Isoxazoline compound containing benzamide as well as preparation method and application of isoxazoline compound

Abstract

The invention belongs to the technical field of organic matter preparation, and provides an isoxazoline compound containing benzamide as well as a preparation method and application thereof.Chemical modification and molecular design are performed on a compound with an isoxazoline structure, a substituent group is introduced to N of an amide group, and the benzamide-containing isoxazoline compound is prepared. A series of high-efficiency compounds which can be used for killing insects or mites in agriculture or forestry and have excellent activity are obtained, and particularly, the compounds have very good biological activity on pests of lepidoptera, hemiptera and the like. When being used at an extremely low concentration, the compound disclosed by the invention also shows an excellent control effect on various pests or pest mites, has insecticidal or acaricidal activity in each stage (such as eggs, larvae (nymphs), pupae and adults) of the life cycle of the pests or pest mites, and has an excellent control effect on the pests or pest mites which have drug resistance to traditional insecticides or acaricides. And the composition also shows excellent control activity.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic matter preparation, and particularly relates to an isoxazoline compound containing benzamide and a preparation method and application thereof. BACKGROUND

[0002] In recent years, due to long-term use of pesticides, fungicides and other pest control agents, pests develop drug resistance, which makes the existing pesticide effect significantly decreased. Although a variety of pesticides (such as isoxazoline compounds disclosed in WO2007 / 026965) have been developed, the pesticides prepared by the prior art still have high toxicity and low insecticidal efficiency.

[0003] Therefore, it is of great significance to study an isoxazoline compound containing benzamide with high efficiency and low toxicity and the application thereof. SUMMARY

[0004] The present application aims at overcoming the defects in the prior art, and provides an isoxazoline compound containing benzamide and a preparation method and application thereof.

[0005] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:

[0006] The present application provides an isoxazoline compound containing benzamide, and the structure of the isoxazoline compound containing benzamide is shown in formula I:

[0007]

[0008] In the formula, R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group.

[0009] As a preferred, the oxygen-containing alkyl is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl or alkoxyalkyl.

[0010] The unsaturated alkyl is C2-C6 alkenyl or C2-C6 alkynyl.

[0011] The aryl-containing alkyl is arylalkyl or heteroarylalkyl.

[0012] The heteroatom-containing hydrocarbon group is halogenated alkyl, cyanoalkyl, halogenated alkenyl, halogenated alkynyl, halogenated cycloalkyl, alkylthio, halogenated alkylthio, halogenated alkoxy, halogenated alkylcarbonyl, halogenated alkoxycarbonyl, alkylaminoalkyl, halogenated alkylaminoalkyl or halogenated alkoxyalkyl.

[0013] The application also provides a preparation method of the benzamide-containing isoxazoline compound, comprising the following steps:

[0014] After the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and the dichloro sulfoxide are initially reacted, triethylamine, acetonitrile and an amino compound are added for reaction, and the benzamide-containing isoxazoline compound is obtained.

[0015] Preferably, the molar volume ratio of the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and the dichloro sulfoxide is 0.65-0.75 mmol: 2-4 mL.

[0016] Preferably, the initial reaction is carried out at a temperature of 40-50°C for 3-5 h.

[0017] Preferably, the amount ratio of the dichloro sulfoxide, the triethylamine and the acetonitrile is 2-4 mL: 1-1.1 mmol: 10-20 mL.

[0018] Preferably, the amino compound has a structural formula of NH2-R.

[0019] wherein R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group;

[0020] The oxygen-containing alkyl is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl or alkoxyalkyl.

[0021] The unsaturated alkyl is C2-C6 alkenyl or C2-C6 alkynyl.

[0022] The aryl-containing alkyl is arylalkyl or heteroarylalkyl.

[0023] The heteroatom-containing hydrocarbon group is halogenated alkyl, cyanoalkyl, halogenated alkenyl, halogenated alkynyl, halogenated cycloalkyl, alkylthio, halogenated alkylthio, halogenated alkoxy, halogenated alkylcarbonyl, halogenated alkoxycarbonyl, alkylaminoalkyl, halogenated alkylaminoalkyl or halogenated alkoxyalkyl.

