EP0975587A1 - Oxime ether compounds, their use and intermediates for preparations of the same - Google Patents

Oxime ether compounds, their use and intermediates for preparations of the same

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Publication number
EP0975587A1
EP0975587A1 EP98911069A EP98911069A EP0975587A1 EP 0975587 A1 EP0975587 A1 EP 0975587A1 EP 98911069 A EP98911069 A EP 98911069A EP 98911069 A EP98911069 A EP 98911069A EP 0975587 A1 EP0975587 A1 EP 0975587A1
Authority
EP
European Patent Office
Prior art keywords
group
alkyl
methyl
mmol
compound according
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.)
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Application number
EP98911069A
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German (de)
French (fr)
Inventor
Taro Hirose
Norio Kimura
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Sumitomo Chemical Co Ltd
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Sumitomo Chemical Co Ltd
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Publication of EP0975587A1 publication Critical patent/EP0975587A1/en
Withdrawn legal-status Critical Current

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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/52—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing groups, e.g. carboxylic acid amidines
    • 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
    • A01N39/00—Biocides, pest repellants or attractants, or plant growth regulators containing aryloxy- or arylthio-aliphatic or cycloaliphatic compounds, containing the group or, e.g. phenoxyethylamine, phenylthio-acetonitrile, phenoxyacetone
    • A01N39/02—Aryloxy-carboxylic acids; Derivatives thereof
    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/52—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
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    • C07C251/32—Oximes
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/54—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/62—Carboxylic acid nitriles containing cyano groups and oxygen atoms being part of oxyimino groups bound to the same carbon skeleton
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    • C07C255/00—Carboxylic acid nitriles
    • C07C255/63—Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C255/64—Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton with the nitrogen atoms further bound to oxygen atoms
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/63—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/58—Derivatives of thiocarboxylic acids, the doubly-bound oxygen atoms being replaced by nitrogen atoms, e.g. imino-thio ethers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/734—Ethers
    • C07C69/736—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
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    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/12—Radicals substituted by oxygen atoms

Definitions

  • the present invention relates to oxime ether compounds, their use and intermediates for preparation of the same . More particularly, the present invention provides compounds having excellent antifungal effects for agriculture and/or horticulture, and excellent insecticidal and/or acaricidal effects .
  • present invention provides oxime ether compounds (hereinafter referred to as present compound) represented by the general formula 4 :
  • R 1 represents hydrogen atom, alkyl group, cycloalkyl group, alkoxyalkyl group, haloalkyl group, cyano group, nitro group or alkoxycarbonyl group
  • one of T, U and V represents CR 2 group, the other one represents CH group or nitrogen atom and the rest one represents CR 3 group or nitrogen atom
  • W represents CR 33 group or nitrogen atom
  • R 2 , R 3 and R 33 are the same or different and represent hydrogen atom, halogen atom, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, nitro group, alkoxycarbonyl group, alkylthio group or haloalkylthio group
  • R 4 represents hydrogen atom, alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group or heterocyclic group, wherein the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group or the heterocyclic group may have one or more substituents,
  • R 5 and R 6 are the same or different and represent alkyl group
  • X represents NR 7 group, oxygen atom or sulfur atom
  • R 7 represents alkyl group optionally having one or more substituents
  • Y represents CH group or nitrogen group
  • Z represents oxygen atom or NH group, provided that when
  • Y is CH group, then Z is oxygen atom, as well as antifungal agents for agriculture and/or horticulture, and insecticidal and/or acaricidal agents containing the same as an active ingredient.
  • the present invention further provides compounds represented by the general formula 5 : [compound 5]
  • R 1 , R 4 , R 6 , T, U, V, , X and Y are as defined above, compounds represented by the general formula 6 :
  • R 1 , R 4 , R 6 , T, U, V, W and X are as defined above, compounds represented by the general formula 7 :
  • R 1 , R 5 , R 6 , T, U, V, W, X and Z are as defined above, and compounds represented by the general formula 8 :
  • examples of the alkyl group representedby R 1 include C1-C10 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, hexyl group, decyl group and the like.
