Amide compounds containing isoxazoline and preparation method and application thereof

Abstract

The present invention provides an amide compound containing isoxazoline, a preparation method and an application thereof, and belongs to the technical field of chemical industry and pesticide. The compound has the following structure:; Its chemical name is 4-(5-(3-chloro-5-trifluoromethylphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl- N ‑(2‑oxo‑2‑(2,2,2‑trifluoroethylamino)ethyl)benzamide. The compound can be used as the main active ingredient of a pesticide composition, and can be used as an insecticide for controlling crop pests and / or mites, and a repellent for repelling crop pests. The present invention discloses a novel amide compound containing an isoxazoline structure. Compared with flurellana, the 5th position of the benzene ring is changed from chlorine to trifluoromethyl, and the activity thereof is increased by 40% to 50%, thereby increasing the toxicity intensity of targeted pest control.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical industry and pesticide, and particularly relates to an amide compound containing isoxazoline and a preparation method and application thereof. Background Art

[0002] Amide compounds containing isoxazoline are isoxazoline insecticides and miticides. They antagonize the γ-aminobutyric acid receptor and glutamate receptor gated chloride ion channels, preventing chloride ions from penetrating into the postsynaptic membrane, interfering with transmembrane signaling in the nervous system, leading to nervous system disorders in insects and death. Isoxazole is an important member of nitrogen-containing heterocycles. Its structure contains oxygen heteroatoms and is an important structural unit for the synthesis of various active compounds. It has a wide range of biological activities.

[0003] In the pesticide field, isoxazole compounds exhibit biological activities such as insecticide and weed killer; among the existing isoxazoline amide compounds, Fluralaner is one of the most commonly used agents. Fluralaner (structure shown in the following formula I) can effectively control agricultural pests.

[0004]

[0005] The use of pesticides has brought huge benefits to agricultural production, but it also has certain side effects, such as pesticide resistance. In the specific chemical control process, due to the long-term use of a certain preparation alone, pests are prone to develop different degrees of resistance, which in turn causes the continuous increase in the dosage of pesticides, which not only increases costs but also pollutes the environment.

[0006] At present, Flurellan has been used in the market for nearly 10 years, and has generally developed obvious drug resistance and tolerance, so it is necessary to explore new isoxazoline compounds for the control during the growth of crops. Summary of the invention

[0007] In view of this, the object of the present invention is to provide an amide compound containing isoxazoline and a preparation method and application thereof, aiming to solve at least one technical problem in the background technology.

[0008] The present invention is achieved in that:

[0009] The first aspect of the present invention provides an amide compound containing isoxazoline, the structural formula of which is shown below, and the chemical name is: 4-(5-(3-chloro-5-trifluoromethylphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl- N -(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide, referred to as MJ01;

[0010] .

[0011] The second aspect of the present invention provides a method for preparing the above-mentioned isoxazoline-containing amide compound, which comprises the following steps:

[0012] 2-Methyl-4-acetylbenzoic acid and 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone undergo a catalytic addition reaction to generate compound A, and the reaction formula is:

[0013] ;

[0014] The compound A is catalytically dehydrated to obtain compound B, and the reaction formula is:

[0015] ;

[0016] The compound B is cyclized with hydroxylamine to obtain compound C, and the reaction formula is:

[0017] ;

[0018] The compound C is subjected to an amidation reaction with 2-amino-N-(2,2,2-trifluoroethyl)acetamide to generate the isoxazoline-containing amide compound, and the reaction formula is:

[0019]

[0020] Furthermore, the preparation method specifically comprises:

[0021] Add 2-methyl-4-acetylbenzoic acid, 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone and a catalyst potassium carbonate solution to a reaction flask, heat the reaction, adjust the pH to a strong acid, extract the organic phase, and then sequentially dry, filter, distill under reduced pressure, purify by crystallization, and dry by suction to obtain a yellow solid, which is the compound A;

[0022] Add compound A, toluene and triethylamine to a reaction bottle, and stir evenly at room temperature; add catalyst 4-dimethylaminopyridine, stir the system and heat it, then drop acetic anhydride, and keep warm for reaction; after the reaction is completed, adjust the pH to 1-2, extract the organic phase; then sequentially dry, filter, vacuum distill, crystallize and purify, and filter and dry to obtain a solid, which is the compound B;

[0023] Add the compound B, tetrabutylammonium bromide and toluene to the reaction flask, cool to 0°C, drop hydroxylamine aqueous solution into the system, gradually warm to room temperature and stir to react after the addition is complete, add concentrated hydrochloric acid to adjust the pH to strong acidity after the reaction is complete, stir and separate, extract the organic phase and concentrate to obtain the crude compound C;

[0024] Toluene, N,N-dimethylformamide and thionyl chloride are added to the crude compound C, and the temperature is raised and stirred to react. After the reaction is completed, the solvent is evaporated, ethyl acetate, 2-amino-N-(2,2,2-trifluoroethyl)acetamide and triethylamine are added, and the reaction is stirred at room temperature until the reaction is completed; then the steps of washing with water, decolorizing, distilling and concentrating, crystallizing and purifying, filtering and drying are performed in sequence to obtain a white powder solid, which is the isoxazoline-containing amide compound.

