WO2021012264A1 - 三唑磺酰胺衍生物及其制备方法和应用 - Google Patents

三唑磺酰胺衍生物及其制备方法和应用 Download PDF

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WO2021012264A1
WO2021012264A1 PCT/CN2019/097704 CN2019097704W WO2021012264A1 WO 2021012264 A1 WO2021012264 A1 WO 2021012264A1 CN 2019097704 W CN2019097704 W CN 2019097704W WO 2021012264 A1 WO2021012264 A1 WO 2021012264A1
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Prior art keywords
alkyl
halogenated
aryl
compound
alkoxy
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PCT/CN2019/097704
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English (en)
French (fr)
Inventor
李义涛
林健
高国良
姚文强
敬德旺
李法霖
Original Assignee
东莞市东阳光农药研发有限公司
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Priority to CN201980051311.1A priority Critical patent/CN112638884B/zh
Priority to PCT/CN2019/097704 priority patent/WO2021012264A1/zh
Publication of WO2021012264A1 publication Critical patent/WO2021012264A1/zh

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    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms

Definitions

  • the present invention relates to the field of pesticides. Specifically, the present invention relates to a triazole sulfonamide derivative, a preparation method of the triazole sulfonamide derivative and its application as a plant disease control agent in agriculture.
  • Biologically active triazole sulfonamide derivatives are one of the goals of new pesticide development and research.
  • indazole sulfonamide developed by Nissan Chemical has high activity against plant blight and downy mildew caused by Oomycetes.
  • Oomycetes diseases are very common and serious diseases on fruit and vegetable crops, and the losses they cause cannot be ignored.
  • triazole sulfonamide derivatives have considerable scalability and structural transformation potential (such as WO 2017143803, CN 106905251, etc.).
  • the novel triazole sulfonamide derivatives disclosed in the present invention have not been reported.
  • the present invention provides a new triazole sulfonamide derivative, which has good control effect on plant pathogenic fungi and can be further developed as a fungicide.
  • the present invention provides a compound having a compound represented by formula (I) or a stereoisomer, nitrogen oxide, salt, (E) or ( Z) Isomers and their mixtures:
  • R 1 and R 2 are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 6-10 aryl, C 3- 8 cycloalkyl-C 1-6 alkyl- or C 6-10 aryl-C 1-6 alkyl-; wherein, the C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 3-8 cycloalkyl, C 6-10 aryl, C 3-8 cycloalkyl-C 1-6 alkyl- or C 6-10 aryl-C 1-6 alkyl-any Optionally by 1, 2, 3, 4 or 5 selected from halogen, hydroxyl, cyano, nitro, amino, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy Or substituted by a halogenated C 1-6 alkoxy substituent;
  • R 1 , R 2 and the nitrogen atom to which they are connected together form an optional group of 1, 2, 3, 4, or 5 selected from halogen, hydroxyl, cyano, nitro, amino, C 1-6 alkyl, 3-10 membered heterocyclic group or 5-10 membered heteroaryl substituted by halogenated C 1-6 alkyl, C 1-6 alkoxy or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 alkyl , Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl, C 6-10 aryl, halogenated C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl- or Halogenated C 6-10 aryl-C 1-6 alkyl-;
  • x 0, 1 or 2;
  • R m and R n are each independently C 1-6 alkyl or C 6-10 aryl;
  • R 4 is optionally substituted by 1, 2, 3, 4 or 5 selected from halogen, hydroxyl, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1- 6 Alkyl or halogenated C 1-6 alkoxy substituent substituted;
  • R 5 is a C 6-10 aryl group or a 5-10 membered heteroaryl group; wherein, R 5 is optionally selected from halogen, hydroxy, cyano, nitro, C 1 -6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl or halogenated C 1-6 alkoxy substituent substituted;
  • R 6 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-6 alkyl-, Phenyl or phenyl-C 1-6 alkyl-;
  • R 5 , R 6 and the carbon atom connected to them form a C 9-10 aryl group or a 9-10 membered heteroaryl group; the C 9-10 aryl group and 9-10 membered heteroaryl group optionally By 1, 2 or 3 selected from halogen, hydroxy, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl or halogenated C 1-6 alkane The substituents of the oxy group are substituted.
  • R 1 and R 2 are each independently hydrogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 6-10 Aryl, C 3-6 cycloalkyl-C 1-3 alkyl- or C 6-10 aryl-C 1-3 alkyl-.
  • R 1 and R 2 are each independently C 1-4 alkyl.
  • R 1 and R 2 are each independently -CH 3 .
  • R 3 is hydrogen, fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halo C 1-4 alkyl, halogenated C 2-4 alkenyl, halogenated C 2-4 alkynyl, C 6-10 aryl, halogenated C 6-10 aryl, C 6-10 aryl-C 1 -3 alkyl - or halo-C 6- 10 aryl group -C 1-3 alkyl -.
  • R 3 is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH (CH 3 ) 2 , -C(CH 3 ) 3 , -CH 2 Cl, -CHF 2 or -CF 3 .
  • R 3 is hydrogen
  • R m and R n are each independently C 1-4 alkyl or phenyl
  • R 4 is optionally selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkyl or Substituents of halogenated C 1-4 alkoxy are substituted.
  • R m and R n are each independently C 1-4 alkyl or phenyl
  • R 4 is optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxyl, cyano, nitro, CH 3 -or CF 3 -.
  • R n is C 1-4 alkyl or phenyl
  • R 4 is optionally selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkyl or Substituents of halogenated C 1-4 alkoxy are substituted.
  • R n is C 1-4 alkyl or phenyl
  • R 4 is optionally substituted with 1, 2 or 3 substituents selected from halogen, hydroxyl, cyano, nitro, CH 3 -or CF 3 -.
  • R 4 is the following sub-structure:
  • R 5 is a C 6-10 aryl group or a 5-10 membered heteroaryl group; wherein, R 5 is optionally selected from halogen, hydroxy, and cyano by 1, 2, 3, 4, or 5 , Nitro, C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkyl or halogenated C 1-4 alkoxy substituents.
  • R 5 is a C 6-10 aryl group or a 5-9 membered heteroaryl group; wherein, R 5 is optionally substituted by 1, 2, 3, 4, or 5 selected from halogen, hydroxyl, cyano Substituents are substituted with a group, a nitro group, a C 1-4 alkyl group, a C 1-4 alkoxy group, a halogenated C 1-4 alkyl group, or a halogenated C 1-4 alkoxy group.
  • R 5 is phenyl, naphthyl, pyridyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1H-1, 2,4-triazolyl or 1H-indolyl;
  • R 5 is optionally selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkyl or Substituents of halogenated C 1-4 alkoxy are substituted.
  • R 5 is phenyl, naphth-1-yl, pyridin-2-yl, pyridin-3-yl, 1H-pyrrol-2-yl, thiophen-2-yl, thiophen-3-yl , 1H-imidazol-1-yl, isoxazol-3-yl, 1H-indol-3-yl or 1H-indol-4-yl;
  • R 5 is optionally selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkyl or Substituents of halogenated C 1-4 alkoxy are substituted.
  • R 5 is phenyl, naphth-1-yl, pyridin-2-yl, pyridin-3-yl, 1H-pyrrol-2-yl, thiophen-2-yl, thiophen-3-yl , 1H-imidazol-1-yl, isoxazol-3-yl, 1H-indol-3-yl or 1H-indol-4-yl;
  • R 5 is optionally selected from fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH 2 CH 2 CH 3 , -CH(CH 3 )CH 2 CH 3 , -CH 2 CH(CH 3 ) 2 , -C(CH 3 ) 3 , -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -OCH(CH 3 ) 2 , -OCH 2 CH 2 CH 2 CH 3 , -OCH(CH 3 ) 2 , -OCH 2 CH 2 CH 2 CH 3 , -OCH(CH 3 )CH 2 CH 3 , -OCH 2 CH(CH 3 ) 2 , -OC(CH 3 ) 3 , -CF 3 or -OCF 3 is substituted by a substituent.
  • R 6 is hydrogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, or phenyl.
  • R 6 is hydrogen, C 1-4 alkyl, or phenyl.
  • R 6 is hydrogen, -CH 3 or phenyl.
  • the present invention provides a compound, which is a compound represented by formula (II) or a stereoisomer, nitrogen oxide, salt, (E) or a compound represented by formula (II) (Z) Isomers and their mixtures:
  • R 4 and R 5 have the meanings described in the present invention.
  • the present invention provides a compound, which is a compound represented by formula (II) or a stereoisomer, nitrogen oxide, salt, (E) or a compound represented by formula (II) (Z) Isomers and their mixtures:
  • R m is optionally substituted by 1 or 2 halogen, hydroxy, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkyl or halogenated C 1- 4 Alkoxy substituted phenyl;
  • R n is C 1-4 alkyl or optionally substituted by halogen, hydroxy, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkyl or halogenated C 1- 4 alkoxy-substituted phenyl;
  • R 5 is optionally substituted by 1, 2 or 3 halogen, hydroxy, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, halo C 1-4 alkyl or halo C 1-4 alkoxy substituted phenyl, naphthyl, pyridin-2-yl or pyridin-3-yl optionally substituted by 1 or 2 halogens, 1H optionally substituted by C 1-4 alkyl -Pyrrol-2-yl or isoxazol-3-yl, thiophen-3-yl, thiophen-2-yl, 1H-imidazol-1-yl, 1H-indol-3-yl or 1H-indole-4 -base.
  • R 4 is the following sub-structure:
  • R 5 is optionally substituted by 1, 2, or 3 fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH(CH 3 ) 2 , -CH 2 CH 2 CH 2 CH 3 , -CH(CH 3 )CH 2 CH 3 , -CH 2 CH(CH 3 ) 2 , -C(CH 3 ) 3 , -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -OCH(CH 3 ) 2 , -CF 3 or -OCF 3 substituted phenyl, naphthalene-1-yl, optionally 1 Or 2 pyridin-2-yl or pyridin-3-yl substituted with fluorine, chlorine, bromine or iodine, optionally by -CH 3 , -CH 2 CH 3 , -
  • R 5 is the following sub-structure:
  • the present invention provides a compound having a compound represented by formula (III) or a stereoisomer of a compound represented by formula (III), nitrogen oxide or a salt thereof:
  • R 4 and R 5 have the meanings described in the present invention.
  • the present invention provides a compound that is a compound having one of the following structures or a stereoisomer, nitrogen oxide, salt, (E) or (Z) isoform of a compound having one of the following structures: Structures and their mixtures:
  • the present invention provides a composition comprising at least one compound according to the present invention.
  • composition of the present invention contains a pesticide-acceptable surfactant and/or carrier.
  • the present invention provides the use of the compound of the present invention or the composition of the present invention as a plant disease control agent in agriculture.
  • the present invention provides a method for controlling plant diseases with the compound of the present invention or the composition of the present invention.
  • the present invention provides a method for applying the compound of the present invention or the composition of the present invention to plants or plant growth sites before or after germination of the plant disease.
  • the articles “a”, “an” and “said” used in the present invention are intended to include “at least one” or “one or more”. Therefore, these articles used in the present invention refer to articles of one or more than one (ie, at least one) object.
  • a component refers to one or more components, that is, there may be more than one component considered to be adopted or used in the embodiment of the described embodiment.
  • Stereoisomers refer to compounds that have the same chemical structure but differ in the arrangement of the atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotamers), geometric isomers (cis/trans) isomers, atropisomers, etc. .
  • Enantiomers refer to two isomers of a compound that cannot be superimposed but are mirror images of each other.
  • Diastereoisomers refer to stereoisomers that have two or more chiral neutralities and whose molecules are not mirror images of each other. Diastereoisomers have different physical properties, such as melting point, boiling point, spectral properties and reactivity. Mixtures of diastereomers can be separated by high-resolution analytical operations such as electrophoresis and chromatography, such as HPLC.
  • optically active compounds that is, they have the ability to rotate the plane of plane-polarized light.
  • the prefixes D and L or R and S are used to indicate the absolute configuration of the molecule with respect to one or more chiral centers.
