CN113195462A - Microbicidal oxadiazole derivatives - Google Patents

Microbicidal oxadiazole derivatives Download PDF

Info

Publication number
CN113195462A
CN113195462A CN201980068308.0A CN201980068308A CN113195462A CN 113195462 A CN113195462 A CN 113195462A CN 201980068308 A CN201980068308 A CN 201980068308A CN 113195462 A CN113195462 A CN 113195462A
Authority
CN
China
Prior art keywords
radical
alkyl
group
methyl
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201980068308.0A
Other languages
Chinese (zh)
Inventor
T·J·霍夫曼
D·斯狄尔利
R·拉詹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Syngenta Crop Protection AG Switzerland
Original Assignee
Syngenta Crop Protection AG Switzerland
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Syngenta Crop Protection AG Switzerland filed Critical Syngenta Crop Protection AG Switzerland
Publication of CN113195462A publication Critical patent/CN113195462A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • 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
    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D413/10—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 carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Toxicology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

A compound having (I): (I) wherein the substituents are as defined in claim 1, are useful as pesticides, especially as fungicides.

Description

Microbicidal oxadiazole derivatives
The present invention relates to microbicidal oxadiazole derivatives, for example as active ingredients, which have microbicidal, in particular fungicidal, activity. The invention also relates to agrochemical compositions comprising at least one of the oxadiazole derivatives, to processes for the preparation of these compounds, and to the use of the oxadiazole derivative or composition in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.
EP 0276432 and WO 2015/185485 describe the use of substituted oxadiazoles for combating phytopathogenic fungi.
According to the present invention there is provided a compound having formula (I):
Figure BDA0003023364140000011
wherein
A is A-1 or A-2;
Figure BDA0003023364140000012
wherein A-1 and A-2 are optionally substituted with one or two groups independently selected from halogen and methyl;
R1is hydroxy, amino, thiol, halogen, C1-3Alkoxy radical, C1-3Haloalkyl, C1-3Haloalkoxy, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-3Alkylamino radical, C1-3Alkoxyamino group, C1-3Haloalkoxyamino group, C1-3Alkylcarbonyloxy, C3-4Alkenyloxy-amino group, C3-4Alkynyloxyamino, N-C1-3alkyl-N-C1-3Alkoxyamino, N-C1-3alkoxy-N' -C1-3Alkylcarbonyl, or C3-6Cycloalkyl radical C1-3An alkoxyamino group;
R2is hydrogen, C1-3Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, phenyl, C2-6Alkenyl, or C2-6An alkynyl group; or
R1And R2Together with the carbon to which they are bonded, form oxo (═ O) or NORaGroup, wherein RaIs C1-5Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, or C3-6Cycloalkyl radical C1-2An alkyl group;
R3and R4Are identical and are selected from halogen and C1-C6An alkyl group; or
R3And R4Together with the carbon to which they are bonded form a3, 4,5, or 6 membered cycloalkyl group;
y is O or S;
z is Z1Or Z2；
Z1represents-OR5Wherein:
R5is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C1-3Haloalkyl, cyano C1-4Alkyl, hydroxy C2-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl radical, C1-3Halogenoalkoxy radical C2-4Alkyl, amino C2-4Alkyl, N-C1-4Alkylamino radical C2-4Alkyl, N-di-C1-4Alkylamino radical C2-4Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-4Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R5Is C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl, heteroaryl C1-2Alkyl, heterocyclic, or heterocyclic C1-2Alkyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R6；
R6Is cyano, fluoro, chloro, bromo, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy;
Z2represents-NR7R8Wherein:
R7is hydrogen, amino, hydroxy, cyano, C1-6Alkyl radical, C1-4Alkoxy radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, cyano C1-4Alkyl radical, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkoxy radical C2-4Alkyl, N-C1-4Alkylamino, N-di-C1-4Alkylamino radical, N-C1-4alkylcarbonyl-N-C1-4Alkylamino radical, amino radical C2-4Alkyl, N-C1-3Alkylamino radical C2-4Alkyl, N-di-C1-3Alkylamino radical C2-4Alkyl, N-C1-3alkyl-N-C1-3Alkoxyamino group C2-4Alkyl radical, C1-3Alkylcarbonylamino group C2-4Alkyl, N-C1-3Alkylcarbonyl- (N-C)1-3Alkyl) amino C2-3Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-3Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R7Is C3-6A cycloalkyl group; c3-6Cycloalkyl radical C1-2An alkyl group; a phenyl group; phenyl radical C1-2An alkyl group; or heteroaryl, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1,2,3 or 4 heteroatoms independently selected from N, O and S; heterocyclyl, wherein the heterocyclyl moiety is a 4-to 6-membered non-aromatic ring comprising 1 or 2 heteroatoms independently selected from N, O and S; and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moiety is each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R9；
R8Is hydrogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, methoxy, 2-methoxyethyl, or cyclopropyl; or
R7And R8Together with the nitrogen atom to which they are bonded form a ring optionally containing a substituent selected from the group consisting of O, S, S (O)2And NR10A4, 5 or 6 membered ring of the further heteroatom or group;
R9is hydroxy, C1-3Alkyl, halogen, C1-3Alkoxy, or C1-3A haloalkyl group; and is
R10Is hydrogen, methyl, methoxy, fluoromethoxy, difluoromethoxy, formyl or acyl; or
Salts or N-oxides thereof.
Surprisingly, it has been found that for practical purposes the novel compounds of formula (I) have a very advantageous level of biological activity for protecting plants against diseases caused by fungi.
According to a second aspect of the present invention there is provided an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I). Such agricultural compositions may further comprise at least one additional active ingredient and/or an agrochemically acceptable diluent or carrier.
According to a third aspect of the present invention there is provided a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I), or a composition comprising such a compound as active ingredient, is applied to the plants, parts thereof or the locus thereof.
According to a fourth aspect of the present invention there is provided the use of a compound having formula (I) as a fungicide. According to this particular aspect of the invention, the use may not include a method of treatment of the human or animal body by surgery or therapy.
As used herein, the term "halogen" refers to fluorine (fluoro), chlorine (chloro), bromine (bromine) or iodine (iododine), preferably fluorine, chlorine or bromine.
As used herein, cyano means a-CN group.
As used herein, the term "hydroxyl" or "hydroxy" means an — OH group.
As used herein, amino means-NH2A group.
As used herein, acyl means-C (O) CH3A group.
As used herein, formyl means a-C (O) H group.
As used herein, the term "C1-6Alkyl "refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, which is free of unsaturation, has from one to six carbon atoms, and is attached to the rest of the molecule by a single bond. C1-5Alkyl radical, C1-4Alkyl radical, C1-3Alkyl and C1-2Alkyl groups should be construed accordingly. C1-6Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, and 1-dimethylethyl (tert-butyl). "C1-2Alkylene "radical means C1-2Alkyl groups are defined accordingly, except that such groups are attached to the rest of the molecule by two single bonds. C1-2An example of alkylene is-CH2-and-CH2CH2-。
As used herein, the term "C1-4Alkoxy "means having the formula RaA group of O-wherein RaIs C as generally defined above1-4An alkyl group. C1-3Alkoxy groups should be construed accordingly. C1-4Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, and tert-butoxy.
As used herein, the term "C1-4Haloalkyl "means C as generally defined above substituted with one or more of the same or different halogen atoms1-4An alkyl group. Term C1-3Haloalkyl and C1-2Haloalkyl should be construed accordingly. C1-4Examples of haloalkyl include, but are not limited to, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, 2,2, 2-trifluoroethyl, and 3,3, 3-trifluoropropyl.
As used herein, the term "C2-6Alkenyl "means a straight or branched hydrocarbon chain radical consisting exclusively of carbon and hydrogen atoms, containing at least one double bond which may have (E) -or (Z) -configuration, having from two to sixA carbon atom, attached to the remainder of the molecule by a single bond. Term C3-5Alkenyl and C3-4Alkenyl groups should be construed accordingly. C2-6Examples of alkenyl groups include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl), and but-1-enyl.
As used herein, the term "C3-4Alkenyloxy "means having the formula RaA group of O-wherein RaIs C as generally defined above3-4An alkenyl group.
As used herein, the term "C3-4Alkenyloxyamino "means a compound of the formula RaGroup of ONH-, wherein RaIs C as generally defined above3-4Alkenyl radical
As used herein, the term "C3-5Haloalkenyl "refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, which contains at least one double bond, which may be in the (E) -or (Z) -configuration, has from three to five carbon atoms, is attached to the rest of the molecule by single bonds, substituted with one or more identical or different halogen atoms.
As used herein, the term "C2-6Alkynyl "refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond. Term C3-5Alkynyl and C3-4Alkynyl should be construed accordingly. C2-6Examples of alkynyl groups include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.
As used herein, the term "C3-4Alkynyloxy "refers to a compound having the formula RaA group of O-wherein RaIs C as generally defined above3-4Alkynyl.
As used herein, the term "C3-4Alkynyloxyamino "means a compound having the formula RaGroup of ONH-, wherein RaIs C as generally defined above3-4Alkynyl.
As used herein, the term "C1-3Alkoxy radical C1-4Alkyl "means having the formulaRb-O-RaA group of (a) wherein RbIs C as generally defined above1-3Alkyl, and RaIs C as generally defined above1-4An alkylene group. Term C1-2Alkoxy radical C1-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl and C1-2Alkoxy radical C2-4Alkyl groups should be construed accordingly.
As used herein, the term "C1-4Haloalkoxy "means C as defined above substituted by one or more of the same or different halogen atoms1-4An alkoxy group. Term C1-3Haloalkoxy and C1-2Haloalkoxy should be construed accordingly. C1-4Examples of haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
As used herein, the term "C1-2Halogenoalkoxy radical C2-4Alkyl "means having the formula Rb-O-RaA group of (a) wherein RbIs C as generally defined above substituted by one or more identical or different halogen atoms1-2Alkyl, and RaIs C as generally defined above2-4An alkylene group.
As used herein, the term "hydroxy C2-4Alkyl "means C as generally defined above substituted with one or more hydroxy groups2-4An alkyl group.
As used herein, the term "cyano C1-4Alkyl "means C as generally defined above substituted with one or more cyano groups1-4An alkyl group.
As used herein, the term "C1-4Alkylcarbonylamino group C2-4Alkyl "means having the formula RaC(O)NHRbA group of (a) wherein RaIs C as generally defined above1-4Alkyl, and RbIs C as generally defined above2-4An alkylene group.
As used herein, the term "C1-2Alkoxy radical C2-4Alkoxy radical C2-4Alkyl "means having the formula RcORbORaA group of (a) whichIn RaAnd RbIs C as generally defined above2-4Alkylene, and RcIs C as generally defined above1-2An alkyl group.
As used herein, the term "C1-4Alkoxycarbonyl radical C1-3Alkyl "means having the formula RaOC(O)RbA group of (a) wherein RaIs C as generally defined above1-4Alkyl, and RbIs C as generally defined above1-3An alkylene group.
As used herein, the term "N-C1-4Alkylamino "refers to a compound having the formula RaA group of NH-, wherein RaIs C as generally defined above1-4An alkyl group. The term N-C1-3Alkylamino should be construed accordingly.
As used herein, the term "N-C1-4Alkylamino radical C2-4Alkyl "means having the formula RaNHRbA group of (a) wherein RaIs C as generally defined above1-4Alkyl, and RbIs C as generally defined above2-4An alkylene group.
As used herein, the term "N, N-di C1-4Alkylamino "refers to a compound having the formula Ra(Rb) A group of N-, wherein RaAnd RbIs C as generally defined above1-4An alkyl group.
As used herein, the term "N, N-di C1-4Alkylamino radical C2-4Alkyl "means having the formula Ra(Rb)NRcA group of (a) wherein RaAnd RbIs C as generally defined above1-4Alkyl, and RcIs C as generally defined above2-4An alkylene group.
As used herein, the term "amino C2-4Alkyl "means having the formula H2NRaA group of (a) wherein RaIs C as generally defined above2-4An alkylene group.
As used herein, the term "C1-4Alkylamino "refers to a compound having the formula RaA group of NH-, wherein RaIs C as generally defined above1-4An alkyl group. Term C1-3Alkylamino should be construed accordingly.
As used herein, the term "C1-3Haloalkoxyamino "means a compound having the formula RaGroup of ONH-, wherein RaIs C as defined above substituted by one or more halogen atoms which may be the same or different1-3An alkyl group.
As used herein, the term "C1-3Alkyl carbonyl radical C1-3Alkyl "means having the formula RbC(O)RaA group of (a) wherein RbIs C as generally defined above1-3Alkyl, and RaIs C as generally defined above1-3An alkylene group.
As used herein, the term "C1-4Alkoxycarbonyl radical C1-3Alkyl "means having the formula RbOC(O)RaA group of (a) wherein RbIs C as generally defined above1-4Alkyl, and RaIs C as generally defined above1-3An alkylene group.
As used herein, the term "C1-3Alkylcarbonyloxy C2-4Alkyl "means having the formula RbC(O)ORaA group of (a) wherein RbIs C as generally defined above1-3Alkyl, and RaIs C as generally defined above2-4An alkylene group.
As used herein, the term "C1-4Alkoxyamino "means a compound having the formula RaGroup of ONH-, wherein RaIs C as generally defined above1-4An alkyl group. Term C1-3The alkoxyamino group should be construed accordingly.
As used herein, the term "N-C1-3alkoxy-N' -C1-3Alkylcarbonyl "means having the formula (R)aO)(RbC (O)) a group of N-, wherein RaAnd RbIs C as generally defined above1-3An alkyl group.
As used herein, the term "N-C1-3alkyl-N-C1-3Alkoxyamino "means having the formula (R)a)(RbO) group of N-, wherein RaAnd RbIs C as generally defined above1-3An alkyl group.
As used herein, the term "N-C1-3alkyl-N-C1-3Alkoxyamino group C2-4Alkyl "means having the formula (R)a)(RbO)NRcA group of (a) wherein RaAnd RbIs C as generally defined above1-3Alkyl, and RcIs C as generally defined above2-4An alkylene group.
As used herein, the term "N-C1-4alkylcarbonyl-N-C1-4Alkylamino means having the formula (R)bC(O))(Ra) A group of N-, wherein RaAnd RbIs C as generally defined above1-4An alkyl group.
As used herein, the term "N, N-di C1-4Alkylamino means having the formula (R)a)(Rb) A group of N-, wherein RaAnd RbEach being C as defined generally above1-4An alkyl group.
As used herein, the term "N, N-di C1-4Alkylamino radical C2-4Alkyl "means having the formula (R)c)(Rb)NRaA group of (a) wherein RbAnd RcEach independently is C as generally defined above1-4Alkyl, and RaIs C as generally defined above2-4An alkylene group.
As used herein, the term "N-C1-3Alkylcarbonyl- (N-C)1-3Alkyl) amino C2-3Alkyl "means having the formula (R)cC(O))(Rb)NRaA group of (a) wherein RbAnd RcEach independently is C as generally defined above1-3Alkyl, and RaIs C as generally defined above2-3An alkylene group.
As used herein, the term "C3-6Cycloalkyl "refers to a stable monocyclic group that is saturated or partially unsaturated and contains 3 to 6 carbon atoms. C3-5Cycloalkyl and C3-4Cycloalkyl groups should be interpreted accordingly. C3-6Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentene-1-yl, cyclopenten-3-yl, and cyclohexen-3-yl.
As used herein, the term "C3-6Cycloalkyl radical C1-2Alkyl "means through C as defined above1-2Alkylene attached to C as defined above for the remainder of the molecule3-6A cycloalkyl ring. C3-6Cycloalkyl radical C1-2Examples of alkyl groups include, but are not limited to, cyclopropyl-methyl and cyclobutyl-ethyl.
As used herein, the term "C3-6Cycloalkyl radical C1-3Alkoxyamino "refers to the group formed by-RaThe ONH-group is attached to C as defined above of the rest of the molecule3-6A cycloalkyl ring, wherein RaIs C as generally defined above1-3An alkylene group.
As used herein, the term "phenyl C1-2Alkyl "means through C as defined above1-2The alkylene groups are attached to the benzene ring in the remainder of the molecule. Phenyl radical C1-2Examples of alkyl groups include, but are not limited to, benzyl.
As used herein, the term "heteroaryl" generally refers to a5 or 6 membered monocyclic aromatic ring group containing 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. The heteroaryl group may be bonded to the remainder of the molecule via a carbon atom or heteroatom. Examples of heteroaryl groups include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, and pyridyl.
As used herein, the term "heterocyclyl" or "heterocyclic" generally refers to a stable, saturated or partially saturated, 4 to 6 membered, non-aromatic, monocyclic ring containing 1,2 or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. The heterocyclic group may be bonded to the remainder of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, tetrahydropyranyl, dioxolanyl, and morpholino.
As used herein, the term "heterocyclyl C1-2Alkyl "means through C as defined above1-2The alkylene group is attached to a heterocyclic ring as defined above for the remainder of the molecule.
The presence of one or more possible asymmetric carbon atoms in the compound having formula (I) means that the compound can exist in chiral isomeric forms, i.e. enantiomeric or diastereomeric forms. Atropisomers may also be present as a result of restricted rotation about a single bond. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms of the compounds having formula (I) and mixtures thereof. Likewise, formula (I) is intended to include all possible tautomers (including lactam-lactam tautomerism and keto-enol tautomerism), when present. The present invention includes all possible tautomeric forms of the compounds having formula (I).
In each case, the compounds of formula (I) according to the invention are in free form, in oxidized form (as N-oxide), in covalently hydrated form, or in salt form (for example in the form of an agronomically usable or agrochemically acceptable salt).
The N-oxide is an oxidized form of a tertiary amine or an oxidized form of a nitrogen-containing heteroaromatic compound. For example, a. albini and s.pietra described them in a book entitled "Heterocyclic N-oxides" published in 1991 by bocardon (Boca Raton) CRC press.
A (A-1, A-2), Z (Z) relating to the compound of formula (I) of the present invention1、Z2)、R1、R2、R3、R4、R5、R6、R7、R8、R9And R10The nomenclature of (A) is generally applicable to the compounds having the formulae (I-I) and (I-II), and A (A-1, A-2), Z (Z)1、Z2)、R1、R2、R3、R4、R5、R6、R7、R8、R9And R10As in tables 1.1 to 1.12 (below), or tables 3.1 to 3.6 (below), compounds of formula (I), table T1 (below)Herein) of compounds 1.1 to 1.33, of compounds 2.1 to 2.18 described in table T2 (below), or of compounds 3.1 and 3.2 described in table T3 (below).
A is A-1 or A-2;
Figure BDA0003023364140000101
wherein A-1 and A-2 are each optionally substituted with one or two groups selected from halogen and methyl.
Preferably, A is A-1 or A-2, wherein A-1 and A-2 are each optionally substituted with one or two groups selected from halogen and methyl, more preferably chlorine, fluorine and methyl. Even more preferably, A is 1, 4-phenylene or 2, 5-thienylene.
R1Is hydroxy, amino, thiol, halogen, C1-3Alkoxy radical, C1-3Haloalkyl, C1-3Haloalkoxy, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-3Alkylamino radical, C1-3Alkoxyamino group, C1-3Haloalkoxyamino group, C1-3Alkylcarbonyloxy, C3-4Alkenyloxy-amino group, C3-4Alkynyloxyamino, N-C1-3alkyl-N-C1-3Alkoxyamino, N-C1-3alkoxy-N' -C1-3Alkylcarbonyl, or C3-6Cycloalkyl radical C1-3An alkoxyamino group.
Preferably, R1Is hydroxy, amino, thiol, halogen, C1-3Alkoxy radical, C1-2Haloalkyl, C1-2Haloalkoxy, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-2Alkylamino radical, C1-3Alkoxyamino group, C1-2Haloalkoxyamino group, C1-3Alkylcarbonyloxy, N-C1-3alkyl-N-C1-3Alkoxyamino, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group.
More preferably, R1Is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkyl carbonylOxy, N-C1-3alkyl-N-C1-3Alkoxyamino, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group. Even more preferably, R1Is hydroxy, thiol, methoxy, methoxyamino, methylcarbonyloxy, N-methyl-N-methoxyamino, or N-methoxy-N' -methylcarbonyl.
R2Is hydrogen, C1-3Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, phenyl, C2-6Alkenyl, or C2-6Alkynyl. Preferably, R2Is hydrogen, methyl, ethyl, n-propyl, cyclopropyl, cyclobutyl, phenyl, prop-2-enyl, or prop-2-ynyl. More preferably, R2Is hydrogen, methyl, ethyl, cyclopropyl, prop-2-enyl, or prop-2-ynyl. Even more preferably, R2Is hydrogen or methyl.
Or R1And R2May form together with the carbon to which they are bonded, oxy (═ O) or ═ NORaGroup, wherein RaIs C1-5Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, or C3-6Cycloalkyl radical C1-2An alkyl group. Preferably, R1And R2Together with the carbon to which they are bonded, form oxo (═ O) or NORaGroup, wherein RaIs C1-3Alkyl radical, C1-3Haloalkyl, C3-4Cycloalkyl, or C3-4Cycloalkyl radical C1-2An alkyl group. More preferably, R1And R2Together with the carbon to which they are bonded, form an oxy (═ O) group.
In one set of embodiments, R1Is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, N-C1-3alkyl-N-C1-3Alkoxyamino, or N-C1-3alkoxy-N' -C1-3Alkylcarbonyl, and R2Is hydrogen or methyl; or R1And R2Together with the carbon to which they are bonded, form an oxy (═ O) group.
In another set of embodiments, R1Is hydroxy, thiol, methoxy amino, methylcarbonylAryloxy, N-methyl-N-methoxyamino, or N-methoxy-N' -methylcarbonyl, and R2Is hydrogen or methyl; or R1And R2Together with the carbon to which they are bonded, form an oxy (═ O) group.
R3And R4Both are identical and are selected from halogen and C1-C6An alkyl group; or
R3And R4Together with the carbon to which they are bonded, form a3, 4,5, or 6 membered cycloalkyl group. Preferably, R3And R4Both are identical and are selected from halogen and C1-C4Alkyl, more preferably, fluorine, bromine, chlorine and C1-C3Alkyl, even more preferably, fluoro, bromo, chloro, methyl and ethyl, and still more preferably, R3And R4Both are the same and are selected from fluoro and methyl; or R3And R4Together with the carbon to which they are bonded form a3, 4, or 5 membered cycloalkyl group, preferably a3 or 4 membered cycloalkyl group, and more preferably a cyclopropyl group.
In one set of embodiments, R3And R4Both are identical and are selected from fluorine and methyl, or R3And R4Together with the carbon to which they are bonded, form a cyclopropyl group.
Y is O or S. In some embodiments, Y is O, and in other embodiments, Y is S.
Z is Z1Or Z2；
Z1represents-OR5Wherein:
R5is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C1-3Haloalkyl, cyano C1-4Alkyl, hydroxy C2-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl radical, C1-3Halogenoalkoxy radical C2-4Alkyl, amino C2-4Alkyl, N-C1-4Alkylamino radical C2-4Alkyl, N-di-C1-4Alkylamino radical C2-4Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-4Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R5Is C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl, heteroaryl C1-2Alkyl, heterocyclic, or heterocyclic C1-2Alkyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R6；
R6Is cyano, fluoro, chloro, bromo, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy.
Preferably, R5Is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C1-3Haloalkyl, cyano C1-2Alkyl, hydroxy C2-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl radical, C1-3Halogenoalkoxy radical C2-4Alkyl, amino C2-4Alkyl radical, C1-3Alkyl carbonyl radical C1-2Alkyl, or C1-3Alkoxycarbonyl radical C1-2An alkyl group; or
R5Is C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl, heteroaryl or heterocyclyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R6。
More preferably, R5Is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2An alkyl group.
In one set of embodiments, R5Is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl or C3-6Cycloalkyl, preferably hydrogen, C1-5Alkyl radical, C3-4Alkenyl radical, C3-4Alkynyl or C3-4Cycloalkyl radicals, more preferably hydrogen, methyl, ethyl,N-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, prop-2-enyl, prop-2-ynyl or cyclopropyl, and most preferably, R is5Is hydrogen, methyl or ethyl.
Z2represents-NR7R8Wherein:
R7is hydrogen, amino, hydroxy, cyano, C1-6Alkyl radical, C1-4Alkoxy radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, cyano C1-4Alkyl radical, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkoxy radical C2-4Alkyl, N-C1-4Alkylamino, N-di-C1-4Alkylamino radical, N-C1-4alkylcarbonyl-N-C1-4Alkylamino radical, amino radical C2-4Alkyl, N-C1-3Alkylamino radical C2-4Alkyl, N-di-C1-3Alkylamino radical C2-4Alkyl, N-C1-3alkyl-N-C1-3Alkoxyamino group C2-4Alkyl radical, C1-3Alkylcarbonylamino group C2-4Alkyl, N-C1-3Alkylcarbonyl- (N-C)1-3Alkyl) amino C2-3Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-3Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R7Is C3-6A cycloalkyl group; c3-6Cycloalkyl radical C1-2An alkyl group; a phenyl group; phenyl radical C1-2An alkyl group; or heteroaryl, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1,2,3 or 4 heteroatoms independently selected from N, O and S; heterocyclyl, wherein the heterocyclyl moiety is a 4-to 6-membered non-aromatic ring comprising 1 or 2 heteroatoms independently selected from N, O and S; and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are each optionally substituted with 1 or 2 substituents which may be the same orIs different from R9；
Preferably, R7Is hydrogen, amino, cyano, C1-5Alkyl radical, C1-4Alkoxy radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, cyano C1-4Alkyl radical, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkoxy radical C2-4Alkyl, N-C1-4Alkylamino, or N, N-di-C1-4An alkylamino group; or
R7Is C3-6A cycloalkyl group; c3-6Cycloalkyl radical C1-2An alkyl group; a phenyl group; phenyl radical C1-2An alkyl group; or heteroaryl, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1,2 or 3 heteroatoms independently selected from N and O; heterocyclyl, wherein the heterocyclyl moiety is a 4-to 6-membered non-aromatic ring comprising 1 or 2 heteroatoms independently selected from N and O; and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moiety is each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R9。
More preferably, R7Is hydrogen, amino, C1-4Alkyl radical, C1-4Alkoxy radical, C3-4Alkenyl radical, C3-4Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl, N-C1-2Alkylamino, N-di-C1-2Alkylamino radical, C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl or heteroaryl, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1 or 2 heteroatoms independently selected from N and O; or a heterocyclic group, whereinThe heterocyclyl moiety is a 4-to 6-membered non-aromatic ring containing 1 or 2 heteroatoms independently selected from N and O.
Even more preferably, R7Is hydrogen, C1-4Alkyl radical, C3-4Alkenyl radical, C3-4Alkynyl, C3-6Cycloalkyl, or C3-6Cycloalkyl radical C1-2Alkyl, still more preferably hydrogen, C1-4Alkyl radical, C3-4Alkenyl radical, C3-4Alkynyl, C3-4Cycloalkyl, or C3-4Cycloalkyl radical C1-2An alkyl group.
In a particularly preferred group of embodiments, R7Is hydrogen, methyl, ethyl, n-propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl or cyclopropylmethyl, more preferably hydrogen, methyl, ethyl, n-propyl, isopropyl or cyclopropyl.
R8Is hydrogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, methoxy, 2-methoxyethyl, or cyclopropyl. Preferably, R8Is hydrogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl or cyclopropyl. More preferably hydrogen, methyl, or prop-2-enyl, and still more preferably, R8Is hydrogen or methyl.
Or R7And R8Together with the nitrogen atom to which they are bonded form a ring optionally containing a substituent selected from the group consisting of O, S, S (O)2And NR10Or a4, 5 or 6 membered ring of the group. Preferably, R7And R8Together with the nitrogen atom to which they are bonded form a compound optionally containing a substituent selected from O and NR10Or a4, 5 or 6 membered ring of the group. More preferably, R7And R8Together with the nitrogen atom to which they are bonded form a4, 5 or 6 membered ring optionally containing a further heteroatom or group selected from O, even more preferably a5 or 6 membered ring containing a further oxygen atom, and most preferably R7And R8Together with the nitrogen atom to which they are bonded, form a morpholino group.
R9Is hydroxy, C1-3Alkyl, halogen, C1-3Alkoxy, or C1-3Haloalkyl group. Preferably, R9Is hydroxy, methyl, ethyl, isopropyl, chloro, fluoro, methoxy, difluoromethyl or trifluoromethyl. More preferably, R9Is methyl, chloro, fluoro, methoxy or trifluoromethyl.
R10Is hydrogen, methyl, methoxy, fluoromethoxy, difluoromethoxy, formyl or acyl. Preferably, R10Is hydrogen, methyl, formyl or acyl. More preferably, R10Is hydrogen or methyl, and most preferably, R10Is hydrogen.
