A benzoyloxy-substituted oxime derivative and its application

Abstract

The present invention relates to a benzoyloxy-substituted oxime derivative and application thereof, wherein the benzoyloxy-substituted oxime derivative is as shown in formula (I), wherein A is phenyl, T is tetrazolyl, R 1 is phenyl or optionally substituted by 1, 2, 3, 4 or 5 groups selected from halogen, cyano, nitro, hydroxyl, C 1‑6 Alkyl, C 1‑6 Alkoxy, halogenated C 1‑6 Phenyl substituted by alkyl or the like; the oxime derivatives of the present invention have the advantages of small dosage and high prevention effect on cucumber downy mildew, and can be further developed and used as fungicides.

Description

Technical Field

[0001] The present invention relates to the field of pesticide fungicides, and in particular, to a novel benzoyloxy-substituted oxime derivative and a preparation method thereof, a composition comprising the oxime derivative, and the use of the oxime derivative and the composition comprising the oxime derivative as a control agent for plant diseases, especially plant diseases caused by plant pathogenic fungi, in agriculture, forestry or horticulture. Background Art

[0002] my country is a large agricultural country with little arable land and a large population. Food problem is one of the important problems that we need to solve urgently. Plant fungal diseases have always been one of the restrictive factors in the production and storage of food crops, causing serious losses to the development stage, nutritional value, and limited shelf life of the products. At present, the prevention and control of plant diseases mainly depends on the use of chemical pesticides. Chemical pesticides are favored by people because of their small dosage and quick effect. However, due to the fine development of the chemical industry and the farmers' inaccurate grasp of the drug application technology, they blindly increase the dosage in pursuit of the effect, resulting in the increasingly serious problems of "drug resistance, rampant pesticide residues, and pesticide residues". Therefore, the research and development of new pesticides with high efficiency, low toxicity, and low residue that can effectively control harmful organisms has become the primary goal of current pesticide creation.

[0003] JP2011012088A, CN108947964A and CN109305964A report the protective effects of various types of oxime compounds on plant fungal diseases, while the benzoyloxy-substituted oxime derivatives involved in the present invention are not specifically disclosed. Summary of the invention

[0004] The present invention relates to a novel benzoyloxy-substituted oxime derivative and a preparation method thereof, a composition comprising the oxime derivative, and the use of the oxime derivative and the composition comprising the oxime derivative as a fungicide in agriculture, forestry or horticulture. The benzoyloxy-substituted oxime derivative of the present invention has excellent prevention effect on diseases caused by plant pathogenic fungi, especially cucumber downy mildew, at low concentrations, and can be developed as a novel fungicide.

[0005] Specifically:

[0006] In one aspect, the present invention relates to a compound, which is a compound represented by formula (I) or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of the compound represented by formula (I):

[0007]

[0008] in:

[0009] R1 is optionally substituted by 1, 2, 3, 4 or 5 groups selected from halogen, cyano, nitro, hydroxyl, carboxyl, amino, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkylthio, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C(=O)C 1-6 Alkyl, -OC(=O)C 1-6 Alkyl or -C(=O)C 1-6 Alkoxy substituted phenyl;

[0010] A is

[0011] R a , R b , R c , R d and R e are independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy or halogenated C 1-6 Alkoxy;

[0012] T is

[0013] R f and R g are independently hydrogen or C 1-6 alkyl.

[0014] In some technical solutions, R 1 is optionally substituted by 1, 2, 3, 4 or 5 groups selected from halogen, cyano, nitro, hydroxyl, carboxyl, amino, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 1-4 Alkylthio, halo 1-4 Alkylthio, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -C(=O)C 1-4 Alkyl, -OC(=O)C 1-4 Alkyl or -C(=O)C 1-4 Alkoxy substituted phenyl.

[0015] In other technical solutions, R 1is optionally substituted by 1, 2, 3, 4 or 5 groups selected from fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, amino, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -C(CH3)3, -CH2Cl, -CH2F, -CHF2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)2, -OCH2CH2CH2CH3, -OC(CH3)3, -OCH2Cl, -OCH2F, -OCH F2, -OCF3, -OCH2CF3, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH(CH3)2, -SCH2CH2CH2CH3, -SC(CH3)3, -SCF3, -SCH2CF3, -NHCH3, -NH CH2CH3, -N(CH3)2, -N(CH2CH3)2, -C(=O)CH3, -C(=O)CH2CH3, -OC(=O)CH3, -OC(=O)CH2CH3, -C(=O)OCH3 or -C(=O)OCH2CH3 substituted phenyl.

[0016] In some other technical solutions, R 1 for

[0017]

[0018] In some technical solutions, A is

[0019] Among them, R a , R b , R c , R d and R e are independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halogenated C 1-4 Alkoxy.

[0020] In some other technical solutions, A is

[0021] Among them, R a , R b , R c , R d and R eEach is independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, -CH3, -CF3, -OCH3 or -OCF3.

[0022] In some technical solutions, T is

[0023] Among them, R f and R g are independently hydrogen or C 1-4 alkyl.

