Preparation and application of isoxazoline derivative containing triazole thioether structure

Abstract

The invention relates to the technical field of pesticide chemistry, and discloses an isoxazoline derivative containing a triazole thioether structure and preparation and application of the isoxazoline derivative, three active fragments of isoxazole, triazole and thioether are innovatively subjected to structural splicing synthesis, and the preparation process is clear in step, mild in reaction condition, excellent in intermediate yield and easy to industrially amplify. The insecticidal activity of the derivative on major agricultural pests such as plutella xylostella, spodoptera frugiperda and ostrinia nubilalis reaches 100%, the activity of the derivative is equivalent to that of fluxazole amide, the derivative can prevent and treat various pests such as cotton bollworm, aphid and rice planthopper, and the derivative is not applied in the field, has no drug resistance of the pests, has the advantages of broad spectrum, high efficiency, difficult generation of drug resistance and the like, can be used for preparing insecticides, and has wide application prospects. A brand new solution is provided for green prevention and control of agricultural pests.

Description

Technical Field

[0001] This invention relates to the field of pesticide chemistry, and more specifically, to the preparation and application of isoxazoline derivatives containing a triazole thioether structure. Background Technology

[0002] In modern agricultural production, pest and disease control is a crucial link in ensuring crop yield and quality, and the research and development of green, efficient, and low-toxicity pesticides has become a core development direction for the industry. Isoxazole insecticides, due to their novel mechanism of action, excellent activity, low toxicity, and long-lasting effect, have led to the successful development of commercial agents such as fluoxazolamide and flurana, which are effective against a wide range of pests. However, with long-term single-use, some pests have developed varying degrees of resistance to these agents, and the targeted efficacy of some derivatives against major agricultural pests such as the diamondback moth and fall armyworm has gradually decreased, making it difficult to meet the control needs in actual production.

[0003] Triazole ring derivatives were initially widely used for plant disease control due to their excellent fungicidal activity. In recent years, research has found that they have potential value in the field of insecticides. As a key pharmacophore in the pesticide and pharmaceutical fields, the triazole structure can endow molecules with good biological activity. However, insecticides with triazole as the core skeleton alone have problems such as a narrow insecticidal spectrum and insufficient target affinity, which limits their application in the control of various pests.

[0004] Thioether compounds play an important role in pesticide development, widely covering multiple fields such as fungicide, acaricide, insecticide, and herbicide. Their structure can effectively regulate the lipophilicity and target affinity of molecules, and are key pharmacophores for forming highly active pesticides. However, the insecticidal activity of single thioether derivatives is relatively weak, and they need to be combined with other active fragments to significantly improve efficacy. Using them alone is difficult to achieve ideal pest control results.

[0005] In existing technologies, isoxazole, triazole, and thioether active fragments are mostly used individually or in pairs in pesticide molecule design. There are no reports of rationally combining these three components, making it difficult for existing insecticides to simultaneously possess the comprehensive advantages of broad-spectrum insecticidal activity, high activity, and low resistance. Addressing this technological gap and the shortcomings of existing pesticides in controlling major agricultural pests, such as resistance and insufficient efficacy, this invention innovatively fuses isoxazole, triazole, and thioether fragments to synthesize a series of isoxazoline derivatives containing triazole thioether structures. This aims to overcome the performance limitations of existing insecticides and provide a novel insecticide with excellent control efficacy against major pests such as diamondback moth, fall armyworm, and corn borer. Summary of the Invention

[0006] In view of this, the present invention proposes a method for the preparation and application of isoxazoline derivatives containing a triazole thioether structure, aiming to solve the problems in the current technology.

[0007] This invention proposes an isoxazoline derivative containing a triazole thioether structure, the general structural formula of which is shown in formula (I):

[0008] Formula (I); Among them: R1, R2, and R3 independently include hydrogen, halogen, cyano, nitro, trifluoromethyl, C1~C6 alkyl or C1~C6 alkoxy; R4 includes hydrogen, halogen, cyano, nitro, C1-C6 alkyl or phenyl substituents; R5 includes hydrogen, halogen, cyano, carbonyl, nitro, C1-C6 alkyl, C1-C6 olefin, C1-C6 alkyne, substituted benzyl, cycloalkyl, and heterocyclic.

[0009] Preferably, in general formula I, R1 is chlorine; R2 is hydrogen or fluorine; R3 is chlorine or trifluoromethyl; R4 is a phenyl substituent; and R5 is methyl, ethyl, propyl, butyl, pentyl, C1-C6 alkyne substituent, o-(fluorine) substituted phenyl, p-(fluorine) substituted phenyl, p-(trifluoromethoxy) substituted phenyl, p-(trifluoromethyl) substituted phenyl, m-(fluorine) substituted phenyl, o / m-(fluorine) substituted phenyl, o / p-(fluorine) substituted phenyl, p-(methyl) substituted phenyl, p-(tert-butyl) substituted phenyl, o-(chlorine) substituted phenyl, p-(chlorine) substituted phenyl, o / m-(chlorine) substituted phenyl, p-(bromine) substituted phenyl, o / p-(chlorine) substituted phenyl, p-(cyano) substituted phenyl, p-(nitro) substituted phenyl, cycloalkyl substituent, or heterocyclic substituent.

[0010] Preferably, the structure of the isoxazoline derivative containing a triazole thioether structure includes:

[0011] Another object of the present invention is to provide a method for preparing the isoxazoline derivative containing the triazole thioether structure, the preparation method comprising the following steps: (1) Compound A, hydroxylamine hydrochloride, sodium carbonate and solvent were mixed and stirred to react, and intermediate 1 was obtained; (2) Chloride intermediate 1 obtained in step (1), and then dispose of the chlorinated product, The mixture is reacted with a solvent to obtain intermediate 2; (3) Hydrolyze the intermediate 2 obtained in step (2) and the base in a solvent to obtain intermediate 3; (4) Take the intermediate 3 obtained in step (3) The reaction with triethylamine in a solvent yields intermediate 4; (5) React intermediate 4 obtained in step (4), N2H4•H2O and solvent to obtain intermediate 5; (6) Take the intermediate 5 obtained in step (5) The reaction in the solvent yields intermediate 6; (7) Take the intermediate 6 obtained in step (6), potassium carbonate, potassium iodide, The compound is reacted with a solvent to yield the target compound; X is a halogen. The synthesis route is as follows: .

