Amidine compound containing oxime ether as well as preparation method and application of amidine compound

Abstract

The invention provides an amidine compound containing oxime ether and a preparation method and application thereof.The amidine compound containing oxime ether has the structure shown in the formula I. The amidine compound containing oxime ether has a remarkable effect on prevention and treatment of agricultural and forestry diseases, especially has a good prevention and treatment effect on cucumber powdery mildew and cucumber downy mildew, and is wide in application prospect.

Description

Technical Field

[0001] The invention belongs to the field of agricultural fungicides and relates to an amidine compound containing oxime ether and a preparation method and application thereof. Background Art

[0002] The long-term use of existing fungicide varieties has led to the development of disease resistance to existing fungicide varieties, so it is required to continuously discover new fungicide varieties with different mechanisms of action.

[0003] Some amidine compounds have been reported in the prior art, for example, CN1016366083A discloses compound KC (structural formula as follows), and such disclosed compounds have certain fungicidal activity, but in many cases the fungicidal activity effect needs to be improved. Therefore, the object of the present invention is to provide an oxime ether-containing amidine compound with improved fungicidal effect.

[0004] Summary of the invention

[0005] In view of the problems existing in the prior art, the object of the present invention is to provide an amidine compound containing oxime ether and a preparation method and application thereof, wherein the compound has an improved bactericidal effect.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In one aspect, the present invention provides an amidine compound containing an oxime ether, wherein the amidine compound containing an oxime ether has a structure shown in Formula I:

[0008]

[0009] in:

[0010] X is selected from CH 2 , NH, O or S;

[0011] R 1 is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C3-C8 cycloalkyl, aryl, C1-C12 haloalkyl or C1-C12 haloalkoxy;

[0012] R 2 Selected from hydrogen or C1-C6 alkyl;

[0013] R 3 is selected from C1-C8 alkyl, C1-C8 haloalkyl or C3-C6 cycloalkylC1-C6 alkyl; or R 2 and R 3Together with the nitrogen atom to which they are attached, they form a three- to six-membered saturated cyclic group which may optionally contain an oxygen atom or a sulfur atom;

[0014] R 4 is selected from hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0015] R 5 is selected from hydrogen or methyl;

[0016] R 6 is selected from hydrogen or methyl;

[0017] R 7 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or C1-C6 haloalkoxy;

[0018] R 8 is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C3-C8 cycloalkyl, aryl, C1-C6 haloalkyl, C1-C6 haloalkoxy, CO 2 CH 3 or CO 2 C 2 H 5 ;

[0019] R 9 Selected from hydrogen, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl or aryl.

[0020] Preferably, the amidine compound containing oxime ether has a structure shown in Formula II:

[0021]

[0022] in:

[0023] X is selected from CH 2 , NH, O or S;

[0024] R 1 Selected from hydrogen;

[0025] R 2 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;

[0026] R 3is selected from methyl, ethyl, hydroxyethyl, 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; or R 2 and R 3 Together with the nitrogen atom to which they are attached, they form pyrrole, piperidine, or morpholine;

[0027] R 4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, difluoromethyl or trifluoromethyl;

[0028] R 5 is selected from hydrogen or methyl;

[0029] R 6 is selected from hydrogen or methyl;

[0030] R 7 is selected from hydrogen, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy;

[0031] R 8 Selected from hydrogen, C1-C6 alkyl, CO 2 CH 3 or CO 2 C 2 H 5 ;

[0032] R 9 Selected from hydrogen, C1-C6 alkyl or C3-C8 cycloalkyl.

[0033] As a preferred technical solution of the present invention, the amidine compound containing oxime ether is any one of the compounds shown in Table 1 below having the general formula II, wherein X is selected from O, R 1 , R 4 , R 7 Selected from hydrogen, R 5 , R 6 Selected from methyl:

[0034]

[0035] Table 1

[0036]

[0037]

[0038] The alkyl group of the present invention refers to a straight chain or branched chain, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like. A haloalkyl group refers to a group in which an alkyl group is substituted by one or more halogen atoms. An alkoxy group 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, tert-butoxy and the like. A haloalkoxy group refers to a group in which an alkoxy group is substituted by one or more halogen atoms. Halogen is F, Cl, Br or I.

[0039] The definition of the term C2-12 alkenyl as used herein encompasses the broadest range of alkenyl defined herein. This definition includes, for example, the following: vinyl, allyl, ethoxypropenyl, but-1-enyl, but-2-enyl, but-3-enyl, hex-1-enyl, hex-2-enyl, hex-3-enyl, hex-4-enyl, hex-5-enyl, hept-1-enyl, hept-2-enyl, hept-3-enyl, hept-4-enyl, hept-5-enyl, hept-6-enyl, oct-1-enyl, oct-2-enyl, oct-3-enyl, oct-4-enyl, oct-5-enyl, oct-6-enyl, oct-7-enyl, non-1-enyl, non-2-enyl, non-3-enyl, non-4-enyl, non-5-enyl, non-6-enyl, non-7-enyl, non-8-enyl, dec-1-enyl, dec-2-enyl, , dec-3-enyl, dec-4-enyl, dec-5-enyl, dec-6-enyl, dec-7-enyl, dec-8-enyl, dec-9-enyl, undec-1-enyl, undec-2-enyl, undec-3-enyl, undec-4-enyl, undec-5-enyl, undec-6-enyl, undec-7-enyl, undec-8-enyl, undec-9-enyl, undec-10-enyl, dodeca-1-enyl, dodeca-2-enyl, dodeca-3-enyl, dodeca-4-enyl, dodeca-5-enyl, dodeca-6-enyl, dodeca-7-enyl, dodeca-8-enyl, dodeca-9-enyl, dodeca-10-enyl, dodeca-11-enyl, buta-1,3-dienyl, penta-1,3-dienyl.

