A class of trifluoromethyl oxadiazole derivatives, their preparation methods and applications

Abstract

The present invention discloses a trifluoromethyl oxadiazole derivative represented by general formula A-1: for each substituent, see the specification. The present invention also discloses a preparation method and uses of the trifluoromethyl oxadiazole derivative, and the trifluoromethyl oxadiazole derivative is particularly suitable for preventing and controlling soybean rust, wheat rust, corn rust, crop anthracnose, etc.

Description

Technical Field

[0001] The present invention belongs to the field of agricultural fungicides, and particularly relates to a class of trifluoromethyl oxadiazole derivatives, a preparation method thereof, and applications thereof. Background Art

[0002] In agriculture, long-term use of the same pesticide variety is likely to cause diseases to develop drug resistance. Therefore, it is necessary to continuously develop new varieties with different action mechanisms. With the improvement of fluorination technology, more and more polyfluoroalkyl groups have been introduced into organic compounds. Due to the pseudo effect, blocking effect of fluorine atoms, as well as the unique physical and chemical properties such as the high electronegativity of fluorine atoms and the liposolubility of fluorine-containing compounds, more and more new fluorine-containing pesticide varieties have been developed, and trifluoromethyl oxadiazole derivatives are one of them.

[0003] Patent CN112004813A discloses a trifluoromethyl oxadiazole derivative, the compound numbered 1 shown by the following formula, and its connection structure connected to the trifluoromethyl oxadiazole group-substituted phenyl is -CO-N-SO-.

[0004]

[0005] Patent WO2018118781A1 discloses a trifluoromethyl oxadiazole derivative, including the compound structure shown by the following formula, and its connection structure connected to the trifluoromethyl oxadiazole group-substituted phenyl is only an isoxazole connection structure.

[0006]

[0007] Patent CN110054596A discloses a trifluoromethyl oxadiazole derivative, including the compound structure shown by the following formula, and its connection structure connected to the trifluoromethyl oxadiazole group-substituted phenyl is an alkylene group.

[0008]

[0009] Although the above patents all disclose trifluoromethyl oxadiazole derivatives, their connection structures connected to the trifluoromethyl oxadiazole group-substituted phenyl are all different. Different connection structures make the compounds exhibit different biological activities. Summary of the Invention

[0010] In order to solve the above technical problems, the present invention provides a trifluoromethyl oxadiazole derivative shown by general formula A-1:

[0011]

[0012] Wherein,

[0013] R1, R2, R3, and R4 are independently selected from hydrogen, halogen, nitro, cyano, C1-C7 alkyl, C1-C7 haloalkyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C1-C7 alkenyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-C7 alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfinyl, or C1-C7 alkylsulfonyl;

[0014] R5 is selected from hydrogen, cyano, C1-C7 alkyl, C1-C7 haloalkyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C1-C7 alkenyl, or aryl or heteroaryl substituted by hydrogen, halogen, nitro, cyano, C1-C7 alkyl, C1-C7 haloalkyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C1-C7 alkenyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-C7 alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfinyl, C1-C7 alkylsulfonyl;

[0015] R7 is selected from one of the following formulas Q-1 and Q-2:

[0016]

[0017] wherein,

[0018] X is selected from oxygen or sulfur;

[0019] R8, R9, and R10 are independently hydrogen, C1-C7 alkyl, C1-C7 haloalkyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C1-C7 alkenyl, C1-C7 alkylalkoxy, C1-C7 haloalkylalkoxy, C1-C7 alkylalkylthio, C1-C7 haloalkylalkylthio, or aryl or heteroaryl substituted by hydrogen, halogen, nitro, cyano, C1-C7 alkyl, C1-C7 haloalkyl, C3-C7 cycloalkyl, C3-C7 halocycloalkyl, C1-C7 alkenyl, C1-C7 alkoxy, C1-C7 haloalkoxy, C1-C7 alkylthio, C1-C7 haloalkylthio, C1-C7 alkylsulfinyl, C1-C7 alkylsulfonyl.

[0020] Furthermore,

[0021] R1, R2, R3, and R4 are independently selected from hydrogen, halogen, nitro, cyano, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C1-C5 alkenyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C1-C5 alkylthio, C1-C5 haloalkylthio, C1-C5 alkylsulfinyl, or C1-C5 alkylsulfonyl;

[0022] R5 is selected from hydrogen, cyano, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C1-C5 alkenyl, or aryl or heteroaryl substituted by hydrogen, halogen, nitro, cyano, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C1-C5 alkenyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C1-C5 alkylthio, C1-C5 haloalkylthio, C1-C5 alkylsulfinyl, C1-C5 alkylsulfonyl;

[0023] R8, R9, and R10 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C1-C5 alkenyl, C1-C5 alkylalkoxy, C1-C5 haloalkylalkoxy, C1-C5 alkylthio, C1-C5 haloalkylthio, or aryl or heteroaryl substituted by hydrogen, halogen, nitro, cyano, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C1-C5 alkenyl, C1-C5 alkoxy, C1-C5 haloalkoxy, C1-C5 alkylthio, C1-C5 haloalkylthio, C1-C5 alkylsulfinyl, C1-C5 alkylsulfonyl.