[0024] Preferably, the molar ratio of the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and the amino compound is 0.65-0.75: 0.8-0.85.

[0025] Preferably, the reaction is carried out at a temperature of 20-30°C for 4-6 h.

[0026] The present application also provides the use of the benzamide-containing isoxazoline compound in insecticide.

[0027] As a preference, the benzamide-containing isoxazoline compound is used in an amount of 1-1000 ppm.

[0028] The present application provides a benzamide-containing isoxazoline compound. The present application introduces substituents on the N of amide group by chemical modification and molecular design of compounds with isoxazoline structure, and obtains a series of compounds with excellent activity for use in agricultural or forestry insecticide or acaricide, especially with good biological activity against Lepidoptera, Hemiptera and other pests.

[0029] The obtained compound of the present application shows excellent control effect on various pests or mites when used at very low concentration, and has insecticidal or acaricidal activity at each stage (such as egg, larva (nymph), pupa and adult) of the life cycle of pests or mites, and also shows excellent control activity on pests or mites with resistance to traditional insecticides or acaricides. DETAILED DESCRIPTION

[0030] The present application provides a benzamide-containing isoxazoline compound, and the structure of the benzamide-containing isoxazoline compound is shown as formula I:

[0031]

[0032] In the formula, R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group.

[0033] In the present application, the oxygen-containing alkyl is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl or alkoxyalkyl.

[0034] The unsaturated alkyl is C2-C6 alkenyl or C2-C6 alkynyl.

[0035] The aryl-containing alkyl is arylalkyl or heteroarylalkyl.

[0036] The heteroatom-containing hydrocarbon group is halogenated alkyl, cyanoalkyl, halogenated alkenyl, halogenated alkynyl, halogenated cycloalkyl, alkylthio, halogenated alkylthio, halogenated alkoxy, halogenated alkylcarbonyl, halogenated alkoxycarbonyl, alkylaminoalkyl, halogenated alkylaminoalkyl or halogenated alkoxyalkyl.

[0037] In the present application, the benzamide-containing isoxazoline compound preferably has the following structure, in order: YC1-YC35.

[0038]

[0039]

[0040]

[0041]

[0042] The present application also provides a preparation method of the benzamide-containing isoxazoline compound, comprising the following steps:

[0043] After the preliminary reaction of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and dichlorosulfoxide, triethylamine, acetonitrile and an amino compound are added for reaction, and the benzamide-containing isoxazoline compound is obtained.

[0044] In the present application, the molar volume ratio of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and dichlorosulfoxide is preferably 0.65-0.75 mmol: 2-4 mL, further preferably 0.66-0.74 mmol: 2.5-3.5 mL, and more preferably 0.68-0.72 mmol: 2.8-3.2 mL.

[0045] In the present application, the temperature of the preliminary reaction is preferably 40-50°C, further preferably 42-48°C, and more preferably 44-46°C; and the time is preferably 3-5 h, further preferably 3.5-4.5 h, and more preferably 3.6-4.4 h.

[0046] In the present application, after the preliminary reaction is completed, the excess dichlorosulfoxide is removed by rotary evaporation.

[0047] In the present application, the amount ratio of dichlorosulfoxide, triethylamine and acetonitrile is preferably 2-4 mL: 1-1.1 mmol: 10-20 mL, further preferably 2.5-3.5 mL: 1.02-1.08 mmol: 12-18 mL, and more preferably 2.8-3.2 mL: 1.04-1.06 mmol: 14-16 mL.

[0048] In the present application, the structural formula of the amino compound is NH2-R;

[0049] wherein R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group;

[0050] said oxygen-containing alkyl group is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl, alkoxyalkyl;

[0051] said unsaturated alkyl group is C2-C6 alkenyl or C2-C6 alkynyl;

[0052] said aromatic-containing alkyl group is aralkyl or heteroaralkyl;

[0053] said heteroatom-containing alkyl group is haloalkyl, cyanoalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, alkylthio, haloalkylthio, haloalkoxy, haloalkylcarbonyl, haloalkoxycarbonyl, alkylaminoalkyl, haloalkylaminoalkyl or haloalkoxyalkyl.