[0024] In some other technical solutions, T is

[0025] Among them, R f and R g Each is independently hydrogen, -CH3 or -CH2CH3.

[0026] In some technical solutions, the present invention provides a compound, which is a compound represented by formula (II) or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of the compound represented by formula (II):

[0027]

[0028] Among them, R 1 Has the meaning described in the present invention.

[0029] In some other technical solutions, the present invention provides a compound, which is a compound represented by formula (II) or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of the compound represented by formula (II):

[0030] Among them, R 1 is optionally substituted by 1 or 2 groups selected from halogen, cyano, nitro, hydroxy, carboxyl, amino, C 1-6 Alkyl or halogenated C 1-6 Alkyl substituted phenyl.

[0031] In other technical solutions, the present invention provides a compound, which is a compound represented by formula (II) or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of the compound represented by formula (II):

[0032] Among them, R 1 is optionally substituted by 1 or 2 groups selected from halogen, cyano, nitro, hydroxy, carboxyl, amino, C 1-4 Alkyl or halogenated C 1-4 Alkyl substituted phenyl.

[0033] In yet other technical solutions, the present invention provides a compound, which is a compound represented by formula (II) or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of the compound represented by formula (II):

[0034] Among them, R 1 It is phenyl which is optionally substituted by 1 or 2 groups selected from fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, carboxyl, amino, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -C(CH3)3, -CH2Cl, -CH2F, -CHF2, -CF3 or -CH2CF3.

[0035] represents the (Z) isomer, (E) isomer or a mixture of the (Z) isomer and the (E) isomer of the compound represented by formula (I); wherein the (Z) isomer of the compound represented by formula (I) is represented by formula (I-1):

[0036]

[0037] The (E) isomer of the compound represented by formula (I) is represented by formula (I-2):

[0038]

[0039] represents the (Z) isomer, (E) isomer or a mixture of the (Z) isomer and the (E) isomer of the compound represented by formula (II); wherein the (Z) isomer of the compound represented by formula (II) is represented by formula (II-1):

[0040]

[0041] The (E) isomer of the compound represented by formula (II) is formula (II-2):

[0042]

[0043] Among them, the (Z) isomer, (E) isomer, and mixtures of (Z) isomers and (E) isomers shown in formula (I) and formula (II) are all included in the present invention. The (Z) isomer, (E) isomer, or mixtures of (Z) isomers and (E) isomers shown in formula (I) or formula (II) can be separated and identified by conventional separation methods, such as column chromatography, high performance liquid chromatography, single crystal diffraction, and nuclear magnetic resonance hydrogen spectroscopy.

[0044] In some technical solutions, the present invention provides a compound, which is a compound represented by formula (II-1) or a nitrogen oxide, stereoisomer or salt thereof of a compound represented by formula (II-1):

[0045]

[0046] Among them, R 1 Has the meaning described in the present invention.

[0047] In some other technical solutions, the present invention provides a compound, which is a compound represented by formula (II-1) or a nitrogen oxide, stereoisomer or salt thereof of a compound represented by formula (II-1):

[0048] Among them, R 1 is optionally substituted by 1 or 2 groups selected from halogen, cyano, nitro, hydroxy, carboxyl, amino, C 1-6 Phenyl substituted with alkyl or halogenated C1-6 alkyl.

[0049] In other technical solutions, the present invention provides a compound, which is a compound represented by formula (II-1) or a nitrogen oxide, stereoisomer or salt thereof of a compound represented by formula (II-1):

[0050] Among them, R 1 is optionally substituted by 1 or 2 groups selected from halogen, cyano, nitro, hydroxy, carboxyl, amino, C 1-4 Alkyl or halogenated C 1-4 Alkyl substituted phenyl.

[0051] In yet other technical solutions, the present invention provides a compound, which is a compound represented by formula (II-1) or a nitrogen oxide, stereoisomer or salt thereof of a compound represented by formula (II-1):

[0052] Among them, R 1 It is phenyl which is optionally substituted by 1 or 2 groups selected from fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, carboxyl, amino, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -C(CH3)3, -CH2Cl, -CH2F, -CHF2, -CF3 or -CH2CF3.

[0053] In some technical solutions, the present invention provides a compound, which is a compound having one of the following structures or a nitrogen oxide, salt, (Z) isomer, (E) isomer or a mixture of (Z) isomer and (E) isomer of a compound having one of the following structures:

[0054]

[0055]

[0056]

[0057] In another aspect, the present invention provides a composition comprising at least one compound of the present invention and an adjuvant commonly used in pesticides.

[0058] In yet another aspect, the present invention provides use of the compound or composition of the present invention as a plant disease control agent in agriculture, forestry or horticulture.

[0059] In another aspect, the present invention provides a method for preventing and controlling plant diseases, comprising: applying an effective amount of the compound of the present invention or a composition comprising an effective amount of the compound of the present invention to plants or plant growth environments by spraying, injecting, pouring, etc. before or after the germination of the plant disease.

[0060] Furthermore, the plant diseases described in the present invention are caused by pathogenic fungi.