[0024] Furthermore,

[0025] R1, R2, R3, and R4 are independently selected from hydrogen, fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoroethylsulfinyl, trifluoroethylsulfonyl;

[0026] R5 is selected from hydrogen, cyano, methyl, ethyl, isopropyl, trifluoromethyl, or aryl or heteroaryl substituted by hydrogen, fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoroethylsulfinyl, trifluoroethylsulfonyl;

[0027] R8, R9, and R10 are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, trifluoroethyl, or aryl or heteroaryl substituted by hydrogen, fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, isopropyl, trifluoromethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoroethylsulfinyl, trifluoroethylsulfonyl.

[0028] Preferably, the trifluoromethyl-containing oxadiazole derivatives are selected from at least one of the following structures:

[0029]

[0030] Some compounds in the general formula A-1 of the present invention can be illustrated by the specific compounds in Table 1 below, but these specific compounds do not limit the present invention.

[0031]

[0032] Among them, R1, R2, R3 and R4 are hydrogen, R5 is methyl, and the nuclear magnetic data of the R7 substituent and the compound are shown in Table 1 below:

[0033] Table 1 List of Some Compounds

[0034]

[0035]

[0036]

[0037]

[0038] The present invention also provides a preparation method of the trifluoromethyl oxadiazole derivatives represented by the general formula A-1 described above. The preparation method includes the following steps:

[0039]

[0040] In the formula, the definitions of R1, R2, R3, R4, R5 and R7 are as described above.

[0041] The trifluoromethyl oxadiazole derivatives described in the present invention can be used for agricultural sterilization, and are particularly suitable for controlling one, two or more combinations of soybean rust, wheat rust, corn rust, and crop anthracnose. When used for formulating agricultural chemical fungicides, the mass percentage content of the trifluoromethyl oxadiazole derivatives described in the present invention in the fungicide is 1-99%, and can be formulated into various liquid agents, emulsifiable concentrates, suspensions, aqueous suspensions, microemulsions, emulsions, aqueous emulsions, powders, wettable powders, soluble powders, granules, water-dispersible granules or capsules. The carriers include at least two kinds, and at least one of them is a surfactant. The carriers can be solid or liquid. Suitable solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicate such as talc; magnesium aluminum silicate such as kaolinite, kaolin, montmorillonite and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylenediamine. Liquid carriers include water and organic solvents. When water is used as a solvent or diluent, organic solvents can also be used as auxiliary agents or antifreeze additives. Suitable organic solvents include aromatic hydrocarbons such as benzene, xylene, toluene, etc.; chlorinated hydrocarbons, such as chlorobenzene, vinyl chloride, chloroform, dichloromethane, etc.; aliphatic hydrocarbons, such as petroleum fractions, cyclohexane, light mineral oil; alcohols, such as isopropyl alcohol, butanol, ethylene glycol, glycerol and cyclohexanol, etc.; and their ethers and esters; and ketones, such as acetone, cyclohexanone, and dimethylformamide and N-methyl-pyrrolidone.

[0042] The surfactant can be an emulsifier, a dispersant or a wetting agent; it can be ionic or non-ionic. Non-ionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty amines, and commercially available emulsifiers: agricultural emulsion 2201B, agricultural emulsion 0203B, agricultural emulsion 100 # 、agricultural emulsion 500 # 、agricultural emulsion 600 # 、agricultural emulsion 600-2 # 、agricultural emulsion 1601, agricultural emulsion 2201, agricultural emulsion NP-10, agricultural emulsion NP-15, agricultural emulsion 507 # 、agricultural emulsion OX-635, agricultural emulsion OX-622, agricultural emulsion OX-653, agricultural emulsion OX-667, Ning emulsion 36 # 。The dispersants include sodium lignosulfonate, Nekal, calcium lignosulfonate, methylnaphthalenesulfonic acid formaldehyde condensate, etc. The wetting agents are: sodium lauryl sulfate, sodium dodecylbenzenesulfonate, alkylnaphthalenesulfonate, etc.

