CN111630044A - Oximino-tetrazole derivatives and application thereof in agriculture - Google Patents

Abstract

The present invention provides an oximino-tetrazole derivative; in particular, the present invention relates to hydroximoyl-tetrazole derivatives of formula (I) or salts, nitroxides, (E) body isomers, (Z) body isomers or mixtures of (E) and (Z) body isomers of hydroximoyl-tetrazole derivatives of formula (I), and methods for their preparation, their use as fungicides, in the form of fungicide compositions thereof, and methods for the control of phytopathogenic fungi using these compounds or compositions; wherein A and Y have the meanings as described in the invention.

Description

Oximino-tetrazole derivatives and application thereof in agriculture Technical Field

The invention relates to the field of pesticides, in particular to hydroximoyl-tetrazole derivatives and a pesticide containing the derivatives as active ingredients, especially a plant pathogenic fungus preventing and removing agent.

Background

In modern agricultural production, however, the diseases on crops generate drug resistance to the existing pesticides due to frequent use of the pesticides for a long time, so that the control effect of the pesticides is reduced, and in order to effectively control the diseases of the crops, the application amount of the pesticides is increased, thereby not only increasing the investment of agricultural production, but also causing pollution to the environment; in order to solve the problem of drug resistance, new compounds for controlling crop diseases are continuously developed.

Disclosure of Invention

The present invention provides a novel oxime derivative, and a composition comprising the same, which oxime derivative and composition thereof are useful for controlling phytopathogenic fungi in agriculture.

Specifically, the method comprises the following steps:

in one aspect, the present invention provides a compound that is a compound having formula (I) or a stereoisomer, a nitroxide, or a salt thereof of the compound of formula (I):

a is

Y is hydrogen or C_1-6An alkyl group;

m is 1,2, 3 or 4;

each R^aIndependently hydrogen, halogen, nitro, cyano, hydroxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_3-8Cycloalkyl, phenyl or phenoxy;

R¹、R²、R³、R⁴and R⁵Each independently hydrogen, halogen, nitro, cyano, hydroxy, amino, mercapto, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkoxy radical, C_1-6Alkylthio, halo C_1-6Alkylthio radical, C_1-6alkoxy-C_1-6Alkyl or halo C_1-6alkoxy-C_1-6An alkyl group.

In some embodiments, Y is hydrogen or C_1-4An alkyl group;

m is 1,2, 3 or 4;

each R^aIndependently hydrogen, halogen, nitro, cyano, hydroxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkoxy radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_2-4Alkenyloxy radical, C_2-4Alkynyloxy or C_3-6A cycloalkyl group;

R¹、R²、R³、R⁴and R⁵Each independently is hydrogen, halogen, nitro, cyano, hydroxy, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group.

In still other embodiments, Y is hydrogen, -CH₃or-CH₂CH₃；

m is 1,2, 3 or 4;

each R^aIndependently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxy, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-CH₂Cl、-CHF₂、-CF₃、-CF(CF₃)₂、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂or-OCF₃；

R¹、R²、R³、R⁴And R⁵Each independently is hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxy, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-CH₂Cl、-CHF₂、-CF₃、-CF(CF₃)₂or-OCF₃。

In still other embodiments of the present invention,

is of the sub-structure:

in some embodiments, the present invention provides a compound that is a stereoisomer, a nitroxide, and a salt thereof, of a compound having or represented by formula (II):

wherein R is¹、R²、R³、R⁴And R⁵Have the meaning as 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, a nitrogen oxide, and a salt thereof of the compound having one of the following structures:

unless otherwise indicated, all stereoisomers, tautomers, racemates, hydrates, solvates, metabolites, metabolic precursors and prodrugs of the compounds of formula (I) or formula (II) of the present invention also fall within the scope of the present invention.

The oxime moiety of the hydroximoyl-tetrazole derivative of the present invention includes (Z) isomer and (E) isomer, (Z) isomer, (E) isomer, and a mixture of the (Z) isomer and the (E) isomer.

In another aspect, the present invention provides a composition comprising at least one compound of the present invention.

In some embodiments, the compositions of the present invention further comprise an agriculturally pharmaceutically acceptable surfactant and/or carrier.

In a further aspect, the present invention provides the use of a compound according to the invention or of a composition according to the invention for combating phytopathogenic fungi.

