WO2020133123A1 - Oxime-tetrazole derivative and application thereof in agriculture - Google Patents

Abstract

An oxime-tetrazole derivative. Specifically, disclosed are the oxime-tetrazole derivative represented by formula (I), or a salt, an nitrogen oxide, (E)- and (Z)-isomers or a mixture thereof the oxime-tetrazole derivative represented by formula (I), a preparation method for the oxime-tetrazole derivative, and a use thereof as a fungicide, a form of a fungicide composition thereof, and a method for preventing and treating phytopathogenic fungi of plants using such compound or composition.

Description

Oxime-tetrazole derivatives and their application in agriculture Technical field

The present invention relates to the field of pesticides, in particular to oxime-tetrazole derivatives and pesticides containing such derivatives as active ingredients, especially phytopathogenic fungus control agents.

Background technique

In modern agricultural production, due to the frequent use of pesticides for a long time, the diseases on the crops are resistant to the existing pesticides, which reduces the control effect of the pesticides. In order to effectively control the diseases of crops, the pesticides will be increased. Application rate, which not only increases the input of agricultural production and causes pollution to the environment; in order to solve the problem of drug resistance, it is necessary to continuously develop new compounds with the prevention and treatment of crop diseases.

Summary of the invention

The present invention provides a novel oxime derivative and a composition containing such a derivative. The oxime derivative and its composition are used to control phytopathogenic fungi in agriculture.

specifically:

In one aspect, the present invention provides a compound having a compound represented by formula (I) or a stereoisomer of a compound represented by formula (I), a nitrogen oxide, and a salt thereof:

A is

Y is hydrogen or C _1-6 alkyl;

m is 1, 2, 3 or 4;

Each R ^{a is} independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy Group, C _2-6 alkenyl, C _2-6 alkynyl, C _2-6 alkenyloxy, C _2-6 alkynyloxy, C _3-8 cycloalkyl, phenyl or phenoxy;

R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, halogen, nitro, cyano, hydroxy, amino, mercapto, C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy, C _1-6 alkylthio, halogenated C _1-6 alkylthio, C _1-6 alkoxy-C _1-6 alkyl Or halogenated C _1-6 alkoxy-C _1-6 alkyl.

In some embodiments, Y is hydrogen or C _1-4 alkyl;

m is 1, 2, 3 or 4;

Each R ^{a is} independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-4 alkyl, halogenated C _1-4 alkyl, C _1-4 alkoxy, halogenated C _1-4 alkoxy Group, C _2-4 alkenyl, C _2-4 alkynyl, C _2-4 alkenyloxy, C _2-4 alkynyloxy or C _3-6 cycloalkyl;

R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-4 alkyl, C _1-4 alkoxy, halo C _{1- 4} alkyl or halogenated C _1-4 alkoxy.

In still other embodiments, Y is hydrogen, -CH ₃ or -CH ₂ CH ₃ ;

m is 1, 2, 3 or 4;

Each R ^{a is} independently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxyl, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH(CH ₃ )CH ₂ CH ₃ , -CH ₂ CH(CH ₃ )CH ₃ , -C(CH ₃ ) ₃ , -CH ₂ Cl, -CHF ₂ ,- CF ₃ , -CF(CF ₃ ) ₂ , -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH(CH ₃ ) ₂ or -OCF ₃ ;

R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxyl, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH(CH ₃ )CH ₂ CH ₃ , -CH ₂ CH(CH ₃ )CH ₃ , -C(CH ₃ ) ₃ , -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH(CH ₃ ) ₂ , -CH ₂ Cl, -CHF ₂ , -CF ₃ , -CF(CF ₃ ) ₂ or- OCF ₃ .

In other embodiments,

It is the following substructure:

In some embodiments, the present invention provides a compound that has a compound represented by formula (II) or a stereoisomer of a compound represented by formula (II), a nitrogen oxide, and a salt thereof:

Among them, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the meanings described in the present invention.

In still other embodiments, the present invention provides a compound that is a compound having one of the following structures or a stereoisomer of a compound having one of the following structures, a nitrogen oxide compound, and a salt thereof:

Unless otherwise specified, all stereoisomers, tautomers, racemates, hydrates, solvates, metabolites, metabolic precursors and pro-compounds of the compounds represented by formula (I) or formula (II) of the present invention Medicines are also within the scope of the present invention.

In the oxime moiety of the oxime-tetrazole derivative of the present invention, there are (Z) isomer and (E) isomer, (Z) isomer, (E) isomer A mixture of (Z) isomers and (E) isomers are included in the present invention.

In another aspect, the invention provides a composition comprising at least one compound according to the invention.

In some embodiments, the compositions described herein further comprise agrochemically acceptable surfactants and/or carriers.

In another aspect, the present invention provides the use of the compound of the present invention or the composition of the present invention for controlling phytopathogenic fungi.