[0061] Detailed description of the invention

[0062] Definitions and general terms

[0063] Certain embodiments of the present invention are now described in detail, examples of which are illustrated by the accompanying structural formula and chemical formula. The present invention is intended to cover all substitutions, modifications and equivalent technical solutions, which are all included in the scope of the present invention as defined in the claims. It should be appreciated by those skilled in the art that many methods and materials similar or equivalent to those described in the present invention can be used to practice the present invention. The present invention is by no means limited to the methods and materials described in the present invention. In the event that one or more of the combined documents, patents and similar materials are different from or contradictory to the present application (including but not limited to defined terms, term applications, described technologies, etc.), the present application shall prevail.

[0064] It should be further appreciated that certain features of the invention, which for clarity are described in multiple separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which for brevity are described in a single embodiment, may also be provided separately or in any suitable sub-combination.

[0065] Unless otherwise specified, all technical terms used in the present invention have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. All patents and publications related to the present invention are incorporated herein by reference in their entirety.

[0066] Unless otherwise indicated, the following definitions used in the present invention shall apply. For purposes of the present invention, chemical elements are consistent with the Periodic Table of the Elements, CAS version, and Handbook of Chemistry and Physics, 75th edition, 1994. In addition, general principles of organic chemistry can be found in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007, the entire contents of which are incorporated herein by reference.

[0067] Unless otherwise specified or there is a clear conflict in context, the articles "a", "an", and "the" as used herein are intended to include "at least one" or "one or more". Therefore, these articles as used herein refer to articles that refer to one or more than one (i.e., at least one) object. For example, "a component" refers to one or more components, i.e., there may be more than one component contemplated for use or use in the implementation of the described embodiment.

[0068] The term “comprise” or “include” is an open expression, that is, including the contents specified in the present invention but not excluding other contents.

[0069] "Stereoisomers" refer to compounds that have the same chemical constitution but differ in the way the atoms or groups are arranged in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotamers), geometric isomers (cis / trans) isomers, atropisomers, and the like.

[0070] "Enantiomers" refer to two non-superimposable isomers of a compound that are mirror images of each other.

[0071] "Diastereoisomers" refer to stereoisomers that have two or more chiral neutrals and whose molecules are not mirror images of each other. Diastereoisomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivity. Diastereomeric mixtures can be separated by high-resolution analytical procedures such as electrophoresis and chromatography, for example HPLC.

[0072] The stereochemical definitions and conventions used in the present invention generally follow those described in SP Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994.

[0073] Many organic compounds exist in optically active forms, i.e. they have the ability to rotate the plane of plane polarized light. When describing an optically active compound, the prefixes D and L or R and S are used to indicate the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are the symbols used to designate the rotation of plane polarized light caused by the compound, where (-) or l indicates that the compound is left-handed. Compounds prefixed with (+) or d are right-handed. A specific stereoisomer is an enantiomer, and a mixture of such isomers is called a mixture of enantiomers. A 50:50 mixture of enantiomers is called a racemic mixture or racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.

[0074] Any asymmetric atom (e.g., carbon, etc.) of the compounds disclosed herein can exist in a racemic or enantiomerically enriched form, such as in the (R)-, (S)-, or (R,S)-configuration. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess in terms of the (R)- or (S)-configuration.

[0075] Depending on the choice of starting materials and process, the compounds of the invention may exist in the form of one of the possible isomers or a mixture thereof, such as a racemate and a diastereomeric mixture (depending on the number of asymmetric carbon atoms). Optically active (R)- or (S)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituents may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents may be in the cis or trans configuration.

[0076] Any resulting mixture of stereoisomers can be separated into the pure or substantially pure geometric isomers, enantiomers, diastereomers on the basis of the differences in the constituent physicochemical properties, for example, by chromatography and / or fractional crystallization.

[0077] Any resulting racemate of the final product or intermediate can be separated into optical antipodes by known methods by methods familiar to those skilled in the art, such as by separation of the diastereoisomeric salts thereof obtained. The racemic product can also be separated by chiral chromatography, such as high performance liquid chromatography (HPLC) using a chiral adsorbent. In particular, enantiomers can be prepared by asymmetric synthesis.

[0078] As described herein, the compounds of the present invention may be optionally substituted with one or more substituents, such as the general formula compounds above, or as specific examples in the embodiments, subclasses, and classes of compounds encompassed by the present invention. It should be understood that the term "optionally substituted" is used interchangeably with the term "substituted or unsubstituted". In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced by a specific substituent. Unless otherwise indicated, an optional substituent group may be substituted at each substitutable position of the group. When more than one position in a given structural formula can be substituted by one or more substituents selected from a specific group, the substituents may be substituted at each position in the same or different manner. Specifically, examples of "one or more" refer to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. The substituents may be, but are not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxy, nitro, amino, carboxyl, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxy-substituted alkyl, hydroxy-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkylacyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylacyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, amide, sulfonyl, aminosulfonyl and the like.

[0079] In addition, it should be noted that, unless explicitly stated otherwise, the description methods used in the present invention, "each... is independently" and "... are each independently" and "... are independently" can be interchanged and should be understood in a broad sense, which can mean that in different groups, the specific options expressed by the same symbols do not affect each other, or that in the same group, the specific options expressed by the same symbols do not affect each other.