[0025] The third aspect of the present invention provides the use of the above-mentioned isoxazoline-containing amide compounds as a main active ingredient for preparing a pesticide composition.

[0026] The pesticide-acceptable salt obtained by reacting the isoxazoline-containing amide compound of the present invention with a chemically acceptable acid or base can also be used as the main active ingredient of the pesticide composition, wherein the chemically acceptable acid can be an inorganic acid (such as hydrochloric acid, sulfuric acid, phosphoric acid or hydrobromic acid, etc.) or an organic acid (such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid or benzoic acid, etc.); the chemically acceptable base can be an inorganic base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate, etc.) or an organic base (such as trimethylamine, triethylamine, etc.); the pesticide-acceptable salt can be a potassium salt, sodium salt, ammonium salt, calcium salt, pyridinium salt, choline salt, hydrochloride, phosphate, acetate, benzenesulfonate or oxalate.

[0027] Furthermore, the pesticide composition also includes a formulation carrier or a formulation adjuvant. The pesticide composition of the present invention can be prepared into various application formulations, such as suspensions, dispersible oil suspensions, microcapsule suspensions, suspoemulsions, wettable powders or water dispersible granules; in addition to the effective main active ingredients, the pesticide composition also includes various auxiliary ingredients that are allowed and acceptable in different pesticide formulations.

[0028] Furthermore, the pesticide composition is used as an insecticide to control crop pests and / or mites, including but not limited to thrips, striped stem borer, fruit fly, and citrus mites.

[0029] Furthermore, the pesticide composition is used as a repellent to repel crop pests.

[0030] Furthermore, the crop pest is cotton bollworm or beet armyworm.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. The present invention discloses a novel amide compound containing an isoxazoline structure. Compared with flurellana, the 5-position of the benzene ring in the compound of the present invention is changed from chlorine to trifluoromethyl, and its activity is increased by 40% to 50%, thereby improving the toxicity intensity of targeted pest control.

[0033] 2. The compound MJ01 of the present invention is a broad-spectrum, highly active and highly selective pesticide compound. It has no cross-resistance with existing γ-aminobutyric acid receptor insecticides and is safe to non-target organisms.

[0034] 3. The compound MJ01 of the present invention has a certain repellent effect on cotton bollworm and beet armyworm, and has an insecticidal effect on crop pests such as thrips nymphs; it can be used to develop new highly active, low-toxic insecticides or repellents.

[0035] 4. The compound MJ01 of the present invention has good biological activity against arthropods such as Ticks, Siphonaptera, Lichens, Hemiptera, Diptera, Lepidoptera, and Acarina, and its mode of action is mainly stomach poison and contact toxicity. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific implementation cases described herein are only used to explain the present invention and are not used to limit the present invention.

[0037] Example 1

[0038] In this example, an amide compound containing isoxazoline was prepared: 4-(5-(3-chloro-5-trifluoromethylphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl- N -(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide, hereinafter referred to as MJ01, has the following synthetic route:

[0039]

[0040] The specific steps of preparing the amide compound containing isoxazoline include:

[0041] S1: preparing 4-[3-(3-chloro-5-trifluoromethylphenyl)-3-trifluoromethyl-3-hydroxy-propionyl]-2-methyl-benzoic acid, i.e., compound A;

[0042] 2-Methyl-4-acetylbenzoic acid (100 g, 0.56 mol, 1.0 eq), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (155.21 g, 1.0 eq), 1500 ml of water and potassium carbonate (120 g) were added to the reaction bottle, and the temperature was raised to T = 60 ° C for 20 h. After the reaction was completed, the pH was adjusted to 1 with hydrochloric acid, and extracted with ethyl acetate (500 mL * 3). The organic phases were combined and dried over 300 g of anhydrous sodium sulfate, the desiccant was filtered out, the solvent was evaporated under reduced pressure, 500 ml of petroleum ether was added, stirred for crystallization, and filtered and dried to obtain 184 g of yellow solid compound A with a yield of 77.5%.