In another aspect, the invention provides methods of using the compounds of the invention or the compositions of the invention for controlling phytopathogenic fungi.

Detailed description of the invention

Definitions and general terms

Some embodiments of the present invention will now be described in detail, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover all alternatives, modifications and equivalent technical solutions, which are included in the scope of the invention as defined by the claims. Those skilled in the art should recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is by no means limited to the methods and materials described in the present invention. In the case where one or more of the incorporated documents, patents, and similar materials are different or contradictory to this application (including but not limited to defined terms, terminology, described technology, etc.), the Application shall prevail.

It should be further recognized that certain features of the invention have been described in separate embodiments for clarity, but can also be provided in combination in a single embodiment. Conversely, various features of the present invention have been described in a single embodiment for the sake of brevity, but can also be provided individually or in any suitable sub-combination.

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

Unless otherwise stated, the following definitions used in the present invention shall apply. For the purposes of the present invention, chemical elements are consistent with the CAS version of the periodic table of elements, and the Handbook of Chemistry and Physics, 75th edition, 1994. In addition, the general principles of organic chemistry can refer to the descriptions in "Organic Chemistry", Thomas Sorrell, University 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 into the present invention by reference.

Unless otherwise stated or there is a clear conflict in the context, the articles "a", "an" and "said" used in the present invention are intended to include "at least one" or "one or more". Therefore, the articles used in the present invention refer to one or more than one (ie at least one) object articles. For example, "a component" refers to one or more components, that is, there may be more than one component that is considered to be employed or used in the implementation of the embodiment.

The term "comprising" is an open-ended expression, that is, it includes the content specified by the present invention, but does not exclude other aspects.

"Stereoisomer" refers to compounds that have the same chemical structure, 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, etc. .

"Enantiomer" refers to two isomers of a compound that cannot overlap but are mirror images of each other.

"Diastereomer" refers to a stereoisomer that has two or more chiral neutrals and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties and reactivity. Diastereomer mixtures can be separated by high-resolution analytical operations such as electrophoresis and chromatography, such as HPLC.

The stereochemical definitions and rules used in the present invention generally follow SPParker, Ed., McGraw-Hill Dictionary of Chemicals (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of "Organic Compounds", John Wiley & Sons, Inc., New York, 1994.

Many organic compounds exist in optically active forms, that is, they have the ability to rotate the plane of plane polarized light. When describing optically active compounds, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule with respect to one or more chiral centers. The prefixes d and l or (+) and (-) are symbols used to specify the rotation of plane polarized light caused by a compound, where (-) or l indicates that the compound is levorotatory. 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 a racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.

Any asymmetric atoms (for example, carbon, etc.) of the compounds disclosed in the present invention can exist in racemic or enantiomerically enriched forms, such as (R)-, (S)-, or (R,S)-configuration forms exist. In certain embodiments, each asymmetric atom has an enantiomeric excess of at least 50%, an enantiomeric excess of at least 60%, an enantiomeric excess of at least 70%, at least in the (R)- or (S)-configuration, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess.

Depending on the choice of starting materials and methods, the compounds of the present invention may be in one of the possible isomers or their mixtures, such as racemates and diastereomer mixtures (this depends on the number of asymmetric carbon atoms) Form exists. Optically active (R)- or (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis or trans configuration.

The resulting mixture of any stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography Method and/or step crystallization method.

The racemates of any resulting end products or intermediates can be resolved into optical enantiomers by methods known to those skilled in the art using known methods, for example, by obtaining the diastereomeric salts obtained Separate. Racemic products can also be separated by chiral chromatography, such as high-performance liquid chromatography (HPLC) using chiral adsorbents. In particular, enantiomers can be prepared by asymmetric synthesis.

As described in the present invention, the compounds of the present invention may be optionally substituted with one or more substituents, such as the compounds of the general formula above, or like the specific examples, subclasses, and inclusions of the present invention in the examples. A class of compounds. 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 specific substituents. Unless otherwise indicated, an optional substituent may be substituted at each substitutable position of the group. When more than one position in the given structural formula can be substituted by one or more substituents selected from specific groups, the substituents may be substituted at the same positions or differently. Specifically, examples of "one or more" refer to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. The substituents described herein may be, but not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxy, nitro, amino, carboxy, alkyl, alkoxy, alkoxyalkyl, alkyl Oxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkane Alkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxy-substituted alkyl, hydroxy-substituted alkyl Amino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkylacyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkane Radical, heterocyclyl, heterocyclylalkyl, heterocyclylacyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, amido, sulfonyl, amino Sulfonyl and so on.

In addition, it should be noted that, unless it is clearly indicated in other ways, the description methods used in the present invention "each...independently" and "...independently each"and"...independently"are interchangeable, both It should be understood in a broad sense, which can mean that the specific options expressed between the same symbols in different groups do not affect each other, or it can mean the specific options expressed between the same symbols in the same group Do not affect each other.