[0080] In various parts of this specification, substituents of compounds disclosed in the present invention are disclosed according to group types or ranges. It is particularly noted that the present invention includes each independent subcombination of the individual members of these group types and ranges. For example, the term "C1-C6 alkyl" or "C 1-6 "Alkyl" specifically refers to methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl and C6 alkyl as disclosed independently.

[0081] The term "alkyl" or "alkyl group" used in the present invention refers to a saturated straight or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms; wherein the alkyl group is optionally substituted with one or more substituents described in the present invention. Unless otherwise specified, the alkyl group contains 1-20 carbon atoms. In one embodiment, the alkyl group contains 1-12 carbon atoms; in one embodiment, the alkyl group contains 1-8 carbon atoms; in another embodiment, the alkyl group contains 1-6 carbon atoms; in another embodiment, the alkyl group contains 1-4 carbon atoms; in another embodiment, the alkyl group contains 1-3 carbon atoms.

[0082] Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), n-butyl (n-Bu, -CH2CH2CH2CH3), Pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), and the like.

[0083] The term "alkoxy" means an alkyl group attached to the rest of the molecule via an oxygen atom, wherein the alkyl group has the meaning as described herein. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH3), ethoxy (EtO, -OCH2CH3), 1-propoxy (n-PrO, n-propoxy, -OCH2CH2CH3), 2-propoxy (i-PrO, i-propoxy, -OCH(CH3)2), and the like.

[0084] The term "alkylthio" means an alkyl group attached to the rest of the molecule via a sulfur atom, wherein the alkyl group has a meaning as described herein. Examples of alkylthio groups include, but are not limited to, methylthio (MeS, -SCH3), ethylthio (EtS, -SCH2CH3), and the like.

[0085] The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0086] The term "haloalkyl" means an alkyl group substituted with one or more halogen atoms, such examples include, but are not limited to, -CF3, -CHF2, -CH2Cl, -CH2CF3, -CH2CHF2, -CH2CH2CF3 and the like.

[0087] The term "haloalkoxy" means an alkoxy group substituted with one or more halogen atoms, such examples include, but are not limited to, -OCF3, -OCHF2, -OCHCl2, -OCH2CHF2, -OCH2CHCl2, -OCH(CH3)CHF2 and the like.

[0088] The term "haloalkylthio" means an alkylthio group substituted with one or more halogen atoms, such examples include, but are not limited to, -SCF3, -SCH2CHF2 and the like.

[0089] The term "cyano" refers to -CN.

[0090] The term "hydroxy" refers to -OH.

[0091] The term "nitro" refers to -NO2.

[0092] The term "carboxyl" refers to -COOH.

[0093] The term "amino" refers to -NH2.

[0094] Salts of the compounds of the present invention include those derived from alkali metals or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium and salts of the formula N+(R A R B R C RD ) of an ammonium cation, wherein R A , R B , R C and R D Independently selected from hydrogen, C1-C6 alkyl and C1-C6 hydroxyalkyl. Salts of the compounds of the present invention can be prepared by treating the compounds of the present invention with a metal hydroxide (e.g., sodium hydroxide) or an amine (e.g., ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine).

[0095] When the compounds of the present invention contain a basic moiety, acceptable salts may be formed from organic and inorganic acids such as acetic acid, propionic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malonic acid, mandelic acid, malic acid, phthalic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, naphthalenesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, camphorsulfonic acid, and similar known acceptable acids.

[0096] Compositions and preparations of the compounds of the present invention

[0097] The compounds of the present invention can generally be used as fungicidal active ingredients in compositions or preparations, and usually also include adjuvants commonly used in pesticides; the adjuvants commonly used in pesticides include surfactants and / or carriers.

[0098] The above-mentioned surfactant can be any surfactant known in the field of pesticide formulations. In the present invention, it is preferably one or more of an emulsifier, a dispersant and a wetting agent.

[0099] The other carriers except the above-mentioned surfactants can be various carriers known in the field of pesticide formulations, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, and synthetic carriers. Specifically, for example: one or more of white carbon black, kaolin, diatomaceous earth, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, amine fertilizer, a mixture of urea and amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, a mixture of anhydrous potassium carbonate and anhydrous potassium bicarbonate, and a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.

[0100] The emulsifier may be any emulsifier known in the field of pesticide formulations. Specifically, the emulsifier may be one or more of calcium dodecylbenzene sulfonate, triphenyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, alkylphenol polyoxyethylene polyoxypropylene ether, fatty amine, ethylene oxide adduct of fatty amide, fatty acid polyoxyethylene ester, rosin acid ethylene oxide adduct, polyol fatty acid ester and ethylene oxide adduct thereof, styrylphenyl polyoxyethylene ether, alkylphenol formaldehyde resin polyoxyethylene ether, terminal hydroxyl polyoxyethylene polyoxypropylene ether, styrylphenol formaldehyde resin polyoxyethylene polyoxypropylene ether and castor oil polyoxyethylene ether.