[0054] In the present application, the molar ratio of the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and the amino compound is preferably 0.65-0.75:0.8-0.85, further preferably 0.66-0.74:0.81-0.84, more preferably 0.68-0.72:0.82-0.83.

[0055] In the present application, the temperature of the reaction is preferably 20-30℃, further preferably 22-28℃, more preferably 24-26℃; the time is preferably 4-6h, further preferably 4.5-5.5h, more preferably 4.6-5.4h; and the reaction is kept under stirring.

[0056] In the present application, after the reaction is completed, the product is washed with water, then extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated under vacuum, the vacuum degree of the vacuum concentration is preferably 0.09-0.1MPa, further preferably 0.092-0.098MPa, more preferably 0.094-0.096MPa; then purified by column chromatography to obtain the benzamide-containing isoxazoline compound.

[0057] The present application also provides the use of the benzamide-containing isoxazoline compound in insect killing.

[0058] In the present application, the dosage of the benzamide-containing isoxazoline compound is preferably 1-1000ppm, further preferably 10-900ppm, more preferably 50-800ppm.

[0059] In the present application, the objects of the insect killing are Lepidoptera, Coleoptera, Homoptera, Hemiptera, Thysanoptera, Isoptera, Diptera, Hymenoptera, Anoplura, Siphunculata, Orthoptera, Blattaria, Pulicida, Ixodida, Nematoda.

[0060] In the present invention, Lepidoptera is specifically: cotton bollworm, night moth, secret night moth, small tiger, diamond, trichoplusia ni, melwitta cuculata, small cabbage moth, yellow bollworm, diamondback moth, rice borer, rice leaf roller, corn borer, codling moth, peach fruit moth, cotton brown banded leaf roller, fruit tree yellow roller, apple brown leaf roller, night small roller, grape and apple leaf roller, grape flower wing small roller, cotton red bollworm, vegetable green caterpillar, spin worm, citrus leaf roller, beet armyworm, grass armyworm, Asian corn borer;

[0061] In the present invention, Coleoptera is specifically: leaf beetle, potato leaf beetle, rice negative mud beetle, cotton boll weevil, rice water weevil, gold needle beetle, Japanese bean beetle, round-headed rhinoceros beetle, pseudo-gram species;

[0062] In the present invention, Homoptera is specifically: black tail leafhopper, pear garden scale;

[0063] In the present invention, Hemiptera is specifically: aphid, tobacco aphid, plantain round tail aphid, orange aphid, alfalfa aphid, long tube aphid, netted aphid, long tube aphid, wheat aphid, wheat netted long tube aphid, wheat two-pronged aphid, wheat double tail aphid, pea aphid, peach aphid, blind bug, rice green bug, rice edge shield, warm blooded bug, tropical blooded bug, gray planthopper, tobacco whitefly, greenhouse whitefly, silk velvet whitefly, brown planthopper, white-backed planthopper, tea green leafhopper;

[0064] In the present invention, Thysanoptera is specifically: western flower thrips, thrips, tea yellow thrips;

[0065] In the present invention, Isoptera is specifically: yellow limb scattered termite, house termite, southern scattered termite, western scattered termite, mulberry scattered termite, yellow thoracic scattered termite, American black leg scattered termite, wet wood termite, column termite, edge termite, large termite, large saw termite, man termite;

[0066] In the present invention, Diptera is specifically: spotted fly, housefly, spotted mosquito, house mosquito, malaria mosquito, toilet fly, waste fly;

[0067] In the present invention, Hymenoptera is specifically: red ant, fire ant, pharaoh ant, harvest ant, bowback ant, small house ant, smelly house ant, paving ant, wasp, long foot wasp;