[0012] Preferably, the solvent in step (1) is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol and water; the molar ratio of compound A, hydroxylamine hydrochloride, sodium carbonate and solvent is 1:(1~3):(1~5):(2~5).

[0013] Preferably, the solvent in step (2) is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol, and water; intermediate 1, chlorinated reagent, The molar ratio of the solvent to the solvent is 1:(1~4):(1~4):(1~3).

[0014] Preferably, in step (3), the alkali is lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium tert-butoxide, sodium acetate, potassium acetate or sodium bicarbonate; and the solvent is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol and water.

[0015] Preferably, the solvent in step (4) is dichloromethane; the base is triethylamine; and intermediate 3... The molar ratio of alkali and solvent is 1:(1~2):(1~2):(1~4).

[0016] Preferably, the solvent in step (5) is methanol; the molar ratio of intermediate 4, N2H4•H2O and solvent is 1:(1~14):(1~4).

[0017] Preferably, the solvent in step (6) is ethanol; intermediate 5, The molar ratio of the solvent to the solvent is 1:(1~2):(1~3).

[0018] Preferably, the solvent in step (7) is acetonitrile; intermediate 6, potassium carbonate, potassium iodide, The molar ratio of the solvent to the solvent is 1:(1~2):(0~1):(1~2):(1~3).

[0019] Another object of the present invention is to provide an application of the isoxazoline derivative containing the triazole thioether structure in the control of agricultural pests.

[0020] Preferably, the application includes the preparation of insecticides; the agricultural pests include diamondback moth, corn borer, cotton bollworm, fall armyworm, armyworm, aphid, and rice planthopper.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows: 1) This invention is a novel pesticide that has not yet been marketed. It is the first time that three active fragments, isoxazole, triazole, and thioether, have been synergistically spliced ​​together to form a unique molecular skeleton. It has not yet been used in agricultural production, and pests have no related resistance basis. It can effectively solve the problem of resistance caused by long-term use of existing pesticides.

[0022] 2) The reaction steps of this invention are clear and controllable, the reaction conditions are mild, the intermediate yield is high, the solvents and reagents used are readily available, no special equipment is required, it is suitable for large-scale production, and reduces industrialization costs.

[0023] 3) It has 100% insecticidal activity against major agricultural pests such as diamondback moth, fall armyworm, and corn borer, which is comparable to the control agent fluoxazolamide. At the same time, it can control a variety of pests such as cotton bollworm, aphid, and rice planthopper, meeting the diversified control needs of different crops and different pests. Detailed Implementation

[0024] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0025] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included within this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0026] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0027] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0028] To better understand the present invention, the following embodiments are provided for further illustration, but the content of the present invention is not limited to the following embodiments.

[0029] Example 1 Preparation of N-((5-(benzylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-1).

[0030] (1) In a round-bottom flask, methyl 4-formyl-2-methylbenzoate (1.0 eq), ethanol (2.0 eq), and water (1.0 eq) were added as solvents. Hydroxylamine hydrochloride (1.3 eq) and sodium carbonate (1.5 eq) were then added sequentially with stirring at room temperature. After the reaction was completed by TLC monitoring, the reaction mixture was poured into a beaker and stirred until the solid precipitated completely. The mixture was then filtered and dried to obtain intermediate 1.

[0031]

[0032] The yield of intermediate 1 was calculated to be 93%.

[0033] (2) Following step (1), intermediate 1 (1.2 eq) and NCS (1.5 eq) were weighed and placed in a round-bottom flask under ice bath conditions. DMF was used as the solvent. After reacting in an ice bath for 0.5 h, the system was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, substituted -5-(3,3,3-trifluoropropane-1-en-2-yl)benzene (1.0 eq) was slowly added in portions to the above reaction system under ice bath conditions. Then, triethylamine (1.5 eq) was slowly added to the system using a constant pressure dropping funnel. The reaction was carried out at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction system was poured into saturated brine and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography to obtain intermediate 2.

[0034]

[0035] The yield of intermediate 2 was calculated to be 95%.

[0036] (3) Weigh intermediate 2 (1.0 eq) into a round-bottom flask, dissolve it in anhydrous ethanol solution, then add lithium hydroxide (1.5 eq) aqueous solution, reflux at 80°C with stirring, and monitor the reaction progress by TLC. After the reaction is complete, evaporate the system to dryness, then pour a small amount of ice water into the solution and stir, filter to remove insoluble matter, adjust the pH of the filtrate to 2-3 with 10% hydrochloric acid, filter out the solid and dry it to obtain intermediate 3.

[0037]

[0038] The yield of intermediate 3 was calculated to be 98%.

[0039] (4) Weigh intermediate 3 (1.0 eq) into a round-bottom flask and dissolve it in dichloromethane under ice bath conditions to form system A. Place thionyl chloride (5.0 eq) in a constant pressure funnel and slowly add it dropwise into system A. Remove the ice bath about 5 minutes after the addition is complete, heat at 50°C under reflux for 3 hours, and monitor the reaction progress by TLC.

[0040] After the reaction was complete, system A was evaporated to dryness and dissolved in dichloroethane. Glycine methyl ester (1.5 eq) was weighed and dissolved in 1,2-dichloroethane, and triethylamine (2.0 eq) was added under ice bath conditions. System A was slowly added dropwise to system B, and after approximately 5 minutes of complete addition, the ice bath was removed, and the mixture was heated to reflux at 70°C. After the reaction was completed, the mixture was extracted with dichloromethane, and the organic layer was collected and purified by column chromatography to obtain intermediate 4.

[0041]

[0042] The yield of intermediate 4 was calculated to be 85%.

[0043] (5) Weigh intermediate 4 (1.0 eq) into a round-bottom flask, dissolve it in anhydrous methanol solution, then add hydrazine hydrate (13.8 eq), and reflux at 80°C with stirring for 5 h. After the reaction is complete, evaporate the system to dryness, add a large amount of water and stir to precipitate the solid, then filter out the solid and dry it to obtain intermediate 5.

[0044]

[0045] The yield of intermediate 5 was calculated to be 98%.

