Isoxazoline compound containing benzo five-membered ring, preparation method of isoxazoline compound and insecticide

Abstract

The invention relates to the technical field of agricultural pest control, in particular to a benzo five-membered ring-containing isoxazoline compound, a preparation method thereof and an insecticide. The benzo five-membered ring-containing isoxazoline compound has a structure as shown in a formula I: # imgabs0 #, wherein X is selected from O, S, C bonded with R1 or N bonded with R1; r1 is selected from H, an alkyl group with 1 to 3 carbon atoms, an alkoxy group with 1 to 3 carbon atoms, a halogenated alkyl group with 1 to 3 carbon atoms or an alkoxy group with 1 to 3 carbon atoms; r2 is selected from H, a halogen atom, a C1-C3 alkyl group or a halogenated C1-C3 alkyl group; r3 and R5 are respectively and independently selected from H, halogen atoms or halogenated C1-C3 alkyl groups; r4 is selected from H or halogen atoms. The benzo five-membered ring-containing isoxazoline compound disclosed by the invention can be used for well preventing and treating invertebrate pests in the agricultural field and is beneficial to improving the yield of crops.

Description

Technical Field

[0001] The present invention relates to the technical field of agricultural pest control, and particularly to a benzofused five-membered ring isoxazoline compound, a preparation method thereof, and an insecticide. Background Art

[0002] In agricultural production, invertebrate pests pose a serious threat to the growth and storage of crops, often resulting in a decrease in crop yield, deterioration of quality, etc. Therefore, establishing a control system for invertebrate pests has important practical significance for ensuring agricultural production safety and improving agricultural production efficiency.

[0003] In the control system of crop diseases and pests, chemical pesticides still play an irreplaceable key role. However, the long-term reliance on chemical insecticides with a single mechanism of action has led to serious resistance problems, resulting in a significant reduction in the sensitivity of various invertebrate pests to existing agents. At the same time, traditional chemical insecticides are facing increasingly strict usage restrictions due to problems such as high toxicity, high residues, and resistance. Therefore, developing new insecticides that are highly efficient, low-cost, environmentally safe, and have different action sites has become a strategic need to address the difficulties in controlling invertebrate pests.

[0004] In view of this, the present invention is specifically proposed. Summary of the Invention

[0005] The purpose of the present invention is to provide a benzofused five-membered ring isoxazoline compound, a preparation method thereof, and an insecticide. The benzofused five-membered ring isoxazoline compound of the present invention can preferably control invertebrate pests in the agricultural field and greatly increase crop yield.

[0006] To achieve the above object of the present invention, in the first aspect, the present invention provides a benzofused five-membered ring isoxazoline compound or an agriculturally acceptable salt thereof. The benzofused five-membered ring isoxazoline compound has a structure shown in Formula I:

[0007]

[0008] In Formula I:

[0009] X is selected from O, S, C bonded to R1, or N bonded to R1;

[0010] R1 is selected from H, C1-C3 alkyl, C1-C3 alkoxy, halogenated C1-C3 alkyl, or halogenated C1-C3 alkoxy;

[0011] R2 is selected from H, a halogen atom, C1-C3 alkyl, or halogenated C1-C3 alkyl;

[0012] R3 and R5 are each independently selected from H, a halogen atom, or halogenated C1-C3 alkyl;

[0013] R4 is selected from H or a halogen atom.

[0014] Optionally, R1 is selected from H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, CF3, OCF3, CHF2, OCHF2, CF2CHF2CF3 or CH2CF3;

[0015] R2 is selected from H, methyl, F, Cl, Br, I or CF3;

[0016] R3 and R5 are each independently selected from H, CF3, CHF2, F, Cl, Br or I;

[0017] R4 is selected from H, F, Cl, Br or I.

[0018] Optionally, R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3, CHF2 or OCHF2;

[0019] R2 is selected from H, methyl, F, Cl or CF3;

[0020] R3 and R5 are each independently selected from H, CF3, F or Cl;

[0021] R4 is selected from H, F or Cl.

[0022] Optionally, R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3 or OCHF2;

[0023] R2 is methyl;

[0024] R3 and R5 are each independently selected from CF3, F or Cl;

[0025] R4 is selected from H, F or Cl.

[0026] Optionally, the agriculturally usable salt of the benzofused five-membered ring isoxazoline compound is selected from one of sulfate, hydrochloride, nitrate and phosphate, preferably one of sulfate, hydrochloride and phosphate.

[0027] The second aspect of the present invention provides a method for preparing the benzofused five-membered ring isoxazoline compound or its agriculturally usable salt described in the first aspect of the present invention, comprising the following steps:

[0028] The compound shown in Formula II reacts with the compound shown in Formula III under the action of an acid-binding agent to obtain the benzofused five-membered ring isoxazoline compound shown in Formula I;

[0029]

[0030] Optionally, the method for preparing the compound represented by Formula II includes the following steps: reacting the compound represented by Formula IV with the compound represented by Formula V under the action of an acid-binding agent and a catalyst to obtain the compound represented by Formula II;

[0031]

[0032] R6 is selected from one of tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, allyloxycarbonyl and trifluoroacetyl; R7 is selected from one of F, Cl, Br and I.