In one group of embodiments, when R7When it is hydrogen, methyl, ethyl, n-propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl or cyclopropylmethyl, R8Is hydrogen, methyl or prop-2-enyl, or R7And R8Together with the nitrogen atom to which they are bonded, form a morpholino group.
In another set of embodiments, when R7When it is hydrogen, methyl, ethyl, n-propyl, isopropyl or cyclopropyl, R8Is hydrogen or methyl, or R7And R8Together with the nitrogen atom to which they are bonded, form a morpholino group.
In the compounds according to the invention having formula (I), preferably:
a is A-1 or A-2;
R1is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O;
z is Z1；
R5Is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl or C3-6A cycloalkyl group.
More preferably, in the compounds according to the invention having formula (I):
a is A-1 or A-2;
R1is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O;
z is Z1(ii) a And is
R5Is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, allyl, prop-2-ynyl, or cyclopropyl.
In a further compound according to the invention having formula (I), preferably:
a is A-1 or A-2;
R1is hydroxy, C1-3Alkoxy radical, C1-3Alkoxyamino or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group;
R2is hydrogen; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O;
z is Z1(ii) a And is
R5Is hydrogen or C1-6An alkyl group.
In a further compound according to the invention having formula (I), more preferably:
a is A-1 or A-2;
R1is hydroxy, methoxy, methoxyamino or N-methoxy-N' -methylcarbonyl;
R2is hydrogen; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from fluorine and methyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O;
z is Z1(ii) a And is
R5Is hydrogen, methyl or ethyl.
In still further compounds according to the invention having formula (I), preferably:
a is A-1 or A-2;
R1is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O or S;
z is Z2；
R7Is hydrogen, C1-6Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-6Cycloalkyl or C3-6Cycloalkyl radical C1-2An alkyl group; and is
R8Is hydrogen, methyl or propen-2-yl.
More preferably, in still further compounds according to the invention having formula (I), more preferably:
a is A-1 or A-2;
R1is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O or S;
z is Z2；
R7Is hydrogen, methyl, ethyl, n-propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl or cyclopropylmethyl; and is
R8Is hydrogen, methyl or propen-2-yl.
In another compound according to the invention having formula (I), preferably:
a is A-1 or A-2;
R1is hydroxy, thiol, C1-3Alkoxy or C1-3An alkylcarbonyloxy group;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O or S;
z is Z2；
R7Is hydrogen, C1-6Alkyl or C3-6A cycloalkyl group;
R8is hydrogen; or
R7And R8Together with the nitrogen to which they are bonded form a compound optionally containing a member selected from O and NR10A4, 5 or 6 membered ring of the further heteroatom or group; and is
R10Is hydrogen, methyl, methoxy, fluoromethoxy, difluoromethoxy, formyl or acyl.
In another compound according to the invention having formula (I), more preferably:
a is A-1 or A-2;
R1is hydroxy, thiol, methoxy or acetoxy;
R2is hydrogen or methyl; or
R1And R2Together with the carbon to which they are bonded form an oxy (═ O) group;
R3and R4Are identical and are selected from fluorine and methyl, or R3And R4Together with the carbon to which they are bonded form a cyclopropyl ring;
y is O or S;
z is Z2；
R7Is methyl, ethyl, n-propyl, isopropyl or cyclopropyl;
R8is hydrogen or methyl; or
R7And R8Together with the nitrogen to which they are bonded, form a morpholino group.
Preferably, the compound according to formula (I) is selected from compounds 1.1 to 1.33 described in table T1 (below), compounds 2.1 to 2.18 described in table T2 (below), or compounds 3.1 and 3.2 described in table T3 (below).
The compounds of the invention may be enantiomers of compounds having formula (I) represented by formula (Ia) or formula (Ia), wherein R is1And R2Are different substituents and R3And R4Are identical and are selected from halogen and C1-6Alkyl, or R3And R4Together with the carbon to which they are attached form a3, 4,5, or 6 membered cycloalkyl group:
Figure BDA0003023364140000181
it will be appreciated that the compounds of formula (I) according to the invention may be in CF with the corresponding covalently hydrated forms (i.e. compounds of formula (I-Ia) and (I-IIa), as shown below, which may be present in tautomeric forms, such as compounds of formula (I-Ib) and (I-IIb)) when in aqueous media3The oxadiazole motif is present in reversible equilibrium. This dynamic equilibrium may be important for the biological activity of the compound having formula (I).
Figure BDA0003023364140000191
The compounds of the invention may be prepared as shown in schemes 1 to 10 below, wherein (unless otherwise specified) the definitions of each variable are as defined above for the compounds of formula (I).
A compound having the formula (I-a) (wherein Y is O) can be prepared by reacting with a compound having the formula (II) (wherein Z represents-OR)5or-NR7R8) And a compound of formula (III), by activation of the carboxylic acid function of the compound of formula (III), which is generally carried out by conversion of the-OH group of the carboxylic acid into a good leaving group, such as a chloride group, for example by using (COCl) before treatment with a compound of formula (II)2Or SOCl2Preferably in a suitable solvent (e.g. dimethylformamide, dichloromethane or tetrahydrofuran), preferably at a temperature between 25 ℃ and 100 ℃ and optionally in the presence of a base such as triethylamine or N, N-diisopropylethylamine or under the conditions described in the literature for amide coupling. See, for example, Valeur, e.; bradley, M.chem.Soc.Rev. [ review of the chemical society]2009,38,606 and chinchialla, r., Najera, c.chem.soc.rev. [ review of chemical society]2011,40,5084. Having the formula (II)The compounds are known or commercially available. This is shown in scheme 1 below.
Figure BDA0003023364140000201
Scheme 1
Compounds having the formula (I-a), also from compounds having the formula (I-c) (wherein R5AIs methyl or ethyl, preferably ethyl), and compounds of formula (IV) wherein Z represents-NR7R8) Obtained by activation of the amine function of the compound of formula (IV), generally by reacting the amine with an aluminium reagent (such as AlMe)3Or DABAL-Me3) The reaction is carried out, followed by treatment with a compound of formula (I-c), preferably activating the ester (compound of formula (I-c)) in a suitable solvent (e.g. dimethylformamide, tetrahydrofuran or 2-methyltetrahydrofuran), preferably at a temperature between 25 ℃ and 100 ℃, or by using a catalyst (such as lanthanum triflate), or under the conditions described in the literature for amide coupling. For an example of a reaction by activating an amine, see Novak, A. et al, Tetrahedron Letters [ ]]2006,47,5767- & 5769, and for an example of a reaction in which an ester is activated by using lanthanum triflate, see Morimoto H. et al, org.Lett. [ organic letters]2014,16,2018-2021. Compounds having formula (IV) are known or commercially available. This is shown in scheme 2 below.
Figure BDA0003023364140000202
Scheme 2
Alternatively, the compound having formula (I-a) may be prepared from the compound having formula (V) by: treatment with trifluoroacetic anhydride, trifluoroacetyl chloride or trifluoroacetyl fluoride in the presence of a base such as pyridine or 4-dimethylaminopyridine in a suitable solvent such as tetrahydrofuran or ethanol at a temperature between 25 ℃ and 75 ℃. For related examples, see: WO 2003/028729 and WO 2010/045251. The reaction is shown in scheme 3 below.
Figure BDA0003023364140000211
Scheme 3
The compound having formula (V) may be prepared from the compound having formula (VI) by: the treatment with hydroxylamine hydrochloride is carried out in the presence of a base, such as triethylamine, in a suitable solvent, such as methanol, at a temperature between 0 ℃ and 100 ℃. For related examples, see Kitamura, s, et al chem.pharm.bull [ chemical and pharmaceutical bulletin ]2001,49,268 and WO 2013/066838. The reaction is shown in scheme 4 below.
Figure BDA0003023364140000212
Scheme 4
The compound having the formula (I-a) can be prepared by reacting a compound having the formula (II) with a compound having the formula (I-c) (wherein R is5AIs hydrogen, methyl or ethyl, preferably methyl) in a suitable solvent (e.g. methanol), optionally in the presence of a base (e.g. triethylamine), at a temperature between 25 ℃ and 65 ℃. Compounds having the formula (II) are known or commercially available. This reaction is shown in scheme 5 below.
Figure BDA0003023364140000221
Scheme 5
A compound having the formula (I-c) (wherein R3Is F, R4Is F, R1Is OH, R5AIs ethyl, and A and R2As defined for the compound having formula (I)) can be prepared by reacting a compound having formula (VII) with ethyl-2, 2-difluoro-2-trimethylsilylacetate, formula (VIII), in a suitable solvent, such as dimethylformamide, dichloromethane or tetrahydrofuran, preferably between 25 ℃ and 100 ℃In the presence of a fluoride anion donor such as tris (dimethylamino) trimethylsulfonium silicate (TASF), tetrabutylammonium fluoride (TBAF), potassium fluoride, cesium fluoride, etc.; similar to Tetrahedron Letters]2000,41,8763-8767 or JP 10101614A. This reaction is shown in scheme 6 below.
Figure BDA0003023364140000222
Scheme 6
A compound having the formula (I-c) (wherein R1Is OH, R5AIs ethyl, and A, Z, R2、R3And R4As defined for the compound having formula (I) can be prepared by reacting a compound having formula (VII) with an O-silylenone acetal having formula (X) in a suitable solvent, such as dimethylformamide, dichloromethane or tetrahydrofuran, preferably at a temperature between 25 ℃ and 100 ℃, in a lewis acid, such as TiCl4Or SnCl2) Or a fluoride anion donor such as tris (dimethylamino) trimethylsulfonium orthosilicate (TASF), tetrabutylammonium fluoride (TBAF), potassium fluoride, cesium fluoride, etc. O-silylketene acetals of the formula (X) can be prepared by conditions known in the literature, such as Tetrahedron Letters]2000,41, 8763-8767; journal of Organic Chemistry]2007, 72, 7125-7134; and Synthesis],1989,3,163-6. The reaction is shown in scheme 7 below.
Figure BDA0003023364140000231
Scheme 7
In addition, compounds having the formula (I-c) (wherein R1Is OH, and A, Z, R2、R3And R4As defined for the compound having formula (I) can be prepared by reacting a compound having formula (III) with an enol ester having formula (XII) in a suitable solventIn the agent (e.g. methyltetrahydrofuran or tetrahydrofuran), it is preferably at a temperature between 25 ℃ and 100 ℃. The enol esters having formula (XII) can be prepared by treating a compound having formula (XIII) with a base such as lithium diisopropylamide in a suitable solvent such as tetrahydrofuran, using conditions known in the literature, for example, Journal of Organic Chemistry],1971,36,1149. The reaction is shown in scheme 8 below.
Figure BDA0003023364140000241
Scheme 8
In addition, compounds having formula (I-a) (wherein R1Is OH, and A, Z, R2、R3And R4As defined for the compound of formula (I) can also be prepared from a carbonyl compound of formula (XVI) in a suitable solvent (e.g. tetrahydrofuran) at a temperature between 60 ℃ and 75 ℃ and subsequently adding a nucleophile (e.g. an alkyl grignard reagent (e.g. C))1-4Alkyl MgBr) in a suitable solvent (e.g. tetrahydrofuran or ethanol) at a temperature between 0 ℃ and 25 ℃. See, for related examples, Cogan, d., Ellman j.a.j.am.chem.soc. [ journal of the american chemical society]1999,121,268. This reaction is shown in scheme 9.
Figure BDA0003023364140000242
Scheme 9
Compounds having the formula (I-b) wherein Y is S can be prepared from compounds having the formula (I-a) by reaction with a suitable sulfur source [ e.g. elemental sulfur (S)8) Lawson's reagent, or P2S5]In an acceptable solvent (e.g., toluene, CH)2Cl2、CHCl3Tetrahydrofuran, tert-butyl methyl ether) at a temperature between 0 ℃ and 100 ℃. For related examples, see Hermant, F. et al Organometallics [ organometallic ]],201433,5643; heyde, c, et al e.j.org.chem. [ european journal of organic chemistry]2000,19,3273. This reaction is shown in scheme 10.
Figure BDA0003023364140000251
Scheme 10
As already indicated, surprisingly, it has now been found that, for practical purposes, the compounds of the invention having formula (I) have a very advantageous level of biological activity for protecting plants from diseases caused by fungi.
The compounds of formula (I) can be used in the agricultural sector and in the relevant fields of use, for example, as active ingredients for controlling plant pests, or on non-living materials for controlling spoilage microorganisms or organisms potentially harmful to humans. These novel compounds are distinguished by excellent activity at low application rates, good plant tolerance and no environmental hazard. They have very useful therapeutic, prophylactic and systemic properties and can be used to protect many cultivated plants. The compounds of formula (I) can be used to inhibit or destroy pests which occur on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of a wide variety of different crops of useful plants, while also protecting, for example, those plant parts which grow later, from phytopathogenic microorganisms.
The present invention further relates to a method for controlling or preventing infestation of plants or plant propagation material susceptible to microbial attack and/or harvested food crops by treating the plants or plant propagation material and/or harvested food crops, wherein an effective amount of a compound of formula (I) is applied to the plants, parts thereof or the locus thereof.
It is also possible to use compounds of the formula (I) as fungicides. As used herein, the term "fungicide" means a compound that controls, modifies, or prevents the growth of fungi. The term "fungicidally effective amount" when used means the amount of such a compound or combination of such compounds that is capable of effecting fungal growth. The effects of control or modification include all deviations from natural development, such as killing, retardation, etc., and prevention includes barrier or other defense constructs in or on the plant to prevent fungal infection.
The compounds of formula (I) can also be used as seed dressings for the treatment of plant propagation material (e.g. seeds, such as fruits, tubers or cereals) or plant cuttings for protection against fungal infections as well as against phytopathogenic fungi present in the soil. The propagation material may be treated with a composition comprising a compound having formula (I): for example, the seeds may be dressed prior to sowing. The active compounds of formula (I) can also be applied to the cereals (coating) by dipping the seeds in a liquid formulation or by coating them with a solid formulation. The composition may also be applied to the planting site at the time of planting the propagation material, for example to the furrow of the seed during sowing. The invention also relates to such a method of treating plant propagation material, and to the plant propagation material so treated.
Furthermore, the compounds of formula (I) may be used in the relevant field for controlling fungi, for example for the protection of industrial materials, including wood and wood-related industrial products, food storage, hygiene management.
In addition, the present invention can also be used to protect non-living materials (e.g., wood, wallboard, and paint) from fungal attack.
The compounds of formula (I) are useful, for example, against disease fungi and fungal vectors as well as phytopathogenic bacteria and viruses. Fungi and fungal vectors and phytopathogenic bacteria and viruses of these diseases are for example:
cephem, alternaria species, trichosporon species, ascochyta species, aspergillus species (including aspergillus flavus, aspergillus fumigatus, aspergillus nidulans, aspergillus niger, aspergillus terreus), aureobasidium species (including aureobasidium pullulans), dermatitidis germinatus, wheat powdery mildew, asparagus lettuce disk stem (Bremia lactucae), plasmodiophora species (including b.dothidea), botrytis cinerea (b.obtusia)), botrytis species (including botrytis cinerea), candida species (including candida albicans, candida glabrata (c.glabrata), candida krusei (c.kurosesii), candida parapsilosis (c.lucita), candida parapsilosis, candida albicans (c.lucita), candida haloperiensis, cercospora coralis, cercospora rosea (c.sphaericoides), candida parapsilosis sp., cercospora species (c.sphaericoides), candida parapsilosis, cercospora species (c.nivea) Cladosporium species, Claviceps, Coccidioides, anthrax species (including banana colletotrichum (C.musae)), Cryptococcus neoformans, Aschersonia species, Septoria species, Helminthosporium species, Eleospora species, Eleoporis species, Epidermophyton, Pyricularia pyricularis, Erysiphelus species (including Asteraceae (E.cichoreaum)), Rhizoctonia botrytis (Eutypa lata), Fusarius species (including Fusarium culmorum, Fusarium graminearum, F.langsehiae, Fusarium moniliforme, Fusarium collopora, Fusarium solani, Fusarium oxysporum, Fusarium exserotina, Fusarium triticum (Gaeumannomyces graminis), Gibberella fujiki), Fusarium japonicum (Gierbella), Gloecium japonicum, Gloecium purpurea, Gloecium japonicum (Gloecium), Gloecium japonicum (Gloecium), Gloecium pilosum (Gloecium), Gloecium japonicum, Gloecium viride), Gloecium viridae (Gloecium, Gloecium pilosum, Gloecium viride), Gloecium viride, Gloecium japonicum, Gloecium virid, Gloecium viride, Gloei, Gloecium viride, Gloei, Gloecium viride, Gloei, Gloecium viride, etc., Gloei, etc., Gloecium viride, etc., Gloei, etc., Gloecium viride, etc., strain, etc., Gloecium viride, etc., Gloecium virid, etc., Gloecium viride, etc., strain, etc., Gloecium, etc., Corp, etc., Cor, etc., strain, etc., Corp, etc., and/or Cor, etc, Helminthosporium species, camelina rust species, histoplasmosis species (including histoplasmosis capsulatum (H.capsulatum)), rhodomyceliophthora, Leptoraphium lindbergi, Leveillospora capsici (Leveillula taurica), pine needle parietal disc (Lophodermatum segatium), Rhizopus nivale (Microdochium nivale), microsporum species, Sclerotinia species, Mucor species, Mycosphaerella species (including Mycosphaerella graminicola, Mallotus niponensis (M.pomi)), Sphinga, Picea spruce, Paracoccidia species, Penicillium species (including Penicillium digitatum, Penicillium), Mucor-like Mucor species, Mucor-fingerling (including Peronospora zeae, Mucor-gracilium and Peronospora sorghum), Peronospora species, Scytium glume-sporum, Phaeophyma solanum, Phomopsis sp Phytophthora species (including phytophthora infestans), plasmopara species (including plasmopara helospora, plasmopara viticola (p.viticola)), geotrichum species, plasmopara viticola species (including plasmopara viticola), Polymyxa graminis (Polymyxa graminis), Polymyxa betanae (Polymyxa betae), rhizoctonia cerealis (pseudosphaera chrysospora herpora herpotrichoides), pseudomonas species, pseudoperonospora species (including pseudoperonospora cucumopara, pseudoperonospora humuloides), pseudoperonospora species (including rhizoctonia solani, pseudoperonospora hum), pseudoperonospora pseudophaea (including rhizoctonia hordei), rhizoctonia tritici (p.recinophythora), rhizoctonia stri stris (p.strifmii), rhizoctonia cerealis (p.p.purpurea), rhizoctonia oryzae (p.rhizoctonia oryzae), rhizoctonia oryzae (p.oryzae), rhizoctonia oryzae (including rhizoctonia oryzae), rhizoctonia oryzae (p, rhizoctonia oryzae) species (p, rhizoctonia oryzae), rhizoctonia oryzae (p) species (including rhizoctonia oryzae) Rhizopus, rhizoctonia species, rhizopus species (including rhizopus oxysporum and rhizopus polytrichoides), anthracnose (schizochytrium pomi), sclerotinia species, rhizoctonia species, septoria species (including septoria nodorum (s.nodorum), septoria tritici (s.tritici)), strawberry powdery mildew (Sphaerotheca macularis), Sphaerotheca unilocusta (Sphaerotheca fusicula), sporotrichum (sporothiothrix) species, rhizopus nodorum (Stagonospora nodorum), Stemphylium (stemphytophyllum) species, breve (stercorium hirsutum), oryza sativa striata (thaneureprucosus), rhizopus moniliformis (thielavia nodorum), trichoderma (stemona), trichoderma (sterreissum), rhizopus oryzae (stevensis), rhizopus basicola (thielavia), trichoderma harzianum (trichoderma harzianum) species, trichoderma harzianum), trichoderma harzianum (rhizopus) species, trichoderma harzianum (rhizopus) species, trichoderma harzianum strain (rhizopus (trichoderma harzianum) species, trichoderma harzianum strain (trichoderma harzianum ) species, trichoderma harzianum strain (trichoderma harzianum strain (trichoderma harzianum) species, trichoderma harzianum strain, trichoderma harzianum, trichoderma harzi, Venturia species, including Venturia inaequalis (V.inaegulis), Verticillium species, and Xanthomonas species.
The compounds of formula (I) may be used, for example, in lawns, ornamentals such as flowers, shrubs, broad-leaved trees or evergreens, e.g., conifers, as well as tree injection, pest management, and the like.
Within the scope of the present invention, the target crops and/or useful plants to be protected typically include perennial and annual crops, such as berry plants, e.g. blackberry, blueberry, cranberry, raspberry and strawberry; cereals, such as barley, maize, millet, oats, rice, rye, sorghum, triticale and wheat; fiber plants such as cotton, flax, hemp, jute, and sisal; field crops such as sugar and feed beet, coffee beans, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees, such as apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear, and plum; grasses, such as bermuda grass, bluegrass, bentgrass, ciliate grass, beefwood, lolium, saint augustum, and zoysia; herbs such as basil, borage, chives, coriander, lavender, lemongrass, peppermint, oregano, parsley, rosemary, sage, and thyme; legumes, such as beans, lentils, peas and soybeans; nuts such as almonds, cashews, peanuts, hazelnuts, peanuts, pecans, pistachios, and walnuts; palm plants, such as oil palm; ornamental plants, such as flowers, shrubs and trees; other trees, such as cacao, coconut, olive and rubber trees; vegetables, such as asparagus, eggplant, broccoli, cabbage, carrot, cucumber, garlic, lettuce, zucchini, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach, and tomato; and grapevines, such as grapes.
The term "useful plants" is to be understood as also including useful plants which, as a result of conventional breeding methods or genetic engineering, are rendered tolerant to herbicides like bromoxynil or to herbicides like for example HPPD inhibitors, ALS inhibitors like for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-acetone-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen oxidase) inhibitors. An example of a crop which has been rendered tolerant to imidazolinones, such as imazethapyr, by conventional breeding methods (mutagenesis) is
Figure BDA0003023364140000291
Summer oilVegetables (canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate-and glufosinate-resistant corn varieties, among others
Figure BDA0003023364140000292
Herculex
Figure BDA0003023364140000294
And
Figure BDA0003023364140000295
commercially available under the trade name.
The term "useful plants" is to be understood as also including useful plants which have been so transformed, by using recombinant DNA techniques, that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, in particular of the genus bacillus.
Examples of such plants are:
Figure BDA0003023364140000296
(maize variety, expressing cryia (b) toxin); YieldGard
Figure BDA0003023364140000297
(maize variety, expressing CryIIIB (b1) toxin); YieldGard
Figure BDA0003023364140000298
(maize variety, expressing cryia (b) and CryIIIB (b1) toxins);
Figure BDA0003023364140000299
(maize variety, expressing Cry9(c) toxin); herculex
Figure BDA00030233641400002910
(maize variety, expressing the CryIF (a2) toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) which acquired salt tolerance to the herbicide glufosinate); nucotn
Figure BDA00030233641400002911
(cotton variety, expressing CryIA (c) toxin); bollgard
Figure BDA00030233641400002913
(cotton variety, expressing CryIA (c) toxin); bollgard
Figure BDA00030233641400002912
(cotton variety, expressing CryIA (c) and CryIIA (b) toxins);
Figure BDA00030233641400002920
(cotton variety, expressing VIP toxin);
Figure BDA00030233641400002914
(potato variety, expressing CryIIIA toxin);
Figure BDA00030233641400002916
Figure BDA00030233641400002915
GT Advantage (GA21 glyphosate tolerant trait),
Figure BDA00030233641400002917
CB Advantage (Bt11 Corn Borer (CB) character),
Figure BDA00030233641400002918
RW (corn rootworm trait) and
Figure BDA00030233641400002919
the term "crop plant" is to be understood as also including crop plants which have been so transformed, by using recombinant DNA techniques, that they are capable of synthesising one or more selectively acting toxins, as are known, for example, from toxin-producing bacteria, especially those of the genus bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from bacillus cereus or bacillus popilliae; or insecticidal proteins from bacillus thuringiensis, such as delta-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip 3A; or insecticidal proteins of bacteria colonizing nematodes, such as certain species of Photorhabdus (Photorhabdus spp.) or Xenorhabdus (Xenorhabdus spp.), e.g. Xenorhabdus luminescens (Photorhabdus luminescens), Xenorhabdus nematophilus (Xenorhabdus nematophilus); toxins produced by animals, such as scorpion toxin, spider toxin, bee toxin, and other insect-specific neurotoxins; toxins produced by fungi, such as streptomycete toxins, phytolectins (lectins), such as pea lectins, barley lectins or snowdrop lectins; lectins (agglutinins); protease inhibitors, such as trypsin inhibitors, serpins, patatin, cystatin, papain inhibitors; ribosome Inactivating Proteins (RIPs), such as ricin, corn-RIP, abrin, luffa seed protein, saporin or bryodin; steroid-metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor, HMG-COA-reductase, ion channel blockers such as sodium or calcium channel blockers, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinase, and glucanase.
Further, within the context of the present invention, δ -endotoxins (e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C) or vegetative insecticidal proteins (Vip) (e.g. Vip1, Vip2, Vip3, or Vip3A) are understood to obviously also include mixed toxins, truncated toxins, and modified toxins. Hybrid toxins are recombinantly produced by a novel combination of the different domains of those proteins (see, e.g., WO 02/15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid substitutions, it is preferred to insert a non-naturally occurring protease recognition sequence into the toxin, for example as in the case of Cry3a055, with the cathepsin-G-recognition sequence being inserted into the Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed in, for example, EP-A-0374753, WO 93/07278, WO 95/34656, EP-A-0427529, EP-A-451878 and WO 03/052073.
Methods for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0367474, EP-A-0401979 and WO 90/13651.
The toxins included in the transgenic plants render the plants tolerant to harmful insects. Such insects may be present in any taxonomic group of insects, but are particularly common to beetles (coleoptera), diptera (diptera) and moths (lepidoptera).
Transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are known and some of them are commercially available. Examples of such plants are:
Figure BDA0003023364140000311
(maize variety, expressing Cry1Ab toxin); YieldGard
Figure BDA0003023364140000312
Figure BDA0003023364140000315
(maize variety, expressing Cry3Bb1 toxin); YieldGard
Figure BDA0003023364140000313
(maize variety expressing Cry1Ab and Cry3Bb1 toxins);
Figure BDA0003023364140000314
(maize variety, expressing Cry9C toxin); herculex
Figure BDA0003023364140000316
(corn variety, expressing Cry1Fa2 toxin and obtaining salt tolerance to the herbicide glufosinate-ammoniumThe drug-property enzyme phosphinothricin N-acetyltransferase (PAT)); nucotn
Figure BDA0003023364140000319
(cotton variety, expressing Cry1Ac toxin); bollgard
Figure BDA0003023364140000317
(cotton variety, expressing Cry1Ac toxin); bollgard
Figure BDA0003023364140000318
(cotton varieties expressing Cry1Ac and Cry2Ab toxins);
Figure BDA00030233641400003110
(cotton variety, expressing Vip3A and Cry1Ab toxins);
Figure BDA00030233641400003112
Figure BDA00030233641400003111
(potato variety, expressing Cry3A toxin);
Figure BDA00030233641400003113
GT Advantage (GA21 glyphosate tolerant trait),
Figure BDA00030233641400003114
CB Advantage (Bt11 Zea maydis (CB) trait) and
Figure BDA00030233641400003115
further examples of such transgenic crops are:
bt11 maize, from Syngenta Seeds (Syngenta Seeds SAS), Hodby road (Chemin de l' Hobit)27, F-31790 Saussurel (St. Sauveur), France, accession number C/FR/96/05/10. Genetically modified maize is made resistant to attack by european corn borers (corn borers and pink stem borers) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the PAT enzyme to gain tolerance to the herbicide glufosinate ammonium.