In each part of this specification, the substituents of the compounds disclosed in the present invention are disclosed according to the type or range of groups. In particular, the present invention includes each independent sub-combination of each member of these group types and ranges. For example, the term "C ₁ -C ₆ alkyl" or "C _1-6 alkyl" particularly refers to independently disclosed methyl, ethyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, and C ₆ alkyl base.

As used herein, the term "alkyl" or "alkyl group" means a saturated linear or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms; wherein the alkyl group is optionally One or more substituents described in this invention are substituted. Unless otherwise specified, alkyl groups contain 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 yet another embodiment, the alkyl group contains 1-4 carbon atoms; in still another embodiment, the alkyl group contains 1-3 carbon atoms.

Examples of alkyl groups include, but are not limited to, methyl (Me, -CH ₃ ), ethyl (Et, -CH ₂ CH ₃ ), n-propyl (n-Pr, -CH ₂ CH ₂ CH ₃ ), isopropyl (i-Pr, -CH(CH ₃ ) ₂ ), n-butyl (n-Bu, -CH ₂ CH ₂ CH ₂ CH ₃ ), isobutyl (i-Bu, -CH ₂ CH (CH ₃ ) ₂ ), sec-butyl (s-Bu, -CH(CH ₃ )CH ₂ CH ₃ ), tert-butyl (t-Bu, -C(CH ₃ ) ₃ ), n-pentyl (-CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyl (-CH(CH ₂ CH ₃ ) ₂ ), 2-methyl -2-butyl(-C(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl-2-butyl(-CH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-1- Butyl (-CH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-1-butyl (-CH ₂ CH(CH ₃ )CH ₂ CH ₃ ), and so on.

The term "alkoxy" means that the alkyl group is connected to the rest of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described in the present invention. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH ₃ ), ethoxy (EtO, -OCH ₂ CH ₃ ), 1-propoxy (n-PrO, n- Propoxy, -OCH ₂ CH ₂ CH ₃ ), 2-propoxy (i-PrO, i-propoxy, -OCH(CH ₃ ) ₂ ), etc.

The term "alkylthio" means that the alkyl group is connected to the rest of the molecule through a sulfur atom, wherein the alkyl group has the meaning as described in the present invention. Examples of alkylthio groups include, but are not limited to, -SCH ₃ , -SCH ₂ CH ₃ , -SCH ₂ CH ₂ CH ₃ , -SCH(CH ₃ ) ₂ and the like.

The term "alkoxy-alkyl" means that the alkyl group is substituted with one or more alkoxy groups, wherein the alkyl and alkoxy groups have the meaning as described in the present invention.

The term "alkenyl" refers to a straight-chain or branched monovalent hydrocarbon group containing 2-12 carbon atoms, in which there is at least one unsaturated site, that is, there is a carbon-carbon sp ² double bond, wherein, the alkenyl group The group may be optionally substituted with one or more substituents described in the present invention, which includes the positioning of "cis" and "tans", or the positioning of "E" and "Z". In one embodiment, the alkenyl group contains 2-8 carbon atoms; in another embodiment, the alkenyl group contains 2-6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 -4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH=CH ₂ ), allyl (-CH ₂ CH=CH ₂ ), propenyl (CH ₃ -CH=CH-), oxo Butenyl (CH ₃ -C(=O)-CH=CH-) and so on.

The term "alkynyl" refers to a linear or branched monovalent hydrocarbon group containing 2-12 carbon atoms, in which there is at least one carbon-carbon sp triple bond, wherein the alkynyl group may be optionally substituted by one or more Substituted by the substituents described in this invention. In one embodiment, the alkynyl group contains 2-10 carbon atoms; in one embodiment, the alkynyl group contains 2-8 carbon atoms; in another embodiment, the alkynyl group contains 2- 6 carbon atoms; in yet another embodiment, the alkynyl group contains 2-4 carbon atoms. Examples of alkynyl groups include, but are not limited to, -C≡CH, -C≡CCH ₃ , -CH ₂ -C≡CH, -CH ₂ -C≡CCH ₃ , -CH ₂ CH ₂ -C≡CH , -CH ₂ -C≡CCH ₂ CH ₃ , -CH ₂ CH ₂ -C≡CCH _3, etc.

The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3-12 carbon atoms. In one embodiment, the cycloalkyl group contains 3-10 carbon atoms; in another embodiment, the cycloalkyl group contains 3-8 carbon atoms; in yet another embodiment, the cycloalkyl group contains 3-6 carbon atoms carbon atom. The cycloalkyl group is optionally substituted with one or more substituents described in the present invention. Such examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl Alkyl, etc.

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

The term "haloalkyl" denotes an alkyl group is substituted with one or more halogen atoms, such examples include, but are not limited _{to, -CF 3, -CHF 2, -CH} 2 Cl, -CH 2 CF 3, - CH ₂ CHF ₂ , -CH ₂ CH ₂ CF ₃ and so on.

