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WO2024199260A1 - 一种吡唑-5-醚类化合物及其制备方法和应用 - Google Patents

一种吡唑-5-醚类化合物及其制备方法和应用 Download PDF

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Publication number
WO2024199260A1
WO2024199260A1 PCT/CN2024/083993 CN2024083993W WO2024199260A1 WO 2024199260 A1 WO2024199260 A1 WO 2024199260A1 CN 2024083993 W CN2024083993 W CN 2024083993W WO 2024199260 A1 WO2024199260 A1 WO 2024199260A1
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Prior art keywords
methyl
pyrazole
hydrogen
substituted
ethyl
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PCT/CN2024/083993
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English (en)
French (fr)
Inventor
吕亮
李宏伟
曹晓峰
王金娥
邓登辉
杜永磊
陈晨
王鼎
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南通泰禾化工股份有限公司
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Publication of WO2024199260A1 publication Critical patent/WO2024199260A1/zh

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present application belongs to the field of agricultural fungicides and relates to a pyrazole-5-ether compound and a preparation method and application thereof.
  • Plant diseases seriously affect plant growth, leading to reduced production of crops, ornamental plants, pastures, and forestry, causing economic losses.
  • pathogens may develop resistance to existing commercial fungicides, thus requiring the continuous invention of new and improved fungicide compounds that are more effective, less costly, less toxic, safer for the environment, and/or have different modes of action.
  • pyrazole ether compounds have been reported in the prior art, among which pyrazole-5-ether compounds, such as CN101631460A discloses KC1 and KC2 (compounds 596 and 599 in the patent, respectively), have herbicidal activity, but there is no report on specific biological test experiments showing that the pyrazole-5-ether compounds have fungicidal activity; pyrazole-3-ether compounds, such as CN116003322A discloses KC3 (compound 22 in the patent), have fungicidal activity against cucumber powdery mildew.
  • the present application provides a pyrazole-5-ether compound and a preparation method and application thereof.
  • the present application provides a pyrazole-5-ether compound, wherein the pyrazole-5-ether compound has a structure shown in Formula I:
  • R 1 is selected from C1-C6 alkyl, C3-C6 cycloalkyl or benzene ring substituted with at least one R 8 ;
  • R 2 is selected from C1-C6 haloalkyl, C3-C6 cycloalkyl, methyl, cyano or phenyl substituted by at least one R 8 ;
  • R3 is selected from hydrogen, halogen, cyano, C1-C6 alkyl or C1-C6 haloalkyl;
  • R4 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or C1-C6 haloalkoxy;
  • R5 is selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy or C1-C6 haloalkyl;
  • R 6 is selected from C1-C8 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl or C1-C6 haloalkyl substituted with at least one R 8 ;
  • R7 is selected from hydrogen or C1-C6 alkyl; or R6 and R7 together with the nitrogen atom to which they are attached form a three-membered to seven-membered saturated cyclic group, which may optionally contain an oxygen atom, a nitrogen atom or a sulfur atom, and the cyclic group may be further The same or different R 8 substitutions;
  • R8 is selected from hydrogen, halogen, cyano, nitro, hydroxyl, amino, C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, amino substituted by C1-C6 alkyl, C1-C6 alkylcarbonylamino, C1-C6 haloalkylcarbonylamino, C1-C6 alkylsulfonylamino, N,N-di(C1-C6 alkyl)sulfonylamino, C1-C6 haloalkylsulfonylamino, heterocyclic acylamino, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, cyano-substituted C1-C6 alkyl, C1-C6 alkylsulfoxide, C1-C6 al
  • R 1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or a benzene ring substituted with at least one R 8 ;
  • R 2 is selected from methyl, cyclopropyl, difluoromethyl, trifluoromethyl, cyano or phenyl substituted by at least one R 8 ;
  • R3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, methyl, difluoromethyl or trifluoromethyl;
  • R4 is selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, fluorine, chlorine, bromine or iodine;
  • R 5 is selected from hydrogen, methyl, methoxy, difluoromethyl, trifluoromethyl, fluorine, chlorine, bromine or iodine;
  • R is selected from methyl, ethyl, n-propyl, isopropyl, 1-methylpropyl, 1-ethylpropyl, 2-methylpropyl, 3-methylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, n-butyl, tert-butyl, 3-methylbutyl, 1,1-dimethyl-3,3-dimethylbutyl, n-pentyl, 4-methyl-2-pentyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, n-hexyl, 2-ethylhexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
  • R 7 is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, neopentyl, isopentyl, 4-methyl-2-pentyl or n-hexyl; or R 6 and R 7 together with the nitrogen atom to which they are attached form tetrahydropyrrole, isoxazolidine, piperidine, azocane, piperazine or morpholine, and the pyrrole, isoxazolidine, piperidine, azocane, piperazine or morpholine may be substituted by the same or different R 8 ;
  • R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, amino, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, tert-butyl, cyanomethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, methoxy, difluoromethoxy, trifluoromethoxy, acetyl, tert-butoxycarbonyl, amino, methylamino, acetylamino, trifluoroacetylamino, methanesulfonyl, trifluoromethanesulfonyl, N,N-dimethylaminosulfonyl, morpholine-4-carboxamido, pyrazolyl, imidazolyl, 1,2,4-triazolyl, 1,2,3-
  • the pyrazole-5-ether compound is any one of the compounds shown in Table 1 below having a general formula I:
  • R 1 is selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, isobutyl or cyclopropyl substituted with at least one R 8 ;
  • R2 is selected from methyl, difluoromethyl or trifluoromethyl
  • R3 is selected from hydrogen, fluorine, chlorine, cyano or methyl
  • R4 is selected from methyl, methoxy or chlorine
  • R5 is selected from methyl or chlorine
  • R6 is selected from methyl, ethyl, n-propyl or isopropyl
  • R7 is selected from hydrogen, methyl, ethyl, n-propyl or isopropyl;
  • R 6 and R 7 together with the nitrogen atom to which they are attached form tetrahydropyrrole, piperidine or azoctane, which may be substituted by the same or different R 8 ;
  • R8 is selected from hydrogen, methyl or fluoro.
  • R1 is selected from methyl, ethyl, n-propyl, isopropyl or tert-butyl;
  • R 2 is selected from trifluoromethyl
  • R3 is selected from hydrogen or methyl
  • R4 is selected from methyl or chlorine
  • R5 is selected from methyl or chlorine
  • R6 is selected from ethyl
  • R7 is selected from methyl
  • R 6 and R 7 together with the nitrogen atom to which they are attached form a piperidine, which may be substituted by the same or different R 8 ;
  • R8 is selected from hydrogen or methyl.
  • the pyrazole-5-ether compound is any one of the following compounds:
  • alkyl group described in this application refers to a straight chain or branched chain form, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl or n-hexyl.
  • Haloalkyl refers to a group in which an alkyl group is substituted by one or more halogen atoms.
  • Alkoxy refers to a group in which an oxygen atom is attached to the end of an alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy or tert-butoxy.
  • Haloalkoxy refers to a group in which an alkoxy group is substituted by one or more halogen atoms. Halogen is F, Cl, Br or I.
  • C1-C6 alkyl used in this application refers to a straight or branched alkyl group having 1 to 6 carbon atoms, including, but not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, and n-hexyl.
  • C1-C6 alkoxy refers to a straight or branched alkoxy group having 1 to 6 carbon atoms, including, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and tert-butoxy.
  • C1-C12 alkoxy has a similar meaning.
  • C3-C8 cycloalkyl refers to a cyclic alkyl group having 3 to 8 carbon atoms in the ring, including but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
  • C2-C12, C1-C6, C3-C8, etc. before the specific group represents the number of carbon atoms contained in the group.
  • C2-C12 represents a group having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms
  • C1-C6 represents a group having 1, 2, 3, 4, 5 or 6 carbon atoms
  • C3-C8 represents a group having 3, 4, 5, 6, 7 or 8 carbon atoms
  • C2-C4 represents a group having 2, 3 or 4 carbon atoms, and so on.
  • the group Represents the attachment position of the group.
  • the present application provides a method for preparing the pyrazole-5-ether compound as described in the first aspect, wherein the preparation method is:
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as described above and will not be repeated here; and R 9 is selected from C1-C6 alkyl.
  • the molar ratio of the compound represented by formula II to the compound represented by formula III is 0.5-2:1, for example 0.5:1, 0.8:1, 1:1, 1.2:1, 1.5:1, 1.8:1 or 2:1.
  • the solvent of the reaction is any one of dichloromethane, chloroform, ethyl acetate, toluene, acetonitrile, tetrahydrofuran, dioxane, ethanol, methanol, N,N-dimethylformamide or dimethyl sulfoxide, or a combination of at least two thereof.