[0043] These preparations can be prepared by general methods. For example, the active substance is mixed with a liquid solvent and / or a solid carrier, and at the same time, surfactants such as emulsifiers, dispersants, stabilizers, wetting agents are added, and other auxiliaries such as binders, defoamers, oxidants, etc. can also be added.

[0044] The trifluoromethyl oxadiazole derivatives and their formulations of the present invention have the following advantages compared with the prior art:

[0045] 1. The compound has a novel structure;

[0046] 2. It has high bactericidal activity and has good activity against soybean rust at a concentration of 2.5 ppm. Detailed implementation manners

[0047] The present invention will be further described below in conjunction with specific embodiments, but the present invention is not limited to these specific implementation manners. Those skilled in the art should recognize that the present invention covers all alternative solutions, improvement solutions and equivalent solutions that may be included within the scope of the claims.

[0048] (1). Compound preparation

[0049] Example 1. Synthesis of intermediate E

[0050]

[0051] (1) Synthesis of intermediate A

[0052] p-Tolunitrile (60 g, 0.51 mol), hydroxylamine hydrochloride (105 g, 1.5 mol), and triethylamine (153.2 g, 1.5 mol) were added to a 1000 mL round-bottom flask. After stirring evenly, 500 mL of absolute ethanol was added, and the mixture was heated and stirred to reflux for 10 h. After the reaction was completed, it was cooled to room temperature, ethanol and unreacted triethylamine were distilled off, water (500 mL) was added, stirred for 1 h, and then filtered to obtain a white solid, which was dried to obtain intermediate A (68 g, 0.45 mol), with a yield of 88.8%.

[0053] 1 H NMR(CDCl3,600MHz)δ:7.46(d,2H,J=7.2Hz,Ph-H),7.12(s,2H,N-H),7.06(d,2H,J=7.2Hz,Ph-H),2.51(s,3H,Ph-CH3). 13 C NMR(CDCl3,150MHz)δ:163.3,139.8,130.3,129.1,125.6,21.3.

[0054] (2) Synthesis of intermediate B

[0055] Intermediate A (68 g, 0.45 mol) was added to a 1000 mL round-bottom flask, dissolved in 500 mL of tetrahydrofuran. After stirring until completely dissolved, 80 mL of trifluoroacetic anhydride was added under an ice bath, and the mixture was stirred at room temperature for 12 h. After the reaction was completed, the tetrahydrofuran was evaporated to dryness, 200 mL of water was added and stirred. Sodium carbonate (about 30 g, 0.28 mol) was added during stirring to neutralize to weak alkalinity, and extracted with ethyl acetate (150 mL * 3). After separation by dry column chromatography, Intermediate B (80 g, 0.35 mol) was obtained with a yield of 78.0%.

[0056] 1 H NMR (CDCl3, 600 MHz) δ: 8.07 (d, 2H, J = 7.2 Hz, Ph-H), 7.53 (d, 2H, J = 7.2 Hz, Ph-H), 2.49 (s, 3H, Ph-CH3). 13 C NMR (CDCl3, 150 MHz) δ: 168.8, 163.2, 131.8, 129.5, 128.1 (d, 2 J C-F = 4.2 Hz), 125.7, 123.1, 116.5 (q, J C-F = 272.1 Hz, -CF3), 21.3.

[0057] (3) Synthesis of Intermediate C

[0058] Intermediate B (40 g, 0.17 mol) was added to a 1000 mL round-bottom flask, 400 mL of carbon tetrachloride was added, and then N-bromosuccinimide (76.5 g, 0.35 mol) and 2,2'-azobis(isobutyronitrile) (5.6 g, 0.018 mol) were added. The mixture was heated and stirred under reflux for 4 h. After the reaction was completed, the carbon tetrachloride was evaporated to dryness, and Intermediate C (48.8 g, 0.16 mol) was obtained by column chromatography separation with a yield of 92.0%.

[0059] 1 H NMR (CDCl3, 600 MHz) δ: 8.07 (d, 2H, J = 7.2 Hz, Ph-H), 7.53 (d, 2H, J = 7.2 Hz, Ph-H), 6.54 (s, 1H, Ph-CBr2H). 13 C NMR (CDCl3, 150 MHz) δ: 168.8, 163.2, 141.3, 129.5, 128.1 (d, 2 J C-F = 4.2 Hz), 126.1, 123.1, 116.5 (q, J C-F = 272.1 Hz, -CF3), 40.8.

