CN112979629A - Oxime derivatives and application thereof in agriculture - Google Patents

Oxime derivatives and application thereof in agriculture Download PDF

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CN112979629A
CN112979629A CN201911273140.5A CN201911273140A CN112979629A CN 112979629 A CN112979629 A CN 112979629A CN 201911273140 A CN201911273140 A CN 201911273140A CN 112979629 A CN112979629 A CN 112979629A
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alkyl
compound
isomer
methyl
phenyl
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CN112979629B (en
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李义涛
林健
卢辉
朱德豆
常青
姚文强
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Dongguan Hec Pesticides R&d Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/713—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with four or more nitrogen atoms as the only ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D419/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention relates to an oxime derivative and application thereof in agriculture, wherein the oxime derivative has a structure shown as a formula (I),
Figure DDA0002314779130000011
wherein R isa、Rb、Rc、RdAnd ReEach independentlyHydrogen, halogen, etc.; t is tetrazolyl, M is 1,3, 4-oxadiazolyl, 1,2, 4-oxadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 4-triazolyl, 1,3, 4-triazolyl, etc.; a is phenyl or optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1‑6Alkyl radical, C1‑6Alkoxy, halo C1‑6Alkyl and the like substituted phenyl; the oxime derivative has the advantages of low consumption and high control effect on cucumber downy mildew, and can be further developed and applied as a bactericide.

Description

Oxime derivatives and application thereof in agriculture
Technical Field
The invention relates to the field of pesticides, in particular to oxime derivatives, a preparation method of the oxime derivatives, a composition containing the oxime derivatives, and application of the oxime derivatives and the composition containing the oxime derivatives in agriculture as plant diseases, especially as plant disease control agents caused by plant pathogenic fungi.
Background
China is a big agricultural country, has little cultivated land and large population, so that the grain problem is one of the important problems to be solved urgently. Plant fungal diseases are always one of the limiting factors in the production and storage processes of food crops, and cause serious losses in the aspects of the problems of the development stage, the nutritional value, the limited shelf life and the like of products. At present, the prevention and control of plant diseases mainly depend on the use of chemical pesticides, and the pesticide is popular among people due to the small dosage and quick response, but the problems of drug resistance, rampant and pesticide residue are gradually serious due to the fine development of the chemical industry and inaccurate medication technology of farmers, and the dosage is increased for blindly pursuing the effect, so that the research and development of novel efficient, low-toxicity and low-residue pesticides capable of effectively controlling pests become the primary target of pesticide creation at present.
The oxime derivatives of the present invention are not reported in the prior art, and have excellent control effects against diseases caused by phytopathogenic fungi, particularly cucumber downy mildew, at low concentrations, and can be developed as novel fungicides.
Disclosure of Invention
The invention provides a novel oxime derivative, a preparation method of the oxime derivative, and application of a composition and/or preparation containing the oxime derivative as a fungicide 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):
Figure BDA0002314779120000011
wherein the content of the first and second substances,
Ra、Rb、Rc、Rdand ReEach independently is hydrogen, halogen, cyano, nitro, hydroxy, C1-6Alkyl radical, C1-6Alkoxy, halo C1-6Alkyl or halo C1-6An alkoxy group;
t is
Figure BDA0002314779120000012
Wherein R isfAnd RgEach independently is hydrogen or C1-6An alkyl group;
m is 1,3, 4-oxadiazolyl, 1,2, 4-oxadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 4-triazolyl, 1,3, 4-triazolyl, 1,2, 5-oxadiazolyl or 1,2, 5-thiadiazolyl;
a is phenyl or optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-6Alkyl radical, C1-6Alkoxy, halo C1-6Alkyl, halo C1-6Alkoxy radical, C1-6Alkylthio, halo C1-6Alkylthio radical, C2-6Alkenyl radical, C2-6Alkynyl, C3-8Cycloalkyl radical, C3-8cycloalkyl-C1-5Alkyl-, -NR6R7、C1-6alkyl-C (═ O) -, C1-6alkoxy-C (═ O) -, C1-6alkyl-C (═ O) O-or C1-6alkyl-S (═ O)2-a substituted phenyl group;
R6and R7Each independently is hydrogen or C1-6An alkyl group;
the conditions are as follows: the compound of formula (I) is not:
a) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
b) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
c) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (3-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime; and
d) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (2-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime.