[0101] The above-mentioned dispersant can be various dispersants known in the field of pesticide formulations. Specifically, the dispersant is one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalenesulfonic acid formaldehyde condensate sodium salt, rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, terminal hydroxyl polyoxyethylene polyoxypropylene ether block copolymer, triphenyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignin sulfonate sodium salt.

[0102] The wetting agent can be any wetting agent known in the field of pesticide formulations. Specifically, the wetting agent can be one or more of sodium dodecyl sulfate, sodium secondary alkyl sulfate, sodium dodecylbenzene sulfonate, fatty alcohol polyoxyethylene ether, alkyl naphthalene sulfonate, and alkylphenol resin polyoxyethylene ether sulfate.

[0103] According to the fungicide composition of the present invention, the fungicide composition may also contain various formulation adjuvants commonly used in the field of pesticide formulations. Specifically, the formulation adjuvant may be one or more of a solvent, a co-solvent, a thickener, an antifreeze agent, an encapsulating material, a protective agent, a defoaming agent, a disintegrant, a stabilizer, a preservative and a binder.

[0104] The above-mentioned solvent may be any solvent known in the field of pesticide formulations. Specifically, the solvent may be one or more of an organic solvent, vegetable oil, mineral oil, solvent oil and water.

[0105] The organic solvent includes one or more of N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethyldecylamide, N,N-dimethylformamide, trimethylbenzene, tetramethylbenzene, xylene, toluene, octane, heptane, methanol, isopropanol, n-butanol, tetrahydrofurfuryl alcohol, tributyl phosphate, 1,4-dioxane and cyclohexanone.

[0106] The vegetable oil includes one or more of methylated vegetable oil, rosin-based vegetable oil, turpentine, epoxidized soybean oil, soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine nut oil.

[0107] The mineral oil includes one or more of liquid wax, motor oil, kerosene and lubricating oil.

[0108] At the same time, the above solvents can also be used as co-solvents.

[0109] The antifreeze agent may be any antifreeze agent known in the field of pesticide formulations. In the present invention, the antifreeze agent is preferably one or more of ethylene glycol, propylene glycol, glycerol and urea.

[0110] The thickener may be any thickener known in the field of pesticide formulations. Specifically, the thickener may be one or more of xanthan gum, polyvinyl alcohol, polypropylene alcohol, polyethylene glycol, white carbon black, diatomaceous earth, kaolin, clay, sodium alginate, magnesium aluminum silicate, sodium aluminum silicate, carboxymethyl cellulose, sodium hydroxypropyl cellulose and organic bentonite.

[0111] The capsule material may be any capsule material known in the field of pesticide formulations, and in the present invention, preferably one or more of polyurethane, polyurea and urea-formaldehyde resin.

[0112] The protective agent can be any protective agent known in the field of pesticide formulations, and in the present invention, polyvinyl alcohol and / or polyethylene glycol are preferred.

[0113] The defoaming agent can be any defoaming agent known in the field of pesticide formulations. In the present invention, it is preferably one or more of organosiloxane, tributyl phosphate and silicone.

[0114] The stabilizer is selected from one or more of triphenyl phosphite, epichlorohydrin and acetic anhydride.

[0115] The preservative is selected from one or more of benzoic acid, sodium benzoate, 1,2-benzisothiazolin-3-one (BIT for short), kasone and potassium sorbate.

[0116] The present invention also provides a preparation prepared from the above-mentioned bactericidal composition, wherein the preparation is in the form of emulsifiable concentrate, aqueous emulsion, microemulsion, soluble liquid, aqueous suspension, suspoemulsion, ultra-low volume spray, oil suspension, microcapsule suspension, water-film spreading oil, wettable powder, water-dispersible granule, dry suspension, soluble powder, soluble granule, emulsifiable powder, emulsifiable granule, granule, solid microcapsule preparation, effervescent tablet, effervescent granule, water-floating dispersible granule or seed coating. The above-mentioned dosage forms can all be prepared by conventional methods in the art.

[0117] The preparation method of the emulsifiable concentrate preparation may include, for example, mixing and stirring the active components, solvent, co-solvent and emulsifier to form a uniform and transparent oil phase, thereby obtaining the emulsifiable concentrate preparation.

[0118] The preparation method of the aqueous emulsion may include, for example, mixing the active ingredient, emulsifier, cosolvent and solvent to form a uniform oil phase; mixing water, thickener, antifreeze agent, etc. to form a uniform water phase. Under high-speed shearing, the water phase is added to the oil phase or the oil phase is added to the water phase to form an aqueous emulsion with good dispersibility.

[0119] The preparation method of the microemulsion is, for example, to mix and stir the active ingredient, emulsifier and solvent into a uniform and transparent oil phase, and then gradually add water under stirring to form a uniform and transparent microemulsion.

[0120] The preparation method of the water / oil suspension is as follows: for example, water or oil can be used as the medium, active components, surfactants and other auxiliary agents are added to a sand mill, ground to a certain particle size, and then filtered. Then, a measured thickener is added to the ground mother liquid, sheared and dispersed evenly, to prepare an oil suspension or a water suspension.