  • the prefixes d and l or (+) and (-) are symbols used to specify the rotation of plane-polarized light caused by the compound, where (-) or l indicates that the compound is levorotatory.
  • Compounds prefixed with (+) or d are dextrorotatory.
  • a specific stereoisomer is an enantiomer, and a mixture of such isomers is called an enantiomeric mixture.
  • a 50:50 mixture of enantiomers is called a racemic mixture or a racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.
  • any asymmetric atom (for example, carbon, etc.) of the compound disclosed in the present invention can exist in a racemic or enantiomerically enriched form, such as (R)-, (S)- or (R,S)-configuration form exist.
  • each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess in the (R)- or (S)- configuration, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess.
  • the compound of the present invention can be one of the possible isomers or a mixture of them, such as racemates and diastereoisomer mixtures (depending on the number of asymmetric carbon atoms) The form exists.
  • Optically active (R)- or (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may have E or Z configuration; if the compound contains a disubstituted cycloalkyl, the substituent of the cycloalkyl may have a cis or trans configuration.
  • Any resulting mixture of stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, and diastereomers based on differences in the physical and chemical properties of the components, for example, by chromatography Method and/or fractional crystallization method.
  • racemate of any final product or intermediate obtained can be resolved into optical enantiomers by methods familiar to those skilled in the art by known methods, for example, by performing diastereomeric salts of the obtained Separate.
  • the racemic product can also be separated by chiral chromatography, such as high performance liquid chromatography (HPLC) using a chiral adsorbent.
  • HPLC high performance liquid chromatography
  • enantiomers can be prepared by asymmetric synthesis.
  • the compounds of the present invention can be optionally substituted by one or more substituents, such as the compounds of the general formula above, or the special examples, subclasses, and subclasses contained in the examples.
  • substituents such as the compounds of the general formula above, or the special examples, subclasses, and subclasses contained in the examples.
  • substituents such as the compounds of the general formula above, or the special examples, subclasses, and subclasses contained in the examples.
  • substituents such as the compounds of the general formula above, or the special examples, subclasses, and subclasses contained in the examples.
  • a class of compounds can be used interchangeably.
  • substituted means that one or more hydrogen atoms in a given structure are replaced by a specific substituent.
  • an optional substituent group can be substituted at each substitutable position of the group.
  • substituents selected from specific groups When more than one position in the given structural formula can be substituted by one or more substituents selected from specific groups, then the substituents can be substituted at each position with the same or different positions.
  • substituents can be substituted at each position with the same or different positions.
  • examples of "one or more" refer to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
  • the substituents mentioned herein can be, but are not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxy, nitro, amino, carboxy, alkyl, alkoxy, alkoxyalkyl, alkane Oxyoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkane Alkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxy-substituted alkyl, hydroxy-substituted alkyl Amino, cyano-substituted alkyl, cyano-substituted alkoxy, cyan
  • C 1 -C 6 alkyl or “C 1-6 alkyl” specifically refers to independently disclosed methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, and C 6 alkyl. base.
  • alkyl or “alkyl group” used in the present invention refers to a saturated linear or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms; wherein the alkyl group is optionally One or more substituents described in this invention are substituted. Unless otherwise specified, alkyl groups contain 1-20 carbon atoms. In one embodiment, the alkyl group contains 1-12 carbon atoms; in one embodiment, the alkyl group contains 1-8 carbon atoms; in another embodiment, the alkyl group contains 1- 6 carbon atoms; in yet another embodiment, the alkyl group contains 1-4 carbon atoms; in yet another embodiment, the alkyl group contains 1-3 carbon atoms.
  • alkyl groups include, but are not limited to, methyl (Me, -CH 3 ), ethyl (Et, -CH 2 CH 3 ), n-propyl (n-Pr, -CH 2 CH 2 CH 3 ), isopropyl (i-Pr, -CH(CH 3 ) 2 ), n-butyl (n-Bu, -CH 2 CH 2 CH 2 CH 3 ), isobutyl (i-Bu, -CH 2 CH (CH 3 ) 2 ), sec-butyl (s-Bu, -CH(CH 3 )CH 2 CH 3 ), tert-butyl (t-Bu, -C(CH 3 ) 3 ), n-pentyl (-CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (-CH(CH 3 )CH 2 CH 2 CH 3 ), 3-pentyl (-CH(CH 2 CH 3 ) 2 ), 2-methyl -2-Butyl (-C(CH 3 ) 2
  • alkoxy means that the alkyl group is connected to the rest of the molecule through an oxygen atom, where the alkyl group has the meaning as described in the present invention.
  • alkoxy groups include, but are not limited to, methoxy (MeO, -OCH 3 ), ethoxy (EtO, -OCH 2 CH 3 ), 1-propoxy (n-PrO, n- Propoxy, -OCH 2 CH 2 CH 3 ), 2-propoxy (i-PrO, i-propoxy, -OCH(CH 3 ) 2 ) and so on.
  • alkenyl means a linear or branched monovalent hydrocarbon group containing 2-12 carbon atoms, in which there is at least one unsaturation site, that is, a carbon-carbon sp 2 double bond, wherein the alkenyl group
  • the group may be optionally substituted with one or more substituents described in the present invention, which includes the positioning of "cis” and “tans", or the positioning of "E” and "Z”.
  • the alkenyl group contains 2-8 carbon atoms; in another embodiment, the alkenyl group contains 2-6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 -4 carbon atoms.
  • alkynyl refers to a linear or branched monovalent hydrocarbon group containing 2-12 carbon atoms, in which at least one carbon-carbon sp triple bond.
  • the alkynyl group contains 2-8 carbon atoms; in another embodiment, the alkynyl group contains 2-6 carbon atoms; in yet another embodiment, the alkynyl group contains 2 -4 carbon atoms.
  • alkynyl groups include, but are not limited to, -C ⁇ CH, -CH 2 -C ⁇ CH, -CH 2 -C ⁇ CCH 3 , -CH 2 CH 2 -C ⁇ CH, -CH 2 -C ⁇ CCH 2 CH 3 and so on.
  • cycloalkyl refers to a monovalent or multivalent saturated monocyclic, bicyclic or tricyclic ring system containing 3-12 carbon atoms.
  • the cycloalkyl group contains 3-10 carbon atoms; in another embodiment, the cycloalkyl group contains 3-8 carbon atoms; in another embodiment, the cycloalkyl group contains 3-6 carbon atoms. carbon atom.
  • the cycloalkyl group is optionally substituted with one or more substituents described in this invention.
  • Examples of this include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl Alkyl, etc.
  • cycloalkylalkyl means that the hydrogen atom in the alkyl group is replaced by one or more cycloalkyl groups, wherein the alkyl group and the cycloalkyl group have the meanings as described in the present invention.
  • halogen refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).
  • haloalkyl means that an alkyl group is substituted by one or more halogen atoms. Examples of this include, but are not limited to, -CF 3 , -CHF 2 , -CH 2 Cl, -CH 2 CF 3 ,- CH 2 CHF 2 , -CH 2 CH 2 CF 3 and so on.
  • haloalkoxy means that the alkoxy group is substituted by one or more halogen atoms. Examples of this include, but are not limited to, -OCF 3 , -OCHF 2 , -OCHCl 2 , -OCH 2 CHF 2 , -OCH 2 CHCl 2 , -OCH(CH 3 )CHF 2 and so on.
  • heterocyclic group refers to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 3-15 ring atoms, wherein The monocyclic, bicyclic or tricyclic ring does not contain an aromatic ring, and at least one ring atom is selected from nitrogen, sulfur and oxygen atoms.
  • the sulfur atom of the ring can optionally be oxidized to S-oxide.
  • the nitrogen atom of the ring can optionally be oxidized to an N-oxygen compound.
  • heterocyclic group typically describes the number of ring atoms in the molecule.
  • piperidinyl is a 6-membered heterocyclic group.
  • aryl means a monocyclic, bicyclic and tricyclic carbocyclic ring system containing 6-14 ring atoms, or 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring system is aromatic Family, where each ring system contains a ring composed of 3-7 atoms, and has one or more attachment points connected to the rest of the molecule.
  • aryl can be used interchangeably with the term “aromatic ring”. Examples of aryl groups may include phenyl, indenyl, naphthyl, and anthracenyl. The aryl group is optionally substituted with one or more substituents described in the present invention.
  • arylalkyl means that the hydrogen atom in the alkyl group is replaced by one or more aryl groups, wherein the alkyl and aryl groups have the meanings as described in the present invention. Examples of such include, but are not limited to, benzyl, phenethyl, and the like.
  • heteroaryl refers to monocyclic, bicyclic and tricyclic ring systems containing 5-12 ring atoms, or 5-10 ring atoms, or 5-6 ring atoms, wherein at least one ring system is aromatic, And at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring composed of 5-7 atoms, and has one or more attachment points connected to the rest of the molecule.
  • heteroaryl can be used interchangeably with the term “heteroaromatic ring” or “heteroaromatic compound”.
  • the heteroaryl group is optionally substituted with one or more substituents described in the present invention.
  • the 5-10 atom heteroaryl group contains 1, 2, 3 or 4 heteroatoms independently selected from O, S and N.
  • heteroaryl groups may include pyridyl, pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,4-triazolyl, indole Kee and so on.
  • 5-9 membered heteroaryl typically describes the number of ring atoms in the molecule.
  • pyridyl is a 6-membered heteroaryl group.
  • linking substituents are described.
  • the Markush variables listed for the group should be understood as the linking group.
  • the Markush group definition of the variable lists “alkyl” or “aryl” it should be understood that the “alkyl” or “aryl” respectively represents the attached Alkylene group or arylene group.
  • alkylene refers to a saturated divalent hydrocarbon group obtained by removing two hydrogen atoms from a saturated hydrocarbon group. Unless otherwise specified, the alkylene group contains 1-12 carbon atoms. In other embodiments, the alkylene group contains 1-6 carbon atoms. In other embodiments, the alkylene group contains 1 -4 carbon atoms. In other embodiments, the alkylene group contains 1-2 carbon atoms. Examples of such include methylene (-CH 2 -), ethylene (-CH 2 CH 2 -), isopropylene (-CH(CH 3 )CH 2 -) and the like.
  • haloalkenyl means that an alkenyl group is substituted with one or more halogen atoms.
  • haloalkynyl means that an alkynyl group is substituted with one or more halogen atoms.
  • haloaryl means that an aryl group is substituted with one or more halogen atoms.
  • haloarylalkyl means that the “arylalkyl” group is substituted with one or more halogen atoms.
  • R 5 and R 6 when R 5 and R 6 are different, It can be expressed as (E) isomer, (Z) isomer or a mixture of (E) isomer and (Z) isomer; wherein the (E) isomer corresponds to Type isomer correspondence
  • the isomers, (E) isomers or the mixture of (Z) isomers and (E) isomers can be separated and confirmed by conventional methods, such as high performance liquid chromatography, proton nuclear magnetic resonance spectroscopy Method and/or single crystal diffraction method.
  • the salts of the compounds of the present invention include those derived from alkali metals or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and having the formula N + (R A R B R C R D) ammonium cation, where R A, R B, R C and R D are independently selected from hydrogen, C 1 -C 6 alkyl and C 1 -C 6 hydroxyalkyl.
  • the salt of the compound with formula (I), formula (II) or formula (III) can be obtained by using metal hydroxides (e.g. sodium hydroxide) or amines (e.g. ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine). , Bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine) are prepared by treating compounds of formula (I), formula (II) or formula (III).
  • acceptable salts can be formed from organic and inorganic acids, such as acetic acid, propionic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, and malonic acid. Acid, mandelic acid, malic acid, phthalic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, naphthalenesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, camphorsulfonic acid and similarly known Accepted acid.
  • organic and inorganic acids such as acetic acid, propionic acid, lactic acid, citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, and malonic acid. Acid, mandelic acid, malic acid, phthalic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methane
  • compositions and formulations of the compounds of the invention are provided.