Wherein (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime corresponds to the formula:
Figure BDA0002314779120000021
(Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime corresponds to the formula:
Figure BDA0002314779120000022
(Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (3-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime corresponds to the formula:
Figure BDA0002314779120000023
(Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (2-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime corresponds to the formula:
Figure BDA0002314779120000024
in some embodiments, M is
Figure BDA0002314779120000025
Figure BDA0002314779120000026
"#" and "#" denote two connections of MTerminating ends, wherein the "#" connecting end of M and-CH2-connected, the "+" connection end of M is connected to a.
In some embodiments, Ra、Rb、Rc、RdAnd ReEach independently is hydrogen, halogen, cyano, nitro, hydroxy, C1-4Alkyl radical, C1-4Alkoxy, halo C1-4Alkyl or halo C1-4An alkoxy group.
In still other embodiments, Ra、Rb、Rc、RdAnd ReEach independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, -CH3、-OCH3、-CF3or-OCF3。
Preferably, and in some embodiments, R isa、Rb、Rc、RdAnd ReEach independently hydrogen.
In some embodiments, RfAnd RgEach independently is hydrogen or C1-4An alkyl group.
In still other embodiments, RfAnd RgEach independently is hydrogen or-CH3。
Preferably, and in some embodiments, R isfAnd RgEach independently is-CH3。
In some embodiments, a is phenyl or optionally substituted with 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-4Alkyl radical, C1-4Alkoxy, halo C1-4Alkyl, halo C1-4Alkoxy radical, C1-4Alkylthio, halo C1-4Alkylthio radical, C2-4Alkenyl radical, C2-4Alkynyl, C3-6Cycloalkyl radical, C3-6cycloalkyl-C1-3Alkyl-, C1-4alkyl-C (═ O) -, C1-4alkoxy-C (═ O) -, C1-4alkyl-C (═ O) O-or C1-4alkyl-S (═ O)2-substituted phenyl.
Preferably, in some embodiments, A is phenyl or optionally substituted by 1,2,3.4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-4Alkyl radical, C1-4Alkoxy, halo C1-4Alkyl or halo C1-4Alkoxy-substituted phenyl.
Further preferably, in some embodiments, a is phenyl or optionally substituted with 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-4Alkyl, -OCH3、-OCH2CH3、-CF3or-OCF3A substituted phenyl group.
In some embodiments, A is phenyl or optionally substituted with 1,2, 3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, cyano, nitro, hydroxy, -CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-OCH3、-OCH2CH3、-CF3or-OCF3A substituted phenyl group.
Yet in some embodiments, a is the following substructure:
Figure BDA0002314779120000031
Figure BDA0002314779120000041
in some embodiments, the present invention provides a compound that is a nitroxide, a salt, (Z) isomer, (E) isomer, or a mixture of (Z) isomer and (E) isomer of a compound having formula (II):
Figure BDA0002314779120000042
wherein M and A have the meanings indicated for the corresponding substituents of formula (I) according to the invention;
the conditions are as follows: the compound of formula (II) is not:
a) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
b) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
c) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (3-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime; and
d) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (2-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime.
In some embodiments, the present invention provides a compound that is a stereoisomer, a nitroxide or a salt thereof of a compound having formula (II-1) or a compound of formula (II-1):
Figure BDA0002314779120000043
wherein M and A have the meanings indicated for the corresponding substituents in formula (I) or formula (II) according to the invention;
the conditions are as follows: the compound represented by the formula (II-1) is not:
a) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
b) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
c) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (3-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
and
d) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (2-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime.