Bt176 maize, from Syngenta Seeds (Syngenta Seeds SAS), Hodby road (Chemin de l' Hobit)27, F-31790 Saussurel (St. Sauveur), France, accession number C/FR/96/05/10. Genetically modified maize is capable of resisting the invasion of European corn borers (corn borers and pink stem borers) by transgenically expressing Cry1Ab toxin. Bt176 maize also transgenically expresses the PAT enzyme to gain tolerance to the herbicide glufosinate ammonium.
MIR604 maize from Syngenta Seeds (Syngenta Seeds SAS), Hodbolt (Chemin de l' Hobit)27, F-31790 Saussurel (St. Sauveur), France, accession number C/FR/96/05/10. Maize that is rendered insect resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3a055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
MON 863 corn, from Monsanto European S.A., 270-272 Tefreund Dawley (Avenue DE Tervuren), B-1150 Brussel, Belgium, accession number C/DE/02/9. MON 863 expresses Cry3Bb1 toxin and is resistant to certain coleopteran insects.
IPC 531 Cotton from Monsanto Europe S.A., 270-272 Tefreund Dawley (Avenue de Tervuren), B-1150 Brussel, Belgium, accession number C/ES/96/02.
6.1507 corn, from Pioneer Overseas Corporation, Texasco Dawley (Avenue Tedesco), 7B-1160 Brussel, Belgium, accession number C/NL/00/10. Genetically modified maize, expressing the protein Cry1F to obtain resistance to certain lepidopteran insects, and expressing the PAT protein to obtain tolerance to the herbicide glufosinate-ammonium.
NK603 XMON 810 maize, from Monsanto European 270-272 Tefreund David, B-1150 Brussel, Belgium, accession number C/GB/02/M3/03. Consists of a conventionally bred hybrid maize variety by crossing the genetically modified varieties NK603 and MON 810. NK603 XMON 810 maize transgenically expressed by AgrobacteriumProtein CP4 EPSPS obtained from strain CP4, making it resistant to herbicides
Figure BDA0003023364140000331
(containing glyphosate), and also Cry1Ab toxin obtained from Bacillus thuringiensis Coxifraga subspecies, rendering it resistant to certain lepidopteran insects, including European corn borer.
The compounds of formula (I) according to the present invention (including any one of compounds 1.1 to 1.33 described in table T1 (below), compounds 2.1 to 2.18 described in table T2 (below), or compounds 3.1 and 3.2 described in table T3 (below)) are useful for controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi on soybean plants (e.g. phakopsora pachyrhizi).
In particular, transgenic soybean plants expressing toxins such as insecticidal proteins, e.g., delta-endotoxins (e.g., Cry1Ac (Cry1Ac Bt protein)). Thus, this may include transgenic soybean plants comprising event MON87701 (see U.S. patent No. 8,049,071 and related applications and patents, and WO 2014/170327 a1 (see, e.g., for intaca RR2 PROTMParagraph [008 ] of Soybean]) Event MON87751 (U.S. patent application publication No. 2014/0373191), or event DAS-81419 (U.S. patent No. 8632978 and related applications and patents).
Other transgenic soybean plants may comprise event SYHT0H2-HPPD tolerance (U.S. patent application publication No. 2014/0201860 and related applications and patents), event MON 89788-glyphosate tolerance (U.S. patent application publication No. 7,632,985 and related applications and patents), event MON 87708-dicamba tolerance (U.S. patent application publication No. US 2011/0067134 and related applications and patents), event DP-356043-5-glyphosate and ALS tolerance (U.S. patent application publication No. US 2010/0184079 and related applications and patents), event a 2704-12-glufosinate tolerance (U.S. patent application publication No. US 2008/0320616 and related applications and patents), event DP-305423-1-ALS tolerance (U.S. patent application publication No. US 2008/0312082 and related applications and patents), Event A5547-127-glufosinate tolerance (U.S. patent application publication No. US 2008/0196127 and related applications and patents), event DAS-40278-9-tolerance to 2, 4-dichlorophenoxyacetic acid and aryloxyphenoxypropionate (see WO 2011/022469, WO 2011/022470, WO 2011/022471, and related applications and patents), event 127-ALS tolerance (WO 2010/080829 and related applications and patents), event GTS 40-3-2-glyphosate tolerance, event DAS-68416-4-2, 4-dichlorophenoxyacetic acid and glufosinate tolerance, event FG 72-glyphosate and isoxaflutole tolerance, event BPS-CV127-9-ALS tolerance and GU 262-glufosinate tolerance or event SYHT04R-HPPD tolerance.
In certain instances, the compounds of formula (I) according to the present invention may show a synergistic interaction between the active ingredients when used for controlling or preventing phytopathogenic diseases, in particular phytopathogenic fungi (such as phakopsora pachyrhizi) on soybean plants, in particular on any transgenic soybean plant as described above.
In addition, to date, no cross-resistance was observed between compounds of formula (I), including any of compounds 1.1 to 1.33 described in Table T1 (below), compounds 2.1 to 2.18 described in Table T2 (below), or compounds 3.1 and 3.2 described in Table T3 (below), and current fungicidal solutions for the control of phakopsora pachyrhizi.
Indeed, fungicidally resistant strains of phakopsora pachyrhizi have been reported in the scientific literature, wherein strains are observed that are resistant to one or more fungicides from at least each of the following classes of fungicidal mode of action: sterol demethylation inhibitors (DMI), quinone outside inhibitors (QoI) and succinate dehydrogenase inhibitors (SDHI). See, for example: "Sensitivity of Phakopsora pachyrhizi toxins in their quinone-outer-inhibitors and methylation-inhibitors, and related resistance mechanisms]"Schmitz HK et al, Pest Manag Sci [ Pest Manag management science](2014)70: 378-; "First detection of a SDH variant with reduced SDHI sensitivity in Phakopsora pachyrhizi [ SDH variants with reduced SDHI sensitivity were First detected in T.pachyrhizi]”
Figure BDA0003023364140000341
K et al, J Plant Dis Prot [ journal of Plant disease protection ]](2018)125: 21-2; "Competitive fitness of Competitive fixness of Phakopsora pachyrhizi isolates with mutations in the CYP51 and CYTB genes [ Competitive fitness of Phoma pachyrhizi isolates with mutations in CYP51 and CYTB genes]"Klosowski AC et al, Phytopathology [ Phytopathology](2016)106: 1278-1284; detection of the mutation F129L in the cytochrome b gene of Phakopsora pachyrhizi (Phakopsora pachyrhizi) by "Detection of the F129L mutation in the cytochrome b gene of the Phakopsora pachyrhizi]"Kloowski AC et al, Pest Manag Sci [ Pest Manag of Pest management](2016)72:1211-1215。
Thus, in a preferred embodiment, compounds of formula (I) (including any one of compounds 1.1 to 1.33 described in Table T1 (below), compounds 2.1 to 2.18 described in Table T2 (below), or compounds 3.1 and 3.2 described in Table T3 (below)) or a fungicidal composition according to the invention comprising a compound of formula (I) are used to control phakopsora pachyrhizi which is resistant to one or more fungicides from any one of the following fungicidal MoA classes: sterol demethylation inhibitors (DMI), quinone outside inhibitors (QoI) and succinate dehydrogenase inhibitors (SDHI).
The compounds of formula (I) (including any one of compounds 1.1 to 1.33 described in table T1 (below), compounds 2.1 to 2.18 described in table T2 (below), or compounds 3.1 and 3.2 described in table T3 (below)) or the fungicidal compositions according to the present invention comprising a compound of formula (I) are useful for controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi, such as phakopsora pachyrhizi, on soybean plants. In particular, there are certain superior soybean plant varieties known in the scientific literature in which R gene stacks conferring a degree of immunity or resistance to a particular phakopsora pachyrhizi have been introgressed into the plant genome, see for example: "Lighting Asian Soybean Rust [ Fighting Asian Soybean Rust ]", Langenbach C et al, Front Plant Science [ Plant Science Front edge ]7(797) 2016).
A elite plant is any plant from the elite line, and thus a elite plant is a representative plant from the elite variety. Non-limiting examples of superior soybean varieties commercially available to farmers or soybean breeders include: AG00802, a0868, AG0902, a1923, AG2403, a2824, a3704, a4324, a5404, AG5903, AG6202, AG 0934; AG 1435; AG 2031; AG 2035; AG 2433; AG 2733; AG 2933; AG 3334; AG 3832; AG 4135; AG 4632; AG 4934; AG 5831; AG 6534; and AG7231 (asgro Seeds, demelein (Des Moines), iowa, usa); BPR0144RR, BPR 4077NRR, and BPR 4390NRR (Bio Plant Research), Camp Point (Camp Point), il, usa); DKB17-51 and DKB37-51 (Decalb Genetics, Decalb, Ill., USA); DP 4546RR, and DP 7870RR (Delta & Pine Land Company, lubock, texas, usa); JG 03R501, JG 32R606C ADD, and JG 55R503C (JGL Inc., greenkasle, indiana, usa); NKS 13-K2 (NK Division of Syngenta Seeds, Inc. (NK Division of Syngenta Seeds), gold Valley, Minnesota, USA); 90M01, 91M30, 92M33, 93M11, 94M30, 95M30, 97B52, P008T22R 2; P16T17R 2; P22T 69R; P25T 51R; P34T07R 2; P35T 58R; P39T 67R; P47T 36R; P46T 21R; and P56T03R2 (Pioneer International, Inc. (Pioneer Hi-Bred International), Manchurn (Johnston), Iowa, USA); SG4771NRR and SG5161NRR/STS (Soygenetics, LLC, Lafaytte, Ind. Naa, USA); S00-K5, S11-L2, S28-Y2, S43-B1, S53-A1, S76-L9, S78-G6 and S0009-M2; S007-Y4; S04-D3; S14-A6; S20-T6; S21-M7; S26-P3; S28-N6; S30-V6; S35-C3; S36-Y6; S39-C4; S47-K5; S48-D9; S52-Y2; S58-Z4; S67-R6; S73-S8; and S78-G6 (Senhengda seed company, Henderson, Kentucky, USA); richer (north star Seed Ltd.), Alberta (Alberta), canada); 14RD62 (Stine Seed Co., Stine Seed Co., Iowa, USA); or Armor 4744 (Armor Seed LLC, alaska, usa).
Thus, in another preferred embodiment, the use of a compound of formula (I) (including any one of compounds 1.1 to 1.33 described in Table T1 (below), compounds 2.1 to 2.18 described in Table T2 (below), or compounds 3.1 and 3.2 described in Table T3 (below)) or a fungicidal composition according to the present invention comprising a compound of formula (I) controls phakopsora pachyrhizi (including its fungicidally resistant strains, as described above) on elite soybean plant varieties, wherein a stack of R genes conferring a degree of immunity or resistance to a particular phakopsora pachyrhizi has been introgressed in the plant genome. Many benefits are expected from such uses, such as improved biological activity, a favorable or broader spectrum of activity (including sensitive and resistant strains of phakopsora pachyrhizi), increased safety, improved crop tolerance, synergistic interactions or enhanced properties, improved onset or longer lasting residual activity, reduced number of applications and/or reduced application rates of compounds and compositions required for effective control of phytopathogens (phakopsora pachyrhizi), thereby achieving beneficial resistance-management practices, reduced environmental impact and reduced operator exposure.
As used herein, the term "locus" means a place in or on which plants are grown, or a place where seeds of cultivated plants are sown, or a place where seeds are to be placed in soil. It includes soil, seeds, and seedlings, along with established vegetation.
The term "plant" refers to all tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves, and fruits.
The term "plant propagation material" is to be understood as meaning the reproductive parts of plants, such as seeds, which parts can be used for the propagation of plants, and vegetative material, such as cuttings or tubers (e.g. potatoes). Mention may be made, for example, of seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Mention may also be made of germinated plants and young plants which are to be transplanted after germination or after ground breaking. These young plants can be protected prior to transplantation by being treated in whole or in part by immersion. Preferably, "plant propagation material" is understood to mean seeds.
The compounds of formula (I) can be used in unmodified form or, preferably, together with adjuvants conventionally used in the art of formulation. For this purpose, they can be conveniently formulated in known manner as emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granules and also encapsulants, for example in polymeric substances. The type of composition, the method of application, such as spraying, atomizing, dusting, spreading, coating or pouring, is selected according to the intended purpose and the prevailing circumstances. The composition may also contain additional adjuvants such as stabilizers, defoamers, viscosity modifiers, binders or tackifiers, as well as fertilizers, micronutrient donors or other formulations for achieving a particular effect.
Suitable carriers and adjuvants, for example for agricultural use, may be solid or liquid and are substances useful in formulation technology, for example natural or regenerated mineral substances, solvents, dispersions, wetting agents, tackifiers, thickeners, binders or fertilizers. Such vectors are described, for example, in WO 97/33890.
Suspension concentrates are aqueous formulations in which highly dispersed solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersants, and may further include wetting agents to enhance activity, as well as anti-foaming agents and crystal growth inhibitors. In use, these concentrates are diluted in water and applied to the area to be treated, usually as a spray. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Wettable powders are in the form of highly dispersible granules which are readily dispersible in water or other liquid carriers. These particles contain the active ingredient held in a solid matrix. Typical solid substrates include fuller's earth, kaolin clays, silicas and other readily wettable organic or inorganic solids. Wettable powders usually contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
Emulsifiable concentrates are homogeneous liquid compositions that are dispersible in water or other liquids and may consist entirely of the active compound with liquid or solid emulsifiers or may also contain liquid carriers such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and are typically applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Particulate formulations include both extrudates and coarser particles and are typically applied undiluted to the area in need of treatment. Typical carriers for granular formulations include sand, fuller's earth, attapulgite clay, bentonite clay, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, stucco, wood flour, ground corn cobs, ground peanut hulls, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate and other organic or inorganic active absorbing or active compound-coated materials. Granular formulations typically contain 5% to 25% active ingredient, which may include surfactants such as heavy aromatic essential oils, kerosene and other petroleum fractions, or vegetable oils; and/or adhesives such as dextrins, glues or synthetic resins.
Dusty powders are free-flowing mixtures of the active ingredient with highly dispersed solids such as talc, clays, flours and other organic and inorganic solids as dispersants and carriers.
Microcapsules are typically droplets or particles of the active ingredient encapsulated within an inert porous shell that allows the encapsulated material to escape to the environment at a controlled rate. The encapsulated droplets typically have a diameter of 1 micron to 50 microns. The encapsulated liquid typically constitutes 50% to 95% of the weight of the capsule and may include a solvent in addition to the active compound. Encapsulated particles are typically porous particles in which a porous membrane seals the particle pores, thereby retaining the active species in liquid form inside the particle pores. The diameter of the particles typically ranges from 1mm to 1 cm and preferably 1mm to 2 mm. The particles are formed by extrusion, agglomeration or spheronization, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and carbon granules. Shell or membrane materials include natural and synthetic rubbers, fibrous materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, and starch xanthates.
Other useful formulations for agrochemical applications include simple solutions of the active ingredient in solvents (e.g., acetone, alkylated naphthalenes, xylene, and other organic solvents) in which the active ingredient is completely dissolved at the desired concentration. Pressurized sprays may also be used in which the active ingredient is dispersed in a highly dispersed form as a result of evaporation of the low boiling dispersant solvent carrier.
Suitable agricultural adjuvants and carriers useful in formulating the compositions of the present invention in the above formulation types are well known to those of ordinary skill in the art.
Liquid carriers that may be utilized include, for example, water, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1, 2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N-dimethylformamide, dimethyl sulfoxide, 1, 4-dioxane, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkylpyrrolidones, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1, 1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, di (proxytol), alkyl pyrrolidones, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1, 1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, methyl alcohol, 1, 2-butyl alcohol, di (di-ethyl-butyl alcohol), methyl alcohol, di (di-butyl alcohol), di (di-ethyl alcohol), di (di-butyl alcohol), di-ethyl alcohol), di (di-butyl alcohol, di-ethyl alcohol, di (di-ethyl alcohol, di-ethyl, Ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl laurate, methyl caprylate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleyl amine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, Methanol, ethanol, isopropanol, and higher molecular weight alcohols such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, and the like, ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is generally chosen as the carrier for dilution of the concentrate.
Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth (kieselguhr), chalk, diatomaceous earth (Diatomaxeous earth), lime, calcium carbonate, bentonite, fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, and lignin.
A wide range of surfactants can be advantageously employed in the liquid and solid compositions, especially those designed to be dilutable with a carrier prior to administration. These agents, when used, typically constitute from 0.1% to 15% by weight of the formulation. They may be anionic, cationic, nonionic or polymeric in nature and may be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surfactants include alkyl sulfates such as diethanolammonium lauryl sulfate; alkyl aryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol-c.sub.18 ethoxylates; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub.16 ethoxylate; soaps, such as sodium stearate; alkyl naphthalene sulfonates such as sodium dibutylnaphthalene sulfonate; salts of dialkyl sulfosuccinates, such as sodium bis (2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethyl ammonium chloride; polyoxyethylene esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono-and dialkyl phosphates.
Other adjuvants commonly used in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, antifoaming agents, opacifiers, compatibilizing agents, antifoam agents, masking agents, neutralising and buffering agents, corrosion inhibitors, dyes, flavour enhancers, spreading agents, penetration aids, micronutrients, emollients, lubricants and fixing agents.
Furthermore, further, other biocidal active ingredients or compositions may be combined with the compositions of the present invention and used in the methods of the present invention and applied simultaneously or sequentially with the compositions of the present invention. When administered simultaneously, these additional active ingredients may be formulated or mixed together with the compositions of the present invention in, for example, a spray can. These further biocidal active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.
Pesticides using their common names mentioned herein are known, for example, from The Pesticide Manual, 15 th edition, British Crop Protection Council 2009.
In addition, the compositions of the present invention may also be administered with one or more systemic acquired resistance inducers ("SAR" inducers). SAR inducers are known and described, for example, in US patent No. US 6,919,298, and include, for example, salicylates and the commercial SAR inducer acibenzol-S-methyl.
The compounds of formula (I) are generally used in the form of agrochemical compositions and can be applied to the crop area or to the crop to be treated simultaneously or sequentially with further compounds. For example, these additional compounds may be fertilizers or micronutrient donors or other preparations that affect plant growth. They may also be selective herbicides or nonselective herbicides, together with insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application-promoting adjuvants customarily employed in the art of formulation.
The compounds of formula (I) may be used in the form of (fungicidal) compositions for the control or protection against phytopathogenic microorganisms, comprising, as active ingredient, at least one compound of formula (I) or at least one preferred individual compound as defined herein, in free form or in agrochemically usable salt form, and at least one of the aforementioned adjuvants.
The present invention therefore provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I), an agriculturally acceptable carrier and optionally adjuvants. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, in addition to comprising a compound having formula (I), the composition may comprise at least one or more pesticidally active compounds, for example additional fungicidal active ingredients.
The compound of formula (I) may be the sole active ingredient of the composition or it may be mixed with one or more additional active ingredients (such as a pesticide, fungicide, synergist, herbicide or plant growth regulator) as appropriate. In some cases, the additional active ingredients may result in unexpected synergistic activity.
Examples of suitable additional active ingredients include the following: acyclic amino acid (acycloamino acid) fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, aromatic fungicides, arsenic-containing fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, plant fungicides, bridging biphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furoamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphate fungicides, organotin fungicides, and the like, Oxathiin fungicides, oxazole fungicides, thiophenamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide (sulfonanilide) fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valiamide (valinamide) fungicides, and zinc fungicides.
Examples of suitable additional active ingredients also include the following: 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-dichloromethylene-1, 2,3, 4-tetrahydro-1, 4-methano-naphthalen-5-yl) -amide, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid methoxy- [ 1-methyl-2- (2,4, 6-trichlorophenyl) -ethyl ] -amide, 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl) -amide (1072957-71-1), 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (4' -methylsulfanyl-biphenyl-2-yl) -amide, 1-methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid [2- (2, 4-dichloro-phenyl) -2-methoxy-1-methyl-ethyl ] -amide, (5-chloro-2, 4-dimethyl-pyridin-3-yl) - (2,3, 4-trimethoxy-6-methyl-phenyl) -methanone, (5-bromo-4-chloro-2-methoxy-pyridin-3-yl) - (2,3, 4-trimethoxy-6-methyl-phenyl) -methanone, 2- {2- [ (E) -3- (2, 6-dichloro-phenyl) -1-methyl-prop-2-ene- (E) -ylideneaminooxymethyl ] -phenyl } -2- [ (Z) -methoxyimino ] -N-methyl-acetamide, 3- [5- (4-chloro-phenyl) -2, 3-dimethyl-isoxazolidin-3-yl ] -pyridine, (E) -N-methyl-2- [2- (2, 5-dimethylphenoxymethyl) phenyl ] -2-methoxy-iminoacetamide, processes for their preparation, pharmaceutical compositions containing them and their use, 4-bromo-2-cyano-N, N-dimethyl-6-trifluoromethylbenzimidazole-1-sulfonamide, α - [ N- (3-chloro-2, 6-xylyl) -2-methoxyacetamido ] -y-butyrolactone, 4-chloro-2-cyano-N, N-dimethyl-5-p-tolylimidazole-1-sulfonamide, N-allyl-4, 5-dimethyl-2-trimethylsilylthiophene-3-carboxamide, N- (l-cyano-1, 2-dimethylpropyl) -2- (2, 4-dichlorophenoxy) propionamide, N- (2-methoxy-5-pyridyl) -cyclopropanecarboxamide, N- (3-chloro-2, 6-xylyl) -2-methoxyacetylamino-butyronitrile, N- (2-chloro-5-pyridyl) -2-butyronitrile-amide, and mixtures thereof, (. + -) cis-1- (4-chlorophenyl) -2- (1H-1,2, 4-triazol-1-yl) -cycloheptanol, 2- (1-tert-butyl) -1- (2-chlorophenyl) -3- (1,2, 4-triazol-1-yl) -propan-2-ol, 2',6' -dibromo-2-methyl-4-trifluoromethoxy-4 '-trifluoromethyl-1, 3-thiazole-5-carboxanilide, 1-imidazolyl-1- (4' -chlorophenoxy) -3, 3-dimethylbut-2-one, (E) -2- [2- [6- (2-cyanophenoxy) pyrimidine-4- Aryloxy ] phenyl ] 3-methoxyacrylate methyl ester, (E) -2- [2- [6- (2-sulfanylaminophenoxy) pyrimidin-4-yloxy ] phenyl ] -3-methoxyacrylate methyl ester, (E) -2- [2- [6- (2-fluorophenoxy) pyrimidin-4-yloxy ] phenyl ] -3-methoxyacrylate methyl ester, (E) -2- [2- [6- (2, 6-difluorophenoxy) pyrimidin-4-yloxy ] phenyl ] -3-methoxyacrylate methyl ester, (E) -2- [2- [3- (pyrimidin-2-yloxy) phenoxy ] phenyl ] -3-methoxyacrylate methyl ester, methyl ester, (E) -methyl 2- [2- [3- (5-methylpyrimidin-2-yloxy) -phenoxy ] phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [3- (phenyl-sulfonyloxy) phenoxy ] phenyl-3-methoxyacrylate, methyl (E) -2- [2- [3- (4-nitrophenoxy) phenoxy ] phenyl ] -3-methoxyacrylate, methyl (E) -2- [ 2-phenoxyphenyl ] -3-methoxyacrylate, methyl (E) -2- [2- (3, 5-dimethyl-benzoyl) pyrrol-1-yl ] -3-methoxyacrylate, (E) -methyl 2- [2- (3-methoxyphenoxy) phenyl ] -3-methoxyacrylate, (E) -methyl 2- [2- (2-phenylethen-1-yl) -phenyl ] -3-methoxyacrylate, (E) -methyl 2- [2- (3, 5-dichlorophenoxy) pyridin-3-yl ] -3-methoxyacrylate, (E) -methyl 2- (2- (3- (1,1,2, 2-tetrafluoroethoxy) phenoxy) phenyl) -3-methoxyacrylate, (E) -methyl 2- (2- [3- (. alpha. -hydroxybenzyl) phenoxy ] phenyl) -3-methoxyacrylate, methyl (E) -2- [3- (. alpha. -hydroxybenzyl) phenoxy ] phenyl ] -3-methoxyacrylate, (E) -methyl 2- (2- (4-phenoxypyridin-2-yloxy) phenyl) -3-methoxyacrylate, methyl (E) -2- [2- (3-n-propyloxy-phenoxy) phenyl ] 3-methoxyacrylate, methyl (E) -2- [2- (3-isopropyloxyphenoxy) phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [3- (2-fluorophenoxy) phenoxy ] phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- (3-ethoxyphenoxy) phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- (4-tert-butyl-pyridin-2-yloxy) Methyl phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [3- (3-cyanophenoxy) phenoxy ] phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [ (3-methyl-pyridin-2-yloxymethyl) phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [6- (2-methyl-phenoxy) pyrimidin-4-yloxy ] phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- (5-bromo-pyridin-2-yloxymethyl) phenyl ] -3-methoxyacrylate, (E) -methyl 2- [2- (3- (3-iodopyridin-2-yloxy) phenoxy) phenyl ] -3-methoxyacrylate, methyl (E) -2- [2- [6- (2-chloropyridin-3-yloxy) pyrimidin-4-yloxy ] phenyl ] -3-methoxyacrylate, methyl (E), (E) -2- [2- (5, 6-dimethylpyrazin-2-ylmethyloximomethyl) phenyl ] -3-methoxyacrylate, methyl (E) -2- {2- [6- (6-methylpyridin-2-yloxy) pyrimidin-4-yloxy ] phenyl } -3-methoxy-acrylate, methyl (E) -2- [2- (6-methylpyridin-2-yloxy) pyrimidin-4-yloxy) phenyl ] -n-3-methoxyacrylate, methyl (E) -n-butyl (E-methyl (E) -n-butyl (E) -n-2-yloxy) phenyl ] -3-methoxyacrylate, methyl (E) -n-butyl (E) -n-2- [ 2-methyl (E-2-yl) phenyl ] -n-methoxyacrylate, (E) (E) -2- {2- (3-methoxyphenyl) methyloxidomethyl ] -phenyl } -3-methoxyacrylate methyl ester, (E) -2- {2- (6- (2-azidophenoxy) -pyrimidin-4-yloxy ] phenyl } -3-methoxyacrylate methyl ester, (E) -2- {2- [ 6-phenylpyrimidin-4-yl) -methyloxidomethyl ] phenyl } -3-methoxyacrylate methyl ester, (E) -2- {2- [ (4-chlorophenyl) -methyloxidomethyl ] -phenyl } -3-methoxyacrylate methyl ester, (E) -2- {2- [6- (2-n-propylphenoxy) -1 Methyl 3, 5-triazin-4-yloxy ] phenyl } -3-methoxyacrylate, (E) -2- {2- [ (3-nitrophenyl) methyloximinomethyl ] phenyl } -3-methoxyacrylate, 3-chloro-7- (2-aza-2, 7, 7-trimethyl-oct-3-en-5-yne), 2, 6-dichloro-N- (4-trifluoromethylbenzyl) -benzamide, 3-iodo-2-propinol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2, 3-diiodo-2-propenylethylcarbamate, methyl (E) -2- {2- [ (3-nitrophenyl) methyloximinomethyl ] phenyl } -3-methoxyacrylate, methyl (E) -2, 6-dichloro-N- (4-trifluoromethylbenzyl) -benzamide, 3-iodo-2-propiolic alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2, 3-diiodo-2-propenylethylcarbamate, methyl (E) -2- {2- [ (3-nitrophenyl) methyloximinomethyl ] phenyl } -3-methoxy-acrylate, and (E) -2-chloro-2-oxa-2-propenyl-propargyl-5-carbaldehyde, 2,3, 3-triiodoallyl alcohol, 3-bromo-2, 3-diiodo-2-propenyl alcohol, 3-iodo-2-propynyl n-butyl carbamate, 3-iodo-2-propynyl n-hexyl carbamate, 3-iodo-2-propynyl cyclohexyl carbamate, 3-iodo-2-propynyl phenyl carbamate; phenol derivatives such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3, 5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophenol, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol, 5-hydroxy-2 (5H) -furanone; 4, 5-dichlorodithiazolinone, 4, 5-benzodithiazolone, 4, 5-trimethylenedithiazolone, 4, 5-dichloro- (3H) -1, 2-dimercapto-3-one, 3, 5-dimethyl-tetrahydro-1, 3, 5-thiadiazin-2-thione, N- (2-p-chlorobenzoylethyl) -hexamethylenetetramine chloride, acibenzolar (acibenzolar), octa-ninety-oic acid (acetyltetracos), gossypr, albendazole, cartap (aldimorph), allicin, allyl alcohol, ametoctradin, amisulbrom, amobam, alanyl phosphonic acid (ampropylfos), dichlofluanid, arsenic (asomate), aureofungin (aureozan), azaconazole, alexidin, oxifamidid (azofamide), oxifamidim (azofamid), azofamid (azofamid), Azoxystrobin, barium polysulfide, benalaxyl-M, mefenoxanil (benodanil), benomyl, hydrazone, metolacron (bentaluron), benthiavalicarb, thiocyan, benzalkonium chloride, festoonic acid (benzamacril), benzomorph (benzamorf), benzohydroxamic acid, benzovindiflupyr (benzovindifluppy), berberine, beclomezine (bexazin), bitertanol (bilozagrol), binapacryl, biphenyl, bitertanol, bixafen (bixafen), blasticidin-S, boscalid, bromothalonil, bromuconazole, bupirimate, buthionine, calcium polysulphide, captafol, captan, moroxydine, carbendazim hydrochloride, propachlor, carvone, CGA41397, fenchlorazol (41397), chlorazol, fenchlorazol chloride, fenchol, fenchlorazol, fenchol, fentrazone, diclofen (fenclofenapyr), diclofen, fenclofenapyr-S, fenpropidin, fenpropiconazole, CGA, fenpropiconazole, ethirimol, climbazole, clotrimazole, clarithron (clozylacon), copper-containing compounds such as copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinoline, copper silicate, copper sulfate, copper resinate, copper zinc chromate, and bordeaux mixture, cresol, thiabendazole, copper chloride (cuprobam), cuprous oxide, cyprosulfamide (cyazofamid), cyclamamide (cycloafuramid), cycloheximide, cyhalonil, cyazofamid (cypendazole), cyproconazole, cyprodinil, dazole, dazomethane, prochloraz (debacarb), fenphostin, dehydroacetic acid, di-2-pyridyl disulfide 1,1' -dioxide, dichlofluanid (dichlofluanid), pyridazone (diomezin), dichlornaphthoquinone (diclofenamid), diclochlotriol (diclozoline), diclozolidinium (diclozoline), diclodinium chloride (difenon), difenoconazole (difenoconazole), cyhalodinil (cyhalodinil), cyhalodinil (cyhalodinil), cyhalodinil (cyhalodinil), cyhalodinil (cyhalodinil), cyhalodinil (cyhalodinil), cyhalodinil (cyhalodinil ), cyhalodinil (cyhalodinil ), cyhalodinil, cyhalodin, Difenzoquat, difluorine, O-diisopropyl-S-benzylthiophosphate, dimefluzole, dimeticonazole, dimethomorph, dimethirimol, diniconazole-M, dinotefuran, dinocap, clodinafop, nitryl (dinopenton), nitrooctyl (dinosulfon), nitrobutyl (dinoterbon), diphenylamine, dipyridazothion, disulfoton, dithianon (dithianon), dithioether, dodecyldimethylammonium chloride, dodecamorph, doxazone, dodecetin, dodecylguanidineacetate, diketene, distemper, enestroburin (enestroburin), epoxiconazole, ethionam (ethaboxam), ethaboxam (ethacryl), ethidium (ethidium), allicin, N-methyl-aminoethylquizaquin (N-methyl-N-ethyl-aminoethylthiopropionic acid) (N-methyl-N-propylidene) or Ethyl ester, hymexazol (etridiazole), famoxadone, fenamidone (fenamidone), disodium bensulide (fenaminosulf), fenapanil, fenarimol, fenbuconazole, mefuramide, fenhexamid, meperidate, fenoxanil, fenpropiconazole (fenpiclonid), fenpiclonil (fenpicoxamid), fenpropidin, fenpropimorph, fenpropiophenone, fentin acetate, triphenyltin hydroxide, fermetfe, ferimzone (ferimzone), fluazinam (fluazinam), fludioxonil, flumetol, flumorph, flupyrad (fluulide), fluopyram, furazamide, triflumizole (flutrimazole), fluoxastrobin, fluquinconazole, flusilazole (flufluflusulfamide), flumidamide (fluquinaniil), flufenpyr (flutolanilide), flutriafol, furazofamide, furazol, furazolidone, furbenfluridone, furazolidone, furbenfluridone, furazolidone, furbenfluridone, furazolidone, levulinate, griseofulvin, iminoctadine, quintoctrazole, hexachlorobutadiene, hexachlorophene, hexaconazole, hexazothion (hexythiofos), amaurodine (hydrargaphhen), hydroxyisoxazole, hymexazol, imazalil sulfate, imibenconazole, iminoctadine triacetate, cumquat chloride (inezin), iodopropynyl butylmethylaminoate (iodocarb), ipconazole, ipfentriflunazole, iprobenfos, iprodione, propineb, isopropylbutylcarbamate, isoprothiolane, isopyrazam, isothiavalicarb, fenamidone (isovalenide), fenpyrazophos (isoproyfos), kasugamycin, ethermethyl, 1864, fenflur 055, 2117908, mancozeb, fenpropineb, fenamidone (fenpropineb), fenamidophos (propiconazole), metominostrobin (metosulam), metominostrobin (metominostrobilurin), metominostrobilurin, metominostrobin (metominostrobilurin), metominostrobin, metominostrobilurin, metominostrobin, metomino, Mercuric chloride, mercurous chloride, meclofenoxaprop (meptyldinocap), metalaxyl, mefenoxam, metam, metamizoxolone (metazoxolon), metconazole, sulfcarb (methasulfocarb), furametpyr, methyl bromide, methyl iodide, methyl isothiocyanate, metiram-zinc, metominostrobin, metrafenone, tiadinil, metiram (milneb), moroxydine (moroxydine), myclobutanil, metulil (myclozolin), metiram (nabam), natamycin, TIAN, thiram, nitrostyrene, phthalazink, fluoropyrimidinol, octhiolone (octhiolone), furamide, organomercurides, orysastrobin, osthol (othanol), oxadixyl (oxadixyl), epoxysulfuron-methyl, thifensulfuron-methyl, copper-octopirox (oxypyr), pyraoxystrobin (oxypyr), pyrazoxol (oxypyr, pyraoxystrobin), pyraoxystrobin (oxypyr), pyraoxystrobin (oxypyr, pyraclostrobin (oxypyr), pyraclostrobin (propiconazole), pyraclostrobin (oxypyr, propoxyphylla, pyraclostrobin (propiconazole), pyraclostrobin (propiconazole), pyraclostrobin (propiconazole), pyraclostrobin (propi, Pencycuron (pencycuron), fluxapyroxad, pentachlorophenol, penthiopyrad (penthiopyrad), cyazoxystrobin, bismeryn, phosdiphen (phosdiphen), phytophthora-Al, phosphoric acids, phthalide, picoxystrobin, carbendazim, polycarbamate, polyoxin D, polyoxiram (polyoxim), metiram (polyram), thiabendazole, prochloraz, procymidone (procymidone), propamidine (propamidine), propamocarb (propamocarb), propiconazole, propineb, propionic acid, proquindoxine (proquinazid), thiocarb (prothiocarb), prothioconazole, fluxapyroxadiflox (pyumetofofen), iparol, pyraclostrobin (pyraclostrobin), pyraclostrobin, pylofen (pynolide), pyrimethanil (pyrimethanil), pyrimethanil (pythiuron (pylox), pyrimethanil (pymetrozine), pyrimethanil (pyloxil), pyrimethanil (pyloxidone (pylox), pyriproxyfen (pymetrozine), pyrimethanil (pymetrozine, pyriproxyfen (pymetrozine), pyrimethanil (pymetrozine, pyrimethanil), pyrimethanil (pymetrozine (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), pyrimethanil (pyrimethanil), quinophthalone (quinazamid), carfentrazone (quinconazole), mefenmanam, quinoxyfen, quintozene, pyridazole (rabenzazole), santonin (santonin), sedaxane (sedaxane), silthiopham, simeconazole (simeconazole), cinzole (sipconazol), sodium pentachlorophenate, spiroxamine, streptomycin, sulfur, dapsone (sultopen), tebuconazole, isobutoxyquinoline (tebufaquizin), phylloquinon, tetrachloronitrobenzene, fotiazem (tecoram), flutriazole, thiabendazole, thiadifluoride (thiadiflour), thiabendazole (thiazofenofen), thiflufenamide, 2- (thiocyanomethylthio) benzothiazole, methyl thiophanate, gram (thiquinonox), selam, tiazem, timidazol (fenbuconazole), fenpyrad (fenpyrad), trimethoprim (trimethoprim), trimethoprim, flutriafolpet, flutriafol, flutriafolpet, flutriafol, flubenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenazol, flubenbenbenbenbenbenbenazol, flubenbenbenbenazol, flubenazol, flubenbenbenbenbenazol, flubenazol, flubenbenbenbenazol, flubenbenbenazol, flubenazol, flubenbenazol, flubenazol, tridemorph, trifloxystrobin, acetamiprid (triflumizole), fluazinam, triflumizole, triticonazole, uniconazole, asomate (urbanide), validamycin, valicarb (valifenalate), weibai, vinclozolin, cyanamide (zarilamid), zineb, ziram, and zoxamide (zoxamide).
The compounds of the present invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include compounds selected from the macrolide class of compounds, such as ivermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives, as described in EP-357460, EP-444964 and EP-594291. Additional anthelmintic agents include semi-synthetic and biosynthetic avermectins/milbemycin derivatives, such as those described in US-5015630, WO-9415944 and WO-9522552. Additional anthelmintic agents include benzimidazoles such as albendazole, canabendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the classes. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines, such as tetraimidazole, levamisole, pyrantel pamoate, octopine or morantel. Additional anthelmintic agents include flukicides (e.g., triclabendazole and clorsulon) and tapecides (e.g., praziquantel and epsiprantel).
The compounds of the invention may be used in combination with derivatives and analogues of anthelmintic agents of the paraherquamide/marcfortine class and with antiparasitic oxazolines as disclosed in US-5478855, US-4639771 and DE-19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO 96/15121 and also with anthelmintically active cyclic depsipeptides such as those described in WO 96/11945, WO 93/19053, WO 93/25543, EP 0626375, EP 0382173, WO 94/19334, EP 0382173 and EP 0503538.
The compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; a pyrethroid; organic phosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid, etc.
The compounds of the present invention may be used in combination with terpene alkaloids, such as those described in international patent application publication No. WO 95/19363 or WO 04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that may be used in combination with the compounds of the present invention include, but are not limited to, the following:
organic phosphoric acid ester: acephate, methyl pyroxaphos, ethyl valefos, methyl valefos, bromophos, ethyl bromophos, cadusafos, chlorethophos (chlorethoxyphos), chlorpyrifos, chlorophenoxyphos, chlorophosphorus chloride, systemic phosphorus-S-methyl sulfone, chloroformithion, diazinon, dichlorvos, butylperoxy, dimethoate, fosetyl, ethiofen, fenamiphos, oxypyrimidine, vazaphosphor, fenamiphos, fenthion, phos, phosmet, fenphos, pyrazofos, difenofos, fosthiazate, heptenophos, clozaphosphor, isoprofos, isoxazolophos, malathion, chlorfenphos, methamidophos, methidathion, methyl parathion, monocrotophos, triazophos, dibromophos, omethoate, methyl oxophos, paraoxon, parathion, methyl parathion, fenphos, thiocarb, thiocyanoto, benbensulbensulbensulbensulbensulbensulbensulbensulbensulbensulam, bensulbensulam, bensulbensulbensulam, bensulbensulam, bensulam, bensulbensulbensulbensulam, bensulbensulam, bensulbensulbensulam, bensulam, bensulbensulbensulam, bensulbensulam, bensulbensulbensulam, bensulam, bensulbensulbensulbensulbensulbensulam, bensulam, bensulbensulbensulam, bensulam, Phosmet, phosphamidon, phorate, phoxim, chlorfenap, chlorfenapyr-methyl, profenofos, propaphos, proethamphos, profenofos, pyrazofos, pyridaphethione, quinalphos, thiofenamiphos, temephos, terbufos, butylpyrimidine phosphate, sethion, disulfoton (thimeton), triazophos, trichlorfon, and phosmet.
Carbamate ester: cotton boll-weevil, aldicarb, 2-butyphenyl methyl carbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, bendiocarb, ethiofencarb, fenoxycarb, fenthiok, furacarb, HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumyl butynyl (methyl) carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, monocarb, triazamate, UC-51717.
Pyrethroid: fluthrin, allethrin, alpha-cypermethrin, 5-benzyl-3-furylmethyl (E) - (1R) -cis-2, 2-dimethyl-3- (2-oxothiolane-3-ylidenemethyl) cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, alpha-cypermethrin, beta-cypermethrin, bioallethrin ((S) -cyclopentyl isomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyfluthrin, cypermethrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, cyfluthrin (D isomer), Prallethrin, cyfluthrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrin (natural product), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluothrin, t-tau-fluvalinate, tefluthrin, tetrabromthrin, zeta-cypermethrin.
Arthropod growth regulator: a) chitin synthesis inhibitors: benzoyl urea: chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, chlorfluazuron, buprofezin, phenthoate, hexythiazox, etoxazole, clofentezine (chlorpfendazine); b) ecdysone antagonists: chlorfenozide, methoxyfenozide, tebufenozide; c) juvenile hormone analogs: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitic agents: fenaminoquinone, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, sulfothiobac, bifenazate, binazate, bromopropylate, BTG-504, BTG-505, toxaphene, cartap, fenaminostrobin, chlordimeform, chlorfenapyr, chromafenozide, clothianidin, cyromazine, difloron (deacloden), chlordiazuron, DBI-3204, diethofencarb, dihydroxymethyl dihydroxy pyrrolidine, dinosaur, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flufenzine (flokite), MTI-800, fenpyroximate, pyrimidifen, flutriathia, bromofluthrin, flufenzine, trifluofen, benzoxyfen (fluroxyfen), benzoxyfen (halofenprox), hydramethylhydrazone, I-220, sodium hydrosilicate, NC-196, Indian mint (nereid), dinotefuran-10825, dinotefuran-2, dinotefuran, tefuran, and so, tefuran, and so, Pyridalyl, propargite, Profenofibrate (procifenbute), pymetrozine, pyridaben, pyriminostrobin, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomastin (silomadine), pleocidin, tebufenpyrad, trichlorfone, tetraantibiotic, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethylpleocidin, tretinoin, propargyl ether, bolacre (vertalelect), YI-5301.
Biological agent: bacillus thuringiensis ssp (aizawai), Bacillus thuringiensis kurstaki (kurstaki), Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, viruses, and fungi.
A bactericide: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, meloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, thiamerin, benazepril, piriprep (pyriprole), cefquinome, florfenicol, buserelin, cefuroxime, tolacin, ceftiofur, carprofen, meflozone, praziquantel, triclabendazole.
The following mixtures of compounds having formula (I) with active ingredients are preferred. The abbreviation "TX" means a compound selected from the group consisting of: a compound as shown in tables 1.1 to 1.12 (below), or in tables 3.1 to 3.6 (below), or compounds 1.1 to 1.33 described in table T1 (below), compounds 2.1 to 2.18 described in table T2 (below), or compounds 3.1 and 3.2 described in table T3 (below):
a compound selected from the group consisting of: petroleum + TX, 1-bis (4-chlorophenyl) -2-ethoxyethanol + TX,2, 4-dichlorophenyl benzene sulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenyl phenyl sulfone + TX, abamectin + TX, acequinome + TX, acetoprolide + TX, profenothrin + TX, aldicarb + TX, aldaxycarb + TX, cis-cypermethrin + TX, cyhalofop + TX, sulfasalazine + TX, tetrathion + TX, phosphamidon + TX, diamidon + oxamate + amiphos, amitraz + TX, miticide + TX, arsenic trioxide + TX, benfop + TX, baprofenon + TX, azobenzene + TX, azophos + TX, benoxaden + TX, benoxaphos (benoxas) +, benoxafos + TX, Benzyl benzoate + TX, bifenazate + TX, bifenthrin + TX, dicofol + TX, bixafen + TX, bromethiofen + TX, bromfenacide + TX, bromophos-ethyl + TX, bromopropylate + TX, buprofezin + TX, butocarbofuran + TX, butoxycarb + TX, butylpyridazole + TX, calcium polysulphide + TX, octachlorocamphene + TX, cloxacarb + TX, carbaryl + TX, carbofuran + TX, thiophosphoryl + TX, acarine + TX, methoxamine + TX, acaricidal ether + acetamidine + TX, chlorfenamidine + TX, chlorfenapyr + TX, fenapyr + TX, fenaminostrobilum + TX, acaricide + TX, dicofol + TX, fenamipide + TX, fenaminostrobilurin + TX, chlorfenadine (chloromebuform) +, chlorflufenozide + TX, chlorpyrifos + propyl, chlorpyrifos + TX, chlorpyrifos + D, chlorpyrifos + TX, chlorpyrifos + D, chlorpyrifos + TX, chlorpyrifos + D, chlorpyrifos + TX, chlorpyrifos + D, etcTick-methyl + TX, chlorfenphos + TX, guaethrin I + TX, guaethrin II + TX, guaethrin + TX, clofentezine + TX, closante + TX, coumaphos + TX, crotamiton + TX, baotoxin + TX, thiabendazole + TX, cyenophos + TX, cyflufen + TX, cyhalothrin + TX, cyhexatin + TX, cypermethrin + TX, DCPM + TX, DDT + TX, tianlepos-O + TX, tianlepos-S + TX, systemic phosphorus-methyl + TX, systemic phosphorus-O-methyl + TX, systemic phosphorus-S-methyl + TX, sulfur uptake (demeton-S-metalaxyl fonn) +, miticide, chlorpyrifos + TX, diazinon + TX, dichlorphos + DDP + TX, dichlorphos + TX, dicliphos + TX, diclodiclodin + TX, chlorothalofop + TX, diclofen + TX, profenofos + TX, dimethoate + TX, diethofencarb + TX, diclofen + CdTX, diclofen-zinc dacryline (dicexene) + TX, dicloflueton + TX, dipon-4 + TX, dipon-6 + TX, clofenthion + TX, amyl nitrate ester + TX, nitrooctyl ester acaricide + TX, nitrobutyl ester + TX, fenamiphos + TX, sulfodiphenyl + TX, disulfoton + TX, DNOC + TX, propargite (dofenapyn) + TX, doramectin + TX, thiodan + TX, indofos + TX, EPN + TX, eprazole + TX, ethion + TX, thion + Fefenthion + fenthion, ethion + fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion, fen, Fenpyroximate + TX, fenpyrazamine + TX, fenpyroximate + TX, flufenpyroximate + TX, flufenvalerate + TX, fipronil + TX, fluacrypyrim + TX, fluazuron + TX, flufenthiuron + TX, flucythrinate + TX, bifenthrin + TX, flufenoxuron + TX, flumethrin + TX, flufenpropathrin + TX, fluvalinate + TX, FMC 1137+ TX, varroamidine + TX, vaboxam hydrochloride + TX, ANthion + TX, carboxim (formcanate) +, gamma-HCH + TX, glyodin + TX, benzoxim + TX, heptenophos + TX, hexadecylcyclopropanecarboxylate + TX, hexythiazox + TX, iodomethane + TX, fenthion + TX, jasmonate I + TX, iodophorate + TX, fenthion + Sulfuron, fenflurazon + fenfluroxypyr, fenthion + MTP, valacil + TX, cyhalothion + TX, valacil + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion + TX, fenthion, fenthio, Dithiafos + TX, methidafen + TX, chlorfenvinphos + TX, methamidophos + TX, methidathion + TX, methomyl + TX, methyl bromide + TX, metomyl + TX, metoclopramide + TX, metolcarb + TX, and dimetachlone+ TX, milbemycin oxime + TX, propaphosphate + TX, monocrotophos + TX, Rogome + TX, Moxidectin + TX, naled) + TX, 4-chloro-2- (2-chloro-2-methyl-propyl) -5- [ (6-iodo-3-pyridyl) methoxy]Pyridazin-3-one + TX, fluvalinate + TX, nicomycin + TX, fenproparb 1:1 zinc chloride complex + TX, omethoate + TX, oxamyl + TX, sulfofenphos + TX, pp' -DDT + TX, parathion + TX, permethrin + TX, fenthion + TX, phenthoate + TX, phorate + TX, phoxim + TX, thiocyclam + TX, phosmet + TX, phosphamidon + TX, phoxim + TX, pirimiphos + TX, chloroturpentine (polychlorites) +, miticide (polynactins) + TX, prochlorhydrin + TX, profenofos + TX, tick-way + TX, propargite + TX, propamocarb TX + TX, propoxur + TX, etothion + TX, ethiprolide + TX, phenthoate + TX, fenphos + TX, I + pyrethrin + II + pyrethrin + pyridaphenthrin + TX, pyridaphenthion + TX, etc, Pyrithion + TX, quinalphos (quintiofos) + TX, R-1492+ TX, glythion + TX, rotenone + TX, octamethrin + TX, captan + TX, selamectin + TX, suthion + TX, spirodiclofen + TX, spiromesifen + TX, SSI-121+ TX, sulam + TX, flubendiamide + TX, thiotep + TX, sulfur + TX, flutenzine + TX, tau-fluvalinate + TX, tebufenpyrad + TX, terbufos + sethoxyfen + TX, tetrachlorfenthion + TX, acaricide + TX, good + TX, thiafenox + TX, carbofuran + TX, monocarb + TX, pirimiphos + TX, fosinate + trimethophos, cloxacarb + TX, sulbactam + TX, fenthion + triazophos + Triprofenozide + TX, triclopyr + Triprofenox, triclopyr + TX, triclopyr, triclocarp + TX, triclocarp, Aphidicol + TX, metaflumizone (vanipronil), chlorfenacin + TX, copper dioctoate + TX, copper sulphate + TX, cyclobutryne + TX, dichloronaphthoquinone + TX, dichlorophen + TX, endothal + TX, triphenyltin + TX, slaked lime + TX, sodium metiram + TX, quinoxaline + TX, quinonamide (quinonamide) + TX, simazine + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, clomiphos + TX, emamectin benzoate + TX, piperazine + TX, spinosad + TX, tobutide + TX, chloraldose + TX, isotridecyl agent + TX, fenthion + TX, pyridine-4-amine + TX, strychnine + TX, 1-hydroxy-1H-pyridine-2-thione + 4, 4-pyridine-1H-pyridine-2-thione + TX, 4-hydroxy-1H-2-thione- (quinoxalin-2-ylamino) benzenesulfonamide + TX, 8-hydroxyquinoline sulfate + TX, bronopol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, polydicine + TX, disodium benrosolute) + TX, formaldehyde + TX, mercurifen + TX, kasugamycin hydrochloride hydrate + TX, bis (dimethyldithiocarbamate) nickel + TX, chloropyridine (nitrapyrin) + TX, octulone (octhialone) + TX, oxolinic acid + TX, oxytetracycline + TX, hydroxyquinoline potassium sulfate + TX, thiabendazole + TX, streptomycin sesquisulfate + TX, phyllophthalein + TX, thimerosal + TX, cotton moth GV + TX, Agrobacterium radiobacter + TX, Sublyseius (Amblyseius spp.) + TX, Novosa alburena + NPV + Smovata, Plumbus apium + TX) +, Bacillus brevis (Aphellus abdominis) + TX, Aphis gossypii (Aphidius colemanii) + TX, Aphis pythium (Aphidoletes aphrodimyza) + TX, Spodoptera lucida NPV + TX, Bacillus firmus) + TX, Bacillus sphaericus (Bacillus sphaericus Neide) + TX, Bacillus thuringiensis (Bacillus thuringiensis Berlini) + TX, Bacillus thuringiensis (Bacillus thuringiensis) TX, Bacillus thuringiensis) + Bacillus thuringiensis (Bacillus thuringiensis subsp. aizawai TX), Bacillus thuringiensis (Bacillus thuringiensis subsp. subtilis, Bacillus thuringiensis) TX) + Bacillus thuringiensis (Bacillus thuringiensis) and Bacillus thuringiensis subsp. sp. sp.javanicus, Bacillus thuringiensis TX) + Bacillus thuringiensis, Bacillus thuringiensis subsp (Bacillus thuringiensis subsp. sp. sp.sp., Codling moth GV + TX, Siberian amoeba (Dacnusa sibirica) + TX, Pisum sativum leaf miner Mesemaphus (Diglyhos isaea) + TX, Encarsia formosa (Encarsia formosa) + TX, Pectinatus serohilus (Eretmocerucus) + TX), Spodoptera frugiperda NPV + TX, Heterorhabdus bacteriovora (Heterorhabditis bacteriophora) and Heterorhabdus heterorhabdus (H.megdis) + TX, Laggera maculata sp (Hippodamia convergens) + TX), Ciceris citrifolia parasite wasp (Leptomonas campestris) (Leptophylla parasitica) + TX, Blind (Macrophophora calluses TX) + cabbage, Spodoptera brassicae NPV + TX, Meconopsis flavipes apis bracteata (Metaphalaena Nostoides) and Trypanosoma esculentaHelvoluus) + TX, Metarrhizium chrysogenum (Metarrhizium anisopliae) var. acridum) + TX, Metarrhizium anisopliae var. chrysoidium (Metarrhizium anisopliae) var. anisoplica) + TX, Neosporophytes Europaea (Neodiprion) NPV and Neosporophytes erythraea (N.lecontei) NPV) + TX, Orchikutsetus species + TX, Paecilomyces fumonis (Paecilomyces fumosoroseus) + TX, Gracillus persicaria (Phytoseiulus persiciparum) (Phytosilus persiciparum) Persiccus) +, Phylloides (Phytoseilus persiciparum) Persimilis) + TX, Spodopterocarpus polysilus chinensis (Spodopterocarpus androgynus) TX) + Stephomopsis, Stephomopsis TX + Stephomopsis TX, Stephomopsis TX + Stephomopsis wire, Stephania pinus TX + Stephania trichothecoides (Stephania spp) +, Oxazaphosphozine (apholate) + TX, bis (aziridine) methylaminophosphine sulfide (bisazer) + TX, busulfan + TX, diflubenzuron + TX, dimaltoff (dimatif) + TX, hexamethylmelamine (hemel) + TX, hexametaphosphate (hempa) + TX, methenamine (methotepa) + TX), methidathion (methiotepa) + TX, methidathion (methethopalate) + TX, pyriproxyfen (morzid) + TX, chlorfluazuron (penfluron) + TX, thiabenda (tepa) + TX, thiohexamethop (thiohemampha) + TX, thiobam + TX, tritylamine + TX, uretonimine + TX, (E) -dec-5-en-1-yl acetate and (E) -dec-5-en-1-ol + E) -tridec-4-ene-1-yl-heptene-2-methyl-4-ene-2-4-yl-methyl-2-heptene-ol, (E, Z) -tetradec-4, 10-dien-1-ylacetate + TX, (Z) -dodec-7-en-1-ylacetate + TX, (Z) -hexadec-11-enal + TX, (Z) -hexadec-11-en-1-ylacetate + TX, (Z) -hexadec-13-en-11-yn-1-ylacetate + TX, (Z) -eicos-13-en-10-one + TX, (Z) -tetradec-7-en-1-al + TX, (Z) -tetradec-9-en-1-ol + TX, (Z) -tetradec-9-en-1-ylacetate + TX, (7E,9Z) -Dodeca-7, 9-dien-1-ylacetate + TX, (9Z,11E) -tetradeca-9, 11-dien-1-ylacetate + TX, (9Z,12E) -tetradeca-9, 12-dien-1-ylacetate + TX, 14-methyloctadec-1-ene + TX, 4-methylnonan-5-ol and 4-methylnonan-5-one + TX, alpha-polylysine (alpha-multistriatin) + TX, Cethol pinus tabularisBeetle pheromone (brevicomin) + TX, dodecadienol (codlelure) + TX, attainable Mongolian (codlemone) + TX, cue lure (cuecure) + TX, decadecane (disparlure) + TX, dodec-8-en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodec-8 + TX, 10-dien-1-yl acetate + TX, dominicare + TX, 4-methyloctanoate + TX, eugenol + TX, south pine bark beetle pheromone (frontalin) + TX, moth cetyl esters (gossyplur) + TX, moth beetle mixture (grandilur) + SIM TX, lure beetle mixture I + TX, lure beetle mixture II + TX, lure beetle mixture III + TX, lure beetle mixture IV + hexedrene mixture IV, hexedrene (sipyre) + alcohol) + TX, small crotyl alcohol (sipenol) + TX, lure beetle TX, and tremule mixture II + TX, Tortoise sex attractant (receptacle) + TX, trimethyldioxytranononane (lineatin) + TX, litlure + TX, pink moth sex attractant (looplure) + TX, trapping ester (medlure) + TX, mecacic acid (megatomoic acid) + TX, insect-trapping ether (methyl eugenol) + TX, insect-trapping alkene (muscalure) + TX, octadeca-2, 13-diene-1-yl acetate + TX, octadeca-3, 13-diene-1-yl acetate + TX, hekang another (orfrapure) + TX, coconut moth-eating rhinoceros pheromone (orytalure) + TX, Fulerkang (ostramone) + TX, lure ring (siglure) + TX, sordidin + TX, phagostimulol (sulcotol) + TX, tetradec-11-ene-1-yl acetate + TX, Bactrocera mediterrae attractant (trimedlure) + TX, Bactrocera mediterrae attractant A + TX, and Bactrocera mediterrae B.1+ TX, Mediterranean fruit fly attractant B2+ TX, Bactrocera minax attractant C, trunc-call + TX,2- (octylthio) ethanol + TX, diethylpropion (butopyronoxyl) + TX, butoxy (polypropylene glycol) + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, deet + TX, desmetryn (dimethyl carbonate) + TX, dimethyl phthalate + TX, ethylhexanediol + TX, hexamide (hexamide) + TX, mequinate (mequine-butyl) + TX, methylneodecanoamide (methylneodecanoamide) + TX, oxamate (oxamate) + TX, pimelin (picardidin) + TX, 1-dichloro-1-nitroethane + TX, 1-dichloro-2 TX, 2-di (4-ethylphenyl) ethane + TX, 1, 2-dichloropropane + 1, 3-propylene, 1-bromo-2-chloroethane + TX,2, 2, 2-trichloro-1- (3, 4-dichlorophenyl) ethyl acetate + TX,2, 2-dichlorovinyl 2-ethylsulfinylethyl-methylphosphoniumAcid ester + TX,2- (1, 3-dithiolan-2-yl) phenyldimethylcarbamate + TX,2- (2-butoxyethoxy) ethylthiocyanate + TX,2- (4, 5-dimethyl-1, 3-dioxolan-2-yl) phenylmethylcarbamate + TX,2- (4-chloro-3, 5-ditolyl-oxy) ethanol + TX, 2-chloroethenyl diethylphosphate + TX, 2-imidazolinone + TX, 2-isovalerylindan-1, 3-dione + TX, 2-methyl (prop-2-ynyl) aminophenylmethylcarbamate + TX, 2-thiocyanoethyllaurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazol-5-yldimethylcarbamate + TX, 4-methyl (prop-2-ynyl) amino-3, 5-xylylmethylcarbamate + TX, 5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate + TX, acephate + TX, acetamiprid + TX, alathion + TX, acrylonitrile + TX, bollworm + TX, chloromethylnaphthalene + TX, allethrin + TX, aloamidin (allosamidin) + TX, methomyl + TX, alpha-ecdysone + TX, aluminum phosphide + TX, methomyl + TX, neonicotin + ethyl methidathion (athidathion) + TX, azadirachtin + TX, pirimiphos + TX, bacillus thuringiensis delta-endotoxin + TX, barium hexafluorosilicate + TX, sodium chloride, sodium, Barium polysulfide + TX, permethrin + TX, Bayer 22/190+ TX, Bayer 22408+ TX, bendiocarb + TX, benfuracarb + TX, bensulam + TX, beta-cyfluthrin + TX, beta-cypermethrin + TX, bioallethrin S-cyclopentenyl isomer + TX, pentoxyfen (biothanomethrin) + TX, bioallethrin + TX, bioresmethrin + TX, bis (2-chloroethyl) ether + TX, bistriflurea + TX, borax + TX, bromophenol phosphorus + TX, bromo-DDT + TX, Symphetamine + TX, zoocarb + TX, tetramethrin + TX, Temiphos (terbuthiofos) + TX, butylphos + TX, cadusafos (cadusafos) + TX, calcium arsenate + TX, cyanide + carbon disulfide + carbon tetrachloride + TX, buthan tetrachloride + TX, buticarbon + TX, valbutarb + valdine + TX, hydrochloride) +, Borneolum + TX, chlordane + TX, chlorkone + TX, chlorfenapyr + TX, chlorfluazuron + TX, chlormephos + TX, chloroform + TX, chloropicrin + TX, chlorodeoxyniumphos + TX, chloropyrazophos (chlorprazophos) + TX, chromafenozide + TX, cis-resmethrin (cis-resmethrin) + TX, cis-resmethrin (cismethrin) + TX, cypermethrin (clocythrin) (alias) + TX, cloethocarb) + TX, clothianidin + TX, copper arsenite + TX, copper arsenate + TX,Copper oleate + TX, methidathion (coumaphos) + TX, cryolite + TX, CS 708+ TX, cyanophos + TX, cyhalothrin + TX, pyrethroid + TX, cyfluthrin + TX, deltamethrin + TX, cyphenothrin + TX, cyromazine + TX, butfenthion + TX, d-limonene + TX, d-tetramethrin + TX, DAEP + TX, dazomet + TX, desmethoprofen-carbofuran (decarbofuran) + TX, deltamethrin + TX, dimidaafos (diamafos) + TX, isochlorophos + TX, dichlofenthion (dichlofenthion) + TX, dichlofenamate) + TX, dicycloderman + TX, dicyclanil + TX, dieldrin + TX, diethyl 5-TX-3-yl phosphate + TX, fludioxonil + TX, tetramethrin + TX, dimethomorph + methomyl + chlorpyrifos + TX, methomyl + TX, methomyl + dimethofen + TX, dimethofen + dimethofen, dimethofen + TX, dimethofen-TX, dimethofen-D, dimethofen-TX + TX, dimethofen-TX, dimethofen-TX, and dimethofen-D-TX, dimethofen, and dimethofen-TX, and dimethofen, and D-TX, Dinotefuran + TX, bendiocarb + TX, bensulide + TX, bendiocarb + TX, thiopyrad + TX, DSP + TX, ecdysterone + TX, EI 1642+ TX, EMPC + TX, S-enynjujue vinegar + TX, EPBP + TX, bayan ether + TX, esfenvalerate + TX, oxford propyl thion (etaphos) + TX, ethiofencarb + TX, ethiprole + TX, ethoprophos + TX, ethyl formate + TX, ethylene dibromide + TX, ethylene dichloride + TX, ethylene oxide + TX, ethofenprox + TX, EXD + TX, vazaphos + fenclofos (fenamiphos) +), picromaphos + TX, ethoprophos + TX, fenobucarb + TX, fenpropathrin + TX, fenfluroxypyr + ucuron + TX, fenpropathrin + flufenpropathrin + ethyl, fenfluroxyphos-S + TX, fenfluroxypyr + TX, fenfluroxypyr + flufenfluroxypyr + TX, fenfluridone + flufenfluridone + TX, fenfluridone + TX, fenfluridone + TX, fenfluridone, Pyriminostrobin + TX, trifloxystrobin + TX, dimefluthrin + TX, disulfoton + TX, fosxate + TX, thiazolone P + TX, thiofenthion + TX, furametpyr + TX, anthurium + TX, gamma-cyhalothrin + TX, guazatine (guazatine) + TX, guazatine + TX, tetrathionate + TX, carboxim + TX, chlorfenapyr + TX, quinolinecarb + TX, imidacloprid + TX, prallethrin + TX, indoxacarb + TX, IPSP + TX, isazofos (isazofos) + TX), carbocloprid + TX, isosbanide + TX, isophosphorus + TX, isoprothiolane + TX, isoprothiolate + TX, isoprothiolane + TX, isoprothiolane + TX, and other, Juvenile hormone II + TX, juvenile hormone III + TX, chlorolane + TX, methoprene + TX, lambda-cyhalothrin + TX, lead arsenate + TX, lepimectin + TX, bromophenol + TX, pyridaphos + TX, fosthiazate (fosthazate) + TX, meta-cumyl methyl carbamate + TX, magnesium phosphide + TX, triazophos + TX, methyltriazophos (mecarpon) + TX, chlorfenamiphos + TX, mercurous chloride + TX, phosmet + TX, metaflumizone + TX, metam potassium salt + TX, metam sodium salt + TX, methanesulfonyl fluoride + TX, crotonylphos + TX, methothrin + TX, methoxyfenozide + TX, methyl isothiocyanate + TX, methylchloroform + TX, dichloromethane + TX, metocloprofenprox + TX, oxadixyl + TX, naphalene + NC-170+ nicotine + TX, nitenpyram + nites, nites + TX, nitenpyram + TX, nites + TX, methamphetamine + TX, and a, Nithiazine + TX, protonicotin + TX, novaluron + TX, O-5-dichloro-4-iodophenyl O-ethyl thiophosphonate + TX, O, O-diethyl O-4-methyl-2-oxo-2H-benzopyran-7-yl thiophosphonate + TX, O, O-diethyl O-6-methyl-2-propyl pyrimidine-4-yl thiophosphonate + TX, O, O ', O' -tetrapropyl dithiopyrophosphate + TX, oleic acid + TX, phosphorus-methyl-TX, p-dichlorobenzene + TX, methyl parathion + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, permethrin + TX, PH 60-38+ TX, Fenthion + TX, phenothrin + TX, parathion + TX, phosphine + TX, methyl phoxim + TX, methamidophos + TX, pirimicarb + TX, pirimiphos-ethyl + TX, polychloroprene isomer + TX, potassium arsenite + TX, potassium thiocyanate + TX, prallethrin + TX, precocious I + TX, precocious II + TX, precocious III + TX, pirimiphos + TX, proffluthrin + TX, methidathion + TX, propaphos + TX, prothioconazole + TX, propylbenzene hydrocarbon pyrethrin (Protrifenbute) + TX, pymetrozine + pyrazole thion + TX, pyrazofos + TX, bendiomphetamine + TX, pyridalyl + TX, pyriproxyfen + TX, picrashifen + TX, picrashiza + TX, fenthion + TX, clodinafur + TX, furethrin + thion + TX, thifenprox + TX, fenugine + rythrin + TX, rythrone + TX, fenugo-TX + TX, kaempferine + TX, Linalodine + TX, sabadilla vera (sabadilla) + TX, octamethylphosphonium + TX, captan + TX, selamectin + TX, SI-0009+ TX, silafluofen + TX, thiapropionitrile + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenate + TX, sodium selenate + TX, sodium thiocyanate + TX, spiro-phenolEthyl sulfofenuron + TX, sulfofenuron (sulcofuron) + TX, sulfophenyl ether sodium salt (sulcofuron-sodium) + TX, sulfuryl fluoride + TX, thioprofos + TX, tar + TX, thiocarb (tazimcarb) + TX, TDE + TX, tebufenozide + TX, butylpyrimidine phosphate + TX, tefluthrin + TX, disulfoton + TX, cyclopentene plus TX, terbufos) + TX, tetrachloroethane + TX, tetramethrin + TX, theta-cypermethrin + TX, thiacloprid + TX, thiamethoxam + TX, thiochlorophos + TX, thiocyclam + TX, thiodicarb + TX, thiofenthiocarb (thionazin) +) + TX, bisultap + TX, bisodium salt of bisodium, tolanilide + TX, tralomethrin + TX, fenthiothrin + TX, metocloprofenprox + TX, tebuconazole + TX, thiofenthiofenthiofenthiofenthiocarb + TX, tebuconazole + TX, thiofenthiofenthiofenthiocarb + TX, thiofenpyrad + TX, thiofenthiocarb + TX, tebuconazole + TX, thiofenthiofenthiofenthiofenthiofenthiofenthiofenthiocarb + TX, tebuconazole + TX, tebucfenpyraclostrobin + TX, and TX, etc, Methiocarb) + TX, trimethacarb (tolprocarb) + TX, nitrapyrin + TX, methoprene + TX, veratridine + TX, veratrine + TX, XMC + TX, methiocarb + TX, zeta-cypermethrin + TX, methiocarb (zetamethrin) + TX, zinc phosphide + TX, triazophos + TX, and brofluthrin + TX, cyantraniliprole + TX, chlorantraniliprole + TX, cyhalodiamide + cyhalodiamide, cyhalodiamide + TX, cyenopyrafen + TX, fluquine (pyrifluquinazon) + TX, spinetoram + TX, sulfoxaflor + TX, butenafloxacin + ethanolamine, permethrin + TX, tefluthrin + TX, triflumylpyrimidine (trifloxystrobin TX) + TX, bis (tributyltin) oxide + TX, bromoacetamide + TX, tetramethamine + chloral + niclosamide, niclosamide + niclosolx + TX, niclosamide + niclosamide, niclosamide + TX, niclosamide + niclosamide, niclosamide + TX, niclosamide + niclosamide, niclosamide + TX, niclosolx + niclosamide, niclosamide + TX, niclosamide + TX, niclosamide, niclosolm + niclosamide, niclosolm + TX, niclosamide, niclosolm + TX, niclosamide + niclosamide, niclosamide + TX, niclosamide, niclosolm + TX, niclosamide + TX, niclosamide, niclosoltx, niclosamide + TX, niclosamide, pyraclostrobin + TX, imidazole cyclophosphate (Imicyafos) + TX, 1, 2-dibromo-3-chloropropane + TX, 1, 3-dichloropropene + TX, 3, 4-dichlorotetrahydrothiophene 1, 1-dioxide + TX, 3- (4-chlorophenyl) -5-methylrhodanine + TX, 5-methyl-6-thio-1, 3, 5-thiadiazin-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, thiochloride (benclothiaz) + TX, cytokinin (cytokinins) + TX, DCIP + TX, furfural + TX, isoamidophos (isamidofos) + TX, kinetin) + TX, Myrothecium verrucaria composition + TX, bendiocarb (phocarbocarb) b + TX, tetrachlorothiophene + TX, xylenol + zeatin + TX, fluthiacetone + TX, Potassium ethyl xanthate + TX, acibenzolar (acibenzolar) + TX, acibenzolar-S-methyl + TX, giant knotweed (Reynoutria sachalinensis) extract + TX, alpha-chlorohydrin + TX, clofibrate + TX, barium carbonate +TX, bismuthylurea + TX, bromomuron + TX, bromodiuron + TX, bromethamine + TX, murinone + TX, cholecalciferol + TX, clomuryn + TX, criminostrobin + TX, rodenticine + TX, rodenticidine + TX, rodenticide + TX, dicresyl + TX, calciferol + TX, flocoumafen + TX, fluoroacetamide + TX, flonicadine + TX, flonicamid hydrochloride) + TX, tolterodine + TX, phosphamidon + TX, phosphorus + TX, rodenticide + TX, dicumyl + TX, hedyol + TX, sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX,2- (2-butoxyethoxy) ethyl piperonate + TX, 5- (1, 3-benzodioxol-5-yl) -3-hexyl-2-enone + TX, farnesol + TX, nerolidol +, Synergistic acetylenic ether + TX, MGK 264+ TX, piperonyl butoxide + TX, synergistic aldehyde (piprost) + TX, propyl isomer + TX, S421+ TX, synergistic powder (sesamex) + TX, sesamolin (sesasmin) + TX, sulfoxide + TX, anthraquinone + TX, copper naphthenate + TX, copper oxychloride + TX, dicyclopentadiene + TX, salen + TX, zinc naphthenate + TX, ziram + TX, imatinib + TX, ribavirin + TX, mercuric oxide + TX, thiophanate methyl + TX, azaconazole + TX, bitertanol + TX, bromuconazole + TX, cyproconazole + TX, difenoconazole + TX, diniconazole + TX, epoxiconazole + TX, fenbuconazole + TX, fluquinconazole + TX, flusilazole + TX, flutriafol-furazol + TX, hexaconazole + TX, imazalil + imidyl, ipconazole + Metronidazole + TX, myclobutanil + TX, paclobutanil + TX, paclobutrazol + TX, fenconazole + TX, fentrazol + TX, Pyrifenox + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyriconazole + TX, simeconazole (simeconazole) + TX, tebuconazole + TX, tetraconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triticonazole + TX, pyrimidinol + TX, fenarimol + TX, bupirimate (bupirimate) + TX, dimethirimol) + TX, ethirimol (ethirimol) + TX, dodecamorph + TX, fenpropidine (fenpropidine) + TX, fenpropimorph + TX, spiroxamine + TX, tridemorph + TX, cyprodinil + TX, pyrimethanil + furametryn (rimol) +, flufen + TX, flutolanil + furazol + TX, fenpropazocarb + furazol + TX, fenpropiconazole + furazolidone + TX, furazolidone + TX, furazolidone + TX, furazolidone + TX, furazolidone + TX, furazolidone, furazolby, furazolidone, carbendazim + TX, debacarb + TX, fuberidazole + TX, thiabendazole + TX, ethephon (chlozolinate) + TX, sclerotiumLi (dichlozoline) + TX, iprodione + TX, metconazole + Methylozoline) + TX, procymidone) + TX, vinclozoline) + TX, boscalid (boscald) + TX, carboxin + TX, meturamide + TX, flutolanil (flutolanil) + TX, mefenamide + TX, carboxin oxide carboxin + TX, penthiopyrad (penthiopyrad) + TX, thifluzamide + TX, difenoconazole + TX, pyrimethanil + TX, difenoconazole + TX, enestrobin (enestroburin) + TX), dimethomoxamine + TX, fluxastrobin + TX, kresoxim-x-X + TX, kresoxim-methyl-x-TX, metominostrobin + TX, trifloxystrobin + TX, pyraclostrobin + TX, fenstrobilurin + TX, fenstrobin + TX, fenstrobilurin + TX, fenstrobin + TX, fentrobin + TX, fenpyroxim + TX, fenstrobin + TX, fenpyroxim + TX, fenstrobin + TX, fenpyroximab, fenstrobin + TX, fenpyroximab, fenstrobin, fenpyroximab, fenpyr + TX, fenpyroximab + TX, fenpyroximab, fenpyr + TX, fenpyr + TX, fenpyr, fenpyroximab + TX, fenpyr + TX, fenpyr, fenpyrmethyl + TX, fenpyr, fenpyrmethyl + TX, fenpyr + TX, fenpyroximab, fenpyr, fenpyrmethyl + TX, fenpyrmethyl, Captan + TX, furazolidone + TX, folpet + TX, tolylfluanid + TX, boldo mixture + TX, cupric oxide + TX, mancozeb + TX, oxine-copper + TX, phthalidyl-M + TX, edifenphos + TX, iprobenfos + TX, tolclofos-methyl + TX, trichlofop-methyl + TX, trichlorfon + TX, benthiavalicarb + TX, blasticidin (blastcidin) -S + Del, dicloneb) + TX, chlorothalonil + TX, cyflufenamid + TX, pyridazone (diclomezine) + TX, niclosamide (diclosan) + TX, ethirimol (diclofenthidiazuron) + TX, dimethomone) + TX, dimethomorph + Delomorph + TX, dithianon) +, pyrazoxam + TX, pyrimethanamide) + + TX, pyrimethanamide (fenpyrazone) +, pyrimethanamide) + TX, pyrimethanamide (fenthifendazole) + TX, pyrimethanil (fenthifenthidiazuron) +, pyrimethanamide) + TX) +, pyrimethanil (fenpyrazone) +, pyrimethanil) + (fenthifenthidiazepoxide) +, pyrimethanil) + (fenpyr) + (fenpyrozone) +, Fluopyram (fluopicolide) + TX, flusulfamide (fluusufamide) + TX, fluxapyroxamid + TX, fenhexamid + TX, fosetyl-aluminum (fosetyl-aluminum) + TX, hymexazol (hymexazol) + TX, propineb + TX, cetrimide (cyazofamid) + TX, metolcarb) +, methalosulfuron + TX, metrafenone + TX, pencycururon) + TX, phthalide + TX, polyoxin (polyoxins) + TX, propamocarb (propamocarb) +, pyribencarb + TX, iodoquinazolinone (quinazid) + TX, pyroquilon (pyroquilon) + TX, pyridinone (pyriproxyfen) + TX, quinclofenadine + TX, thifluzamide + TX, validamycin + TX, validazole + trimethoprim + TX, validamycin + TX, valoxanil + TX, trimethoprim + TX, fluxazol (valoxanil + TX), flufenamid + TX, flufenamid (valoxanil + TX), flufenazamide + TX, flufenazamide, flufenamide, flufenacet, flufenapyr, flufenamide + TX, flufenamide, flufenacetrimazol, flufenacetm + TX, flufenapyr, flufenamidox, flufenamide, flufenamid (metofenamid (metofenamidox, flufenamid (metofenamide, flufenamide, flufenamid (metofenamidox, flufenamid (metofenamidide) + TX, mandipropamid (mandipropamid) + TX, isopyrazam) + TX, sedaxane (sedaxane) + TX, benzovindiflupyr + TX, fluxapyroxad + TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5' -trifluoro-biphenyl-2-yl) -amide + TX, iprodione + TX, diflufenican (diflufenide) + TX, isofluram (isofluroxypram) + TX, isotianil + TX, dimedone + TX, 6-ethyl-5, 7-dioxo-pyrrolo [4, 5-d-b-roxy ] (isofluroxypyr) + TX)][1,4]Dithiino [1,2-c]Isothiazole-3-carbonitrile + TX,2- (difluoromethyl) -N- [ 3-Ethyl-1, 1-dimethyl-indan-4-yl]Pyridine-3-carboxamide + TX, 4- (2, 6-difluorophenyl) -6-methyl-5-phenyl-pyridazine-3-carbonitrile + TX, (R) -3- (difluoromethyl) -1-methyl-N- [1,1, 3-trimethylindan-4-yl]Pyrazole-4-carboxamide + TX, 4- (2-bromo-4-fluoro-phenyl) -N- (2-chloro-6-fluoro-phenyl) -2, 5-dimethyl-pyrazol-3-amine + TX, 4- (2-bromo-4-fluorophenyl) -N- (2-chloro-6-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine + TX, fluoroanilide (fluindapyr) + TX, toluate + TX, lvbenmixixianan + TX, dichlorobenzoxy) + TX, mandibene (mandestrin) + TX, 3- (4, 4-difluoro-3, 4-dihydro-3, 3-dimethylisoquinolin-1-yl) quinolone + TX, TX,2- [ 2-fluoro-6- [ (8-fluoro-2-methyl-3-quinolinyl) oxy]Phenyl radical]Propan-2-ol + TX, thiapiprolin (oxathiapirol) + TX, tert-butyl N- [6- [ [ [ (1-methyltetrazol-5-yl) -phenyl-methylene]Amino group]Oxymethyl radical]-2-pyridyl]Carbamate + TX, pyraziflumiomid (pyraziflumumid) + TX, sulfluramid (dipyrfluxam) + TX, trolprocarb + TX, trifloxystrobin + TX, ipfentrifluconazole + TX,2- (difluoromethyl) -N- [ (3R) -3-ethyl-1, 1-dimethyl-indan-4-yl]Pyridine-3-carboxamide + TX, N '- (2, 5-dimethyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-carboximidamide + TX, N' - [4- (4, 5-dichlorothiazol-2-yl) oxy-2, 5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, [2- [3- [2- [1- [2- [3, 5-bis (difluoromethyl) pyrazol-1-yl]Acetyl group]-4-piperidinyl group]Thiazol-4-yl]-4, 5-dihydroisoxazol-5-yl]-3-chloro-phenyl]Mesylate + TX, but-3-ynyl N- [6- [ [ (Z) - [ (1-methyltetrazol-5-yl) -phenyl-methylene]Amino group]Oxymethyl radical]-2-pyridyl]Carbamate + TX, methyl N- [ [5- [4- (2, 4-dimethylphenyl) triazol-2-yl]-2-methyl-phenyl]Methyl radical]Carbamate + TX, 3-chloro-6-methyl-5-phenyl-4- (2,4, 6-trifluoroetherphenyl) pyridazine + TX, pyridine chlorideMethyl (pyridichloromethyl) + TX, 3- (difluoromethyl) -1-methyl-N- [1,1, 3-trimethylindan-4-yl]Pyrazole-4-carboxamide + TX, 1- [2- [ [1- (4-chlorophenyl) pyrazol-3-yl]Oxymethyl radical]-3-methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 1-methyl-4- [ 3-methyl-2- [ [ 2-methyl-4- (3,4, 5-trimethylpyrazol-1-yl) phenoxy]Methyl radical]Phenyl radical]Tetrazol-5-one + TX, aminopyrifen + TX, ametoctradin + TX, amisulbrom + TX, penflufen + TX, (Z,2E) -5- [1- (4-chlorophenyl) pyrazol-3-yl]oxy-2-methoxyimino-N, 3-dimethyl-3-pentanamide + TX, (florylpicoxamid + TX, and benazemide (fenpicoxamid) + TX, isobutoxyquinoline + TX, ipflufenoquin + TX, quinofumelin + TX, iprothioxamide + TX, N- [2- [2, 4-dichloro-phenoxy ] -phenoxy]Phenyl radical]-3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide + TX, N- [2- [ 2-chloro-4- (trifluoroethermethyl) phenoxy ] phenoxy]Phenyl radical]-3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide + TX, benzothiostrobin + TX, Cyanoxastrobin + TX, 5-amino-1, 3, 4-thiadiazole-2-thiol zinc salt (2:1) + TX, Fluopyramide + TX, Fluothiazolinone + TX, Fluoroetheramide + TX, pyrapopolyne + TX, Picarbazole (picarbuzrazox) + TX,2- (difluoromethyl) -N- (3-ethyl-1, 1-dimethyl-indan-4-yl) pyridine-3-carboxamide + TX,2- (difluoromethyl) -N- ((3R) -1,1, 3-trimethylindan-4-yl) pyridine-3-carboxamide + TX, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1,2, 4-triazol-1-yl) propyl ] methyl ester]-3-pyridyl]Oxy radical]Cyantrobenzene + TX, metytetraprole + TX,2- (difluoromethyl) -N- ((3R) -1,1, 3-trimethylindan-4-yl) pyridine-3-carboxamide + TX, alpha- (1, 1-dimethylethyl) -alpha- [4'- (trifluoroethermethoxy) [1,1' -diphenyl]-4-yl]-5-pyrimidinemethanol + TX.
The active ingredient mixture of a compound of formula (I) (selected from one of the compounds as shown in tables 1.1 to 1.12 (below), or in tables 3.1 to 3.6 (below), or compounds 1.1 to 1.33 described in table T1 (below), compounds 2.1 to 2.18 described in table T2 (below), or compounds 3.1 and 3.2 described in table T3 (below)) is preferably in a mixing ratio of 100:1 to 1:6000, in particular from 50:1 to 1:50, more in particular in a ratio of from 20:1 to 1:20, even more in particular from 10:1 to 1:10, very in particular from 5:1 and 1:5, particularly preferably from 2:1 to 1:2, and the ratio of from 4:1 to 2:1 is likewise preferred, in particular in a ratio of 1:1, or 5:2, or 4:1, or 2:1, and the ratio of from 4:1 to 2:1, particularly in each case of 1:1, or 5, or 4:2, or 4:1, or 4:1, or 2, or 4, or 2,1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, or 1, or 2, Or a ratio of 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4: 750. Those mixing ratios are by weight.
The mixture as described above may be used in a method of controlling pests which comprises applying a composition comprising a mixture as described above to the pests or their environment, except for methods for treating the human or animal body by surgery or therapy and diagnostic methods carried out on the human or animal body.
Mixtures comprising compounds as shown in tables 1.1 to 1.12 (below), or in tables 3.1 to 3.6 (below), or compounds 1.1 to 1.33 as described in table T1 (below), compounds 2.1 to 2.18 as described in table T2 (below), or compounds 3.1 and 3.2 as described in table T3 (below) and one or more active ingredients as described above may be applied, for example, in the form of a single "ready-to-use mixture", in the form of a combined spray mixture (e.g., "tank mix") consisting of separate formulations of the individual active ingredient components, and in the form of a combination of the individual active ingredients when applied in a sequential manner, i.e., one after the other in a reasonably short time (e.g., hours or days). The order of administering the compounds as shown in tables 1.1 to 1.12 (below), or in tables 3.1 to 3.6 (below), or compounds 1.1 to 1.33 as described in table T1 (below), compounds 2.1 to 2.18 as described in table T2 (below), or compounds 3.1 and 3.2 as described in table T3 (below) and one or more active ingredients as described above is not necessary for the practice of the invention.
The compositions according to the invention may also comprise other solid or liquid auxiliaries, such as stabilizers, for example non-epoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (for example silicone oils), preservatives, viscosity regulators, adhesives and/or tackifiers, fertilizers or other active ingredients for achieving a specific effect, for example bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, screening and/or compressing the solid active ingredients; and in the presence of at least one auxiliary, for example by intimately mixing the active ingredient with the one or more auxiliaries and/or by grinding the active ingredient together with the one or more auxiliaries. The methods for preparing the compositions and the use of the compounds (I) for preparing the compositions are also subjects of the present invention.
Another aspect of the present invention relates to the use of a fungicide or an insecticidal mixture comprising at least one compound of formula (I) or at least one preferably individual compound as defined above, or of a composition comprising at least one compound of formula (I) or at least one preferably individual compound as defined above in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, for example useful plants (for example crop plants), their propagation material (for example seeds), harvested crops (for example harvested food crops), or non-living material from insects or phytopathogenic microorganisms, preferably fungal organisms, of a compound of formula (I), or preferably of individual compounds as defined herein.
Another aspect of the present invention relates to a method of controlling or preventing infestation of a plant (e.g. a useful plant such as a crop plant), propagation material thereof (e.g. seeds), harvested crop (e.g. harvested food crop), or non-living material by insects or phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans, especially fungal organisms, which method comprises applying a compound of formula (I), or preferably a separate compound as defined above, as active ingredient to the plant, to a part of the plant or to the locus thereof, to propagation material thereof, or to any part of the non-living material.
By controlling or preventing is meant that infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans, especially fungal organisms, is reduced to such a level that improvement is demonstrated.
A preferred method of controlling or preventing infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects is foliar application, which comprises applying a compound of formula (I), or an agrochemical composition containing at least one of the compounds. The frequency of application and rate of application will depend on the risk of infestation by the respective pathogen or insect. However, the compounds of formula (I) may also penetrate the plants through the roots via the soil (systemic action) by soaking the locus of the plants with a liquid formulation or by applying the compounds in solid form, for example in granular form, to the soil (soil application). In rice crops, such granules may be applied to irrigated paddy fields. The compounds of formula (I) can also be applied to seeds (coatings) by impregnating the seeds or tubers with a liquid formulation of the fungicide or coating them with a solid formulation.
Formulations, for example compositions comprising a compound of formula (I) and, if desired, solid or liquid adjuvants or monomers for encapsulating a compound of formula (I), can be prepared in known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and optionally surface-active compounds (surfactants).
Advantageous application rates are generally from 5g to 2kg of active ingredient (a.i.)/hectare (ha), preferably from 10g to 1kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as a seed soaking agent, suitable dosages are from 10mg to 1g of active substance per kg of seed.
When the combination according to the invention is used for treating seeds, a ratio of from 0.001 to 50g of compound of the formula (I) per kg of seed, preferably from 0.01 to 10g per kg of seed, is generally sufficient.
Suitably, the composition of the compound having formula (I) according to the invention is administered prophylactically (meaning prior to the development of the disease) or curatively (meaning after the development of the disease).
The compositions OF the present invention may be used in any conventional form, for example, in a two-pack, powder for dry seed treatment (DS), emulsion for seed treatment (ES), flowable concentrate for seed treatment (FS), solution for seed treatment (LS), water dispersible powder for seed treatment (WS), capsule suspension for seed treatment (CF), gel for seed treatment (GF), Emulsion Concentrate (EC), Suspension Concentrate (SC), Suspoemulsion (SE), Capsule Suspension (CS), water dispersible granule (WG), Emulsifiable Granule (EG), water-in-oil Emulsion (EO), oil-in-water Emulsion (EW), Microemulsion (ME), dispersible oil suspension (OD), oil suspension (OF), oil soluble liquid concentrate (OL), soluble concentrate (SL), ultra-low volume Suspension (SU), ultra-low volume liquid concentrate (UL), The parent drug (TK), Dispersible Concentrate (DC), Wettable Powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Such compositions can be produced in a conventional manner, for example by mixing the active ingredients with suitable formulation inerts (diluents, solvents, fillers and optionally other formulation ingredients such as surfactants, biocides, antifreeze agents, stickers, thickeners and compounds which provide an adjuvant effect). Conventional sustained-release formulations intended to sustain the drug effect for a long period of time may also be used. In particular, formulations to be applied in spray form, such as water dispersible concentrates (e.g., EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules, may contain surfactants (e.g., wetting and dispersing agents) and other compounds that provide an adjuvant effect, such as condensation products of formaldehyde with naphthalene sulfonate, alkyl aryl sulfonate, lignosulfonate, fatty alkyl sulfate and ethoxylated alkyl phenol and ethoxylated fatty alcohol.
The seed-dressing formulations are applied to the seeds in a manner known per se using the combinations and diluents according to the invention in the form of suitable seed-dressing formulations, for example in the form of aqueous suspensions or dry powders having good adhesion to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the individual active ingredients or the combination of active ingredients in encapsulated form, for example as slow-release capsules or microcapsules.
Typically, the formulation comprises from 0.01 to 90% by weight of an active agent consisting of at least a compound of formula (I), optionally together with other active agents, in particular microbicides or preservatives, etc., from 0 to 20% of an agriculturally acceptable surfactant and from 10 to 99.99% of a solid or liquid formulation inert agent and one or more adjuvants. Concentrated forms of the compositions typically contain between about 2% and 80%, preferably between about 5% and 70% by weight of active agent. The application forms of the formulations can, for example, contain from 0.01 to 20%, preferably from 0.01 to 5%, by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will typically use dilute formulations.
However, it is preferred to formulate commercial products as concentrates, and the end user will typically use dilute formulations.
Table 1.1:this table discloses 104 specific compounds having the formula (T-1):
Figure BDA0003023364140000681
wherein A is A-1, R3Is F, R4Is F, R1Is R2As defined in Table 2, and NR7R8As defined below in table 1, and Y ═ O.
Each of tables 1.2 to 1.12 (following Table 1.1) makes available 104 individual compounds of formula (T-1), wherein A, R1、R2、R3、R4And Y is specifically defined in the following tables 1.2 to 1.12, which refer to Table 1 (wherein-NR)7R8Is specifically defined) and table 2 (wherein R is1And R2Is specifically defined).
TABLE 1
Figure BDA0003023364140000691
TABLE 2
Figure BDA0003023364140000692
TABLE 1.2: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-1, R3Is F, R4Is F, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
Table 1.3:this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3Is F, R4Is F, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ O.
TABLE 1.4: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3Is F, R4Is F, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
TABLE 1.5: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-1, R3Is Me, R4Is Me, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ O.
TABLE 1.6: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-1, R3Is Me, R4Is Me, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
TABLE 1.7: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3Is Me, R4Is Me, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ O.
TABLE 1.8: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3Is Me, R4Is Me, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
TABLE 1.9: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-1, R3And R4Together form a cyclopropyl ring, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ O.
TABLE 1.10: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-1, R3And R4Together form a cyclopropyl ring, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
TABLE 1.11: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3And R4Together form a cyclopropyl ring, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ O.
TABLE 1.12: this table discloses 104 specific compounds having the formula (T-1) wherein A is A-2, R3And R4Together form a cyclopropyl ring, R1And R2As defined in Table 2, -NR7R8As defined in table 1, and Y ═ S.
TABLE 3.1: this table discloses 88 specific compounds having the formula (T-3):
Figure BDA0003023364140000711
wherein A is A-1, R3Is F, R4Is F, and R1、R2As defined above in Table 2, and R5As defined below in table 3.
Each of tables 3.2 to 3.6 (following Table 3.1) makes available 88 individual compounds of formula (T-3), wherein A, R1、R2、R3And R4Are specifically defined in tables 3.2 to 3.6, which refer to Table 3 (wherein R is5Is specifically defined) and table 2 (wherein R is1And R2Is specifically defined).
TABLE 3
Figure BDA0003023364140000712
TABLE 3.2: this table discloses 88 specific compounds having the formula (T-3) wherein A is A-1, R3Is Me, R4Is Me, R1And R2As defined above in Table 2, and R5As defined above in table 3.
TABLE 3.3: this table discloses 88 specific compounds having the formula (T-3) wherein A is A-1, R3And R4Together form a cyclopropyl ring, R1And R2As defined above in Table 2, and R5As defined above in table 3.
TABLE 3.4: this table discloses 88 specific compounds having the formula (T-3) wherein A is A-2, R3Is F, R4Is F, R1And R2As defined in Table 2, and R5As defined above in table 3.
TABLE 3.5: this table discloses 88 specific compounds having the formula (T-3) wherein A is A-2, R3Is Me, R4Is Me, R1And R2As defined above in Table 2, and R5As defined above in table 3.
TABLE 3.6: this table discloses 88 specific compounds having the formula (T-3) wherein A is A-2, R3And R4Together form a cyclopropyl ring, R1And R2As defined in Table 2 above, and R5As defined above in table 3.
Examples of the invention
The following examples serve to illustrate the invention. The compounds of the invention may be distinguished from known compounds by greater efficacy at low rates of administration, as evidenced by one of ordinary skill in the art using the experimental procedures outlined in the examples, using lower rates of administration (if necessary), e.g., 50ppm, 12.5ppm, 6ppm, 3ppm, 1.5ppm, 0.8ppm, or 0.2 ppm.
The compounds of formula (I) may have any number of benefits, including in particular a favorable level of biological activity for protecting plants from diseases caused by fungi or superior properties for use as agrochemical active ingredients (e.g. higher biological activity, a favorable activity spectrum, increased safety (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
Throughout this specification, temperatures are given in degrees Celsius (. degree. C.) and "mp" means melting point. LC/MS means liquid chromatography mass spectrometry, and the description of apparatus and method a is as follows:
the description of the LC/MS apparatus and method A is:
SQ detector 2 from Waters corporation
