CN114685392A - Phenyl-tetrazole oxime derivative and preparation method and application thereof - Google Patents

Abstract

The invention relates to a phenyl-tetrazole oxime derivative and a preparation method and application thereof, wherein the phenyl-tetrazole oxime derivative has a structure shown in a formula (I),

wherein R is¹、R²、T、R^a、R^b、R^c、R^dAnd R^eHave the meaning as described in the present invention; the phenyl-tetrazole oxime derivative has excellent control effects on cucumber downy mildew, rice sheath blight, cucumber gray mold, cucumber powdery mildew and the like, and can be further developed and applied as a pesticide bactericide.

Description

Phenyl-tetrazole oxime derivative and preparation method and application thereof

Technical Field

The invention relates to the field of pesticides, in particular to a phenyl-tetrazole oxime derivative, a preparation method thereof and application thereof as a bactericide in agriculture.

Background

In modern agricultural production, various pesticides are required to be frequently used to ensure the healthy growth of crops, however, the pesticides are frequently used for a long time, so that part of diseases on the crops generate drug resistance to the existing pesticides, the prevention and treatment effect of the existing pesticides is reduced, the using dosage of the pesticides needs to be increased in order to achieve the purpose of preventing and treating the diseases, and the great burden is caused to the economy and the environment; in order to meet the requirement of modern pesticides on environmental protection, new compounds with excellent control effect need to be continuously developed.

Disclosure of Invention

The invention provides a compound, and a composition or a preparation containing the compound, and application of the compound as a bactericide in agriculture.

Specifically, the method comprises the following steps:

in one aspect, the present invention provides a compound having the formula (I), or a nitroxide, salt, (Z) isomer, (E) isomer, or a mixture of (Z) isomer and (E) isomer of the compound of formula (I):

wherein,

R¹is C_6-14Aryl or 6-10 membered heteroaryl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, carboxy, amino, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy, -NH (C)_1-6Alkyl) or-N (C)_1-6Alkyl radical)₂Substitution;

R²is hydrogen, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl or C_3-8cycloalkyl-CH₂-；

R^a、R^b、R^c、R^dAnd R^eEach independently of the others is hydrogen, halogen, cyano, nitro, C_1-6Alkyl radical, C_1-6Alkoxy radicalRadical, halo C_1-6Alkyl or halo C_1-6An alkoxy group;

t is

R^fAnd R^gEach independently is hydrogen or C_1-6An alkyl group.

In some embodiments, R¹Is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, carboxy, amino, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy, -NH (C)_1-4Alkyl) or-N (C)_1-4Alkyl radical)₂And (4) substitution.

In other embodiments, R¹Is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, cyano, nitro, hydroxy, carboxy, amino, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OCH₂CH₂CH₂CH₃、-OC(CH₃)₃、-CF₃、-OCF₃、-NH(CH₃) or-N (CH)₃)₂And (4) substitution.

Preferably, in some embodiments, R¹Is phenyl, pyridin-3-yl or quinolin-3-yl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, carboxy, amino, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy, -NH (C)_1-4Alkyl) or-N (C)_1-4Alkyl radical)₂And (4) substitution.

Preferably, some implementationsIn the scheme, R¹Is phenyl, pyridin-3-yl or quinolin-3-yl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, cyano, nitro, hydroxy, carboxy, amino, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OCH₂CH₂CH₂CH₃、-OC(CH₃)₃、-CF₃、-OCF₃、-NH(CH₃) or-N (CH)₃)₂And (4) substitution.

Said pyridin-3-yl group being

Said quinolin-3-yl being

Representing the position of attachment of the structural formula to the rest of the molecule.

In still other embodiments, R¹Is composed of

In some embodiments, R²Is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl or C_3-6cycloalkyl-CH₂-。

In other embodiments, R²Is hydrogen, -CH₃、-CH₂CH₃、-CH＝CH₂、-CH₂-CH＝CH₂、-CH≡CH₂、-CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-。

Preferably, in some embodiments, R²Is hydrogen.

In some embodiments, R^a、R^b、R^c、R^dAnd R^eEach independently of the others is hydrogen, halogen, cyano, nitro, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group.

In other embodiments, R^a、R^b、R^c、R^dAnd R^eEach independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, -CH₃、-OCH₃、-CF₃or-OCF₃。

Preferably, in some embodiments, R^a、R^b、R^c、R^dAnd R^eEach independently hydrogen.

In some embodiments, T is

R^fAnd R^gEach independently is hydrogen or C_1-4An alkyl group.

In other embodiments, T is

R^fAnd R^gEach independently is hydrogen, -CH₃or-CH₂CH₃。

Preferably, in some embodiments, T is

Wherein R is^fis-CH₃。

In some embodiments, the present invention provides a compound that is a nitroxide, a stereoisomer, or a salt thereof, having formula (I-a):

wherein R is¹、R²、T、R^a、R^b、R^c、R^dAnd R^eHave the meaning as described in the present invention; the compound shown in the formula (I-A) is a (Z) type isomer of the compound shown in the formula (I).