  • the compound of the present invention can generally be used as an active ingredient of a bactericide in a composition or preparation, and usually also includes an agrochemically acceptable surfactant and/or carrier.
  • the above-mentioned surfactants can be various surfactants known in the field of pesticide formulations, such as anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants, block polymers, polyelectrolytes, and their mixture.
  • Such surfactants can be used as emulsifiers, dispersants, wetting agents, penetration enhancers or auxiliary agents.
  • Suitable anionic surfactants are alkali metal, alkaline earth metal or ammonium salts of sulfonic acid, sulfuric acid, phosphoric acid, carboxylic acid, and mixtures thereof.
  • sulfonates are alkyl aryl sulfonates, diphenyl sulfonates, ⁇ -olefin sulfonates, lignosulfonates, fatty acid and oil sulfonates, ethoxylated alkyl phenols Sulfonates, sulfonates of alkoxylated arylphenols, sulfonates of condensed naphthalene, sulfonates of dodecyl- and tridecylbenzene, sulfonates of naphthalene and alkylnaphthalene, sulfonates Succinate or sulfosuccinamate.
  • Examples of sulfates are the sulfates of fatty acids and oils, the sulfates of ethoxylated alkylphenols, the sulfates of alcohols, the sulfates of ethoxylated alcohols, or the sulfates of fatty acid esters.
  • Examples of phosphates are phosphate esters.
  • Examples of carboxylates are alkyl carboxylates and carboxylated alcohol or alkylphenol ethoxylates.
  • Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants and mixtures thereof.
  • alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters that have been alkoxylated with 1-50 equivalents.
  • Ethylene oxide and/or propylene oxide can be used for the alkoxylation, preferably ethylene oxide.
  • N-substituted fatty acid amides are fatty acid glucamide or fatty acid alkanolamide.
  • esters are fatty acid esters, glycerides or monoglycerides.
  • sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides.
  • polymeric surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.
  • Suitable cationic surfactants are quaternary surfactants, such as quaternary ammonium compounds having 1 or 2 hydrophobic groups, or salts of long-chain primary amines.
  • Suitable amphoteric surfactants are alkyl betaines and imidazolines.
  • Suitable block polymers are A-B or A-B-A type block polymers containing blocks of polyoxyethylene and polyoxypropylene, or A-B-C type block polymers containing alkanol, polyoxyethylene and polyoxypropylene.
  • Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali metal salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamine or polyvinylamine.
  • the above-mentioned carriers may be various carriers known in the field of pesticide formulations, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, and synthetic carriers. Specifically, for example: white carbon black, kaolin, diatomaceous earth, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, amine Mixture of fertilizer, urea and amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, anhydrous potassium carbonate and anhydrous bicarbonate One or more of potassium mixture and anhydrous sodium carbonate and anhydrous sodium bicarbonate mixture.
  • the fungicide composition may also contain various formulation auxiliaries commonly used in the field of pesticide formulations, specifically, the formulation auxiliaries may be solvents, cosolvents, and thickeners. , Antifreeze, capsule material, protective agent, defoamer, disintegrant, stabilizer, preservative, adhesive, chelating agent.
  • Suitable solvents are water and organic solvents, such as medium to high boiling point mineral oil fractions, such as kerosene, diesel; oils of vegetable or animal origin; aliphatic, cyclic and aromatic hydrocarbons, such as toluene, paraffin, tetralin , Alkylated naphthalene; alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycols; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonate, Fatty acid esters, ⁇ -butyrolactone; fatty acids; phosphonates; amines; amides, such as N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.
  • mineral oil fractions such as kerosene, diesel
  • oils of vegetable or animal origin oils of vegetable or animal origin
  • aliphatic, cyclic and aromatic hydrocarbons such as toluene
  • the above-mentioned solvents can also be used as auxiliary solvents.
  • Suitable thickeners are selected from polysaccharides (e.g. xanthan gum, carboxymethyl cellulose), inorganic clays (organically modified or unmodified), polycarboxylates and silicates.
  • Suitable antifreeze agents are selected from ethylene glycol, propylene glycol, glycerol, urea, glycerin and mixtures thereof.
  • Suitable bladder materials are selected from polyurethane, polyurea, urea-formaldehyde resin and their mixtures.
  • Suitable protective agents are selected from polyvinyl alcohol and/or polyethylene glycol.
  • Suitable antifoaming agents are selected from polysiloxanes, silicone milks, long-chain alcohols, fatty acids and their salts, and fluorine-containing organic substances and their mixtures.
  • Suitable disintegrants are selected from bentonite, urea, ammonium sulfate, aluminum chloride, citric acid, succinic acid, sodium bicarbonate, and mixtures thereof.
  • Suitable stabilizers are selected from triphenyl phosphite, epichlorohydrin, acetic anhydride and mixtures thereof.
  • Suitable preservatives are selected from benzoic acid, sodium benzoate, 1,2-benzisothiazolin-3-one (abbreviated as BIT), casson, potassium sorbate, and mixtures thereof.
  • Suitable binders are selected from polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylates, biological or synthetic waxes, and cellulose ethers.
  • the fungicide of the present invention can be applied in the form of its formulation or the use form prepared therefrom, such as aerosol, capsule suspension, cold-fogging concentrate, hot-fogging concentrate, capsule Granules, fine granules, flowable concentrates for seed treatment, ready-to-use solutions, dustable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, Large granules, micro granules, oil dispersible powders, oil miscible flow concentrates, oil miscible liquids, aerosols (under pressure), gas-producing products, foams, pastes, suspension concentrates, suspension emulsions Concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, powders and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, can Wet powders, natural products and synthetic substances imp
  • the compound of the present invention can be used as a plant disease control agent, namely as a fungicide. Therefore, the present invention may also include a method for controlling plant diseases caused by phytopathogenic fungi, the method comprising applying an effective amount of the compound of the present invention to the plant or part thereof or to the seed of the plant to be protected or comprising Compound fungicidal composition.
  • the compounds and/or compositions of the present invention can provide control of diseases caused by broad-spectrum phytopathogenic fungi of the Basidiomycetes, Ascomycetes, Oomycetes and Deuteromycetes. They can effectively control a broad spectrum of plant diseases, especially leaf pathogens in ornamental crops, lawn crops, vegetable crops, field crops, cereal crops and fruit tree crops.
  • pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, citrus foot rot (Phytophthora parasitica), Phytophthora (Phytophthora) cinnamomi) and squash blight (Phytophthora capsici), Pythium species diseases such as Pythium aphanidermatum, and Peronosporaceae species diseases such as Peronospora grape Pathogens (Plasmopara viticola), Downy mildew diseases (Peronospora spp.) (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp.
  • Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, citrus foot rot (Phytophthora parasitica), Phytophthora (Phytophthora) cinnam
  • pathogens include Rhizoctonia species ( Rhizoctonia spp.) (such as Rhizoctonia solani); Fusarium species diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum ); Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora betic ); and other types and strains closely related to these pathogens.
  • composition or combination is also effective against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae and others.
  • the strain has resistance activity.
  • the use method of the fungicide composition of the present invention is simple. Before or after the germination of the plant disease, it is applied to the crops and the place where the crops grow according to conventional methods, such as soil mixing, spraying, spraying, pouring, etc.
  • the application amount is based on the climatic conditions Or depending on the crop status, usually 10-5000g per mu, diluted to 10-400mg/L (preferably 100-300mg/L) for application.
  • the diluent is preferably water.
  • the bactericidal effect of the fungicidal composition of the present invention is usually related to external factors such as climate, but the influence of climate can be mitigated by using an appropriate formulation.
  • composition of the present invention can also be mixed with other compounds with bactericidal, insecticidal or herbicidal properties, and can also be used with nematicides, acaricides, protective agents, herbicide safeners, growth regulators, phytonutrients or soil regulators And so on mixed use.
  • the compound of the present invention can be prepared by the method described in the present invention, unless there is further description, wherein the definition of each substituent is as described in the present invention.
  • the chemical reactions described in the present invention can be used to appropriately prepare many other compounds of the present invention, and other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention.
  • the synthesis of non-exemplified compounds according to the present invention can be successfully completed by those skilled in the art through modification methods, such as appropriate protection of interfering groups, by using other known reagents (in addition to those described in the present invention), Or make some conventional modifications to the reaction conditions.
  • the reactions disclosed in the present invention or known reaction conditions are also recognized to be applicable to the preparation of other compounds of the present invention.
  • the reaction in the present invention is carried out at room temperature, wherein the room temperature is 0-35°C.
  • Proton NMR of the present invention the test conditions: at room temperature, Bruker (Bruker) 400MHz or a 600MHz NMR instrument, to CDC1 3, d 6 -DMSO, CD 3 OD or d 6 - acetone solutions (reported in ppm Unit), using TMS (0ppm) or chloroform (7.26ppm) as the reference standard.
  • s singlet
  • d doublet, doublet
  • t triplet, triplet
  • q quartet, quartet
  • m multiplet, Multiplet
  • br broadened, broad peak
  • dd doublet of doublets, doublet of doublets
  • dt doublet of triplets, doublet of triplets.
  • the coupling constant is expressed in Hertz (Hz).
  • the mass spectrometry test conditions used in the present invention are: low-resolution mass spectrometry (MS) data determination conditions are: Agilent 6120 Quadrupole HPLC-MS (column model: Zorbax SB-C18, 2.1x 30mm, 3.5 ⁇ m, 6min, flow rate is 0.6mL/ min, mobile phase: the ratio of 5%-95% (CH 3 CN containing 0.1% formic acid) in (H 2 O containing 0.1% formic acid)), UV detection at 210/254nm, using electrospray ionization mode (ESI).
  • MS mass spectrometry
  • the target compound of formula (I-1) can be prepared through synthetic scheme one.
  • the compound of formula (a) and the compound of formula (b) undergo a condensation reaction to obtain the compound of formula (c);
  • the compound of formula (c) and the intermediate O undergo a nucleophilic substitution reaction to obtain the target compound of formula (I-1);
  • R 4 , R 5 and R 6 have the meanings described in the present invention.
  • Step B Synthesis of 3,3'-disulfanediyl bis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide)
  • Step C Synthesis of 1-(N,N-dimethylaminosulfonyl)-1H-1,2,4-triazole-3-sulfonyl chloride
  • the solution was transferred to a separatory funnel, left to stand for liquid separation, the organic phase was washed three times with water (30 mL), and the solvent was evaporated under reduced pressure with a rotary evaporator to obtain 48.11 g of white powder with a yield of 87.8%.
  • Test target Cucumber Downy Mildew, Cucumber Powdery Mildew
  • Test treatment The compound was dissolved into 1% EC with DMF for later use.
  • the in vivo pot method was used to evaluate the bactericidal activity of these compounds against test targets at 200 ppm, 100 ppm, 50 ppm, and 25 ppm.
  • Example 18 Compound Control effect (%) Compound Control effect (%) Example 2 90 Example 3 80 Example 4 80 Example 5 100 Example 7 80 Example 8 100 Example 9 90 Example 17 80 Example 18 90 Example 20 90 Example 21 100 Example 22 100 Example 23 80 Example 24 80 Example 25 90 Example 26 80 Example 27 100 Example 28 100 Example 29 100 Example 30 100 Example 31 100 Example 32 100 Example 33 100 Example 34 100 Example 35 100 Example 36 100 Example 37 80 Example 38 90
  • Example 27 In addition, at a concentration of 50 ppm, the compound of the present invention in Example 27, Example 29, Example 31, Example 32, Example 36, Example 42, Example 43 and Example 44 still had the effect of preventing cucumber downy mildew. Above 80%; at a concentration of 200 ppm, the compounds of Example 27 and Example 32 of the present invention also have 80% control effect on cucumber powdery mildew.