The term "haloalkoxy" means that the alkoxy group is substituted with one or more halogen atoms, such examples include, but are not limited to, -OCF ₃ , -OCHF ₂ , -OCHCl ₂ , -OCH ₂ CHF ₂ , -OCH ₂ CHCl ₂ , -OCH(CH ₃ )CHF ₂ and so on.

The term "haloalkylthio" means that the alkylthio group is substituted with one or more halogen atoms, wherein the alkylthio group has the meaning as described in the present invention.

The term "haloalkoxy-alkyl" means that the "alkoxy-alkyl" group is substituted with one or more halogen atoms, wherein the "alkoxy-alkyl" group has the meaning as described in the present invention.

The term "alkenyloxy" means that an alkenyl group is connected to the rest of the molecule through an oxygen atom, wherein the alkenyl group has the meaning as described in the present invention.

The term "alkynyloxy" means that an alkynyl group is connected to the rest of the molecule through an oxygen atom, wherein the alkynyl group has the meaning as described in the present invention.

In the oxime portion of the oxime derivative described in the present invention, there are stereostructures of the (Z) and (E) forms, and both stereoisomers and mixtures thereof are included in the present invention. The two stereoisomers can be separated according to methods well known to those skilled in the art.

Salts of the compounds described in 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 ammonium cations having the chemical formula N ⁺ (R ^A R ^B R ^C R ^D ), where R ^A , R ^B , R ^C and R ^{D are} independently selected from hydrogen, C ₁ -C ₆ alkyl and C ₁ -C ₆ hydroxyalkyl. Salts of compounds of formula (I) or (II) can be obtained by using metal hydroxides (eg sodium hydroxide) or amines (eg ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, diallyl) Amine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine) are prepared by treating compounds of formula (I) or formula (II).

When the compound of the present invention contains a base moiety, acceptable salts can 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, propanediol 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 the like are known Accepted acid.

Compositions and formulations of compounds of the present invention

The compounds of the present invention are generally useful as fungicidal active ingredients in compositions, ie, formulations, and generally also include pesticide-acceptable surfactants and/or carriers.

The above surfactants may be various surfactants known in the field of pesticide formulations, such as anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants, block polymers, polyelectrolytes, and their mixture. Such surfactants can be used as emulsifiers, dispersants, wetting agents, penetration enhancers or adjuvants.

Suitable anionic surfactants are alkali metal, alkaline earth metal or ammonium salts of sulfonic acid, sulfuric acid, phosphoric acid, carboxylic acid, and mixtures thereof. Examples of sulfonates are alkyl aryl sulfonates, diphenyl sulfonates, alpha-olefin sulfonates, lignin sulfonates, sulfonates of fatty acids and oils, ethoxylated alkylphenols Sulfonates, alkoxylated arylphenol sulfonates, condensed naphthalene sulfonates, dodecyl- and tridecylbenzene sulfonates, naphthalene and alkyl naphthalene sulfonates, sulfonates Succinate or sulfosuccinate. Examples of sulfates are sulfates of fatty acids and oils, sulfates of ethoxylated alkylphenols, sulfates of alcohols, sulfates of ethoxylated alcohols or sulfates of fatty acid esters. An example of phosphate is phosphate ester. Examples of carboxylates are alkyl carboxylates and carboxylated alcohols or alkylphenol ethoxylates.

Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymer surfactants and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters that have been alkoxylated with 1-50 equivalents. Ethylene oxide and/or propylene oxide can be used for alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamide or fatty acid alkanolamide. Examples of esters are fatty acid esters, glycerides or monoglycerides. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides. Examples of polymer surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.

Suitable cationic surfactants are quaternary surfactants, for example quaternary ammonium compounds with 1 or 2 hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkyl betaines and imidazolines. Suitable block polymers are A-B or A-B-A type block polymers containing blocks of polyoxyethylene and polyoxypropylene, or A-B-C type block polymers containing alkanol, polyoxyethylene and polyoxypropylene. A suitable polyelectrolyte is polyacid or polybase. Examples of polyacids are alkali metal salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamine or polyvinylamine.

The above carrier may 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: 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, mixture of urea and amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, anhydrous potassium carbonate and anhydrous bicarbonate One or more of a mixture of potassium and a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.

According to the fungicide composition of the present invention, the fungicide composition may further contain various auxiliary agents commonly used in the field of pesticide formulations, specifically, the auxiliary agents for the preparation may be solvents, co-solvents, thickeners , Antifreeze, capsules, protective agents, defoamers, disintegrants, stabilizers, preservatives, adhesives, chelating agents one or more.

Suitable solvents are water and organic solvents, such as medium to high boiling mineral oil fractions, such as kerosene, diesel; oils of vegetable or animal origin; aliphatic, cyclic, and aromatic hydrocarbons, such as toluene, paraffin, tetralin , Alkylated naphthalene; alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycols; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonate, Fatty acid esters, γ-butyrolactone; fatty acids; phosphonates; amines; amides, such as N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.