In other embodiments, the present invention provides a compound that is a nitroxide, a stereoisomer, or a salt thereof of a compound having, or of a compound of formula (I-B):

wherein R is¹、R²、T、R^a、R^b、R^c、R^dAnd R^eHave the meaning as described in the present invention; the compound shown in the formula (I-B) is an (E) type isomer of the compound shown in the formula (I).

In some embodiments, the present invention provides a compound that is a nitroxide, a stereoisomer, or a salt thereof, having formula (I-a):

wherein,

R^a、R^b、R^c、R^dand R^eEach independently is hydrogen;

t is

Wherein R is^fIs C_1-4An alkyl group;

R¹is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1 or 2 substituents selected from halogen, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy, -NH (C)_1-4Alkyl) or-N (C)_1-4Alkyl radical)₂Substitution;

R²is hydrogen.

In other embodiments, T is

Wherein R is^fis-CH₃；

R¹Is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1 or 2 groups selected from fluoro, chloro, bromo, iodo, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OCH₂CH₂CH₂CH₃、-OC(CH₃)₃、-CF₃、-OCF₃、-NH(CH₃) or-N (CH)₃)₂And (4) substitution.

In some embodiments, the present invention provides a compound that is a compound having one of the following structures, or a nitroxide, a salt, (Z) isomer, (E) isomer, or a mixture of (Z) and (E) isomers of a compound having one of the following structures:

in another aspect, the present invention provides a composition comprising at least one compound according to the invention and adjuvants customary in agro-pharmaceutical industry.

In yet another aspect, the invention provides the use of a compound according to the invention or a composition according to the invention as a fungicide in agriculture.

In yet another aspect, the present invention provides the use of a compound according to the present invention or a composition according to the present invention for controlling plant diseases.

Specifically, the plant disease is caused by a plant pathogenic fungus.

Preferably, the plant diseases are cucumber downy mildew, rice sheath blight, cucumber gray mold and cucumber powdery mildew.

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 designate 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, e.g., 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, for example, by chromatography and/or fractional crystallization, depending on the differences in the physicochemical properties of the components.

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, heterocyclylacyl, 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, which means 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 (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 "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 atoms, examples of which include, but are not limited to, -CF₃，-CHF₂，-CH₂Cl，-CH₂CF₃，-CH₂CHF₂，-CH₂CH₂CF₃And so on.

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 so on.

The term "aryl" denotes monocyclic, bicyclic and tricyclic carbon ring systems containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, wherein each ring system comprises a ring of 3 to 7 atoms with one or more attachment points to the rest of the molecule. The term "aryl" may be used interchangeably with the term "aromatic ring". Examples of the aryl group may include phenyl, indenyl, naphthyl and anthryl. The aryl group is optionally substituted with one or more substituents described herein.

The term "heteroaryl" denotes monocyclic, bicyclic and tricyclic ring systems containing 5 to 12 ring atoms, or 5 to 10 ring atoms, or 5 to 6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring of 5 to 7 atoms with one or more attachment points to the rest of the molecule. The term "heteroaryl" may be used interchangeably with the terms "heteroaromatic ring" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, a heteroaryl group of 5-10 atoms contains 1,2, 3, or 4 heteroatoms independently selected from O, S, and N. Examples of heteroaryl groups include, but are not limited to, pyridin-3-yl, quinolin-3-yl, benzopiperidinyl, benzothien-3-yl, and the like.

The term "cyano" refers to — CN.

The term "hydroxy" refers to-OH.

The term "nitro" means-NO₂。

The term "carboxy" refers to-COOH.

The term "amino" refers to the group-NH₂。

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 optionally be substituted with one or more of those described hereinSubstituents, which include the positioning of "cis" and "tan", or 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. Examples of alkynyl groups include, but are not limited to, ethynyl (-CH ≡ CH), propargyl (-CH ≡ CH)₂C ≡ CH), and the like.

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, cycloalkyl groups contain 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.

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 the compounds of the invention may be prepared by reaction with a metal hydroxide (e.g., sodium hydroxide) or an amine (e.g., ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, diallylamine, 2-butoxyethylamine, morpholine, cyclododecaneAmine or benzylamine) by treatment of a compound described herein.

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 invention are generally useful as fungicide active ingredients in compositions or formulations, usually also including adjuvants commonly used in agro-pharmaceutical practice; the adjuvant comprises a surfactant and/or a carrier.

The surfactant may be any of various surfactants known in the field of pesticide formulation, and one or more of an emulsifier, a dispersant and a wetting agent are preferred in the present invention.

The carrier other than the surfactant may be any of various carriers known in the field of pesticide formulation, 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 emulsifier may be any emulsifier known in the field of pesticide formulation, and specifically, the emulsifier may be one or more of calcium dodecylbenzenesulfonate, trisphenethylphenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene polyoxypropylene ether, fatty amine, ethylene oxide adduct of fatty amide, fatty acid polyoxyethylene ester, rosin acid ethylene oxide adduct, polyhydric alcohol fatty acid ester and ethylene oxide adduct thereof, styrylphenyl polyoxyethylene ether, alkylphenol formaldehyde resin polyoxyethylene ether, hydroxyl-terminated polyoxyethylene polyoxypropylene ether, styrylphenol formaldehyde resin polyoxyethylene polyoxypropylene ether and castor oil polyoxyethylene ether.