The inventors of the present application have found that in the compound represented by the formula (II) or the formula (II-1), when A is the same, M is
Figure BDA0002314779120000051
Figure BDA0002314779120000052
The compound has better control effect on cucumber downy mildew; for example, at a dose of 6.25mg/L, the control effect of example 26, example 27 and example 43 on cucumber downy mildew is 85%, 85% and 95%, while the control effect of example 39 and example 47 on cucumber downy mildew is less than 70%; in addition, under the dosage of 6.25mg/L, the control effect of the example 5 and the example 6 on the cucumber downy mildew is 100 percent, and the control effect of the example 41 and the example 42 on the cucumber downy mildew is less than 70 percent.
Wherein the content of the first and second substances,
Figure BDA0002314779120000053
represents Z-isomer, E-isomer or a mixture of Z-isomer and E-isomer of the compound represented by the formula (I); wherein the Z-isomer of the compound shown in the formula (I) is shown in the formula (I-1):
Figure BDA0002314779120000054
the E-isomer of the compound shown in the formula (I) is shown in the formula (I-2):
Figure BDA0002314779120000055
wherein the content of the first and second substances,
Figure BDA0002314779120000057
represents Z-isomer, E-isomer or a mixture of Z-isomer and E-isomer of the compound represented by the formula (II); wherein the Z-isomer of the compound shown in the formula (II) is shown in the formula (II-1):
Figure BDA0002314779120000058
the E-isomer of the compound represented by the formula (II) is represented by the formula (II-2):
Figure BDA0002314779120000059
wherein, Z-type isomer, E-type isomer or mixture of Z-type isomer and E-type isomer shown in formula (I) and formula (II) are all included in the invention, Z-type isomer, E-type isomer or mixture of Z-type isomer and E-type isomer shown in formula (I) and formula (II) can be separated and confirmed by conventional methods, such as high performance liquid chromatography, nuclear magnetic resonance hydrogen spectrometry and/or single crystal diffraction method.
In some embodiments, the present invention provides a compound that is 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:
Figure BDA0002314779120000061
Figure BDA0002314779120000071
Figure BDA0002314779120000081
in another aspect, the present invention provides a composition comprising at least one compound of the present invention as an active ingredient.
Further, the composition comprises an agriculturally pharmaceutically acceptable auxiliary material.
Furthermore, the agriculturally and pharmaceutically acceptable auxiliary materials comprise a surfactant and/or a carrier.
In still another aspect, the present invention provides use of the compound of the present invention or the composition of the present invention as a plant disease control agent in agriculture.
Further, the plant diseases according to the present invention are caused by phytopathogenic fungi.
Still further, the plant diseases according to the present invention include cucumber downy mildew.
In yet another aspect, the present invention provides a method for controlling plant diseases by the compound of the present invention or the composition of the present invention.
Further, the method for controlling plant diseases by using the compound or the composition of the invention is to apply the compound or the composition of the invention to plants and plant growing sites by spraying, pouring and the like before or after the plant diseases germinate.
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" C1-6Alkyl "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, methylthio (MeS, -SCH)3) Ethylthio (EtS, -SCH)2CH3) 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 "haloalkylthio" denotes an alkylthio group substituted with one or more halogen atoms, examples of which include, but are not limited to, -SCF3，-SCH2CHF2And so on.
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 "tans", 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.
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 "cycloalkylalkyl" denotes an alkyl group substituted by one or more cycloalkyl groups, wherein the alkyl group and the cycloalkyl group have the meaning as described herein.