[0068] In the present invention, Mallophaga is specifically: feather louse;

[0069] In the present invention, Anoplura is specifically: blood louse, pudendal louse, louse;

[0070] In the present invention, Orthoptera is specifically: black locust, east Asian locust, desert locust, mole cricket;

[0071] In the present invention, Blattaria is specifically: oriental cockroach, german cockroach, american cockroach, long whisker cockroach, australian cockroach, brown banded cockroach, pennsylvania wood cockroach, black thoracic cockroach, cane cockroach;

[0072] In this invention, the order Siphonaptera specifically refers to fleas and human fleas;

[0073] In this invention, the order Acari is specifically defined as: Tetranychidae, Eriopodidae, Eriophyridae, Phytoseiidae, and Flocculationidae, including but not limited to spider mites, spider mites, Tetranychus carmineus, Tetranychus orientalis, Tetranychus two-spotted, Tetranychus citrus rust mite, Tetranychus purpureus, cattle tick, Tetranychus mutata, Tetranychus rubrum ... scabies mite, and dust mite;

[0074] In this invention, the nematode class specifically includes: canine filarial nematode, root-knot nematode, cyst nematode, crown nematode, needle-piercing nematode, root-rot nematode, kidney-shaped nematode, decorative ring nematode, stem nematode, leaf bud nematode, and rice paddy root-burrowing nematode.

[0075] In this invention, the isoxazoline compounds containing benzamide can be combined with antibiotic insecticides, macrolide insecticides, abamectin insecticides, mirtamicin insecticides, arsenic-containing insecticides, biological insecticides, plant-added protective insecticides, phytochemicals, carbamate insecticides, benzofuranylmethyl carbamate insecticides, dinitrophenol insecticides, oxime carbamate insecticides, phenylmethyl carbamate insecticides, dinitrophenol insecticides, fluoride insecticides, formamidins, fumigants, etc. Vaporized insecticides, inorganic insecticides, chitin synthesis inhibitors, juvenile hormones, ecdysone enhancers, ecdysone, precocious hormones, insect growth regulators, nereistoxin analogs, neonicotinoid insecticides, nitroguanidine insecticides, nitromethylene insecticides, pyridylmethylamine insecticides, organochlorine insecticides, cyclodiene insecticides, organophosphate insecticides, organothiophosphate insecticides, aliphatic organothiophosphate insecticides, heterocyclic organothiophosphate insecticides Insecticides, benzothiaran organothiophosphate insecticides, benzotriazine organothiophosphate insecticides, isoindole organothiophosphate insecticides, isoxazole organothiophosphate insecticides, pyrazolopyrimidine organothiophosphate insecticides, pyridine organothiophosphate insecticides, pyrimidine organothiophosphate insecticides, quinoxaline organothiophosphate insecticides, thiadiazole organothiophosphate insecticides, triazole organothiophosphate insecticides, phenyl organothiophosphate insecticides Phosphonate insecticides, thiophosphonate insecticides, phenylethyl thiophosphonate insecticides, phenylphenyl thiophosphonate insecticides, aminophosphate insecticides, thiophosphoramide insecticides, diphosphamide insecticides, oxadiazine insecticides, phthalimide insecticides, pyrazole insecticides, pyrethroid insecticides, pyrethroid ether insecticides, pyrimidine amine insecticides, pyrrole insecticides, quaternary ketone acid insecticides, thiourea insecticides, urea insecticides, and unclassified insecticides may be used in any combination.

[0076] In the present application, the obtained benzamide-containing isoxazoline compound can be used to prepare wettable powder, wettable liquid, soluble powder, dispersible liquid, aqueous solution, microemulsion, emulsion, aqueous emulsion, sprayable solution, suspension, dispersible oil suspension, powder, microcapsule suspension, water dispersible granule, water soluble granule, granule for sowing and soil application, aerosol, ultra-low volume agent and wax product.

[0077] The technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.