[0043] S2: preparing 4-[3-(3-chloro-5-trifluoromethylphenyl)-3-trifluoromethyl-allyl]-2-methyl-benzoic acid, i.e., compound B;

[0044] Compound A (100 g, 1.0 eq), 200 ml of toluene and triethylamine (24 g, 1.0 eq) were added to the reaction flask, and the mixture was stirred at room temperature for 1 h. 4-Dimethylaminopyridine DMAP (5 g, 0.17 eq) was added, the system was stirred and heated to 60 °C, acetic anhydride (49 g, 2.0 eq) was added dropwise, and the mixture was kept warm for 20 h. After the reaction was completed, concentrated hydrochloric acid was added to adjust the pH to 1-2, the liquid was separated, the aqueous phase was extracted with ethyl acetate (500 mL*2), the organic phases were combined, dried over 300 g of anhydrous sodium sulfate, the desiccant was filtered out, the solvent was removed by distillation, 300 mL of petroleum ether was added, the mixture was stirred at 50 °C for 1 h, the system was cooled to 0 °C-5 °C, the mixture was kept warm for crystallization for 1.0 h, filtered, the filter cake was collected, and the filter cake was dried at 50 °C with air blast to obtain 81 g of compound B with a yield of 84.6%.

[0045] S3: Preparation of 4-(5-(3-chloro-5-trifluoromethylphenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, i.e., compound C;

[0046] Compound B (100 g, 1.0 eq), tetrabutylammonium bromide (30 g, 0.3 eq) and 1000 mL of toluene were added to the reaction bottle, and the temperature was lowered to 0°C. A 50% mass concentration aqueous solution of hydroxylamine (36 g, 2.2 eq) was added dropwise to the system. After the addition was completed, the temperature was gradually raised to room temperature and stirred overnight. After the reaction was completed, concentrated hydrochloric acid was added to adjust the pH to 1, stirred for 10 min, separated, the aqueous phase was extracted once with 200 mL of ethyl acetate, the organic phases were combined, concentrated to obtain compound C, and used directly in the next step.

[0047] S4: Synthesis of 4-(5-(3-chloro-5-trifluoromethylphenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl- N -(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide, i.e., target compound MJ01;

[0048] To the crude compound C obtained in S3, 1000 mL of toluene, 0.1 mL of N,N-dimethylformamide DMF, and thionyl chloride (45 g, 1.5 eq) were added, the temperature was raised to 80 ° C and stirred for 5 h. After the reaction was completed, the solvent was evaporated, 1000 mL of ethyl acetate, 2-amino-N-(2,2,2-trifluoroethyl)acetamide (42.6 g, 1.1 eq) and triethylamine (62.6 g, 2.5 eq) were added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was washed with 500 mL of water, decolorized with 10 g of activated carbon, and then distilled and concentrated to about 200 mL of ethyl acetate. 1000 mL of petroleum ether was added. After the addition, the temperature was lowered to room temperature and stirred for crystallization for 2 h. The mixture was filtered and dried with air at 50 ° C to obtain 81 g of a white powder solid, i.e., the target compound MJ01 of the present invention.

[0049] The raw materials and reagents involved in the above examples are all commercially available, and the chemical reaction process is within the skill of a person skilled in the art. The white powder solid obtained in step S4 was identified by mass spectrometry using hydrogen and carbon spectra, and the results are as follows:

[0050] 1 H NMR (500 MHz, CDCl3) δ 7.58-7.42 (m, 6H), 6.91-6.85 (m, 1H), 6.75-6.69 (m, 1H), 4.21 (d, J = 5.33 Hz, 2H ) , 4.09 ( d, J = 17.2 Hz, 1H), 4.01-3.91 (m, 2H), 3.72 (d, J = 17.2 Hz, 1H), 2.47 (s, 3H);

[0051] 13 C NMR (150 MHz, CDCl3) δ 170.1, 169.5, 155.5, 139.1, 137.6, 137.4,135.6, 108.09, 125.5, 124.5, 124.0, 130.0, 129.7, 128.1, 127.8, 128.0,127.9, 87.5, 67.9, 43.9, 40.9, 19.9;

[0052] ESI [M+H] + : 589.1;

[0053] HPLC: Column: InertSustain C18 (250 mm × 4.6 mm × 5 µm); Detection wavelength: 245 nm; Flow rate: 0.8 mL / min; Temperature: 30°C; Injection volume: 10 μL; Solvent: acetonitrile; Concentration: 0.2 mg / mL; Run time: 15 min; Mobile phase: acetonitrile: phosphoric acid aqueous solution (0.1%) = 75:25; t R =8.58min, purity: 99.0%;

[0054] The results show that the structure of the product obtained in Example 1 is consistent with the theoretical derivation, specifically:

[0055] .

[0056] White powder solid MJ01 is easily soluble in dichloromethane and DMF; its melting point mp is 316℃; the compound has a certain repellent effect on cotton bollworm and beet armyworm, and has insecticidal effect on crop pests such as mosaic thrips, striped stem borer, fruit fly, etc.; it can be used to develop new highly active and low-toxic insecticides or repellents.

[0057] Example 2

[0058] The isoxazoline-containing amide compound MJ01 prepared in Example 1 is used as the original drug to prepare a suitable formulation of pesticide, such as a suspension, a dispersible oil suspension, a microcapsule suspension, a suspoemulsion, a wettable powder or a water-dispersible granule. This example selects a dispersible oil suspension as an example, and selects suitable adjuvants to prepare pesticides of different concentrations, and its components are shown in Table 1.