In another aspect, the present invention provides methods for the use of the compounds according to the invention or of the compositions according to the invention for combating phytopathogenic fungi.

Detailed description of the invention

Definitions and general terms

Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. One skilled in the art will 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 in no way limited to the methods and materials described herein. In the event that one or more of the incorporated documents, patents, and similar materials differ or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, and the like), this application controls.

It will be further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.

The following definitions, as used herein, should be applied unless otherwise indicated. For the purposes of the present invention, the chemical elements are in accordance with the CAS version of the periodic Table of the elements, and the handbook of chemistry and Physics, 75 th edition, 1994. In addition, general principles of Organic Chemistry can be referred to as described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausaltito: 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.

The articles "a," "an," and "the" as used herein are intended to include "at least one" or "one or more" unless otherwise indicated or clearly contradicted by context. Thus, as used herein, the articles refer to one or to more than one (i.e., to at least one) of the objects. 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 embodiments of the described embodiments.

The term "comprising" is open-ended, i.e. includes the elements indicated in the present invention, but does not exclude other elements.

"stereoisomers" refers to compounds having the same chemical structure but differing in the arrangement of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.

"enantiomer" refers to two isomers of a compound that are not overlapping but are in mirror image relationship to 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 points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers may be separated by high resolution analytical procedures such as electrophoresis and chromatography, e.g., HPLC.

The stereochemical definitions and rules used in the present invention generally follow the general definitions of S.P. 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.

Many organic compounds exist in an optically active form, i.e., they have the ability to rotate the plane of plane polarized light. In describing optically active compounds, the prefixes D and L or R and S are used to denote the absolute configuration of a molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are the symbols used to specify the rotation of plane polarized light by the compound, where (-) or l indicates that the compound is left-handed. Compounds prefixed with (+) or d are dextrorotatory. A particular stereoisomer is an enantiomer and a mixture of such isomers is referred to as an enantiomeric mixture. A50: 50 mixture of enantiomers is referred to as a racemic mixture or racemate, which may occur when there is no stereoselectivity or stereospecificity in the chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of a compound disclosed herein can exist in racemic or enantiomerically enriched forms, such as 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 the (R) -or (S) -configuration.

Depending on the choice of starting materials and methods, the compounds of the invention may exist as one of the possible isomers or as mixtures thereof, for example as racemates and mixtures of non-corresponding isomers (depending on the number of asymmetric carbon atoms). 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 substituents may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituents of the cycloalkyl group may have cis or trans configuration.

Any resulting mixture of stereoisomers may be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, depending on differences in the physicochemical properties of the components, for example, by chromatography and/or fractional crystallization.

The racemates of any of the resulting end products or intermediates can be resolved into the optical enantiomers by known methods using methods familiar to those skilled in the art, e.g., by separation of the diastereomeric salts obtained. The racemic product can also be separated by chiral chromatography, e.g., High Performance Liquid Chromatography (HPLC) using a chiral adsorbent. In particular, enantiomers can be prepared by asymmetric synthesis.

The compounds of the invention may be optionally substituted with one or more substituents, as described herein, in compounds of the general formula above, or as specifically exemplified, sub-classes, and classes of compounds encompassed by the invention. It is understood that the term "optionally substituted" may be 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 with a particular 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 formula can be substituted with one or more substituents selected from a particular group, the substituents may be substituted at each position, identically or differently. Specifically, examples of "one or more" refer to 1,2, 3, 4, 5, 6, 7, 8, 9, or 10. Wherein said substituent may be, but is not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxyl, nitro, amino, carboxyl, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxyl-substituted alkyl, hydroxyl-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkanoyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, amido, sulfonyl, aminosulfonyl, and the like.

In addition, unless otherwise explicitly indicated, the descriptions of the terms "… independently" and "… independently" and "… independently" used in the present invention are interchangeable and should be understood in a broad sense to mean that the specific items expressed between the same symbols do not affect each other in different groups or that the specific items expressed between the same symbols in the same groups do not affect each other.

In the various parts of this specification, substituents of the disclosed compounds are disclosed in terms of group type or range. It is specifically intended that the invention includes each and every independent subcombination of the various members of these groups and ranges. For example, the term "C₁-C₆Alkyl "or" C_1-6Alkyl "means in particular independently disclosed methyl, ethyl, C₃Alkyl radical, C₄Alkyl radical, C₅Alkyl and C₆An alkyl group.