The dispersing agent can be various dispersing agents known in the field of pesticide formulation, and specifically, the dispersing agent is one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalene sulfonic acid formaldehyde condensation product sodium salt, rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, hydroxyl-terminated polyoxyethylene polyoxypropylene ether block copolymer, triphenyl polyoxyethylene phenol phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignosulfonate sodium salt.

The wetting agent can be various wetting agents known in the field of pesticide formulation, and specifically, the wetting agent can be one or more of sodium dodecyl sulfate, secondary alkyl sodium sulfate, sodium dodecyl benzene sulfonate, fatty alcohol-polyoxyethylene ether, alkyl naphthalene sulfonate and alkylphenol resin polyoxyethylene ether sulfate.

According to the bactericide composition, various preparation auxiliaries commonly used in the field of pesticide formulation can be further contained, and specifically, the preparation auxiliaries can be one or more of a solvent, a cosolvent, a thickening agent, an antifreezing agent, a capsule wall material, a protective agent, an antifoaming agent, a disintegrating agent, a stabilizing agent, a preservative and a binder.

The solvent may be any of various solvents known in the field of pesticide formulation, and specifically, the solvent may be one or more of an organic solvent, a vegetable oil, a mineral oil, a solvent oil and water.

Wherein the organic solvent comprises one or more of N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N-dimethyldecanamide, N-dimethylformamide, trimethylbenzene, tetramethylbenzene, dimethylbenzene, methylbenzene, octane, heptane, methanol, isopropanol, N-butanol, tetrahydrofurfuryl alcohol, tributyl phosphate, 1, 4-dioxane and cyclohexanone.

The vegetable oil comprises one or more of methylated vegetable oil, rosin-based vegetable oil, turpentine oil, epoxidized soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine seed oil.

The mineral oil comprises one or more of liquid wax, engine oil, kerosene and lubricating oil.

Meanwhile, the solvent can also be used as a cosolvent.

The antifreeze can be various antifreeze agents known in the field of pesticide formulation, and the invention is preferably one or more of ethylene glycol, propylene glycol, glycerol and urea.

The thickener can be various thickeners known in the field of pesticide formulation, and specifically can be one or more of xanthan gum, polyvinyl alcohol, polypropylene alcohol, polyethylene glycol, white carbon black, diatomite, kaolin, clay, sodium alginate, magnesium aluminum silicate, sodium aluminum silicate, carboxymethyl cellulose, sodium hydroxypropyl cellulose and organic bentonite.

The capsule material can be various capsule materials known in the field of pesticide formulation, and the invention is preferably one or more of polyurethane, polyurea and urea-formaldehyde resin.

The protective agent may be any of various protective agents known in the field of pesticide formulation, and polyvinyl alcohol and/or polyethylene glycol is preferred in the present invention.

The defoaming agent may be any of those known in the field of agricultural agent formulation, and in the present invention, one or more of organosiloxane, tributyl phosphate and silicone are preferable.

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

The antiseptic is selected from one or more of benzoic acid, sodium benzoate, 1, 2-benzisothiazolin-3-one (BIT), Kathon and potassium sorbate.

The invention also provides a preparation prepared from the bactericide composition, and the preparation is in the form of missible oil, aqueous emulsion, microemulsion, soluble liquid, aqueous suspension, suspoemulsion, ultra-low volume spray, oil suspension, microcapsule suspension, water surface spreading oil, wettable powder, water dispersible granule, dry suspension, soluble powder, soluble granule, emulsifiable powder, emulsifiable granule, solid microcapsule preparation, effervescent tablet, effervescent granule, water floating dispersion granule or seed coating. The above formulations can be prepared by methods conventional in the art.

The preparation method of the emulsifiable concentrate preparation can comprise, for example, mixing and stirring the active components, the solvent, the cosolvent and the emulsifier to form a uniform transparent oil phase, so as to obtain the emulsifiable concentrate preparation.

The preparation method of the aqueous emulsion can comprise, for example, mixing the active ingredient, the emulsifier, the cosolvent and the solvent to form a uniform oil phase; mixing water, thickener, antifreeze, etc. to obtain uniform water phase. Under high-speed shearing, adding the water phase into the oil phase or adding the oil phase into the water phase to form the aqueous emulsion with good dispersibility.

The microemulsion may be prepared, for example, by mixing and stirring the active ingredient, emulsifier, and solvent to form a uniform transparent oil phase. Under stirring, water is gradually added to form a uniform and transparent microemulsion.

The preparation method of the water/oil suspending agent comprises the following steps: for example, water or oil can be used as a medium, and an auxiliary agent such as an active component and a surfactant is added into a sanding kettle, and after grinding to a certain particle size, filtration is performed. And adding the weighed thickening agent into the ground mother liquor, and uniformly shearing and dispersing. Making into oil suspension or water suspension.

The preparation method of the water dispersible granule and the soluble granule comprises the following steps: for example, the active ingredients, the dispersing agent, the wetting agent, the carrier and the like are uniformly mixed, then are pulverized into a certain particle size through air flow, are added with water for kneading, are finally added into a granulator for granulation, and are dried to obtain the water dispersible granules or the soluble granules.