  • examples of the cycloalkyl group represented by R 1 include C3-C10 cycloalkyl group such as cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclodecyl group and the like.
  • alkoxyalkyl group represented by R 1 examples include C2-C10 alkoxyalkyl group such as methoxymethyl group, 2-ethoxyethyl group, 4-methoxybutyl group, 5-pentyloxypentyl group and the like.
  • Examples of the haloalkyl group represented by R 1 include C1-C5 haloalkyl group such as trifluoromethyl group, chloromethyl group, 2-fluoroethyl group and the like.
  • Examples of the alkoxycarbonyl group represented by R 1 include C2-C5 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, n- butoxycarbony1 group, i-propoxycarbonyl group, i- butoxycarbonyl group, t-butoxycarbonyl group and the like.
  • Examples of the halogen atom represented by R 2 , R 3 or R 33 include chlorine atom, bromine atom, fluorine atom and the like.
  • alkyl group represented by R 2 , R 3 or R 33 examples include C1-C5 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group and the like.
  • Examples of the alkoxy group represented by R 2 , R 3 or R 33 include C1-C5 alkoxy group such as methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, pentyloxy group and the like.
  • Examples of the haloalkyl group represented by R 2 , R 3 or R 33 include C1-C5 haloalkyl group such as trifluoromethyl group and the like.
  • haloalkoxy group represented by R 2 , R 3 or R 33 examples include C1-C5 haloalkoxy group such as trifluoromethoxy group, difluoromethoxy group, bromodifluoromethoxy group, chlorodifluoromethoxy group, 1, 1, 2 , 2 , -tetrafluoroethoxy group, 2, 2, 2-trifluoroethoxy group and the like.
  • alkoxycarbonyl group represented by R 2 , R 3 or R 33 examples include C2-C5 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, n- propoxycarbonyl group, n-butoxycarbonyl group, i- propoxycarbonyl group, i-butoxycarbonyl group, t- butoxycarbonyl group and the like.
  • alkylthio group represented by R 2 , R 3 or R 33 examples include C1-C5 alkylthio group such as methylthio group, ethylthio group, n-propylthio group, n-butylthio group, n- pentylthio group, i-propylthio group, i-butylthio group, t- butylthio group and the like.
  • haloalkylthio group represented by R 2 , R 3 or R 33 examples include C1-C5 haloalkylthio group such as trifluoromethylthio group, difluoromethylthio group, bromodifluoromethylthio group, chlorodifluoromethylthio group, 1, 1, 2,2, -tetrafluoroethylthio group, 2,2,2- trifluoroethylthio group and the like.
  • Examples of the alkyl group represented by R 4 include C1-C10 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 1- methylpropyl group, pentyl group, 1-methylbutyl group, 1- ethylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 2 , 2-dimethylpropyl group, 1,2-dimethylpropyl group, 1,1- dimethylpropyl group, hexyl group, 1-methylpentyl group, 1- ethylpentyl group, 3 , 3-dimethylbutyl group, heptyl group, 3 , 7-dimethyloctyl group and the like.
  • C1-C10 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 1- methylpropyl
  • alkenyl group represented by R 4 examples include
  • C3-C10 alkenyl group such as allyl group, l-methyl-2-propenyl group, 2-methyl-2-propenyl group, 3-methyl-2-propenyl group,
  • alkynyl group represented by R 4 examples include C3-C10 alkynyl group such as propargyl group, 1-methyl-2- propynyl, 3-methyl-2-propynyl group and the like.
  • Examples of the cycloalkyl group representedby R 4 include C5-C10 cycloalkyl group such as cyclopentyl group, cyclohexyl group and the like.
  • Examples of the cycloalkenyl group represented by R 4 include C5-C10 cycloalkenyl group such as cyclopentenyl group, cyclohexenyl group and the like.