  • the reaction temperature is greater than or equal to room temperature and less than or equal to the boiling point of the reaction solvent, for example, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, 85°C, 90°C, etc., or the reaction is carried out at the boiling point of the solvent, i.e., under reflux.
  • the reaction time is 0.5-48 hours, for example 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours or 48 hours.
  • the compound represented by formula III is prepared by the following method: the compound represented by formula IV and the compound represented by formula V are reacted in the presence of a catalyst to obtain the compound represented by formula III, and the reaction formula is as follows:
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 9 are as described above and will not be repeated here.
  • the reaction is carried out in the presence of an acidic substance, and the acidic substance is an organic acid and/or an inorganic acid.
  • the organic acid is any one of p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid and acetic acid, or a combination of at least two thereof.
  • the inorganic acid is any one of hydrochloric acid, hydrobromic acid, sulfuric acid, zinc chloride, ammonium chloride, and ferric chloride, or a combination of at least two thereof.
  • the reaction in the preparation of the compound represented by formula III, can be carried out in a suitable solvent, and the solvent of the reaction is any one of dichloromethane, chloroform, ethyl acetate, toluene, acetonitrile, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, isopropanol, n-butanol, water, N,N-dimethylformamide or dimethyl sulfoxide, or a combination of at least two thereof.
  • the solvent of the reaction is any one of dichloromethane, chloroform, ethyl acetate, toluene, acetonitrile, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, isopropanol, n-butanol, water, N,N-dimethylformamide or dimethyl sulfoxide, or a combination of at least two thereof.
  • the reaction temperature is greater than or equal to 0° C. and less than or equal to the boiling point of the reaction solvent.
  • the reaction time is 0.5-48 hours.
  • the compound represented by formula IV is prepared by the following method: the compound represented by formula VI is reduced in the presence of a reducing agent to obtain the compound represented by formula IV, and the reaction formula is as follows:
  • R 1 , R 2 , R 3 , R 4 and R 5 are as described above and will not be repeated here.
  • the reducing agent is any one of hydrogen, hydrazine hydrate, iron powder, zinc powder, stannous chloride or sodium dithionite, or a combination of at least two thereof.
  • the reaction is carried out in the presence of a catalyst, and the catalyst is preferably any one of palladium carbon, palladium dioxide, Raney nickel, ferric chloride or basic ferric oxide, or a combination of at least two thereof.
  • the solvent of the reaction is any one of dichloromethane, chloroform, ethyl acetate, toluene, acetonitrile, tetrahydrofuran, dioxane, ethanol, methanol, N,N-dimethylformamide, saturated aqueous ammonium chloride solution, acetic acid, hydrochloric acid, water or dimethyl sulfoxide, or a combination of at least two thereof.
  • the reaction temperature is greater than or equal to 0° C. and less than or equal to the boiling point of the reaction solvent.
  • the reaction time is 0.5-48 hours.
  • the compound represented by formula VI is prepared by the following method: the compound represented by formula VII is reacted with the compound represented by formula VIII to obtain the compound represented by formula VI, and the reaction formula is as follows:
  • L is fluorine or chlorine; in addition, the definitions of R 1 , R 2 , R 3 , R 4 , and R 5 are as described above and will not be repeated here.
  • the molar ratio of the compound represented by formula VII to the compound represented by formula VIII is 1-3:1.
  • the reaction is carried out in the presence of a basic substance, and the basic substance is an organic base and/or an inorganic base.
  • the organic base is any one of triethylamine, N,N-dimethylaniline, pyridine, sodium methoxide, sodium ethoxide, sodium tert-butoxide or potassium tert-butoxide, or a combination of at least two thereof.
  • the inorganic base is any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium hydride, or a combination of at least two thereof.
  • the solvent of the reaction is any one of dichloromethane, chloroform, acetone, toluene, acetonitrile, tetrahydrofuran, dioxane, methanol, ethanol, N,N-dimethylformamide, dimethyl sulfoxide or hexamethylphosphoric triamide, or a combination of at least two thereof.
  • the reaction temperature is greater than or equal to 0°C and less than or equal to the boiling point of the reaction solvent, for example, 0°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, 85°C, 90°C, etc., or the reaction is carried out at the boiling point of the solvent, i.e., under reflux.
  • the reaction time is 0.5-48 hours.
  • Table 2 shows representative compounds of the intermediate compounds described in Formula VI of the present application, but the present application is not limited thereto.
  • the present application provides the use of the pyrazole-5-ether compound as described in the first aspect in preventing and controlling plant diseases.
  • the pyrazole-5-ether compounds described in the present application have unexpectedly high fungicidal activity and have a good control effect on plant diseases.
  • the plant diseases include diseases of Oomycetes, Ascomycetes, Basidiomycetes or Deuteromycetes.
  • the plant diseases include but are not limited to: wheat rust, wheat powdery mildew, wheat fusarium wilt, wheat root rot, wheat eye spot, wheat take-all, wheat glumen blight, cucumber downy mildew, cucumber powdery mildew, melon powdery mildew, bitter melon powdery mildew, cucumber anthracnose, cucumber wilt, cucumber gray mold, grape downy mildew, tomato early blight, tomato late blight, rice sheath blight, rice blast, watermelon vine blight, peanut scab, peanut black spot, citrus scab, pepper root rot, cotton verticillium wilt, cotton wilt, rapeseed black stem disease, rapeseed sclerotinia, pear black spot, ginseng rust, corn rust, corn curvature, corn large spot, mango stem rot, apple ring rot, apple rot, banana leaf spot, soybean rust or potato late blight.
  • the plant diseases include wheat rust, wheat powdery mildew, wheat fusarium head blight, cucumber powdery mildew, cucumber downy mildew or soybean rust.
  • the present application provides a fungicide composition, comprising an active component and a pesticide-acceptable carrier, wherein the active component is the pyrazole-5-ether compound as described above.
  • the fungicide composition described in the present application can be used in agriculture, forestry, health and other fields.
  • the weight percentage of the active ingredient is 1%-99%, for example, 1%, 3%, 5%, 8%, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.
  • the pesticidally acceptable carrier comprises a surfactant.
  • the surfactant is an ionic surfactant or a non-ionic surfactant.
  • the surfactant includes an emulsifier, a dispersant or a wetting agent; wherein the emulsifier can be polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene fatty amine and a commercially available emulsifier (Nongru 2201B, Nongru 0203B, Nongru 100#, Nongru 500#, Nongru 600#, Nongru 600-2#, Nongru 1601, Nongru 2201, Nongru NP-10, Nongru NP-15, Nongru 507#, Nongru OX-635, Nongru OX-622, Nongru OX-653, Nongru OX-667, Ningru 36#); the dispersant includes sodium lignin sulfonate, pull open powder, calcium lignin sulfonate, methyl naphthalene sulfonic acid formaldehyde condensate, etc.; the wetting agent includes sodium lauryl sulfate, sodium dodecylbenzene sulfon
  • the pesticide-acceptable carrier comprises a solid carrier and/or a liquid carrier.
  • the solid carrier includes natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates 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 and hexamethylenediamine.
  • the liquid carrier includes water and organic solvents. When water is used as a solvent or diluent, the organic solvent can also be used as an adjuvant or antifreeze additive.
  • 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 isopropanol, butanol, ethylene glycol, glycerol and cyclohexanol, etc.; and their ethers and esters; and ketones such as acetone, cyclohexanone, dimethylformamide and N-methyl-pyrrolidone.
  • 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
  • the active component can be mixed with a liquid carrier and/or a solid carrier, and a surfactant (such as an emulsifier, dispersant, stabilizer, wetting agent) can be added at the same time.
  • a surfactant such as an emulsifier, dispersant, stabilizer, wetting agent
  • Other auxiliary agents such as adhesives, defoaming agents, oxidants, etc. can also be added.
  • the present application provides a method for preventing and controlling plant diseases, the method comprising: applying an effective dose of the fungicide composition as described above to the plant disease to be controlled or to the medium in which it grows.