The term "alkyl" or "alkyl group" as used herein, denotes a saturated, straight or branched chain, monovalent hydrocarbon group containing from 1 to 20 carbon atoms; wherein the alkyl group is optionally substituted with one or more substituents described herein. Unless otherwise specified, alkyl groups contain 1-20 carbon atoms. In one embodiment, the alkyl group contains 1 to 12 carbon atoms; in one embodiment, the alkyl group contains 1 to 8 carbon atoms; in another embodiment, the alkyl group contains 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 4 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 3 carbon atoms.

Examples of alkyl groups include, but are not limited to, methyl (Me, -CH)₃) Ethyl group (Et, -CH)₂CH₃) N-propyl (n-Pr, -CH)₂CH₂CH₃) Isopropyl group (i-Pr, -CH (CH)₃)₂) N-butyl (n-Bu, -CH)₂CH₂CH₂CH₃) Isobutyl (i-Bu, -CH)₂CH(CH₃)₂) Sec-butyl (s-Bu, -CH (CH)₃)CH₂CH₃) Tert-butyl (t-Bu, -C (CH)₃)₃) N-pentyl (-CH)₂CH₂CH₂CH₂CH₃) 2-pentyl (-CH (CH)₃)CH₂CH₂CH₃) 3-pentyl (-CH (CH)₂CH₃)₂) 2-methyl-2-butyl (-C (CH)₃)₂CH₂CH₃) 3-methyl-2-butyl (-CH (CH)₃)CH(CH₃)₂) 3-methyl-1-butyl (-CH)₂CH₂CH(CH₃)₂) 2-methyl-1-butyl (-CH)₂CH(CH₃)CH₂CH₃) And so on.

The term "alkoxy" means an alkyl group attached to the rest of the molecule through 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, -OCH)₃) Ethoxy (EtO, -OCH)₂CH₃) 1-propoxy (n-PrO, n-propoxy, -OCH)₂CH₂CH₃) 2-propoxy (i-PrO, i-propoxy, -OCH (CH)₃)₂) And so on.

The term "alkylthio" means an alkyl group attached to the rest of the molecule through a sulfur atom, wherein the alkyl group has the meaning as described herein. Examples of alkylthio groups include, but are not limited to, -SCH₃、-SCH₂CH₃、-SCH₂CH₂CH₃、-SCH(CH₃)₂And so on.

The term "alkoxy-alkyl" denotes an alkyl group substituted by one or more alkoxy groups, wherein alkyl and alkoxy groups have the meaning as described herein.

The term "alkenyl" denotes a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one site of unsaturation, i.e. one carbon-carbon sp²A double bond, wherein the alkenyl group may be optionally substituted with one or more substituents described herein, including the positioning of "cis" and "tansOr the positioning of "E" and "Z". In one embodiment, the alkenyl group contains 2 to 8 carbon atoms; in another embodiment, the alkenyl group contains 2 to 6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH ═ CH)₂) Allyl (-CH)₂CH＝CH₂) Allyl (CH)₃-CH ═ CH-), oxo butenyl (CH)₃-C (═ O) -CH ═ CH-) and the like.

The term "alkynyl" denotes a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one carbon-carbon sp triple bond, wherein the alkynyl radical may be optionally substituted with one or more substituents as described herein. In one embodiment, alkynyl groups contain 2-10 carbon atoms; in one embodiment, alkynyl groups contain 2-8 carbon atoms; in another embodiment, alkynyl groups contain 2-6 carbon atoms; in yet another embodiment, alkynyl groups contain 2-4 carbon atoms. Examples of alkynyl groups include, but are not limited to, -C.ident.CH, -C.ident.CCH₃、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C≡CH、-CH₂-C≡CCH₂CH₃、-CH₂CH₂-C≡CCH₃And so on.

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

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

The term "haloalkyl" denotes an alkyl group substituted with one or more halogen atomsWhere substituted, such examples include, but are not limited to, -CF₃，-CHF₂，-CH₂Cl，-CH₂CF₃，-CH₂CHF₂，-CH₂CH₂CF₃And the like.

The term "haloalkoxy" denotes an alkoxy group substituted with one or more halogen atoms, examples of which include, but are not limited to, -OCF₃，-OCHF₂，-OCHCl₂，-OCH₂CHF₂，-OCH₂CHCl₂，-OCH(CH₃)CHF₂And the like.