The above solvent can also be used as a co-solvent.

Suitable thickeners are selected from polysaccharides (eg xanthan gum, carboxymethyl cellulose), inorganic clays (organically modified or unmodified), polycarboxylates and silicates.

Suitable antifreeze agents are selected from ethylene glycol, propylene glycol, glycerin, urea, glycerin and mixtures thereof.

Suitable bladders are selected from polyurethane, polyurea, urea-formaldehyde resin and mixtures thereof.

Suitable protective agents are selected from polyvinyl alcohol and/or polyethylene glycol.

Suitable defoamers are selected from polysiloxanes, silicone milks, long-chain alcohols, fatty acids and their salts, and fluorine-containing organics and mixtures thereof.

Suitable disintegrants are selected from bentonite, urea, ammonium sulfate, aluminum chloride, citric acid, succinic acid, sodium bicarbonate and mixtures thereof

Suitable stabilizers are selected from triphenyl phosphite, epichlorohydrin, acetic anhydride and mixtures thereof.

Suitable preservatives are selected from benzoic acid, sodium benzoate, 1,2-benzisothiazolin-3-one (abbreviated as BIT), carson, potassium sorbate, and mixtures thereof.

Suitable binders are selected from polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylate, biowax or synthetic wax, and cellulose ether.

The fungicides of the present invention can be applied in the form of their formulations or the use forms prepared therefrom, such as aerosols, capsule suspensions, cold-fogging concentrates, hot-mist concentrates, capsules Granules, fine granules, flowable concentrates for seed treatment, ready-to-use solutions, dustable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, Large granules, micro granules, oil-dispersible powders, oil-miscible flow concentrates, oil-miscible liquids, aerosols (under pressure), gas-generating products, foams, pastes, suspension concentrates, suspension milk Concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, powders and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, can be Wet powders, natural products and synthetic materials impregnated with active substances, as well as microcapsules in polymer and seed coating materials, and ULV (ultra low volume) cold mist and hot mist formulations. The above use forms can be prepared by conventional means in the art.

Application of compounds and compositions of the invention

The compounds of the present invention can be used as plant disease control agents. Therefore, the present invention may also include a method for controlling plant diseases caused by phytopathogenic fungi, which method comprises applying an effective amount of a compound of the present invention to the plant to be protected or a part thereof or to the plant seed to be protected or comprising Fungicidal composition of the compound. The compounds and/or compositions of the present invention can provide control of diseases caused by broad-spectrum plant pathogenic fungi of the Basidiomycetes, Ascomycetes, Oomycetes, and Semimycetes. They can effectively control broad-spectrum plant diseases, especially leaf pathogens of ornamental crops, lawn crops, vegetable crops, field crops, cereal crops and fruit tree crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora diseases of cinnamomi and Phytophthora capsici, diseases of Pythium species such as Pythium aphanidermatum, and diseases of Peronosporaceae species such as grape downy mildew Plasmopara viticola, Peronospora diseases (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora diseases (including cucumber downy mildew) (Pseudoperonospora cubensis) and Bremia lactucae); Ascomycetes (including Alternaria) such as Alternaria solani and Alternaria brassicae, Cocci (Guignardia) diseases such as grape black rot fungus (Guignardia bidwell), genus Venturia (Venturia) diseases such as apple astrosporium (Venturia inaequalis), spores (Septoria) diseases (Septoria nodorum) and leaves Blight fungus (Septoria tritici), powdery mildew diseases such as powdery mildew (Erysiphe spp.) (including wheat powdery mildew (Erysiphe Graminis) and powdery mildew (Erysiphe polygoni)), grape powdery mildew (Uncinula) necatur, Cucumber powdery mildew (Sphaerotheca fuligena) and apple powdery mildew (Podosphaera leucotricha), wheat-based rot fungus (Pseudocercosporella herpotrichoides), Botrytis genus (Botrytis) diseases such as strawberry Botrytis cinerea (Botrytis cinerea), peach brown rot fungus (Monilinia) fructicola), Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as corn plaque Pathogens (Helminthosporium triticirepentis), Pyrenophora teres, anthracnose pathogens such as Glomerella or Colletotrichum spp. Diseases (such as Colletotrichum graminicola and Colletotrichum orb. )), and Gaeumannomyces Graminis; Basidiomycetes, including rust fungus caused by Puccinia spp. (such as Puccinia reconcondita, Puccinia striiformis), Leaf rust fungus (Puccinia hordei), Puccinia graminis and Puccinia arachidis, coffee rust fungus (Hemileia vastatrix) and soybean rust fungus (Phakopsora pachyrhizi); other pathogens include Rhizoctonia species ( Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium species diseases such as Fusarium pink (Fusarium roseum), Fusarium graminearum (Fusarium graminearum) and Fusarium oxysporum (Fusarium oxysporum) ); Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personsatum, Cercospora arachidicola and Cercospora beticola ); and other categories and strains closely related to these pathogens. In addition to their fungicidal activity, the composition or combination is effective against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and others The strain is resistant.