[0059] Table 1

[0060]

[0061] In Table 1, CO / 40 (short for ethoxylated castor oil) and polyethylene glycol 400 are both emulsifiers; NS500LQ (short for nonionic hydroxy polyethylene oxide block copolymer) is a dispersant; N,N-dimethylacetamide and N-butylpyrrolidone are cosolvents, and isopropyl alcohol is solvent oil.

[0062] According to the formula in Table 1, MJ01, N,N-dimethylacetamide and N-butylpyrrolidone were added to the preparation kettle; after stirring for 45 minutes until the solution was clear, CO / 40, NS500LQ and polyethylene glycol 400 were added, and finally the solution was supplemented to 100% with isopropanol, and then stirred for 15 minutes, filtered with a 200-mesh sieve, and packaged after the HPLC analysis was qualified; the conditions of the HPLC method included: column temperature: 40℃±2℃; flow rate: 1.5mL / min; mobile phase: acetonitrile: phosphoric acid aqueous solution (0.1%) = 75:25; injection volume: 10μL; wavelength: 245nm; retention time: about 8.5min.

[0063] In this example, a comparative preparation was also prepared, using flurellan as the original drug to prepare a dispersible oil suspension, and then preparing pesticides of different concentrations, the components of which are shown in Table 2.

[0064] Table 2

[0065]

[0066] In Table 2, CO / 40 (short for ethoxylated castor oil) and polyethylene glycol 400 are both emulsifiers; NS500LQ (short for nonionic hydroxylated polyethylene oxide block copolymer) is a dispersant; N,N-dimethylacetamide and N-butylpyrrolidone are cosolvents, and isopropyl alcohol is solvent oil.

[0067] According to the formula in Table 2, add flurana, N,N-dimethylacetamide and N-butylpyrrolidone to the preparation kettle; stir for 45 minutes until the solution is clear, add CO / 40, NS500LQ and polyethylene glycol 400, and finally make up to 100% with isopropanol, stir for 15 minutes, filter with a 200-mesh sieve, and package after passing the HPLC analysis; the conditions of the HPLC include: column temperature: 40℃±2℃; flow rate: 1.5mL / min; mobile phase: acetonitrile: phosphoric acid aqueous solution (0.1%) = 75:25; injection volume = 10μL; wavelength: 245nm; retention time: about 8.6min.

[0068] Example 3

[0069] Indoor biological activity evaluation: Thrips.

[0070] Test target: Thrips nymphs were used as test insects. They were collected from cabbage fields in Leizhou City, Guangdong Province, and fed with indoor self-grown and un-pesticided cabbage leaves for 3 hours. Healthy 2nd-instar nymphs were selected for use.

[0071] Test conditions: temperature 24℃~26℃; humidity RH60%~80%; light intensity L:D=14h:10h.

[0072] Preparation of medicine:

[0073] (1) Preparation of test group: Weigh a certain amount of preparations 1 to 9 prepared in Example 2, add clean water to 100 mL, prepare a 200 mg / L solution, and then dilute with clean water to the required concentration. Select solutions with concentrations of active ingredient MJ01 of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions;

[0074] (2) Preparation of control group: Weigh a certain amount of the flurana preparations prepared in Example 2, i.e., control 1 to control 9, add clean water to 100 mL to prepare a 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with active ingredient flurana concentrations of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions.

[0075] Test method: leaf tube film method.

[0076] Fill 1.5mL Axygen centrifuge tubes with each test solution of the test group and the control group, pour out the solution and dry after 4 hours; set one replicate for each tube, and treat 4 replicates for each concentration, use scissors to cut a small hole with a diameter of about 3mm~5mm at the bottom of the Axygen centrifuge tube; take fresh cabbage leaves, wipe them clean, and use a hole puncher to make a leaf disc with a diameter of 1cm for testing; soak the cabbage leaf disc in the test solution of each concentration for 10s; place the treated leaf disc at room temperature to dry naturally, use tweezers to put the leaf disc together with a 1cm² dry filter paper into the Axygen centrifuge tube of the corresponding test solution concentration, one piece per tube, to form a leaf tube drug film; inoculate 30 healthy test insects of the same size into each Axygen centrifuge tube. Investigation method: Investigate the reaction symptoms and the number of dead insects 3 days after drug administration; touch the insect body lightly with a brush, and it is considered dead if the insect body cannot coordinate movement. Mortality rate = number of dead insects / total number of insects*100%. The experimental results are shown in Table 3.

[0077] Table 3

[0078]

[0079] Note: The data in Table 3 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0080] As shown in Table 3, the MJ01 preparations of Example 2 of the present invention all showed good insecticidal effects on thrips. The MJ01 dispersed oil suspensions provided by preparations 1 to 9 of the present invention were diluted with water to an effective ingredient concentration of 0.5 mg / L and 0.2 mg / L, and the test insect mortality rate after 3 days of medication was 100%; at a dose of 0.1 mg / L, the test insect mortality rate after 3 days of medication was 83.33% ± 2.00% ~ 100%, and at a dose of 0.05 mg / L, the test insect mortality rate after 3 days of medication was 60.00% ± 1.00% ~ 90.70% ± 1.00%. All MJ01 preparations have excellent insecticidal activity performance, and the activity differences between the formulations at the same concentration are not significant.