The preparation method of the soluble powder and the wettable powder comprises the following steps: for example, the active ingredients, various adjuvants and fillers such as other carriers can be thoroughly mixed and pulverized by a micronizer.

The germicide composition of the present invention may be provided in the form of a finished formulation, i.e., the components of the composition have been mixed; or in separate formulations which are self-mixing in a tub or tank prior to use and optionally diluted by mixing with water depending on the concentration of active desired.

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 or parts thereof to be protected or to the seeds of the plants to be protected an effective amount of a compound according to the present invention or of a fungicidal composition comprising a compound according to the present invention. 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 capsici (Phytophthora parasita), Phytophthora cinnamomi (Phytophthora cinmamani) and Phytophthora cucumeria (Phytophora capsicii), Pythium species diseases such as Pythium turfgrasum (Pythium aphanidermatum), and Peronosporaceae (Peronospora) species diseases such as Plasmopara viticola (Plasmopara viticola), Peronospora species diseases (Peronospora spp) (including Phytopora tabacuminata and Pseudoperonospora parasitica (Peronospora Pseudoperonospora), including Pseudoperonospora tabacuminata and Pseudoperonospora parasitica (Pseudoperonospora solani)); 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 as Pseudoperonospora cinerea (Potentilla cinerea), Scleroti cinerea (Potentilla cinerea) diseases (Potentilla cinerea), Scleroti cinerea) diseases (Potentilla cinerea), Scedodes (Scleroti cinerea) diseases (Botrytum cinerea), Scedodes (Potentilla cinerea) diseases (Potentilla cinerea), Scytum cinerea), Scedodes (Potentilla cinerea), Scedodes (Botrytum cinerea) diseases (Potentilla cinerea) diseases (Pothium cinerea), and Gracilaria (Botrytum cinerea) diseases (Botrytum cinerea), and Gracilaria (Botrytum cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea) diseases (Pothium cinerea), and Gracilaria (Pothium cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea (Botrytum cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea (Botrytum cinerea) diseases (Botrytum cinerea), and Gracilaria cinerea) diseases (Botrytum cinerea), and Botrytum cine, Pyricularia oryzae (Magnaporthe grisea), Ralstonia viticola (Phomopsis viticola), Helminthosporium (Helminthosporium) diseases such as northern leaf blight (Helminthosporium tritici reptilis), Moss reticulata (Pyrenophora teres), anthracnose bacteria such as Heplodia nigra (Glomeella) or Colletotrichum spp. diseases (such as Colletotrichum graminicola and Colletotrichum citrulli (Colletotrichum orbiculare)), and Triticum triticum gracilis (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 clouded (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 bactericide composition of the invention is simple in use method, and is applied to crops and places where the crops grow by a conventional method, such as soil mixing, spraying, pouring and the like before or after the plant diseases germinate, wherein the application amount is determined according to climatic conditions or crop states, generally, the effective amount applied per mu is 10-5000g, and the bactericide composition is diluted to be applied at 10-400mg/L (preferably 100-300 mg/L). The diluent is preferably water.

The bactericidal effect of the bactericide composition of the present invention is generally related to external factors such as climate, but the influence of climate can be alleviated by using appropriate dosage forms.

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

The following schemes describe the preparation of the compounds of the present invention, which may be prepared by the methods described herein, unless further indicated. The starting materials, reagents and the like used for preparing the compounds of the present invention are commercially available; or starting materials, reagents, etc. may be prepared by methods conventional in the art. In this specification, a structure is dominant if there is any difference between the chemical name and the chemical structure. In the present invention, the room temperature is 5 ℃ to 35 ℃ unless otherwise specified.

The test conditions of the nuclear magnetic resonance hydrogen spectrum of the invention are as follows: brookfield (Bruker) nuclear magnetic instrument at 400MHz or 600MHz in CDC1 at room temperature₃Or d⁶DMSO as solvent (reported in ppm) with TMS (0ppm) as reference standard. When multiple peaks occur, the following abbreviations will be used: s (singleton), d (doublet), t (triplet), q (quatet), m (multiplet), br (broadenerd, broad), and the likePeaks), dd (doublet of doublets), dt (doublet of triplets).

The conditions for the low resolution Mass Spectrometry (MS) data determination of the invention are: agilent 6120 Quadrupole HPLC-MS (column model: Zorbax SB-C18,2.1X30mm,3.5 μm,6min, flow rate 0.6mL/min, mobile phase 5% -95% (CH with 0.1% formic acid)₃CN) in (H containing 0.1% formic acid)₂Proportion in O)), at 210/254nm with UV detection, using electrospray ionization mode (ESI).

Synthetic schemes

The target compound of formula (I) may be prepared by the above synthetic scheme. Specifically, a compound shown in a formula (a) and a compound shown in a formula (b) are subjected to substitution reaction under an alkaline condition (such as potassium carbonate) to obtain a target compound shown in a formula (I);

wherein R is¹、R²、T、R^a、R^b、R^c、R^dAnd R^eHas the meaning of the invention, hal is fluorine, chlorine, bromine or iodine.