[0060] (4) Synthesis of Intermediate D

[0061] The intermediate C (48.8 g, 0.16 mol) was added to a 1000 mL round-bottom flask, 250 mL of dimethyl sulfoxide and potassium carbonate (10 g, 0.06 mol) were added, and the mixture was stirred at 100 °C for 2 h. After the reaction was completed, 500 mL of water was added, and the mixture was extracted with ethyl acetate (150 mL × 3). The intermediate D (20 g, 0.08 mol) was obtained by column chromatography separation, with a yield of 50.0%.

[0062] 1 H NMR (CDCl3, 600 MHz) δ: 10.12 (s, 1H, -CHO), 8.32 (d, 2H, J = 7.2 Hz, Ph-H), 8.06 (d, 2H, J = 7.2 Hz, Ph-H). 13 C NMR (CDCl3, 150 MHz) δ: 190.8, 168.8, 163.2, 136.9, 131.6, 130.4, 128.1 (d, 2 J C-F = 4.2 Hz), 126.1, 123.1, 116.5 (q, J C-F = 272.1 Hz, -CF3).

[0063] (5) Synthesis of intermediate E

[0064] The intermediate D (40 g, 0.16 mol) was added to a 500 mL round-bottom flask and dissolved in 300 mL of tetrahydrofuran. Another 500 mL round-bottom flask was taken, and hydroxylamine hydrochloride (30 g, 0.43 mol) and sodium acetate (30 g, 0.37 mol) were added and dissolved in 300 mL of water. The aqueous solution was added dropwise to the tetrahydrofuran solution, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the tetrahydrofuran was evaporated to dryness, and the yellow solid was filtered out and dried to obtain the intermediate E (30 g, 0.11 mol), with a yield of 66.3%.

[0065] 1 H NMR (CDCl3, 600 MHz) δ: 8.33 (d, 2H, J = 7.2 Hz, Ph-H), 8.05 (d, 2H, J = 7.2 Hz, Ph-H), 7.79 (s, 1H, ethene-H). 13 C NMR (CDCl3, 150 MHz) δ: 168.8, 163.2, 149.2, 136.9, 129.7, 128.4, 128.1 (d, 2 J C-F = 4.2 Hz), 127.6, 116.5 (q, J C-F = 272.1 Hz, -CF3).

[0066] Example 2, Synthesis of Intermediate I

[0067]

[0068] (1) Synthesis of Intermediate F

[0069] Add 1,1 - methoxyacetone (110 g, 0.93 mol) and diethyl oxalate (122 g, 1.02 mol) into a 2000 mL three - necked flask, and stir at - 15 °C for 0.5 h. Dropwise add 330 g of sodium ethoxide at - 15 °C within 1 h. After dropping, stir at room temperature for 4 h and let stand for 12 h. Take 210 mL of hydrazine hydrate sulfate (20%), add it to the system at - 5 °C, stir for 0.5 h, remove the ice bath and stir at room temperature for 3 h. After the reaction is completed, add 1000 mL of water and stir for 0.5 h, distill off ethanol, extract with ethyl acetate (300 mL×3), dry, and separate by column chromatography to obtain Intermediate F (60 g, 0.30 mol) with a yield of 31.9%.

[0070] 1 H NMR(CDCl3, 600 MHz) δ: 7.32(s, 1H, pyrazole - H), 5.56(s, 1H, CH), 4.34(q, 2H, J = 7.2 Hz, CH2), 3.41(s, 6H, CH3), 1.32(t, 3H, J = 6 Hz, CH3). 13 C NMR(CDCl3, 150 MHz) δ: 168.2, 144.6, 135.8, 116.9, 108.9, 61.2, 53.8, 13.9.

[0071] (2) Synthesis of Intermediate G

[0072] Add Intermediate F (60 g, 0.30 mol) into a 500 mL round - bottom flask, add 400 mL of acetic acid aqueous solution (250 mL of acetic acid + 150 mL of water), stir at 60 °C for 3 h. After distilling off part of the acetic acid aqueous solution, filter to obtain a yellow solid, dry it to obtain Intermediate G (30 g, 0.20 mol). Extract the mother liquor with ethyl acetate (100 mL×2), separate by column chromatography to obtain Intermediate G (10 g, 0.06 mol). After combining, a total of Intermediate G (40 g, 0.26 mol) is obtained with a yield of 86.3%.

[0073] 1 H NMR(CDCl3, 600 MHz) δ: 9.92(s, 1H, - CHO), 7.32(s, 1H, pyrazole - H), 4.34(q, 2H, J = 7.2 Hz, CH2), 1.32(t, 3H, J = 6 Hz, CH3). 1313C NMR (CDCl3, 150 MHz) δ: 186.9, 163.6, 151.0, 140.4, 108.6, 60.9, 13.8.