The method of using the fungicide composition of the present invention is simple. Before or after germination of plant diseases, it is applied to crops and crop growth sites according to conventional methods, such as soil mixing, spraying, spraying, pouring, etc., and the application amount depends on the climate. Depends on the conditions or crop conditions, generally apply 10-5000g per mu, diluted to 10-400mg/L application. The diluent is preferably water.

The fungicidal composition of the present invention, its fungicidal effect is usually related to external factors such as climate, but by using an appropriate dosage form can reduce the impact of climate.

The composition of the present invention can also be used in combination with other compounds having bactericidal, insecticidal or herbicidal properties, and can also be mixed with nematicides, acaricides, protective agents, herbicide safeners, growth regulators, phytonutrients or soil regulators Etc. mixed use.

General synthesis process

In this specification, if there is any difference between the chemical name and the chemical structure, the structure is dominant. Generally, the compound of the present invention can be prepared by the method described in the present invention, unless otherwise specified, wherein the definition of the substituent is as shown in (I).

Those skilled in the art will recognize that the chemical reactions described in the present invention can be used to properly prepare many other compounds of the present invention, and other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention Inside. For example, the synthesis of non-exemplified compounds according to the present invention can be successfully accomplished by those skilled in the art through modification methods, such as appropriate protection of interfering groups, by using other known reagents (in addition to those described in the present invention), Or the reaction conditions can be modified routinely. In addition, the reactions disclosed in the present invention or known reaction conditions are also generally applicable to the preparation of other compounds of the present invention. In addition, in some embodiments, unless otherwise specified, the reaction of the present invention is performed at room temperature, where the room temperature is -10 to 40°C.

The following synthetic schemes describe the steps for preparing the disclosed compounds.

Synthesis scheme

Synthesis scheme one

The target compound 1-1 can be prepared by Synthesis Scheme 1. Intermediate a and intermediate b are reacted in a basic system to obtain the target compound I-1.

detailed description

The following examples are used to illustrate the present invention, but cannot be used to limit the scope of the present invention.

Intermediate M: Synthesis of (6-(bromomethyl)pyridin-2-yl)carbamic acid tert-butyl ester

Step 1: Synthesis of 6-((tert-butyl ester) amino) methyl picolinate

Dissolve methyl 2-aminopyridine-6-carboxylate (20.00 g, 131.45 mmol) in tetrahydrofuran (200 mL), add di-tert-butyl dicarbonate (45.6 g, 210.32 mmol) and 4-dimethylaminopyridine (0.1 g) The reaction was heated and stirred at 60°C for 6 hours. Concentrate under reduced pressure to remove tetrahydrofuran to obtain 32g of light yellow liquid, yield: 96%.

Step 2: Synthesis of (6-(hydroxymethyl)pyridin-2-yl)carbamic acid tert-butyl ester

Dissolve methyl 6-((tert-butylester)amino)picolinate (32g, 126.85mmol) and anhydrous calcium chloride (28.16g, 253.70mmol) in absolute ethanol (300mL) and add them in portions at 0°C Sodium borohydride (14.4g, 380.55mmol), stirred at room temperature for 3 hours after addition. Dichloromethane was added for extraction (300 mL), washed with water (100 mL) and saturated brine (100 mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 26.8 g of light yellow liquid, yield: 94% .

Step 3: Synthesis of (6-(bromomethyl)pyridin-2-yl)carbamic acid tert-butyl ester

At room temperature, (6-(hydroxymethyl)pyridin-2-yl)carbamic acid tert-butyl ester (10g, 44.59mmol) and carbon tetrabromide (42.59g, 128.42mmol) were dissolved in dichloromethane (200mL), Potassium carbonate (26.69g, 193.08mmol) was added, and at 0°C, a solution of triphenylphosphine (33.68g, 128.42mmol) in methylene chloride (100mL) was slowly dropped into the mixed system, and the mixture was stirred at room temperature after completion of the dropwise addition 4 hours. After removing insoluble materials by suction filtration, it was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography [petroleum ether/ethyl acetate (v/v)=9/1] to obtain 3.8 g of light yellow liquid with a yield of 29%.

LC-MS: m/z 287.0 [M+H] ⁺ .

Intermediate N1: Synthesis of (Z)-(1-methyl-1H-tetrazol-5-yl)(4-phenoxyphenyl) ketoxime

Step 1: Synthesis of 4-phenoxybenzoyl chloride

4-Phenoxybenzoic acid (2.14 g, 10 mmol) was dissolved in dichlorosulfoxide (10 mL), and the temperature was raised to 80° C. and refluxed for 3 hours. Cooled to room temperature, concentrated under reduced pressure to remove excess dichlorosulfoxide, added toluene (10 mL), and concentrated again under reduced pressure to remove volatile materials, to obtain 2.3 g of brown oily liquid, yield: 98%.