The term "alkylene" denotes the removal of two from a saturated straight or branched chain hydrocarbonSaturated divalent hydrocarbon radicals resulting from hydrogen atoms. Unless otherwise specified, the alkylene group contains 1 to 12 carbon atoms. In one embodiment, the alkylene group contains 1 to 8 carbon atoms; in one embodiment, the alkylene group contains 1 to 6 carbon atoms; in another embodiment, the alkylene group contains 1 to 4 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 3 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 2 carbon atoms. Examples of this include methylene (-CH)2-, ethylene (-CH)2CH2-, propylene (-CH)2CH2CH2-)，-CH(CH3)CH2-，-C(CH3)2-，-CH2CH2CH(CH3)-，-CH2CH2C(CH3)2-, and the like.
In the various parts of this specification, linking substituents are described. Where the structure clearly requires a linking group, the markush variables listed for that group are understood to be linking groups. For example, if the structure requires a linking group and the markush group definition for that variable recites "alkyl" or "aryl," it is understood that the "alkyl" or "aryl" represents an attached alkylene group or arylene group, respectively.
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 the formula N + (R)ARBRCRD) Ammonium cation of (2), wherein R isA、RB、RCAnd RDIndependently selected from hydrogen, C1-C6Alkyl and C1-C6A hydroxyalkyl group. The salt of the compound represented by the formula (I), the formula (II) or the formula (II-1) can be prepared by treating the compound represented by the formula (I), the formula (II) or the formula (II-1) with a metal hydroxide (e.g., sodium hydroxide) or an amine (e.g., 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 invention are generally useful as fungicide active ingredients in compositions and/or formulations, typically also comprising agriculturally acceptable adjuvants; the auxiliary material 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, trisethylphenol 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, polyol 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 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 bactericide composition of the invention is simple in use method, and can be 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 germination of plant diseases, wherein the application amount is determined according to climatic conditions or crop conditions, the effective amount of the bactericide composition applied per mu is generally 10-5000g, and the bactericide composition is diluted to be applied at 10-400mg/L (preferably 300mg/L) for application. 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 0 ℃ 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 temperature3，d6-DMSO，CD3OD or d6Acetone as solvent (reported in ppm) with TMS (0ppm) or chloroform (7.26ppm) as reference standard. When multiple peaks occur, the following abbreviations will be used: s (singleton), d (doublet), t (triplet), q (quatet), m (multiplet), br (broad), dd (doublet of doublets)Dt (doublet of triplets, double triplets). Coupling constants are expressed in hertz (Hz).
The conditions for the low resolution Mass Spectrometry (MS) data determination of the invention are: agilent 6120Quadrupole HPLC-MS (column model: Zorbax SB-C18,2.1X 30mm,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
Synthesis scheme I
Figure BDA0002314779120000161
The target compound shown in the formula (II-1) can be prepared by the first synthesis scheme. Carrying out condensation reaction on the intermediate T and a compound Q under an alkaline condition (such as potassium carbonate, cesium carbonate and the like) to obtain a target compound shown as a formula (II-1);
wherein M and A have the meanings given in the description.
Examples
An intermediate T: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone oxime
Figure BDA0002314779120000162
Step A: synthesis of N-methyl-2-oxo-2-phenylacetamide
Methyl benzoylformate (164g,1mol) was dissolved in a methanol (500mL) solution at 0 deg.C, and aqueous methylamine solution (101g,1.3mol) was added dropwise, after the addition was complete, the reaction mixture was allowed to cool to room temperature and stirred for 2 hours. The solvent was removed under reduced pressure, ethyl acetate (300mL) was added, and the mixture was washed with water (200mL), 1N sodium hydroxide (200mL), 1N hydrochloric acid (200mL) and saturated brine (200mL) in this order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 130g of a pale yellow solid, yield: 80 percent.
And B: synthesis of (Z) -N-methyl-2-oxo-2-phenylaminoacetyl chloride
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 mixture was allowed to stand at room temperature and stirred for reaction for 2 hours, followed by heating under reflux for reaction for 8 hours. The solvent was removed under reduced pressure, toluene (100mL) was added, and after stirring at room temperature for 8 hours, concentration under reduced pressure gave 70g of a brown oily liquid, yield: 96 percent.