[0033] Optionally, the method for preparing the compound represented by Formula III includes the following steps:

[0034] (a) Reacting the compound represented by Formula VI with the compound represented by Formula VII to obtain the compound represented by Formula VIII;

[0035] (b) Reacting the compound represented by Formula VIII with hydroxylamine hydrochloride to obtain the compound represented by Formula IX;

[0036] (c) Reacting the compound represented by Formula IX with thionyl chloride in the presence of an acid-binding agent to obtain the compound represented by Formula III;

[0037]

[0038] The third aspect of the present invention provides the use of the benzofused five-membered ring isoxazoline compound or its agriculturally acceptable salt described in the first aspect of the present invention in pesticides.

[0039] Optionally, the pesticide is used to control invertebrate pests.

[0040] Optionally, the pesticide is used to control at least one of Lepidoptera insects and Hemiptera insects.

[0041] Optionally, the pesticide is used to control at least one of aphids, diamondback moths, striped stem borers, rice leaf folders, armyworms, oriental leafhoppers and tomato leafminers.

[0042] The fourth aspect of the present invention provides a pesticide, which includes at least one of the benzofused five-membered ring isoxazoline compound or its agriculturally acceptable salt described in the first aspect of the present invention in a biologically effective amount.

[0043] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0044] The benzofused five-membered ring isoxazoline compound of the present invention can preferably control invertebrate pests in the agricultural field, especially diamondback moths, striped stem borers and armyworms, which helps to increase the yield of crops. Detailed implementation manners

[0045] The technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments. However, those skilled in the art will understand that the following described embodiments are some embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention. For those conditions not specified in the embodiments, they shall be carried out according to conventional conditions or conditions recommended by the manufacturer. For the reagents or instruments not indicated by the manufacturer, they are all conventional products that can be obtained through commercial purchase. The compound structures of the present invention are all determined by nuclear magnetic resonance hydrogen spectrum. The starting materials in the embodiments of the present invention are known and can be purchased on the market, or can be synthesized by using or according to methods known in the art.

[0046] In the first aspect of the present invention, there is provided a benzofused five-membered ring isoxazoline compound or its agriculturally usable salt. The benzofused five-membered ring isoxazoline compound has a structure as shown in Formula I:

[0047]

[0048] In Formula I:

[0049] X is selected from O, S, C bonded to R1 or N bonded to R1;

[0050] R1 is selected from H, C1-C3 alkyl, C1-C3 alkoxy, halogenated C1-C3 alkyl or halogenated C1-C3 alkoxy;

[0051] R2 is selected from H, a halogen atom, C1-C3 alkyl or halogenated C1-C3 alkyl;

[0052] R3 and R5 are each independently selected from H, a halogen atom or halogenated C1-C3 alkyl;

[0053] R4 is selected from H or a halogen atom.

[0054] C bonded to R1 means that the position of X is C and there is an R1 substituent on C; N bonded to R1 means that the position of X is N and there is an R1 substituent on N.

[0055] C1-C3 alkyl refers to a straight-chain or branched-chain hydrocarbon group with 1 to 3 carbon atoms composed only of carbon and hydrogen atoms, and may include, for example: methyl, ethyl, n-propyl, isopropyl; C1-C3 alkoxy may include methoxy, ethoxy, propoxy, isopropoxy; halogenated C1-C3 alkyl refers to a C1-C3 alkyl substituted by at least one halogen atom, and may include, for example: halogen-substituted methyl, halogen-substituted ethyl, halogen-substituted n-propyl, halogen-substituted isopropyl; halogenated C1-C3 alkoxy refers to a C1-C3 alkoxy substituted by at least one halogen atom, and may include, for example: halogen-substituted methoxy, halogen-substituted ethoxy, halogen-substituted propoxy, halogen-substituted isopropoxy; halogen atoms include fluorine, chlorine, bromine, and iodine.

[0056] In some specific embodiments of the present invention, R1 is selected from H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, CF3, OCF3, CHF2, OCHF2, CF2CHF2CF3 or CH2CF3;

[0057] R2 is selected from H, methyl, F, Cl, Br, I or CF3;

[0058] R3 and R5 are each independently selected from H, CF3, CHF2, F, Cl, Br or I;

[0059] R4 is selected from H, F, Cl, Br or I.

[0060] In some specific embodiments of the present invention, R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3, CHF2 or OCHF2;

[0061] R2 is selected from H, methyl, F, Cl or CF3;

[0062] R3 and R5 are each independently selected from H, CF3, F or Cl;

[0063] R4 is selected from H, F or Cl.

[0064] In some specific embodiments of the present invention, R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3 or OCHF2;

[0065] R2 is methyl;

[0066] R3 and R5 are each independently selected from CF3, F or Cl;

[0067] R4 is selected from H, F or Cl.

[0068] In some specific embodiments of the present invention, the agriculturally usable salts of the benzofused five-membered ring isoxazoline compounds are selected from one of sulfate, hydrochloride, nitrate, and phosphate, preferably one of sulfate, hydrochloride, and phosphate. Specifically, the agriculturally usable salts can be formed by reacting a compound having the structure shown in Formula I with a corresponding acid, such as sulfuric acid, hydrochloric acid, nitric acid, or phosphoric acid.