[0081] As the control group, at a concentration of 0.5 mg / L, the mortality rate of the test insects 3 days after the drug was 100%; at a dose of 0.2 mg / L, the mortality rate of the test insects 3 days after the drug was 85.00%±1.00%~100%; at a dose of 0.1 mg / L, the mortality rate of the test insects 3 days after the drug was 61.00±1.50%~80.00%±2.50%; at a dose of 0.05 mg / L, the mortality rate of the test insects 3 days after the drug was 32.00%±2.00%~43.20%±1.50%.

[0082] From the data comparison in Table 3, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a thrips insecticide, the effect of MJ01 of the present invention is significantly better than that of Frelan.

[0083] Example 4

[0084] Indoor biological activity evaluation: Panonychus citri.

[0085] Test target: The citrus mites collected outdoors were placed in an indoor constant temperature incubator for breeding and bred for more than 3 generations. Healthy, normally developed, and physiologically consistent citrus mites were selected as test mites. The breeding parameters were set to a temperature of 24℃~26℃, a humidity of RH60%~80%, and a photoperiod of L / D=14h / 10h. No chemical agents were exposed during the breeding period.

[0086] Indoor preparation of medicine:

[0087] 1) Preparation of test group: Weigh a certain amount of preparations 1 to 9 prepared in Example 2, add clean water to 100 mL, prepare 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with concentrations of active ingredient MJ01 of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions;

[0088] 2) Preparation of control group: Weigh a certain amount of the flurana preparations prepared in Example 2, i.e., control 1 to control 9, add clean water to 100 mL to prepare a 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with active ingredient flurana concentrations of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions.

[0089] Test method: glass slide immersion method.

[0090] (1) Stick a 2 cm × 2 cm double-sided tape on one end of the slide, leaving only 2 mm to 3 mm width at the edge of the slide;

[0091] (2) Use a No. 0 brush to pick out healthy and uniformly growing female adult mites, and gently stick their backs on a glass slide with double-sided tape, avoiding sticking to the mouthparts, antennae and legs of the mites. Attach 30 female adult mites to each glass slide. Then place the glass slide in a large culture dish, add a wet cotton ball, and cover it with a glass plate. Place it at 25°C and examine it under a microscope after 2 hours to determine whether there are any dead or inactive individuals. If any dead or inactive individuals are found, remove them and add healthy live mites before testing again.

[0092] (3) Immerse the glass slide with the healthy female adult mites pasted on it into the test solution of the test group and the control group, shake gently for 5 seconds, take it out and place it on the filter paper, and then use a small piece of filter paper to gently absorb the excess solution around the mite body and on the tape; repeat each gradient treatment 4 times, place it in the original large culture dish after treatment with each concentration of the drug, and examine it under a binocular stereo microscope at room temperature after 48 hours. Gently touch the limbs of the harmful mite with a No. 0 brush. If the mite’s feet do not move, it is recorded as dead. Record the number of dead mites and the number of live mites; mortality rate = number of dead mites / total number of mites*100%. The experimental results are shown in Table 4.

[0093] Table 4

[0094]

[0095] Note: The data in Table 4 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0096] As shown in Table 4, the MJ01 preparations of Example 2 of the present invention all showed good acaricidal effects on Panonychus citri. The MJ01 dispersed oil suspensions provided by preparations 1 to 9 of the present invention were diluted with water to an effective ingredient concentration of 0.5 mg / L and 0.2 mg / L, and the test mite mortality rate 48 hours after the drug application was 100%; at a dose of 0.1 mg / L, the test mite mortality rate 48 hours after the drug application was 89.67%±1.00%~100%, and at a dose of 0.05 mg / L, the test mite mortality rate 48 hours after the drug application was 66.67%±2.50%~100.00%. All MJ01 preparations showed excellent acaricidal activity, and the activity differences between the formulations at the same concentration were not significant.

[0097] As the control group, at a concentration of 0.5 mg / L, the mortality rate of flurellan dispersible oil suspension was 100% 48 hours after medication; at a dose of 0.2 mg / L, the mortality rate of the test mites 48 hours after medication was 83.00%±2.00%~100%; at a dose of 0.1 mg / L, the mortality rate of the test mites 3 days after medication was 69.10%±2.00%~100.00%; at a dose of 0.05 mg / L, the mortality rate of the test mites 48 hours after medication was 44.20%±1.00%~65.00±1.50%.

[0098] From the data comparison in Table 4, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a miticide for Panonychus citri, the effect of MJ01 of the present invention is significantly better than that of Flulan.