[0046] (6) Weigh intermediate 5 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous ethanol, then add methyl isothiocyanate (1.5 eq), and heat to reflux at 80°C with stirring for 6 h. After the reaction is complete, evaporate the system to dryness, add 2M sodium hydroxide solution, and heat to reflux at 80°C with stirring for 1 h. After the reaction is complete, cool the system to room temperature, adjust the pH of the filtrate to 2 with 10% hydrochloric acid, filter out the solid and dry it, and purify it by column chromatography to obtain intermediate 6.

[0047]

[0048] The yield of intermediate 6 was calculated to be 92%.

[0049] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add benzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-1.

[0050]

[0051] The yield of the target compound Y-1 was calculated to be 45%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 5.7 Hz, 2H), 7.48 (d, J = 10.3Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.30 (s, 5H), 6.51 (t, J = 5.7 Hz, 1H), 4.89 (s, 2H), 4.52 (d, J = 5.7 Hz, 2H), 4.07 (d, J = 17.2 Hz, 1H), 3.68 (d, J= 17.2 Hz, 1H), 3.31 (s, 3H), 2.43 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 168.91, 155.91, 155.56, 154.08, 153.89,143.26, 137.65, 137.48, 136.22, 132.98, 129.68, 129.37, 128.82, 128.34,128.12, 127.63, 127.57, 124.85, 124.49, 123.27, 123.13, 122.60, 87.19, 86.95,49.27, 44.08, 35.12, 29.82, 27.91, 19.97. Example 2 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-2-methyl-N-((4-methyl-5-((4-methylbenzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-2) Steps (1) to (6) are the same as in Example 1; (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add 4-methylbenzyl bromide (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-2.

[0052]

[0053] The yield of the target compound Y-2 was calculated to be 50%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 8.23 ​​(t, J = 5.7 Hz, 1H), 7.55 (dd, J = 7.0Hz, 3H), 7.47 (s, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.08 – 6.98 (m, 4H), 4.64(d, J = 5.6 Hz, 2H), 4.16 (s, 2H), 4.02 (d, J = 17.2 Hz, 1H), 3.62 (d, J =17.2 Hz, 1H), 3.35 (s, 3H), 2.44 (s, 3H), 2.27 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.15, 155.81, 155.66, 153.79, 153.29,151.45, 137.87, 137.70, 137.57, 133.35, 133.02, 132.98, 129.45, 129.02,128.82, 128.50, 128.12, 127.53, 126.95, 124.36, 123.16, 123.01, 87.05, 86.80,43.98, 38.15, 34.13, 30.36, 29.76, 21.18, 20.10. Example 3 Preparation of N-((5-((4-bromobenzyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-3) Steps (1) to (6) are the same as in Example 1; (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat under reflux at 60 °C and stir to activate for 0.5 h, then add p-bromobenzyl bromide (1.5 eq), heat under reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-3.

[0054]

[0055] The yield of the target compound Y-3 was calculated to be 57%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 7.99 (t, J = 5.7 Hz, 1H), 7.56 (d, J = 6.0Hz, 2H), 7.52 – 7.49 (m, 1H), 7.46 (s, 1H), 7.43 (d, J = 9.9 Hz, 1H), 7.34(d, J = 8.4 Hz, 2H), 7.12 – 7.07 (m, 2H), 4.65 (d, J = 5.8 Hz, 2H), 4.20 (s,2H), 4.04 (d, J = 17.2 Hz, 1H), 3.64 (d, J = 17.3 Hz, 1H), 3.43 (s, 3H), 2.43(s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.13, 155.84, 155.63, 153.83, 153.42,151.08, 137.72, 137.48, 135.71, 133.00, 132.96, 131.87, 130.68, 129.52,129.11, 128.54, 128.03, 127.55, 126.99, 124.38, 123.20, 123.05, 121.95,120.32, 87.10, 86.85, 44.01, 37.23, 34.14, 30.45, 29.77, 20.10. Example 4 Preparation of N-((5-((4-cyanobenzyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-4) Steps (1) to (6) are the same as in Example 1; (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat under reflux at 60 °C and stir to activate for 0.5 h, then add 4-cyanobenzyl bromide (1.5 eq), heat under reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-4.

[0056]

[0057] The yield of the target compound Y-4 was calculated to be 59%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.79 (t, J = 5.8 Hz, 1H), 7.56 (t, J = 5.6Hz, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 5.9 Hz, 3H), 7.38 (d, J = 8.3Hz, 2H), 4.66 (d, J = 5.7 Hz, 2H), 4.31 (s, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.3 Hz, 1H), 3.48 (s, 3H), 2.41 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.09, 155.81, 155.67, 155.45, 153.79,153.56, 150.64, 142.28, 137.67, 137.35, 135.65, 132.55, 132.48, 131.57,129.77, 129.58, 129.17, 127.91, 127.54, 125.36, 124.36, 123.16, 123.02,118.52, 112.92, 111.65, 87.11, 86.87, 43.98, 36.99, 34.13, 33.68, 31.03, 30.48, 20.04. Example 5 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-2-methyl-N-((4-methyl-5-((3-nitrobenzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-5) Steps (1) to (6) are the same as in Example 1; (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add 3-nitrobenzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-5.

[0058]

[0059] The yield of the target compound Y-5 was calculated to be 42%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.11 (t, J = 2.3 Hz, 1H), 8.05 (d, J = 10.9Hz, 1H), 7.91 (t, J = 5.7 Hz, 1H), 7.64 (d, J = 7.4 Hz, 1H), 7.56 (d, J = 6.3Hz, 2H), 7.51 – 7.46 (m, 2H), 7.43 (t, J = 8.0 Hz, 2H), 4.67 (d, J = 5.7 Hz, 2H), 4.39 (s, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 3.51(s, 3H), 2.42 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.14, 155.84, 155.68, 153.83, 153.65,150.67, 148.28, 139.07, 137.74, 137.43, 135.25, 133.01, 132.98, 129.75,129.54, 129.14, 128.03, 127.56, 124.38, 123.88, 123.19, 123.05, 122.89,87.12, 86.87, 44.03, 36.62, 34.11, 30.52, 29.79, 20.10. Example 6 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-N-((5-((2-fluorobenzyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Y-6).

[0060] Steps (1) to (6) are the same as in Example 1.

[0061] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add 2-fluorobenzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-6.