[0040] The definition of the term C2-12 alkynyl as used herein encompasses the broadest range of alkynyl defined herein. This definition includes, for example, the following meanings: ethynyl, prop-1-ynyl and prop-2-ynyl.

[0041] The definition of the term C5-18 aryl as used herein includes the maximum scope of the aryl group defined herein having 5 to 18 atoms. Specifically, this definition includes the following meanings: cyclopentadienyl, phenyl, cycloheptatrienyl, cyclooctatetraenyl, naphthyl and anthracenyl.

[0042] The term "C1-C12 alkyl" used in the present invention refers to a straight or branched alkyl group having 1 to 12 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, etc. The term "C1-C12 alkoxy" refers to a straight or branched alkoxy group having 1 to 12 carbon atoms, including but not limited to methoxy, ethoxy, n-propoxy, isopropoxy and tert-butoxy, etc. The term "C1-C12 haloalkoxy" has a similar meaning.

[0043] The term "C3-C8 cycloalkyl" used in the present invention 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, cyclooctyl, etc. C4-C8 cyclic alkenyl includes cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. C4-C8 cyclic alkynyl also includes cyclopentynyl, cyclohexynyl, cycloheptynyl and cyclooctynyl.

[0044] In the present invention, C1-C12, C1-C6, C3-C8, etc. before the specific group represent the number of carbon atoms contained in the group. For example, C1-C12 represents a group having 1, 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.

[0045] On the other hand, the present invention provides a method for preparing the amidine compound containing oxime ether as described above, wherein the preparation method comprises:

[0046] The compound represented by formula III is reacted with the compound represented by formula IV to obtain the amidine compound containing oxime ether represented by formula II, and the reaction formula is as follows:

[0047]

[0048] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 The definition of R is as described above and will not be repeated here. 10 Selected from C1-C6 alkyl.

[0049] Preferably, the molar ratio of the compound represented by formula III to the compound represented by formula IV 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.

[0050] Preferably, 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.

[0051] Preferably, 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.

[0052] Preferably, 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.

[0053] Preferably, the compound represented by formula IV is prepared by the following method: the compound represented by formula VI is reacted with the compound represented by formula V in the presence of a catalyst to obtain the compound represented by formula III, and the reaction formula is as follows:

[0054]

[0055] Where R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 The limitations are as stated above and will not be repeated here.

[0056] Preferably, in the preparation of the compound represented by formula IV, 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.

[0057] The organic acid is any one of p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid and acetic acid, or a combination of at least two of them.

[0058] 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.

[0059] Preferably, no solvent is added during the preparation of the compound represented by formula IV.

[0060] Preferably, in the preparation of the compound represented by formula IV, the reaction 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.

[0061] Preferably, in the preparation of the compound represented by formula IV, 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, 3°C, 5°C, 8°C, 10°C, 15°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.

[0062] Preferably, in the preparation of the compound represented by formula IV, 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.

[0063] Preferably, the compound of formula VI is prepared by the following method: the compound of formula VII is reacted to obtain the compound of formula VI, and the reaction formula is as follows:

[0064]

[0065] Where R 4 , R 5 , R 6 , R 7 , R 8 , R 9 The limitations are as stated above and will not be repeated here.

[0066] Preferably, the molar ratio of the compound represented by formula VII to the compound represented by the hydrochloride salt 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.

[0067] Preferably, in the preparation of the compound shown in formula VI, the solvent of the reaction is an aliphatic hydrocarbon, an aromatic hydrocarbon, an ether such as ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, dimethyl sulfoxide, dimethylformamide or dimethylacetamide. Particularly preferred reaction solvents are methanol, ethanol, propanol, tetrahydrofuran or dioxane. At least two combinations of the above-mentioned solvents can also be used as reaction solvents.

[0068] Preferably, in the preparation of the compound shown in formula VI, the alkali of the reaction is generally an inorganic base, such as alkali metal or alkaline earth metal hydroxide, alkali metal or alkaline earth metal oxide, alkali metal or alkaline earth metal hydride, alkali metal amide, alkali metal or alkaline earth metal carbonate such as lithium carbonate, sodium carbonate, potassium carbonate or calcium carbonate, and alkali metal bicarbonate, alkali metal or alkaline earth metal alkoxide. In addition, there is also an organic base, such as tertiary amine such as trimethylamine, triethylamine, tributylamine, diisopropylethylamine and N-methyl piperidine, pyridine, substituted pyridine, and dicyclic amine. Sodium carbonate, potassium carbonate, sodium bicarbonate and tertiary amine are particularly preferred. Bases are usually used in catalytic amounts; however, they can also be used in equimolar amounts, in excess, or as solvents if appropriate.

[0069] Preferably, in the preparation of the compound represented by formula VI, 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, 3°C, 5°C, 8°C, 10°C, 15°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.

[0070] Preferably, in the preparation of the compound represented by formula VI, 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.

[0071] Preferably, the compound represented by formula VII is prepared by the following method: the compound represented by formula VIII is reduced in the presence of a reducing agent to obtain the compound represented by formula VII, and the reaction formula is as follows:

[0072]

[0073] Where R 4 , R 5 , R 6 , R 7 , R 8 The limitations are as stated above and will not be repeated here.

[0074] Preferably, in the preparation of the compound represented by formula VII, 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.

[0075] Preferably, in the preparation of the compound represented by formula VII, 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.

[0076] Preferably, in the preparation of the compound represented by formula VII, 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.

[0077] Preferably, in the preparation of the compound represented by formula VII, 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, 3°C, 5°C, 8°C, 10°C, 15°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.

[0078] Preferably, in the preparation of the compound represented by formula VII, 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.