[0099] Example 5

[0100] Indoor biological activity evaluation: Chilo suppressalis.

[0101] Test target: The Chilo suppressalis collected outdoors was raised with rice seeds in an indoor artificial climate for more than 3 generations. The raising parameters were set as temperature 24℃~26℃, humidity RH60%~80%, photoperiod L / D=14h / 10h, and no contact with any chemical agents during the raising period. Healthy, normally developed, and physiologically consistent 3rd-instar Chilo suppressalis larvae were selected as test insects.

[0102] Preparation of medicine:

[0103] 1) Preparation of test group: Weigh a certain amount of preparations 1 to 9 prepared in Example 2, add clean water to 100 mL, prepare 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with concentrations of active ingredient MJ01 of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions;

[0104] 2) Preparation of control group: Weigh a certain amount of the flurana preparations prepared in Example 2, i.e., control 1 to control 9, add clean water to 100 mL to prepare a 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with active ingredient flurana concentrations of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions.

[0105] Test method: immersion method;

[0106] Put wild rice stem strips into the test solution of the test group and the control group, immerse them for 10 seconds, take them out and dry them, and then put them in disposable culture dishes lined with filter paper. Put 10 larvae of Chilo suppressalis in each culture dish. Repeat 4 times for each treatment group, and then transfer the culture dishes to the incubator for culture.

[0107] Investigation method: Observe the survival and death of Chilo suppressalis larvae 5 days after application. Touch the insect body lightly with a brush. If the insect body cannot coordinate movement, it is judged as dead. Mortality rate = number of dead insects / total number of insects*100%. The experimental results are shown in Table 5.

[0108] Table 5

[0109]

[0110] Note: The data in Table 5 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0111] As shown in Table 5, the MJ01 preparation of Example 2 of the present invention all showed good insecticidal effects on Chilo suppressalis. The MJ01 dispersed oil suspension provided by preparations 1 to 9 of the present invention, when diluted with water to an effective ingredient concentration of 0.5 mg / L and 0.2 mg / L, had a test insect mortality rate of 100.00% 5 days after the drug administration; at a dose of 0.1 mg / L, the test insect mortality rate 5 days after the drug administration was 88.30% ± 1.00% ~ 100.00%, and at a dose of 0.05 mg / L, the test insect mortality rate 5 days after the drug administration was 69.50% ± 2.50% ~ 100.00%. All MJ01 preparations showed excellent insecticidal activity, and the activity differences between the formulations at the same concentration were not significant.

[0112] As the control group, at a concentration of 0.5 mg / L, the mortality rate of the test insects 5 days after the drug was 100%; at a dose of 0.2 mg / L, the mortality rate of the test insects 5 days after the drug was 86.00%±1.50%~100.00%; at a dose of 0.1 mg / L, the mortality rate of the test insects 5 days after the drug was 69.10%±2.00%~100.00%; at a dose of 0.05 mg / L, the mortality rate of the test insects 5 days after the drug was 46.20%±1.00%~65.20%±2.50%.

[0113] From the data comparison in Table 5, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a Chilo suppressalis insecticide, the effect of MJ01 of the present invention is significantly better than that of Frelan.

[0114] Example 6

[0115] Indoor biological activity evaluation: fruit flies (taking Bactrocera indica as an example).

[0116] Test target: Bactrocera indica was collected from grapefruit, and bred continuously for more than 3 generations in the laboratory. The adults of Bactrocera indica from the same batch 10 days after emergence were selected as test insects, and starved with clean water for 24 hours before the test. The breeding conditions were as follows: temperature (25±1)℃, relative humidity 75%±1%, and photoperiod L / D=16h / 8h.

[0117] Preparation of medicine:

[0118] 1) Preparation of test group: Weigh a certain amount of preparations 1 to 9 prepared in Example 2, add 10% sucrose solution by mass, and then add clean water to 100 mL to prepare 200 mg / L solution, and then dilute with clean water to the required concentration, and select solutions with concentrations of active ingredient MJ01 of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions;

[0119] 2) Preparation of control group: Weigh a certain amount of the flurana preparation prepared in Example 2, i.e., control 1 to control 9, add 10% sucrose solution by mass, add clean water to 100 mL, prepare 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with the concentration of the active ingredient flurana of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions.

[0120] Test method: liquid feeding method;

[0121] Immerse a sponge (5cm×5cm×5cm) in the test solution of the test group and the control group for 30s, then take it out and leave it naturally until the test solution stops dripping. Place the sponge in a conical flask with a volume of 1000mL; introduce 30 adult citrus fruit flies (half male and half female) into the conical flask, seal it with a punctured lid and place it in an artificial climate box, and continue to raise it under the conditions of temperature = 25℃±1℃, relative humidity = 75%±1%, and photoperiod L / D = 16h / 8h, with 4 replicates for each concentration.