[0078] The preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid is provided in the embodiments of the present application, and the specific process is as follows:

[0079] (1) Preparation of (Z)-4-[(hydroxyimino)methyl]-2-methylbenzoic acid methyl ester:

[0080] 40.0 mmol of 1, 9 mL of an aqueous solution of hydroxylamine hydrochloride (the content of hydroxylamine hydrochloride is 48.0 mmol), and 10 mL of anhydrous ethanol are added to a round-bottom flask, the reaction solution is adjusted to pH 7 with a saturated sodium carbonate solution, and stirring is performed at 25°C for 1 h. After the reaction is completed, ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum concentration (the vacuum degree is 0.098 MPa), and anhydrous ethanol recrystallization are sequentially performed to obtain yellow solid product 2 (6.6 g, the yield is 85%).

[0081]

[0082] (2) Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid methyl ester:

[0083] 20.0 mmol of 2, 30 mmol of N-chlorosuccinimide are added to a round-bottom flask, stirring is performed at 40°C for 40 min, 24.0 mmol of 2a and 30.0 mmol of triethylamine are added, stirring is performed at 25°C for 18 h, after the reaction is completed, water washing is performed for 3 times, ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum concentration (the vacuum degree is 0.098 MPa), and column chromatography purification are sequentially performed to obtain light yellow solid 3 (7.2 g, the yield is 80%).

[0084]

[0085] (3) Preparation of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid:

[0086] Into a round bottom flask, 10.0 mmol of 3 and 15 mL of aqueous sodium hydroxide solution (sodium hydroxide content of 30.0 mmol) were added, and the reaction was stirred at 80°C under reflux for 1 h. After the reaction was completed, the reaction solution was poured into 50 mL of ice water, and the pH of the solution was adjusted to 3.5 with concentrated hydrochloric acid. The reaction solution was filtered under suction through a Buchner funnel, and the filter cake was dried at 70°C for 300 min to obtain 4 as a yellow solid (4.1 g, yield 93%).

[0087]

[0088] Example 1

[0089] Compound YC1:

[0090]

[0091] Preparation of Compound YC1:

[0092] Into a 50 mL round bottom flask, 0.69 mmol of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfoxide were added, and the reaction was stirred at 45°C for 4 h. After the reaction was completed, the excess dichlorosulfoxide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of m-chloroaniline were added, and the reaction was stirred at 25°C for 5 h. After the reaction was completed, the reaction solution was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.31 g of Compound YC1 as a yellow solid, with a yield of 82%.

[0093] Example 2

[0094] Compound YC2:

[0095]

[0096] Preparation of Compound YC2:

[0097] Into a 50 mL round bottom flask, 0.69 mmol of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfoxide were added, and the reaction was stirred at 45°C for 4 h. After the reaction was completed, the excess dichlorosulfoxide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of m-chloroaniline were added, and the reaction was stirred at 25°C for 5 h. After the reaction was completed, the reaction solution was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.31 g of Compound YC1 as a yellow solid, with a yield of 82%.

[0098] Example 3

[0099] Preparation of compound YC6:

[0100]

[0101] Preparation of compound YC6:

[0102] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation. Then, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of 2,6-difluoroaniline were added, and the reaction was stirred at 25 °C for 5 h. The reaction was completed, and the reaction mixture was washed with water three times, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.29 g of compound YC6 as a yellow solid in a yield of 76%.

[0103] Example 4

[0104] Preparation of compound YC7:

[0105]

[0106] Preparation of compound YC7:

[0107] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation. Then, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of 2,2-difluoroethanamine were added, and the reaction was stirred at 25 °C for 5 h. The reaction was completed, and the reaction mixture was washed with water three times, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.29 g of compound YC7 as a yellow solid in a yield of 81%.

[0108] Example 5

[0109] Preparation of compound YC8:

[0110]

[0111] Preparation of compound YC8:

[0112] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of A-trifluoromethylethylamine were added, and the reaction was stirred at 25 °C for 5 h. The reaction was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.27 g of compound YC8 as a yellow solid in a yield of 75%.