Examples

Intermediate 1: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone oxime

The first step is as follows: synthesis of N-methyl-2-oxo-2-phenylacetamide

Methyl benzoylformate (164g,1mol) was dissolved in a solution of methanol (500mL) at 0 deg.C, and an aqueous methylamine solution (40%, 101g,1.3mol) was added dropwise, the addition was complete, and the reaction was stirred at room temperature for 2 hours. TLC, concentrated under reduced pressure to remove the solvent, diluted with ethyl acetate (300mL), washed sequentially with water (200mL), 1N sodium hydroxide (200mL), 1N hydrochloric acid (200mL) and saturated brine (200mL), dried over anhydrous sodium sulfate, filtered, and concentrated the filtrate under reduced pressure to give 130g of a pale yellow solid, yield: 80.4 percent.

LC-MS:(M+1)m/z＝164.1.

The second step is that: synthesis of (Z) -N-methyl-2-oxo-2-phenylacetyliminochloride

N-methyl-2-oxo-2-phenylacetamide (65g,0.4mol) was dissolved in a mixed solution of N, N-dimethylformamide (2.9g,0.04mol) and chloroform (500mL) at 0 ℃ and thionyl chloride (71.4g,0.6mol) was added dropwise thereto, the reaction was completed dropwise, the mixture was stirred at room temperature for 2 hours, and then the mixture was heated to 60 ℃ to react for 8 hours. TLC, concentrated under reduced pressure to remove the solvent, diluted with toluene (100mL), stirred at room temperature for 8 hours, and concentrated under reduced pressure to give 70g brown oily liquid, yield: 96.2 percent.

LC-MS:(M+1)m/z＝182.0.

The third step: synthesis of (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone

Sodium azide (6.5g,100mmol) and tetrabutylammonium bromide (1.62g,5mmol) were dissolved in a mixed solution of toluene (20mL) and water (20mL) at room temperature, a toluene solution (60mL) of (Z) -N-methyl-2-oxo-2-phenylacetyliminochloride (18.2g,100mmol) was added dropwise, and the reaction was stirred at room temperature for 2 hours. TLC monitored the reaction was complete, diluted with toluene (20mL), washed with water (100mL x3) and saturated brine (100mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to give 15.4g brown oily liquid, yield: 85.4 percent.

LC-MS:(M+1)m/z＝189.1.

The fourth step: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone oxime

(1-methyl-1H-tetrazol-5-yl) (phenyl) methanone (15g,80mmol) and hydroxylamine hydrochloride (11.1g,160mmol) were dissolved in ethanol (100mL) at room temperature, warmed to 48 deg.C, stirred for 12 hours and monitored by TLC for completion. Concentration under reduced pressure to remove ethanol, dilution with water (100mL), extraction with ethyl acetate (50mL × 3), combination of the organic phases, washing with saturated brine (100mL), concentration under reduced pressure, and separation of the residue by silica gel column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 4/1] gave 5.6g of a pale yellow solid, yield: 34.1 percent.

LC-MS:(M+1)m/z＝204.1.

Intermediate 2: synthesis of 2-chloro-N-phenylacetamide

Aniline (0.47g,5.0mmol), triethylamine (0.51g,5.0mol), and dichloromethane (30mL) were added to a 100mL single-neck flask, chloroacetyl chloride (0.68g,6.0mmol) was added dropwise with stirring at 0 deg.C, after the addition was complete, the reaction was stirred at room temperature for 2 hours, and the reaction was monitored by TLC for completion. The reaction was quenched with water (50mL), extracted with dichloromethane (20mLx3), and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 0.58g of a yellow oily liquid in 68% yield.

LC-MS:(M+1)m/z＝170.0.

The intermediate compounds in table 1 were prepared with the corresponding starting materials and chloroacetyl chloride as starting materials, with reference to the preparation of intermediate 2, or with reference to the preparation of the prior art.

TABLE 1

Example 1: synthesis of (Z) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) -N-phenylacetamide

Intermediate 1 (i.e. (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) ketoxime) (0.41g,2mmol), anhydrous potassium carbonate (0.55g,4mmol) and N, N-dimethylformamide (15mL) were added to a 50mL single vial, a solution of intermediate 2 (i.e.: 2-chloro-N-phenylacetamide) (0.68g,4mmol) in N, N-dimethylformamide (5mL) was added dropwise, the reaction was stirred at room temperature for 12H, TLC monitored for completion of the starting reaction; the reaction was quenched with water (150mL), extracted with ethyl acetate (50mL × 3), the organic phases were combined and dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was silica gel-mixed and purified by column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 4/1] to give 0.42g of a white solid, yield: 62.6 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.56(s,1H),7.47(d,J＝8.3Hz,3H),7.39(d,J＝8.1Hz,2H),7.32-7.28(m,3H),7.25–7.23(m,2H),4.25(s,2H),3.93(s,3H).

LC-MS:(M+1)m/z＝337.1.

Example 2: synthesis of (Z) -N- (3-chloro-2-methylphenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 3 (i.e.: 2-chloro-N- (3-chloro-2-methylphenyl) acetamide) (0.87g,4mmol) were prepared according to the preparation method of example 1 to give 0.51g of a white solid in yield: 65.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.51(s,1H),7.42(d,J＝8.3Hz,3H),7.33(d,J＝8.3Hz,2H),7.30-7.27(m,1H),7.22–7.20(m,2H),4.22(s,2H),3.90(s,3H),2.51(s,3H).