[0079] Preferably, the compound represented by formula VIII is prepared by the following method: the compound represented by formula IX reacts with the compound represented by formula X to obtain the compound represented by formula VIII, and the reaction formula is as follows:

[0080]

[0081] Where L is fluorine or chlorine, and R 4 , R 5 , R 6 , R 7 , R 8 The limitations are as stated above and will not be repeated here.

[0082] Preferably, the molar ratio of the compound represented by Formula IX to the compound represented by Formula X is 1-3:1, for example 1:1, 1.2:1, 1.5:1, 1.8:1, 2:1, 2.3:1, 2.5:1, 2.8:1 or 3:1.

[0083] Preferably, in the preparation of the compound represented by formula VIII, 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.

[0084] Preferably, 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.

[0085] Preferably, 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.

[0086] Preferably, in the preparation of the compound represented by formula VIII, 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.

[0087] Preferably, in the preparation of the compound represented by formula VIII, 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.

[0088] Preferably, in the preparation of the compound represented by formula VIII, 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.

[0089] In another aspect, the present invention provides the use of the oxime ether-containing amidine compound as described above in preventing and controlling plant diseases.

[0090] The amidine compounds containing oxime ethers of the present invention have unexpectedly high fungicidal activity and have a good control effect on plant diseases.

[0091] In the present invention, the plant diseases include diseases of Oomycetes, Ascomycetes, Basidiomycetes or Deuteromycetes.

[0092] Preferably, 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.

[0093] Preferably, the plant diseases include wheat rust, wheat powdery mildew, wheat fusarium head blight, cucumber powdery mildew, cucumber downy mildew or soybean rust.

[0094] In another aspect, the present invention provides a fungicide composition, comprising an active component and a pesticide-acceptable carrier, wherein the active component is the amidine compound containing oxime ether as described above.

[0095] The fungicide composition of the present invention can be used in agriculture, forestry, sanitation and other fields.

[0096] Preferably, in the fungicide composition, 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%.

[0097] Preferably, the pesticidally acceptable carrier comprises a surfactant.

[0098] In the present invention, the surfactant is an ionic surfactant or a nonionic surfactant.

[0099] The surfactant includes an emulsifier, a dispersant or a wetting agent. The emulsifier can be polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene fatty amine and commercially available emulsifiers (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#). Dispersants include sodium lignin sulfonate, pull-open powder, calcium lignin sulfonate, methyl naphthalene sulfonic acid formaldehyde condensate, etc. Wetting agents include sodium lauryl sulfate, sodium dodecylbenzene sulfonate, sodium alkyl naphthalene sulfonate, etc.

[0100] Preferably, the pesticide-acceptable carrier comprises a solid carrier and / or a liquid carrier.

[0101] Preferably, 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. Liquid carriers include water and organic solvents. When water is used as a solvent or diluent, organic solvents can also be used as adjuvants 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 isopropanol, butanol, ethylene glycol, glycerol and cyclohexanol, etc.; and their ethers and esters; and ketones such as acetone, cyclohexanone, dimethylformamide and N-methyl-pyrrolidone.

[0102] In the preparation process of the fungicide composition, 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. Other auxiliary agents (such as adhesives, defoaming agents, oxidants, etc.) can also be added.

[0103] In another aspect, the present invention provides a method for controlling plant diseases, comprising: applying an effective dose of the fungicide composition as described above to the plant diseases to be controlled or to the medium in which the plant diseases are grown.

[0104] Preferably, the effective dose is 10-1000g per hectare, for example 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g, 600g, 700g, 800g, 900g or 1000g, preferably 20-500g per hectare.

[0105] The composition of the present invention 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. For example, 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.

[0106] For certain applications, such as in agriculture, one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers may be added to the fungicidal composition of the present invention, thereby producing additional advantages and effects.

[0107] Compared with the prior art, the present invention has the following beneficial effects:

[0108] The amidine compound containing oxime ether and having a structure shown in formula I of the present invention has a significant effect on preventing and controlling agricultural and forestry diseases, especially has a good prevention and control effect on cucumber powdery mildew and cucumber downy mildew. When the concentration of the amidine compound containing oxime ether is 10 ppm, the prevention and control effect on cucumber powdery mildew is ≥90%, and when the concentration is 100 ppm, the prevention and control effect on cucumber downy mildew is ≥90%. In addition, the preparation method thereof is simple and efficient, and is easy to be mass-produced, and has broad application prospects. DETAILED DESCRIPTION

[0109] The technical scheme of the present invention is further described below by specific implementation methods. Those skilled in the art should understand that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention. Unless otherwise specified in the embodiments and the present invention: when the compounds are characterized by nuclear magnetic resonance hydrogen spectrum test, the corresponding samples are dissolved in deuterated dimethyl sulfoxide (DMSO-d 6 ) or deuterated chloroform (CDCl 3 ), a 400 MHz nuclear magnetic resonance instrument was used to obtain hydrogen spectrum data, and the chemical shift unit was ppm (ie, δ: ppm); the eluent used for column chromatography purification was prepared according to the volume ratio of petroleum ether (abbreviated as PE): ethyl acetate (abbreviated as EA) as shown.

[0110] Synthesis Example

[0111] Example 1

[0112] Preparation of (E)-N'-(4-((1-phenyl-1H-oximino-3-yl)oxy)-2,5-dimethylphenyl)-N-ethyl-N-methylformamidine (Compound 2):

[0113]

[0114] Step 1: Synthesis of 1-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)ethan-1-one:

[0115] 1-Chloro-2,5-dimethyl-4-nitrobenzene (10g, 54.1mmol) and potassium carbonate (9.0g, 64.8mmol) were added to 40ml of DMF, heated to reflux, p-hydroxyacetophenone (7.35g, 54.1mmol) was added, and 5ml of toluene was added dropwise for water separation. After 6 hours, TLC showed that the reaction was complete, and the reaction solution was cooled to room temperature, and then water was added for quenching. Solids precipitated, the solids were washed with water, and the filter cake was obtained by suction filtration, and then ethanol was used for pulping. Finally, it was dried in an oven at 60°C to obtain 13.0g of brown solids with a yield of 82.8%.