[0062]

[0063] The yield of the target compound Y-6 was calculated to be 48%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 5.7 Hz, 2H), 7.51 (s, 2H), 7.47(d, J = 9.2 Hz, 1H), 7.25 – 7.16 (m, 2H), 7.05 – 6.97 (m, 2H), 4.69 (d, J =5.2 Hz, 2H), 4.30 (s, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.67 (d, J = 10.3 Hz, 1H), 3.41 (s, 3H), 2.46 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.13, 161.84, 159.86, 155.86, 155.65,153.83, 153.47, 151.11, 137.74, 137.53, 133.05, 133.01, 131.09, 131.06,130.09, 130.02, 129.50, 129.12, 128.08, 127.56, 124.40, 124.36, 123.90,123.78, 123.21, 123.06, 115.77, 115.60, 87.10, 86.85, 44.05, 34.20, 31.63, 30.40, 29.80, 20.13. Example 7 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-2-methyl-N-((4-methyl-5-((4-(trifluoromethyl)benzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-7).

[0064] Steps (1) to (6) are the same as in Example 1.

[0065] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add 4-trifluoromethylbenzyl bromide (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-7.

[0066]

[0067] The yield of the target compound Y-7 was calculated to be 42%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.00 (t, J = 5.7 Hz, 1H), 7.55 (d, J = 5.7Hz, 2H), 7.50 (d, J = 8.0 Hz, 3H), 7.47 – 7.42 (m, 2H), 7.38 (d, J = 8.6 Hz,2H), 4.65 (d, J = 5.7 Hz, 2H), 4.32 (s, 2H), 4.04 (d, J = 17.2 Hz, 1H), 3.66(d, J = 17.2 Hz, 1H), 3.47 (s, 3H), 2.42 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.14, 155.83, 155.63, 153.82, 153.51,150.97, 140.80, 137.73, 137.44, 132.98, 132.95, 131.20, 130.21, 129.95,129.53, 129.38, 129.13, 128.02, 127.53, 125.70, 125.67, 125.06, 124.83,124.33, 123.19, 123.05, 87.10, 86.86, 43.99, 36.95, 34.12, 29.77, 22.77, 20.08. Example 8 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-2-methyl-N-((4-methyl-5-((4-(trifluoromethoxy)benzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-8).

[0068] Steps (1) to (6) are the same as in Example 1.

[0069] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add 4-trifluoromethoxybenzyl bromide (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-8.

[0070]

[0071] The yield of the target compound Y-8 was calculated to be 40%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.12 (t, J = 5.7 Hz, 1H), 7.55 (d, J = 6.3Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.47 – 7.40 (m, 2H), 7.25 (d, J = 8.6 Hz,2H), 7.08 (d, J = 8.6 Hz, 2H), 4.65 (d, J = 5.7 Hz, 2H), 4.24 (s, 2H), 4.03(d, J = 17.2 Hz,1H), 3.64 (d, J = 17.2 Hz, 1H), 3.43 (s, 3H), 2.42 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 169.12, 155.83, 155.63, 153.81, 153.46,151.07, 148.77, 137.73, 137.47, 135.43, 132.99, 132.94, 130.48, 129.49,129.08, 128.06, 127.52, 124.83, 124.31, 123.18, 123.03, 121.22, 119.39,87.08, 86.84, 43.96, 36.94, 34.10, 30.40, 20.08. Example 9 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((5-((2,4-dichlorobenzyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Y-9).

[0072] Steps (1) to (6) are the same as in Example 1.

[0073] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat under reflux at 60 °C and stir to activate for 0.5 h, then add 2,4-dichlorobenzyl bromide (1.5 eq), heat under reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-9.

[0074]

[0075] The yield of the target compound Y-9 was calculated to be 37%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 6.3 Hz, 2H), 7.52 – 7.50 (t,3H), 7.47 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 2.3 Hz, 1H), 7.10 (dd, J = 8.0,2.3 Hz, 1H), 4.69 (d, J = 5.7 Hz, 2H), 4.38 (s, 2H), 4.07 (d, J = 17.2 Hz,1H), 3.67 (d, J = 17.2 Hz, 1H), 3.46 (s, 3H), 2.46 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.06, 155.89, 155.57, 153.87, 153.35,151.08, 137.78, 137.40, 134.94, 134.68, 133.19, 132.08, 129.67, 129.62,129.27, 127.95, 127.57, 127.40, 124.47, 123.26, 123.11, 87.15, 86.90, 44.10,34.97, 34.38, 30.44, 29.83, 20.15. Example 10 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((4-methyl-5-(methylthio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-10).

[0076] Steps (1) to (6) are the same as in Example 1.

[0077] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add iodomethane (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-10.

[0078]

[0079] The yield of the target compound Y-10 was calculated to be 35%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 5.7 Hz, 2H), 7.52 (s, 1H), 7.50– 7.46 (m, 2H), 4.73 (d, J = 5.7 Hz, 2H), 4.08 (d, J = 17.2 Hz, 1H), 3.69 (d,J = 17.2 Hz, 1H), 3.61 (s, 3H), 2.67 (s, 3H), 2.47 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.16, 155.88, 155.66, 153.86, 153.20,153.09, 137.71, 137.55, 133.05, 133.01, 129.54, 129.12, 128.05, 127.58,124.41, 123.24, 123.09, 87.13, 86.88, 44.12, 34.11, 30.38, 29.81, 20.12,14.99. Example 11 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((5-(ethylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Y-11).

[0080] Steps (1) to (6) are the same as in Example 1.

[0081] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add bromoethane (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-11.

[0082]

[0083] The yield of the target compound Y-11 was calculated to be 46%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 5.7 Hz, 2H), 7.55 – 7.50 (m,2H), 7.46 (d, J = 8.0 Hz, 1H), 4.72 (d, J = 5.7 Hz, 2H), 4.08 (d, J = 17.2Hz, 1H), 3.68 (d, J = 17.8 Hz, 1H), 3.61 (s, 3H), 3.16 (q, J = 7.4 Hz, 2H), 2.47 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.12, 155.90, 155.62, 153.88, 152.93,152.21, 137.75, 137.54, 133.07, 133.03, 129.60, 129.19, 128.02, 127.59,124.46, 123.27, 123.13, 87.15, 86.90, 44.15, 34.37, 30.46, 29.83, 27.60,20.14, 15.02. Example 12 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((4-methyl-5-(propylthio)-4H-1,2,4-triazol-3-yl)methyl)benzamide (Y-12).

[0084] Steps (1) to (6) are the same as in Example 1.