[0074] (3) Synthesis of Intermediate H

[0075] Add intermediate G (40 g, 0.26 mol) into a 500 mL round-bottom flask, dissolve it with 200 mL of acetonitrile, then add potassium carbonate (70 g, 0.45 mol). After stirring evenly at room temperature, add dimethyl sulfate (40 g, 0.31 mol) dropwise within 1 h, and stir at room temperature for 10 h. After the reaction is completed, filter the insoluble substances, evaporate the solvent from the solution, and separate by column chromatography to obtain intermediate H (22 g, 0.13 mol), with a yield of 50.5%.

[0076] 1 1H NMR (CDCl3, 600 MHz) δ: 9.89 (s, 1H, -CHO), 7.42 (s, 1H, pyrazole-H), 4.43 (q, 2H, J = 7.2 Hz, CH2), 4.26 (s, 3H, CH3), 1.40 (t, 3H, J = 6 Hz, CH3). 13 13C NMR (CDCl3, 150 MHz) δ: 186.9, 159.2, 148.2, 133.7, 111.9, 60.9, 39.9, 13.8.

[0077] (4) Synthesis of Intermediate I

[0078] Under anhydrous and anaerobic conditions, add methyltriphenylphosphonium iodide (70 g, 0.13 mol) into 200 mL of dehydrated tetrahydrofuran. After stirring evenly, add potassium tert-butoxide (20 g, 0.18 mol) all at once under an ice bath. After stirring for 1 h under the ice bath, add intermediate H (22 g, 0.13 mol), and stir at room temperature for 10 h. After the reaction is completed, add 100 mL of water and 100 mL of saturated ammonium chloride solution, stir evenly, collect the organic phase, extract the aqueous phase with ethyl acetate (100 mL * 3), combine the organic phases, dry, and separate by column chromatography to obtain intermediate I (14 g, 0.08 mol), with a yield of 64.3%.

[0079] 11H NMR (CDCl3, 600 MHz) δ: 6.92 (s, 1H, pyrazole-H), 6.66 (dd, 1H, J1 = 6 Hz, J2 = 9 Hz, CH=CH2), 5.75 (d, 1H, J = 9.6 Hz, CH=CH2), 5.30 (d, 1H, J = 9.6 Hz, CH=CH2), 4.34 (q, 2H, J = 7.2 Hz, CH2), 4.13 (s, 3H, CH3), 1.38 (t, 3H, J = 6 Hz, CH3). 13 13C NMR (CDCl3, 150 MHz) δ: 159.2, 152.0, 133.9, 129.3, 120.3, 109.8, 60.9, 39.9, 13.8.

[0080] Example 2, Synthesis of Intermediate K

[0081]

[0082] (1) Synthesis of Intermediate J

[0083] Add intermediate E (19 g, 0.08 mol) to a 500 mL round-bottom flask, dissolve it in 100 mL of N,N-dimethylformamide, then add chlorosuccinimide (16 g, 0.09 mol), stir at room temperature for 3 h. After the reaction is completed, add intermediate I (14 g, 0.08 mol), add 20 mL of triethylamine and stir at room temperature for 10 h. After the reaction is completed, add 250 mL of water and stir evenly, extract with ethyl acetate (100 mL × 5), dry and separate by column chromatography to obtain intermediate J (26 g, 0.06 mol), with a yield of 71.7%.

[0084] 1 1H NMR (CDCl3, 600 MHz) δ: 8.18 (d, 2H, J = 7.2 Hz, Ph-H), 7.87 (d, 2H, J = 7.2 Hz, Ph-H), 6.93 (s, 1H, pyrazole-H), 5.83 (t, 1H, J = 7.2 Hz, CH), 4.34 (q, 2H, J = 7.2 Hz, CH2), 4.16 (s, 3H,,CH3), 3.73 (d, 2H, J = 7.2 Hz, CH2), 1.36 (t, 3H, J = 7.2 Hz, CH3), 13 13C NMR (CDCl3, 150 MHz) δ: 168.8, 163.2, 160.8, 156.2, 152.3, 133.6, 130.4, 129.7, 128.1 (d, 2 J C-F = 4.2 Hz), 127.6, 116.5 (q, J C-F= 272.1 Hz, -CF3), 108.4, 67.8, 58.9, 43.8, 39.9, 13.4. HRMS m / z(ESI): Calculated for C 19 H 17 F3N5O4([M + H] + ): 436.1227 found 436.1233.