An ionization method comprises the following steps: electrospray ionization
Polarity: positive and negative ions
Capillary (kV)3.0, taper hole (V)30.00, extractor (V)2.00, source temperature (deg.C) 150, desolvation temperature (deg.C) 350, taper hole gas flow (L/Hr)0, desolvation gas flow (L/Hr)650
The mass range is as follows: 100 to 900Da
DAD wavelength range (nm): 210 to 500
The method comprises the following steps: waters acquisition UPLC, using the following HPLC gradient conditions:
(solvent A: water/methanol 20:1+ 0.05% formic acid, and solvent B: acetonitrile + 0.05% formic acid)
Figure BDA0003023364140000731
Column type: waters acquisition UPLC HSS T3; column length: 30 mm; inner diameter of column: 2.1 mm; granularity: 1.8 microns; temperature: at 60 ℃.
Where necessary, enantiomerically pure final compounds can be obtained, where appropriate, from racemic materials via standard physical separation techniques (such as reverse phase chiral chromatography) or by stereoselective synthetic techniques (for example by using chiral starting materials).
Formulation examples
Figure BDA0003023364140000732
The active ingredient is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable mill to provide a wettable powder which can be diluted with water to give a suspension of the desired concentration.
Figure BDA0003023364140000733
The active ingredient is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable grinding machine to provide a powder which can be used directly for seed treatment.
Emulsifiable concentrates
Figure BDA0003023364140000741
Emulsions with any desired dilution which can be used in plant protection can be obtained from such concentrates by dilution with water.
Figure BDA0003023364140000742
The ready-to-use dust powder is obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable grinder. Such powders may also be used for dry dressing of seeds.
Extruder granules
Figure BDA0003023364140000743
The active ingredient is mixed with the adjuvant and milled, and the mixture is wetted with water. The mixture was extruded and then dried in an air stream.
Coated granules
Active ingredient [ compound having formula (I) ] 8%
Polyethylene glycol (molecular weight 200) 3%
89 percent of kaolin
The finely ground active ingredient is applied homogeneously to the kaolin moistened with polyethylene glycol in a mixer. In this way dust-free coated granules are obtained.
Suspension concentrates
Figure BDA0003023364140000751
The finely ground active ingredient is intimately mixed with the auxiliaries to give a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. With such dilutions, living plants as well as plant propagation material can be treated and protected against microbial infestation by spraying, pouring or dipping.
Flowable concentrate for seed treatment
Figure BDA0003023364140000752
The finely ground active ingredient is intimately mixed with the auxiliaries to give a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. With such dilutions, living plants as well as plant propagation material can be treated and protected against microbial infestation by spraying, pouring or dipping.
Sustained release capsule suspension
28 parts of a combination of compounds of the formula I are mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate/polymethylene-polyphenylisocyanate mixture (8: 1). This mixture was emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of defoamer and 51.6 parts of water until the desired particle size was reached. To this emulsion was added 2.8 parts of a mixture of 1, 6-hexanediamines in 5.3 parts of water. The mixture was stirred until the polymerization reaction was complete.
The obtained capsule suspension was stabilized by adding 0.25 parts of thickener and 3 parts of dispersant. The capsule suspension formulation contained 28% active ingredient. The diameter of the media capsule is 8-15 microns.
The resulting formulation is applied to the seeds as an aqueous suspension in a device suitable for this purpose.
AIBN ═ azobisisobutyronitrile
DIBAL-H ═ diisobutylaluminum hydride
DIPEA ═ N, N-di-isopropylethylamine
EtOAc ═ ethyl acetate
HCl ═ hydrochloric acid
mp is melting point
Degree centigrade
Normal (N ═ normal)
NBS ═ N-bromosuccinimide
M is equal to mole
TFAA ═ trifluoroacetic anhydride
THF ═ tetrahydrofuran
RtRetention time (in minutes)
LC/MS liquid chromatography-mass spectrometry (a description of the apparatus and method for LC/MS analysis is given above)
Preparation examples
Example 1:this example illustrates 2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Phenyl radical]Preparation of Ethyl propionate (Compound 2.11 of Table T2)
Figure BDA0003023364140000771
Step 1: preparation of N' -hydroxy-4-methyl-benzamidine
Figure BDA0003023364140000772
To a suspension of 4-methylbenzonitrile (35g, 0.29mol) in ethanol (220mL) and water (440mL) was added hydroxylamine hydrochloride (41.1g, 0.58mol), potassium carbonate (65.4g, 0.47mol) and 8-hydroxyquinoline (0.22g, 1.5mmol) at room temperature. The reaction mixture was heated at 80 ℃ for 4 hours. The mixture was then cooled to room temperature and diluted to pH 8 with 2N HCl. The volatiles were removed under reduced pressure and the reaction contents were filtered, washed with water, and dried in vacuo to afford 39.1g of the title compound. LC/MS (method a) retention time 0.23 min, 151.0(M + H).
Step 2: preparation of 3- (p-tolyl) -5- (trifluoromethyl) -1,2, 4-oxadiazole
Figure BDA0003023364140000773
To a solution of N' -hydroxy-4-methyl-benzamidine (38.7g, 0.25mol) in 2-methyltetrahydrofuran (750mL) was added TFAA at 0 ℃. The reaction mixture was stirred at 15 ℃ for two hours and then diluted with water. The organic layer was separated, washed successively with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and water, then dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (heptane/EtOAc eluent gradient 99:1 to 90:10) to afford 54.1g of the title compound as a clear oil (which solidified upon storage). LC/MS (method a) retention time 1.15 min, no mass was detected.
1H NMR(400MHz,CDCl3)δppm:8.00(d,2H),7.32(d,2H),2.45(s,3H)。
19F NMR(400MHz、CDCl3)δppm：-65.41(s)。
Step 3 a: 3- [4- (bromomethyl) phenyl]Preparation of (E) -5- (trifluoromethyl) -1,2, 4-oxadiazole
Figure BDA0003023364140000781
A mixture of 3- (p-tolyl) -5- (trifluoromethyl) -1,2, 4-oxadiazole (56.0g, 0.24mol) and NBS (45.4g, 0.25mol) in tetrachloromethane (480mL) was heated to 70 ℃ under argon. AIBN (4.0g, 24mmol) was added and the reaction mixture was stirred at 65 ℃ for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 100:0 to 95:5) to afford 44.7g of the title compound as a white solid. mp: 58 ℃ to 63 ℃.
1H NMR(400MHz,CDCl3)δppm:8.11(d,2H),7.55(d,2H),4.53(s,2H)。
19F NMR(400MHz、CDCl3)δppm：-65.32(s)。
The by-product 3- [4- (dibromomethyl) phenyl ] -5- (trifluoromethyl) -1,2, 4-oxadiazole was isolated as a white solid, mp: 61-66 ℃.
Figure BDA0003023364140000782
1H NMR(400MHz,CDCl3)δppm:8.15(d,2H),7.73(d,2H),6.68(s,1H)。
19F NMR(400MHz、CDCl3)δppm：-65.34(s)。
And step 3 b: 3- [4- (bromomethyl) phenyl]Preparation of (E) -5- (trifluoromethyl) -1,2, 4-oxadiazole
Figure BDA0003023364140000783
To a 1:9 ratio mixture of 3- [4- (bromomethyl) phenyl ] -5- (trifluoromethyl) -1,2, 4-oxadiazole and 3- [4- (dibromomethyl) phenyl ] -5- (trifluoromethyl) -1,2, 4-oxadiazole (10.2g) in acetonitrile (95mL), water (1.9mL), and DIPEA (6.20mL, 35.7mmol) was added diethyl phosphite (4.7mL, 35.7mmol) at 5 ℃. The mixture was stirred at 5-10 ℃ for 2 hours, 1M HCl was added, and volatiles were removed under reduced pressure. The resulting white slurry was extracted with dichloromethane and the combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 9:1) to afford 7.10g of the title compound as a white solid. mp: 58 ℃ to 63 ℃.
1H NMR(400MHz,CDCl3)δppm:8.11(d,2H),7.55(d,2H),4.53(s,2H)。
19F NMR(400MHz、CDCl3)δppm：-65.32(s)。
And 4, step 4: 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Preparation of benzaldehyde
Figure BDA0003023364140000791
DIBAL-H1.0M in toluene (16mL, 16.0mmol) was added dropwise to a solution of N-methoxy-N-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide (4.1g, 13.3mmol) in 2-methyltetrahydrofuran (90mL) under argon at-78 ℃ in a 75mL multi-necked flask equipped with a stirrer. The mixture was stirred at-78 ℃ for two hours and at 0 ℃ for one hour. Complete conversion was observed by LC/MS. The mixture was quenched by dropwise addition of saturated aqueous ammonium chloride solution. Precipitation of a white solid occurred, and 4M HCl was added until complete dissolution. The mixture was extracted with ethyl acetate, the combined organics were dried over magnesium sulfate and reduced under pressure to provide the crude product as a beige solid. The crude product was subjected to flash chromatography on silica gel (heptane/EtOAc eluent gradient 99:1 to 90:10) to afford 2.9g of the title compound mp as a white solid: 40-50 ℃.
1H NMR(400MHz,CDCl3)δppm:10.12(s,1H),8.31(d,2H),8.05(d,2H)。
19F NMR(400MHz、CDCl3)δppm：-65.29(s)。
And 5:2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Phenyl radical]Preparation of Ethyl propionate (Compound 2.11 in Table T2)
Figure BDA0003023364140000801
To a stirred solution of ethyl 2, 2-difluoro-2-trimethylsilylacetate (1.8g, 9.09mmol) and 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzaldehyde (2.0g, 8.26mmol) in dry THF (30mL) was added tetrabutyl difluorotriphenylammonium silicate (0.5g, 0.83mmol) at 0 deg.C. The reaction mass was stirred at room temperature for 12 hours. The reaction mass was diluted with 45mL of water and the mixture was extracted with ethyl acetate. The combined organics were dried over magnesium sulfate and reduced under pressure to provide the crude product. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 70:30) to afford 0.6g of the title compound as a white solid.
1H NMR(400MHz,DMSO-d6)δppm:8.10(d,J＝8.44Hz,2H)7.70(d,J＝8.19Hz,2H)6.87(d,J＝5.75Hz,1H)5.24(br d,J＝17.73Hz,1H)4.32(q,J＝7.11,1.65Hz,2H)1.26(t,J＝7.09Hz,3H)。
19F NMR(377MHz,DMSO-d6)δppm:-64.71(s,1F)-109.98(d,1F)-120.61(d,1F)。
Example 2:this example illustrates 2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Phenyl radical]Preparation of propionic acid (Compound 2.10 of Table T2)
Figure BDA0003023364140000802
To a stirred solution of ethyl 2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanoate (2.4g, 6.6mmol) in THF (10mL/g) was added a solution of LiOH (0.3g, 13mmol) in water (10mL/g) at ambient temperature. The resulting mixture was stirred at ambient temperature for 6 hours. The reaction mass was then acidified with 1N HCl. Precipitation of a white solid occurred, which was collected by filtration. The resulting white solid was washed with water and dried in vacuo to provide 1.5g of 2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propionic acid as a white solid.
1H NMR(400MHz,DMSO-d6)δppm:8.08(d,J＝8.31Hz,2H)7.68(d,J＝8.19Hz,2H)5.15-5.24(m,1H)。
19F NMR (proton decoupled, 377MHz, DMSO-d6) delta ppm-59.95 (s,1F) -106.3(d,1F), -116.14(d, 1F).
LCMS:M+H:338.9(RT 1.28min)。
Example 3: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoro-methyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanamide (compound 1.22 of Table T1)
Figure BDA0003023364140000811
To a stirred solution of 2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanoic acid (135mg, 0.40mmol) in dichloromethane (10mL/g) were added ethylamine hydrochloride (35.8mg, 0.44mmol), N- (3-dimethylaminopropyl) -N' -ethylcarbodiimide hydrochloride (102mg, 0.52mmol) and 1-hydroxybenzotriazole hydrate (30mg, 0.20mmol), followed by triethylamine (0.17mL, 1.20mmol) and allowed to stir for 16 h. The reaction mass was diluted with 15mL of water and the mixture was extracted with dichloromethane. The combined organics were dried over magnesium sulfate and evaporated to afford the crude product. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 90:10 to 50:50) to provide 60mg of the title compound as a white solid.
1H NMR(400MHz,DMSO-d6)δppm:8.69(br s,1H)8.08(d,J＝8.44Hz,2H)7.66(d,J＝8.31Hz,2H)6.63(d,J＝5.75Hz,1H)5.25(m,1H)3.15(m,2H)1.02(t,J＝7.21Hz,3H)。
19F NMR (proton decoupled, 377MHz, DMSO-d6) delta ppm-64.71 (s,1F), -112.04(d,1F), -121.9(d, 1F).
MS：M+H:366(RT 1.482min)。
Example 4: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-methoxy-3- [4- [5- (trifluoro-methyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanamide (compound 1.14 of Table T1)
Figure BDA0003023364140000821
To a stirred solution of N-ethyl-2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanamide (90mg, 0.25mmol) in acetonitrile (10mL/g) was added potassium carbonate, potassium carbonate (85mg, 0.62mmol) and dimethyl sulfate (47mg, 0.37 mmol). The resulting reaction mixture was allowed to stir at 60 ℃ for 16 hours. The mixture was quenched by dropwise addition of saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate and the combined organics were dried over magnesium sulfate and evaporated to afford the crude product as a beige solid. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 50:50) to provide 16mg of the title compound as a white solid.
1H NMR(400MHz,CDCl3)δppm:8.15-8.19(d,J＝8.2,2H)7.61(m,J＝8.19Hz,2H)6.34(s,1H)4.92(dd,J＝18.71,6.24Hz,1H)3.35-3.44(q,2H)3.40(s,3H)1.20(t,J＝7.34Hz,3H)。
19F NMR(377MHz、CDCl3)δppm：-65.34(s,1F)-111.4(d,1F)-124.7(d,1F)。
LCMS:M+H:380.1(Rt:1.507min)。
Example 5: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-oxo-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanamide (Compound 1.17 of Table T1)
Figure BDA0003023364140000822
To a stirred solution of N-ethyl-2, 2-difluoro-3-hydroxy-3- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] propanamide (100mg, 0.27mmol) in dichloromethane (3mL, 30mL/g) was added dess-martin periodinane (144mg, 0.33mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 12 hours. The mixture was quenched by dropwise addition of saturated aqueous sodium bicarbonate. The mixture was extracted with dichloromethane and the combined organics were washed with copious amounts of water. The organic layer was then dried over magnesium sulfate and evaporated to provide a crude material. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 50:50) to provide 22mg of the title compound as a white solid.
1H NMR(400MHz,CDCl3)δppm:8.26-8.34(m,4H)6.51(br s,1H)3.44(q,2H)1.25(t,3H)。
19F NMR (proton decoupled, 377MHz, CDCl)3)δppm:-65.27(s,1F)-108.46(s,2F)。
LCMS:M+H:363.9(RT:1.507min)。
Example 6: this example illustrates the preparation of ethyl 2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoro-methyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propionate (compound 2.3 of Table T2)
Figure BDA0003023364140000831
Step 1: preparation of N' -hydroxy-5-methyl-thiophene-2-carboxamidine
Figure BDA0003023364140000832
To a suspension of 5-methylthiophene-2-carbonitrile (9.0g, 73mmol) in ethanol (365mL) was added triethylamine (20.6mL, 146mmol) with stirring at room temperature, followed by the batchwise introduction of hydroxylamine hydrochloride (10.3g, 146 mmol). The reaction contents were heated at reflux for 3.5 h, cooled to 25 ℃ and concentrated under reduced pressure to afford 32.0g of the title compound as a crude residue which was used for the next conversion without further purification. LC/MS (method a) retention time 0.24 min, 156(M + H).
Step 2: preparation of 3- (5-methyl-2-thienyl) -5- (trifluoromethyl) -1,2, 4-oxadiazole
Figure BDA0003023364140000841
To a suspension of crude N' -hydroxy-5-methyl-thiophene-2-carboxamidine (32.0g) in tetrahydrofuran (1000mL) was introduced pyridine (24mL, 292mmol) and the contents cooled to 10 ℃. To this suspension was added trifluoroacetic anhydride (30.9mL, 219mL) dropwise. The reaction mixture was allowed to warm to 25 ℃ overnight and then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with 1M aqueous HCl, water and saturated Na2CO3And (4) washing with an aqueous solution. The organic layer was dried over sodium sulfate, filtered, and the volatiles were removed under reduced pressure. The crude residue was purified by flash chromatography on silica gel (using a cyclohexane/EtOAc eluent gradient) to afford 13.1g of the title compound as a clear oil. LC/MS (method a) retention time 1.13 min, no mass was detected.
1H NMR(400MHz,CDCl3)δppm:7.68(d,1H),6.84(d,1H),2.57(s,3H)。
19F NMR(400MHz、CDCl3)δppm：-65.44(s)。
Step 3 a: 3- [5- (bromomethyl) -2-thienyl ] radical]Preparation of (E) -5- (trifluoromethyl) -1,2, 4-oxadiazole
Figure BDA0003023364140000842
To a solution of 3- (5-methyl-2-thienyl) -5- (trifluoromethyl) -1,2, 4-oxadiazole (13.1g, 55.7mmol) and tetrachloromethane (111mL) was added AIBN (0.93g, 5.6mmol) and then NBS (11.02g, 61.3mmol) under argon. The contents were heated at 70 ℃ for 18 hours. The mixture was cooled to 25 ℃ and then diluted with dichloromethane and water. The layers were separated, the organic phase was dried over sodium sulfate, and the volatiles were removed under reduced pressure. The crude residue was purified by flash chromatography on silica gel (using a cyclohexane/EtOAc eluent gradient) to afford 3.86g of the title compound as a yellow oil. LC/MS (method a) retention time 1.14 min, no mass was detected.
1H NMR(400MHz,CDCl3)δppm:8.11(d,1H),7.55(d,1H),4.53(s,2H)。
19F NMR(400MHz、CDCl3)δppm：-65.31(s)。
By-product, 3- [5- (dibromomethyl) -2-thienyl ] -5- (trifluoromethyl) -1,2, 4-oxadiazole (13.0g) as a yellow amorphous solid.
Figure BDA0003023364140000851
1H NMR(400MHz,CDCl3)δppm:7.73(d,1H),7.32(d,1H),6.91(s,1H)。
And 4, step 4: 5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Preparation of thiophene-2-carbaldehyde
Figure BDA0003023364140000852
4-methylmorpholine-N-oxide (7.33g, 60.68mmol) and activated in acetonitrile (8mL/mmol) at a temperature of 0 deg.C
Figure BDA0003023364140000853
Of molecular sieves (50g)To the stirred solution was added 3- [5- (bromomethyl) -2-thienyl ] as a solution in 10ml of acetonitrile]-5- (trifluoromethyl) -1,2, 4-oxadiazole (5g, 15.1 mmol). The reaction was stirred at 10 ℃ for an additional 3 hours. The solid was filtered and then dried in vacuo. The resulting crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 1:0 to 1:0.1) to afford 2.4g of the title compound as a pale yellow solid.
1H NMR(400MHz,CDCl3)δppm:10.02(s,1H)7.97(d,J＝3.91Hz,1H)7.84(d,J＝3.91Hz,1H)。
And 5: preparation of ethyl 2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propionate (compound 2.3 of Table T2)
Figure BDA0003023364140000861
To a stirred solution of ethyl 2, 2-difluoro-2-trimethylsilylacetate (261mg 1.33mmol) and 5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] thiophene-2-carbaldehyde (300mg, 1.21mmol) in dry tetrahydrofuran (3mL, 37mmol) was added tetrabutyl difluorotriphenylammonium silicate (67mg 0.12mmol) at 0 ℃. The reaction mass was then allowed to stir at ambient temperature for 12 hours and diluted with water. The contents were extracted with ethyl acetate and the total combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 1:0 to 1:1) to provide 110mg of the title compound as a white solid.
1H NMR(400MHz,CDCl3)δppm:1.35(t,3H)4.38(m,2H)5.50(dd,1H)7.24(d,1H)7.81(d,1H)。
19F NMR (proton decoupled, 377MHz, CDCl)3)δppm:-65.32(s,1F)-112.26(d,1F)-120.15(d,1F)。
Example 7: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoro-methyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propanamide (compound 1.4 of Table T1)
Figure BDA0003023364140000862
To a stirred solution of ethyl 2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propionate (400mg, 1.07mmol) in toluene (10ml/g) was added ethylamine (2.0mol/l) in tetrahydrofuran (2.7ml, 5.37mmol) followed by bis (trimethylaluminum) -1, 4-diazabicyclo [2.2.2] octane adduct (421mg, 1.61mmol) at 0 ℃. The resulting mixture was stirred at 70 ℃ overnight. The reaction mixture was quenched by slowly adding water (40 mL). The contents were extracted with ethyl acetate and the total combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 90:1 to 60:40) to provide 320mg of the title compound as a white solid; mp 141 and 143 ℃.
1H NMR(400MHz,DMSO-d6)δppm:8.82(t,J＝5.82Hz,1H)7.85(d,J＝3.76Hz,1H)7.27(d,J＝3.76Hz,1H)7.20(d,J＝6.02Hz,1H)5.51(m,1H)3.12-3.23(m,2H)1.04(t,J＝7.28Hz,3H)。
19F NMR (proton decoupled, 376MHz, DMSO-d6) δ ppm-64.74 (s,1F) -111.76(s,1F) -122.61(s, 1F).
Example 8: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-oxo-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propanamide (Compound 1.3 of Table T1)
Figure BDA0003023364140000871
To a stirred solution of N-ethyl-2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propanamide (130mg, 0.35mmol) in dichloromethane (3mL/mmol) was added dess-martin periodinane (225mg, 0.53mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 12 hours. The mixture was quenched by dropwise addition of saturated aqueous sodium bicarbonate solution, extracted with dichloromethane, and the combined organics were washed with copious amounts of water, then dried over magnesium sulfate and evaporated to afford a crude material. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 80:20) to provide 65mg of the title compound as a white solid.
1H NMR(400MHz,CDCl3)δppm:8.21(d,J＝4.68Hz,1H)7.94(d,J＝4.16Hz,1H)6.38-6.59(m,1H)3.42(quin J＝6.85Hz,2H)1.24(t,J＝7.27Hz,3H)。
19F NMR(377MHz、CDCl3)δppm：-65.21(s,1F)-109.88(s,1F)。
LCMS:M+H:369.9(Rt:1.50min)。
Example 9: this example illustrates the preparation of N-ethyl-2, 2-difluoro-3-hydroxy-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] butanamide (compound 1.1 of Table T1)
Figure BDA0003023364140000872
To a solution of N-ethyl-2, 2-difluoro-3-oxo-3- [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] propanamide (40mg, 0.10mmol) in tetrahydrofuran (10mL/mmol, 0.309mmol) at-78 deg.C was added dropwise a solution of methyl magnesium chloride (1M) in THF (0.15mL, 0.15 mmol). The resulting reaction mass was stirred at-78 ℃ for 2 hours. The mixture was quenched by dropwise addition of saturated aqueous ammonium chloride solution. The resulting mixture was extracted with ethyl acetate, and the combined organics were dried over magnesium sulfate and evaporated to provide a crude material. The crude product was subjected to flash chromatography on silica gel (cyclohexane/EtOAc eluent gradient 99:1 to 70:30) to provide 12mg of the title compound as a colorless gummy material.
1H NMR(400MHz,DMSO-d6)δppm:7.75(d,J＝3.91Hz,1H)7.13(d,J＝3.91Hz,1H)6.41(brs,1H)5.38(s,1H)3.23-3.35(m,2H)1.77(s,3H)1.08(t,J＝7.27Hz,3H)。
19F NMR (proton decoupled, 377MHz, DMSO-d6) delta ppm-64.74 (s,1F) -114.9(d, 1F).
tTable T1: process for preparing compounds according to formula (I)Melting point (mp) data and/or retention time (R):
Figure BDA0003023364140000881
Figure BDA0003023364140000891
Figure BDA0003023364140000901
Figure BDA0003023364140000911
Figure BDA0003023364140000921
Figure BDA0003023364140000931
Figure BDA0003023364140000941
Figure BDA0003023364140000951
ttable T2: melting point (mp) data and/or retention time (R) of a compound according to formula (I):
Figure BDA0003023364140000952
Figure BDA0003023364140000961
Figure BDA0003023364140000971
Figure BDA0003023364140000981
Figure BDA0003023364140000991
ttable T3: melting point (mp) data and/or retention time (R) of a compound according to formula (I):
Figure BDA0003023364140000992
Figure BDA0003023364140001001
biological examples
General example of leaf disk testing in well plates:
leaf disks or leaf segments of different plant species were cut from plants grown in the greenhouse. The cut leaf disks or leaf segments were placed on water agar in a multiwell plate (24-well format). Leaf discs were sprayed with the test solution either before (prophylactic) or after (therapeutic) inoculation. The compounds to be tested were prepared as DMSO solutions (maximum 10mg/ml) diluted to the appropriate concentration with 0.025% Tween20 just prior to spraying. The inoculated leaf discs or leaf segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the corresponding test system. Depending on the disease system, a single assessment of disease level was made 3 to 14 days after inoculation. The percent disease control relative to untreated test leaf discs or leaf segments is then calculated.
General example of liquid culture assay in well plates:
mycelial fragments or conidia suspensions of the fungus (freshly prepared from liquid cultures of the fungus or from low temperature storage) were mixed directly into the nutrient broth. A DMSO solution of test compound (maximum 10mg/ml) was diluted by a factor of 50 with 0.025% Tween20 and 10 μ Ι of this solution was pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spore/mycelium fragment was then added to give the final concentration of test compound. The test plates are incubated in the dark at 24 ℃ and 96% relative humidity. Depending on the disease system, inhibition of fungal growth was determined photometrically after 2 to 7 days and the percentage antifungal activity was calculated relative to the untreated test article.
Example 1: against Puccinia recondita (Puccinia) Fungicidal activity of recordigaf Wheat/leaf disc prevention method (Brown rust)
Wheat leaf segment cultivar Kanzler was placed on agar in multi-well plates (24-well format) and sprayed with formulated test compound diluted in water. Leaf discs were inoculated with a spore suspension of the fungus 1 day after application. Inoculated leaf sections were incubated at 19 ℃ and 75% relative humidity (rh) in a climatic chamber under a 12 hour light/12 hour dark light regimen, and compound activity was assessed as the percentage of disease control when appropriate levels of disease damage occurred in untreated test leaf sections (7 to 9 days post-application) compared to untreated.
In this test, the following compounds gave at least 80% disease control at 200ppm in the applied formulation when compared to untreated control leaf discs showing extensive disease development under the same conditions.
Compounds (from table T1)1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.20, 1.21, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.29, 1.30, 1.31.
Compounds (from table T2)2.4, 2.13.
Compound (from table T3) 3.1.
Example 2: fungicidal activity/wheat/leaf disc treatment against puccinia recondita (brown rust)
Wheat leaf segment cultivar Kanzler was placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. The plates were stored in the dark at 19 ℃ and 75% relative humidity. 1 day after inoculation, formulated test compound diluted in water was applied. The leaf sections were incubated at 19 ℃ and 75% relative humidity in a climatic chamber under a 12 hour light/12 hour dark light regimen, and compound activity was assessed as the percentage of disease control when appropriate levels of disease damage occurred in untreated test leaf sections (6 to 8 days post-application) compared to untreated.
In this test, the following compounds gave at least 80% disease control at 200ppm in the applied formulation when compared to untreated control leaf discs showing extensive disease development under the same conditions.
Compounds (from table T1)1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.20, 1.21, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.29, 1.30, 1.31.
Compounds (from table T2)2.1, 2.2, 2.4, 2.6, 2.7.
Example 3: fungicidal activity/soybean/leaf disc prophylaxis against phakopsora pachyrhizi (asian soybean rust)
The soybean leaf discs were placed on water agar in a multi-well plate (24-well format) and sprayed with formulated test compound diluted in water. One day after application, leaf discs were inoculated by spraying the spore suspension on the lower leaf surface. In a climatic chamber, leaf disks were kept at 20 ℃ with 12h illumination/day and 75% rh after an incubation period of 24-36 hours in the dark at 20 ℃ and 75% rh. The activity of the compounds was assessed as the percentage of disease control when appropriate levels of disease damage occurred in untreated test leaf discs (12 to 14 days post-administration) compared to untreated.
In this test, the following compounds gave at least 80% disease control at 200ppm in the applied formulation when compared to untreated control leaf discs showing extensive disease development under the same conditions.
Compound (from table T1)1.5, 1.9, 1.13, 1.16, 1.17, 1.23, 1.24, 1.27, 1.28, 1.29, 1.30, and 1.31.
Compound (from table T2) 2.6.
Example 4: against the fruit shell fungus (glomeriella lavandularis) (cucurbita spp. anthracis) (Colletotrichumlagenarium)) fungicidal Activity/cucumber/prevention method of liquid cultures (anthracnose)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plate was incubated at 24 ℃ and the inhibition of growth was measured photometrically 3 to 4 days after administration.
In this test, the following compounds gave at least 80% disease control at 20ppm in the applied formulation when compared to untreated controls showing extensive disease development under the same conditions.
Compound (from table T1)1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.20, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.29, 1.30, 1.31.
Compounds (from table T2)2.2, 2.4, 2.5, 2.6, 2.7, 2.13, 2.14, 2.16, 2.17, 2.18.
Compound (from table T3) 3.1.
Example 5: fungicidal Activity/liquid culture against Mycosphaerella graminicola (Septoria tritici) (leaf blight)
Conidia of the fungus from frozen storage were directly mixed into nutrient broth (PDB-potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates were incubated at 24 ℃ and the inhibition of growth was determined photometrically 4-5 days after administration.
In this test, the following compounds in the applied formulation gave at least 80% disease control at 20ppm when compared to untreated controls showing extensive disease development under the same conditions
Compound (from table T1) 1.14.