[0085] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat under reflux at 60 °C and stir to activate for 0.5 h, then add bromopropane (1.5 eq), heat under reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-12.

[0086]

[0087] The yield of the target compound Y-12 was calculated to be 50%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 8.37 (t, J = 5.7 Hz, 1H), 7.55 (d, J = 5.7Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 5.7 Hz, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 3.57 (s, 3H), 3.01 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 1.65 (h, J = 7.4Hz, 2H), 0.94 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.16, 155.77, 155.68, 153.75, 153.12,152.13, 137.63, 137.55, 133.01, 132.97, 129.37, 128.90, 128.38, 128.10,127.51, 124.82, 124.24, 123.12, 122.97, 122.56, 87.02, 86.78, 44.02, 35.02,34.01, 30.44, 29.72, 22.81, 20.04, 13.17. Example 13 Preparation of N-((5-(butthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-13).

[0088] Steps (1) to (6) are the same as in Example 1.

[0089] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C for 0.5 h with stirring, then add bromobutane (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-13.

[0090]

[0091] The yield of the target compound Y-13 was calculated to be 53%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.35 (t, J = 5.7 Hz, 1H), 7.55 (d, J = 6.3Hz, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.43 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 6.3 Hz, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 3.57 (s, 3H), 3.04 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 1.60 (p, J = 7.4Hz, 2H), 1.35 (dt, J = 14.9, 7.4 Hz, 2H), 0.85 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.15, 155.76, 155.67, 153.73, 153.10,152.18, 137.62, 137.52, 133.00, 132.96, 129.36, 128.90, 128.36, 128.07,127.51, 126.84, 124.81, 124.24, 123.10, 122.96, 122.55, 87.26, 87.01, 86.77,86.52, 44.00, 33.99, 32.82, 31.36, 30.43, 29.71, 21.72, 20.02, 13.53. Example 14 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((5-(isopropylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Y-14).

[0092] Steps (1) to (6) are the same as in Example 1.

[0093] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add 2-iodopropane (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-14.

[0094]

[0095] The yield of the target compound Y-14 was calculated to be 53%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.43 (t, J = 5.7 Hz, 1H), 7.56 (d, J = 6.0Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.43 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 4.66 (d, J = 5.7 Hz, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.3 Hz, 1H), 3.60 (s, 3H), 3.59 – 3.54 (m, 1H), 2.40 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.22, 155.80, 155.69, 153.78, 153.13,151.31, 137.64, 137.59, 133.03, 132.99, 129.39, 128.92, 128.43, 128.12,127.54, 126.90, 124.29, 123.15, 123.00, 87.04, 86.80, 86.55, 64.90, 44.05,39.63, 34.18, 30.65, 29.74, 23.42, 20.04. Example 15 Preparation of N-((5-(but-2-yn-1-ylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-15).

[0096] Steps (1) to (6) are the same as in Example 1.

[0097] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C for 0.5 h with stirring, then add 1-bromo-2-butyne (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-15.

[0098]

[0099] The yield of the target compound Y-15 was calculated to be 58%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.28 (t, J = 5.7 Hz, 1H), 7.55 (d, J = 6.0Hz, 2H), 7.52 – 7.46 (t, 1H), 7.44 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 4.66(d, J = 5.8 Hz, 2H), 4.06 (d, J = 17.3 Hz, 1H), 3.71 (d, J = 2.6 Hz, 1H), 3.64 (s, 3H), 2.55 (s, 2H), 2.39 (s, 3H), 1.73 (t, J = 2.5 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.30, 155.86, 153.84, 153.75, 150.80,137.71, 137.60, 133.09, 133.05, 129.48, 129.04, 128.49, 128.14, 127.62,126.98, 124.91, 124.38, 123.20, 123.06, 120.39, 87.12, 86.88, 81.09, 73.22,44.09, 40.91, 34.16, 30.84, 29.80, 23.24, 20.09, 3.76. Example 16 Preparation of N-((5-((cyanomethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-16).

[0100] Steps (1) to (6) are the same as in Example 1.

[0101] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add bromoacetonitrile (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-16.

[0102]

[0103] The yield of the target compound Y-16 was calculated to be 55%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.33 (t, J = 5.9 Hz, 1H), 7.55 (d, J = 6.0Hz, 2H), 7.51 (d, J = 8.1 Hz, 1H), 7.45 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 4.67 (d, J = 5.9 Hz, 2H), 4.06 (d, J = 17.3 Hz, 1H), 3.83 (s, 2H), 3.70 (d, J= 17.4 Hz, 1H), 3.66 (s, 3H), 2.38 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.26, 155.89, 155.77, 154.64, 153.75,148.20, 137.68, 137.34, 132.97, 132.93, 129.39, 129.02, 128.47, 128.11,127.57, 127.46, 126.93, 124.42, 123.09, 122.94, 115.78, 87.07, 86.82, 64.97,43.94, 36.57, 33.93, 30.92, 20.03, 18.57. Example 17 Preparation of N-((5-((cyclopropylmethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-17).

[0104] Steps (1) to (6) are the same as in Example 1.

[0105] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add bromomethylcyclopropane (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-17.

[0106]

[0107] The yield of the target compound Y-17 was calculated to be 56%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.33 – 8.29 (m, 1H), 7.56 (d, J = 6.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 7.9 Hz, 1H), 4.66(d, J = 5.8 Hz, 2H), 4.07 (d, J = 17.2 Hz, 1H), 3.69 (d, J = 17.3 Hz, 1H), 3.61 (s, 3H), 2.98 (d, J = 7.4 Hz, 2H), 2.42 (s, 3H), 1.10 – 1.02 (m, 1H),0.57 – 0.51 (m, 2H), 0.21 – 0.17 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 169.17, 155.81, 155.67, 153.80, 153.21,152.19, 137.68, 137.55, 133.03, 133.00, 129.43, 128.96, 128.14, 127.54,124.85, 124.30, 123.17, 123.02, 122.59, 87.06, 86.82, 44.07, 39.51, 34.09,30.57, 29.76, 20.09, 10.95, 5.96. Example 18 Preparation of N-((5-((cyclobutylmethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-18) Steps (1) to (6) are the same as in Example 1.

[0108] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add bromomethylcyclobutane (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-18.