The term "haloalkylthio" denotes an alkylthio group substituted by one or more halogen atoms, wherein the alkylthio group has the meaning as described herein.

The term "haloalkoxy-alkyl" denotes an "alkoxy-alkyl" group substituted with one or more halogen atoms, wherein the "alkoxy-alkyl" group has the meaning as described herein.

The term "alkenyloxy" means an alkenyl group attached to the rest of the molecule through an oxygen atom, wherein the alkenyl group has the meaning as described herein.

The term "alkynyloxy" denotes an alkynyl group attached to the rest of the molecule through an oxygen atom, wherein the alkynyl group has the meaning as described herein.

In the oxime site in the oxime derivative according to the present invention, there are stereo structures of the (Z) body and the (E) body, and both stereoisomers and mixtures thereof are included in the present invention. The two stereoisomers may be separated according to methods well known to those skilled in the art.

Salts of the compounds of the present invention include those derived from alkali or alkaline earth metals as well as those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium and those of formula N⁺(R^AR^BR^CR^D) Ammonium cation of (2), wherein R is^A、R^B、R^CAnd R^DIndependently selected from hydrogen, C₁-C₆Alkyl and C₁-C₆A hydroxyalkyl group. Salts of compounds of formula (I) or (II) may be prepared by treating a compound of formula (I) or (II) with a metal hydroxide, such as sodium hydroxide, or an amine, such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, diallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine.

When a compound of the invention comprises a base moiety, acceptable salts can be formed from organic and inorganic acids, such as acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.

Compositions and formulations of the compounds of the invention

The compounds of the present invention are generally useful as fungicide active ingredients in compositions, i.e., formulations, typically further comprising an agriculturally acceptable surfactant and/or carrier.

The surfactant may be any of various surfactants known in the art of pesticide formulation, such as anionic, cationic, nonionic and amphoteric surfactants, block polymers, polyelectrolytes, and mixtures thereof. Such surfactants may 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 acids, sulfuric acids, phosphoric acids, carboxylic acids and mixtures thereof. Examples of sulfonates are alkylarylsulfonates, diphenylsulfonates, alpha-olefin sulfonates, lignosulfonates, sulfonates of fatty acids and oils, sulfonates of ethoxylated alkylphenols, sulfonates of alkoxylated arylphenols, sulfonates of condensed naphthalenes, sulfonates of dodecyl-and tridecylbenzenes, sulfonates of naphthalenes and alkylnaphthalenes, sulfosuccinates or sulfosuccinamates. 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 a phosphate is a phosphate ester. Examples of carboxylates are alkyl carboxylates and also carboxylated alcohol or alkylphenol ethoxylates.

Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters which have been alkoxylated by 1 to 50 equivalents. Ethylene oxide and/or propylene oxide may be used for the alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides. Examples of polymeric surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.

Suitable cationic surfactants are quaternary surfactants, such as quaternary ammonium compounds having 1 or 2 hydrophobic groups, or salts of long chain primary amines. Suitable amphoteric surfactants are alkyl betaines and imidazolines. Suitable block polymers are block polymers of the A-B or A-B-A type comprising blocks of polyoxyethylene and polyoxypropylene, or block polymers of the A-B-C type comprising alkanols, polyoxyethylene and polyoxypropylene. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali metal salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamine or polyvinylamine.

The carrier may be any of various carriers known in the field of agricultural chemical preparations, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, and synthetic carriers. Specifically, for example: white carbon black, kaolin, diatomite, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, an amine fertilizer, a mixture of urea and an 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.

The fungicide composition according to the present invention may further contain various formulation auxiliaries commonly used in the field of pesticide formulation, and specifically, the formulation auxiliaries may be one or more of a solvent, a cosolvent, a thickener, an antifreeze, a capsule material, a protectant, an antifoaming agent, a disintegrant, a stabilizer, a preservative, a binder, and a chelating agent.

Suitable solvents are water and organic solvents, such as mineral oil fractions of medium to high boiling point, e.g. kerosene, diesel oil; oils of vegetable or animal origin; aliphatic, cyclic and aromatic hydrocarbons, such as toluene, paraffins, tetrahydronaphthalene, alkylated naphthalenes; alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycols; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonate, fatty acid ester, γ -butyrolactone; a fatty acid; a phosphonate ester; amines; amides, such as N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.