[0085] (2) Synthesis of Intermediate K

[0086] Add intermediate J (26 g, 0.06 mol) to a 200 mL round-bottom flask, add 100 mL of tetrahydrofuran and 10 mL of 10% sodium hydroxide solution, stir at room temperature for 2 h. After the reaction is completed, adjust the pH to acidic with hydrochloric acid, filter to obtain a light yellow solid, and dry to obtain intermediate K (20 g, 0.05 mol), with a yield of 82.2%.

[0087] 1 H NMR(CDCl3, 600 MHz) δ: 8.15 (d, 2H, J = 7.2 Hz, Ph-H), 7.97 (d, 2H, J = 7.2 Hz, Ph-H), 6.74 (s, 1H, pyrazole-H), 5.89 (t, 1H, J = 7.2 Hz, CH), 4.05 (s, 3H, CH3), 3.73 (q, 2H, J = 7.2 Hz, CH2), 13 C NMR(CDCl3, 150 MHz) δ: 168.8, 163.2, 160.8, 156.2, 152.3, 133.6, 130.4, 129.7, 128.1 (d, 2 J C-F = 4.2 Hz), 127.6, 116.5 (q, J C-F = 272.1 Hz, -CF3), 108.4, 67.8, 43.8, 39.9. HRMS m / z(ESI): Calculated for C 17 H 13 F3N5O4([M + H] + ): 408.0914, found 408.0901.

[0088] Example 3. Synthesis of Target Compound L3

[0089]

[0090] Intermediate K (0.3 g, 0.75 mmol) was added to a 50 mL round-bottom flask, 15 mL of dichloromethane was added. After stirring evenly, 1 mL of oxalyl chloride was slowly added dropwise. After stirring at room temperature until all solids disappeared, all the solvents were rotary evaporated. 15 mL of tetrahydrofuran was added, 0.75 mmol of aniline was added during stirring. After stirring evenly, triethylamine was added dropwise. After stirring at room temperature for 3 h, 20 ml of saturated brine was added, separated, the organic phase was dried with anhydrous sodium sulfate, the solvent was distilled off under atmospheric pressure, and the viscous residue was purified by column chromatography to obtain 0.21 g of white solid.

[0091] 1 H NMR (CDCl3, 600 MHz) δ: 8.15 (d, 2H, J = 7.2 Hz, Ph-H), 7.84 (d, 2H, J = 7.2 Hz, Ph-H), 7.57 (d, 2H, J = 7.2 Hz, Ph-H), 7.36 (t, 2H, J = 7.2 Hz, Ph-H), 7.16 (t, 2H, J = 7.2 Hz, Ph-H), 6.77 (s, 1H, pyrazole-H), 5.86 (t, 1H, J = 7.2 Hz, CH), 4.17 (s, 3H, CH3), 4.12 (q, 2H, J = 7.2 Hz, CH2), 3.75 (d, 2H, J = 7.2 Hz, CH2), 13 C NMR (CDCl3, 150 MHz) δ: 168.8, 163.2, 160.8, 156.2, 152.3, 140.9, 133.6, 130.4, 129.7, 128.9, 128.1 (d, 2 J C-F = 4.2 Hz), 127.6, 121.6, 116.5 (q, J C-F = 272.1 Hz, -CF3), 108.4, 67.8, 43.8, 39.9. HRMS m / z (ESI): Calculated for C 23 H 18 F3N6O3 ([M+H] + ): 483.1392 found 483.1387.

[0092] (II) Formulation preparation

[0093] The following examples are prepared according to mass ratios.

[0094] Example 4 30% suspension concentrate

[0095] Compound L3 30%

[0096] Ethylene glycol 10%

[0097] Nonylphenol polyethylene glycol ether 6%

[0098] Sodium lignosulfonate 10%

[0099] Carboxymethyl cellulose 1%

[0100] 37% aqueous formaldehyde solution 0.2%

[0101] 75% silicone oil emulsion 0.8%

[0102] Water to make up 100%

[0103] Mix compound L3 and other components thoroughly. The resulting suspending agent can be diluted with water to obtain dilutions of any desired concentration.

[0104] Example 5 30% aqueous suspension

[0105] Compound L57 30%

[0106] Sodium dodecylnaphthalenesulfonate 4%

[0107] Hemicellulose 3%

[0108] Propylene oxide 8%

[0109] Water to make up 100%

[0110] Crush compound L57 with 80% of the water to be added and sodium dodecylsulfonate in a ball mill. Dissolve hemicellulose and propylene oxide in the remaining 20% of the water, and then stir and add the above components.

[0111] Example 6 30% emulsifiable concentrate

[0112] Compound L1 30%

[0113] Phosphorous acid 10%

[0114] Ethoxylated triglyceride 15%

[0115] Toluene to make up 100%

[0116] Dissolve phosphorous acid in toluene, add compound L1 and ethoxylated triglyceride to obtain a clear solution.