[0069] The second aspect of the present invention provides a method for preparing the benzofused five-membered ring isoxazoline compound or its agriculturally usable salt of the first aspect of the present invention, comprising the following steps:

[0070] The compound shown in Formula II reacts with the compound shown in Formula III under the action of an acid-binding agent to obtain the benzofused five-membered ring isoxazoline compound shown in Formula I;

[0071]

[0072] Specific synthetic routes are referred to as follows:

[0073]

[0074] Among them, the definitions of X, R2, R3, R4, and R5 are the same as those in the structure shown in Formula I described above.

[0075] In some specific embodiments of the present invention, in the reaction of the compounds shown in Formula II and Formula III, the acid-binding agent includes at least one of triethylamine, potassium carbonate, sodium carbonate, diisopropylethylamine (DIPEA), and N-methylmorpholine (NMM).

[0076] In some specific embodiments of the present invention, the reaction of the compounds shown in Formula II and Formula III is carried out in an organic solvent. Further, the organic solvent includes at least one of dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, toluene, and xylene.

[0077] In some specific embodiments of the present invention, the temperature of the reaction of the compounds shown in Formula II and Formula III is 15 - 30 °C, for example, it can be room temperature but is not limited thereto.

[0078] In some specific embodiments of the present invention, the method for preparing the compound shown in Formula II includes the following steps: The compound shown in Formula IV reacts with the compound shown in Formula V under the action of an acid-binding agent and a catalyst to obtain the compound shown in Formula II;

[0079]

[0080] R6 is selected from one of tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, allyloxycarbonyl and trifluoroacetyl; R7 is selected from one of F, Cl, Br and I.

[0081] In some specific embodiments of the present invention, in the reaction of the compounds shown in Formula IV and Formula V, the acid-binding agent includes at least one of triethylamine, potassium carbonate, sodium carbonate, diisopropylethylamine (DIPEA) and N-methylmorpholine (NMM); the catalyst includes potassium iodide.

[0082] In some specific embodiments of the present invention, the reaction of the compounds shown in Formula IV and Formula V is carried out in a solvent. Further, the solvent includes N,N-dimethylformamide.

[0083] In some specific embodiments of the present invention, the reaction temperature of the compounds shown in Formula IV and Formula V is 0 to 30 °C.

[0084] In some specific embodiments of the present invention, when R6 is tert-butoxycarbonyl, the preparation of the compound shown in Formula IV includes: D-cycloserine reacts with di-tert-butyl dicarbonate in a solvent under the action of a base to obtain the compound shown in Formula IV. Further, the solvent includes at least one of dichloromethane, dichloroethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, toluene, xylene and water; the base includes at least one of triethylamine, DIPEA, NMM, sodium hydroxide, potassium hydroxide, potassium carbonate and sodium carbonate; the reaction temperature of D-cycloserine and di-tert-butyl dicarbonate is 0 to 30 °C.

[0085] The compound shown in Formula V can be purchased externally or prepared by methods known to those skilled in the art. In some specific embodiments of the present invention, the compound shown in Formula V includes any one of 5-chloro-1H-indene, 5-chlorobenzofuran and 5-chlorobenzothiophene.

[0086] Taking R6 as tert-butoxycarbonyl as an example, the synthetic route for preparing the compound shown in Formula II starting from D-cycloserine is as follows:

[0087]

[0088] In some specific embodiments of the present invention, the preparation method of the compound shown in Formula III includes the following steps:

[0089] (a) The compound shown in Formula VI reacts with the compound shown in Formula VII to obtain the compound shown in Formula VIII;

[0090] (b) The compound shown in Formula VIII reacts with hydroxylamine hydrochloride to obtain the compound shown in Formula IX;

[0091] (c) The compound shown in Formula IX reacts with thionyl dichloride to obtain the compound shown in Formula III;

[0092]

[0093]

[0094] In some specific embodiments of the present invention, the reaction of step (a) is carried out in the presence of a base and a solvent. The base includes triethylamine and potassium carbonate, and the solvent includes dichloroethane; the reaction temperature can be 50-90 °C.

[0095] In some specific embodiments of the present invention, the reaction of step (b) is carried out under the action of a base. The base includes sodium hydroxide (which can be added in the form of an aqueous solution). The solvent for the reaction of step (b) includes tetrahydrofuran. The reaction temperature of step (b) can be 0-10 °C.

[0096] In some specific embodiments of the present invention, in step (c), the reaction temperature is 15-30 °C. Further, in step (c), DMF can be added to catalyze the reaction.

[0097] The compound shown in Formula VI can be prepared by outsourcing or by methods known to those skilled in the art. In some specific embodiments of the present invention, the compound shown in Formula VI includes any one of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one and 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone.

[0098] The compound shown in Formula VII can be prepared by outsourcing or by methods known to those skilled in the art. In some specific embodiments of the present invention, the compound shown in Formula VII includes 4-acetyl-2-methylbenzoic acid.

[0099] The synthetic route for preparing the compound shown in Formula III using the compound shown in Formula VI and the compound shown in Formula VII as starting materials is as follows:

[0100]

[0101] According to the embodiments of the present invention, the preparation of the compound shown in Formula III can be carried out with reference to the method described in the publication number CN117800929A, but is not limited thereto.

[0102] After each step of the reaction of the present invention is completed, the reaction mixture can be post-treated in a conventional manner, such as by removing the solvent under reduced pressure, solvent extraction, washing with water, purification by column chromatography, etc., but is not limited thereto.