And C: 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-phenylimidoacetyl chloride (18.2g,100mmol) was added dropwise, and the reaction was stirred at room temperature for 2 hours after completion of the addition. Toluene (20mL) was added, washed with water (100 mL. times.3) and brine (100mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 15.4g of a brown oily liquid, yield: 85 percent.
Step D: 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, and the reaction was stirred at 48 ℃ for 12 hours. After removal of the solvent under reduced pressure, water (100mL) was added, ethyl acetate was extracted (50mL × 3), the organic phase was washed with saturated brine (100mL), concentrated under reduced pressure, and the residue was separated by column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 4/1] to give 5.6g of a pale yellow solid, yield: 34 percent.
1H NMR(400MHz,CDCl3)δ(ppm):10.48(s,1H),7.41(dd,J＝12.9,7.2Hz,3H),7.32(t,J＝7.4Hz,2H),3.97(s,3H)；
LC-MS:m/z 204.1[M+H]+。
Example 1: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5-phenyl-1, 3, 4-oxadiazol-2-yl) methyl) oxime
Figure BDA0002314779120000171
Step A: synthesis of benzoyl hydrazine
Methyl benzoate (2.52mL,22.03mmol) and hydrazine hydrate (5.34mL,110.2mmol) were dissolved well in methanol (100mL) at room temperature and heated to 80 ℃ for 8 hours under reflux. After cooling to room temperature and removal of the solvent under reduced pressure, water (200mL) was added, extraction with ethyl acetate (100mL × 2), washing with saturated brine (100mL), organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 2.43g of a white solid, yield: 81 percent.
And B: synthesis of ethyl 5-phenyl-1, 3, 4-oxadiazole-2-carboxylate
Benzoyl hydrazine (2.43g,17.85mmol) and triethylamine (4.96mL,35.7mmol) were dissolved in dichloromethane (200mL), oxalyl chloride monoethyl ester (2.2mL,19.63mmol) was added dropwise at 0 deg.C, after the addition was completed, the reaction was stirred at room temperature for 8 hours, triethylamine (2.48mL,17.85mmol) and p-toluenesulfonyl chloride (3.4g,17.85mmol) were added, and after the addition was completed, the reaction was stirred at room temperature for 8 hours. Dichloromethane (100mL) was added, washed successively with water (150mL), saturated brine (150mL), the organic phases were combined, concentrated under reduced pressure, and the residue was separated by column chromatography to give [ petroleum ether)/ethyl acetate (v/v) ═ 8/1] 2.71g of a white solid, yield: and 69 percent.
And C: synthesis of (5-phenyl-1, 3, 4-oxadiazol-2-yl) methanol
Ethyl 5-phenyl-1, 3, 4-oxadiazole-2-carboxylate (2.71g,12.42mmol) and calcium chloride (2.76g,24.84mmol) were suspended in ethanol (150mL), and sodium borohydride (1.41g,37.26mmol) was added at 0 ℃ to stir the reaction at room temperature for 4 hours. The reaction was quenched with water (100mL), extracted with ethyl acetate (100mL x 2), and the organic phase was washed with saturated brine (100mL x 3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 1.75g of a white solid, yield: 80 percent.
Step D: synthesis of 2- (bromomethyl) -5-phenyl-1, 3, 4-oxadiazole
(5-phenyl-1, 3, 4-oxadiazol-2-yl) methanol (1.75g,9.93mmol) was dissolved in anhydrous dichloromethane (70mL), a solution of phosphorus tribromide (0.94mL,9.93mmol) in dichloromethane (2mL) was added dropwise at 0 ℃ and, after completion of addition, the mixture was allowed to warm to room temperature and the reaction was stirred for 5 hours. Concentrated under reduced pressure, and the residue was separated by column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 6/1] to give 1.13g of a white solid, yield: and 47 percent.