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Abstract

提供了一种三唑磺酰胺衍生物及其制备方法和应用；具体地，提供了式（I）所示的三唑磺酰胺衍生物或式（I）所示三唑磺酰胺衍生物的立体异构体、氮氧化物或其盐，及三唑磺酰胺衍生物的制备方法，及它们在农业中作为杀菌剂的用途，及其杀菌剂组合物的形式，以及用这些化合物或组合物来防治植物病害的方法；其中，R 1、R 2、R 3、x、R 4、R 5和R 6具有本发明所述的含义。（I）

Description

三唑磺酰胺衍生物及其制备方法和应用 技术领域
本发明涉及农药领域，具体地，本发明涉及一种三唑磺酰胺衍生物、三唑磺酰胺衍生物的制备方法及其在农业中作为植物病害防治剂的应用。
背景技术
具有生物活性的三唑磺酰胺类衍生物是新农药开发研究的目标之一，其中日产化学开发的吲唑磺菌胺对由卵菌纲引起的植物疫病和霜霉病具有较高的活性。卵菌纲病害是果蔬作物上非常常见及危害较为严重的一类病害，其造成的损失也是不容忽视的。但目前为止，能够有效防止卵菌纲病害的药剂并不是很多，而三唑磺酰胺类衍生物具有相当的可拓展性和结构改造潜力(如WO 2017143803、CN 106905251等)。本发明公开的新型三唑磺酰胺衍生物未见报道。
发明内容
本发明提供一种新的三唑磺酰胺衍生物，该类衍生物对植物病原真菌的防治效果好，可作为杀菌剂进行进一步地开发。
具体地，一方面，本发明提供一种化合物，其为具有式(I)所示的化合物或式(I)所示的化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
Figure PCTCN2019097704-appb-000001
其中，
R 1和R 2各自独立地为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-或C 6-10芳基-C 1-6烷基-；其中，所述的C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-或C 6-10芳基-C 1-6烷基-任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、氨基、C 1-6烷基、卤代C 1-6烷基、C 1-6烷氧基或卤代C 1-6烷氧基的取代基取代；
或R 1、R 2和与之相连的氮原子一起形成任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、氨基、C 1-6烷基、卤代C 1-6烷基、C 1-6烷氧基或卤代C 1-6烷氧基取代的3-10元杂环基或5-10元杂芳基；
R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、C 1-6烷基、C 2-6烯基、C 2-6炔基、卤代C 1-6烷基、卤代C 2-6烯基、卤代C 2-6炔基、C 6-10芳基、卤代C 6-10芳基、C 6-10芳基-C 1-6烷基-或卤代C 6-10芳基-C 1-6烷基-；
x为0、1或2；
R 4为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-、C 6-10芳基-C 1-6烷基-、5-6元杂芳基、-C(＝O)OC 1-6烷基、R mS(＝O) 2-或-C(＝O)R n；
R m和R n各自独立地为C 1-6烷基或C 6-10芳基；
其中，R 4任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代；
R 5为C 6-10芳基或5-10元杂芳基；其中，R 5任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代；
R 6为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 3-8环烷基-C 1-6烷基-、苯基或苯基-C 1-6烷基-；
或R 5、R 6和与之相连接的碳原子形成C 9-10芳基或9-10元杂芳基；所述的C 9-10芳基和9-10元杂芳基 任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代。
在一些实施方案中，R 1和R 2各自独立地为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基、C 6-10芳基、C 3-6环烷基-C 1-3烷基-或C 6-10芳基-C 1-3烷基-。
还在一些实施方案中，R 1和R 2各自独立地为C 1-4烷基。
还在一些实施方案中，R 1和R 2各自独立地为氢、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-CH 2CH 2CH 2CH 3、-CH(CH 3)CH 2CH 3、-CH 2CH(CH 3) 2、-C(CH 3) 3、-CH＝CH 2、-CH 2CH＝CH 2、-CH＝CHCH 3、-CH 2CH 2CH＝CH 2、-CH 2CH＝CHCH 3、-CH＝CHCH 2CH 3、-C≡CH、-CH 2-C≡CH、-CH 2CH 2-C≡CH、环丙基、环丁基、环戊基、环己基、苯基或苄基。
又还在一些实施方案中，R 1和R 2各自独立地为-CH 3。
在一些实施方案中，R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、C 1-4烷基、C 2-4烯基、C 2-4炔基、卤代C 1-4烷基、卤代C 2-4烯基、卤代C 2-4炔基、C 6-10芳基、卤代C 6-10芳基、C 6-10芳基-C 1-3烷基-或卤代C 6- 10芳基-C 1-3烷基-。
还在一些实施方案中，R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-C(CH 3) 3、-CH 2Cl、-CHF 2或-CF 3。
又还在一些实施方案中，R 3为氢。
在一些实施方案中，R 4为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基、苯基、苄基、C 3-6环烷基-C 1-3烷基-、吡啶基、吡嗪基、哒嗪基、-C(＝O)OC 1-4烷基、R mS(＝O) 2-或-C(＝O)R n；
R m和R n各自独立地为C 1-4烷基或苯基；
其中，R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
还在一些实施方案中，R 4为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基、苯基、苄基、C 3-6环烷基-C 1-3烷基-、吡啶基、吡嗪基、哒嗪基、-C(＝O)OC 1-4烷基、R mS(＝O) 2-或-C(＝O)R n；
R m和R n各自独立地为C 1-4烷基或苯基；
其中，R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、CH 3-或CF 3-取代基取代。
还在一些实施方案中，R 4为氢、C 1-4烷基、-C(＝O)OC 1-4烷基、苯基-S(＝O) 2-或-C(＝O)R n；
R n为C 1-4烷基或苯基；
其中，R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
还在一些实施方案中，R 4为氢、C 1-4烷基、-C(＝O)OC 1-4烷基、苯基-S(＝O) 2-或-C(＝O)R n；
R n为C 1-4烷基或苯基；
其中，R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、CH 3-或CF 3-取代基取代。
还在一些实施方案中，R 4为氢、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-C(＝O)CH 3或-C(＝O)OCH 3；
或R 4为以下子结构式：
Figure PCTCN2019097704-appb-000002
Figure PCTCN2019097704-appb-000003
在一些实施方案中，R 5为C 6-10芳基或5-10元杂芳基；其中，R 5任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
还在一些实施方案中，R 5为C 6-10芳基或5-9元杂芳基；其中，R 5任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
在一些实施方案中，R 5为苯基、萘基、吡啶基、吡咯基、噻吩基、呋喃基、咪唑基、吡唑基、恶唑基、异恶唑基、噻唑基、1H-1,2,4-三唑基或1H-吲哚基；
其中，R 5任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
或R 5、R 6和与之相连接的碳原子形成
Figure PCTCN2019097704-appb-000004
还在一些实施方案中，R 5为苯基、萘-1-基、吡啶-2-基、吡啶-3-基、1H-吡咯-2-基、噻吩-2-基、噻吩-3-基、1H-咪唑-1-基、异恶唑-3-基、1H-吲哚-3-基或1H-吲哚-4-基；
其中，R 5任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代。
还在一些实施方案中，R 5为苯基、萘-1-基、吡啶-2-基、吡啶-3-基、1H-吡咯-2-基、噻吩-2-基、噻吩-3-基、1H-咪唑-1-基、异恶唑-3-基、1H-吲哚-3-基或1H-吲哚-4-基；
其中，R 5任选地被1、2或3个选自氟、氯、溴、碘、羟基、氰基、硝基、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-CH 2CH 2CH 2CH 3、-CH(CH 3)CH 2CH 3、-CH 2CH(CH 3) 2、-C(CH 3) 3、-OCH 3、-OCH 2CH 3、-OCH 2CH 2CH 3、-OCH(CH 3) 2、-OCH 2CH 2CH 2CH 3、-OCH(CH 3)CH 2CH 3、-OCH 2CH(CH 3) 2、-OC(CH 3) 3、-CF 3或-OCF 3的取代基取代。
在一些实施方案中，R 6为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基或苯基。
还在一些实施方案中，R 6为氢、C 1-4烷基或苯基。
还在一些实施方案中，R 6为氢、-CH 3或苯基。
还在一些实施方案中，
Figure PCTCN2019097704-appb-000005
为以下子结构式：
Figure PCTCN2019097704-appb-000006
Figure PCTCN2019097704-appb-000007
还在一些实施方案中，本发明提供一种化合物，其为具有式(II)所示的化合物或式(II)所示的化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
Figure PCTCN2019097704-appb-000008
其中，R 4和R 5具有本发明所述的含义。
还在一些实施方案中，本发明提供一种化合物，其为具有式(II)所示的化合物或式(II)所示的化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
Figure PCTCN2019097704-appb-000009
其中，
R 4为氢、C 1-4烷基、-C(＝O)OC 1-4烷基、R mS(＝O) 2-或-C(＝O)R n；
R m为任选地被1或2个卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基取代的苯基；
R n为C 1-4烷基或任选地被卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1- 4烷氧基取代的苯基；
R 5为任选地被1、2或3个卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基取代的苯基、萘基、任选地被1或2个卤素取代的吡啶-2-基或吡啶-3-基、任选地被C 1-4烷基取代的1H-吡咯-2-基或异恶唑-3-基、噻吩-3-基、噻吩-2-基、1H-咪唑-1-基、1H-吲哚-3-基或1H-吲哚-4-基。