Claims (16)

1. A compound having the formula (I):
Figure FDA0003023364130000011
wherein
A is A-1 or A-2;
Figure FDA0003023364130000012
wherein A-1 and A-2 are optionally substituted with one or two groups independently selected from halogen and methyl;
R1is hydroxy, amino, thiol, halogen, C1-3Alkoxy radical, C1-3Haloalkyl, C1-3Haloalkoxy, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-3Alkylamino radical, C1-3Alkoxyamino group, C1-3Haloalkoxyamino group, C1-3Alkylcarbonyloxy, C3-4Alkenyloxy-amino group, C3-4Alkynyloxyamino, N-C1-3alkyl-N-C1-3Alkoxyamino, N-C1-3alkoxy-N' -C1-3Alkylcarbonyl, or C3-6Cycloalkyl radical C1-3An alkoxyamino group;
R2is hydrogen, C1-3Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, phenyl, C2-6Alkenyl, or C2-6An alkynyl group; or
R1And R2Together with the carbon to which they are bonded, form oxo (═ O) or NORaGroup, wherein RaIs C1-5Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl, or C3-6Cycloalkyl radical C1-2An alkyl group;
R3and R4Are identical and are selected from halogen and C1-C6An alkyl group; or
R3And R4Together with the carbon to which they are bonded form a3, 4,5, or 6 membered cycloalkyl group;
y is O or S;
z is Z1Or Z2；
Z1represents-OR5Wherein:
R5is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C1-3Haloalkyl, cyano C1-4Alkyl, hydroxy C2-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl radical, C1-3Halogenoalkoxy radical C2-4Alkyl, amino C2-4Alkyl, N-C1-4Alkylamino radical C2-4Alkyl, N-di-C1-4Alkylamino radical C2-4Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-4Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R5Is C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl, heteroaryl C1-2Alkyl, heterocyclic, or heterocyclic C1-2Alkyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R6；
R6Is cyano, fluoro, chloro, bromo, methyl, ethyl, difluoromethyl, trifluoromethylFluoromethyl, methoxy, ethoxy, or difluoromethoxy;
Z2represents-NR7R8Wherein:
R7is hydrogen, amino, hydroxy, cyano, C1-6Alkyl radical, C1-4Alkoxy radical, C3-5Alkenyl radical, C3-5Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, cyano C1-4Alkyl radical, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkoxy radical C2-4Alkyl, N-C1-4Alkylamino, N-di-C1-4Alkylamino radical, N-C1-4alkylcarbonyl-N-C1-4Alkylamino radical, amino radical C2-4Alkyl, N-C1-3Alkylamino radical C2-4Alkyl, N-di-C1-3Alkylamino radical C2-4Alkyl, N-C1-3alkyl-N-C1-3Alkoxyamino group C2-4Alkyl radical, C1-3Alkylcarbonylamino group C2-4Alkyl, N-C1-3Alkylcarbonyl- (N-C)1-3Alkyl) amino C2-3Alkyl radical, C1-3Alkyl carbonyl radical C1-3Alkyl radical, C1-3Alkoxycarbonyl radical C1-3Alkyl, or C1-3Alkylcarbonyloxy C2-4An alkyl group; or
R7Is C3-6A cycloalkyl group; c3-6Cycloalkyl radical C1-2An alkyl group; a phenyl group; phenyl radical C1-2An alkyl group; or heteroaryl, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1,2,3 or 4 heteroatoms independently selected from N, O and S; heterocyclyl, wherein the heterocyclyl moiety is a 4-to 6-membered non-aromatic ring comprising 1 or 2 heteroatoms independently selected from N, O and S; and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moiety is each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R9；
R8Is hydrogen, methyl, ethyl, propylIsopropyl, prop-2-enyl, prop-2-ynyl, methoxy, 2-methoxyethyl, or cyclopropyl; or
R7And R8Together with the nitrogen atom to which they are bonded form a ring optionally containing a substituent selected from the group consisting of O, S, S (O)2And NR10A4, 5 or 6 membered ring of the further heteroatom or group;
R9is hydroxy, C1-3Alkyl, halogen, C1-3Alkoxy, or C1-3A haloalkyl group; and is
R10Is hydrogen, methyl, methoxy, fluoromethoxy, difluoromethoxy, formyl or acyl; or
Salts or N-oxides thereof.
2. The compound of claim 1, wherein R1Is hydroxy, thiol, C1-3Alkoxy radical, C1-3Alkoxyamino group, C1-3Alkylcarbonyloxy, N-C1-3alkyl-N-C1-3Alkoxyamino, or N-C1-3alkoxy-N' -C1-3An alkylcarbonyl group.
3. A compound according to claim 1 or claim 2, wherein R2Is hydrogen, methyl, ethyl, n-propyl, cyclopropyl, cyclobutyl, phenyl, prop-2-enyl, or prop-2-ynyl.
4. A compound according to any one of claims 1 to 3, wherein R3And R4Both are identical and are selected from fluorine and methyl, or R3And R4Together with the carbon to which they are bonded, form a cyclopropyl group.
5. The compound of any one of claims 1 to 4, wherein Z is Z2And R is7Is hydrogen, amino, C1-4Alkyl radical, C1-4Alkoxy radical, C3-4Alkenyl radical, C3-4Alkynyl, C3-4Alkenyloxy radical, C3-4Alkynyloxy, C1-4Haloalkyl, C3-5Haloalkenyl, C1-4Haloalkoxy, hydroxy C2-4Alkyl radical, C1-2Alkoxy radical C2-4Alkyl radical, C1-2Halogenoalkoxy radical C2-4Alkyl, N-C1-2Alkylamino, N-di-C1-2Alkylamino radical, C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2An alkyl group, or a heteroaryl group, wherein the heteroaryl moiety is a5 or 6 membered monocyclic aromatic ring comprising 1 or 2 heteroatoms independently selected from N and O; or heterocyclyl, wherein the heterocyclyl moiety is a 4-to 6-membered non-aromatic ring comprising 1 or 2 heteroatoms independently selected from N and O.
6. The compound of any one of claims 1 to 5, wherein Z is Z2And R is8Is hydrogen, methyl, or prop-2-enyl.
7. The compound of any one of claims 1 to 4, wherein Z is Z2And R is7And R8Together with the nitrogen atom to which they are bonded form a compound optionally containing a substituent selected from O and NR10Or a4, 5 or 6 membered ring of the group.
8. A compound according to any one of claims 1 to 6, wherein R9Is hydroxy, methyl, ethyl, isopropyl, chloro, fluoro, methoxy, difluoromethyl or trifluoromethyl.
9. The compound of any one of claims 1 to 4, wherein Z is Z1And R is5Is hydrogen, C1-5Alkyl radical, C3-5Alkenyl radical, C3-5Alkynyl, C1-3Haloalkyl, cyano C1-2Alkyl, hydroxy C2-4Alkyl radical, C1-3Alkoxy radical C1-3Alkyl radical, C1-3Halogenoalkoxy radical C2-4Alkyl, amino C2-4Alkyl radical, C1-3Alkyl carbonyl radical C1-2Alkyl, or C1-3Alkoxycarbonyl radical C1-2An alkyl group; orA
C3-6Cycloalkyl radical, C3-6Cycloalkyl radical C1-2Alkyl, phenyl C1-2Alkyl, heteroaryl or heterocyclyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 or 2 substituents, which may be the same or different, selected from R6(ii) a Wherein
R6Is cyano, fluoro, chloro, bromo, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy.
10. The compound of any one of claims 1 to 9, wherein Y is O.
11. The compound of any one of claims 1 to 10, wherein a is a-1.
12. The compound of any one of claims 1 to 10, wherein a is a-2.
13. An agrochemical composition comprising a fungicidally effective amount of a compound according to any one of claims 1 to 12.
14. The composition of claim 13, further comprising at least one additional active ingredient and/or an agrochemically acceptable diluent or carrier.
15. A method for controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound according to any one of claims 1 to 12, or a composition comprising said compound as active ingredient, is applied to the plants, parts thereof or the locus thereof.
16. Use of a compound according to any one of claims 1 to 12 as a fungicide.
CN201980068308.0A 2018-10-17 2019-10-03 Microbicidal oxadiazole derivatives Withdrawn CN113195462A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN201811039292 2018-10-17
IN201811039292 2018-10-17
PCT/EP2019/076837 WO2020078732A1 (en) 2018-10-17 2019-10-03 Microbiocidal oxadiazole derivatives