LC-MS:(M+1)m/z＝385.1.

Example 3: synthesis of (Z) -N- (2-fluoro-3-methylphenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 4 (i.e.: 2-chloro-N- (2-fluoro-3-methylphenyl) acetamide) (0.81g,4mmol) were prepared according to the procedure of example 1 to give 0.45g of a white solid in yield: 61.1 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.27(m,1H),7.23–7.20(m,2H),4.27(s,2H),3.92(s,3H),2.55(s,3H).

LC-MS:(M+1)m/z＝369.1.

Example 4: synthesis of (Z) -N- (2-bromo-4-fluorophenyl) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 5 (i.e., N- (2-bromo-4-fluorophenyl) -2-chloroacetamide) (1.06g,4mmol) were prepared according to the preparation method of example 1 to give 0.53g of a white solid in yield: 61.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.51(s,1H),7.42(d,J＝8.2Hz,3H),7.35(d,J＝8.3Hz,2H),7.31-7.27(m,1H),7.22–7.20(m,2H),4.22(s,2H),3.90(s,3H).

LC-MS:(M+1)m/z＝433.0.

Example 5: synthesis of (Z) -N- (3-fluorophenyl) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 6 (2-chloro-N- (3-fluorophenyl) acetamide) (0.75g,4mmol) were prepared according to the preparation method of example 1 to give 0.44g of a white solid in yield: and (3.2).

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.27(m,2H),7.23–7.20(m,2H),4.24(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝355.1.

Example 6: synthesis of (Z) -N- (2-bromo-6-fluorophenyl) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 7 (i.e., N- (2-bromo-6-fluorophenyl) -2-chloroacetamide) (1.06g,4mmol) were prepared according to the preparation method of example 1 to give 0.57g of a white solid in yield: 66.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.50(s,1H),7.43(d,J＝8.4Hz,3H),7.35(d,J＝8.3Hz,2H),7.31-7.27(m,1H),7.21–7.18(m,2H),4.22(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝433.0.

Example 7: synthesis of (Z) -N- (3, 4-difluorophenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 8 (i.e., 2-chloro-N- (3, 4-difluorophenyl) acetamide) (0.82g,4mmol) were prepared according to the procedure for the preparation of example 1 to give 0.45g of a white solid in yield: 60.2 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.27(m,2H),7.23–7.20(m,1H),4.24(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝373.1.

Example 8: synthesis of (Z) -N- (2, 6-dibromophenyl) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 9 (i.e., 2-chloro-N- (2, 6-dibromophenyl) acetamide) (1.31g,4mmol) were prepared according to the procedure for the preparation of example 1 to give 0.59g of a white solid in yield: 60.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.50(s,1H),7.43(d,J＝8.4Hz,3H),7.35(d,J＝8.3Hz,2H),7.31-7.27(m,2H),7.21–7.18(m,1H),4.22(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝493.0.

Example 9: synthesis of (Z) -N- (2, 4-dichlorophenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 10 (i.e., 2-chloro-N- (2, 4-dichlorophenyl) acetamide) (0.95g,4mmol) were prepared according to the procedure for example 1 to give 0.54g of a white solid in yield: 67.2 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.51(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.28(m,2H),7.23–7.20(m,1H),4.24(s,2H),3.93(s,3H).

LC-MS:(M+1)m/z＝405.1.

Example 10: synthesis of (Z) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) -N- (2- (trifluoromethoxy) phenyl) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 11 (i.e.: 2-chloro-N- (2- (trifluoromethoxy) phenyl) acetamide) (1.02g,4mmol) were prepared according to the preparation method of example 1 to give 0.45g of a white solid in yield: 54.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.52(s,1H),7.44(d,J＝8.4Hz,3H),7.36(d,J＝8.3Hz,2H),7.31-7.27(m,2H),7.21–7.18(m,2H),4.25(s,2H),3.94(s,3H).

LC-MS:(M+1)m/z＝421.1.

Example 11: synthesis of (Z) -N- (3-isopropoxyphenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 12 (2-chloro-N- (3-isopropoxyphenyl) acetamide) (0.91g,4mmol) were prepared according to the method of example 1 to give a white solid 0.49g, yield: and (3.2).

¹H NMR(400MHz,CDCl₃)δ(ppm):8.51(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.28(m,2H),7.23–7.20(m,1H),7.11(s,1H),4.56(dq,J＝12.0,6.0Hz,1H),4.24(s,2H),3.93(s,3H),1.35(d,J＝6.0Hz,6H).

LC-MS:(M+1)m/z＝395.2.

Example 12: synthesis of (Z) -N- (3-bromophenyl) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 13 (i.e., N- (3-bromophenyl) -2-chloroacetamide) (0.99g,4mmol) were prepared according to the preparation method of example 1 to give 0.42g of a white solid in yield: 51.3 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.52(s,1H),7.44(d,J＝8.4Hz,3H),7.36(d,J＝8.3Hz,2H),7.31-7.27(m,3H),7.18(s,1H),4.25(s,2H),3.94(s,3H).