[0113] Example 6

[0114] Compound YC9:

[0115]

[0116] Preparation of compound YC9:

[0117] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of A-trifluoromethylethylamine were added, and the reaction was stirred at 25 °C for 5 h. The reaction was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.27 g of compound YC8 as a yellow solid in a yield of 75%.

[0118] Example 7

[0119] Compound YC10:

[0120]

[0121] Preparation of compound YC10:

[0122] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of isopropylamine were added, and the reaction was stirred at 25 °C for 5 h. The reaction was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.29 g of compound YC10 as a yellow solid in a yield of 87%.

[0123] Example 8

[0124] Compound YC18:

[0125]

[0126] Preparation of compound YC18:

[0127] Into a 50 mL round-bottom flask was placed 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of isopropylamine were added, and the reaction was stirred at 25 °C for 5 h. The reaction was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to obtain 0.29 g of compound YC10 as a yellow solid in a yield of 87%.

[0128] Example 9

[0129] Compound YC19:

[0130]

[0131] Preparation of compound YC19:

[0132] A 50 mL round-bottom flask was charged with 0.69 mmol of 4-(5-(3,5-dichloro-4- fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid, 3 mL of dichlorosulfide, and the reaction was stirred at 45 °C for 4 h. The excess dichlorosulfide was removed by rotary evaporation, 1.04 mmol of triethylamine, 15 mL of acetonitrile, and 0.83 mmol of 2-chloro-4-methylaniline were added, and the reaction was stirred at 25 °C for 5 h. The reaction was washed with water three times, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under vacuum (0.098 MPa), and purified by column chromatography to give 0.27 g of compound YC19 as a yellow solid in a yield of 70%.

[0133] The compounds YC1-YC35 were respectively subjected to the following performance tests: 1 The H NMR data were detected, and the detection results are shown in Table 1.

[0134] Table 1: H NMR detection results of compounds YC1-YC35 1 H NMR detection results

[0135]

[0136]

[0137]

[0138]

[0139]

[0140]

[0141]

[0142]

[0143]

[0144] The compounds YC1-YC35 were respectively subjected to the following performance tests:

[0145] Insecticidal activity detection:

[0146] The compounds YC1-YC35 were respectively dissolved in DMSO and prepared into test solutions with concentrations of 10 μg / mL and 50 μg / mL.

[0147] Cabbage leaves were dipped in different test solutions for 10 seconds, air-dried, and placed in Petri dishes. Second instar Plutella xylostella were introduced into the Petri dishes. Corn leaves were dipped in different test solutions for 10 seconds, air-dried, and placed in Petri dishes. Third instar Ostrinia furnacalis, Spodoptera exigua and Popillia japonica were introduced into the Petri dishes. Tea shoots were dipped in the test solutions for 30 seconds, and placed in clean glass tubes. Healthy third instar Empoasca vitis were introduced into the tubes.

[0148] Two milliliters of the test solution were sprayed on the host plants (radish seedlings and broad bean seedlings), and air-dried. The western flower thrips (initially eclosed) and the broad bean aphid (3 days old) were introduced onto the host plants. Each experimental unit was repeated three times to obtain the treated experimental units;

[0149] The treated experimental units were placed in a growth chamber at 26°C, 75% RH (relative humidity), and 16h:8h (light:dark photoperiod). The results were checked after 48 hours. If the insects could not normally crawl with a needle, they were considered dead. The formula for correcting the mortality rate is shown in equation (III):

[0150] Corrected mortality rate (%) = (T-C) x 100 / (100%-C) equation (III);

[0151] wherein T is the mortality rate of the test compound group, %;

[0152] C is the mortality rate of the blank control group, %.

[0153] Test results:

[0154] The compounds with a mortality rate of more than 80% for Plutella xylostella at a concentration of 10 μg / mL were YC1, YC2, YC4, YC5, YC6, YC7, YC8, YC9, YC10, YC11, YC12, YC13, YC14, YC18, YC21, YC26, YC27, YC28, YC29, and YC31.