Publications (1)

Publication Number Publication Date
CN113195462A true CN113195462A (en) 2021-07-30

Family

ID=68233965

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980068308.0A Withdrawn CN113195462A (en) 2018-10-17 2019-10-03 Microbicidal oxadiazole derivatives

Country Status (3)

Country Link
CN (1) CN113195462A (en)
BR (1) BR112021007156A2 (en)
WO (1) WO2020078732A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115385858B (en) * 2022-08-18 2024-03-01 河南师范大学 Photocatalytic preparation method of 2-phenyl-2H-indazole-3-carboxamide compound

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61107392A (en) 1984-10-31 1986-05-26 株式会社東芝 Image processing system
BR8600161A (en) 1985-01-18 1986-09-23 Plant Genetic Systems Nv CHEMICAL GENE, HYBRID, INTERMEDIATE PLASMIDIO VECTORS, PROCESS TO CONTROL INSECTS IN AGRICULTURE OR HORTICULTURE, INSECTICIDE COMPOSITION, PROCESS TO TRANSFORM PLANT CELLS TO EXPRESS A PLANTINIDE TOXIN, PRODUCED BY CULTURES, UNITED BY BACILLA
EP0276432A3 (en) 1986-12-12 1988-10-26 Ciba-Geigy Ag Pesticides
AU613521B2 (en) 1988-09-02 1991-08-01 Sankyo Company Limited 13-substituted milbemycin derivatives, their preparation and use
US5169629A (en) 1988-11-01 1992-12-08 Mycogen Corporation Process of controlling lepidopteran pests, using bacillus thuringiensis isolate denoted b.t ps81gg
EP0374753A3 (en) 1988-12-19 1991-05-29 American Cyanamid Company Insecticidal toxines, genes coding therefor, antibodies binding them, transgenic plant cells and plants expressing these toxines
US5015630A (en) 1989-01-19 1991-05-14 Merck & Co., Inc. 5-oxime avermectin derivatives
NO176766C (en) 1989-02-07 1995-05-24 Meiji Seika Kaisha Process for the preparation of a compound having anthelmintic activity
GB8910624D0 (en) 1989-05-09 1989-06-21 Ici Plc Bacterial strains
CA2015951A1 (en) 1989-05-18 1990-11-18 Mycogen Corporation Novel bacillus thuringiensis isolates active against lepidopteran pests, and genes encoding novel lepidopteran-active toxins
EP0427529B1 (en) 1989-11-07 1995-04-19 Pioneer Hi-Bred International, Inc. Larvicidal lectins and plant insect resistance based thereon
JPH085894B2 (en) 1990-03-01 1996-01-24 三共株式会社 Milbemycin ether derivative
JPH0570366A (en) 1991-03-08 1993-03-23 Meiji Seika Kaisha Ltd Composition for medicine
UA48104C2 (en) 1991-10-04 2002-08-15 Новартіс Аг Dna fragment including sequence that codes an insecticide protein with optimization for corn, dna fragment providing directed preferable for the stem core expression of the structural gene of the plant related to it, dna fragment providing specific for the pollen expression of related to it structural gene in the plant, recombinant dna molecule, method for obtaining a coding sequence of the insecticide protein optimized for corn, method of corn plants protection at least against one pest insect
JP2874342B2 (en) 1992-03-17 1999-03-24 藤沢薬品工業株式会社 Depsipeptide derivatives, their preparation and their use
US5478855A (en) 1992-04-28 1995-12-26 Yashima Chemical Industry Co., Ltd. 2-(2,6-difluorophenyl)-4-(2-ethoxy-4-tert-butylphenyl)-2-oxazoline
DE4317458A1 (en) 1992-06-11 1993-12-16 Bayer Ag Use of cyclic depsipeptides with 18 ring atoms for the control of endoparasites, new cyclic depsipeptides with 18 ring atoms and process for their preparation
TW262474B (en) 1992-09-01 1995-11-11 Sankyo Co
GB9300883D0 (en) 1993-01-18 1993-03-10 Pfizer Ltd Antiparasitic agents
EP0685469A4 (en) 1993-02-19 1996-04-03 Meiji Seika Kaisha Pf1022 derivative, cyclic depsipeptide.
DE4317457A1 (en) 1993-05-26 1994-12-01 Bayer Ag Octacyclodepsipeptides with endoparasiticidal activity
ATE173264T1 (en) 1994-01-14 1998-11-15 Pfizer ANTIPARASIC PYRROLOBENZOXAZINE COMPOUNDS
GB9402916D0 (en) 1994-02-16 1994-04-06 Pfizer Ltd Antiparasitic agents
US5530195A (en) 1994-06-10 1996-06-25 Ciba-Geigy Corporation Bacillus thuringiensis gene encoding a toxin active against insects
DE4437198A1 (en) 1994-10-18 1996-04-25 Bayer Ag Process for sulfonylation, sulfenylation and phosphorylation of cyclic depsipeptides
DE4440193A1 (en) 1994-11-10 1996-05-15 Bayer Ag Use of dioxomorpholines to control endoparasites, new dioxomorpholines and processes for their production
DE19520936A1 (en) 1995-06-08 1996-12-12 Bayer Ag Ectoparasiticides means
ATE216999T1 (en) 1996-03-11 2002-05-15 Syngenta Participations Ag PYRIMIDINE-4-ONE DERIVATIVES AS PESTICIDES
JPH10101614A (en) 1996-09-27 1998-04-21 Daikin Ind Ltd Production of alpha alpha-difluoro-beta-hydroxy ester
WO2002015701A2 (en) 2000-08-25 2002-02-28 Syngenta Participations Ag Bacillus thuringiensis crystal protein hybrids
US7230167B2 (en) 2001-08-31 2007-06-12 Syngenta Participations Ag Modified Cry3A toxins and nucleic acid sequences coding therefor
JP2005509606A (en) 2001-10-03 2005-04-14 ファルマシア・コーポレーション Prodrugs of substituted polycyclic compounds useful for selectively inhibiting the coagulation cascade
AU2002361696A1 (en) 2001-12-17 2003-06-30 Syngenta Participations Ag Novel corn event
CA2480456C (en) 2002-04-04 2011-11-22 Valent Biosciences Corp. Enhanced herbicide composition
GB0303439D0 (en) 2003-02-14 2003-03-19 Pfizer Ltd Antiparasitic terpene alkaloids
ES2388548T3 (en) 2005-04-08 2012-10-16 Bayer Cropscience Nv Elite event A2704-12 and methods and cases to identify this event in biological samples
BRPI0610462B1 (en) 2005-04-11 2018-02-27 Bayer Cropscience Nv METHODS FOR IDENTIFYING THE ELITE A5547-127 EVENT IN BIOLOGICAL SAMPLES, CONFIRMING SEED PURPOSE AND FOR CREATING SEEDS FOR THE PRESENCE OF THIS EVENT, KITS AND PROBES FOR THE PERFORMANCE OF THESE EVENTS
PT1885176T (en) 2005-05-27 2016-11-28 Monsanto Technology Llc Soybean event mon89788 and methods for detection thereof
US7951995B2 (en) 2006-06-28 2011-05-31 Pioneer Hi-Bred International, Inc. Soybean event 3560.4.3.5 and compositions and methods for the identification and detection thereof
BRPI0716347B8 (en) 2006-10-31 2022-12-06 Du Pont ISOLATED POLYNUCLOTIDE, METHODS TO IDENTIFY WHETHER A BIOLOGICAL SAMPLE COMPRISES A POLYNUCLOTIDE, TO DETECT THE PRESENCE OF A POLYNUCLOTIDE, TO DETECT THE PRESENCE OF A SEQUENCE, TO SELECT SEEDS AND TO PRODUCE AN ALS INHIBITOR TOLERANT PAIR, DNA PRIMER PAIRS AND CONSTRUCTION OF AN EXPRESSION DNA
AU2008321220A1 (en) 2007-11-15 2009-05-22 Monsanto Technology Llc Soybean plant and seed corresponding to transgenic event MON87701 and methods for detection thereof
MX2011004055A (en) 2008-10-17 2011-06-24 Xenon Pharmaceuticals Inc Spiro-oxindole compounds and their use as therapeutic agents.
MX2011007274A (en) 2009-01-07 2012-03-29 Brasil Pesquisa Agropec Soybean event 127 and methods related thereto.
IN2012DN01800A (en) 2009-08-19 2015-06-05 Dow Agrosciences Llc
BR112012003884A2 (en) 2009-08-19 2015-09-01 Dow Agrosciences Llc Event aad-1 of 40278-9, related transgenic maize strains and event-specific identification.
AU2010284285B2 (en) 2009-08-19 2015-08-20 Dow Agrosciences Llc Control of AAD-1 monocot volunteers in fields of dicot crops
KR101376028B1 (en) 2009-09-17 2014-03-19 몬산토 테크놀로지 엘엘씨 Soybean transgenic event mon 87708 and methods of use thereof
TWI667347B (en) 2010-12-15 2019-08-01 瑞士商先正達合夥公司 Soybean event syht0h2 and compositions and methods for detection thereof
BR102012019436B8 (en) 2011-07-26 2022-10-11 Dow Agrosciences Llc SOYBEAN EVENT DETECTION METHOD PDAB9582.814.19.1
WO2013066838A1 (en) 2011-10-31 2013-05-10 Glaxosmithkline Llc Compounds and methods
BR112015026129A2 (en) 2013-04-19 2017-10-17 Bayer Cropscience Ag method to fight pests
KR102180294B1 (en) 2013-06-14 2020-11-18 몬산토 테크놀로지 엘엘씨 Soybean Transgenic Event MON87751 And Methods For Detection And Use Thereof
PL3151669T3 (en) 2014-06-06 2021-04-19 Basf Se Use of substituted oxadiazoles for combating phytopathogenic fungi
WO2017222952A1 (en) * 2016-06-23 2017-12-28 Merck Sharp & Dohme Corp. 3- heteroaryl substituted 5-trifluoromethyl oxadiazoles as histone deacetylase 6 (hdac6) inhibitors
WO2018219797A1 (en) * 2017-06-02 2018-12-06 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
WO2019097054A1 (en) * 2017-11-20 2019-05-23 Syngenta Participations Ag Microbiocidal oxadiazole derivatives

Also Published As

Publication number Publication date
WO2020078732A1 (en) 2020-04-23
BR112021007156A2 (en) 2021-07-20

Similar Documents

Publication Publication Date Title
ES2953141T3 (en) Fungicide compounds
CN112789265B (en) Microbiocidal compounds
CN109890209B (en) Microbicidal oxadiazole derivatives
CN109071522B (en) Microbicidal oxadiazole derivatives
WO2018158365A1 (en) Microbiocidal oxadiazole derivatives
CN108368099B (en) Microbicidal oxadiazole derivatives
CN113382988A (en) Microbicidal 2-acylamino-thiazole-4-carboxamide derivatives
CN113166082A (en) Microbiocidal thiazole derivatives
WO2018162643A1 (en) Microbiocidal oxadiazole derivatives
WO2021224102A1 (en) Microbiocidal compounds
JP7472163B2 (en) Microbicidal thiazole derivatives
KR20230019877A (en) microbicidal derivatives
CN112154141A (en) Microbicidal pyridine carboxamide derivatives
EP3606913B1 (en) Microbiocidal oxadiazole derivatives
JP2024515096A (en) Microbicide Quinoline/Quinoxaline Isoquinoline Derivatives
JP2024512693A (en) Microbicidal quinoline/quinoxaline benzothiazine derivatives
CN113195462A (en) Microbicidal oxadiazole derivatives
WO2019011928A1 (en) Microbiocidal oxadiazole derivatives
WO2019011926A1 (en) Microbiocidal oxadiazole derivatives
WO2021219780A1 (en) Microbiocidal compounds
CN115443273A (en) Microbicidal quinoline dihydro- (thiazine) oxazine derivatives
WO2021219778A1 (en) Microbiocidal compounds
TW202124370A (en) Microbiocidal dihydroisoquinoline derivatives
CN114072384A (en) Microbicidal picolinamide derivatives
WO2020025807A1 (en) Microbiocidal 1,2,5-oxadiazol-3(2h)-one derivatives

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication
WW01 Invention patent application withdrawn after publication

Application publication date: 20210730