The solvents mentioned above can also be used as cosolvents.

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

Suitable antifreeze agents are selected from the group consisting of ethylene glycol, propylene glycol, glycerol, urea, glycerol and mixtures thereof.

Suitable capsule materials are selected from the group consisting of polyurethanes, polyureas, urea-formaldehyde resins and mixtures thereof.

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

Suitable antifoaming agents are selected from the group consisting of polysiloxanes, silicone emulsions, long chain alcohols, fatty acids and salts thereof, and fluoro-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 the group consisting of triphenyl phosphite, epichlorohydrin, acetic anhydride and mixtures thereof.

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

Suitable binders are selected from polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylates, biological or synthetic waxes and cellulose ethers.

The fungicides according to the invention can be applied in their formulated form or in the use forms prepared therefrom, such as aerosols, capsule suspensions, cold-fogging concentrates, hot-fogging concentrates, encapsulated granules, fine granules, flowable concentrates for seed treatment (flowable concentrates), ready-to-use solutions, dustable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, macrogranules, microgranules, oil-dispersible powders, oil-miscible flowable concentrates, oil-miscible liquids, gas agents (under pressure), gas-generating products, foams, pastes, suspension concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, dusts and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, wettable powders, natural and synthetic substances impregnated with active substances, and microcapsules in polymers and seed coatings, and ULV (ultra low volume) cold and hot fog formulations. The above forms of use can be prepared by conventional means in the art.

Application of the inventive compounds and compositions

The compound of the present invention is useful as a plant disease control agent. The present invention therefore also comprises a method for controlling plant diseases caused by phytopathogenic fungi, which comprises applying to the plants to be protected or to parts thereof or to the seeds of the plants to be protected an effective amount of a compound according to the invention or of a fungicidal composition comprising said compound. The compounds and/or compositions of the present invention provide control of diseases caused by a broad spectrum of phytopathogenic fungi of the classes Basidiomycetes, Ascomycetes, Oomycetes and Deuteromycetes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal and fruit crops. These pathogens include: oomycetes, including Phytophthora (Phytophthora) diseases such as Phytophthora infestans, Phytophthora sojae (Phytophthora megasporum), Phytophthora citri (Phytophthora parasitica), Phytophthora citrullus (Phytophthora parasiti), Phytophthora cinnamomi (Phytophthora cinnamomi) and Phytophthora cucurbitae (Phytophthora capsici), Pythium graminum (Pythium) species diseases such as Pythium turtium (Pythium aphanidermatum) diseases, and Peronosporaceae (Peronospora) species diseases such as Plasmopara viticola (Plasmopara viticola), Peronospora (Peronospora spp.) (including P. nicotianae (Peronospora tabacina) and P. parasitica (Pseudoperonospora Pseudoperonospora), including P. nicotianae (Pseudoperonospora cinerea) and P. Pseudoperonospora (Pseudoperonospora Pseudoperonospora) diseases including P); ascomycetes (including Alternaria (Alternaria) such as Alternaria solani and Phytophthora brassicae (Alternaria solani), Mycoporia globosa (Guignardia) diseases such as Staphylococcus viticola (Guignardia bidwell), Venturia (Venturia) diseases such as Venturia mali (Venturia inaequalis), Sphaerotheca (Sepia) diseases such as Microphyllum nodosum (Septorium nodorum) and Phytophthora parasitica (Septorii), Powderzia (Powdery) diseases such as Erysiphe graminis (Erysiphe spp.) and Sphaerotheca (Septoria oryzae), Powder Erysiphe (Erysiphe) diseases such as Microphyllum graminis (Erysiphe sp.) and Pseudoperonospora cinerea (Ostericola), Staphylococcus viticola (Uncinula necator), Pseudoperonospora cucumerina (Sphaerothecoides) and Pseudoperonospora cinerea (Botrytis), Scleroti cinerea) diseases such as Microphyllum cinerea (Botrytium cinerea), Scleroti cinerea) diseases such as Microphyllum cinerea (Botrytum cinerea), Scleroti cinerea (Potentilla) diseases such as Microphyllum cinerea (Botrytum cinerea), Scleroti cinerea) diseases such as Microphyllum cinerea (Potentilla cinerea), Scleroti cinerea (Potentilla cinerea), Scleroti cinerea) diseases such, Pyricularia oryzae (Magnaporthe grisea), Rhizoctonia solani (Phomopsis viticola), Helminthosporium (Helminthosporium) diseases such as northern leaf blight (Helminthosporium tritici reptilis), Moss reticulata (Pyrenophora teres), anthrax bacteria such as Hedychium nigrum (Glomerella) or Anthrax (Colletochium spp.) diseases (such as Colletotrichum graminicum (Colestochium graminicum) and watermelon anthrax (Colletochium orbiculosum)), and wheat holothrix graminis (Gaeumannomyces graminis); basidiomycetes, including rust diseases caused by the genus Puccinia (Puccinia spp.), such as Puccinia recondita (Puccinia recondita), Puccinia striiformis (Puccinia striiformis), Puccinia purpurea (Puccinia hordei), Puccinia graminis (Puccinia graminis) and Puccinia arachidis (Puccinia arachidis), coffee rust (hemix) and soybean rust (Phakopsora pachyrhizi); other pathogens include Rhizoctonia species (Rhizoctonia spp.) (such as Rhizoctonia solani); fusarium species diseases such as Fusarium roseum (Fusarium roseum), Fusarium graminearum (Fusarium graminearum), and Fusarium oxysporum (Fusarium oxysporum); verticillium dahliae (Verticillium dahliae); sclerotium rolfsii (sclerotiotium rolfsii); physalospora piricola (Rynchosporium secalis); black acerola (Cercosporium personatum), Episra nigrella (Cercospora arachidicola), and Episra fuscospora (Cercospora betacola); and other classes and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have a resistant activity against bacteria such as Erwinia amylovora (Erwinia amylovora), Xanthomonas campestris (Xanthomonas campestris), Pseudomonas syringae (Pseudomonas syringae) and other species.