还在一些实施方案中，R 4为氢、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-C(＝O)CH 3或-C(＝O)OCH 3；
或R 4为以下子结构式：
Figure PCTCN2019097704-appb-000010
还在一些实施方案中，R 5为任选地被1、2或3个氟、氯、溴、碘、羟基、氰基、硝基、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-CH 2CH 2CH 2CH 3、-CH(CH 3)CH 2CH 3、-CH 2CH(CH 3) 2、-C(CH 3) 3、-OCH 3、-OCH 2CH 3、-OCH 2CH 2CH 3、-OCH(CH 3) 2、-CF 3或-OCF 3取代的苯基、萘-1-基、任选地被1或2个氟、氯、溴或碘取代的吡啶-2-基或吡啶-3-基、任选地被-CH 3、-CH 2CH 3、-CH 2CH 2CH 3或-CH(CH 3) 2取代的1H-吡咯-2-基或异恶唑-3-基、噻吩-3-基、噻吩-2-基、1H-咪唑-1-基、1H-吲哚-3-基或1H-吲哚-4-基。
又还在一些实施方案中，R 5为以下子结构式：
Figure PCTCN2019097704-appb-000011
Figure PCTCN2019097704-appb-000012
还在一些实施方案中，本发明提供一种化合物，其为具有式(III)所示的化合物或式(III)所示的化合物的立体异构体、氮氧化物或其盐：
Figure PCTCN2019097704-appb-000013
其中，R 4和R 5具有本发明所述的含义。
还在一些实施方案中，本发明提供一种化合物，其为具有下列之一结构的化合物或具有下列之一结构化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
Figure PCTCN2019097704-appb-000014
Figure PCTCN2019097704-appb-000015
Figure PCTCN2019097704-appb-000016
Figure PCTCN2019097704-appb-000017
另一方面，本发明提供一种组合物，其包含至少一种本发明所述的化合物。
进一步地，本发明所述的组合物包含农药学上可接受的表面活性剂和/或载体。
又另一方面，本发明提供本发明所述的化合物或本发明所述的组合物在农业中作为植物病害防治剂的应用。
又另一方面，本发明提供一种本发明化合物或本发明组合物防治植物病害的方法。
进一步地，本发明提供一种在植物病害萌发前或萌发后，向植物或植物生长场所施用本发明所述化合 物或本发明所述组合物的方法。
本发明的详细说明
定义和一般术语
现在详细描述本发明的某些实施方案，其实例由随附的结构式和化学式说明。本发明意图涵盖所有的替代、修改和等同技术方案，它们均包括在如权利要求定义的本发明范围内。本领域技术人员应认识到，许多与本发明所述类似或等同的方法和材料能够用于实践本发明。本发明绝不限于本发明所述的方法和材料。在所结合的文献、专利和类似材料的一篇或多篇与本申请不同或相矛盾的情况下(包括但不限于所定义的术语、术语应用、所描述的技术，等等)，以本申请为准。
应进一步认识到，本发明的某些特征，为清楚可见，在多个独立的实施方案中进行了描述，但也可以在单个实施例中以组合形式提供。反之，本发明的各种特征，为简洁起见，在单个实施方案中进行了描述，但也可以单独或以任意适合的子组合提供。
除非另外说明，本发明所使用的所有科技术语具有与本发明所属领域技术人员的通常理解相同的含义。本发明涉及的所有专利和公开出版物通过引用方式整体并入本发明。
除非另外说明，应当应用本发明所使用的下列定义。出于本发明的目的，化学元素与元素周期表CAS版，和《化学和物理手册》，第75版，1994一致。此外，有机化学一般原理可参考"Organic Chemistry",Thomas Sorrell,University Science Books,Sausalito:1999,和"March's Advanced Organic Chemistry"by Michael B.Smith and Jerry March,John Wiley&Sons,New York:2007中的描述，其全部内容通过引用并入本发明。
除非另有说明或者上下文中有明显的冲突，本发明所使用的冠词“一”、“一个(种)”和“所述”旨在包括“至少一个”或“一个或多个”。因此，本发明所使用的这些冠词是指一个或多于一个(即至少一个)宾语的冠词。例如，“一组分”指一个或多个组分，即可能有多于一个的组分被考虑在所述实施方案的实施方式中采用或使用。
术语“包含”为开放式表达，即包括本发明所指明的内容，但并不排除其他方面的内容。
“立体异构体”是指具有相同化学构造，但原子或基团在空间上排列方式不同的化合物。立体异构体包括对映异构体、非对映异构体、构象异构体(旋转异构体)、几何异构体(顺/反)异构体、阻转异构体，等等。
“对映异构体”是指一个化合物的两个不能重叠但互成镜像关系的异构体。
“非对映异构体”是指有两个或多个手性中性并且其分子不互为镜像的立体异构体。非对映异构体具有不同的物理性质，如熔点、沸点、光谱性质和反应性。非对映异构体混合物可通过高分辨分析操作如电泳和色谱，例如HPLC来分离。
本发明所使用的立体化学定义和规则一般遵循S.P.Parker,Ed.,McGraw-Hill Dictionary of Chemical Terms(1984)McGraw-Hill Book Company,New York；and Eliel,E.and Wilen,S.,“Stereochemistry of Organic Compounds”,John Wiley&Sons,Inc.,New York,1994中的描述。
许多有机化合物以光学活性形式存在，即它们具有使平面偏振光的平面发生旋转的能力。在描述光学活性化合物时，使用前缀D和L或R和S来表示分子关于其一个或多个手性中心的绝对构型。前缀d和l或(+)和(-)是用于指定化合物所致平面偏振光旋转的符号，其中(-)或l表示化合物是左旋的。前缀为(+)或d的化合物是右旋的。一种具体的立体异构体是对映异构体，这种异构体的混合物称作对映异构体混合物。对映异构体的50:50混合物称为外消旋混合物或外消旋体，当在化学反应或过程中没有立体选择性或立体特异性时，可出现这种情况。
本发明公开化合物的任何不对称原子(例如，碳等)都可以以外消旋或对映体富集的形式存在，例如(R)-、(S)-或(R,S)-构型形式存在。在某些实施方案中，各不对称原子在(R)-或(S)-构型方面具有至少50％对映体过量，至少60％对映体过量，至少70％对映体过量，至少80％对映体过量，至少90％对映体过 量，至少95％对映体过量，或至少99％对映体过量。
依据起始物料和方法的选择，本发明化合物可以以可能的异构体中的一个或它们的混合物，例如外消旋体和非对应异构体混合物(这取决于不对称碳原子的数量)的形式存在。光学活性的(R)-或(S)-异构体可使用手性合成子或手性试剂制备，或使用常规技术拆分。如果化合物含有一个双键，取代基可能为E或Z构型；如果化合物中含有二取代的环烷基，环烷基的取代基可能有顺式或反式构型。
所得的任何立体异构体的混合物可以依据组分物理化学性质上的差异被分离成纯的或基本纯的几何异构体，对映异构体，非对映异构体，例如，通过色谱法和/或分步结晶法。
可以用已知的方法将任何所得终产物或中间体的外消旋体通过本领域技术人员熟悉的方法拆分成光学对映体，如，通过对获得的其非对映异构的盐进行分离。外消旋的产物也可以通过手性色谱来分离，如，使用手性吸附剂的高效液相色谱(HPLC)。特别地，对映异构体可以通过不对称合成制备。
像本发明所描述的，本发明的化合物可以任选地被一个或多个取代基所取代，如上面的通式化合物，或者像实施例里面特殊的例子，子类，和本发明所包含的一类化合物。应了解“任选取代的”这个术语与“取代或非取代的”这个术语可以交换使用。一般而言，术语“取代的”表示所给结构中的一个或多个氢原子被具体取代基所取代。除非其他方面表明，一个任选的取代基团可以在基团各个可取代的位置进行取代。当所给出的结构式中不只一个位置能被选自具体基团的一个或多个取代基所取代，那么取代基可以相同或不同地在各个位置取代。具体地，“一个或多个”的实例是指1、2、3、4、5、6、7、8、9或10个。其中所述的取代基可以是，但并不限于，氘，氟，氯，溴，碘，氰基，羟基，硝基，氨基，羧基，烷基，烷氧基，烷氧基烷基，烷氧基烷氧基，烷氧基烷氨基，芳氧基，杂芳基氧基，杂环基氧基，芳基烷氧基，杂芳基烷氧基，杂环基烷氧基，环烷基烷氧基，烷氨基，烷氨基烷基，烷氨基烷氨基，环烷基氨基，环烷基烷氨基，烷硫基，卤代烷基，卤代烷氧基，羟基取代的烷基，羟基取代的烷氨基，氰基取代的烷基，氰基取代的烷氧基，氰基取代的烷氨基，氨基取代的烷基，烷基酰基，杂烷基，环烷基，环烯基，环烷基烷基，杂环基，杂环基烷基，杂环基酰基，芳基，芳基烷基，芳氨基，杂芳基，杂芳基烷基，杂芳基氨基，酰胺基，磺酰基，氨基磺酰基等等。
另外，需要说明的是，除非以其他方式明确指出，在本发明中所采用的描述方式“各…独立地为”与“…各自独立地为”和“…独立地为”可以互换，均应做广义理解，其既可以是指在不同基团中，相同符号之间所表达的具体选项之间互相不影响，也可以表示在相同的基团中，相同符号之间所表达的具体选项之间互相不影响。
在本说明书的各部分，本发明公开化合物的取代基按照基团种类或范围公开。特别指出，本发明包括这些基团种类和范围的各个成员的每一个独立的次级组合。例如，术语“C 1-C 6烷基”或“C 1-6烷基”特别指独立公开的甲基、乙基、C 3烷基、C 4烷基、C 5烷基和C 6烷基。
本发明使用的术语“烷基”或“烷基基团”，表示含有1至20个碳原子，饱和的直链或支链一价烃基基团；其中所述烷基基团任选地被一个或多个本发明描述的取代基所取代。除非另外详细说明，烷基基团含有1-20个碳原子。在一实施方案中，烷基基团含有1-12个碳原子；在一实施方案中，烷基基团含有1-8个碳原子；在另一实施方案中，烷基基团含有1-6个碳原子；在又一实施方案中，烷基基团含有1-4个碳原子；还在一实施方案中，烷基基团含有1-3个碳原子。
烷基基团的实例包含，但并不限于，甲基(Me、-CH 3)，乙基(Et、-CH 2CH 3)，正丙基(n-Pr、-CH 2CH 2CH 3)，异丙基(i-Pr、-CH(CH 3) 2)，正丁基(n-Bu、-CH 2CH 2CH 2CH 3)，异丁基(i-Bu、-CH 2CH(CH 3) 2)，仲丁基(s-Bu、-CH(CH 3)CH 2CH 3)，叔丁基(t-Bu、-C(CH 3) 3)，正戊基(-CH 2CH 2CH 2CH 2CH 3)，2-戊基(-CH(CH 3)CH 2CH 2CH 3)，3-戊基(-CH(CH 2CH 3) 2)，2-甲基-2-丁基(-C(CH 3) 2CH 2CH 3)，3-甲基-2-丁基(-CH(CH 3)CH(CH 3) 2)，3-甲基-1-丁基(-CH 2CH 2CH(CH 3) 2)，2-甲基-1-丁基(-CH 2CH(CH 3)CH 2CH 3)，等等。
术语“烷氧基”表示烷基基团通过氧原子与分子其余部分相连，其中烷基基团具有如本发明所述的含义。烷氧基基团的实例包括，但并不限于，甲氧基(MeO、-OCH 3)，乙氧基(EtO、-OCH 2CH 3)，1-丙氧基(n-PrO、n-丙氧基、-OCH 2CH 2CH 3)，2-丙氧基(i-PrO、i-丙氧基、-OCH(CH 3) 2)等等。
术语“烯基”表示含有2-12个碳原子的直链或支链一价烃基，其中至少有一个不饱和位点，即有一个碳-碳sp 2双键，其中，所述烯基基团可以任选地被一个或多个本发明所描述的取代基所取代，其包括“cis”和“tans”的定位，或者“E”和“Z”的定位。在一实施方案中，烯基基团包含2-8个碳原子；在另一实施方案中，烯基基团包含2-6个碳原子；在又一实施方案中，烯基基团包含2-4个碳原子。烯基基团的实例包括，但并不限于，乙烯基(-CH＝CH 2)，烯丙基(-CH 2CH＝CH 2)，丙烯基(CH 3-CH＝CH-)，氧代的丁烯基(CH 3-C(＝O)-CH＝CH-)等等。
术语“炔基”表示含有2-12个碳原子的直链或支链一价烃基，其中至少有一个碳-碳sp三键。在一实施方案中，炔基基团包含2-8个碳原子；在另一实施方案中，炔基基团包含2-6个碳原子；在又一实施方案中，炔基基团包含2-4个碳原子。炔基基团的实例包括，但并不限于，-C≡CH、-CH 2-C≡CH、-CH 2-C≡CCH 3、-CH 2CH 2-C≡CH、-CH 2-C≡CCH 2CH 3等等。