[0103] The third aspect of the present invention provides the use of the benzofused five-membered ring isoxazoline compound of the first aspect of the present invention or its agriculturally applicable salt in pesticides.

[0104] In some specific embodiments of the present invention, the insecticide is used to control invertebrate pests. The invertebrate pests of the present invention include arthropods, gastropods, nematodes, and worms that are pests of economic importance.

[0105] In some specific embodiments of the present invention, the insecticide is used to control at least one of Lepidoptera insects and Hemiptera insects.

[0106] In some specific embodiments of the present invention, the insecticide is used to control at least one of aphids, Plutella xylostella, Chilo suppressalis, Cnaphalocrocis medinalis, Mythimna separata, Euscelis bilobatus, and Tuta absoluta.

[0107] The fourth aspect of the present invention provides an insecticide comprising at least one of a biologically effective amount of the benzofused five-membered ring isoxazoline compound of the first aspect of the present invention or its agriculturally usable salt.

[0108] The insecticide of the present invention may comprise a single benzofused five-membered ring isoxazoline compound provided by the present invention or its agriculturally usable salt, or two or more benzofused five-membered ring isoxazoline compounds provided by the present invention or their agriculturally usable salts.

[0109] The biologically effective amount in the present invention refers to the amount of a biologically active compound that, when applied to (i.e., contacted with) the pests to be controlled or their environment, or plants, seeds from which the plants grow, or the location of the plants (e.g., growth medium), is sufficient to produce the desired biological effect, thereby protecting the plants from damage by pests or achieving other desired effects (e.g., enhancing plant vigor). The compounds of the present invention can also be prophylactically applied to places where pests or parasites are expected to appear.

[0110] In addition, the insecticide of the present invention may further comprise an insecticidal or acaricidal agent having a mode of action classified according to IRAC regulations as an active ingredient, and compound application has obvious synergistic and potentiating effects.

[0111] In some specific embodiments of the present invention, in the insecticide, the mass ratio of the benzofused five-membered ring isoxazoline compound of the first aspect of the present invention or its agriculturally usable salt to other active ingredients can be 1:5000 to 10:1, for example, it can be 1:5000, 1:4000, 1:3000, 1:2000, 1:1000, 1:500, 1:100, 1:50, 1:1, 3:1, 5:1, 8:1, 10:1, or a range composed of any two of them.

[0112] The insecticide of the present invention can be formulated into insecticides in conventional dosage forms, such as solutions, emulsions, suspensions, powders, dusts, pastes, granules, molded products, capsules and mixtures thereof. Based on this, in some specific embodiments of the present invention, the insecticide further includes auxiliaries to formulate the active ingredient into an insecticide in the corresponding dosage form.

[0113] In some specific embodiments of the present invention, the auxiliaries include, but are not limited to, any one or more of solvents, liquid carriers, solid carriers, fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesives, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, fungicides, antifreezes, defoamers, colorants, tackifiers and binders.

[0114] In view of the economy and diversity of the compounds, some compounds are preferably synthesized in the present invention. Among the many synthesized compounds, some are listed in the following examples. The compounds in the examples are only for better illustrating the present invention, but do not limit the present invention. For those skilled in the art, this should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following compounds only.

[0115] Example 1

[0116] This example provides a benzofused five-membered ring isoxazoline compound, and the specific synthesis route is as follows:

[0117]

[0118] A method for preparing a benzofused five-membered ring isoxazoline compound, comprising the following steps:

[0119] (1) Dissolve 4.1 g (0.04 mol) of D-cycloserine in a solution obtained by mixing 50 mL of tetrahydrofuran and 50 mL of water, add dropwise 4.44 g (0.044 mol) of triethylamine, and after the addition is complete, cool the solution to 0 °C. Add dropwise a solution of 9.34 g (0.043 mol) of di-tert-butyl dicarbonate in tetrahydrofuran (15 mL) thereto, complete the addition within 30 min and keep warm for 3 h, and then raise the temperature to room temperature and react overnight. After removing the solvent by reduced pressure distillation, slowly add dropwise a 2 mol / L hydrochloric acid aqueous solution to adjust the pH to 2-3, and a large amount of white solid appears. Filter and dry to obtain 6.2 g of a white solid (compound shown in formula IV), and the yield is 76%. 1 H NMR (600 Hz, CDCl3): δ 8.01 (s, 1H, NH), 7.97 (s, 1H, NH), 4.62 (t, 1H, CH), 4.16 (d, 2H, CH2), 1.45 (s, 3H, CH3), 1.40 (s, 3H, CH3), 1.50 (s, 3H, CH3).

[0120] (2) Dissolve 5.05 g (0.025 mol) of the compound shown in Formula IV prepared in step (1) in 60 mL of N,N-dimethylformamide, then add 8.64 g (0.0625 mol) of potassium carbonate and 4.6 g (0.0275 mol) of potassium iodide, and stir at room temperature for 30 min. Cool the reaction mixture to 0 °C, and then add 4.1 (0.0275 mol) of 5-chloro-1H-indene (the compound shown in Formula V) in batches (such as in two batches). Stir the reaction solution at room temperature overnight. Remove the solvent under vacuum, add 50 mL of ethyl acetate and 80 mL of water for extraction. Wash the organic layer with saturated brine, dry it over anhydrous sodium sulfate, filter, and concentrate to obtain 4.03 g of a white solid (the compound shown in Formula II), with a yield of 70%. 1 1H NMR (600 Hz, CDCl3): δ 7.56 (s, 1H, Ar), 7.40 (d, 1H, Ar), 6.99 (d, 1H, Ar), 6.58 (s, 1H, CH), 6.39 (s, 1H, CH), 3.22 (d, 2H, CH2), 4.26 (d, 2H, CH2), 3.65 (t, 1H, CH), 2.02 (br, 2H, NH2).