LC-MS:(M+1)m/z＝415.0.

Example 13: synthesis of (Z) -N- (2-fluoro-5-methylphenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 14 (i.e., 2-chloro-N- (2-fluoro-5-methylphenyl) acetamide) (0.81g,4mmol) were prepared according to the procedure for the preparation of example 1 to give 0.40g of a white solid in yield: 54.1 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.27(m,1H),7.23–7.20(m,2H),4.27(s,2H),3.92(s,3H),2.55(s,3H).

LC-MS:(M+1)m/z＝369.1.

Example 14: synthesis of (Z) -N- (4- (tert-butyl) phenyl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 15 (i.e., N- (4- (tert-butyl) phenyl) -2-chloroacetamide) (0.90g,4mmol) were prepared according to the preparation method of example 1 to give 0.48g of a white solid in yield: 61.7 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.52(s,1H),7.44(d,J＝8.4Hz,3H),7.36(d,J＝8.3Hz,2H),7.26(dd,J＝9.4Hz,2H),7.19(dd,J＝10.8Hz,2H),4.25(s,2H),3.94(s,3H),1.33(s,9H).

LC-MS:(M+1)m/z＝393.2.

Example 15: synthesis of (Z) -N- (4-chloropyridin-3-yl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 16 (2-chloro-N- (4-chloropyridin-3-yl) acetamide) (0.82g,4mmol) were prepared according to the method of example 1 to give 0.37g of a white solid in yield: 50.1 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.45(d,J＝8.1Hz,3H),7.36(d,J＝8.2Hz,2H),7.31-7.27(m,1H),7.23–7.20(m,2H),4.27(s,2H),3.92(s,3H).

LC-MS:(M+1)m/z＝372.1.

Example 16: synthesis of (Z) -N- (2-bromopyridin-3-yl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 17 (i.e.: N- (2-bromopyridin-3-yl) -2-chloroacetamide) (0.99g,4mmol) were prepared according to the method of example 1 to give 0.45g of a white solid in yield: 54.1 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.49(s,1H),7.43(d,J＝8.5Hz,3H),7.34(d,J＝8.1Hz,2H),7.30-7.27(m,1H),7.24–7.20(m,2H),4.25(s,2H),3.90(s,3H).

LC-MS:(M+1)m/z＝416.0.

Example 17: synthesis of (Z) -N- (6-fluoropyridin-3-yl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 18 (i.e.: 2-chloro-N- (6-fluoropyridin-3-yl) acetamide) (0.76g,4mmol) were prepared according to the preparation method of example 1 to give 0.39g of a white solid in yield: 55.5 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.55(s,1H),7.42(d,J＝8.1Hz,3H),7.34(d,J＝8.2Hz,2H),7.30-7.26(m,1H),7.22–7.19(m,2H),4.24(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝356.1.

Example 18: synthesis of (Z) -N- (6- (dimethylamino) pyridin-3-yl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 19 (i.e.: 2-chloro-N- (6- (dimethylamino) pyridin-3-yl) acetamide) (0.86g,4mmol) were prepared according to the procedure of example 1 to give 0.47g of a white solid in yield: 62.2 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.49(s,1H),7.43(d,J＝8.5Hz,3H),7.34(d,J＝8.1Hz,2H),7.27(s,1H),7.24–7.20(m,2H),4.24(s,2H),3.90(s,3H),3.13(s,6H).

LC-MS:(M+1)m/z＝381.2.

Example 19: synthesis of (Z) -N- (5-chloropyridin-3-yl) -2- (((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 20 (i.e.: 2-chloro-N- (5-chloropyridin 3-yl) acetamide) (0.82g,4mmol) were prepared according to the procedure for the preparation of example 1 to give 0.38g of a white solid in yield: 51.2 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.55(s,1H),7.42(d,J＝8.1Hz,3H),7.34(d,J＝8.2Hz,2H),7.30(s,1H),7.22–7.19(m,1H),7.13(s,1H),4.24(s,2H),3.91(s,3H).

LC-MS:(M+1)m/z＝372.1.

Example 20: synthesis of (Z) -2- ((((1-methyl-1H-tetrazol-5-yl) (phenyl) methylene) amino) oxy) -N- (quinolin-3-yl) acetamide

Intermediate 1(0.38g,2mmol) and intermediate 21 (i.e.: 2-chloro-N- (quinolin-3-yl) acetamide) (0.89g,4mmol) were prepared according to the procedure for the preparation of example 1 to give 0.51g of a white solid in yield: 66.2 percent.

¹H NMR(400MHz,CDCl₃)δ(ppm):8.53(s,1H),7.64–7.60(m,3H),7.43(d,J＝8.5Hz,3H),7.34(d,J＝8.1Hz,2H),7.27(s,1H),7.24–7.20(m,2H),4.24(s,2H),3.93(s,3H).

LC-MS:(M+1)m/z＝388.1.

And (3) bioassay test:

and (3) test treatment: the compound was dissolved in N, N-dimethylformamide to 1% EC (cream) for use. The bactericidal activity of these compounds at different doses against the test target was evaluated using the in vivo potting method.