术语“环烷基”表示含有3-12个碳原子的，单价或多价的饱和单环、双环或三环体系。在一实施方案中，环烷基包含3-10个碳原子；在另一实施方案中，环烷基包含3-8个碳原子；在又一实施方案中，环烷基包含3-6个碳原子。所述环烷基基团任选地被一个或多个本发明所描述的取代基所取代。这样的实例包括，但并不限于，环丙基，环丁基，环戊基，环己基，环庚基，环辛基，环壬基，环癸基，环十一烷基，环十二烷基，等等。
术语“环烷基烷基”表示烷基基团中的氢原子被一个或多个环烷基基团所取代，其中烷基和环烷基基团具有如本发明所述的含义。
术语“卤素”是指氟(F)、氯(Cl)、溴(Br)或碘(I)。
术语“卤代烷基”表示烷基基团被一个或多个卤素原子所取代，这样的实例包含，但并不限于，-CF 3，-CHF 2，-CH 2Cl，-CH 2CF 3，-CH 2CHF 2，-CH 2CH 2CF 3等等。
术语“卤代烷氧基”表示烷氧基基团被一个或多个卤素原子所取代，这样的实例包含，但并不限于，-OCF 3，-OCHF 2，-OCHCl 2，-OCH 2CHF 2，-OCH 2CHCl 2，-OCH(CH 3)CHF 2等等。
术语“杂环基”术语“杂环基”和“杂环”在此处可交换使用，都是指包含3-15个环原子的饱和或部分不饱和的单环、双环或三环，其中单环、双环或三环中不包含芳香环，且至少一个环原子选自氮、硫和氧原子。除非另外说明，杂环基可以是碳基或氮基，且-CH 2-基团可以任选地被-C(＝O)-替代。环的硫原子可以任选地被氧化成S-氧化物。环的氮原子可以任选地被氧化成N-氧化合物。
术语“3-12元杂环基”，“3-10元杂环基”，“3-8元杂环基”或“3-6元杂环基”，其中“3-12元”、“3-10元”、“3-8元”或“3-6元”典型地描述分子中成环原子的数目。例如，哌啶基是6元杂环基。
术语“芳基”表示含有6-14个环原子，或6-12个环原子，或6-10个环原子的单环、双环和三环的碳环体系，其中，至少一个环体系是芳香族的，其中每一个环体系包含3-7个原子组成的环，且有一个或多个附着点与分子的其余部分相连。术语“芳基”可以和术语“芳香环”交换使用。芳基基团的实例可以包括苯基，茚基，萘基和蒽基。所述芳基基团任选地被一个或多个本发明所描述的取代基所取代。
术语“芳基烷基”表示烷基基团中的氢原子被一个或多个芳基基团所取代，其中烷基和芳基基团具有如本发明所述的含义。这样的实例包括，但并不限于，苄基，苯乙基等等。
术语“杂芳基”表示含有5-12个环原子，或5-10个环原子，或5-6个环原子的单环、双环和三环体系，其中至少一个环体系是芳香族的，且至少一个环体系包含一个或多个杂原子，其中每一个环体系包含5-7个原子组成的环，且有一个或多个附着点与分子其余部分相连。术语“杂芳基”可以与术语“杂芳环”或“杂芳族化 合物”交换使用。所述杂芳基基团任选地被一个或多个本发明所描述的取代基所取代。在一实施方案中，5-10个原子组成的杂芳基包含1，2，3或4个独立选自O，S和N的杂原子。杂芳基的实例可以包括吡啶基、吡咯基、噻吩基、呋喃基、咪唑基、吡唑基、恶唑基、异恶唑基、噻唑基、1,2,4-三唑基、吲哚基等等。
术语“5-9元杂芳基”、“5-10元杂芳基”、“9-10元杂芳基”或“5-6元杂芳基”，其中“5-9元”、“5-10元”、“9-10元”、“5-6元”典型地描述分子中成环原子的数目。例如，吡啶基是6元杂芳基。
在本发明书的各部分，描述了连接取代基。当该结构清楚地需要连接基团时，针对该基团所列举的马库什变量应理解为连接基团。例如，如果该结构需要连接基团并且针对该变量的马库什基团定义列举了“烷基”或“芳基”，则应当理解，该“烷基”或“芳基”分别代表连接的亚烷基基团或亚芳基基团。
术语“亚烷基”表示从饱和烃基中去掉两个氢原子所得到的饱和的二价烃基基团。除非另外详细说明，亚烷基基团含有1-12个碳原子，另外一些实施例是，亚烷基基团含有1-6个碳原子，另外一些实施例是，亚烷基基团含有1-4个碳原子，另外一些实施例是，亚烷基基团含有1-2个碳原子。这样的实例包括亚甲基(-CH 2-)，亚乙基(-CH 2CH 2-)，亚异丙基(-CH(CH 3)CH 2-)等等。
术语“卤代烯基”表示烯基基团被一个或多个卤素原子所取代。
术语“卤代炔基”表示炔基基团被一个或多个卤素原子所取代。
术语“卤代芳基”表示芳基基团被一个或多个卤素原子所取代。
术语“卤代芳基烷基”表示“芳基烷基”基团被一个或多个卤素原子所取代。
其中，R 5和R 6不同时，
Figure PCTCN2019097704-appb-000018
可以表示为(E)型异构体、(Z)型异构体或(E)型异构体和(Z)型异构体的混合物；其中所述的(E)型异构体对应
Figure PCTCN2019097704-appb-000019
型异构体对应
Figure PCTCN2019097704-appb-000020
体异构体、(E)体异构体或(Z)体异构体和(E)体异构体的混合物可以通过常规方法进行分离、确认，如高效液相色谱法、核磁共振氢谱法和/或单晶衍射法。
本发明所述化合物的盐，包括衍生自碱金属或碱土金属的那些以及衍生自氨和胺的那些。优选的阳离子包括钠、钾、镁以及具有化学式N +(R AR BR CR D)的铵阳离子，其中R A、R B、R C和R D独立地选自氢、C 1-C 6烷基和C 1-C 6羟基烷基。具有式(I)、式(II)或式(III)的化合物的盐可以通过用金属氢氧化物(例如氢氧化钠)或胺(例如氨、三甲胺、二乙醇胺、2-甲硫基丙胺、双烯丙基胺、2-丁氧基乙胺、吗啉、环十二胺或苄胺)对具有式(I)、式(II)或式(III)化合物进行处理来制备。
当本发明的化合物包含一个碱部分时，可接受的盐可以由有机酸和无机酸形成，例如乙酸、丙酸、乳酸、柠檬酸、酒石酸、琥珀酸、富马酸、马来酸、丙二酸、扁桃酸、苹果酸、邻苯二甲酸、盐酸、氢溴酸、磷酸、硝酸、硫酸、甲磺酸、萘磺酸、苯磺酸、甲苯磺酸、樟脑磺酸以及类似地已知可接受的酸。
本发明化合物的组合物和制剂
本发明的化合物一般可用作组合物或制剂中的杀菌剂活性成分，通常还包括农药学上可接受表面活性剂和/或载体。
上述表面活性剂可以为农药制剂领域所公知的各种表面活性剂，如阴离子表面活性剂、阳离子表面活性剂、非离子表面活性剂和两性表面活性剂，嵌段聚合物，聚电解质，以及它们的混合物。该类表面活性剂可以用作乳化剂、分散剂、润湿剂、渗透促进剂或辅助剂。
合适的阴离子表面活性剂是磺酸、硫酸、磷酸、羧酸的碱金属、碱土金属或铵盐以及它们的混合物。磺酸盐的实例是烷基芳基磺酸盐、二苯基磺酸盐、α-烯烃磺酸盐、木素磺酸盐、脂肪酸和油的磺酸盐、乙氧基化烷基酚的磺酸盐、烷氧基化芳基酚的磺酸盐、缩合萘的磺酸盐、十二烷基-和十三烷基苯的磺酸盐、萘和烷基萘的磺酸盐、磺基琥珀酸盐或磺基琥珀酰胺酸盐。硫酸盐的实例是脂肪酸和油的硫酸盐、乙氧基化烷基酚的硫酸盐、醇的硫酸盐、乙氧基化醇的硫酸盐或脂肪酸酯的硫酸盐。磷酸盐的实例是磷酸盐酯。羧酸盐的实例是烷基羧酸盐以及羧化醇或烷基酚乙氧基化物。
合适的非离子表面活性剂是烷氧基化物，N-取代的脂肪酸酰胺，胺氧化物，酯类，糖基表面活性剂，聚合物表面活性剂及其混合物。烷氧基化物的实例是诸如已经被1-50当量烷氧基化的醇、烷基酚、胺、酰胺、芳基酚、脂肪酸或脂肪酸酯的化合物。可以将氧化乙烯和/或氧化丙烯用于烷氧基化，优选氧化乙烯。N-取代的脂肪酸酰胺的实例是脂肪酸葡糖酰胺或脂肪酸链烷醇酰胺。酯类的实例是脂肪酸酯，甘油酯或甘油单酯。糖基表面活性剂的实例是脱水山梨醇、乙氧基化脱水山梨醇、蔗糖和葡萄糖酯或烷基聚葡糖苷。聚合物表面活性剂的实例是乙烯基吡咯烷酮、乙烯醇或乙酸乙烯酯的均聚物或共聚物。
合适的阳离子表面活性剂是季型表面活性剂，例如具有1或2个疏水性基团的季铵化合物，或长链伯胺的盐。合适的两性表面活性剂是烷基甜菜碱和咪唑啉类。合适的嵌段聚合物是包含聚氧乙烯和聚氧丙烯的嵌段的A-B或A-B-A类型嵌段聚合物，或包含链烷醇、聚氧乙烯和聚氧丙烯的A-B-C类型嵌段聚合物。合适的聚电解质是聚酸或聚碱。聚酸的实例是聚丙烯酸的碱金属盐或聚酸梳状聚合物。聚碱的实例是聚乙烯基胺或聚乙烯胺。
上述载体可以为农药制剂领域所公知的各种载体，包括各种硅酸盐类、碳酸盐类、硫酸盐类、氧化物类、磷酸盐类、植物载体类、合成载体类。具体地，例如：白炭黑、高岭土、硅藻土、粘土、滑石、有机膨润土、浮石、二氧化钛、糊精、纤维素粉、轻质碳酸钙、可溶性淀粉、玉米淀粉、锯末粉、尿素、胺肥、尿素和胺肥的混合物、葡萄糖、麦芽糖、蔗糖、无水碳酸钾、无水碳酸钠、无水碳酸氢钾、无水碳酸氢钠、凹凸棒土、无水碳酸钾与无水碳酸氢钾的混合物和无水碳酸钠与无水碳酸氢钠的混合物中的一种或多种。
根据本发明的杀真菌剂组合物，该杀真菌剂组合物还可以含有农药制剂领域所常用的各种制剂用助剂，具体地，该制剂用助剂可以为溶剂、助溶剂、增稠剂、防冻剂、囊材、保护剂、消泡剂、崩解剂、稳定剂、防腐剂、粘合剂、螯合剂中的一种或多种。
合适的溶剂是水和有机溶剂，如中到高沸点的矿物油馏分，例如煤油、柴油；植物或动物来源的油；脂族、环状和芳族烃类，例如甲苯、石蜡、四氢萘、烷基化萘；醇类，如乙醇、丙醇、丁醇、苄醇、环己醇；二醇类；DMSO；酮类，例如环己酮；酯类，例如乳酸酯、碳酸酯、脂肪酸酯、γ-丁内酯；脂肪酸；膦酸酯；胺类；酰胺类，例如N-甲基吡咯烷酮，脂肪酸二甲基酰胺；以及它们的混合物。
上述溶剂也可以作为助溶剂使用。
合适的增稠剂选自多糖(例如黄原胶、羧甲基纤维素)、无机粘土(有机改性或未改性的)、聚羧酸盐和硅酸盐。
合适的防冻剂选自乙二醇、丙二醇、丙三醇、尿素、甘油及其它们的混合物。
合适的囊材选自聚氨酯、聚脲、脲醛树脂及其它们的混合物。
合适的保护剂选自聚乙烯醇和/或聚乙二醇。
合适的消泡剂选自聚硅氧烷、硅酮乳、长链醇、脂肪酸及其盐、以及含氟有机物及其它们的混合物。
合适的崩解剂选自膨润土、尿素、硫酸铵、氯化铝、柠檬酸、丁二酸、碳酸氢钠及其它们的混合物。
合适的稳定剂选自亚磷酸三苯酯、环氧氯丙烷、醋酐及其它们的混合物。
合适的防腐剂选自苯甲酸、苯甲酸钠、1,2-苯并异噻唑啉-3-酮(简称BIT)、卡松、山梨酸钾及其它们的混合物。
合适的粘合剂选自聚乙烯吡咯烷酮、聚乙酸乙烯酯、聚乙烯醇、聚丙烯酸酯、生物蜡或合成蜡以及纤维素醚。
本发明所述杀真菌剂可以以其制剂形式或由其制备的使用形式施用，所述使用形式例如气溶胶、胶囊悬浮剂、冷雾浓缩剂(cold-fogging concentrate)、热雾浓缩剂、胶囊化的颗粒剂、细颗粒剂、用于种子处理的流动性浓缩剂(flowable concentrate)、即用型溶液、可撒粉的粉剂、可乳化的浓缩剂、水包油乳剂、油包水乳剂、大颗粒剂、微颗粒剂、油分散性粉末剂、油混溶性流动浓缩剂、油混溶性液体、气剂(在压力下)、产气产品、泡沫剂、糊剂、悬浮浓缩剂、悬乳浓缩剂、可溶性浓缩剂、混悬剂、可湿性粉剂、可溶性粉剂、粉剂和颗粒剂、水溶性和水分散性的颗粒剂或片剂、用于种子处理的水溶性或水分散性粉剂，可湿性粉剂、经活性物质浸渍的天然产物及合成物质，以及聚合物和种子包衣材料中的微胶囊，以及ULV(ultra low volume)冷雾和热雾制剂。上述使用形式均可由本领域的常规手段制备得到。
本发明化合物及组合物的应用