[0121] (3) Take 26.1 g (0.1 mol) of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one (the compound shown in Formula VI), 17.8 g (0.1 mol) of 4-acetyl-2-methylbenzoic acid, 16.6 g (0.12 mol) of potassium carbonate, and 12.1 g (0.12 mol) of triethylamine, add them to 300 mL of dichloroethane, and heat to 80 °C for reaction for about 20 h. After the reaction is complete, concentrate and remove the solvent under reduced pressure, and obtain a white solid product (the compound shown in Formula VIII) by silica gel column chromatography. The structure is characterized to be consistent by 1H NMR.

[0122] Take 16.8 g (0.04 mol) of the compound shown in Formula VIII and add it to 200 mL of tetrahydrofuran. Stir and dissolve at room temperature, then cool to 0 °C and slowly add 27.8 g of a 50% aqueous solution of hydroxylamine hydrochloride (0.2 mol). After addition, slowly dropwise add an aqueous sodium hydroxide solution (9.6 g of sodium hydroxide + 48 g of water), control the temperature at 5 °C, and stir for 3 h after addition. Add 10% dilute hydrochloric acid to the reaction solution to adjust the pH to about 2, and then add MTBE for extraction. Collect the organic phase. Concentrate and remove the solvent under reduced pressure, and obtain a white solid product (the compound shown in Formula IX) by silica gel column chromatography. The structure is characterized to be consistent by 1H NMR.

[0123] To a reaction flask containing 6.34 g (0.015 mol) of the compound shown in Formula IX, 30 mL of dichloromethane, 3.6 g of thionyl chloride and 1 drop of N,N-dimethylformamide were successively added, and the reaction was carried out at room temperature for 5 h. The solvent was removed by concentration, and the concentrated solution was dissolved in 30 mL of tetrahydrofuran. 7 mL of triethylamine was added dropwise thereto at room temperature. Then, 4 g (0.0185 mol) of the compound shown in Formula II was dissolved in 50 mL of tetrahydrofuran and added dropwise into the aforementioned reaction flask, and the reaction was carried out overnight at room temperature. After the reaction was completed, the solvent was removed under reduced pressure, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration and concentration, a brownish-yellow viscous solid was obtained, which was recrystallized from n-hexane to obtain 4.76 g of a yellow solid (the compound shown in Formula I), and the yield was 50.1%. 1 H NMR (600 Hz, CDCl3): δ 7.56 (s, 1H, Ar), 7.41 (d, 1H, Ar), 6.99 (d, 1H, Ar), 6.59 (s, 1H, CH), 6.39 (s, 1H, CH), 3.23 (d, 2H, CH2), 4.30 (d, 2H, CH2), 4.62 (t, 1H, CH), 8.01 (s, 1H, NH), 7.90 (d, 1H, Ar), 7.60 (d, 1H, Ar), 7.70 (s, 1H, Ar), 2.35 (s, 3H, CH3), 3.29 (s, 2H, CH2), 7.06 (s, 1H, Ar), 7.10 (s, 1H, Ar).

[0124] Examples 2 to 4

[0125] Referring to the preparation method of Reference Example 1 and replacing the corresponding reaction raw materials, other compounds in Table 1 can be prepared. The general formula of the compounds is shown below, and the corresponding different substituents are shown in Table 1.

[0126]

[0127] Table 1 Data of Different Compounds

[0128]

[0129]

[0130] In the preparation of the compound of Example 2, the compound shown in Formula V in Example 1 was replaced with an equimolar amount of The compound shown in Formula VI was replaced with an equimolar amount of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone;

[0131] In the preparation of the compound of Example 3, the compound shown in Formula V in Example 1 was replaced with an equimolar amount of The compound shown in Formula VI is replaced with an equimolar amount of 1-(3-chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanone;

[0132] In the preparation of the compound of Example 4, the compound shown in Formula V in Example 1 is replaced with an equimolar amount of The compound shown in Formula VI is replaced with an equimolar amount of 1-(3-chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanone.

[0133] Among them, the compounds shown in Formula V of Examples 2 to 4 can be obtained by carrying out N-methylation, N-ethylation or N-trifluoromethylation reactions of 5-chloro-1H-indene with CH3I, C2H5I or CF3I respectively under the action of NaH at the 1-position.

[0134] Example 5

[0135] This example provides a benzofused five-membered ring isoxazoline compound, and the specific synthesis route is as follows:

[0136]

[0137] A method for preparing a benzofused five-membered ring isoxazoline compound, comprising the following steps:

[0138] (1) The preparation of the compound shown in Formula IV is the same as step (1) in Example 1.