  • Examples of the aryl group represented by R 4 include phenyl group, a -naphthyl group, ⁇ -naphthyl group and the like.
  • Examples of the heterocyclic group represented by R 4 include 2-pyridyl group, 4-pyridyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 3-pyrazolyl group, 2-thiazolyl group, 2-imidazolyl group, 3- (1, 2 , 4-triazolyl group) and the like.
  • Examples of the substituent ofthe alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group and the heterocyclic group as R 4 include :
  • halogen atom chlorine atom, bromine atom, fluorine atom and the like
  • R 8 represents hydrogen atom, C1-C10 alkyl group [such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group and the like] , C1-C5 haloalkyl group
  • C3-C6 cycloalkyl group such as cyclopropyl group, cyclopentyl group, cyclohexyl group an the like]
  • C2-C10 alkoxyalkyl group such as 2- methoxyethyl group and the like
  • C1-C10 acyl group such as formyl group, acetyl group, propanoyl group, pivaloyl group, C1-C10 alkanoyl group optionally substituted with halogen atom (chlorine atom, bromine atom, fluorine atom and the like) such as chloroacetyl group and the like, benzoyl group and the like]
  • C2-C11 alkoxycarbonyl group such as trifluoromethyl group, difluoromethyl group, bromodifluoromethyl group, 1, 1, 2, 2 , -tetrafluoroethyl group, 2, 2, 2 -trifluoroethyl group and the like
  • phenyl, a -naphthyl or ⁇ -naphthyl) sulfonyl group [such as p-toluenesulfonyl group and the like] , C1-C5 haloalkylsulfonyl group and the like [such as trifluoromethanesulfonyl group, trichloromethanesulfonyl group, 2,2,2, -trifluoroethanesulfonyl group and the like], C1-C5 alkylsulfinyl group [such as methylsulfinyl group and the like] or C1-C5 haloalkylsulfinyl group [such as trifluoromethanesulfinyl group and the like] , or phenyl group [the phenyl group may be substituted with halogen atom (ex.
  • R 9 and R 10 are taken together to represent tetramethylene group, pentamethylene group or 3- oxapentamethylene group ⁇ ;
  • R 13 and R 14 are the same or different and represent hydrogen atom, C1-C10 alkyl group [such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group and the like] , C3-C6 cycloalkyl group
  • phenyl group [such as cyclopropyl group, cyclopentyl group and cyclohexyl group] , or phenyl group [the phenyl group may be substituted with halogen atom (ex. chlorine atom, bromine atom, fluorine atom and the like) , C1-C5 alkyl group (such as methyl group, ethyl group, tert-butyl group and the like) , trifluoromethyl group, cyano group or nitro group; such as 4-chlorophenyl group, 4-trifluoromethylphenyl group, 4-ethylphenyl group, 3,4- dichlorophenyl group, 3 , 5-dichlorophenyl group, 2-chloro-6- fluorophenyl group, 4-fluorophenyl group, 4-cyanophenyl group, 4-nitrophenyl group and the like] ⁇ :
  • C1-C5 alkylthio group [such as methylthio group, ethylthio group, propylthio group, isopropylthio group, pentylthio group and the like] ;
  • C1-C5 haloalkylthio group [such as 2,2,2- trifluoroethylthio group, 4-chlorobutylthio group and the like] ;
  • C1-C10 acyl group [such as C1-C10 alkanoyl group (ex. formyl group, acetyl group, propanoyl group, butanoyl group, pentanoyl group, isobutanoyl group and the like) optionally substituted with halogen atom (ex.