  • the effective dose is 10-1000 g per hectare, preferably 20-500 g per hectare.
  • composition of the present application can be applied to the disease or its growth medium in the form of a preparation.
  • the general formula compound I is dissolved or dispersed in a carrier as an active ingredient or formulated into a preparation so that it is easier to disperse when used as a fungicide.
  • these chemical preparations can be formulated into various liquids, emulsifiable concentrates, suspensions, aqueous suspensions, microemulsions, emulsions, aqueous emulsions, powders, wettable powders, soluble powders, granules, water-dispersible granules or capsules.
  • one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers may be added to the fungicidal composition of the present application, thereby producing additional advantages and effects.
  • the pyrazole-5-ether compound having the structure shown in Formula I of the present application has a significant effect on preventing and controlling agricultural and forestry diseases, especially cucumber powdery mildew, cucumber downy mildew, soybean rust, and wheat fusarium head blight.
  • the concentration of the pyrazole-5-ether compound is 10 ppm
  • the control effect on cucumber powdery mildew is ⁇ 90%
  • the concentration is 100 ppm
  • the control effect on cucumber downy mildew is ⁇ 90%
  • the concentration of the pyrazole-5-ether compound is 10 ppm
  • the control effect on soybean rust is ⁇ 90%
  • the concentration of the pyrazole-5-ether compound is 100 ppm, the inhibition rate of wheat fusarium head blight spore germination is ⁇ 90%
  • the preparation method thereof is simple and efficient, easy to mass produce, and has broad application prospects.
  • Step 3 Synthesis of (E)-N-[4-(1-methyl-3-trifluoromethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]formamidine ethyl ether:
  • Step 4 Synthesis of (E)-N'-[4-(1-methyl-3-trifluoromethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine:
  • Step 3 Synthesis of (E)-N-[4-(1-methyl-3-difluoromethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]formamidine ethyl ether:
  • Step 4 Synthesis of (E)-N'-[4-(1-methyl-3-difluoromethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine:
  • 6-(2,5-Dimethyl-4-nitrophenoxy)-1,3-dimethyl-1H-pyrazole (1.9 g, 7.3 mmol) was added to 30 mL of anhydrous ethanol, and reduced iron powder (814.0 mg, 14.6 mmol) was added, and 10 mL of saturated aqueous ammonium chloride solution was added dropwise.
  • the reaction mixture was refluxed. After 8 hours, the reaction mixture was cooled to room temperature, filtered through diatomaceous earth, rinsed with ethanol, and the ethanol was evaporated. 50 mL of water and 50 mL of ethyl acetate were added, and the organic layer was separated and extracted.
  • Step 3 Synthesis of (E)-N-[4-(1,3-dimethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]formamidine ethyl ether:
  • Step 4 Synthesis of (E)-N'-[4-(1,3-dimethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine:
  • Step 3 Synthesis of (E)-N-[2-methyl-4-(1,3-dimethyl-1H-pyrazole-5-oxy)-5-chlorophenyl]formamidine ethyl ether:
  • Step 4 Synthesis of (E)-N'-[2-methyl-4-(1,3-dimethyl-1H-pyrazole-5-oxy)-5-chlorophenyl]-N-ethyl-N-methylformamidine:
  • Step 4 Synthesis of (E)-N-[2-methyl-4-(1-ethyl-3-trifluoromethyl-1H-pyrazole-5-oxy)-5-chlorophenyl]formamidine ethyl ether:
  • Step 5 Synthesis of (E)-N'-[4-(1-ethyl-3-trifluoromethyl-1H-pyrazole-5-oxy)-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine:
  • Table 1 can be prepared by similar methods to those in Synthesis Examples 1-5.
  • Table 4 below gives the NMR data of some compounds synthesized in Synthesis Examples 1-5 (the sample solvent is DMSO-d6, and the solvent of the compounds marked with * is CDCl 3 ).
  • a fungicide preparation was prepared from the prepared pyrazole-5-ether compound, and a suspension concentrate having a concentration of 30% of compound 2 was prepared according to the mass ratio shown in Table 5.
  • the preparation method is as follows: Compound 2 and other components are fully mixed to obtain a 30% suspension, and the suspension is diluted with water to obtain a dilution with a desired concentration.
  • the compounds of the present application obtained above were tested on a variety of pathogens. Unless otherwise specified in the examples and the present application:
  • the sample preparation method is to weigh 10 mg of the original drug of the sample to be tested, dissolve it in 1 mL of DMF, prepare a 10000 ppm mother solution, and dilute the mother solution to the required concentration with 0.05% Tween-80 water for activity testing.
  • Test Example 1 Fungicidal activity of compounds against wheat powdery mildew
  • the screening adopts the live pot test method.
  • Use a throat sprayer to evenly spray the agent on the wheat leaves at the one-leaf and one-heart stage. Repeat 3 times each time. After spraying, place it indoors to dry naturally. 24 hours after the agent treatment, shake off the wheat powdery mildew spores produced about 10 days after inoculation evenly on the wheat leaves after the application. 10 days after the inoculation of spores, wait for the control to stabilize the disease and conduct an investigation. The survey results are expressed in 100-0, with "100" representing disease-free and "0" representing the most serious disease level.
  • Test Example 2 Fungicidal activity of compounds against soybean rust
  • the screening adopts the in vivo pot test method, that is, the sample of the compound to be tested is dissolved with a small amount of solvent (the type of solvent, such as acetone, methanol, DMF, etc., is selected according to its solubility for the sample, and the volume ratio of the solvent amount to the spray liquid is equal to or less than 0.05), and diluted with water containing 0.1% Tween 80 to prepare the test solution of the required concentration.
  • Two-leaf soybeans are cultured in the greenhouse as the test host plants of soybean rust (Phakopsora pachyrhizi).
  • the compound of the present application is sprayed on the leaves according to the designed concentration.
  • a blank control of spraying clear water is set up, repeated 3 times, and the pathogen is inoculated 24 hours after the treatment.
  • the plants are placed in an artificial climate chamber for moisturizing culture (temperature: 25°C during the day, 20°C at night, relative humidity: 95-99%).
  • the test material is cultured for 24 hours, it is moved to the greenhouse for culture.
  • the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated.
  • the results of the investigation were expressed in accordance with "A Manual of Assessment Keys for Plant Diseases" compiled by the American Society of Plant Diseases, using a scale of 100 to 0, with "100" representing no disease and "0" representing the most severe degree of disease.
  • the control effect of the existing compound KC3 on soybean rust is 22% at a concentration of 10 ppm, and the control effect on soybean rust is 0 at a concentration of 4 ppm.
  • Test Example 3 Fungicidal activity of compounds against cucumber powdery mildew
  • the screening adopts the in vivo pot test method, that is, the sample of the compound to be tested is dissolved with a small amount of solvent (the type of solvent, such as acetone, methanol, DMF, etc., is selected according to its solubility for the sample, and the volume ratio of the solvent amount to the spray liquid is equal to or less than 0.05), and diluted with water containing 0.1% Tween 80 to prepare the test solution of the required concentration.
  • Two-leaf cucumber seedlings cultured in the greenhouse are used as the test host plants of cucumber powdery mildew (Erysiphe cichoracearum). Foliar spray treatment is carried out with the compound of the present application according to the designed concentration.
  • a blank control of spraying with clear water is set up, repeated 3 times, and the pathogen is inoculated 24 hours after the treatment.
  • the plants are placed in an artificial climate chamber for moisturizing culture (temperature: 25°C during the day, 20°C at night, relative humidity: 95-99%).
  • the test material is cultured for 24 hours, it is moved to the greenhouse for culture.
  • the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated.
  • the results of the survey were expressed on a scale of 100 to 0, with "100" representing no disease and "0" representing the most severe degree of disease.
  • the present application uses the above-mentioned embodiments to illustrate the pyrazole-5-ether compounds and their preparation methods and applications, but the present application is not limited to the above-mentioned embodiments, which does not mean that the present application must rely on the above-mentioned embodiments to be implemented.
  • Those skilled in the art should understand that any improvement to the present application, equivalent replacement of the raw materials of the present application products, addition of auxiliary components, and selection of specific methods, etc., all fall within the scope of protection and disclosure of the present application.