[0116] Step 2: Synthesis of 1-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)ethan-1-one:

[0117] 1-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)ethane-1-one (5 g, 17.57 mmol) was added to 30 ml of anhydrous ethanol, and reduced iron powder (2.95 g, 52.72 mmol) was added. 10 ml of saturated aqueous ammonium chloride solution was added dropwise, and the reaction was refluxed. After 2 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, 30 ml of water and 50 ml of ethyl acetate were added, and the liquid was separated and extracted. The organic layer was taken, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA = 20:1) to obtain 2.84 g of yellow solid, with a yield of 63.53%.

[0118] Step 3: Synthesis of (E)-1-(4-(4-amino-2,5-dimethylphenoxy)phenyl)ethan-1-one O-methyloxime:

[0119] 1-[4-(2,5-dimethyl-4-aminophenoxy)phenyl[ethane-1-one (2.84 g, 11.18 mmol) was added to 30 ml of a mixed solvent of anhydrous ethanol and pyridine in a volume ratio of 10:1, and then methylhydroxylamine hydrochloride (1.03 g, 12.35 mmol) was added, and the mixture was heated under reflux for reaction. After 3 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, and ethanol and pyridine were distilled out under reduced pressure. Then 100 ml of water and 50 ml of ethyl acetate were added, and the organic layer was extracted, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=4:1) to obtain 2.20 g of light yellow solid, with a yield of 69.2%.

[0120] Step 4: Synthesis of ethyl (E)-N-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate:

[0121] (E)-1-(4-(4-Amino-2,5-dimethylphenoxy)phenyl)ethane-1-one O-methyloxime (0.30 g, 1.05 mmol), triethyl orthoformate (1.55 g, 10.5 mmol) and p-toluenesulfonic acid monohydrate (20 mg, 0.11 mmol) were added to a reaction flask, and the temperature was raised to reflux for reaction for 3 hours. The reaction solution was cooled to room temperature and distilled under reduced pressure until no liquid was dropped to obtain 360 mg of a yellow oil, which was directly carried out to the next step without separation.

[0122] Step 5: Synthesis of (E)-N-ethyl-N'-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)-N-methylformamide:

[0123] Ethyl (E)-N-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 1.05 mmol) was dissolved in 10 ml of dichloromethane, and methylethylamine (0.18 g, 3.15 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.16 g of compound 2 as a yellow oil with a yield of 59.3%.

[0124] Compound 2 1 HNMR(400MHz,DMSO)δ7.67(s,1H),7.62–7.58(m,2H),6.83–6.79(m,2H),6.75(s,1H),6.73(s,1H),3.8 8(s,3H),3.49(q,J=7.1Hz,2H),2.93(s,3H),2.14(s,3H),2.12(s,3H),2.02(s,3H),1.31–1.23(m,3H).

[0125] Example 2

[0126] Preparation of (E)-1-(4-(2,5-dimethyl-4-(((E)-pyrrolidin-1-ylmethylene)amino)phenoxy)phenyl)ethan-1-one O-methyloxime (Compound 11):

[0127]

[0128] Ethyl (E)-N-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 1.05 mmol) was dissolved in 10 ml of dichloromethane, and pyrrolidine (0.22 g, 3.15 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.23 g of compound 11 as a yellow oil with a yield of 61.07%.

[0129] Compound 11 1 H NMR(400MHz,DMSO)δ7.82(s,1H),7.66-7.55(m,2H),6.85-6.77(m,2H),6.74(s,1H),6.71(s, 1H),3.88(s,3H),3.48(m,4H),2.14(s,3H),2.13(s,3H),2.02(s,3H),1.89(d,J=15.6Hz,4H).

[0130] Example 3

[0131] Preparation of (E)-1-(4-(2,5-dimethyl-4-(((E)-piperidin-1-ylmethylene)amino)phenoxy)phenyl)ethan-1-one O-methyloxime (Compound 12):

[0132]

[0133] Ethyl (E)-N-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 1.05 mmol) was dissolved in 10 ml of dichloromethane, and piperidine (0.27 g, 3.15 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.25 g of compound 12 as a yellow oil with a yield of 63.07%.

[0134] Compound 12 1HNMR (400MHz, DMSO) δ7.61(d,J=1.4Hz,2H),7.59(d,J=2.1Hz,1H),6.85–6.77(m,2H),6.75(s,1H),6.72(s,1H),3.88(s, 3H), 3.49 (d, J = 11.0Hz, 4H), 2.14 (s, 3H), 2.12 (s, 3H), 2.02 (s, 3H), 1.63 (dt, J = 11.0, 5.2Hz, 2H), 1.52 (q, J = 6.0Hz, 4H).

[0135] Example 4

[0136] Preparation of (E)-N'-(4-(4-(((E)-1-(ethoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)-N-ethyl-N-methylformamide (Compound 14):

[0137]

[0138] Step 1: Synthesis of 1-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)ethan-1-one:

[0139] 1-Chloro-2,5-dimethyl-4-nitrobenzene (10g, 54.1mmol) and potassium carbonate (9.0g, 64.8mmol) were added to 40ml of DMF, heated to reflux, and p-hydroxyacetophenone (7.35g, 54.1mmol) was added, and then 5ml of toluene was added dropwise for fractionation. After 6 hours, TLC showed that the reaction was complete, and the reaction solution was cooled to room temperature, and then water was added for quenching. Solids precipitated, and then washed with water to remove DMF, and the filter cake was obtained by suction filtration, and then ethanol was used for pulping. Finally, it was dried in an oven at 60°C to obtain 13.0g of brown solids with a yield of 82.8%.