[0139] (2) The compound shown in Formula II refers to step (2) in Example 1, the difference being that 5-chloro-1H-indene in step (2) of Example 1 is replaced with an equimolar amount of 5-chlorobenzofuran. The yield of the compound shown in Formula II is 82.6%, and the 1H NMR data: 1 H NMR(600Hz, CDCl3):δ7.87(s,1H,Ar),7.57(d,1H,Ar),7.40(d,1H,Ar),7.52(d,1H,Ar),6.66(d,1H,Ar),4.01(d,2H,CH2),3.60(t,1H,CH),2.00(br,2H,NH2).

[0140] (3) The compound shown in Formula I refers to step (3) in Example 1, the difference being that 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one in step (3) of Example 1 is replaced with an equimolar amount of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone. The yield of the compound shown in Formula I is 52.8%, and the 1H NMR data: 11H NMR (600 Hz, CDCl3): δ 7.87 (s, 1H, Ar), 7.57 (d, 1H, Ar), 7.40 (d, 1H, Ar), 6.52 (d, 1H, Ar), 6.66 (d, 1H, Ar), 4.05 (d, 2H, CH2), 4.62 (t, 1H, CH), 8.03 (s, 1H, NH), 7.90 (d, 1H, Ar), 7.60 (d, 1H, Ar), 7.70 (s, 1H, Ar), 2.35 (s, 3H, CH3), 3.29 (s, 2H, CH2), 7.08 (s, 1H, Ar), 7.10 (s, 1H, Ar), 7.21 (s, 1H, Ar).

[0141] Examples 6 - 7

[0142] Referring to the preparation method of Reference Example 5 and replacing the corresponding reaction raw materials, other compounds in Table 2 can be prepared. The general formula of the compounds is as follows, and the corresponding different substituents are shown in Table 2.

[0143]

[0144] Data of Different Compounds in Table 2

[0145] Number X <![CDATA[R2]]> <![CDATA[R3]]> <![CDATA[R4]]> <![CDATA[R5]]> Example 6 O <![CDATA[CH3]]> Cl F Cl Example 7 O <![CDATA[CH3]]> Cl H <![CDATA[CF3]]>

[0146] In the preparation of the compound of Example 6, the compound shown in Formula VI in Example 5 was replaced with an equimolar amount of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one;

[0147] In the preparation of the compound of Example 7, the compound shown in Formula VI in Example 5 was replaced with an equimolar amount of 1-(3-chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanone.

[0148] Example 8

[0149] This example provides a benzofused five-membered ring isoxazoline compound. The specific synthesis route is as follows:

[0150]

[0151] A preparation method of a benzofused five-membered ring isoxazoline compound, comprising the following steps:

[0152] (1) The preparation of the compound shown in Formula IV is the same as step (1) in Example 1.

[0153] (2) For the compound shown in Formula II, refer to Step (2) in Reference Example 1, except that 5-chloro-1H-indene in Step (2) of Example 1 is replaced with an equimolar amount of 5-chlorobenzothiophene. The yield of the compound shown in Formula II is 78.6%, and the 1H NMR data are as follows: 1 1H NMR (600 Hz, CDCl3): δ 8.16 (s, 1H, Ar), 7.69 (d, 1H, Ar), 7.84 (d, 1H, Ar), 7.40 (d, 1H, Ar), 7.29 (d, 1H, Ar), 4.26 (d, 2H, CH2), 3.65 (t, 1H, CH), 2.00 (br, 2H, NH2).

[0154] (3) For the compound shown in Formula I, refer to Step (3) in Reference Example 1, except that 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one in Step (3) of Example 1 is replaced with an equimolar amount of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone. The yield of the compound shown in Formula I is 56.7%, and the 1H NMR data are as follows: 1 1H NMR (600 Hz, CDCl3): δ 8.16 (s, 1H, Ar), 7.69 (d, 1H, Ar), 7.84 (d, 1H, Ar), 7.40 (d, 1H, Ar), 7.29 (d, 1H, Ar), 4.30 (d, 2H, CH2), 4.62 (t, 1H, CH), 8.05 (s, 1H, NH), 7.90 (d, 1H, Ar), 7.60 (d, 1H, Ar), 7.60 (s, 1H, Ar), 2.36 (s, 3H, CH3), 3.04 (s, 2H, CH2), 7.08 (s, 1H, Ar), 7.08 (s, 1H, Ar), 7.25 (s, 1H, Ar).

[0155] Examples 9 - 10

[0156] Referring to the preparation method of Reference Example 8 and replacing the corresponding reaction raw materials, other compounds in Table 3 can be prepared. The general formula of the compounds is as follows, and the corresponding different substituents are shown in Table 3.

[0157]

[0158] Table 3 Data of Different Compounds

[0159] Number X <![CDATA[R2]]> <![CDATA[R3]]> <![CDATA[R4]]> <![CDATA[R5]]> Example 9 S <![CDATA[CH3]]> Cl F Cl Example 10 S <![CDATA[CH3]]> Cl H <![CDATA[CF3]]>

[0160] In the preparation of the compound of Example 9, the compound shown in Formula VI in Example 8 is replaced with an equimolar amount of 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethan-1-one;

[0161] In the preparation of the compound of Example 10, the compound shown in Formula VI in Example 8 was replaced with an equimolar amount of 1-(3-chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanone.

[0162] Examples 11 - 13

[0163] Referring to the preparation method of Reference Example 1 and replacing the corresponding reaction raw materials, other compounds in Table 4 can be prepared. The general formula of the compounds is shown below, and the corresponding different substituents are shown in Table 4.