[0121] The preparation method of the above-mentioned water-dispersible granules and soluble granules is, for example, to mix the active components, dispersant, wetting agent, carrier, etc. uniformly, then pulverize to a certain particle size by air flow, then add water for kneading, and finally add to a granulator for granulation. After drying, water-dispersible granules or soluble granules can be obtained.

[0122] The preparation method of the above-mentioned soluble powder and wettable powder is, for example, to fully mix the active components, various adjuvants and other fillers such as carriers, and grind them with an ultra-fine grinder.

[0123] The bactericidal composition of the present invention can be provided in the form of a finished preparation, that is, the various substances in the composition have been mixed; it can also be provided in the form of a separate preparation, which can be mixed in a bucket or tank before use and selectively mixed with water for dilution according to the required concentration of the active substance.

[0124] Application of the compounds and compositions of the present invention

[0125] The compounds of the present invention can be used as plant disease control agents. Therefore, the present invention can also include a method for controlling plant diseases caused by plant pathogenic fungi, the method comprising applying an effective amount of the compounds of the present invention or a fungicidal composition comprising the compounds to the plant to be protected or its part. The compounds and / or compositions of the present invention can provide control for diseases caused by a wide spectrum of plant pathogenic fungi of the classes Basidiomycetes, Ascomycetes, Oomycetes and Deuteromycetes. They can effectively control a wide spectrum of plant diseases, especially foliar pathogens of ornamental crops, turf crops, vegetable crops, field crops, cereal crops and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi, and Phytophthora capsici, Pythium species diseases such as Pythium aphanidermatum, and Peronosporaceae species diseases such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp.) diseases (including Pseudoperonospora cubensis and Bremia lactucae); Ascomycetes (including Alternaria such as Alternaria solani and Alternaria brassicae, Guignardia such as Guignardia bidwell, Venturia such as Venturia inaequalis, Septoria such as Septorianodorum and Septoria tritici, powdery mildew such as Erysiphe spp.) (including Erysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis), Pyrenophora teres, anthracnose pathogens such as Glomerella or Colletotrichum spp. diseases (e.g., Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (e.g., Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis, and Puccinia arachidis), Hemileia vastatrix, and Phakopsora pachyrhizi; other pathogens include Rhizoctonia spp.) (such as Rhizoctonia solani); Fusarium species diseases such as Fusarium roseum, Fusarium graminearum, and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola, and Cercospora beticola; and other closely related species and fungi. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other species.

[0126] The method of using the fungicidal compound or composition of the present invention is simple. Before or after the emergence of plant diseases, the fungicidal compound or composition is applied to plants, plant parts or plant growth sites by conventional methods, such as mixing with soil, spraying, injection, pouring, etc. The application amount depends on the climatic conditions or the state of the crop. Generally, 10-5000 g per mu is applied, diluted to 10-400 mg / L (preferably 100-300 mg / L). The diluent is preferably water.

[0127] The fungicidal effect of the fungicidal compound or composition of the present invention is usually related to external factors such as climate, but the influence of climate can be mitigated by using appropriate formulations.

[0128] The compounds or compositions of the present invention may also be used in combination with other compounds having fungicidal, insecticidal or herbicidal properties, or with nematicides, miticides, protectants, herbicide safeners, growth regulators, plant nutrients or soil conditioners.

[0129] General synthesis process

[0130] The following scheme describes the preparation of the compounds of the present invention. Unless otherwise specified, the compounds of the present invention can be prepared by the methods described in the present invention. The raw materials, reagents, etc. used to prepare the compounds of the present invention are all commercially available, or can be prepared by conventional methods in the art. In this specification, if there is any difference between the chemical name and the chemical structure, the structure is dominant. In the preparation process of the compounds of the present invention, unless otherwise specified, the preparation process of the compounds is carried out at room temperature. "Room temperature" refers to a temperature of about 15°C-35°C or about 20°C-30°C or about 23°C-28°C or about 25°C. In the context of the present invention, whether or not the words "about" or "approximately" are used, all numbers disclosed herein are approximate values.

[0131] Synthesis scheme

[0132] Synthesis Scheme 1

[0133]

[0134] The target compound represented by formula (II-1) can be prepared by synthetic scheme 1. Compound (Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methanone oxime reacts with the compound represented by formula (a) under alkaline conditions (such as potassium carbonate, cesium carbonate, etc.) to obtain the target compound represented by formula (II-1);

[0135] Wherein, X is fluorine, chlorine, bromine or iodine, R 1 Has the meaning described in the present invention. Example

[0136] Intermediate 1: Preparation of (Z)-(1-methyl-1H-tetrazolyl-5-yl)(phenyl)methanone oxime

[0137]

[0138] Step 1: Preparation of N-methyl-2-oxo-2-phenylacetamide

[0139] Under 0°C, methyl benzoylformate (164 g, 1 mol) was dissolved in methanol (500 mL), and methylamine aqueous solution (101 g, 1.3 mol) was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and ethyl acetate (300 mL) was added for dilution. The mixture was washed with water (200 mL), 1N sodium hydroxide (200 mL), 1N hydrochloric acid (200 mL) and saturated brine (200 mL) in sequence, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain 130 g of a light yellow solid with a yield of 80%.