  • C2-C11 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butyloxycarbonyl group, octyloxycarbonyl group and the like;
  • N-(C1-C10 alkyl) carbamoyl group [such as N- methylcarbamoyl group, N-ethylcarbamoyl group and the like] ;
  • N,N-di(Cl-C10 alkyl ) carbamoyl group [such as N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group and the like] ;
  • aryl group such as phenyl group, a -naphthyl group, ⁇ -naphthyl group and the like ; the aryl group may be substituted with halogen atom [such as chlorine atom, bromine atom, fluorine atom and the like] , C1-C10 alkyl group [such as methyl group, ethyl group, tert-butyl group and the like] , C3-C10 cycloalkyl group [such as cyclopropyl group, cyclopentyl group, cyclohexyl group and the like] , C1-C5 haloalkyl group [such as trifluoromethyl group and the like] , hydroxy group, C1-C10 alkoxy group [such as methoxy group, ethoxy group, propyloxy group, isopropyloxy group and the like] , C1-C5 haloalkoxy group [such as trifluoro
  • heterocyclic group such as 2-pyridyl group, 3- pyridyl group, 4-pyridyl group, 2-pyrimidinyl group, 4- pyrimidinyl group, 5-pyrimidinyl group, 1-pyrazolyl group, 3-pyrazolyl group, 4-pyrazolyl group, 5-pyrazolyl group, 2- thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 4- isoxazolyl group, 1- (1, 2, 4-triazolyl) group, 3-(l,2,4- triazolyl) group, 3-oxolanyl, succinimid-1-yl group, maleinimid-1-yl group, phthalimid-1-yl group and the like; the heterocyclic group may be substituted with one or more halogen atom [ex.
  • C1-C10 alkyl group such as methyl group, ethyl group, tert-butyl group and the like]
  • C3-C10 cycloalkyl group such as cyclopropyl group, cyclopentyl group, cyclohexyl group and the like]
  • C1-C5 haloalkyl group such as trifluoromethyl group and the like]
  • hydroxy group, C1-C10 alkoxy group such as methoxy group, ethoxy group and the like]
  • amino group or C1-C10 alkylthio group such as methylthio group, ethylthio group and the like] ⁇ .
  • Examples of the alkyl group represented by R 5 or R 6 include C1-C5 alkyl group such as methyl group, ethyl group, propyl group and the like. Inter alia, methyl group is preferable from a viewpoint of antifungal effect for agriculture and horticulture.
  • Examples of the alkyl group represented by R 7 include C1-C5 alkyl group such as methyl group, ethyl group, propyl group and the like.
  • Examples of the substituent of R7 are halogen atom [such as chlorine atom, bromine atom, fluorine atom and the like] , C1-C5 alkoxy group [such as methoxy group, ethoxy group and the like] , C2-C5 alkoxycarbonyl group [such as methoxycarbonyl group, ethoxycarbonyl group and the like] , N-(C1-C5 alkyl) carbamoyl group [such as N-methylcarbamoyl group, N-ethylcarbamoyl group and the like], N,N-di(Cl-C5 alkyl) carbamoyl group [such as N,N-dimethylcarbamoyl group) , N,N-diethylcarbamoyl group and the like] , cyano group and the like.
  • halogen atom such as chlorine atom, bromine atom, fluorine atom and the like
  • 6-membered cyclic aromatic ring containing T, U, V and W examples include benzene ring, pyridine ring, pyrimidine ring and the like.
  • the present compounds wherein RI is methyl group, T is C-CH 3 , U is CH, V is CH, W is CH, R5 is methyl group, R6 is methyl group, X is oxygen atom, Y is CH and Z is oxygen atom are preferred.
  • Examples of the preferred compound include methyl 2- ⁇ 5- (1-benzyloxyiminoethyl) -2- methylphenoxy ⁇ -3-methoxyacrylate, methyl 3- [5- ⁇ l- (2 , 4- dichlorobenzyloxyimino) ethyl ⁇ -2-methylphenoxy] -3- methoxyacrylate, methyl 2- ⁇ 5- (1-propargyloxyiminoethyl) -2- methylphenoxy ⁇ -3-methoxyacrylate, methyl 2- ⁇ 5-(l-n- propyloxyiminoethyl) -2-methylphenoxy ⁇ -3-methoxyacrylate, and the like.