[0155] The compounds with a mortality rate of more than 80% for Ostrinia furnacalis at a concentration of 10 μg / mL were YC2, YC5, YC6, YC7, YC8, YC18, YC28, and YC29.

[0156] The compounds with a mortality rate of more than 80% for Spodoptera exigua at a concentration of 50 μg / mL were YC1, YC2, YC4, YC5, YC6, YC7, YC8, YC9, YC10, YC11, YC12, YC13, YC14, YC17, YC18, YC21, YC22, YC25, YC26, YC27, YC28, YC29, and YC31.

[0157] The compounds with a mortality rate of more than 80% on the beet armyworm at a concentration of 50 μg / mL are YC2, YC4, YC5, YC6, YC7, YC8, YC10, YC12, YC18, YC28, and YC29.

[0158] The compounds with a mortality rate of more than 80% on the western flower thrips at a concentration of 50 μg / mL are YC2, YC6, YC7, YC8, YC18, YC28, and YC29.

[0159] The compounds with a mortality rate of more than 80% on the pea aphid at a concentration of 50 μg / mL are YC7, YC8, and YC9.

[0160] The compounds with a mortality rate of more than 80% on the tea green leafhopper at a concentration of 50 μg / mL are YC7, YC8, and YC18.

[0161] Miticidal activity detection:

[0162] The compounds YC1 to YC35 were dissolved in DMSO and prepared into test solutions with a concentration of 10 μg / mL, respectively.

[0163] The double-sided adhesive tape was cut into 2 cm long and pasted on one end of a microscope slide, the paper on the tape was removed with tweezers, and the size-uniform and active T. cinnabarinus were selected with a brush and pasted on the back of the tape, 4 rows and 10 individuals per row. The slide was placed in a 25℃, 80% RH (relative humidity), 16h:8h (light:dark photoperiod) artificial climate box for 4h, observed with binoculars, and the dead or inactive individuals were removed.

[0164] The slide with the mites was immersed in the test solution, gently shaken for 5s, and then taken out, and the mite bodies and the excess solution around the mite bodies were quickly absorbed with a water-absorbing paper. The slide was placed in the artificial climate box, and the results were checked with binoculars after 24h. The mite bodies were gently touched with a brush, and the mites without movement were considered dead, and the mortality rate was calculated according to formula (III).

[0165] Test results:

[0166] The compounds with a mortality rate of more than 80% on the T. cinnabarinus at a concentration of 10 μg / mL are YC2, YC6, YC7, YC8, YC18, and YC29.

[0167] Insecticidal activity detection of different compounds:

[0168] Comparative Example 1

[0169] The compound in patent CN1930136 has the following structural formula:

[0170] The compound in patent CN1930136 has the following structural formula:

[0171] Comparative Example 2

[0172] The compound in patent WO2009005015 has the structural formula:

[0173]

[0174] Comparative Example 3

[0175] The compound in patent WO2009005015 has the structural formula:

[0176]

[0177] Comparative Example 4

[0178] The compound in the prior application of Chinese invention patent (application number: 202510517596.0) has the structural formula:

[0179]

[0180] Comparative Example 5

[0181] The compound in Chinese invention patent (application number: 202510316859.1) has the structural formula:

[0182]

[0183] Comparative Example 6

[0184] The commercially available fluoxastrobin was purchased from Shanghai Zhixin Biomedicine Technology Co., Ltd.

[0185] The compounds YC8, YC18, the compound shown in Comparative Example 1, the compound shown in Comparative Example 2, the compound described in Comparative Example 3 and the compound shown in Comparative Example 4 were respectively dissolved with DMSO, and were respectively configured into the test solutions with the concentration of 0.1 mg / L, 1 mg / L and 10 mg / L;

[0186] The cabbage pieces were respectively immersed in different test solutions for 10 s, and after air-drying, they were placed in culture dishes, and 2nd instar Plutella xylostella were respectively placed in the culture dishes, and the process was repeated three times to obtain the treated experimental units;

[0187] The treated experimental units were placed in a growth chamber at 26℃, 75% RH (relative humidity), 16h:8h (light:dark photoperiod). After 48h, the results were checked, and the insects were considered dead if they could not crawl normally by touching the insects with a probe. The calculation formula for correcting the mortality rate is shown in formula (III). The results obtained are shown in Table 2.