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Abstract

一种吡唑-5-醚类化合物具有式I所示结构，其对于防治农业、林业上的病害具有显著效果，尤其对小麦白粉病、黄瓜白粉、大豆锈病具有很好的防治效果，应用前景广泛。

Description

一种吡唑-5-醚类化合物及其制备方法和应用 技术领域
本申请属于农用杀菌剂领域，涉及一种吡唑-5-醚类化合物及其制备方法和应用。
背景技术
植物病害严重影响植物的生长，可导致农作物、观赏植物、牧场、林业减产，造成经济损失。随着现有杀菌剂长期、大量的使用，可使病原体对现有商业杀菌剂产生抗药性，因而需要不断发明新型的和改进的更有效、成本更低、毒性更小、环境更安全和/或具有不同作用方式的新杀菌化合物。
现有技术中已经报道了一些吡唑醚类化合物，其中吡唑-5-醚类化合物，例如CN101631460A公开了KC1、KC2(分别为该专利中化合物596和599)，这些公开的化合物具有除草活性，但未有关于吡唑-5-醚类化合物具有杀菌活性的具体生物测试实验情况报道；吡唑-3-醚类化合物，例如CN116003322A公开了KC3(该专利中化合物22)，对黄瓜白粉病具有杀菌活性。
在本领域中，开发出更加高效的杀菌剂以满足农业以及林木业需求仍然是被期望的。
发明内容
本申请提供一种吡唑-5-醚类化合物及其制备方法和应用。
第一方面，本申请提供一种吡唑-5-醚类化合物，所述吡唑-5-醚类化合物具有式I所示结构：
其中，
R1选自至少被1个R8取代的C1-C6烷基、C3-C6环烷基或苯环；
R2选自C1-C6卤代烷基、C3-C6环烷基、甲基、氰基或至少被1个R8取代的苯基；
R3选自氢、卤素、氰基、C1-C6烷基或C1-C6卤代烷基；
R4选自卤素、C1-C6烷基、C1-C6烷氧基、C1-C6卤代烷基或C1-C6卤代烷氧基；
R5选自氢、卤素、C1-C6烷基、C1-C6烷氧基或C1-C6卤代烷基；
R6选自至少被1个R8取代的C1-C8烷基、C3-C6环烷基、C3-C6环烷基或C1-C6卤代烷基；
R7选自氢或C1-C6烷基；或R6和R7连同它们所连接的氮原子一起形成三元至七元饱和的环状基团，该环状基团可以任选地含有氧原子、氮原子或硫原子，环状基团可以进一步被 相同或不同的R8取代；
R8选自氢、卤素、氰基、硝基、羟基、氨基、C1-C6烷基、C1-C6环烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、被C1-C6烷基取代的氨基、C1-C6烷基羰基氨基、C1-C6卤代烷基羰基氨基、C1-C6烷基磺酰基氨基、N,N-二(C1-C6烷基)磺酰基氨基、C1-C6卤代烷基磺酰基氨基、杂环酰基氨基、C1-C6烷基羰基、C1-C6烷氧基羰基、氰基取代C1-C6烷基、C1-C6烷基亚砜基、C1-C6烷基砜基、C1-C6卤代烷基亚砜基、C1-C6卤代烷基砜基、取代苯基、杂环或杂环取代C1-C6烷基。
本申请中，作为优选技术方案，在式I中，
R1选自至少被1个R8取代的甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基环丙基、环丁基、环戊基、环己基或苯环；
R2选自甲基、环丙基、二氟甲基、三氟甲基、氰基或至少被1个R8取代的苯基；
R3选自氢、氟、氯、溴、碘、氰基、甲基、二氟甲基或三氟甲基；
R4选自甲基、二氟甲基、三氟甲基、甲氧基、二氟甲氧基、三氟甲氧基、氟、氯、溴或碘；
R5选自氢、甲基、甲氧基、二氟甲基、三氟甲基、氟、氯、溴或碘；
R6选自甲基、乙基、正丙基、异丙基、1-甲基丙基、1-乙基丙基、2-甲基丙基、3-甲基丙基、1,1-二甲基丙基、2,2-二甲基丙基、正丁基、叔丁基、3-甲基丁基、1,1-二甲基-3,3-二甲基丁基、正戊基、4-甲基-2-戊基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、正己基、2-乙基己基、环丙基、环丁基、环戊基、环己基或环丙基甲基；
R7选自氢、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、2-戊基、新戊基、异戊基、4-甲基-2-戊基或正己基；或R6和R7连同它们所连接的氮原子一起形成四氢吡咯、异噁唑烷、哌啶、氮杂环辛烷、哌嗪或吗啉，所述吡咯、异噁唑烷、哌啶、氮杂环辛烷、哌嗪或吗啉可以被相同或不同的R8取代；
R8选自氢、氟、氯、溴、碘、氰基、硝基、羟基、氨基、甲基、乙基、正丙基、异丙基、异丁基、正丁基、叔丁基、氰基甲基、二氟甲基、三氟甲基、五氟乙基、七氟异丙基、甲氧基、二氟甲氧基、三氟甲氧基、乙酰基、叔丁氧基羰基、氨基、甲氨基、乙酰氨基、三氟乙酰氨基、甲磺酰胺基、三氟甲磺酰胺基、N,N-二甲胺基磺酰胺基、吗啉-4-甲酰胺基、吡唑基、咪唑基、1,2,4-三唑基、1,2,3-三唑基、1,3,4-三唑基、吡唑啉基、咪唑啉基、1,2,4-三唑烷基、吡啶基、嘧啶基、哒嗪基、吡嗪基、噁二唑基、噻二唑基、异噁唑烷基或异噁唑啉基。
作为本申请的优选技术方案，所述吡唑-5-醚类化合物为具有通式I的如下表1所示化合物中的任意一种：
表1












进一步优选地，在式I中，
R1选自至少被1个R8取代的甲基、乙基、正丙基、异丙基、叔丁基、异丁基或环丙基；
R2选自甲基、二氟甲基或三氟甲基；
R3选自氢、氟、氯、氰基或甲基；
R4选自甲基、甲氧基或氯；
R5选自甲基或氯；
R6选自甲基、乙基、正丙基或异丙基；
R7选自氢、甲基、乙基、正丙基或异丙基；
或R6和R7连同它们所连接的氮原子一起形成四氢吡咯、哌啶或氮杂环辛烷，所述四氢吡咯、哌啶或氮杂环辛烷可以被相同或不同的R8取代；
R8选自氢、甲基或氟。
进一步优选地，在式I中，
R1选自甲基、乙基、正丙基、异丙基或叔丁基；
R2选自三氟甲基；
R3选自氢或甲基；
R4选自甲基或氯；
R5选自甲基或氯；
R6选自乙基；
R7选自甲基；
或R6和R7连同它们所连接的氮原子一起形成哌啶，所述哌啶可以被相同或不同的R8取代；
R8选自氢或甲基。
最优选地，所述吡唑-5-醚类化合物为如下化合物中的任意一种：
本申请所述烷基是指直链或支链形式，例如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、特丁基、正戊基、异戊基或正己基等基团。卤代烷基是指烷基被一个或多个卤原子取代的基团。烷氧基是指烷基末端连有氧原子的基团，例如甲氧基、乙氧基、正丙氧基、异丙氧基或特丁氧基等。卤代烷氧基是指烷氧基被一个或多个卤原子取代的基团。卤素为F、Cl、Br或I。
本申请所用术语“C1-C6烷基”是指具有1至6个碳原子的直链或支链烷基，非限制性地包括甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、特丁基、正戊基、异戊基、和正己基等。术语“C1-C6烷氧基”是指具有1至6个碳原子的直链或支链烷氧基，非限制性地包括甲氧基、乙氧基、正丙氧基、异丙氧基和特丁氧基等。术语“C1-C12烷氧基”具有类似的含义。
本申请所用术语“C3-C8环烷基”是指在环上具有3至8个碳原子的环状烷基，非限制性地包括环丙基、环丁基、环戊基、环己基、环庚基和环辛基等。
在本申请中，所述特定基团之前的C2-C12、C1-C6、C3-C8等表示基团中所含碳原子个数，例如C2-C12表示碳原子数可以为2、3、4、5、6、7、8、9、10、11或12的基团，C1-C6表示碳原子数可以为1、2、3、4、5或6的基团，C3-C8表示碳原子数可以为3、4、5、6、7或8的基团，C2-C4表示碳原子数可以为2、3或4的基团等等，以此类推。
在本申请中基团中代表基团的连接位置。
第二方面，本申请提供了如第一方面所述的吡唑-5-醚类化合物的制备方法，所述制备方法为：
将式II与式III所示化合物反应得到式I所示吡唑-5-醚类化合物，反应式如下：
其中，R1、R2、R3、R4、R5、R6、R7的限定如上文所述，在此不再赘述；以及R9选自C1-C6烷基。
优选地，所述式II所示化合物与式III所示化合物的摩尔比为0.5-2:1，例如0.5:1、0.8:1、1:1、1.2:1、1.5:1、1.8:1或2:1。
优选地，所述反应的溶剂为二氯甲烷、氯仿、乙酸乙酯、甲苯、乙腈、四氢呋喃、二氧六环、乙醇、甲醇、N,N-二甲基甲酰胺或二甲基亚砜等中的任意一种或至少两种的组合。
优选地，所述反应的温度为大于等于室温小于等于反应溶剂的沸点，例如20℃、25℃、30℃、35℃、40℃、45℃、50℃、60℃、70℃、75℃、80℃、85℃、90℃等，或者在溶剂沸点即回流状态下进行反应。
优选地，所述反应的时间为0.5-48小时，例如0.5小时、1小时、3小时、5小时、8小时、10小时、12小时、15小时、18小时、20小时、23小时、25小时、28小时、30小时、33小时、35小时、38小时、40小时、44小时或48小时。
优选地，式III所示化合物通过以下方法制备得到：式IV与式V化合物在催化剂存在下反应得到式III所示化合物，反应式如下：
其中，R1、R2、R3、R4、R5、R9的限定如上文所述，在此不再赘述。
优选地，在式III所示化合物的制备中，所述反应在酸性物质存在下进行，所述酸性物质为有机酸和/或无机酸。
所述有机酸为对甲苯磺酸、甲磺酸、三氟乙酸、乙酸中的任意一种或至少两种的组合。
所述无机酸为盐酸、氢溴酸、硫酸、氯化锌、氯化铵、三氯化铁中的任意一种或至少两种的组合。
优选地，在式III所示化合物的制备中，可以不加溶剂。
优选地，在式III所示化合物的制备中，反应可以在合适的溶剂中进行，所述反应的溶剂为二氯甲烷、氯仿、乙酸乙酯、甲苯、乙腈、四氢呋喃、1,4二氧六环、甲醇、乙醇、异丙醇、正丁醇、水、N,N-二甲基甲酰胺或二甲基亚砜中的任意一种或至少两种的组合。
优选地，在式III所示化合物的制备中，所述反应的温度为大于等于0℃小于等于反应溶剂的沸点。
优选地，在式III所示化合物的制备中，所述反应的时间为0.5-48小时。
优选地，式IV所示化合物通过以下方法制备得到：式VI所示化合物在还原剂存在下还原得到式IV所示化合物，反应式如下：
其中，R1、R2、R3、R4、R5的限定如上文所述，在此不再赘述。
优选地，在式IV所示化合物的制备中，所述还原剂为氢气、水合肼、铁粉、锌粉、氯化亚锡或连二亚硫酸钠中的任意一种或至少两种的组合。
优选地，在式IV所示化合物的制备中，所述反应在催化剂存在下进行，所述催化剂优选钯碳、二氧化钯、兰尼镍、三氯化铁或碱式氧化铁中的任意一种或至少两种的组合。
优选地，在式IV所示化合物的制备中，所述反应的溶剂为二氯甲烷、氯仿、乙酸乙酯、甲苯、乙腈、四氢呋喃、二氧六环、乙醇、甲醇、N,N-二甲基甲酰胺、饱和氯化铵水溶液、乙酸、盐酸、水或二甲基亚砜中的任意一种或至少两种的组合。
优选地，在式IV所示化合物的制备中，所述反应的温度为大于等于0℃小于等于反应溶剂的沸点。
优选地，在式IV所示化合物的制备中，所述反应的时间为0.5-48小时。
优选地，式VI所示化合物通过以下方法制备得到：式VII与式VIII所示化合物反应得到式VI所示化合物，反应式如下：
其中，L为氟或氯；此外，其中，R1、R2、R3、R4、R5的限定如上文所述，在此不再赘述。
优选地，式VII所示化合物与式VIII所示化合物的摩尔比为1-3:1。
优选地，在式VI所示化合物的制备中，所述反应在碱性物质存在下进行，所述碱性物质为有机碱和/或无机碱。
优选地，所述有机碱为三乙胺、N,N-二甲基苯胺、吡啶、甲醇钠、乙醇钠、叔丁醇钠或叔丁醇钾中的任意一种或至少两种的组合。
优选地，所述无机碱为氢氧化钠、氢氧化钾、碳酸钠、碳酸钾或氢化钠中的任意一种或至少两种的组合。
优选地，在式VI所示化合物的制备中，所述反应的溶剂为二氯甲烷、氯仿、丙酮、甲苯、乙腈、四氢呋喃、二氧六环、甲醇、乙醇、N,N-二甲基甲酰胺、二甲基亚砜或六甲基磷酰三胺中的任意一种或至少两种的组合。
优选地，在式VI所示化合物的制备中，所述反应的温度为大于等于0℃小于等于反应溶剂的沸点，例如0℃,20℃、25℃、30℃、35℃、40℃、45℃、50℃、60℃、70℃、75℃、80℃、85℃、90℃等，或者在溶剂沸点即回流状态下进行反应。
优选地，在式VI所示化合物的制备中，所述反应的时间为0.5-48小时。
在本申请中，所用原料式VIII化合物中部分化合物为市售试剂，部分化合物可以参照文献合成，如有机化学(2015),35(1),100-108；Pest Management Science(2014),70(8),1207-1214；Molecules(2022),27(19),6274；New Journal of Chemistry(2019),43(7),3000-3010。
在本申请中，表2示出了本申请式VI所述中间体化合物的代表性化合物，但本申请并不限定于此。
表2