  • R 44 represents R 4 except for hydrogen, R 1 , R 5 , R 6 , T, U, V, W, X, Y and Z are as defined above, and L 1 represents a leaving group such as halogen atom (such as chlorine atom, bromine atom, iodine atom and the like) , sulfonate ester group (such as mesyloxy group, tosyloxy group and the like) , sulfate ester group (methoxysulfonyloxy group, ethoxysulfonyloxy group and the like) .
  • halogen atom such as chlorine atom, bromine atom, iodine atom and the like
  • sulfonate ester group such as mesyloxy group, tosyloxy group and the like
  • sulfate ester group methoxysulfonyloxy group, ethoxysulfonyloxy group and the like
  • R 1 , R 4 , R 5 , R 6 , T, U, V, , X, Y and L 1 are as defined above
  • L 2 is alkoxy group (ex. C1-C5 alkoxy group such as methoxy group, ethoxy group and the like) , aryloxy group (phenoxy group and the like) or acyloxy group (ex. C1-C5 acyloxy group such as acetoxy group and the like) when Y is CH group
  • L 2 is alkoxy group (ex. C1-C5 alkoxy group such as methoxy, group, ethoxy group, isoamyloxy group, butoxy group, tert- butoxy group and the like) or chlorine atom when Y is nitrogen.
  • R 1 , R 44 , R 5 , R 6 , T, U, V, W, X and 1 are as defined above,
  • R 1 , R 5 , R 6 , T, U, V, W, X, Y, L 1 and L 2 are as defined above, and R 11 represents alkyl group (ex. C1-C5 alkyl group such as methyl group, ethyl group, propyl group, butyl group and the like) or two R 11 ' s are taken together to represent alkylene group (ex. C2-C5 alkylene group such as ethylene group, 1, 2-dimethylethylene group, propylene group and the like).
  • a raw material compound 6 in the above Scheme 8 and a raw material compound [X] in the above Scheme 11 can be prepared, for example, according to the following Scheme 12
  • Process 12c L 11 — CH 2 C0 2 R 6
  • Process 12 b L 11 — CH 2 C0 2 R 6
  • L 1 represents halogen atom (such as chlorine atom, bromine atom, iodine atom and the like) or sulfonate ester group (such as mesyloxy group, tosyloxy group and the like) .
  • R 11 represents cyano group, alkoxycarbonyl group or nitro group
  • R 44 , L 1 , L 2 , X, T, U, V and W are as defined above
  • X' represents a group which can be synthetic-chemically derived into X-H group in process 13c
  • when X represents oxygen atom then X' represents an oxygen ether group such as benzyloxy group, methoxymethyloxy group, methylthiomethyloxy group, benzyloxymethyloxy group, tetrahydropyran-2-yloxy group and the like
  • when X represents sulfur atom then X' represents sulfur ether group such as methoxymethylthio group, isobutoxymethylthio group, tetrahydropyran-2-ylmethylthio group and the like
  • X' represents nitro group or N(R 7 )R 20 group (wherein R 7 is as defined above and R 20 represents acyl
  • a reaction temperature is usually in a range of 0 to 150 2 C
  • a reaction time is usually in a range of 1 to 24 hours
  • a molar ratio of the hydroxylamine derivative relative to the carbonyl compound is usually in a range of 1 to 5.
  • Hydroxylamine derivative may be used as a salt with an acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid or the like.
  • an acid catalyst or base catalyst may be used in the reaction.
  • a molar ratio of the catalyst relative to the hydroxylamine derivative is usually in a range of 0.01 to 100.
  • the acid catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, carboxylic acids such as acetic acid, trifluoroacetic acid, oxalic acid, benzoic acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like and a mixture thereof .
  • the acid catalyst may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
  • the base catalyst examples include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, potassium carbonate and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2- picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N, -diethylaniline and the like and a mixture thereof .
  • inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, potassium carbonate and the like
  • alkali metal alkoxides such as sodium methoxide, sodium e
  • the base catalyst may form a salt with mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like. Examples thereof include sodium acetate and the like. If necessary, a solvent may be used in the reaction.
  • mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like. Examples thereof include sodium acetate and the like.
  • a solvent may be used in the reaction.
  • the solvent examples include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, organic acid solvents such as acetic acid and the like, ester solvent
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
  • a reaction temperature is in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours
  • the reaction is usually carried out in the presence of a base, and a molar ratio of the base relative to the electrophilic reagent is usually in a range of 1 to 10.
  • the base include inorganic salts such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, potassium carbonate, sodium hydride, potassium hydride, silver oxide and the like, alkali metal alkoxides such as potassium-tert-butoxide, sodium methoxide, sodium ethoxide, and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2- picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N, N-diethylaniline, and the line and a mixture thereof.
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N, N-diethylaniline and the like, ester solvents
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours.
  • a reaction reagent used for acetalizing carbonyl compound [X] is an alcohol compound represented by R 11 OH, which is usually used at two or more moles excessive amount relative to carbonyl compound [X] .
  • the alcohol compound may be used also as a reaction solvent.
  • reaction reagent used for acetalizing carbonyl compound [X] is an alkylenediol compound which is corresponding to an acetal moiety, which is usually used at one mole or more excessive amount relative to carbonyl compound [X] .
  • the reaction is usually carried out in the presence of an acid catalyst and a molar ratio of the acid catalyst relative to carbonyl compound [X] is usually in a range of 0.01 to 100.
  • the acid catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, carboxylic acids such as acetic acid, trifluoroacetic acid, oxalic acid, benzoic acid and the like, sulfonic acids such as p- toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethane sulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof.
  • the acid catalyst may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
  • Orthoesters as a reaction reagent can be further added to the reaction to accelerate the reaction and a molar ratio of the orthoesters to be used relative to carbonyl compound [X] is in a range of 1 to an amount useable as a solvent.
  • the orthoesters include methyl orthoformate, ethyl orthoformate and the like.
  • a solvent may be used in the reaction.
  • the solvent include ether solvents such as 1,4- dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours
  • the reaction is usually carried out in the presence of a base.
  • a base examples include inorganic bases such as sodium hydride, potassium hydride and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, and alkali metal amides such as sodium amide, lithium amide, lithium diisopropylamide, sodium hexamethyldisilazide, lithium hexamethyldisilazide and the like and a mixture thereof.
  • a solvent may be used in the reaction.
  • the solvent examples include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N-dimethylaniline, N, N-diethylaniline and the like, ester solvents such as ethyl formate, butyl acetate
  • reaction solution can be treated with an aqueous acidic solution such as dilute hydrochloric acid, subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • aqueous acidic solution such as dilute hydrochloric acid
  • a reaction temperature is usually in a range of 0 to 150 2 C
  • a reaction time is usually in a range of 1 to 24 hours
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as dichloroethane, carbon tetrachloride, monochlorobenzene and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethyl
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours.
  • a molar ratio of 2-chloro-2- (hydroxyimino) acetate ester to be used for the reaction relative to compound [II] or [VII] is usually in a range of 1 to 10.
  • a method of preparing 2-chloro-2- (hydroxyimino) acetate ester is described, for example, in U.S. P. No. 3584032.
  • the reaction is usually carried out in the presence of a base and a molar ratio of the base relative to compound [II] or [VII] is usually in a range of 1 to 100.
  • the base include inorganic beses such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4- dimethylaminopyridine , quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and a mixture thereof.
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, organic acid solvents, organic
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 100 hours
  • a molar ratio of the acid relative to compound [XVI] is usually in a range of 0.001 to an amount useable as a solvent.