[0109]

[0110] The yield of the target compound Y-18 was calculated to be 48%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 8.34 (t, J = 5.7 Hz, 1H), 7.56 (d, J = 6.0Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 4.65 (d, J = 5.7 Hz, 2H), 4.07 (d, J = 17.2 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 3.57 (s, 3H), 3.11 (d, J = 7.6 Hz, 2H), 2.52 (p, J = 7.8 Hz, 1H), 2.41(s, 3H), 2.08 – 2.00 (m, 2H), 1.86 – 1.75 (m, 2H), 1.68 – 1.60 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 169.14, 155.78, 155.66, 153.77, 153.13,152.07, 137.67, 137.54, 133.03, 132.99, 132.71, 129.39, 128.93, 128.40,128.13, 127.52, 126.87, 124.25, 123.13, 122.99, 87.04, 86.79, 44.04, 39.34,34.88, 34.04, 30.47, 29.73, 27.59, 20.06, 17.78. Example 19 Preparation of N-((5-((2-cyclopropyl-2-oxoethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Y-19).

[0111] Steps (1) to (6) are the same as in Example 1.

[0112] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add α-bromocyclopropaneethyl ketone (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Y-19.

[0113]

[0114] The yield of the target compound Y-19 was calculated to be 48%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.96 (t, J = 5.6 Hz, 1H), 7.55 (d, J = 6.0Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J = 7.9 Hz, 1H), 4.63 (d, J = 5.7 Hz, 2H), 4.21 (s, 2H), 4.06 (d, J = 17.3 Hz, 1H), 3.69 (d, J= 17.3 Hz, 1H), 3.62 (s, 3H), 2.39 (s, 3H), 2.04 (td, J = 8.3, 3.9 Hz, 1H),1.07 – 1.00 (m, 2H), 0.98 – 0.90 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 203.44, 169.12, 155.81, 155.75, 153.80,153.43, 151.06, 137.69, 137.44, 133.02, 132.98, 129.46, 129.05, 128.50,128.05, 127.56, 127.49, 126.95, 124.35, 123.16, 123.01, 87.09, 86.84, 69.95,65.04, 44.02, 43.68, 34.09, 30.64, 29.75, 20.01, 15.57, 12.19. Example 20 Preparation of N-((5-(benzylthio)-4-ethyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Z-1).

[0115] Steps (1) to (5) are the same as in Example 1.

[0116] (6) Weigh intermediate 5 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous ethanol, then add ethyl isothiocyanate (1.5 eq), and heat under reflux at 80°C for 6 h. After the reaction is complete, evaporate the system to dryness, add 2M sodium hydroxide solution, and heat under reflux at 80°C for 1 h. After the reaction is complete, cool the system to room temperature, adjust the pH of the filtrate to 2 with 10% hydrochloric acid, filter out the solid and dry it, and purify it by column chromatography to obtain intermediate 6.

[0117]

[0118] The yield of intermediate 6 was calculated to be 97%.

[0119] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add benzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Z-1.

[0120]

[0121] The yield of the target compound Z-1 was calculated to be 48%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.97 (t, J = 5.6 Hz, 1H), 7.57 – 7.52 (m,3H), 7.49 (s, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.25 – 7.19 (m, 5H), 4.69 (d, J = 5.6 Hz, 2H), 4.28 (s, 2H), 4.02 (d, J = 17.2 Hz, 1H), 3.87 (q, J = 7.3 Hz, 2H), 3.60 (d, J = 17.3 Hz, 1H), 2.47 (s, 3H), 1.19 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.07, 155.86, 155.62, 153.84, 152.59,150.93, 137.81, 137.56, 136.52, 133.05, 133.01, 129.54, 129.12, 129.00,128.80, 128.13, 127.98, 127.56, 124.85, 124.41, 123.20, 123.06, 122.59,87.09, 86.84, 44.04, 39.17, 38.11, 34.25, 29.80, 20.15, 15.37. Example 21 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-N-((4-ethyl-5-((4-methylbenzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Z-2).

[0122] Steps (1) to (6) are the same as in Example 20.

[0123] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat and reflux at 60 °C with stirring for 0.5 h, then add 4-methylbenzyl bromide (1.5 eq), heat and reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Z-2. The yield of the target compound Z-2 was calculated to be 53%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 8.54 (t, J = 5.8 Hz, 1H), 7.55 (dd, J =13.7, 7.0 Hz, 3H), 7.46 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.2Hz, 2H), 7.02 (d, J = 6.4 Hz, 2H), 4.67 (d, J = 5.8 Hz, 2H), 4.19 (s, 2H), 3.99 (d, J = 17.2 Hz, 1H), 3.89 (q, J = 8.1 Hz, 2H), 3.60 (d, J = 17.3 Hz,1H), 2.44 (s, 3H), 2.26 (s, 3H), 1.18 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.07, 162.58, 155.71, 155.64, 153.70,152.67, 150.88, 150.80, 137.73, 137.69, 137.56, 133.24, 132.98, 132.94,129.36, 128.87, 128.77, 128.18, 127.47, 124.78, 124.27, 123.05, 122.91,122.52, 86.95, 86.71, 43.87, 39.11, 37.66, 36.48, 33.97, 21.09, 20.05, 15.25. Example 22 Preparation of N-((5-((4-bromobenzyl)thio)-4-ethyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Z-3).

[0124] Steps (1) to (6) are the same as in Example 20.

[0125] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add p-bromobenzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Z-3.

[0126]

[0127] The yield of the target compound Z-3 was calculated to be 59%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.05 (t, J = 5.6 Hz, 1H), 7.55 (d, J = 6.0Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 7.9 Hz, 1H),7.35 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 4.68 (d, J = 5.7 Hz, 2H),4.25 (s, 2H), 4.03 (d, J = 17.2 Hz, 1H), 3.92 (q, J = 7.3 Hz, 2H), 3.63 (d, J= 17.3 Hz, 1H), 2.45 (s, 3H), 1.22 (q, J = 6.6 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.05, 155.83, 155.61, 153.81, 152.73,150.55, 137.80, 137.48, 135.73, 133.00, 132.96, 131.84, 130.71, 129.53,129.09, 128.10, 127.54, 124.83, 124.36, 123.19, 123.04, 122.57, 121.90,87.08, 86.84, 44.01, 39.23, 36.96, 34.15, 29.77, 20.12, 15.38. Example 23 Preparation of N-((5-((4-cyanobenzyl)thio)-4-ethyl-4H-1,2,4-triazol-3-yl)methyl)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (Z-4).