Step 2: Synthesis of N-methoxy-N-methyl-4-phenoxybenzamide

At 0°C, dissolve dimethylolamine hydrochloride (1.2g, 12mmol) in dichloromethane (10mL), add triethylamine (2.8mL, 20mmol) dropwise, and then add 4-phenoxybenzyl dropwise A dichloromethane solution (5 mL) of acid chloride (2.3 g, 10 mmol) was reacted at room temperature for 6 hours. After adding dichloromethane (100 mL), washing with water (150 mL), saturated sodium bicarbonate (150 mL), and saturated brine (150 mL) in this order, the organic phases were combined, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography [Petroleum ether/ethyl acetate (v/v)=10/1] was isolated to obtain 1.4 g of pale yellow liquid with a yield of 54%.

Step 3: Synthesis of (1-methyl-1H-tetrazol-5-yl) (4-phenoxyphenyl) ketone

At 0°C, 1-methyl-1H-tetrazole (504 mg, 6 mmol) was dissolved in tetrahydrofuran (10 mL), isopropyl magnesium chloride (3.0 mL) was added dropwise, and after 15 minutes of reaction, N-methoxy was added dropwise -N-methyl-4-phenoxybenzamide (1.3 g, 5 mmol) in tetrahydrofuran (5 mL), and react at room temperature for 2 hours. The reaction was quenched with saturated ammonium chloride (100 mL), extracted with ethyl acetate (50 mL x 3), washed with saturated brine (100 mL), the organic phases were combined, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography [petroleum ether/acetic acid] Ethyl ester (v/v)=20/1] to give 476 mg of white solid in 34% yield.

Step 4: Synthesis of (Z)-(1-methyl-1H-tetrazol-5-yl)(4-phenoxyphenyl) ketoxime

At room temperature, (1-methyl-1H-tetrazol-5-yl)(4-phenoxyphenyl)methanone (420 mg, 1.5 mmol) and hydroxylamine hydrochloride (261 mg, 3.8 mmol) were dissolved in pyridine (10 mL ), and the temperature was raised to 60°C to reflux for 6 hours. Concentrate under reduced pressure to remove pyridine, add water (100 mL), extract with ethyl acetate (50 mL x 3), wash with saturated brine (100 mL), combine organic phases, concentrate under reduced pressure, and separate the residue by silica gel column chromatography [petroleum ether/ Ethyl acetate (v/v) = 4/1] to give 251 mg of light yellow liquid with a yield of 57%.

LC-MS: m/z 296.9 [M+H] ⁺ .

Using different phenoxybenzene carboxylic acid compounds as starting materials, through the similar synthesis method of intermediate N1, the intermediates in Table 1 can be obtained.

Table 1

Example 1: (Z)-tert-butyl(6-((((((1-methyl-1H-tetrazol-5-yl)(4-phenoxyphenyl)methylene)amino)oxy)oxy) Synthesis of methyl)pyridin-2-yl)carbamate

At room temperature, (Z)-(1-methyl-1H-tetrazol-5-yl)(4-phenoxyphenyl)methanone oxime (251mg, 0.85mmol), (6-(bromomethyl )Pyridine-2-yl)carbamic acid tert-butyl ester (244 mg, 0.85 mmol) and potassium carbonate (176 mg, 1.28 mmol) were added to the reaction flask, N,N-dimethylformamide (10 mL) was added, and the reaction was stirred for 12 hour. Quench the reaction with water (50 mL), extract with ethyl acetate (30 mL x 3), wash with saturated brine (50 mL), combine the organic phases, concentrate under reduced pressure, and separate the residue by silica gel column chromatography [petroleum ether/ethyl acetate] (v/v)=5/1], 300 mg of white solid was obtained with a yield of 70%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ (ppm): 9.79 (s, 1H), 7.75 (d, J=5.9 Hz, 2H), 7.53-7.38 (m, 4H), 7.21 (t, J= 7.3Hz, 1H), 7.06(dd, J=14.6, 8.4Hz, 4H), 7.00(dd, J=5.8, 1.8Hz, 1H), 5.25(s, 2H), 4.04(s, 3H), 1.47( s,9H);

LC-MS: m/z 502.8 [M+H] ⁺ .

Intermediate (6-(bromomethyl)pyridin-2-yl)carbamic acid tert-butyl ester and corresponding intermediate N2, intermediate N3, intermediate N4, intermediate N5, intermediate N6, intermediate N7, intermediate Body N8, Intermediate N9, Intermediate N10, Intermediate N11, Intermediate N12, Intermediate N13, or Intermediate N14 were prepared by a similar synthesis method as in Example 1, and the target compound in Table 2 can be obtained. Example 3, Example 4, Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11, Example 12, Example 13, and Example 14.