The fungicide composition of the invention is simple in use method, and can be applied to crops and places where crops grow by conventional methods such as soil mixing, spraying, pouring and the like before or after plant diseases germinate, wherein the application amount is determined according to climatic conditions or crop conditions, generally 10-5000g is applied per mu, and the diluted application amount is 10-400 mg/L. The diluent is preferably water.

The fungicidal compositions of the present invention have a fungicidal effect which is usually associated with external factors such as climate, but the effect of climate can be alleviated by using appropriate formulations.

The compositions of the present invention may also be used in admixture with other compounds having fungicidal, insecticidal or herbicidal properties, as well as with nematicides, acaricides, protectants, herbicidal safeners, growth regulators, plant nutrients or soil conditioners, and the like.

General synthetic procedure

In this specification, a structure is dominant if there is any difference between the chemical name and the chemical structure. In general, the compounds of the present invention may be prepared by the methods described herein, wherein the substituents are as defined in (I), unless otherwise indicated.

Those skilled in the art will recognize that: the chemical reactions described herein may be used to suitably prepare a number of other compounds of the invention, and other methods for preparing the compounds of the invention are considered to be within the scope of the invention. For example, the synthesis of those non-exemplified compounds according to the present invention can be successfully accomplished by those skilled in the art by modification, such as appropriate protection of interfering groups, by the use of other known reagents (other than those described herein), or by some routine modification of reaction conditions. In addition, the reactions disclosed herein or known reaction conditions are also recognized as being applicable to the preparation of other compounds of the present invention. In addition, in some embodiments, the reaction of the present invention is carried out at room temperature, wherein the room temperature is-10 to 40 ℃, unless otherwise specified.

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

Synthetic schemes

Synthesis scheme I

The target compound I-1 can be prepared by the first synthesis scheme. And reacting the intermediate a and the intermediate b in an alkaline system to obtain the target compound I-1.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

An intermediate M: synthesis of tert-butyl (6- (bromomethyl) pyridin-2-yl) carbamate

Step 1: synthesis of methyl 6- ((tert-butyloxycarbonyl) amino) picolinate

Methyl 2-aminopyridine-6-carboxylate (20.00g,131.45mmol) was dissolved in tetrahydrofuran (200mL), di-tert-butyl dicarbonate (45.6g,210.32mmol) and 4-dimethylaminopyridine (0.1g) were added, and the reaction was stirred at 60 ℃ for 6 hours. The tetrahydrofuran was removed by concentration under reduced pressure to give 32g of a pale yellow liquid, yield: 96 percent.