[0122] Investigation method: Observe the survival and death of adult citrus fruit flies 48 hours after application. Touch the insect body lightly with a brush. If the insect body cannot coordinate movement, it is judged as dead. Mortality rate = number of dead insects / total number of insects*100%. The experimental results are shown in Table 6.

[0123] Table 6

[0124]

[0125] Note: The data in Table 6 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0126] As shown in Table 6, the MJ01 preparations of Example 2 of the present invention all showed good insecticidal effects on fruit flies. The MJ01 dispersed oil suspensions provided by preparations 1 to 9 of the present invention were diluted with water to an effective ingredient concentration of 0.5 mg / L and 0.2 mg / L, and the test insect mortality rate 48 hours after the drug was 100.00%; at a dose of 0.1 mg / L, the test insect mortality rate 48 hours after the drug was 92.00%±1.50%~100.00%, and at a dose of 0.05 mg / L, the test insect mortality rate 48 hours after the drug was 76.00%±2.50%~100.00%. All MJ01 preparations have excellent insecticidal activity, and the activity differences between the formulations at the same concentration are not significant.

[0127] As the control group, at the concentration of 0.5 mg / L, the mortality rate of the test insects 48 hours after the drug was 100.00%; at the dose of 0.2 mg / L, the mortality rate of the test insects 48 hours after the drug was 83.00%±2.00%~100.00%; at the dose of 0.1 mg / L, the mortality rate of the test insects 48 hours after the drug was 70.10%±2.00%~100.00%; at the dose of 0.05 mg / L, the mortality rate of the test insects 48 hours after the drug was 49.10%±2.00%~75.00%±1.50%.

[0128] From the data comparison in Table 6, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a fruit fly insecticide, the effect of MJ01 of the present invention is significantly better than that of Frelan.

[0129] Example 7

[0130] Pest repellency test: cotton bollworm and beet armyworm;

[0131] Preparation of medicine:

[0132] 1) Preparation of test group: Weigh a certain amount of preparations 1 to 9 prepared in Example 2, add clean water to 100 mL, prepare 200 mg / L solution, and then dilute with clean water to the required concentration, and select solutions with concentrations of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L of the active ingredient MJ01 as test solutions.

[0133] 2) Preparation of control group: Weigh a certain amount of the flurana preparations prepared in Example 2, i.e., control 1 to control 9, add clean water to 100 mL to prepare a 200 mg / L solution, then dilute with clean water to the required concentration, and select solutions with active ingredient flurana concentrations of 0.5 mg / L, 0.2 mg / L, 0.1 mg / L, and 0.05 mg / L as test solutions.

[0134] 1. Detect the repellent effect of MJ01 on cotton bollworm.

[0135] Test target: The cotton bollworm collected outdoors was raised in an indoor constant temperature incubator, with the parameters set at 24℃~26℃, RH60%~80%, and a photoperiod of L / D=14h / 10h. The adult was raised to eclosion, mating and laying eggs. The obtained F1 generation larvae were used for subsequent tests, and no chemical agents were exposed during the raising period. The 2nd instar larvae with normal development and consistent physiological conditions were selected for the test, and the food intake was measured after being starved for 12 hours.

[0136] Test method:

[0137] (1) Place cotton plants at the bud stage in a breathable container and spray 100 mL of the test solution of each test group and control group evenly on the leaf surface of the cotton plants. Set 10 replicates for each concentration.

[0138] (2) Place the treated cotton plants in a cotton bollworm incubator, with one cotton bollworm placed in each incubator, and use cotton plants sprayed with clean water as a control group;

[0139] (3) Every day, cotton plants were removed and feeding patches were printed with sulfuric acid paper to calculate the feeding area. If any cotton bollworms died, new cotton bollworms were added in time and observed for 24 hours. After the observation period, the total feeding area was measured and the repellency rates of MJ01 and Flurellana against cotton bollworms were calculated. The results are shown in Table 7.

[0140] Calculate the repellency rate = (S 对照 -S 处理 ) / S 对照 ×100%,S 处理 and S 对照 These are the feeding areas of the test solution spraying treatment group and the clear water control group, respectively.

[0141] Table 7

[0142]

[0143] Note: The data in Table 7 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0144] As shown in Table 7, the MJ01 preparations of Example 2 of the present invention all showed good repellent effects on cotton bollworms. The MJ01 dispersed oil suspensions provided by preparations 1 to 9 of the present invention had a 24-hour repellency rate of 100% for cotton bollworms when diluted with water to an effective ingredient concentration of 0.5 mg / L; at a dose of 0.2 mg / L, the 24-hour repellency rate for cotton bollworms was 88.9%±2.00%~100%; at a dose of 0.1 mg / L, the 24-hour repellency rate for cotton bollworms was 69.5%±2.00%~98.0%±1.00%, and at a dose of 0.05 mg / L, the 24-hour repellency rate for cotton bollworms was 60.2%±2.00%~90.15%±1.00%. All MJ01 preparations had excellent anthelmintic activity, and the activity differences between the formulations at the same concentration were not significant.

