction was completed, water and ethyl acetate were added for extraction, and the mixture was dried, concentrated under reduced pressure, and purified by column chromatography to obtain intermediate 9. (10) Preparation of intermediate 10: Intermediate 9 and hydrazine hydrate were condensed and refluxed in glacial acetic acid. After the reaction was completed, the reaction mixture was cooled to room temperature, extracted with water and ethyl acetate, dried, concentrated under reduced pressure, and purified by column chromatography to obtain intermediate 10; (11) Preparation of intermediate 11: Take the intermediate 10 and dimethyl sulfate into toluene, condense and reflux, and after the reaction is completed, wait for the reaction to cool to room temperature, pour the reaction solution into ice water, let it stand, precipitate flocs, and filter to obtain the intermediate 11; (12) Preparation of intermediate 12: Take intermediate 11 and NBS / NCS and add them to glacial acetic acid. Heat the reaction solution. After the reaction is completed, cool the reaction solution to room temperature, add ethyl acetate and water for extraction; separate the organic layer, wash with saturated brine, dry, concentrate, and perform column chromatography to obtain intermediate 12; (13) Preparation of intermediate 13: Take intermediate 12 and add it to glacial acetic acid, add concentrated H2SO4 and chromium trioxide, react at room temperature, after the reaction is completed, pour the reaction solution into ice water, let it stand, filter it with suction, wash it with water, and recrystallize it to obtain intermediate 13; (14) Preparation of the target compound phenylpyrazole derivative: Take intermediate 5 / 7 / 13 and add them to DMF, add K2CO3 and stir at room temperature, then add intermediate 8 and react at room temperature. After the reaction is complete, the system is washed with saturated sodium chloride solution, extracted with water and ethyl acetate, dried, concentrated under reduced pressure, and purified by column chromatography to obtain a phenylpyrazole derivative.

4. The method for preparing a phenylpyrazole derivative according to claim 3, characterized in that: In step (1), the molar ratio of the 2,4-disubstituted-5-methylacetophenone, dimethyl carbonate and sodium hydride is: 2,4-disubstituted-5-methylacetophenone: dimethyl carbonate: sodium hydride = 1:4:3; the amount of toluene is controlled by adding 1 mL of toluene per millimole of 2,4-disubstituted-5-methylacetophenone; in step (2), the molar ratio of the intermediate 1 and methylhydrazine sulfate is: Intermediate 1: methylhydrazine sulfate = 1:4; the amount of ethanol is controlled by adding 1 mL of ethanol per millimole of intermediate 1; in step (3), the molar ratio of the intermediate 2, cesium carbonate and difluoroethyl bromoacetate / bromopropane / iodomethane is: intermediate 2: cesium carbonate: difluoroethyl bromoacetate / bromopropane / iodomethane = 1:1.3:1.5; the amount of DMF is controlled by adding DMF per millimole of intermediate 2. 1mL is used for control; in step (4), the molar ratio of the intermediate 3 and NBS is: intermediate 3:NBS=1:3; the amount of DMF is controlled by adding 1mL of DMF per millimole of intermediate 3; in step (5), the molar ratio of the intermediate 4 and chromium trioxide is: intermediate 4:chromium trioxide=1:3; the amount of acetic acid is controlled by adding 1mL of acetic acid per millimole of intermediate 4, and the amount of sulfuric acid is controlled by adding 0.1mL of sulfuric acid per millimole of intermediate 4; in step (6), the molar ratio of the intermediate 4, NBS and BPO is: intermediate 4:NBS:BPO=1:1:0.1; the amount of dimethyl carbonate is controlled by adding 1mL of dimethyl carbonate per millimole of intermediate 4; in step (7), the amount of DMSO is controlled by adding DMSO per millimole of intermediate 6. The amount of water is controlled by adding 1 mL of water per mmol of the intermediate 6.

5. The method for preparing a phenylpyrazole derivative according to claim 3, characterized in that: In step (8), the molar ratio of the alcohol / mercapto / amino / oxime, 1-chloro substituted chloroformate and pyridine is: alcohol / mercapto / amino / oxime: 1-chloro substituted chloroformate: pyridine = 2:1:1.5; the amount of dichloromethane is controlled by adding 1 mL of dichloromethane per millimole of 1-chloro substituted chloroformate; in step (9), the 2,4-disubstituted-5-methylacetophenone, ethyl trifluoroacetate and The amount of sodium hydride used is calculated in a molar ratio of: 2,4-disubstituted-5-methylacetophenone: ethyl trifluoroacetate: sodium hydride = 1:4:3; the amount of tetrahydrofuran used is controlled by adding 1 mL of tetrahydrofuran per millimole of 2,4-disubstituted-5-methylacetophenone; in step (10), the amount of intermediate 9 and hydrazine hydrate used is calculated in a molar ratio of: intermediate 9: hydrazine hydrate = 1:2; the amount of glacial acetic acid used is calculated by adding 1 mL of tetrahydrofuran per millimole of 2,4-disubstituted-5-methylacetophenone. The amount of intermediate 9 is controlled by adding 1 mL of glacial acetic acid; in step (11), the amount of intermediate 10 and dimethyl sulfate is calculated in molar ratio as follows: intermediate 10: dimethyl sulfate = 1:3; the amount of toluene is controlled by adding 1 mL of toluene per millimole of intermediate 10; in step (12), the amount of intermediate 11 and NBS / NCS is calculated in molar ratio as follows: intermediate 11: NBS / NCS = 1:3; the amount of acetic acid is controlled by adding 1 mL of acetic acid per millimole of intermediate 11; in step (13), the amount of intermediate 12 and chromium trioxide is calculated in molar ratio as follows: intermediate 12: chromium trioxide = 1:3; the amount of glacial acetic acid is controlled by adding 1 mL of glacial acetic acid per millimole of intermediate 12, and the amount of sulfuric acid is controlled by adding 0.1 mL of sulfuric acid per millimole of intermediate 12.

6. The method for preparing a phenylpyrazole derivative according to claim 3, characterized in that: In step (14), the molar ratio of the intermediate 5 / 7 / 13, intermediate 8 and K2CO3 is: intermediate 5 / 7 / 13: intermediate 8: K2CO3 = 1:1.2:1.4; the amount of DMF is controlled by adding 1 mL of DMF per millimole of intermediate 5 / 7 / 13.

7. Use of the phenylpyrazole derivatives as claimed in claim 1 in the preparation of weed killers and weed growth enzyme inhibitors.

8. Use of the phenylpyrazole derivatives as claimed in claim 17 in the preparation of weed control and weed growth enzyme inhibitors, characterized in that: The weeds are crabgrass, barnyard grass, ramie, amaranth, ryegrass, purslane, nightshade, dandelion, clover, goosegrass, foxtail grass, duckweed, big-leaf nepeta, oats, bluegrass, sudan grass, cassia seed, hairy vetch, alfalfa, snake pea, plantain, astragalus, licorice, marigold, morning glory, zinnia, grain amaranth, cloud leaf grass, and horse hoof tendon.

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