[0117] Example 7 60% wettable powder

[0118] Compound L8 60%

[0119] Sodium dodecylnaphthalenesulfonate 2%

[0120] Sodium lignosulfonate 9%

[0121] Diatomaceous earth to make up 100%

[0122] Mix compound L8, sodium dodecylnaphthalenesulfonate, sodium lignosulfonate and diatomaceous earth together and pulverize them in a pulverizer until the particles reach the standard.

[0123] (III) Biological Activity Test

[0124] Example 8: Preventive effect on soybean rust caused by Phakopsora pachyrhizi on soybeans

[0125] The test compound is dissolved in a small amount of N,N-dimethylformamide and then diluted with water containing 0.1% Tween 80 to the concentration to be tested. Spray the leaves of potted soybean seedlings with an aqueous suspension containing the active ingredient or its mixture at the concentration described below until dripping. Allow the plants to air dry. Cultivate the test plants in a greenhouse at 23 - 27 °C and 60 - 80% relative humidity for 2 days. Then inoculate the plants with the spores of Phakopsora pachyrhizi. To ensure successful artificial inoculation, transfer the plants to a humid chamber at a relative humidity of about 95% and 20 - 24 °C and keep them for 24 hours. Cultivate the test plants in a greenhouse at 23 - 27 °C and 60 - 80% relative humidity for 14 days. Evaluate the degree of fungal invasion on the leaves by visual inspection of the diseased leaf area percentage.

[0126] In this test, at 12.5 ppm, the control effects of compounds L1, L2, L3, L5, L6, L7, L8, L9, L10, L11, L13, L14, L15, L17, L18, L19, L20, L22, L24, L26, L28, L30, L32, L33, L34, L36, L38, L40, L42, L44, L46, L47, L49, L51, L53, L55, L57, L59, L61, L63, L65, L67, L69 are 100%.

[0127] Example 9: Therapeutic effect on soybean rust caused by Phakopsora pachyrhizi on soybeans Inoculate the leaves of potted soybean seedlings with the spores of Phakopsora pachyrhizi. To ensure successful artificial inoculation, transfer the plants to a humid chamber at a relative humidity of about 95% and 20 - 24 °C and keep them for 24 hours. The next day, spray the plants with an aqueous suspension containing the active ingredient or its mixture at the concentration described below until dripping. Allow the plants to air dry. Then, cultivate the test plants in a greenhouse at 23 - 27 °C and 60 - 80% relative humidity for 14 days. Evaluate the degree of fungal invasion on the leaves by visual inspection of the diseased leaf area percentage.

[0128] In this test, at 25 ppm, the control effects of compounds L1, L2, L3, L5, L6, L7, L8, L9, L10, L11, L13, L14, L15, L17, L18, L19, L20, L22, L24, L26, L28, L30, L32, L33, L34, L36, L38, L40, L42, L44, L46, L47, L49, L51, L53, L55, L57, L59, L61, L63, L65, L67, L69 were 100%.

[0129] Example 10: Therapeutic effect on brown rust of wheat caused by Puccinia recondita

[0130] The first two developed leaves of potted wheat seedlings were inoculated with spores of Puccinia recondita. To ensure successful artificial inoculation, the plants were transferred to a humid chamber without light with a relative humidity of 95 - 99% and a temperature of 20 - 24 °C and kept for 24 hours. The next day, the plants were cultured in a greenhouse at 20 - 24 °C and a relative humidity of 65 - 70% for 3 days. Then, the plants were sprayed to runoff with an aqueous suspension containing the active ingredient or its mixture at the concentration described below. The plants were air-dried. Then, the test plants were cultured in a greenhouse at 20 - 24 °C and a relative humidity of 65 - 70% for 8 days. The degree of fungal infestation on the leaves was evaluated visually as the percentage of diseased leaf area.

[0131] In this test, at 50 ppm, the control effects of compounds L1, L2, L3, L5, L6, L7, L8, L9, L10, L11, L13, L14, L15, L17, L18, L19, L20, L22, L24, L26, L28, L30, L32, L33, L34, L36, L38, L40, L42, L44, L46, L47, L49, L51, L53, L55, L57, L59, L61, L63, L65, L67, L69 were over 95%.

[0132] Example 11: Preventive effect on brown rust of wheat caused by Puccinia recondita.