[0188] Table 2: Activity detection results of different compounds

[0189]

[0190] As shown in Table 2, the compounds YC8 and YC18 prepared in the present application can have a mortality rate of more than 60% for the diamondback moth at a small amount of addition (0.1 mg / L), while the compounds shown in Comparative Examples 1-5 can have a mortality rate of only up to 37% for the diamondback moth at a small amount of addition. Thus, the compounds obtained in the present application have high insecticidal activity.

[0191] The above only describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. An isoxazoline compound containing benzamide, characterized in that, The benzamide-containing isoxazoline compound has the structure shown in formula I: R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group.

2. The isoxazoline compound containing benzamide as described in claim 1, characterized in that, The oxygen-containing alkyl is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl or alkoxyalkyl. The unsaturated alkyl is C2-C6 alkenyl or C2-C6 alkynyl. The aryl-containing alkyl is arylalkyl or heteroarylalkyl. The heteroatom-containing hydrocarbon group is haloalkyl, cyanoalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, alkylthio, haloalkylthio, haloalkoxy, haloalkylcarbonyl, haloalkoxycarbonyl, alkylaminoalkyl, haloalkylaminoalkyl or haloalkoxyalkyl.

3. The process for producing the benzamide-containing isoxazoline compound according to claim 1 or 2, characterized by, The method comprises the following steps: After the preliminary reaction of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and dichlorosulfide, triethylamine, acetonitrile and an amino compound are added for reaction, and the benzamide-containing isoxazoline compound is obtained.

4. The method for preparing isoxazoline compounds containing benzamide as described in claim 3, characterized in that, The molar volume ratio of the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and dichlorosulfide is 0.65-0.75 mmol:2-4 mL.

5. The method for preparing the isoxazoline compound containing benzamide as described in claim 4, characterized in that, The temperature of the preliminary reaction is 40-50°C, and the time is 3-5 h.

6. The method for preparing isoxazoline compounds containing benzamide as described in claim 5, characterized in that, The amount ratio of the dichlorosulfide, triethylamine and acetonitrile is 2-4 mL:1-1.1 mmol:10-20 mL.

7. The method for preparing the isoxazoline compound containing benzamide as described in claim 6, characterized in that, The amino compound has the structural formula NH2-R; R is halogen, cyano, nitro, amino, C1-C6 alkyl, aryl, oxygen-containing alkyl, unsaturated alkyl, aryl-containing alkyl, heteroaryl, C3-C6 cycloalkyl or heteroatom-containing hydrocarbon group. The oxygen-containing alkyl is C1-C6 alkoxy, carbonyl, formyl, alkylcarbonyl, alkoxycarbonyl or alkoxyalkyl. The unsaturated alkyl is C2-C6 alkenyl or C2-C6 alkynyl. The aryl-containing alkyl is arylalkyl or heteroarylalkyl. The heteroatom-containing hydrocarbon group is haloalkyl, cyanoalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, alkylthio, haloalkylthio, haloalkoxy, haloalkylcarbonyl, haloalkoxycarbonyl, alkylaminoalkyl, haloalkylaminoalkyl or haloalkoxyalkyl. The molar ratio of the 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid and the amino compound is 0.65-0.75:0.8-0.

85.

8. The method for preparing the isoxazoline compound containing benzamide as described in claim 7, characterized in that, The temperature of the reaction is 20-30°C, and the time is 4-6 h.

9. The benzamide-containing isoxazoline compound of claim 1 or 2 is used in insecticide.

10. Use of the isoxazoline compound containing benzamide according to claim 9 for combating insects, characterized in that, The amount of the benzamide-containing isoxazoline compound is 1-1000 ppm.

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