[0128] Steps (1) to (6) are the same as in Example 20.

[0129] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add 4-cyanobenzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Z-4.

[0130]

[0131] The yield of the target compound Z-4 was calculated to be 42%; the spectral data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.86 (t, J = 5.9 Hz, 1H), 7.55 (d, J = 6.0Hz, 2H), 7.52 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.0 Hz, 1H), 7.46 – 7.43 (m,2H), 7.39 (d, J = 8.5 Hz, 2H), 4.67 (d, J = 5.7 Hz, 2H), 4.36 (s, 2H), 4.05(d, J = 17.2 Hz, 1H), 3.94 (q, J = 7.3 Hz, 2H), 3.68 (d, J = 17.3 Hz, 1H),2.43 (s, 3H), 1.22 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 168.98, 155.77, 155.64, 153.76, 152.87,150.04, 142.32, 137.74, 137.33, 132.94, 132.90, 132.43, 129.78, 129.56,129.12, 127.97, 127.51, 124.79, 124.33, 123.13, 122.98, 122.53, 118.54,111.58, 87.07, 86.82, 43.96, 39.24, 36.76, 34.12, 29.72, 20.06, 15.39. Example 24 Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazo-3-yl)-N-((4-ethyl-5-((3-nitrobenzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)-2-methylbenzamide (Z-5).

[0132] Steps (1) to (6) are the same as in Example 20.

[0133] (7) Weigh intermediate 6 (1.0 eq) into a round-bottom flask, dissolve it with anhydrous acetonitrile, then add finely ground potassium carbonate (1.2 eq) and potassium iodide (0.8 eq), heat to reflux at 60 °C and stir to activate for 0.5 h, then add 3-nitrobenzyl bromide (1.5 eq), heat to reflux at 110 °C. After the reaction is complete, evaporate the system to dryness, extract with ethyl acetate, collect the organic phase, dry it, and then purify it by column chromatography to obtain the target compound Z-5.

[0134] The yield of the target compound Z-5 was calculated to be 45%; the spectral data are as follows: 1H NMR (500 MHz, CDCl3) δ 8.21 (t, J = 5.8 Hz, 1H), 8.11 (t, J = 2.0Hz, 1H), 8.03 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H), 7.64 – 7.61 (m, 1H), 7.54 (d,J = 6.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.7 Hz, 2H), 7.41 (d,J = 7.9 Hz, 1H), 4.67 (d, J = 5.8 Hz, 2H), 4.39 (s, 2H), 4.04 (d, J = 17.2Hz, 1H), 3.97 (q, J = 7.3 Hz, 2H), 3.67 (d, J = 17.3 Hz, 1H), 2.42 (s, 3H), 1.23 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 168.98, 155.77, 155.64, 153.76, 152.87,150.04, 142.32, 137.74, 137.33, 132.94, 132.90, 132.43, 129.78, 129.56,129.12, 127.97, 127.51, 124.79, 124.33, 123.13, 122.98, 122.53, 118.54,111.58, 87.07, 86.82, 43.96, 39.24, 36.76, 34.12, 29.72, 20.06, 15.39. Effect verification 1) Insecticidal activity test against diamondback moth The leaf-dipping method was used to test the activity of the synthesized target compound against diamondback moth. First, fresh cabbage leaves were washed, dried, and cut into small leaves of roughly the same size and shape.

[0135] Place suitable filter paper at the bottom of the petri dish for later use. Prepare pesticide solutions at concentrations of 100 μg / mL and 50 μg / mL. Immerse chopped cabbage leaves in the pesticide solution for 30 seconds, then remove and place them in petri dishes. Perform triplicate for each pesticide concentration. After the cabbage leaves have air-dried, add 15 second-instar diamondback moths to each petri dish and transfer them to an AI-controlled climate incubator (temperature 26°C, humidity 85%, light / dark ratio 16:2). After 48 hours, remove the leaves and count the number of dead diamondback moths (larvae are considered dead if they cannot crawl normally when lightly touched). Record the data and calculate the mortality rate. The insecticidal activity calculation formula is as follows: Mortality rate = (Number of deaths including pesticide use - Number of deaths without pesticide use) / Total number of diamondback moths released × 100% At concentrations of 100 μg / mL and 50 μg / mL, the isoxazoline compounds containing triazole thioether structures prepared in Examples 1-24 of this invention exhibited 100% insecticidal activity against the diamondback moth. The results indicate that the compounds provided by this invention possess good insecticidal activity against the diamondback moth, comparable to the control agent fluoxazolamide (100%). This suggests that these compounds have promising potential for use in controlling the agricultural pest, the diamondback moth.

[0136] 2) Insecticidal activity test against fall armyworm The target compound was dissolved in dimethyl sulfoxide (DMSO) to prepare a 5000 mg / L stock solution, which was then serially diluted to different concentrations with 0.05% (w / v) Triton X-100. Equal volumes of DMSO and 0.05% (w / v) Triton X-100 were added to a blank. The prepared feed was added to 24-well plates. After the feed cooled and solidified, 100 μL of the target compound solution was added to the surface of the feed. After drying at room temperature, third-instar larvae were transferred to each well. Each concentration was repeated three times (24 larvae per replicate). Finally, the 24-well plates were stored in an incubator at 26°C and 85% relative humidity with a light / dark ratio of 16:8. After 48 hours, the plates were removed, and the number of dead fall armyworms was counted (larvae were considered dead if they could not crawl normally when lightly touched). Data were recorded, and the mortality rate was calculated. The insecticidal activity was calculated using the following formula: Mortality rate = (TC) / T × 100%; where T is the number of live parasites before the test and C is the number of live parasites after the test. At concentrations of 200 μg / mL and 100 μg / mL, the isoxazoline compounds containing triazole thioether structures prepared in Examples 1-24 of this invention exhibited 100% insecticidal activity against fall armyworm. The results indicate that the compounds provided by this invention possess good insecticidal activity against fall armyworm, comparable to the control agent fluoxazolamide (100%). This suggests that these compounds have promising potential for use in controlling the agricultural pest fall armyworm.