[0140] Step 2: Synthesis of 1-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)ethan-1-one:

[0141] 1-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)ethane-1-one (5 g, 17.57 mmol) was added to 30 ml of anhydrous ethanol, and reduced iron powder (2.95 g, 52.72 mmol) was added. 10 ml of saturated aqueous ammonium chloride solution was added dropwise, and the reaction was refluxed. After 2 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, 30 ml of water and 50 ml of ethyl acetate were added, and the liquid was separated and extracted. The organic layer was taken, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent was PE:EA=3:1) to obtain 2.84 g of yellow solid, with a yield of 63.53%.

[0142] Step 3: Synthesis of (E)-1-(4-(4-amino-2,5-dimethylphenoxy)phenyl)ethan-1-one O-ethyl oxime:

[0143] 1-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)ethane-1-one (3 g, 11.81 mmol) was added to 30 ml of a mixed solvent of anhydrous ethanol and pyridine in a volume ratio of 10:1, and then ethylhydroxylamine hydrochloride (1.26 g, 13.00 mmol) was added, and the mixture was heated to reflux for reaction. After 3 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, and ethanol and pyridine were distilled out under reduced pressure. Then 100 ml of water and 50 ml of ethyl acetate were added, and the organic layer was extracted, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=4:1) to obtain 2.30 g of light yellow solid, with a yield of 65.25%.

[0144] Step 4: Synthesis of ethyl (E)-N-(4-(((E)-1-(ethoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate:

[0145] (E)-1-(4-(4-amino-2,5-dimethylphenoxy)phenyl)ethane-1-one O-ethyl oxime (0.50 g, 1.68 mmol), triethyl orthoformate (2.48 g, 16.8 mmol) and p-toluenesulfonic acid monohydrate (32 mg, 0.17 mmol) were added to a reaction flask, and the temperature was raised to reflux for 3 hours. The reaction solution was cooled to room temperature and distilled under reduced pressure until no liquid was dropped to obtain 600 mg of a yellow oil, which was directly carried out to the next step without separation.

[0146] Step 5: Synthesis of (E)-N-ethyl-N'-(4-(((E)-1-(methoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)-N-methylformamide (Compound 14):

[0147] Ethyl (E)-N-(4-(((E)-1-(ethoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 0.85 mmol) was dissolved in 10 ml of dichloromethane, methylethylamine (0.15 g, 2.54 mmol) was added, and the temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, 30 ml of water was added, and the mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.21 g of yellow oil with a yield of 69.30%.

[0148] Compound 141 H NMR (400MHz, DMSO) δ7.64–7.57(m,2H),6.84–6.79(m,2H),6.76(s,1H),6.72(s,1H),4.14(q,J=7.0Hz,2H),4.03( q,J=7.1Hz,2H),2.94(s,3H),2.14(s,3H),2.13(s,3H),2.03(s,3H),1.24(t,J=7.0Hz,3H),1.16(t,J=6.8Hz,3H).

[0149] Example 5

[0150] Preparation of (E)-1-(4-(2,5-dimethyl-4-(((E)-pyrrolidin-1-ylmethylene)amino)phenoxy)phenyl)ethan-1-one O-ethyl oxime (Compound 23):

[0151]

[0152] Ethyl (E)-N-(4-(((E)-1-(ethoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 0.85 mmol) was dissolved in 10 ml of dichloromethane, pyrrolidine (0.20 g, 2.54 mmol) was added, and the temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, 30 ml of water was added, and the mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.21 g of yellow oil with a yield of 66.30%.

[0153] Compound 23 1 H NMR (400MHz, DMSO) δ7.82 (s, 1H), 7.66-7.56 (m, 2H), 6.83-6.76 (m, 2H), 6.73 (d, J = 11.6Hz, 2H), 4.14 (q, J = 7. 0Hz,2H),3.49(m,4H),2.14(s,3H),2.13(s,3H),2.02(s,3H),1.89(d,J=14.7Hz,4H),1.25(d,J=7.0Hz,3H).

[0154] Example 6

[0155] Preparation of (E)-1-(4-(2,5-dimethyl-4-(((E)-piperidin-1-ylmethylene)amino)phenoxy)phenyl)ethan-1-one O-ethyl oxime (Compound 24):

[0156]

[0157] Ethyl (E)-N-(4-(((E)-1-(ethoxyimino)ethyl)phenoxy)-2,5-dimethylphenyl)carboxylate (0.30 g, 0.85 mmol) was dissolved in 10 ml of dichloromethane, and pyrrolidine (0.22 g, 2.54 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 6 hours. The reaction solution was cooled to room temperature, 30 ml of water was added, and the mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.21 g of compound 24 as a yellow oil with a yield of 62.90%.

[0158] Compound 24 1 H NMR (400MHz, DMSO) δ7.61(s,2H),7.59(d,J=2.2Hz,1H),6.84–6.77(m,2H),6.75(s,1H),6.72(s,1H),4.14(q,J=7.0Hz,2H),3 .34(s,4H),2.14(s,3H),2.11(s,3H),2.02(s,3H),1.63(tt,J=6.3,3.8Hz,2H),1.52(q,J=5.8Hz,4H),1.24(t,J=7.0Hz,3H).