[0133] The first two developed leaves of potted wheat seedlings were sprayed to runoff with an aqueous suspension containing the active ingredient or its mixture at the concentration described below. The next day, the plants were inoculated with spores of Puccinia recondita. To ensure successful artificial inoculation, the plants were transferred to a humid chamber without light with a relative humidity of 95 - 99% and a temperature of 20 - 24 °C and kept for 24 hours. Then, the test plants were cultured in a greenhouse at 20 - 24 °C and a relative humidity of 65 - 70% for 6 days. The degree of fungal infestation on the leaves was evaluated visually as the percentage of diseased leaf area.

[0134] In this test, the control effects of compounds L1, L2, L3, L5, L6, L7, L8, L9, L10, L11, L13, L14, L15, L17, L18, L19, L20, L22, L24, L26, L28, L30, L32, L33, L34, L36, L38, L40, L42, L44, L46, L47, L49, L51, L53, L55, L57, L59, L61, L63, L65, L67, L69 at 25 ppm were over 90%.

[0135] Example 12: Comparative test of some compounds in the present invention against Phakopsora pachyrhizi on soybeans with compounds in the prior art

[0136] The leaves of potted soybean seedlings were inoculated with spores of Phakopsora pachyrhizi. To ensure successful artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and a temperature of 20 - 24 °C and kept for 24 hours. The next day, the plants were sprayed to runoff with an aqueous suspension containing different concentrations of the active ingredient or its mixture as described in Table 2 below. The plants were air-dried. Then, the test plants were cultivated in a greenhouse at 23 - 27 °C and a relative humidity of 60 - 80% for 14 days. The degree of fungal infestation on the leaves was evaluated visually as the percentage of diseased leaf area.

[0137] A comparative test was carried out on compounds L2, L3, L5, L8, L15, L36, L57, L59 of the present invention and the compounds mentioned in the prior art. Two different concentrations of 5 ppm and 2.5 ppm were prepared respectively, and each test was repeated 3 times and the average value was taken. The results of the comparative test are shown in Table 2 below

[0138] Table 2 Results of the comparative test

[0139]

[0140]

[0141] According to the results of the comparative test, it can be seen that the activity of the compounds of the present invention against soybean rust is significantly better than that of the compounds disclosed in the prior art.

Claims

1. A class of trifluoromethyl oxadiazole derivatives is shown by the following general formula A-1: Wherein, R1, R2, R3, and R4 are all hydrogen; R5 is methyl; R7 is selected from one of the following formulas Q-1 and Q-2: In the formula, X is selected from oxygen or sulfur; R8 is selected from hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, or phenyl substituted by hydrogen, halogen, nitrile, C1-C2 alkyl, halomethyl, or methoxy; R9 and R10 are independently hydrogen, C1-C5 alkyl, C3-C6 cycloalkyl, or phenyl substituted by hydrogen, halogen, nitro, nitrile, C1-C2 alkyl, isopropyl, or C1-C2 alkoxy.

2. The trifluoromethyl oxadiazole derivative according to claim 1, characterized in that: R1, R2, R3, and R4 are all hydrogen; R5 is methyl; R8 is selected from hydrogen, methyl, ethyl, cyclopentyl, cyclohexyl, or phenyl substituted by hydrogen, fluorine, chlorine, nitrile, methyl, ethyl, trifluoromethyl, or methoxy; R9 and R10 are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, cyclohexyl, or phenyl substituted by hydrogen, fluorine, chlorine, nitro, nitrile, methyl, ethyl, isopropyl, or methoxy.

3. The trifluoromethyl oxadiazole derivative according to claim 2, characterized in that: The trifluoromethyl oxadiazole derivative is selected from at least one of the following structures: 。 4. A method for preparing a trifluoromethyl oxadiazole derivative represented by the general formula A-1 as described in claim 1, characterized in that: The preparation method includes the following steps: In the formula, the definitions of R1, R2, R3, R4, R5, and R7 are as described in claim 1.

5. Use of a trifluoromethyl oxadiazole derivative represented by general formula A-1 as described in claim 1, characterized in that: The trifluoromethyl oxadiazole derivative is used for agricultural sterilization.

6. Use of the trifluoromethyl oxadiazole derivative according to claim 5, characterized in that: The trifluoromethyl oxadiazole derivative is used for preventing and controlling crop rust, anthracnose, and brown rust.

7. Use of the trifluoromethyl oxadiazole derivative according to claim 6, characterized in that: The trifluoromethyl oxadiazole derivative is used for preventing and controlling soybean rust, wheat rust, corn rust, and crop anthracnose.

8. An agrochemical fungicide, characterized in that: The agricultural chemical fungicide contains 1-99% by mass of the trifluoromethyl oxadiazole derivative shown by the general formula A-1 as described in claim 1, and the rest is an agriculturally acceptable carrier.

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