[0140] Step 2: Preparation of (Z)-N-methyl-2-oxo-2-phenylacetylimidoyl chloride

[0141] At 0°C, N-methyl-2-oxo-2-phenylacetamide (65 g, 0.4 mol) was dissolved in a mixed solution of N,N-dimethylformamide (2.9 g, 0.04 mol) and chloroform (500 mL), and thionyl chloride (71.4 g, 0.6 mol) was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours, and then heated under reflux for overnight reaction. The solvent was removed under reduced pressure, toluene (100 mL) was added for dilution, and the mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure to obtain 70 g of a brown oily liquid with a yield of 96%.

[0142] Step 3: Preparation of (1-methyl-1H-tetrazolyl-5-yl)(phenyl)methanone

[0143] At room temperature, sodium azide (6.5 g, 100 mmol) and tetrabutylammonium bromide (1.62 g, 5 mmol) were dissolved in a mixed solution of toluene (20 mL) and water (20 mL), and a toluene solution (60 mL) of (Z)-N-methyl-2-oxo-2-phenylacetylimidoyl chloride (18.2 g, 100 mmol) was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours, toluene (20 mL) was added for dilution, and the mixture was washed with water (100 mL x 3) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 15.4 g of a brown oily liquid with a yield of 85%.

[0144] Step 4: Preparation of (Z)-(1-methyl-1H-tetrazolyl-5-yl)(phenyl)ketone oxime

[0145] At room temperature, (1-methyl-1H-tetrazol-5-yl)(phenyl)methanone (15 g, 80 mmol) and hydroxylamine hydrochloride (11.1 g, 160 mmol) were dissolved in ethanol (100 mL), heated to 48 ° C, stirred for 12 hours, and the solvent was removed under reduced pressure. Water (100 mL) was added for dilution, and ethyl acetate (50 mL x 3) was used for extraction. The organic phase was washed with saturated brine (100 mL), and the organic phases were combined and concentrated under reduced pressure. The residue was purified by column chromatography [petroleum ether / ethyl acetate (v / v) = 4 / 1] to obtain 5.6 g of a light yellow solid with a yield of 34%.

[0146] 1 H NMR (400MHz, CDCl3) δ10.48 (s, 1H), 7.41 (dd, J = 12.9, 7.2Hz, 3H), 7.32 (t, J = 7.4Hz, 2H), 3.97 (s, 3H).

[0147] LC-MS: m / z 204.1[M+H] + .

[0148] Intermediate 2: Preparation of 6-(bromomethyl)pyridin-2-ylbenzoate

[0149]

[0150] Step 1: Preparation of 6-methylpyridin-2-ylbenzoate

[0151]

[0152] At room temperature, 2-hydroxy-6-methylpyridine (10.9 g, 100 mmol) was dissolved in dichloromethane (100 mL), pyridine (7.91 g, 100 mmol) was added, and the mixture was stirred at 0°C. Benzoyl chloride (14.1 g, 100 mmol) was slowly added dropwise. After the addition was completed in 2 hours, the mixture was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure, diluted with water (100 mL), extracted with ethyl acetate (50 mL x 3), the organic phases were combined, washed with saturated brine (100 mL), and concentrated under reduced pressure. The residue was subjected to column chromatography [petroleum ether / ethyl acetate (v / v) = 4 / 1] to obtain 19.5 g of yellow powder with a yield of 91.5%.

[0153] LC-MS: m / z = 214.10 [M+H] + .

[0154] Step 2: Preparation of 6-(bromomethyl)pyridin-2-ylbenzoate

[0155]

[0156] At room temperature, 6-methylpyridin-2-ylbenzoate (2.13 g, 10 mmol) was dissolved in carbon tetrachloride (150 mL), and N-bromosuccinimide (1.78 g, 10 mmol) and azobisisobutyronitrile (0.164 g, 1 mmol) were added, and the mixture was reacted at 80°C for 12 hours under nitrogen protection. The residue was filtered and washed three times with carbon tetrachloride (30 mL), the organic phases were combined, and the solvent was removed under reduced pressure to obtain 2.55 g of white powder with a yield of 87.3%.

[0157] LC-MS: m / z = 291.80 [M+H] + .

[0158] Using 2-hydroxy-6-methylpyridine and the corresponding benzoyl chloride derivative as reaction raw materials, refer to the preparation method of intermediate 2, or refer to the preparation method in the prior art, to prepare the intermediate compounds in Table 1.

[0159] Table 1

[0160]

[0161]

[0162]

[0163]

[0164] Example 1: Preparation of (Z)-6-(((((1-methyl-1H-tetrazol-5-yl)(phenyl)methylene)amino)oxy)methyl)pyridin-2-ylbenzoate

[0165]

[0166] (Z)-(1-methyl-1H-tetrazolyl-5-yl)(phenyl)methanone oxime (203 mg, 1 mmol), potassium carbonate (276 mg, 2 mmol), N,N-dimethylformamide (30 mL) were added to a reaction flask, and 6-(bromomethyl)pyridin-2-ylbenzoate (292 mg, 1 mmol) was added, and the mixture was reacted at room temperature for 6 hours. Ethyl acetate (50 mL) was added, and the mixture was washed with saturated brine (50 mL x 3). The organic phase was dried, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was separated by silica gel column chromatography [petroleum ether / ethyl acetate (v / v) = 5 / 1] to obtain 250 mg of a white solid, with a yield of 60.3%.