  • Examples of the acid to be used in the reaction include carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid, benzoic acid and the like, sulfonic acids such as methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid and the like, mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, perchloric acid and the like, Lewis acids such as zinc chloride, aluminium chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride, trimethylsilyl iodide and the like, and a mixture thereof.
  • carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid, benzoic acid and the like
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroe
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • process 13c comprises a process represented by the following Scheme 14:
  • R 11 , R 44 , R 7 , T, U, V, W and L 1 are as defined above, and R 21 represents hydrogen atom, alkyl group such as methyl group, or haloalkyl group such as chloromethyl group, trichloromethyl group and trifluoromethyl group.
  • Process 14a is a reducing reaction carried out using zinc , iron, tin or tin (II) chloride usually in the presence of an acid.
  • a reaction temperature is usually in a range of 0 to 150 a C, and a reaction time is usually in a range of 1 to 100 hours.
  • a molar ratio of the acid relative to compound [XVII] is usually in a range of 1 to an amount useable as a solvent.
  • Examples of the acid to be used in the reaction include carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid and the like, sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid and the like, mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid and the like, and a mixture thereof .
  • carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid and the like
  • sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid and the like
  • mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid and the like, and a mixture thereof .
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, and a mixture thereof.
  • alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • An acylation reaction represented by process 14b is carried out using an acylating reagent such as R 21 COOH itself, or ester, acid halide or anhydride thereof.
  • a molar ratio of the acylating reagent relative to compound [XVIII] is usually in a range of 1 to an amount useable as a solvent.
  • a reaction temperature is usually in a range of 0 to 200 a C, and a reaction time is usually in a range of 1 to 200 hours.
  • the reaction may be carried out in the presence of an acid or base catalyst as necessary.
  • a molar ratio of the catalyst relative to raw material compound [XVIII] is in a range of 0.0001 to 100.
  • the acid catalyst examples include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof.
  • the acid catalyst may form a salt with alkali metal such as sodium, potassium and the like, or organic base such as pyridine, triethylamine, N,N- di ethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
  • the base catalyst examples include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, barium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, alkali metal amides such as sodium amide, lithium amide, lithium diisopropylamide, sodium hexamethyldisilazide, lithium hexamethyldisilazide and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and
  • the base catalyst may form a salt with mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like.
  • mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like.
  • carboxylic acids such as acetic acid, benzoic acid and the like
  • Lewis acids such as zinc chloride and the like.
  • a solvent may be used in the reaction.
  • the solvent examples include ether solvents such as 1,4- dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N-dimethylform
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours.
  • a molar ratio of compound R 7 -L 1 relative to compound [XIX] is usually in a range of 1 to 10.
  • the reaction is usually carried out in the presence of a base and a molar.ratio of the base relative to compound R 7 -L 1 is usually in a range of 1 to 10.
  • the base include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate, sodium hydride, potassium hydride, silver oxide and the like, alkali metal alkoxides such as potassium-tert-butoxide, sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4- dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and a mixture thereof.
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- di ethylaniline, N, N-diethylaniline and the like,
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • a reaction temperature is usually in a range of 0 to 150 a C
  • a reaction time is usually in a range of 1 to 24 hours.
  • the reaction is carried out usually in the presence of a base or an acid and a molar ratio of the base or the acid relative to compound [XX] is usually in a range of 0.001 to 1000.
  • the base examples include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, alkali metal alkoxides such as potassium-t-butoxide, sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, and a mixture thereof.
  • inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like
  • alkali metal alkoxides such as potassium-t-butoxide, sodium methoxide, sodium ethoxide and the like
  • alkaline earth metal alkoxides such as magnesium ethoxide and the like
  • the acid examples include mineral acids such as hydrochloric acid, perchloric acid, hydrobromic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof.
  • mineral acids such as hydrochloric acid, perchloric acid, hydrobromic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like
  • sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like
  • Lewis acids
  • the acid may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
  • a solvent may be used in the reaction.