[0159] Example 7

[0160] Preparation of methyl (E)-2-(4-(4-(((E)-(ethyl(methyl)amino)methylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate (Compound 26):

[0161]

[0162] Step 1: Synthesis of 1,4-dimethyl-2-nitro-5-phenoxybenzene:

[0163] 1-Chloro-2,5-dimethyl-4-nitrobenzene (10 g, 54.1 mmol) and potassium carbonate (9.0 g, 64.8 mmol) were added to 40 ml of DMF, the temperature was raised to reflux, phenol (5.08 g, 54.1 mmol) was added, and the reaction was refluxed. After 6 hours, TLC showed that the reaction was complete, the reaction solution was cooled to room temperature, 150 ml of water was added, and the liquid was separated and extracted. The organic layer was taken, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent PE: EA = 10: 1) to obtain 7.88 g of yellow solid, with a yield of 60.05%.

[0164] Step 2: Synthesis of methyl 2-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)-2-oxoacetate:

[0165] 1,4-Dimethyl-2-nitro-5-phenoxybenzene (5 g, 20.57 mmol) was added to 40 ml of CH 2 Cl 2 In the mixture, the temperature was raised to reflux and AlCl 3 (8.20 g, 61.72 mmol), methyl 2-chloro-2-oxoacetate (2.76 g, 22.63 mmol), reflux reaction. After 8 hours, TLC showed that the reaction was complete, the reaction solution was cooled to room temperature, and the reaction solution was added dropwise to a beaker containing water while stirring. 2 Cl 2 The organic layer was separated and extracted with water, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA = 10:1) to obtain 5.59 g of green oil with a yield of 82.65%.

[0166] Step 3: Synthesis of methyl 2-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)-2-oxoacetate:

[0167] 2-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)-2-oxoacetate (6 g, 18.24 mmol) was added to 30 ml of anhydrous methanol, and reduced iron powder (3.06 g, 54.71 mmol) was added. 10 ml of saturated aqueous ammonium chloride solution was added dropwise, and the reaction was refluxed. After 2 hours, TLC showed that the reaction was complete. The mixture was filtered while hot to obtain a filtrate. The filtrate was added with 30 ml of water and 50 ml of ethyl acetate, and the mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=20:1) to obtain 3.96 g of a yellow solid with a yield of 72.56%.

[0168] Step 4: Synthesis of (E)-methyl 2-(4-(4-amino-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0169] Methyl 2-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)-2-oxoacetate (5 g, 16.72 mmol) was added to 30 ml of a mixed solvent of anhydrous methanol and pyridine in a volume ratio of 10:1, and then methylhydroxylamine hydrochloride (1.53 g, 18.39 mmol) was added, and the mixture was heated under reflux for reaction. After 3 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, and methanol and pyridine were distilled out under reduced pressure. Then 100 ml of water and 50 ml of ethyl acetate were added, and the organic layer was extracted, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 3.53 g of light yellow solid, with a yield of 64.28%.

[0170] Step 5: Synthesis of methyl (E)-2-(4-(4-((((E)-ethoxymethylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0171] (E)-2-(4-(4-amino-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetic acid methyl ester (0.50 g, 1.46 mmol), triethyl orthoformate (2.16 g, 14.6 mmol) and p-toluenesulfonic acid monohydrate (26 mg, 0.14 mmol) were added to a reaction flask, and the temperature was raised to reflux for reaction for 3 hours. The reaction solution was cooled to room temperature and distilled under reduced pressure until no liquid was dropped to obtain 560 mg of a yellow oil, which was directly carried out to the next step without separation.

[0172] Step 6: Synthesis of methyl ((E)-2-(4-(4-(((E)-(ethyl(methyl)amino)methylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0173] Methyl (E)-2-(4-(4-((((E)-ethoxymethylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate (0.30 g, 0.78 mmol) was dissolved in 10 ml of dichloromethane, and ethylmethylamine (0.14 g, 2.34 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 3 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.17 g of compound 26 as a brown oil with a yield of 55.56%.

[0174] Compound 26 1 HNMR (400 MHz, DMSO-d 6)δ7.47(d,J=8.4Hz,2H),7.21(s,1H),6.88(d,J=8.5Hz,2H),6.80(s,2H),4.03(q,J=7.1Hz, 2H),3.91(s,3H),3.86(s,3H),2.95(s,3H),2.14(s,3H),1.99(s,3H),1.17(t,J=7.1Hz,3H).

[0175] Example 8

[0176] Synthesis of methyl (E)-2-(4-(2,5-dimethyl-4-(((E)-piperidin-1-ylmethylene)amino)phenoxy)phenyl)-2-(methoxyimino)acetate (Compound 30):

[0177]

[0178] Methyl (E)-2-(4-(4-((((E)-ethoxymethylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate (0.30 g, 0.78 mmol) was dissolved in 10 ml of dichloromethane, and piperidine (0.20 g, 2.34 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 3 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.24 g of compound 30 as a brown oil with a yield of 72.60%.

[0179] Compound 30 1 HNMR (400MHz, DMSO) δ7.79(d,J=8.3Hz,1H),7.48(d,J=8.1Hz,2H),7.21(s,1H),6.88(d,J=8.3Hz,2H),6.6 7(s,1H),4.32(t,J=4.9Hz,4H),3.92(s,3H),3.87(s,3H),2.33(s,3H),2.14(s,3H),1.98(d,J=6.4Hz,6H).

[0180] Example 9

[0181] Preparation of ethyl ((E)-2-(4-(4-(((E)-(ethyl(methyl)amino)methylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate (Compound 33):

[0182]

[0183] Step 1: Synthesis of 1,4-dimethyl-2-nitro-5-phenoxybenzene:

[0184] 1-Chloro-2,5-dimethyl-4-nitrobenzene (10 g, 54.1 mmol) and potassium carbonate (9.0 g, 64.8 mmol) were added to 40 ml of DMF, the temperature was raised to reflux, phenol (5.08 g, 54.1 mmol) was added, and the reaction was refluxed. After 6 hours, TLC showed that the reaction was complete, the reaction solution was cooled to room temperature, 150 ml of water was added, and the liquid was separated and extracted. The organic layer was taken, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent PE: EA = 10: 1) to obtain 7.88 g of yellow solid, with a yield of 60.05%.