Step 2: synthesis of tert-butyl (6- (hydroxymethyl) pyridin-2-yl) carbamate

Methyl 6- ((tert-butyloxycarbonyl) amino) picolinate (32g,126.85mmol) and anhydrous calcium chloride (28.16g,253.70mmol) were dissolved in anhydrous ethanol (300mL), and sodium borohydride (14.4g,380.55mmol) was added portionwise at 0 ℃ and stirred at room temperature for 3 hours after the addition was complete. Extraction with dichloromethane (300mL), washing with water (100mL) and saturated brine (100mL × 3), and drying over anhydrous sodium sulfate, concentration under reduced pressure gave 26.8g of a pale yellow liquid, yield: 94 percent.

And step 3: synthesis of tert-butyl (6- (bromomethyl) pyridin-2-yl) carbamate

Tert-butyl (6- (hydroxymethyl) pyridin-2-yl) carbamate (10g,44.59mmol) and carbon tetrabromide (42.59g,128.42mmol) were dissolved in dichloromethane (200mL) at room temperature, potassium carbonate (26.69g,193.08mmol) was added, a solution of triphenylphosphine (33.68g,128.42mmol) in dichloromethane (100mL) was slowly added dropwise to the mixture at 0 ℃ and the mixture was stirred at room temperature for 4 hours after completion of the addition. After insoluble matter was removed by suction filtration, the mixture was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 9/1], to give 3.8g of a pale yellow liquid in 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) methanone oxime

Step 1: synthesis of 4-phenoxybenzoyl chloride

4-Phenoxybenzoic acid (2.14g,10mmol) was dissolved in thionyl chloride (10mL) and heated to 80 ℃ for reflux reaction for 3 hours. Cooled to room temperature, concentrated under reduced pressure to remove excess thionyl chloride, toluene (10mL) was added and concentrated again under reduced pressure to remove volatiles to give 2.3g of a brown oily liquid, yield: 98 percent.

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

Dimethylhydroxylamine hydrochloride (1.2g,12mmol) was dissolved in methylene chloride (10mL) at 0 ℃ and triethylamine (2.8mL, 20mmol) was added dropwise, followed by addition of a solution of 4-phenoxybenzoyl chloride (2.3g,10mmol) in methylene chloride (5mL) and reaction at room temperature for 6 hours. Dichloromethane (100mL) was added, and after washing with water (150mL), saturated sodium bicarbonate (150mL), and saturated brine (150mL), in that order, the organic phases were combined, concentrated under reduced pressure, and the residue was separated by silica gel column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 10/1], yielding 1.4g of a pale yellow liquid with a yield of 54%.

And step 3: synthesis of (1-methyl-1H-tetrazol-5-yl) (4-phenoxyphenyl) methanone

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

And 4, step 4: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (4-phenoxyphenyl) methanone oxime

(1-methyl-1H-tetrazol-5-yl) (4-phenoxyphenyl) methanone (420mg,1.5mmol) and hydroxylamine hydrochloride (261mg,3.8mmol) were dissolved in pyridine (10mL) at room temperature, and the reaction was refluxed at 60 ℃ for 6 hours. Pyridine was removed by concentration under reduced pressure, water (100mL) was added, extraction was performed with ethyl acetate (50mL × 3), the mixture was washed with saturated brine (100mL), the organic phases were combined, concentrated under reduced pressure, and the residue was separated by silica gel column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 4/1] to give 251mg of a pale yellow liquid, yield 57%.

LC-MS:m/z 296.9[M+H]⁺。

Using different phenoxybenzene carboxylic acids as starting materials, the intermediates in Table 1 were obtained by a similar synthesis method to intermediate N1.

TABLE 1

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

(Z) - (1-methyl-1H-tetrazol-5-yl) (4-phenoxyphenyl) methyl ketoxime (251mg,0.85mmol), (6- (bromomethyl) pyridin-2-yl) carbamic acid tert-butyl ester (244mg,0.85mmol) and potassium carbonate (176mg,1.28mmol) were added to a reaction flask at room temperature, N-dimethylformamide (10mL) was added, and the reaction was stirred for 12 hours. The reaction was quenched with water (50mL), extracted with ethyl acetate (30mL × 3), washed with saturated brine (50mL), the organic phases were combined and concentrated under reduced pressure, and the residue was separated by silica gel column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 5/1] to give 300mg of a white solid in 70% yield.