本发明的化合物可用作植物病害防治剂，即作为杀菌剂使用。因此，本发明还可包括用于控制由植物病原真菌引起的植物病害的方法，所述方法包括向待保护植物或其部分或向待保护植物种子施用有效量的本发明的化合物或包含所述化合物的杀真菌组合物。本发明的化合物和/或组合物可对由担子菌纲、子囊菌纲、卵菌纲和半知菌纲广谱植物病原真菌引起的病害提供控制。它们可有效地控制广谱植物病害，尤其是观赏作物、草坪作物、蔬菜作物、大田作物、谷类作物和果树作物的叶片病原体。这些病原体包括：卵菌纲，包括疫霉属(Phytophthora)病害诸如致病疫霉菌(Phytophthora infestans)、大豆疫霉病菌(Phytophthora megasperma)、柑桔脚腐病菌(Phytophthora parasitica)、樟疫霉菌(Phytophthora cinnamomi)和南瓜疫病菌(Phytophthora capsici)的病害，草腐霉枯萎属(Pythium)物种病害诸如坪草腐霉枯萎病菌(Pythium aphanidermatum)的病害，以及霜霉科(Peronosporaceae)物种病害诸如葡萄霜霉病菌(Plasmopara viticola)，霜霉属病害(Peronospora spp.)(包括烟草霜霉菌(Peronospora tabacina)和寄生霜霉菌(Peronospora parasitica))，假霜霉属(Pseudoperonospora spp.)病害(包括黄瓜霜霉病菌(Pseudoperonospora cubensis)和盘梗霉菌病菌(Bremia lactucae))；子囊菌(包括链格孢属(Alternaria)病菌如番茄早疫病菌(Alternaria solani)和甘蓝黑斑病菌(Alternaria brassicae)，球座菌属(Guignardia)病害如葡萄黑腐病菌(Guignardia bidwell)，黑星菌属(Venturia)病害如苹果黑星病菌(Venturia inaequalis)，壳针孢属(Septoria)病害如颖枯病菌(Septoria nodorum)和叶枯病菌(Septoria tritici)，白粉(powdery mildew)病害如白粉菌属病菌(Erysiphe spp.)(包括小麦白粉病菌(Erysiphe graminis)和萝白粉病菌(Erysiphe polygoni))、葡萄白粉病菌(Uncinula necatur)、黄瓜白粉病菌(Sphaerotheca fuligena)和苹果白粉病菌(Podosphaera leucotricha)、小麦基腐病菌(Pseudocercosporella herpotrichoides)，灰霉菌属(Botrytis)病害如草莓灰霉病菌(Botrytis cinerea)、桃褐腐病菌(Monilinia fructicola)，菌核菌属(Sclerotinia)病害如油菜菌核病菌(Sclerotinia sclerotiorum)、稻瘟病菌(Magnaporthe grisea)、葡萄枝枯病菌(Phomopsis viticola)，蠕形菌属(Helminthosporium)病害如玉米大斑病菌(Helminthosporium tritici repentis)、网纹病菌(Pyrenophora teres)，炭疽病菌如黑果病菌(Glomerella)或炭疽菌属(Colletotrichum spp.)病害(如粱炭疽病菌(Colletotrichum graminicola)和西瓜炭疽病菌(Colletotrichum orbiculare))，和小麦全蚀病菌(Gaeumannomyces graminis)；担子菌，包括由锈菌属(Puccinia spp.)造成的锈菌病害(如隐匿柄锈菌(Puccinia recondita)、条锈菌(Puccinia striiformis)、叶锈菌(Puccinia hordei)、杆锈菌(Puccinia graminis)和柄锈菌(Puccinia arachidis))，咖啡锈菌(Hemileia vastatrix)和大豆锈菌(Phakopsora pachyrhizi)；其它病原体包括丝核菌属物种(Rhizoctonia spp.)(如立枯丝核菌(Rhizoctonia solani))；镰刀菌属(Fusarium)物种病害诸如粉红镰刀菌(Fusarium roseum)、禾谷镰刀菌(Fusarium graminearum)和尖孢镰刀菌(Fusarium oxysporum)；大丽轮枝菌(Verticillium dahliae)；白绢菌(Sclerotium rolfsii)；云纹菌(Rynchosporium secalis)；黑涩病菌 (Cercosporidium personatum)、黑斑病菌(Cercospora arachidicola)和褐斑病菌(Cercospora beticola)；以及其它与这些病原体密切相关的类别和菌种。除了它们的杀真菌活性之外，所述组合物或组合还对细菌诸如梨火疫病菌(Erwinia amylovora)、野油菜黄单胞菌(Xanthomonas campestris)、丁香假单胞菌(Pseudomonas syringae)以及其它菌种具有抵抗活性。
本发明的杀菌剂组合物的使用方法简单，在植物病害萌发之前或萌发之后，向作物及作物生长的场所按常规方法施用，如拌土、喷雾、喷射、浇注等，其施用量根据气候条件或作物状态而定，一般情况下每亩施用10-5000g，稀释成10-400mg/L(优选为100-300mg/L)施用。稀释剂优选为水。
本发明的杀菌剂组合物，其杀菌效果通常与外界因素如气候有关，但通过使用适当的剂型可以减缓气候的影响。
本发明的组合物还可与其它具有杀菌、杀虫或除草性能的化合物混合使用，也可与杀线虫剂、杀螨剂、防护剂、除草安全剂、生长调节剂、植物营养素或土壤调节剂等混合使用。
一般合成过程
在本说明书中，如果在化学名称和化学结构间存在任何差异，结构是占优的。一般地，本发明的化合物可以通过本发明所描述的方法制备得到，除非有进一步的说明，其中各取代基的定义如本发明所述。
所属领域的技术人员将认识到：本发明所描述的化学反应可以用来合适地制备许多本发明的其他化合物，且用于制备本发明的化合物的其它方法都被认为是在本发明的范围之内。例如，根据本发明那些非例证的化合物的合成可以成功地被所属领域的技术人员通过修饰方法完成，如适当的保护干扰基团，通过利用其他已知的试剂(除了本发明所描述的)，或将反应条件做一些常规的修改。另外，本发明所公开的反应或已知的反应条件也公认地适用于本发明其他化合物的制备。另外，在一些实施方案中，如无特殊说明，本发明所述的反应是在室温下进行，其中室温为0～35℃。
本发明核磁共振氢谱的测试条件是：室温条件下，布鲁克(Bruker)400MHz或600MHz的核磁仪，以CDC1 3，d 6-DMSO，CD 3OD或d 6-丙酮为溶剂(报导以ppm为单位)，用TMS(0ppm)或氯仿(7.26ppm)作为参照标准。当出现多重峰的时候，将使用下面的缩写：s(singlet，单峰)，d(doublet，双峰)，t(triplet，三重峰)，q(quartet，四重峰)，m(multiplet，多重峰)，br(broadened，宽峰)，dd(doublet of doublets，双二重峰)，dt(doublet of triplets，双三重峰)。偶合常数，用赫兹(Hz)表示。
本发明所用质谱测试条件为：低分辨率质谱(MS)数据测定的条件是：Agilent 6120 Quadrupole HPLC-MS(柱子型号：Zorbax SB-C18,2.1x 30mm,3.5μm,6min,流速为0.6mL/min，流动相：5％-95％(含0.1％甲酸的CH 3CN)在(含0.1％甲酸的H 2O)中的比例))，在210/254nm用UV检测，用电喷雾电离模式(ESI)。
下列合成方案描述了制备本发明公开化合物的步骤。
合成方案
合成方案一
Figure PCTCN2019097704-appb-000021
式(I-1)目标化合物可以通过合成方案一制备得到。式(a)化合物与式(b)化合物发生缩合反应得到 式(c)化合物；式(c)化合物与中间体O发生亲核取代反应得到式(I-1)目标化合物；
其中，R 4、R 5和R 6具有本发明所述的含义。
实施例
中间体O：1-(N,N-二甲胺基磺酰基)-1H-1,2,4-三氮唑-3-磺酰氯的合成
Figure PCTCN2019097704-appb-000022
步骤A：1,2-二(1H-1,2,4-三氮唑-3-基)二硫烷的合成
Figure PCTCN2019097704-appb-000023
将3-巯基-1,2,4-三氮唑(101.0g,1.00mol)溶于二氯甲烷(500mL)，加入吡啶(79.0g,1.00mol)，在0℃下，缓慢滴加苯磺酰氯(88.30g,0.50mol)，2h滴加完毕后，室温搅拌18h。用旋转蒸发仪减压蒸去二氯甲烷，剩余物在机械搅拌条件下加入水(500mL)，搅拌1h后，过滤，滤渣分别用水(800mL)和乙酸乙酯(300mL)洗涤，风干，得到黄色粉末95.2g，产率为95.2％。
LC-MS:(M+1)m/z＝201.1。
步骤B：3,3'-二硫烷二基双(N,N-二甲基-1H-1,2,4-三氮唑-1-磺酰胺)的合成
Figure PCTCN2019097704-appb-000024
氮气保护下，将1,2-二(1H-1,2,4-三氮唑-3-基)二硫烷(60.0g,0.30mol)溶于N,N-二甲基甲酰胺(300mL)，加入碳酸钾(69.0g,0.50mol)后，在0℃下，缓慢滴入N,N-二甲胺基磺酰氯(93.34g,0.65mol)，2h滴加完毕，继续反应6h。反应完成后，反应液缓慢倒入到水中，搅拌1h后，过滤，固体风干得到白色粉末107.2g，产率为86.3％。
LC-MS:(M+1)m/z＝415.0。
步骤C：1-(N,N-二甲胺基磺酰基)-1H-1,2,4-三氮唑-3-磺酰氯的合成
Figure PCTCN2019097704-appb-000025
将3,3'-二硫烷二基双(N,N-二甲基-1H-1,2,4-三氮唑-1-磺酰胺)(41.40g,0.10mol)溶于1,2-二氯乙烷(300mL)，加入水(300mL)，冷却至0℃，加入乙酸(100mL)，控制温度在10℃到25℃，在2小时内持续通入氯气(35.50g,0.50mol)，继续反应半小时。反应完成后，溶液转移至分液漏斗，静置分液，有机相用水(30mL)洗涤三次，用旋转蒸发仪减压蒸去溶剂，得到白色粉末48.11g，产率为87.8％。
LC-MS:(M+1)m/z＝274.8。
中间体O1：(E)-1-苯亚甲基-2-甲基肼的合成
Figure PCTCN2019097704-appb-000026
将含量40％的甲基肼(1.26g,11.0mmol)加入到100mL单口瓶中，并加入四氢呋喃(30mL)，在0℃下搅拌10分钟，再将苯甲醛(1.06g,10.0mmol)溶于四氢呋喃(10mL)，缓慢滴加至反应体系中，室温下反应3小时。TLC监测反应进度，待反应结束后，加水(20mL)淬灭，乙酸乙酯萃取(20mL x 3)，有机相用无水硫酸钠干燥，然后过滤，滤液用旋转蒸发仪减压除去溶剂，残留物经柱层析分离[乙酸乙酯/石油 醚(v/v)＝1/3]，得到白色固体1.26g，收率：94％。
1H NMR(400MHz,CDCl 3)δ(ppm):7.74(s,1H),7.52(dd,J＝7.1,2.1Hz,2H),7.34(dd,J＝6.4,2.3Hz,2H),5.62(s,1H),4.58(s,1H),3.53(s,3H)；
LC-MS:(M+1)m/z＝135.1。
参照中间体O1((E)-1-苯亚甲基-2-甲基肼)的制备方法，分别采用相应的肼与甲醛衍生物进行反应，即可得到表1中的中间体化合物。
表1
Figure PCTCN2019097704-appb-000027
Figure PCTCN2019097704-appb-000028
Figure PCTCN2019097704-appb-000029
Figure PCTCN2019097704-appb-000030
实施例1：(E)-3-((2-苯亚甲基-1-甲基肼)磺酰基)-N,N-二甲基-1H-1,2,4-三唑-1-磺酰胺的合成
Figure PCTCN2019097704-appb-000031
将中间体(E)-1-苯亚甲基-2-甲基肼(0.52g,4.0mmol)、吡啶(0.64g,8.0mmol)和四氢呋喃(30mL)加入到100mL的单口瓶中，室温搅拌均匀后，缓慢将1-(N,N-二甲胺基磺酰基)-1H-1,2,4-三氮唑-3-磺酰氯(1.64g,6.0mmol)加到反应体系中，室温下搅拌反应12小时后。加水(20mL)淬灭，用乙酸乙酯萃取(15mL x 3)，无水硫酸镁干燥，过滤，滤液用旋转蒸发仪减压除去溶剂，残留物经柱层析分离[乙酸乙酯/石油醚(v/v)＝1/3]，得到白色固体0.65g，收率：44％。
1H NMR(400MHz,CDCl 3)δ(ppm):8.58(s,1H),7.74(s,1H),7.62(dd,J＝7.1,2.1Hz,2H),7.37-7.32(m,3H),3.53(s,3H),2.95(s,6H)；
LC-MS:(M+1)m/z＝373.1。
参照实施例1的类似合成方法，将中间体O(1-(N,N-二甲胺基磺酰基)-1H-1,2,4-三氮唑-3-磺酰氯)分别表1中相应的中间体化合物与进行反应，即可得到表2中的目标化合物。
表2
Figure PCTCN2019097704-appb-000032
Figure PCTCN2019097704-appb-000033
Figure PCTCN2019097704-appb-000034
Figure PCTCN2019097704-appb-000035