[0137] 3) Insecticidal activity test against corn borer Solutions of the test compounds at concentrations of 200 μg / mL and 100 μg / mL were added to 24-well plates. After drying at room temperature, third-instar larvae were transferred to each well. Each concentration was repeated three times (24 larvae per replicate). The plates were incubated at 26°C and 85% relative humidity with a light / dark ratio of 16:8 for 48 hours. The larvae were then removed, and the mortality rate of the corn borer was assessed (larvae were considered dead if they could not crawl normally when lightly touched). The insecticidal activity was calculated using the following formula: Mortality rate = (TC) / T × 100%; where T is the number of live worms before the test and C is the number of live worms after the test.

[0138] At concentrations of 200 μg / mL and 100 μg / mL, the isoxazoline compounds containing triazole thioether structures prepared in Examples 1-24 of this invention exhibited 100% insecticidal activity against the corn borer. The results indicate that the compounds provided by this invention possess good insecticidal activity against the corn borer, comparable to the control agent fluoxazolamide (100%). This suggests that these compounds have promising potential for use in controlling the agricultural pest, the corn borer.

[0139] In summary, the compounds described in this invention exhibit good insecticidal activity against agricultural pests such as diamondback moth, fall armyworm, and corn borer, and can be used as candidate insecticides for the control of these pests in agricultural pest management.

[0140] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the specific implementation of the present invention. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. An isoxazoline derivative containing a triazole thioether structure, characterized in that, The general structural formula of the isoxazoline derivatives containing the triazole thioether structure is shown in formula (I): Equation (I); Among them: R1, R2, and R3 independently include hydrogen, halogen, cyano, nitro, trifluoromethyl, C1~C6 alkyl or C1~C6 alkoxy; R4 includes hydrogen, halogen, cyano, nitro, C1-C6 alkyl or phenyl substituents; R5 includes hydrogen, halogen, cyano, carbonyl, nitro, C1-C6 alkyl, C1-C6 olefin, C1-C6 alkyne, substituted benzyl, cycloalkyl, and heterocyclic.

2. The isoxazoline derivative containing a triazole thioether structure according to claim 1, characterized in that, In general formula I, R1 is chlorine; R2 is hydrogen or fluorine; R3 is chlorine or trifluoromethyl; R4 is a phenyl substituent; and R5 is methyl, ethyl, propyl, butyl, pentyl, C1-C6 alkyne substituent, o-(fluorine) substituted phenyl, p-(fluorine) substituted phenyl, p-(trifluoromethoxy) substituted phenyl, p-(trifluoromethyl) substituted phenyl, m-(fluorine) substituted phenyl, o / m-(fluorine) substituted phenyl, o / p-(fluorine) substituted phenyl, p-(methyl) substituted phenyl, p-(tert-butyl) substituted phenyl, o-(chlorine) substituted phenyl, p-(chlorine) substituted phenyl, o / m-(chlorine) substituted phenyl, p-(bromine) substituted phenyl, o / p-(chlorine) substituted phenyl, p-(cyano) substituted phenyl, p-(nitro) substituted phenyl, cycloalkyl substituent, or heterocyclic substituent.

3. The isoxazoline derivative containing a triazole thioether structure according to claim 1 or 2, characterized in that, The structures of the isoxazoline derivatives containing a triazole thioether structure include: ； ； ； ； ； ； ； ； ； ； ； 。 4. The method for preparing the isoxazoline derivative containing a triazole thioether structure according to any one of claims 1 to 3, characterized in that, The preparation method includes the following steps: (1) Compound A, hydroxylamine hydrochloride, sodium carbonate and solvent were mixed and stirred to react, and intermediate 1 was obtained; (2) Chloride intermediate 1 obtained in step (1), and then dispose of the chlorinated product, The mixture is reacted with a solvent to obtain intermediate 2; (3) Hydrolyze the intermediate 2 obtained in step (2) and the base in a solvent to obtain intermediate 3; (4) Take the intermediate 3 obtained in step (3) The reaction with triethylamine in a solvent yields intermediate 4; (5) React intermediate 4 obtained in step (4), N2H4•H2O and solvent to obtain intermediate 5; (6) Take the intermediate 5 obtained in step (5) The reaction in the solvent yields intermediate 6; (7) Take the intermediate 6 obtained in step (6), potassium carbonate, potassium iodide, The compound is reacted with a solvent to yield the target compound; X is a halogen. The synthesis route is as follows: 。 5. The method for preparing isoxazoline derivatives containing a triazole thioether structure according to claim 4, characterized in that, The solvent mentioned in step (1) is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol and water; the molar ratio of compound A, hydroxylamine hydrochloride, sodium carbonate and solvent is 1:(1~3):(1~5):(2~5).

6. The method for preparing isoxazoline derivatives containing a triazole thioether structure according to claim 4 or 5, characterized in that, The solvent in step (2) is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol, and water; intermediate 1, chlorinated reagent, The molar ratio of the solvent to the solvent is 1:(1~4):(1~4):(1~3).

7. The method for preparing isoxazoline derivatives containing a triazole thioether structure according to claim 6, characterized in that, In step (3), the alkali is lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium tert-butoxide, sodium acetate, potassium acetate or sodium bicarbonate; the solvent is one or more of methanol, ethanol, triethylamine, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, n-propanol and water.

8. The method for preparing isoxazoline derivatives containing a triazole thioether structure according to claim 4, 5, or 7, characterized in that, The solvent mentioned in step (4) is dichloromethane; the base is triethylamine; intermediate 3, The molar ratio of alkali to solvent is 1:(1~2):(1~2):(1~4). The solvent mentioned in step (5) is methanol; the molar ratio of intermediate 4, N2H4•H2O and solvent is 1:(1~14):(1~4); The solvent mentioned in step (6) is ethanol; intermediate 5, The molar ratio of the solvent to the solvent is 1:(1~2):(1~3); The solvent mentioned in step (7) is acetonitrile; intermediate 6, potassium carbonate, potassium iodide, The molar ratio of the solvent is 1:(1~2):(0~1):(1~2):(1~3).

9. The application of isoxazoline derivatives containing a triazole thioether structure as described in any one of claims 1 to 3 in the control of agricultural pests.

10. The application of the isoxazoline derivative containing a triazole thioether structure according to claim 9 in the control of agricultural pests, characterized in that, The application includes the preparation of insecticides; the agricultural pests include diamondback moth, corn borer, cotton bollworm, fall armyworm, armyworm, aphid, and rice planthopper.

Images