在本申请中，在表3中示出了本申请式IV所述中间体化合物的代表性化合物，但本申请并不限定于此。
表3

第三方面，本申请提供了如第一方面所述的吡唑-5-醚类化合物在防治植物病害中的应用。
本申请所述的吡唑-5-醚类化合物具有意想不到的高杀菌活性，对植物病害具有很好的控制效果。
在本申请中，所述植物病害包括卵菌纲(Oomycetes)、子囊菌纲(Ascomycetes)、担子菌纲(Basidiomycetes)或半知菌纲(Deuteromycetes)病害。
优选地，所述植物病害包括但不限于：小麦锈病、小麦白粉病、小麦赤霉病、小麦根腐病、小麦纹枯病、小麦全蚀病、小麦颖枯病、黄瓜霜霉病、黄瓜白粉病、甜瓜白粉病、苦瓜白粉病、黄瓜炭疽病、黄瓜枯萎病、黄瓜灰霉病、葡萄霜霉病、番茄早疫病、番茄晚疫病、水稻纹枯病、水稻稻瘟病、西瓜蔓枯病、花生疮痂病、花生黑斑病、柑橘疮痂病、辣椒根腐病、棉花黄萎病、棉花枯萎病、油菜黑茎病、油菜菌核病、梨黑星病、人参锈腐病、玉米锈病、玉米弯孢病、玉米大斑病、芒果蒂腐病、苹果轮纹病、苹果腐菌烂病、香蕉叶斑病、大豆锈病或马铃薯晚疫病。
优选地，所述植物病害包括小麦锈病、小麦白粉病、小麦赤霉病、黄瓜白粉病、黄瓜霜霉病或大豆锈病。
第四方面，本申请提供了一种杀菌剂组合物，所述杀菌剂组合物包括活性组分和农药学上可接受的载体，所述活性组分为如上所述的吡唑-5-醚类化合物。
本申请所述杀菌剂组合物可以用于农业、林业、卫生等领域。
优选地，所述杀菌剂组合物中，所述活性成分的重量百分含量为1％-99％，例如1％、3％、5％、8％、10％、15％、18％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％或99％。
优选地，所述农药学上可接受的载体包括表面活性剂。
在本申请中，所述表面活性剂为离子型表面活性剂或非离子型表面活性剂。
所述表面活性剂包括乳化剂、分散剂或湿润剂；其中，所述乳化剂可以为聚氧乙烯脂肪酸脂、聚氧乙烯脂肪醇醚、聚氧乙烯脂肪氨以及市售的乳化剂(农乳2201B、农乳0203B、农乳100#、农乳500#、农乳600#、农乳600-2#、农乳1601、农乳2201、农乳NP-10、农乳NP-15、农乳507#、农乳OX-635、农乳OX-622、农乳OX-653、农乳OX-667、宁乳36#)；所述分散剂包括木质素磺酸钠、拉开粉、木质素磺酸钙、甲基萘磺酸甲醛缩合物等；所述湿润剂包括月桂醇硫酸钠、十二烷基苯磺酸钠、烷基萘磺酸钠等。
优选地，所述农药学上可接受的载体包括固体载体和/或液体载体。
优选地，所述固体载体包括天然的或合成的粘土和硅酸盐，例如天然硅石和硅藻土；硅酸镁例如滑石；硅酸铝镁例如高岭石、高岭土、蒙脱土和云母；白碳黑、碳酸钙、轻质碳酸钙；硫酸钙；石灰石；硫酸钠；胺盐如硫酸铵、六甲撑二胺。所述液体载体包括水和有机溶剂，当用水做溶剂或稀释剂时，有机溶剂也能用做辅助剂或防冻添加剂。合适的有机溶剂包括芳烃例如苯、二甲苯、甲苯等；氯代烃，例如氯代苯、氯乙烯、三氯甲烷、二氯甲烷等；脂肪烃，例如石油馏分、环己烷、轻质矿物油；醇类，例如异丙醇、丁醇、乙二醇、丙三醇和环己醇等；以及它们的醚和酯；还有酮类，例如丙酮、环己酮以及二甲基甲酰胺和N-甲基-吡咯烷酮。
在杀菌剂组合物的配制过程中可以将活性组分与液体载体和/或固体载体混合，同时加入表面活性剂(如乳化剂、分散剂、稳定剂、湿润剂)，还可以加入其它助剂(如粘合剂、消泡剂、氧化剂等)。
第五方面，本申请提供一种防治植物病害的方法，所述方法为：向需要控制的植物病害或其生长的介质上施用有效剂量的如上所述的杀菌剂组合物。
优选地，所述有效剂量为每公顷10-1000g，优选每公顷20-500g。
本申请的组合物可以制剂的形式施用在病害或其生长介质上。通式化合物I作为活性组分溶解或分散于载体中或配制成制剂以便作为杀菌剂使用时更易于分散。例如：这些化学制剂可被配制成各种液剂、乳油、悬浮剂、水悬剂、微乳剂、乳剂、水乳剂、粉剂、可湿性粉剂、可溶性粉剂、颗粒剂、水分散型颗粒剂或胶囊剂。
对于某些应用，例如在农业上可在本申请的杀菌组合物中加入一种或多种其它的杀菌剂、杀虫剂、除草剂、植物生长调节剂或肥料等，由此可产生附加的优点和效果。
相对于现有技术，本申请具有以下有益效果：
本申请的具有式I所示结构的吡唑-5-醚类化合物对于防治农业、林业上病害具有显著效果，尤其对黄瓜白粉病、黄瓜霜霉病、大豆锈病、小麦赤霉病具有很好的防治效果，在吡唑-5-醚类化合物浓度为10ppm时对黄瓜白粉病的防治效果≥90％，100ppm时对黄瓜霜霉病的防治效果≥90％；在吡唑-5-醚类化合物浓度为10ppm时对大豆锈病的防治效果≥90％；在吡唑-5-醚类化合物浓度为100ppm时对小麦赤霉病孢子萌发的抑制率≥90％，并且其制备方法简单高效、易于规模化生产，应用前景广泛。
具体实施方式
下面通过具体实施方式来进一步说明本申请的技术方案。本领域技术人员应该明了，所述实施例仅仅是帮助理解本申请，不应视为对本申请的具体限制。如无特别说明实施例和本申请中：对化合物进行核磁氢谱测试表征时相应样品都溶于氘代二甲基亚砜(DMSO-d6)或氘代氯仿(CDCl3)中，用400MHz核磁共振仪测试得到氢谱数据，化学位移单位为ppm(即δ：ppm)；柱色谱提纯用淋洗液为按照所示(简称PE)：乙酸乙酯(简称EA)体积比配置而成。
合成实施例
实施例1：化合物16的制备
步骤1：5-(2,5-二甲基-4-硝基苯氧基)-1-甲基-3-三氟甲基-1H-吡唑的合成：
1-氯-2,5-二甲基-4-硝基苯(2.3g,12.5mmol)和碳酸钾(2.1g,15.1mmol)加入到20mL DMF中，加入1-甲基-3-三氟甲基-1H-吡唑-5-醇(2.1g,12.6mmol)，回流反应，TLC监测反应结束后反应液冷却至室温，加入100mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得1.55g淡黄色固体，收率39.0％。
步骤2：2,5-甲基-4-(1-甲基-3-三氟甲基-1H-吡唑-5-氧基)苯胺的合成：
5-(2,5-二甲基-4-硝基苯氧基)-1-甲基-3-三氟甲基-1H-吡唑(1.5g,4.8mmol)加入到30mL无水乙醇中，加入还原铁粉(1.0g,17.6mmol)，滴加10mL饱和氯化铵水溶液，回流反应， 8小时后反应液冷却至室温，硅藻土过滤，乙醇润洗，蒸除乙醇，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得1.24g黄色固体，收率91.0％。
步骤3：(E)-N-[4-(1-甲基-3-三氟甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚的合成：
2,5-甲基-4-(1-甲基-3-三氟甲基-1H-吡唑-5-氧基)苯胺(1.31g,4.6mmol)、原甲酸三乙酯(6.8g,46.0mmol)和对甲苯磺酸一水合物(310mg,1.0mmol)加入到反应瓶中，升温至回流反应8小时，反应液冷却至室温，加压蒸馏至无液滴滴下，得棕色油状物，不经分离，直接进行下一步。
步骤4：(E)-N'-[4-(1-甲基-3-三氟甲基-1H-吡唑-5-氧基)-2,5-二甲基苯基]-N-乙基-N-甲基甲脒的合成：
(E)-N-[4-(1-甲基-3-三氟甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚(250mg,0.73mmol)溶于10mL二氯甲烷中，加入甲乙胺(250mg,4.2mmol)，升温至回流反应，2小时后反应完毕，反应液冷却至室温，加入20mL水，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得180mg黄色油状化合物16，收率69.5％。
化合物16的1H NMR(DMSO-d6,δ[ppm]):7.61(br S,1H),6.90(s,1H),6.72(s,1H),5.74(s,1H),3.81(s,3H),3.33(br s,2H),2.99–2.88(m,3H),2.13(s,6H),1.13(t,J＝6.8Hz,3H).
实施例2：化合物77的制备
步骤1：5-(2,5-二甲基-4-硝基苯氧基)-1-甲基-3-二氟甲基-1H-吡唑的合成：
1-氯-2,5-二甲基-4-硝基苯(3.0g,16.2mmol)和碳酸钾(4.5g,32.3mmol)加入到20mL DMF中，加入1-甲基-3-二氟甲基-1H-吡唑-5-醇(2.6g,17.8mmol)，回流反应，TLC监测反应结束后反应液冷却至室温，加入100mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得1.3g淡黄色固体，收率27.0％。
步骤2：2,5-甲基-4-(1-甲基-3-二氟甲基-1H-吡唑-5-氧基)苯胺的合成：
5-(2,5-二甲基-4-硝基苯氧基)-1-甲基-3-二氟甲基-1H-吡唑(1.3g,4.4mmol)加入到30mL无水乙醇中，加入还原铁粉(490mg,8.8mmol)，滴加10mL饱和氯化铵水溶液，回流反应，8小时后反应液冷却至室温，硅藻土过滤，乙醇润洗，蒸除乙醇，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得830mg淡红色油状物，收率71.2％。
步骤3：(E)-N-[4-(1-甲基-3-二氟甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚的合成：
2,5-甲基-4-(1-甲基-3-二氟甲基-1H-吡唑-5-氧基)苯胺(830mg,3.1mmol)、原甲酸三乙酯(4.6g,31.1mmol)和对甲苯磺酸一水合物(58.0mg,0.3mmol)加入到反应瓶中，升温至回 流反应8小时，反应液冷却至室温，加压蒸馏至无液滴滴下，得棕色油状物，不经分离，直接进行下一步。
步骤4：(E)-N'-[4-(1-甲基-3-二氟甲基-1H-吡唑-5-氧基)-2,5-二甲基苯基]-N-乙基-N-甲基甲脒的合成：