Step E: synthesis of (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5-phenyl-1, 3, 4-oxadiazol-2-yl) methyl) oxime
2- (bromomethyl) -5-phenyl-1, 3, 4-oxadiazole (0.24g,1mmol), (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone oxime (0.2g,0.98mmol) and potassium carbonate (0.17g,1.23mmol) and N, N-dimethylformamide (10mL) were added to the reaction flask and the reaction stirred at room temperature for 12 hours. The reaction was quenched with water (150mL), extracted with ethyl acetate (50mL × 3), the organic phases were combined, washed with saturated brine (100mL), concentrated under reduced pressure, and the residue was separated by column chromatography [ petroleum ether/ethyl acetate (v/v) ═ 3/1] to give 0.13g of a white solid, yield: 36 percent.
1H NMR(400MHz,CDCl3)δ(ppm):8.10–8.01(m,2H),7.61–7.44(m,6H),7.39(t,J＝7.5Hz,2H),5.51(s,2H),4.07(s,3H)；
LC-MS:m/z 362.1[M+H]+。
The preparation was carried out by referring to a similar preparation method to example 1 or a preparation method in the prior art using the corresponding materials and intermediate T as starting materials, to obtain the target compounds in table 1.
TABLE 1
Figure BDA0002314779120000181
Figure BDA0002314779120000191
Figure BDA0002314779120000201
Figure BDA0002314779120000211
Figure BDA0002314779120000221
Figure BDA0002314779120000231
The target compounds shown in table 2 can be obtained by preparing the intermediate T and its corresponding intermediate as starting materials by a similar preparation method to that of example 1 or a preparation method in the prior art.
TABLE 2
Figure BDA0002314779120000241
Figure BDA0002314779120000251
Figure BDA0002314779120000261
Figure BDA0002314779120000271
Figure BDA0002314779120000281
Figure BDA0002314779120000291
Figure BDA0002314779120000301
Biological test example
This test example was used to determine the bactericidal activity of the compounds prepared in the examples.
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 (2-3X 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 tables A-C.
TABLE A controlling effect of the compounds of the invention on cucumber downy mildew at a concentration of 50mg/L
Compound (I) Control effect (%) Compound (I) Control effect (%)
Example 16 88 Example 18 85
Example 19 100 Example 21 85
Example 22 92 Example 25 98
EXAMPLE 41 100 Example 42 95
Example 43 100 Example 44 100
Example 48 98 Example 52 95
Example 54 80 Example 56 90
TABLE B controlling effect of the compounds of the invention against cucumber downy mildew at a concentration of 25mg/L
Figure BDA0002314779120000302
Figure BDA0002314779120000311
TABLE C controlling effect of the compounds of the invention against cucumber downy mildew at a concentration of 12.5mg/L
Compound (I) Control effect (%)
Example 10 100
Example 12 100
Example 13 85
Example 14 90
Example 19 95
Example 22 80
Example 25 85
Example 27 100
Example 31 87
Example 32 98
In addition, the control effect of the compositions of examples 2,4, 5, 6, 8, 9, 26, 27, 32 and 43 on cucumber downy mildew is 80-100% at a concentration of 6.25 mg/L.
From the test results, the compound has obvious control effect on plant diseases, particularly cucumber downy mildew, at low concentration, and can be further developed to be used as a pesticide bactericide.