1) Pseudoperonospora cubensis test (Pseudoperonospora cubensis)

Selecting 1 potted cucumber seedling with consistent growth vigor in true leaf period (removing growing point), spraying, air drying, inoculating 24 hr later, taking fresh cucumber downy mildew diseased leaf, washing off sporocyst on back of diseased leaf with distilled water by writing brush, and making into sporangium suspension (2-3x 10)⁵one/mL). Uniformly spraying and inoculating on cucumber seedlings by using an inoculation sprayer (the pressure is 0.1MPa), transferring inoculated test materials to a phytotron, and keeping the relative humidity at 100% and the temperature atThe temperature is about 21 ℃, the temperature is kept about 21 ℃ after 24 hours, the relative humidity is kept about 95 percent for moisture induction, and after 5 days, classification investigation is carried out according to the disease condition of blank control, and the control effect is calculated according to the disease index.

2) Cucumber gray mold (Botrytis cinerea)

The method adopts a leaf inoculation method. Two potted cucumber seedlings with the same growth vigor of the true leaf period are selected, and after the agent is sprayed and dried, a fungus cake is inoculated on the leaves. And (3) after 24-26 ℃ dark light moisture preservation is carried out for 24 hours, natural illumination moisture preservation culture is carried out for about 3 days. After the contrast is fully developed, the diameter of the lesion spot of each inoculation point is measured by a caliper, and the control effect is calculated.

The test results are shown below:

TABLE 2 control of cucumber downy mildew by compounds at different concentrations

Note: means that the compound is not subjected to a control effect test at that concentration

As can be seen from Table 2, the compounds of the present invention in examples 1 to 19 had excellent control effect against cucumber downy mildew at various concentrations, and the compounds of the present invention in example 20 had control effect against cucumber downy mildew at concentrations of 100mg/L, 50mg/L and 25mg/L of 100%, 60% and 30% in this order. In addition, the compound of the invention still has excellent control effect on cucumber downy mildew at low concentration, such as the control effect on cucumber downy mildew of example 2, example 4, example 5, example 6, example 7, example 8, example 9, example 10, example 11 and example 13 is between 70 and 100 percent at the concentration of 12.5 mg/L; at the concentration of 6.25mg/L, the control effect of the embodiment 5, the embodiment 6, the embodiment 7 and the embodiment 8 on cucumber downy mildew is between 70 and 100 percent.

In addition, at the concentration of 200mg/L, the control effect of the compounds of the invention on cucumber gray mold in example 5, example 6, example 7, example 8, example 13 and example 14 is between 70 and 100 percent.

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 (10)

1. A compound having the formula (I), or a nitroxide, salt, (Z) isomer, (E) isomer, or a mixture of (Z) isomer and (E) isomer of the compound of formula (I):

wherein,

R¹is C_6-14Aryl or 6-10 membered heteroaryl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, carboxy, amino, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_1-6Alkoxy, -NH (C)_1-6Alkyl) or-N (C)_1-6Alkyl radical)₂Substitution;

R²is hydrogen, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl or C_3-8cycloalkyl-CH₂-；

R^a、R^b、R^c、R^dAnd R^eEach independently of the others is hydrogen, halogen, cyano, nitro, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl or halo C_1-6An alkoxy group;

t is

R^fAnd R^gEach independently is hydrogen or C_1-6An alkyl group.

2. The compound of claim 1, wherein:

R¹is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, carboxy, amino, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy, -NH (C)_1-4Alkyl) or-N (C)_1-4Alkyl radical)₂Substitution;

R²is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl or C_3-6cycloalkyl-CH₂-。

3. The compound of claim 2, wherein:

R¹is phenyl, pyridyl or quinolyl; wherein R is¹Optionally substituted by 1,2, 3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, cyano, nitro, hydroxy, carboxy, amino, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OCH₂CH₂CH₂CH₃、-OC(CH₃)₃、-CF₃、-OCF₃、-NH(CH₃) or-N (CH)₃)₂Substitution;

R²is hydrogen, -CH₃、-CH₂CH₃、-CH＝CH₂、-CH₂-CH＝CH₂、-CH≡CH₂、-CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-。

4. A compound according to claim 3, wherein:

R¹is composed of

5. The compound of claim 1, wherein:

R^a、R^b、R^c、R^dand R^eEach independently of the others is hydrogen, halogen, cyano, nitro, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group;

t is

R^fAnd R^gEach independently is hydrogen or C_1-4An alkyl group.

6. The compound of claim 5, wherein:

R^a、R^b、R^c、R^dand R^eEach independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, -CH₃、-OCH₃、-CF₃or-OCF₃；

T is

R^fAnd R^gEach independently is hydrogen, -CH₃or-CH₂CH₃。

7. The compound according to any one of claims 1 to 6, which is a nitroxide, a stereoisomer or a salt thereof having the formula (I-A) or a compound represented by the formula (I-A):

8. a compound which is a compound having one of the following structures, or a nitroxide, a salt, (Z) isomer, (E) isomer, or a mixture of (Z) isomer and (E) isomer of a compound having one of the following structures:

9. a composition comprising a compound according to any one of claims 1 to 8 and customary auxiliaries in agriculture.

10. Use of a compound according to any one of claims 1 to 8 or a composition according to claim 9 as a fungicide in agriculture.