(E)-N-[4-(1-甲基-3-二氟甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚(333.0mg,1.0mmol)溶于10mL二氯甲烷中，加入甲乙胺(365.0mg,6.2mmol)，升温至回流反应，2小时后反应完毕，反应液冷却至室温，加入20mL水，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝3:1)，得233.0mg淡黄色油状化合物77，收率67.2％。
化合物77的1H NMR(DMSO-d6,δ[ppm]):7.61(s,1H),7.19(t,J＝53.4Hz,1H),6.77(s,1H),6.65(s,1H),5.90(d,J＝1.2Hz,1H),3.75(s,3H),3.32-3.35(m,2H),2.92(s,3H),2.11(s,3H),2.09(s,3H),1.11(d,J＝7.2Hz,2H).
实施例3：化合物99的制备
步骤1：5-(2,5-二甲基-4-硝基苯氧基)-1,3-二甲基-1H-吡唑的合成：
1-氯-2,5-二甲基-4-硝基苯(3.0g,16.2mmol)和碳酸钾(4.5g,32.3mmol)加入到30mL DMF中，加入1,3-二甲基-1H-吡唑-5-醇(1.99g,17.8mmol)，回流反应，TLC监测反应结束后反应液冷却至室温，加入100mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝10:1)，得1.9g淡橘黄色固体，收率45.1％。
步骤2：2,5-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)苯胺的合成：
6-(2,5-二甲基-4-硝基苯氧基)-1,3-二甲基-1H-吡唑(1.9g,7.3mmol)加入到30mL无水乙醇中，加入还原铁粉(814.0mg,14.6mmol)，滴加10mL饱和氯化铵水溶液，回流反应，8小时后反应液冷却至室温，硅藻土过滤，乙醇润洗，蒸除乙醇，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得1.1g黄色固体，收率64.7％。
步骤3：(E)-N-[4-(1,3-二甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚的合成：
2,5-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)苯胺(1.1g,4.7mmol)、原甲酸三乙酯(7.0g,47.1mmol)和对甲苯磺酸一水合物(89.6mg,0.47mmol)加入到反应瓶中，升温至回流反应8小时，反应液冷却至室温，加压蒸馏至无液滴滴下，得棕色油状物，不经分离，直接进行下一步。
步骤4：(E)-N'-[4-(1,3-二甲基-1H-吡唑-5-氧基)-2,5-二甲基苯基]-N-乙基-N-甲基甲脒的合成：
(E)-N-[4-(1,3-二甲基-1H-吡唑-5氧基)-2,5-二甲基苯基]甲脒乙醚(337.0mg,1.0mmol)溶 于10mL二氯甲烷中，加入甲乙胺(416.0mg,6.0mmol)，升温至回流反应，2小时后反应完毕，反应液冷却至室温，加入20mL水，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝3:1)，得273.0mg淡黄色固体状化合物99，收率77.7％。
化合物99的1H NMR(DMSO-d6,δ[ppm]):7.62(s,1H),6.78(s,1H),6.68(s,1H),5.12(s,1H),3.59(s,3H),3.32(br s,2H),2.92(s,3H),2.12(s,3H),2.11(s,3H),2.02(s,3H),1.12(t,J＝7.2Hz,3H)。
实施例4：化合物114的制备
步骤1：5-(2-氯-5-甲基-4-硝基苯氧基)-1,3-二甲基-1H-吡唑的合成：
1-氯-2-氟-4-甲基-5-硝基苯(1.69g,8.9mmol)和碳酸钾(1.5g,10.68mmol)加入到20mL DMF中，加入1,3-二甲基-1H-吡唑-5-醇(1.0g,8.9mmol)，回流反应，10小时后反应液冷却至室温，加入100mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得1.4g黄色固体，收率71.1％。
步骤2：2-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)-5-氯苯胺的合成：
5-(2-氯-5-甲基-4-硝基苯氧基)-1,3-二甲基-1H-吡唑(3.24g,11.5mmol)加入到30mL无水乙醇中，加入还原铁粉(1.6g,28.6mmol)，滴加10mL饱和氯化铵水溶液，回流反应，4小时后反应液冷却至室温，硅藻土过滤，乙醇润洗，蒸除乙醇，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝2:1)，得1.9g黄色固体，收率67.1％。
步骤3：(E)-N-[2-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)-5-氯苯基]甲脒乙醚的合成：
2-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)-5-氯苯胺(1.9g,7.6mmol)、原甲酸三乙酯(11.3g,76.0mmol)和对甲苯磺酸一水合物(144.6mg,0.76mmol)加入到反应瓶中，升温至回流反应3小时，反应液冷却至室温，加压蒸馏至无液滴滴下，得棕色油状物，不经分离，直接进行下一步。
步骤4：(E)-N'-[2-甲基-4-(1,3-二甲基-1H-吡唑-5-氧基)-5-氯苯基]-N-乙基-N-甲基甲脒的合成：
(E)-N-[2-甲基-4-(1,3-二甲基-1H-吡唑-5氧基)-5-氯苯基]甲脒乙醚(335.0mg,1.1mmol)溶于10mL二氯甲烷中，加入甲乙胺(389.4mg,6.6mmol)，升温至回流反应，TLC监测反应完毕后将反应液冷却至室温，加入20mL水，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝2:1)，得249.0mg黄色固体状化合物114，收率70.6％。
化合物114的1H NMR(DMSO-d6,δ[ppm]):7.76(s,1H),7.04(d,J＝0.8Hz,1H),7.01(s,1H),5.22(s,1H),3.61(s,3H),3.48–3.34(m,2H),2.92(s,3H),2.14(s,3H),2.03(s,3H),1.13(d,J＝7.2Hz,3H).
实施例5：化合物175的制备
步骤1：1-乙基-3-(三氟甲基)-1H-吡唑-5-醇的合成：
将三氟乙酰乙酸乙酯(2.00g,10.86mmol)与乙基肼草酸盐(1.96g,13.04mmol)依次加入装有30mL乙醇的烧瓶中，反应升温至回流。TLC监测反应完毕后将反应液冷却至室温，减压除去溶剂，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物不经后处理直接用于下一步。
步骤2：5-(2,5-二甲基-4-硝基苯氧基)-1-乙基-3-三氟甲基-1H-吡唑的合成：
1-氯-2,5-二甲基-4-硝基苯(1.65g,8.9mmol)和碳酸钾(1.48g,10.68mmol)加入到20mLDMF中，加入1-乙基-3-(三氟甲基)-1H-吡唑-5-醇(1.60g,8.9mmol)，回流反应，10小时后反应液冷却至室温，加入100mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝5:1)，得2.1g黄色固体，收率71.7％。
步骤3：2,5-甲基-4-(1-乙基-3-三氟甲基-1H-吡唑-5-氧基)-苯胺的合成：
5-(2,5-二甲基-4-硝基苯氧基)-1-乙基-3-三氟甲基-1H-吡唑(3.79g,11.5mmol)加入到30mL无水乙醇中，加入还原铁粉(1.6g,28.6mmol)，滴加10mL饱和氯化铵水溶液，回流反应，4小时后反应液冷却至室温，硅藻土过滤，乙醇润洗，蒸除乙醇，加入50mL水和50mL乙酸乙酯，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝2:1)，得2.4g棕色油状液体，收率69.7％。
步骤4：(E)-N-[2-甲基-4-(1-乙基-3-三氟甲基-1H-吡唑-5-氧基)-5-氯苯基]甲脒乙醚的合成：
2,5-甲基-4-(1-乙基-3-三氟甲基-1H-吡唑-5-氧基)-苯胺(2.27g,7.6mmol)、原甲酸三乙酯(11.26g,76.0mmol)和对甲苯磺酸一水合物(144.6mg,0.76mmol)加入到反应瓶中，升温至回流反应3小时，反应液冷却至室温，减压蒸馏至无液滴滴下，得棕色油状物，不经分离，直接进行下一步。
步骤5：(E)-N'-[4-(1-乙基-3-三氟甲基-1H-吡唑-5-氧基)-2,5-二甲基苯基]-N-乙基-N-甲基甲脒的合成：
(E)-N-[2-甲基-4-(1-乙基-3-三氟甲基-1H-吡唑-5-氧基)-5-氯苯基]甲脒乙醚(390.9mg,1.1mmol)溶于10mL二氯甲烷中，加入甲乙胺(389.4mg,6.6mmol)，升温至回流反应，TLC监测反应完毕后将反应液冷却至室温，加入20mL水，分液萃取，取有机层，饱和氯化钠水洗，无水硫酸钠干燥，减压下浓缩，残余物经柱色谱提纯(淋洗液为PE:EA＝2:1)，得200.0mg黄色油状化合物175，收率49.4％。
化合物175的1H NMR(400MHz,DMSO-d6)δ7.67(s,1H),6.91(s,1H),6.73(s,1H),5.72(s,1H),4.17(q,J＝7.2Hz,2H),3.33–3.41(m,2H),2.92(s,3H),2.13(s,6H),1.39(t,J＝7.2Hz,3H),1.13(t,J＝7.1Hz,4H).
除上面描述的化合物外，表1中化合物参照合成实施例1-5中相似的方法可制备得到，下文表4中给出了参照合成实施例1-5合成的部分化合物的核磁数据(样品溶解溶剂为DMSO-d6，带*的化合物溶剂为CDCl3)。
表4