Figure PCTCN2019097704-appb-000036
Figure PCTCN2019097704-appb-000037
Figure PCTCN2019097704-appb-000038
Figure PCTCN2019097704-appb-000039
Figure PCTCN2019097704-appb-000040
Figure PCTCN2019097704-appb-000041
Figure PCTCN2019097704-appb-000042
活性测试例
试验靶标：黄瓜霜霉病菌、黄瓜白粉病菌
试验处理：化合物用DMF溶解成1％EC备用。采用活体盆栽法，评价这些化合物在200ppm、100ppm、50ppm、25ppm下对试验靶标的杀菌活性。
1)黄瓜霜霉病菌测试(Pseudoperonosporacubensis)
选择1张真叶期(摘去生长点)长势一致的盆栽黄瓜苗，喷雾处理后自然晾干，处理后24小时后进行接种，取新鲜黄瓜霜霉病病叶，用毛笔蘸取蒸馏水洗下病叶背面孢子囊，配成孢子囊悬浮液(2-3x 10 5个/mL)。用接种喷雾器(压力0.1MPa)在黄瓜苗上均匀喷雾接种，接种后的试材移至人工气候室，保持相对湿度100％，温度为21℃左右，24小时后保持温度21℃左右，相对湿度95％左右保湿诱发，5天后视空白对照发病情况进行分级调查，按病指计算防效。
2)黄瓜白粉病菌测试(Sphaerothecafuliginea)
选择一张真叶期、长势一致黄瓜苗，喷雾处理后阴干24小时。洗取黄瓜叶片上的新鲜白粉病菌孢子，用双层纱布过滤，制成孢子浓度为10万个/mL左右的悬浮液，喷雾接种。接种后的试材移入人工气候内，相对湿度保持在60～70％之间，温度保持21～23℃，10天左右视空白对照发病情况进行分级调查，按病指计算防效。
试验结果如表3-4所示。
表3 本发明化合物在200ppm浓度下对黄瓜霜霉病的防效
化合物 防效(％) 化合物 防效(％)
实施例2 90 实施例3 80
实施例4 80 实施例5 100
实施例7 80 实施例8 100
实施例9 90 实施例17 80
实施例18 90 实施例20 90
实施例21 100 实施例22 100
实施例23 80 实施例24 80
实施例25 90 实施例26 80
实施例27 100 实施例28 100
实施例29 100 实施例30 100
实施例31 100 实施例32 100
实施例33 100 实施例34 100
实施例35 100 实施例36 100
实施例37 80 实施例38 90
化合物 防效(％) 化合物 防效(％)
实施例39 95 实施例40 100
实施例41 100 实施例42 100
实施例43 100 实施例44 100
实施例45 80 实施例46 100
实施例47 80 实施例51 80
表4 本发明化合物在100ppm浓度下对黄瓜霜霉病的防效
化合物 防效(％) 化合物 防效(％)
实施例8 80 实施例21 80
实施例27 100 实施例28 80
实施例29 100 实施例30 90
实施例31 100 实施例32 100
实施例33 80 实施例36 90
实施例40 80 实施例41 85
实施例42 90 实施例43 90
实施例44 90 实施例46 90
另外，在50ppm浓度下，本发明化合物实施例27、实施例29、实施例31、实施例32、实施例36、实施例42、实施例43和实施例44对黄瓜霜霉病的防效仍在80％以上；在200ppm浓度下，本发明化合物实施例27、实施例32对黄瓜白粉病也有80％的防效。
上述试验结果可知本发明化合物对植物病原性真菌，尤其是对黄瓜霜霉病菌具有很好的防治效果，其中部分化合物(实施例32)在更低浓度下(如25ppm下)对黄瓜霜霉病的防效仍在80％以上；具备较好的开发前景。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于上述实施方式中的具体细节，在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，这些简单变型均属于本发明的保护范围。

Claims (10)

  1. 一种化合物，其为具有式(I)所示的化合物或式(I)所示的化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
    Figure PCTCN2019097704-appb-100001
    其中，
    R 1和R 2各自独立地为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-或C 6-10芳基-C 1-6烷基-；其中，所述的C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-或C 6-10芳基-C 1-6烷基-任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、氨基、C 1-6烷基、卤代C 1-6烷基、C 1-6烷氧基或卤代C 1-6烷氧基的取代基取代；
    或R 1、R 2和与之相连的氮原子一起形成任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、氨基、C 1-6烷基、卤代C 1-6烷基、C 1-6烷氧基或卤代C 1-6烷氧基取代的3-10元杂环基或5-10元杂芳基；
    R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、C 1-6烷基、C 2-6烯基、C 2-6炔基、卤代C 1-6烷基、卤代C 2-6烯基、卤代C 2-6炔基、C 6-10芳基、卤代C 6-10芳基、C 6-10芳基-C 1-6烷基-或卤代C 6-10芳基-C 1-6烷基-；
    x为0、1或2；
    R 4为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 6-10芳基、C 3-8环烷基-C 1-6烷基-、C 6-10芳基-C 1-6烷基-、5-6元杂芳基、-C(＝O)OC 1-6烷基、R mS(＝O) 2-或-C(＝O)R n；
    R m和R n各自独立地为C 1-6烷基或C 6-10芳基；
    其中，R 4任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代；
    R 5为C 6-10芳基或5-10元杂芳基；其中，R 5任选地被1、2、3、4或5个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代；
    R 6为氢、C 1-6烷基、C 2-6烯基、C 2-6炔基、C 3-8环烷基、C 3-8环烷基-C 1-6烷基-、苯基或苯基-C 1-6烷基-；
    或R 5、R 6和与之相连接的碳原子形成C 9-10芳基或9-10元杂芳基；所述的C 9-10芳基和9-10元杂芳基任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-6烷基、C 1-6烷氧基、卤代C 1-6烷基或卤代C 1-6烷氧基的取代基取代。
  2. 根据权利要求1所述的化合物，其中，
    R 1和R 2各自独立地为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基、C 6-10芳基、C 3-6环烷基-C 1-3烷基-或C 6-10芳基-C 1-3烷基-；
    R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、C 1-4烷基、C 2-4烯基、C 2-4炔基、卤代C 1-4烷基、卤代C 2-4烯基、卤代C 2-4炔基、C 6-10芳基、卤代C 6-10芳基、C 6-10芳基-C 1-3烷基-或卤代C 6-10芳基-C 1-3烷基-。
  3. 根据权利要求2所述的化合物，其中，
    R 1和R 2各自独立地为氢、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-CH 2CH 2CH 2CH 3、-CH(CH 3)CH 2CH 3、-CH 2CH(CH 3) 2、-C(CH 3) 3、-CH＝CH 2、-CH 2CH＝CH 2、-CH＝CHCH 3、-CH 2CH 2CH＝CH 2、-CH 2CH＝CHCH 3、-CH＝CHCH 2CH 3、-C≡CH、-CH 2-C≡CH、-CH 2CH 2-C≡CH、环丙基、环丁基、环戊基、环己基、苯基或苄基；
    R 3为氢、氟、氯、溴、碘、羟基、氰基、硝基、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-C(CH 3) 3、-CH 2Cl、-CHF 2或-CF 3。
  4. 根据权利要求1所述的化合物，其中，
    R 4为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基、苯基、苄基、C 3-6环烷基-C 1-3烷基-、吡啶基、吡嗪基、哒嗪基、-C(＝O)OC 1-4烷基、R mS(＝O) 2-或-C(＝O)R n；
    R m和R n各自独立地为C 1-4烷基或苯基；
    其中，R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代；
    或者R 4任选地被1、2或3个选自卤素、羟基、氰基、硝基、甲基或三氟甲基的取代基所取代。
  5. 根据权利要求4所述的化合物，其中，
    R 4为氢、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-C(＝O)CH 3或-C(＝O)OCH 3；
    或R 4为以下子结构式：
    Figure PCTCN2019097704-appb-100002
  6. 根据权利要求1所述的化合物，其中，
    R 5为苯基、萘基、吡啶基、吡咯基、噻吩基、呋喃基、咪唑基、吡唑基、恶唑基、异恶唑基、噻唑基、1H-1,2,4-三唑基或1H-吲哚基；
    其中，R 5任选地被1、2或3个选自卤素、羟基、氰基、硝基、C 1-4烷基、C 1-4烷氧基、卤代C 1-4烷基或卤代C 1-4烷氧基的取代基取代；
    R 6为氢、C 1-4烷基、C 2-4烯基、C 2-4炔基、C 3-6环烷基或苯基；
    或R 5、R 6和与之相连接的碳原子形成
    Figure PCTCN2019097704-appb-100003
  7. 根据权利要求6所述的化合物，其中，
    R 5为苯基、萘-1-基、吡啶-2-基、吡啶-3-基、1H-吡咯-2-基、噻吩-2-基、噻吩-3-基、1H-咪唑-1-基、异恶唑-3-基、1H-吲哚-3-基或1H-吲哚-4-基；
    其中，R 5任选地被1、2或3个选自氟、氯、溴、碘、羟基、氰基、硝基、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH(CH 3) 2、-CH 2CH 2CH 2CH 3、-CH(CH 3)CH 2CH 3、-CH 2CH(CH 3) 2、-C(CH 3) 3、-OCH 3、-OCH 2CH 3、-OCH 2CH 2CH 3、-OCH(CH 3) 2、-OCH 2CH 2CH 2CH 3、-OCH(CH 3)CH 2CH 3、-OCH 2CH(CH 3) 2、-OC(CH 3) 3、-CF 3或-OCF 3的取代基取代；
    R 6为氢、-CH 3或苯基。
  8. 根据权利要求1-7任意一项所述的化合物，其为具有下列之一结构的化合物或具有下列之一结构化合物的立体异构体、氮氧化物、盐、(E)或(Z)异构体以及它们的混合物：
    Figure PCTCN2019097704-appb-100004
    Figure PCTCN2019097704-appb-100005
    Figure PCTCN2019097704-appb-100006
    Figure PCTCN2019097704-appb-100007
  9. 一种组合物，包含权利要求1-8任意一项所述的化合物。
  10. 一种权利要求1-8任意一项所述的化合物或权利要求9所述的组合物作为植物病害防治剂的应用。
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