Table 2

Activity test

Test case

This test example was used to determine the fungicidal activity of the compounds prepared in the examples. The test target in this test example is cucumber downy mildew. Use N,N-dimethylformamide to dissolve into 1% emulsifiable concentrate. The in vivo pot method was used to evaluate the fungicidal activity of these compounds against the test target at a dose of 200 mg/L. The test method adopts the SOP (Fungicide Volume) for biological activity evaluation of the created pesticide.

Cucumber Downy Mildew (Pseudoperonospora cubensis):

Select a potted cucumber seedling with the same growth trend in the true leaf stage (removal of the growth point), dry it naturally after spraying, inoculate it 24 hours after the treatment, take the fresh cucumber downy mildew diseased leaves, and dip them in distilled water with a brush to wash the disease The sporangia on the back of the leaves are made into a sporangia suspension (2-3×10 ⁵ /mL). Inoculate the cucumber seedlings evenly with an inoculation sprayer (pressure 0.1MPa). The inoculated test material is moved to an artificial climate room and maintained at a relative humidity of 100% at a temperature of approximately 21°C. After 24 hours, the temperature is maintained at approximately 21°C and a relative humidity of 95 Moisture induced by about 3%, and a graded investigation of the incidence of the blank control in the backsight after 5 days, and the prevention effect was calculated according to the disease index.

The test results are shown in Table 3.

Table 3 Control effect of the compound of the present invention on cucumber downy mildew at a dose of 200 mg/L

Examples	Control effect on cucumber downy mildew (%)
Example 1	100
Example 2	100
Example 3	100

Examples	Control effect on cucumber downy mildew (%)
Example 4	100
Example 5	100
Example 6	90
Example 8	95
Example 10	100
Example 11	100
Example 12	100
Example 13	98
Example 14	95

It can be known from the above test results that the compound of the present invention has a good control effect on phytopathogenic fungi, especially on cucumber downy mildew, and has the value of further research and development.

The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical idea of the present invention, various simple modifications can be made to the technical solution of the present invention. These simple modifications All belong to the protection scope of the present invention.

Claims (7)

1. A compound which has a compound represented by formula (I) or a stereoisomer of a compound represented by formula (I), a nitrogen oxide, and a salt thereof:

   

   among them,

   A is

   

   Y is hydrogen or C _1-6 alkyl;

   m is 1, 2, 3 or 4;

   Each R ^{a is} independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-6 alkyl, halogenated C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkoxy Group, C _2-6 alkenyl, C _2-6 alkynyl, C _2-6 alkenyloxy, C _2-6 alkynyloxy, C _3-8 cycloalkyl, phenyl or phenoxy;

   R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-6 alkyl, C _1-6 alkoxy, halo C _{1- 6} alkyl or halogenated C _1-6 alkoxy.
2. The compound according to claim 1, wherein

   Y is hydrogen or C _1-4 alkyl;

   m is 1, 2, 3 or 4;

   Each R ^{a is} independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-4 alkyl, halogenated C _1-4 alkyl, C _1-4 alkoxy, halogenated C _1-4 alkoxy Group, C _2-4 alkenyl, C _2-4 alkynyl, C _2-4 alkenyloxy, C _2-4 alkynyloxy or C _3-6 cycloalkyl;

   R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, halogen, nitro, cyano, hydroxy, C _1-4 alkyl, C _1-4 alkoxy, halo C _{1- 4} alkyl or halogenated C _1-4 alkoxy.
3. The compound according to claim 2, wherein

   Y is hydrogen, -CH ₃ or -CH ₂ CH ₃ ;

   m is 1, 2, 3 or 4;

   Each R ^{a is} independently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxyl, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH(CH ₃ )CH ₂ CH ₃ , -CH ₂ CH(CH ₃ )CH ₃ , -C(CH ₃ ) ₃ , -CH ₂ Cl, -CHF ₂ ,- CF ₃ , -CF(CF ₃ ) ₂ , -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH(CH ₃ ) ₂ or -OCF ₃ ;

   R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxyl, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ CH ₃ , -CH(CH ₃ )CH ₂ CH ₃ , -CH ₂ CH(CH ₃ )CH ₃ , -C(CH ₃ ) ₃ , -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH(CH ₃ ) ₂ , -CH ₂ Cl, -CHF ₂ , -CF ₃ , -CF(CF ₃ ) ₂ or- OCF ₃ .
4. The compound according to claim 3, wherein

   

   It is the following substructure:

   
5. The compound according to any one of claims 1 to 4, which is a compound having one of the following structures or a stereoisomer, a nitrogen oxide, and a salt of a compound having one of the following structures:

   

   

   

   
6. A composition comprising at least one compound according to any one of claims 1-5.
7. Use of a compound according to any one of claims 1 to 5 or a composition according to claim 6 for controlling phytopathogenic fungi.