[0164]

[0165] Table 4 Data of Different Compounds

[0166] Number X <![CDATA[R2]]> <![CDATA[R3]]> <![CDATA[R4]]> <![CDATA[R5]]> Example 11 N-H <![CDATA[CH3]]> Cl H Cl Example 12 <![CDATA[N-CH3]]> <![CDATA[CH3]]> Cl F Cl Example 13 <![CDATA[N-CH2CH3]]> <![CDATA[CH3]]> Cl H <![CDATA[CF3]]>

[0167] The synthetic routes of the compounds of Examples 11 - 13 are referred to as follows:

[0168]

[0169] In the preparation of the compound of Example 11, 5-chloro-1H-indene in step (2) of Example 1 was replaced with an equimolar amount of 5-chloroindole; the compound shown in Formula VI in step (3) of Example 1 was replaced with an equimolar amount of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone;

[0170] In the preparation of the compound of Example 12, 5-chloro-1H-indene in step (2) of Example 1 was replaced with an equimolar amount of 5-chloro-1-methylindole;

[0171] In the preparation of the compound of Example 13, the compound shown in Formula V in Example 1 was replaced with an equimolar amount of The compound shown in Formula VI in step (3) of Example 1 was replaced with an equimolar amount of 1-(3-chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanone.

[0172] Among them, the compound shown in Formula V of Example 13 can be obtained by the 1-position ethylation reaction of 5-chloroindole with C2H5I under the action of NaH.

[0173] Comparative Example 1

[0174] Comparative Example 1 provides a control compound with the following structural formula (recorded in WO2005 / 085216):

[0175]

[0176] Experimental Example

[0177] Insecticidal activity determination: The insecticidal activity determination experiments were carried out on Plutella xylostella, Mythimna separata, and Chilo suppressalis using the compounds of the present invention and control compounds respectively.

[0178] The determination method includes: After dissolving the test compound with a mixed solvent of acetone / methanol (V / V = 1 / 1), it is diluted to the required concentration with an aqueous solution of 0.1 wt% Tween 80. Using Plutella xylostella, Mythimna separata, and Chilo suppressalis as the test targets, the Airbrush spraying method was used for activity determination.

[0179] Specifically, the insecticidal activity determination methods and results for Plutella xylostella, Mythimna separata, and Chilo suppressalis are as follows.

[0180] (1) Insecticidal activity determination against Plutella xylostella

[0181] Determination method: The cabbage leaves were punched into leaf discs with a diameter of 2 cm. The pressure of the Airbrush spraying treatment was 10 psi (equivalent to about 0.7 kg / cm 2 ). The front and back sides of each leaf disc were sprayed, and the spraying amount of the test compound was 0.5 mL. After air-drying, 10 third-instar larvae were introduced into each treatment, and each treatment was repeated 3 times. After treatment, it was placed in an observation chamber at 25 °C and a relative humidity of 60% - 70% for cultivation. The number of surviving insects was investigated 3 days after treatment, and the mortality rate was calculated.

[0182] Mortality rate = number of dead insects / total number of insects × 100%;

[0183] Corrected mortality rate = (treatment mortality rate - control mortality rate) / (1 - control mortality rate) × 100%;

[0184] Determination results:

[0185] At a dose of 0.313 mg / L, 3 days after treatment, the mortality rates of the compounds of Examples 1, 3, 5, 6, 8, 9, and 12 against Plutella xylostella were all above 90%; the mortality rate of the control compound of Comparative Example 1 was only 65%.

[0186] At a dose of 0.156 mg / L, 3 days after treatment, the mortality rates of the compounds of Examples 1, 5, and 8 against Plutella xylostella were all above 90%.

[0187] (2) Insecticidal activity determination against Mythimna separata

[0188] Determination method: The corn leaves were cut into leaf segments of 2 cm. The pressure of the Airbrush spraying treatment was 10 psi (equivalent to about 0.7 kg / cm 2 ). The front and back sides of each leaf segment were sprayed, and the spraying amount of the test compound was 0.5 mL. After air-drying, 10 third-instar larvae were introduced into each treatment, and each treatment was repeated 3 times. After treatment, it was placed in an observation chamber at 25 °C and a relative humidity of 60% - 70% for cultivation. The number of surviving insects was investigated 3 days after treatment, and the mortality rate was calculated.

[0189] Mortality rate = (Number of dead insects / Total number of insects) × 100%;

[0190] Adjusted mortality rate = (Treatment mortality rate - Control mortality rate) / (1 - Control mortality rate) × 100%;

[0191] Test results:

[0192] At a dose of 0.313 mg / L, 3 days after treatment, the mortality rates of the compounds of Examples 1, 2, 4, 5, 6, 7, 8, 9, 11, and 12 against Mythimna separata were all above 90%; the mortality rate of the control compound in Comparative Example 1 was only 70%.