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):
Figure FDA0002314779110000011
wherein the content of the first and second substances,
Ra、Rb、Rc、Rdand ReEach independently is hydrogen, halogen, cyano, nitro, hydroxy, C1-6Alkyl radical, C1-6Alkoxy, halo C1-6Alkyl or halo C1-6An alkoxy group;
t is
Figure FDA0002314779110000012
Wherein R isfAnd RgEach independently is hydrogen or C1-6An alkyl group;
m is
Figure FDA0002314779110000013
Figure FDA0002314779110000014
"#" and "#" indicate two connecting ends of M, wherein the "#" connecting end of M is connected with-CH2-to connect, the "+" connection end of M to a;
a is phenyl or optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-6Alkyl radical, C1-6Alkoxy, halo C1-6Alkyl, halo C1-6Alkoxy radical, C1-6Alkylthio, halo C1-6Alkylthio radical, C2-6Alkenyl radical, C2-6Alkynyl, C3-8Cycloalkyl radical, C3-8cycloalkyl-C1-5Alkyl-, -NR6R7、-C(＝O)-C1-6Alkyl, -C (═ O) -C1-6Alkoxy radical, C1-6alkyl-C (═ O) O-or C1-6alkyl-S (═ O)2-a substituted phenyl group;
R6and R7Each independently is hydrogen or C1-6An alkyl group;
the conditions are as follows: the compound of formula (I) is not:
a) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-trifluoromethylphenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
b) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (4-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime;
c) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (3-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime; and
d) (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methanone O- ((5- (2-bromophenyl) -1,3, 4-oxadiazol-2-yl) methyl) oxime.
2. The compound of claim 1, wherein,
Ra、Rb、Rc、Rdand ReEach independently is hydrogen, halogen, cyano, nitro, hydroxy, C1-4Alkyl radical, C1-4Alkoxy, halo C1-4Alkyl or halo C1-4An alkoxy group;
Rfand RgEach independently is hydrogen or C1-4An alkyl group.
3. The compound of claim 2, wherein,
Ra、Rb、Rc、Rdand ReEach independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxy, -CH3、-OCH3、-CF3or-OCF3；
RfAnd RgEach independently is hydrogen or-CH3。
4. The compound of claim 1, wherein:
a is phenyl or optionally substituted by 1,2, 3,4 or 5 substituents selected from halogen, cyano, nitro, hydroxy, C1-4Alkyl radical, C1-4Alkoxy, halo C1-4Alkyl, halo C1-4Alkoxy radical, C1-4Alkylthio, halo C1-4Alkylthio radical, C2-4Alkenyl radical, C2-4Alkynyl, C3-6Cycloalkyl radical, C3-6cycloalkyl-C1-3Alkyl-, -C (═ O) -C1-4Alkyl, -C (═ O) -C1-4Alkoxy, -C (═ O) O-C1-4Alkyl or C1-4alkyl-S (═ O)2-substituted phenyl.
5. The compound of claim 4, wherein:
a is phenyl or optionally substituted by 1,2, 3,4 or 5 groups selected from fluoro, chloro, bromo, iodo, cyano, nitro, hydroxy, -CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-OCH3、-OCH2CH3、-CF3or-OCF3A substituted phenyl group.
6. The compound according to any one of claims 1 to 5, which is a nitroxide, a salt, (Z) -isomer, (E) -isomer, or a mixture of (Z) -isomer and (E) -isomer of a compound having formula (II) or a compound of formula (II):
Figure FDA0002314779110000021
7. 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:
Figure FDA0002314779110000022
Figure FDA0002314779110000031
Figure FDA0002314779110000041
Figure FDA0002314779110000051
Figure FDA0002314779110000061
8. a composition comprising at least one compound according to any one of claims 1 to 7 and an agriculturally acceptable adjuvant.
9. A compound according to any one of claims 1 to 7 or a composition according to claim 8 for use as a plant disease control agent in agriculture.
10. A method for controlling a plant disease, which comprises applying a compound of any one of claims 1 to 7 or a composition of claim 8 to a plant or a plant growing locus before or after germination of the plant disease.
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Citations (1)

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Publication number Priority date Publication date Assignee Title
JP2011012088A (en) * 2010-08-10 2011-01-20 Nippon Soda Co Ltd Oxime compound or salt thereof, and fungicide

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011012088A (en) * 2010-08-10 2011-01-20 Nippon Soda Co Ltd Oxime compound or salt thereof, and fungicide

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