[0185] Step 2: Synthesis of methyl 2-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)-2-oxoacetate:

[0186] 1,4-Dimethyl-2-nitro-5-phenoxybenzene (5 g, 20.57 mmol) was added to 40 ml of CH 2 Cl 2 In the mixture, the temperature was raised to reflux and AlCl 3 (8.20 g, 61.72 mmol), methyl 2-chloro-2-oxoacetate (2.76 g, 22.63 mmol), reflux reaction. After 8 hours, TLC showed that the reaction was complete, the reaction solution was cooled to room temperature, and the reaction solution was added dropwise to a beaker containing water while stirring. 2 Cl 2 The organic layer was separated and extracted with water, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA = 10:1) to obtain 5.59 g of green oil with a yield of 82.65%.

[0187] Step 3: Synthesis of ethyl 2-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)-2-oxoacetate:

[0188] 2-(4-(2,5-dimethyl-4-nitrophenoxy)phenyl)-2-oxoacetate (6 g, 18.24 mmol) was added to 30 ml of anhydrous ethanol, and reduced iron powder (3.06 g, 54.71 mmol) was added. 10 ml of saturated aqueous ammonium chloride solution was added dropwise, and the reaction was refluxed. After 2 hours, TLC showed that the reaction was complete. The mixture was filtered while hot to obtain a filtrate. The filtrate was added with 30 ml of water and 50 ml of ethyl acetate, and the mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=20:1) to obtain 3.58 g of a yellow solid with a yield of 62.80%.

[0189] Step 4: Synthesis of (E)-ethyl 2-(4-(4-amino-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0190] Ethyl 2-(4-(2,5-dimethyl-4-aminophenoxy)phenyl)-2-oxoacetate (5 g, 15.97 mmol) was added to 30 ml of a mixed solvent of anhydrous ethanol and pyridine in a ratio of 10:1, and then methylhydroxylamine hydrochloride (1.46 g, 17.57 mmol) was added, and the mixture was heated to reflux for reaction. After 3 hours, TLC showed that the reaction was complete. The reaction solution was cooled to room temperature, and ethanol and pyridine were distilled out under reduced pressure. Then 100 ml of water and 50 ml of ethyl acetate were added, and the organic layer was extracted, washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 3.50 g of light yellow solid, with a yield of 64.10%.

[0191] Step 5: Synthesis of ethyl (E)-2-(4-(4-((((E)-ethoxymethylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0192] (E)-2-(4-(4-amino-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetic acid ethyl ester (0.50 g, 1.46 mmol), triethyl orthoformate (2.16 g, 14.6 mmol) and p-toluenesulfonic acid monohydrate (26 mg, 0.14 mmol) were added to the reaction flask, and the temperature was raised to reflux for reaction for 3 hours. The reaction solution was cooled to room temperature and distilled under reduced pressure until no liquid was dropped to obtain 580 mg of a yellow oil, which was directly carried out to the next step without separation.

[0193] Step 6: Synthesis of ethyl ((E)-2-(4-(4-(((E)-(ethyl(methyl)amino)methylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate:

[0194] Ethyl (E)-2-(4-(4-((((E)-ethoxymethylene)amino)-2,5-dimethylphenoxy)phenyl)-2-(methoxyimino)acetate (0.30 g, 0.75 mmol) was dissolved in 10 ml of dichloromethane, and ethylmethylamine (0.13 g, 2.26 mmol) was added. The temperature was raised to reflux for reaction. The reaction was completed after 3 hours. The reaction solution was cooled to room temperature, and 30 ml of water was added. The mixture was separated and extracted. The organic layer was washed with saturated sodium chloride water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: PE:EA=3:1) to obtain 0.19 g of compound 33 as a brown oil with a yield of 61.69%.

[0195] Compound 33 1 H NMR (400 MHz, DMSO-d 6 )δ7.68(d,J=9.2Hz,1H),7.49–7.43(m,2H),6.87(dd,J=8.8,1.9Hz,2H),6.78(s,1H),6.72(s,1H),4.35(q,J=7.1Hz,2H),4.03(q ,J=7.1Hz,2H),3.91(d,J=1.4Hz,3H),2.94(d,J=5.7Hz,3H),2.13(s,3H),2.01(s,3H),1.32–1.25(m,3H),1.13(t,J=7.1Hz,3H).

[0196] In addition to the compounds described above, the compounds in Table 1 are prepared or can be prepared by methods similar to those in Synthesis Examples 1-9. The following Table 2 gives the NMR data of some of the compounds synthesized with reference to Synthesis Examples 1-8.

[0197] Table 2

[0198]

[0199]

[0200]

[0201] Preparation Example 1

[0202] In this example, a fungicide preparation is prepared from the prepared amidine compound containing oxime ether, and a suspension having a concentration of 30% of compound 2 is prepared according to the mass ratio.

[0203] Table 3

[0204] Compound 2 30％ Ethylene glycol 10％ Nonylphenol polyglycol ether 6％ Sodium lignin sulfonate 10％ Carboxymethyl cellulose 1％ 37% formaldehyde aqueous solution 0.2％ 75% silicone oil aqueous solution 0.8％ water Top up to 100%

[0205] 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.

[0206] The 30% suspension concentrates of other compounds of the present application are prepared according to the preparation method of the 30% suspension concentrate of the above compound 2, and the obtained suspension concentrate can be diluted with water to obtain a dilution of the desired concentration when necessary.

[0207] Biological Activity Test Example

[0208] The compounds of the present invention obtained above were tested on various pathogens. Unless otherwise specified, in the examples and the present invention: the sample preparation method is to weigh 10 mg of the original drug of the sample to be tested, dissolve it with 1 mL DMF, prepare a 10000 ppm mother solution, and dilute the mother solution with 0.05% Tween-80 water to the required concentration for activity testing.