本申请的其他通式I化合物可参照上述方法合成。
制剂实施例1
在本实施例中，由制备得到的吡唑-5-醚类化合物来制备杀菌剂制剂，按照表5中所示质量配比配制得到化合物2的浓度为30％悬浮剂。
表5
制备方法为：将化合物2及其它组分充分混合，由此得到的30％悬浮剂。并且用水稀释所得悬浮剂可得到所需浓度的稀释液。
生物活性测试实施例
用上述获得的本申请化合物对多种病菌进行了试验。如无特别说明实施例和本申请中：样品配制方法为称取待测样品原药10mg，用1mL DMF溶解，配制成10000ppm母液，用0.05％吐温-80水将母液稀释至所需浓度进行活性测试。
测试实施例1：化合物对小麦白粉病的杀菌活性
在本实施例中，对制备得到的吡唑-5-醚类化合物防治小麦白粉病(Blumeria graminis(DC.)Speer)的效果进行测定，方法如下：
筛选采用活体盆栽测定方法。用喉头喷雾器将药剂均匀喷洒于一叶一心期的小麦叶片上，每次处理3次重复，喷施后放置于室内自然晾干。药剂处理后24h，将接种后10d左右产生的小麦白粉病孢子均匀抖落于施药后的小麦叶片上。接种孢子后10d，待对照发病稳定时进行调查。调查结果用100～0来表示，以“100”级代表无病和“0”级代表最严重的发病程度。
化合物18、66、68、102、117、132、143、149、179、186、225、230、250、251、254、255、259、260在浓度为40ppm时对小麦白粉病的防治效果≥80％。
化合物16、69、175、176、177、178、185、186、188、189、207、212、215在浓度为10ppm时对小麦白粉病的防治效果>70％。
按照相同方法，本申请化合物与KC1、KC2和KC3的活性对比结果见表6。
表6本申请化合物与KC1、KC2和KC3对小麦白粉病的防治效果(防效，％)
测试实施例2：化合物对大豆锈病的杀菌活性
在本实施例中，对制备得到的吡唑-5-醚类化合物防治大豆锈病(Phakopsora pachyrhizi)的效果进行测定，方法如下：
筛选采用活体盆栽测定方法，即将待测化合物样品用少量溶剂(溶剂的种类如丙酮、甲醇、DMF等，依据其对样品的溶解能力而选择，溶剂量与喷液量的体积比等于或小于0.05)溶解，用含有0.1％吐温80的水稀释，配制成所需浓度待测液。温室培养两叶期大豆作为大豆锈病(Phakopsora pachyrhizi)的试验寄主植物。用本申请化合物按照设计浓度进行叶面喷雾处理。另设喷清水的空白对照，3次重复，处理后24h后进行病菌接种。接种后，将植物放在人工气候室中保湿培养(温度：昼25℃、夜20℃，相对湿度：95-99％)。试验材料培养24h后，移置温室培养。待对照充分发病后(通常为一周时间)进行化合物防病效果评估。结果调查参照美国植物病学会编写的《A Manual of Assessment Keys for Plant Diseases》，用100～0来表示，以“100”级代表无病和“0”级代表最严重的发病程度。
化合物176、212、242、243、254、255在浓度为10ppm时对大豆锈病的防治效果>90％。
化合物16、175、199、201、207、208在浓度为4ppm时对大豆锈病的防治效果>80％。
按照以上方法，现有化合物KC3在浓度为10ppm时对大豆锈病的防治效果为22％，在浓度为4ppm时对大豆锈病的防治效果为0。
测试实施例3：化合物对黄瓜白粉病的杀菌活性
在本实施例中，对制备得到的吡唑醚类化合物对防治黄瓜白粉病(Erysiphe cichoracearum)的效果进行测定，方法如下：
筛选采用活体盆栽测定方法，即将待测化合物样品用少量溶剂(溶剂的种类如丙酮、甲醇、DMF等，依据其对样品的溶解能力而选择，溶剂量与喷液量的体积比等于或小于0.05)溶解，用含有0.1％吐温80的水稀释，配制成所需浓度待测液。温室培养的两叶期黄瓜苗作为黄瓜白粉病(Erysiphe cichoracearum)的试验寄主植物。用本申请化合物按照设计浓度进行叶面喷雾处理。另设喷清水的空白对照，3次重复，处理后24h后进行病菌接种。接种后，将植物放在人工气候室中保湿培养(温度：昼25℃、夜20℃，相对湿度：95-99％)。试验材料培养24h后，移置温室培养。待对照充分发病后(通常为一周时间)进行化合物防病效果评估。结果调查用100～0来表示，以“100”级代表无病和“0”级代表最严重的发病程度。
化合物180、185、186、190、192、198、208、212、214、217在浓度为4ppm时对黄瓜白粉病的防治效果≥90％。
化合物185、186、190、198、212、214在浓度为2.5ppm时对黄瓜白粉病的防治效果>90％。
按照以上方法，在浓度为2.5ppm时，现有化合物KC1、KC2对黄瓜白粉病的防治效果为0，KC3对黄瓜白粉病的防治效果为22.22％。
本申请通过上述实施例来说明本申请的吡唑-5-醚类化合物及其制备方法和应用，但本申请并不局限于上述实施例，即不意味着本申请必须依赖上述实施例才能实施。所属技术领域的技术人员应该明了，对本申请的任何改进，对本申请产品各原料的等效替换及辅助成分的添加、具体方式的选择等，均落在本申请的保护范围和公开范围之内。