[0193] (3) Assay of the activity against Chilo suppressalis

[0194] Assay method: ① Preparation of rice straw: Cultivate rice in plastic cups with a diameter of 4.5 cm and a height of 4 cm in a constant temperature room (temperature 26 - 28 °C, relative humidity 60% - 80%, light 16 hL - 18 hD). When the rice grows to the 4 - 5 leaf stage, select healthy and uniformly growing rice seedlings for chemical treatment, with 3 replicates for each treatment. ② Preparation of test targets: Continuously rear Chilo suppressalis indoors, the third instar larvae. ③ Spraying and insect inoculation on rice stems. Using the spraying method, uniformly spray the whole rice seedlings, with 15 mL of medicine used for each treatment. First, treat the blank control, and then repeat the above experimental operations in the order of increasing experimental concentration. After the rice seedlings are sprayed, place them in a cool place to dry the medicine, cut about 5 cm of the stem at the base of the stem to feed the test insects. Prepare a glass petri dish with a diameter of 90 mm, line the bottom of the dish with filter paper, add water to keep it moist, place about 5 rice stems in each dish, inoculate 10 larvae, seal the petri dish with non-woven fabric, and place it in a constant temperature room for cultivation. Investigate the number of remaining live insects 3 days after treatment.

[0195] Mortality rate = (Number of dead insects / Total number of insects) × 100%;

[0196] Adjusted mortality rate = (Treatment mortality rate - Control mortality rate) / (1 - Control mortality rate) × 100%;

[0197] Test results:

[0198] At a dose of 1 mg / L, 3 days after treatment, the mortality rates of the compounds of Examples 1, 2, 3, 4, 5, 6, 8, and 12 against Chilo suppressalis were all above 90%; the mortality rate of the control compound in Comparative Example 1 was only 45%.

[0199] From the above test results, it can be seen that the benzofused five-membered ring isoxazoline compounds of the present invention have excellent control effects on pests such as Plutella xylostella, Mythimna separata, Chilo suppressalis, and aphids.

[0200] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A benzofused five-membered ring isoxazoline compound or its agriculturally usable salt, characterized in that, The benzofused five-membered ring isoxazoline compound has the structure shown in Formula I: In Formula I: X is selected from O, S, C bonded to R1, or N bonded to R1; R1 is selected from H, C1-C3 alkyl, C1-C3 alkoxy, halo C1-C3 alkyl, or halo C1-C3 alkoxy; R2 is selected from H, a halogen atom, C1-C3 alkyl, or halo C1-C3 alkyl; R3 and R5 are each independently selected from H, a halogen atom, or halo C1-C3 alkyl; R4 is selected from H or a halogen atom.

2. The benzofused five-membered ring isoxazoline compound or its agriculturally-usable salt according to claim 1, characterized in that, R1 is selected from H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, CF3, OCF3, CHF2, OCHF2, CF2CHF2CF3, or CH2CF3; R2 is selected from H, methyl, F, Cl, Br, I, or CF3; R3 and R5 are each independently selected from H, CF3, CHF2, F, Cl, Br, or I; R4 is selected from H, F, Cl, Br, or I.

3. The benzofused five-membered ring isoxazoline compound or its agriculturally-usable salt according to claim 1, wherein R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3, CHF2, or OCHF2; R2 is selected from H, methyl, F, Cl, or CF3; R3 and R5 are each independently selected from H, CF3, F, or Cl; R4 is selected from H, F, or Cl.

4. The benzofused five-membered ring isoxazoline compound or its agriculturally usable salt according to claim 1, characterized in that, R1 is selected from H, methyl, ethyl, methoxy, CF3, OCF3, or OCHF2; R2 is methyl; R3 and R5 are each independently selected from CF3, F, or Cl; R4 is selected from H, F, or Cl.

5. The benzofused five-membered ring isoxazoline compound or its agriculturally-usable salt according to claim 1, characterized in that, The agriculturally usable salt is selected from one of sulfate, hydrochloride, nitrate, and phosphate.

6. A method for preparing the benzofused five-membered ring isoxazoline compound or its agriculturally-usable salt according to any one of claims 1 to 5, characterized in that, It includes the following steps: The compound shown in Formula II reacts with the compound shown in Formula III under the action of an acid-binding agent to obtain the benzofused five-membered ring isoxazoline compound shown in Formula I; 7. The preparation method according to claim 6, characterized in that, The preparation method of the compound shown in Formula II includes the following steps: The compound shown in Formula IV reacts with the compound shown in Formula V under the action of an acid-binding agent and a catalyst to obtain the compound shown in Formula II; R6 is selected from one of tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, allyloxycarbonyl, and trifluoroacetyl; R7 is selected from one of F, Cl, Br, and I.

8. The preparation method according to claim 6, characterized in that, The preparation method of the compound shown in Formula III includes the following steps: (a) The compound shown in Formula VI reacts with the compound shown in Formula VII to obtain the compound shown in Formula VIII; (b) The compound shown in Formula VIII reacts with hydroxylamine hydrochloride to obtain the compound shown in Formula IX; (c) The compound shown in Formula IX reacts with thionyl chloride to obtain the compound shown in Formula III; 9. The use of the benzofused five-membered ring isoxazoline compound or its agriculturally usable salt according to any one of claims 1-5 in an insecticide; Preferably, the insecticide is used to control invertebrate pests; Preferably, the insecticide is used to control at least one of Lepidoptera insects and Hemiptera insects; Preferably, the insecticide is used to control at least one of aphids, Plutella xylostella, Chilo suppressalis, Cnaphalocrocis medinalis, Mythimna separata, Euscelis bilobatus, and Tuta absoluta.

10. An insecticide comprising a biologically effective amount of the benzofused five-membered ring isoxazoline compound or its agriculturally usable salt according to any one of claims 1-5.

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