[0145] As the control group, the flurellan dispersible oil suspension had a 24-hour repellency rate of 100% against cotton bollworm at a dose of 0.5 mg / L; at a dose of 0.2 mg / L, the 24-hour repellency rate against cotton bollworm was 75.00%±1.00%~100%; at a dose of 0.1 mg / L, the 24-hour repellency rate against cotton bollworm was 61.00%±1.50%~80.00%±2.50%; at a dose of 0.05 mg / L, the 24-hour repellency rate against cotton bollworm was 33.90%±1.50%~49.20%±1.50%.

[0146] From the data comparison in Table 7, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a cotton bollworm repellent, the effect of MJ01 of the present invention is significantly better than that of Frelan.

[0147] 2. Detect the repellent effect of MJ01 on Spodoptera exigua.

[0148] Test target: The collected beet armyworm adults were artificially raised in an indoor constant temperature incubator; artificial breeding conditions: the constant temperature incubator was set at (27±1)℃, relative humidity (70±5)%, light intensity 10000lx, and photoperiod L / D = 14h / 10h. The 2nd instar larvae were used for subsequent tests until the adults emerged, mated and laid eggs, and no chemical agents were exposed during the breeding period. The 2nd instar larvae with normal development and consistent physiological conditions were selected for the test, and the food intake was measured after being starved for 12h.

[0149] Test method: Select the middle leaves of cabbage with good growth, no mosaic and no pests; punch leaf discs with a diameter of 3 cm with a hole puncher, and soak the leaf discs in the test solution for 10 minutes and then dry them naturally. Lay 2 leaf discs soaked in water as a control and 2 leaf discs soaked in the test solution in an artificial incubator. The 2 leaf discs treated with the test solution and the 2 leaf discs soaked in water as a control are arranged in a cross shape. Inoculate one beet armyworm larva in each incubator; set 10 groups of replicates for each concentration;

[0150] After the 24-hour test, the remaining area of ​​the leaf disc was measured and the feeding area was calculated. The feeding area = initial area of ​​the leaf disc - remaining area of ​​the leaf disc. The repellency rate was calculated as (S 对照 -S 处理 ) / S 对照 ×100%,S 处理 and S 对照 They are the feeding areas of the test solution immersion treatment group and the clear water control group, and the results are shown in Table 8.

[0151] Table 8

[0152]

[0153] Note: The data in Table 8 are mean ± standard deviation. Different superscript letters in the same column indicate statistically significant differences (P<0.05), while the same letters indicate no statistically significant differences (P>0.05).

[0154] As shown in Table 8, the MJ01 preparations of Example 2 of the present invention all showed good repellent effects on Spodoptera exigua. The MJ01 dispersed oil suspensions provided by Preparations 1 to 9 of the present invention were diluted with water to an effective ingredient concentration of 0.5 mg / L and 0.2 mg / L, and the 24-hour Spodoptera exigua repellency rate was 100%; at a dose of 0.1 mg / L, the 24-hour Spodoptera exigua repellency rate was 78.10%±2.00%~100%, and at a dose of 0.05 mg / L, the 24-hour Spodoptera exigua repellency rate was 74.90%±2.50%~96.80%±2.00%. All MJ01 preparations showed excellent insect repellent activity, and the activity differences between the formulations at the same concentration were not significant.

[0155] As the control group, the 24-hour beet armyworm repellency rate of flurellan dispersible oil suspension was 100% at a concentration of 0.5 mg / L; at a dose of 0.2 mg / L, the 24-hour beet armyworm repellency rate was 83.20%±2.00%~100%; at a dose of 0.1 mg / L, the 24-hour beet armyworm repellency rate was 68.10%±2.00%~86.10%±1.50%; at a dose of 0.05 mg / L, the 24-hour beet armyworm repellency rate was 43.90%±1.50%~69.00%±1.50%.

[0156] From the data comparison in Table 8, it can be seen that at low concentrations, the activity of the control group (Frelan) is significantly different from that of the test group (MJ01). As a repellent for beet armyworm, the effect of MJ01 of the present invention is significantly better than that of Frelan.

[0157] The above-described embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the present invention. It should be pointed out that, for a person of ordinary skill in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the attached claims.

Claims

1. An application of an amide compound containing isoxazoline, characterized in that: The isoxazoline-containing amide compound is used to prepare a pesticide composition, wherein the isoxazoline-containing amide compound or a pesticide-acceptable salt thereof is the main active ingredient of the pesticide composition; the pesticide composition is used as a repellent for repelling crop pests; the crop pests to be repelled are cotton bollworm or beet armyworm; The structure of the isoxazoline-containing amide compound is shown in the following formula: 。 2. The use of the isoxazoline-containing amide compound according to claim 1, characterized in that: The pesticide composition also includes a formulation carrier or a formulation adjuvant.

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