Claims (10)

  1. 一种吡唑-5-醚类化合物，其具有式I所示结构：
    其中，
    R1选自至少被1个R8取代的C1-C6烷基、C3-C6环烷基或苯环；
    R2选自C1-C6卤代烷基、C3-C6环烷基、甲基、氰基或至少被1个R8取代的苯基；
    R3选自氢、卤素、氰基、C1-C6烷基或C1-C6卤代烷基；
    R4选自卤素、C1-C6烷基、C1-C6烷氧基、C1-C6卤代烷基、C1-C6卤代烷氧基；
    R5选自氢、卤素、C1-C6烷基、C1-C6烷氧基或C1-C6卤代烷基；
    R6选自至少被1个R8取代的C1-C8烷基、C3-C6环烷基、C3-C6环烷基或C1-C6卤代烷基；
    R7选自氢或C1-C6烷基；或R6和R7连同它们所连接的氮原子一起形成三元至七元饱和的环状基团，该环状基团可以任选地含有氧原子、氮原子或硫原子，环状基团可以进一步被相同或不同的R8取代；以及
    R8选自氢、卤素、氰基、硝基、羟基、氨基、C1-C6烷基、C1-C6环烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、被C1-C6烷基取代的氨基、C1-C6烷基羰基氨基、C1-C6卤代烷基羰基氨基、C1-C6烷基磺酰基氨基、N,N-二(C1-C6烷基)磺酰基氨基、C1-C6卤代烷基磺酰基氨基、杂环酰基氨基、C1-C6烷基羰基、C1-C6烷氧基羰基、氰基取代C1-C6烷基、C1-C6烷基亚砜基、C1-C6烷基砜基、C1-C6卤代烷基亚砜基、C1-C6卤代烷基砜基、取代苯基、杂环或杂环取代C1-C6烷基。
  2. 根据权利要求1所述的吡唑-5-醚类化合物，其中，
    R1选自至少被1个R8取代的甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基环丙基、环丁基、环戊基、环己基或苯环；
    R2选自甲基、环丙基、二氟甲基、三氟甲基、氰基或至少被1个R8取代的苯基；
    R3选自氢、氟、氯、溴、碘、氰基、甲基、二氟甲基或三氟甲基；
    R4选自甲基、二氟甲基、三氟甲基、甲氧基、二氟甲氧基、三氟甲氧基、氟、氯、溴或碘；
    R5选自氢、甲基、甲氧基、二氟甲基、三氟甲基、氟、氯、溴或碘；
    R6选自甲基、乙基、正丙基、异丙基、1-甲基丙基、1-乙基丙基、2-甲基丙基、3-甲基丙基、1,1-二甲基丙基、2,2-二甲基丙基、正丁基、叔丁基、3-甲基丁基、1,1-二甲基-3,3-二甲基丁基、正戊基、4-甲基-2-戊基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、正己基、2-乙基己基、环丙基、环丁基、环戊基、环己基或环丙基甲基；
    R7选自氢、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、2-戊基、新戊基、异戊基、4-甲基-2-戊基或正己基；或R6和R7连同它们所连接的氮原子一起形成四氢吡咯、异噁唑烷、哌啶、氮杂环辛烷、哌嗪或吗啉，所述四氢吡咯、异噁唑烷、哌啶、氮杂环辛烷、哌嗪或吗啉可以被相同或不同的R8取代；以及
    R8选自氢、氟、氯、溴、碘、氰基、硝基、羟基、氨基、甲基、乙基、正丙基、异丙基、 环丙基、异丁基、正丁基、叔丁基、环丁基、氰基甲基、二氟甲基、三氟甲基、五氟乙基、七氟异丙基、甲氧基、二氟甲氧基、三氟甲氧基、乙酰基、叔丁氧基羰基、氨基、甲氨基、乙酰氨基、三氟乙酰氨基、甲磺酰胺基、三氟甲磺酰胺基、N,N-二甲胺基磺酰胺基、吗啉-4-甲酰胺基、吡唑基、咪唑基、1,2,4-三唑基、1,2,3-三唑基、1,3,4-三唑基、吡唑啉基、咪唑啉基、1,2,4-三唑烷基、吡啶基、嘧啶基、哒嗪基、吡嗪基、噁二唑基、噻二唑基、异噁唑烷基或异噁唑啉基。
  3. 根据权利要求2所述的吡唑-5-醚类化合物，其中，
    R1选自至少被1个R8取代的甲基、乙基、正丙基、异丙基、叔丁基、异丁基或环丙基；
    R2选自甲基、二氟甲基或三氟甲基；
    R3选自氢、氟、氯、氰基或甲基；
    R4选自甲基、甲氧基或氯；
    R5选自甲基或氯；
    R6选自甲基、乙基、正丙基或异丙基；
    R7选自氢、甲基、乙基、正丙基或异丙基；或
    R6和R7连同它们所连接的氮原子一起形成四氢吡咯、哌啶或氮杂环辛烷，所述四氢吡咯、哌啶或氮杂环辛烷可以被相同或不同的R8取代；以及
    R8选自氢、甲基或氟。
  4. 根据权利要求3所述的吡唑-5-醚类化合物，其中，
    R1选自甲基、乙基、正丙基、异丙基或叔丁基；
    R2选自三氟甲基；
    R3选自氢或甲基；
    R4选自甲基或氯；
    R5选自甲基或氯；
    R6选自乙基；
    R7选自甲基
    R6和R7连同它们所连接的氮原子一起形成哌啶，所述哌啶可以被相同或不同的R8取代；以及
    R8选自氢或甲基。
  5. 根据权利要求1-4中任一项所述的吡唑-5-醚类化合物，其中，所述吡唑-5-醚类化合物为如下化合物中的任意一种：

  6. 根据权利要求1-5中任一项所述的吡唑-5-醚类化合物在防治植物病害中的应用。
  7. 一种杀菌剂组合物，其包括：活性组分和农药学上可接受的载体，其中，所述活性组分为如权利要求1-5中任一项所述的吡唑-5-醚类化合物。
  8. 根据权利要求7所述杀菌剂组合物，其中，所述活性成分的重量百分含量为1-99％。
  9. 一种防治植物病害的方法，其包括：向需要控制的植物病害或其生长的介质上施用有效剂量的如权利要求7-8所述的杀菌剂组合物；
  10. 根据权利要求9所述的防治植物病害的方法，其中，所述有效剂量为每公顷10-1000g，优选为每公顷20-500g。
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CN1342137A (zh) * 1999-02-06 2002-03-27 阿方蒂农科有限公司 N2－苯基脒衍生物
CN101263129A (zh) * 2005-09-13 2008-09-10 拜尔农科股份公司 农药噻唑氧基取代的苯脒衍生物
CN101631460A (zh) * 2007-03-12 2010-01-20 拜尔作物科学股份公司 N2-苯基脒类作为除草剂的用途以及包含该n2-苯基脒类的除草剂
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WO2023284761A1 (zh) * 2021-07-13 2023-01-19 南通泰禾化工股份有限公司 一种吡唑醚类化合物及其制备方法和应用

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CN1342137A (zh) * 1999-02-06 2002-03-27 阿方蒂农科有限公司 N2－苯基脒衍生物
CN101263129A (zh) * 2005-09-13 2008-09-10 拜尔农科股份公司 农药噻唑氧基取代的苯脒衍生物
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