[0167] 1 H NMR (400MHz, CDCl3) δ (ppm): 8.01 (m, 2H), 7.83-7.80 (m, 3H), 7.56-7.45 (m, 4H), 7.24 (d, J = 10.5Hz, 1H), 6.51 (d, J = 7.2Hz, 1H), 6.32 (d, J = 10.6Hz, 1H), 6.22 (d, J = 8.5Hz, 1H), 5.51 (s, 2H), 4.13 (s, 3H).

[0168] LC-MS: m / z=415.10[M+H] + .

[0169] The intermediate 1((Z)-(1-methyl-1H-tetrazolyl-5-yl)(phenyl)methanone oxime, the corresponding structure is ) and the corresponding intermediates in Table 1 are used as raw materials, and the target compounds in Table 2 can be obtained by referring to the preparation method of Example 1 or the preparation method in the prior art.

[0170] Table 2

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177] Biological activity test

[0178] Test target: Cucumber downy mildew

[0179] Test treatment: The compounds were dissolved in N,N-dimethylformamide to 1% EC for later use. The in vivo pot culture method was used to evaluate the fungicidal activity of these compounds at different doses against the test targets.

[0180] Cucumber Downy Mildew Test (Pseudoperonosporacubensis)

[0181] Select the potted cucumber seedlings with the same growth in the 1 true leaf stage (remove the growth point), spray them and dry them naturally. Inoculate them 24 hours after treatment. Take fresh cucumber leaves infected with downy mildew, use a brush to dip in distilled water to wash off the sporangium on the back of the infected leaves, and prepare a sporangium suspension (2-3x10 5 / mL). Use an inoculation sprayer (pressure 0.1MPa) to evenly spray inoculation on cucumber seedlings. Move the inoculated test materials to an artificial climate room and maintain a relative humidity of 100% and a temperature of about 21°C. After 24 hours, maintain a temperature of about 21°C and a relative humidity of about 95% to induce moisture. After 5 days, conduct a graded investigation based on the incidence of the blank control and calculate the prevention effect according to the disease index.

[0182] The test results are as follows:

[0183] At a dosage of 50 mg / L, the control effects of Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11, Example 12, Example 13, Example 14, Example 15, Example 16, Example 17, Example 18, Example 19, and Example 20 on cucumber downy mildew were ≥ 90%. The control effects of compound K1 and compound K2 on cucumber downy mildew at a dosage of 50 mg / L are shown in Table 3:

[0184] Table 3 The protective effect of the compounds on cucumber downy mildew at a dosage of 50 mg / L

[0185]

[0186]

[0187] At a dosage of 25 mg / L, the protection efficacy of Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11, Example 12, Example 13, Example 14, Example 15, Example 16, Example 17, Example 18, Example 19, and Example 20 against cucumber downy mildew is ≥80%.

[0188] At a dosage of 12.5 mg / L, the protective efficacy of Example 14, Example 15, Example 16, and Example 17 against cucumber downy mildew was ≥80%.

[0189] From the above test results, it can be seen that the compounds of the present invention have significant protective effects on plant diseases, especially cucumber downy mildew, at low concentrations, and can be further developed for use as pesticide fungicides.

[0190] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

Claims

1. A compound, which is a compound represented by formula (I) or a salt thereof: (I)； in: R 1 is optionally substituted by 1 or 2 selected from halogen, -C 1-4 Alkyl, -halogenated C 1-4 Alkyl substituted phenyl; A is ; R a , R b , R c , R d and R e each independently is hydrogen; T is ; R f It is -CH3.

2. The compound according to claim 1, wherein: R 1 It is phenyl which is optionally substituted by 1 or 2 groups selected from fluorine, chlorine, bromine, iodine, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -C(CH3)3, -CH2Cl, -CH2F, -CHF2, -CF3, -CH2CF3.

3. The compound according to claim 2, wherein: R 1 for , , , , , , , , , , , , , , , , , , , , , , , , , or .

4. The compound according to claim 1, which is a compound represented by formula (II) or a salt thereof: (II)。 5. A compound having one of the following structures or a salt thereof: (1)、 (2)、 (3)、 (4)、 (5)、 (6)、 (7)、 (8)、 (9)、 (10)、 (11)、 (12)、 (13)、 (14)、 (15)、 (16)、 (17)、 (18)、 (19) or (20).

6. A composition comprising the compound according to any one of claims 1 to 5 and an adjuvant for pesticides.

7. Use of the compound according to any one of claims 1 to 5 or the composition according to claim 6 as a plant disease control agent in agriculture, forestry or horticulture, wherein: The plant disease is cucumber downy mildew.

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