¹H NMR(400MHz,DMSO-d₆)(ppm):9.79(s,1H),7.75(d,J＝5.9Hz,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]⁺。

The intermediate tert-butyl (6- (bromomethyl) pyridin-2-yl) carbamate and the corresponding intermediate N2, intermediate N3, intermediate N4, intermediate N5, intermediate N6, intermediate N7, intermediate N8, intermediate N9, intermediate N10, intermediate N11, intermediate N12, intermediate N13, or intermediate N14 were prepared by a similar synthetic procedure as in example 1 to give the target compounds example 2, 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 in table 2.

TABLE 2

Activity assay

Test example

This test example was used to determine the fungicidal activity of the compounds prepared in the examples. The test target in this test example was cucumber downy mildew. Dissolving the mixture into 1 percent missible oil by using N, N-dimethylformamide for later use. The fungicidal activity of these compounds against the test targets was evaluated at a dose of 200mg/L using the in vivo potting method. The test method adopts the constructed pesticide bioactivity evaluation SOP (bactericide roll).

Pseudoperonospora cubensis (Pseudoperonospora cubensis):

selecting 1 potted cucumber seedling with consistent growth vigor in true leaf period (removing growing point), spraying, air drying, inoculating after 24 hr, taking fresh cucumber downy mildew diseased leaf, washing off sporocyst on back of diseased leaf with distilled water by using writing brush, and making into sporangium suspension (2-3 × 10)⁵one/mL). Uniformly spraying and inoculating on cucumber seedlings by using an inoculation sprayer (the pressure is 0.1MPa), transferring the inoculated test material to an artificial climate chamber, keeping the relative humidity at 100% and the temperature at about 21 ℃, keeping the temperature at about 21 ℃ after 24h, keeping the relative humidity at about 95% for moisture induction, carrying out grading investigation according to blank control disease occurrence conditions after 5d, and calculating the control effect according to disease indexes.

The test results are shown in table 3.

TABLE 3 controlling effect of the compounds of the invention against cucumber downy mildew at a dose of 200mg/L

Examples	Control Effect against cucumber downy mildew (%)
Example 1	100
Example 2	100
Example 3	100

Examples	Control Effect against 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

From the test results, the compound has good control effect on plant pathogenic fungi, especially on cucumber downy mildew, and has further research and development value.

The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

Claims (7)

1. A compound which is a stereoisomer, a nitroxide or a salt thereof having or being of formula (I):

   

   wherein the content of the first and second substances,

   a is

   

   Y is hydrogen or C_1-6An alkyl group;

   m is 1,2, 3 or 4;

   each R^aIndependently hydrogen, halogen, nitro, cyano, hydroxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_3-8Cycloalkyl, phenyl or phenoxy;

   R¹、R²、R³、R⁴and R⁵Each independently is hydrogen, halogen, nitro, cyano, hydroxy, C_1-6Alkyl, aryl, heteroaryl, and heteroaryl,C_1-6Alkoxy, halo C_1-6Alkyl or halo C_1-6An alkoxy group.
2. The compound of claim 1, wherein,

   y is hydrogen or C_1-4An alkyl group;

   m is 1,2, 3 or 4;

   each R^aIndependently hydrogen, halogen, nitro, cyano, hydroxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkoxy radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_2-4Alkenyloxy radical, C_2-4Alkynyloxy or C_3-6A cycloalkyl group;

   R¹、R²、R³、R⁴and R⁵Each independently is hydrogen, halogen, nitro, cyano, hydroxy, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group.
3. The compound of claim 2, wherein,

   y is hydrogen, -CH₃or-CH₂CH₃；

   m is 1,2, 3 or 4;

   each R^aIndependently hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxy, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-CH₂Cl、-CHF₂、-CF₃、-CF(CF₃)₂、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂or-OCF₃；

   R¹、R²、R³、R⁴And R⁵Each independently is hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, hydroxy, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-CH₂Cl、-CHF₂、-CF₃、-CF(CF₃)₂or-OCF₃。
4. The compound of claim 3, wherein,

   

   is of the sub-structure:

   
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 nitroxide or a salt thereof of a compound having one of the following structures:

   

   

   

   
6. a composition comprising at least one compound of 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 combating phytopathogenic fungi.