[0209] Test Example 1 fungicidal activity of the compound against cucumber powdery mildew

[0210] In this example, the effect of the prepared amidine compounds containing oxime ether on the prevention and treatment of cucumber powdery mildew (Erysiphecichoracearum) was determined as follows:

[0211] 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 amount 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. The two-leaf cucumber seedlings cultured in the greenhouse are used as the test host plants of cucumber powdery mildew (Erysiphe cichoracearum). The compound of the present invention 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. After inoculation, 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%). After the test material is cultured for 24 hours, it is moved to the greenhouse for culture. After the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated. The survey results are expressed on a scale of 100 to 0, with "100" representing no disease and "0" representing the most severe degree of disease.

[0212] The control effect of compounds 2, 14, 15, 24 and 26 on cucumber powdery mildew at a concentration of 100 ppm was ≥ 90%.

[0213] According to the same method, the compounds 2, 14 and KC of the present application were screened in parallel. The results are shown in Table 4.

[0214] Table 4 Control effect of compounds 2, 14 and KC on cucumber powdery mildew

[0215]

[0216] Test Example 2 fungicidal activity of the compound against cucumber downy mildew

[0217] In this example, the effect of the prepared amidine compounds containing oxime ether on the prevention and treatment of cucumber downy mildew (Pseudoperonospora cubensis) was determined as follows:

[0218] 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 amount 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. The two-leaf cucumber seedlings cultured in the greenhouse are used as the test host plants of cucumber downy mildew (Pseudoperonospora cubensis). The compound of the present invention 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. After inoculation, 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%). After the test material is cultured for 24 hours, it is moved to the greenhouse for culture. After the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated. The results of the survey were expressed in accordance with "A Manual of Assessment Keys for Plant Diseases" compiled by the American Society of Plant Pathology, using a scale of 100 to 0, with "100" representing no disease and "0" representing the most severe degree of disease.

[0219] The control effect of compounds 21 and 29 on cucumber downy mildew at a concentration of 100 ppm is ≥90%.

[0220] The present invention illustrates the amidine compounds containing oxime ethers and the preparation method and application thereof through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. An amidine compound containing an oxime ether, characterized in that: The amidine compound containing oxime ether has a structure shown in Formula I: in: X is selected from CH2, NH, O or S; R 1 is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C3-C8 cycloalkyl, aryl, C1-C12 haloalkyl or C1-C12 haloalkoxy; R 2 Selected from hydrogen or C1-C6 alkyl; R 3 is selected from C1-C8 alkyl, C1-C8 haloalkyl or C3-C6 cycloalkylC1-C6 alkyl; or R 2 and R 3 Together with the nitrogen atom to which they are attached, they form a three- to six-membered saturated cyclic group which may optionally contain an oxygen atom or a sulfur atom; R 4 is selected from hydrogen, halogen, C1-C6 alkyl or C1-C6 haloalkyl; R 5 is selected from hydrogen or methyl; R 6 is selected from hydrogen or methyl; R 7 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or C1-C6 haloalkoxy; R 8 is selected from hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C3-C8 cycloalkyl, aryl, C1-C6 haloalkyl, C1-C6 haloalkoxy, CO2CH3 or CO2C2H5; R 9 Selected from hydrogen, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl or aryl.

2. The amidine compound containing oxime ether according to claim 1, characterized in that The amidine compound containing oxime ether has a structure shown in Formula II: in: X is selected from CH2, NH, O or S; R 1 Selected from hydrogen; R 2 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; R 3 is selected from methyl, ethyl, hydroxyethyl, 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; or R 2 and R 3 Together with the nitrogen atom to which they are attached, they form pyrrole, piperidine, or morpholine; R 4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, difluoromethyl or trifluoromethyl; R 5 is selected from hydrogen or methyl; R 6 is selected from hydrogen or methyl; R 7 is selected from hydrogen, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy; R 8 Selected from hydrogen, C1-C6 alkyl, CO2CH3 or CO2C2H5; R 9 Selected from hydrogen, C1-C6 alkyl or C3-C8 cycloalkyl.

3. The amidine compound containing oxime ether according to claim 2, characterized in that: X is selected from O; R 1 Selected from hydrogen; R 2 is selected from hydrogen or methyl; R 3 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 or 2-ethylhexyl; or R 3 and R 2 Together with the nitrogen atom to which they are attached, they form pyrrole, piperidine or morpholine R 4 Selected from hydrogen; R 5 is selected from hydrogen or methyl; R 6 is selected from hydrogen or methyl; R 7 Selected from hydrogen; R 8 Selected from hydrogen, C1-C6 alkyl, CO2CH3 or CO2C2H5; R 9 Selected from hydrogen, C1-C6 alkyl or C3-C8 cycloalkyl.

4. The amidine compound containing oxime ether according to any one of claims 1 to 3, characterized in that: The amidine compound containing oxime ether is any one of the following compounds:

5. Use of the amidine compound containing oxime ether according to any one of claims 1 to 4 in preventing and controlling plant diseases.

6. A fungicide composition, characterized in that: The fungicide composition comprises an active component and a pesticide acceptable carrier, wherein the active component is an amidine compound containing an oxime ether as claimed in any one of claims 1 to 4; Preferably, in the fungicide composition, the weight percentage of the active ingredient is 1-99%.

7. A method for preventing and controlling plant diseases, characterized in that The method comprises: applying an effective dose of the fungicide composition according to claim 6 to the plant disease to be controlled or the medium in which it grows; Preferably, the effective dose is 10-1000 g per hectare; more preferably, the effective dose is 20-500 g per hectare.

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