  • the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, nitro compound solvent
  • reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
  • compound [X] when X represents sulfur atom, compound [X] can be also prepared, for example, by reacting diazonium compound [XXII] and thiolate salt [XXIII] according to the following Scheme 15. Diazonium salt [XXII] can be prepared by the known methods .
  • R 1 , R 6 , T, U, V and W are as defined above, and L " represents halogen ion such as chlorine ion, bromine ion, or monoanion of strong acid such as sulfuric acid ion, nitric acid ion and the like.
  • L " represents halogen ion such as chlorine ion, bromine ion, or monoanion of strong acid such as sulfuric acid ion, nitric acid ion and the like.
  • the present compound is usually used by formulating into emulsifiable concentrate, water dispersible powder, suspension, dust or granule by mixing with solid carrier, liquid carrier, surfactant or other adjuvants for formulation although it may be used as it is without addition of any other ingredients.
  • These formulations contain as an active ingredient the present compound usually at a weight ratio of 0.1 to 99.9%, preferably 1 to 90%.
  • Examples of the solid carrier used for such formulation include fine powders or granules of caolin clay, attapulgite, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, maize rachis powder, walnut shell powder, urea, ammonium sulfate, synthetic hydrated silicon oxide and the like, and examples of the liquid carrier include aromatic hydrocarbons such as xylene, methylnaphthalene and the like, alcohols such as isopropanol, ethylene glycol, cellosolve and the like, ketones such as acetone, cyclohexanone, isophorone and the like, vegetable oils such as soybean oil, cotton seed oil and the like, dimethyl sulfoxide, acetonitrile, water and the like.
  • aromatic hydrocarbons such as xylene, methylnaphthalene and the like
  • alcohols such as isopropanol, ethylene glycol, cellosolve and the like
  • surfactant examples include anionic surfactants such as alkylsulfate salt, alkyl (aryl) sulfonate salt, dialkylsulfosuccinate salt, polyoxyethylene alkyl aryl ether phosphate salt, naphthalenesulfonate formalin condensate and the like, nonionic surfactant such as polyoxyethylene alkyl ether, polyoxyethylene alkyl polyoxypropylene block copolymer, sorbi an fatty acid ester and the like.
  • anionic surfactants such as alkylsulfate salt, alkyl (aryl) sulfonate salt, dialkylsulfosuccinate salt, polyoxyethylene alkyl aryl ether phosphate salt, naphthalenesulfonate formalin condensate and the like
  • nonionic surfactant such as polyoxyethylene alkyl ether, polyoxyethylene alkyl polyoxypropylene block copolymer, sorbi an
  • the adjuvant for formulation examples include lignin sulfonate salt, alginate salt, polyvinyl alcohol, gum arabic, CMC (carboxylmethyl cellulose) , PAP (isopropyl acid phosphate) and the like.
  • the present compound is applied by, for example, foliage application, soil treatment, seed disinfection although they can be usually used by any application method known to those skilled in the art.
  • an amount of the present compound to be applied may vary depending upon kind of subject plant (crop and the like) , kind of subject disease, occurrence degree of disease, formulation form, application method, application time, weather conditions and may be usually 0.01 to 50 g/are, preferably 0.05 to 10 g/are.
  • the application concentration of the present compound is usually 0.0001 to 0.5%, preferably 0.0005 to 0.2%, and dust, granule or the like is applied as it is without any dilution.
  • the present compound may be used as an agricultural and/or horticultural antifungal agent for farmland, paddy field, orchard, tea plantation, pasture, lawn area and potentiated antifungal effect can be expected by using by mixing with other agricultural and/or horticultural antifungal agent.
  • Example of the other agricultural and horticultural antifungal agent include azole antifungal compound such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromoconazole, epoxyconazole, difenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, myclobutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole (RPA 400727), bitertanol, imazalil, flutriafol and the like, cyclic amine antifungal compound such as fenpropimorph, tridemorph, fenpropidin and the like, benzimidazole antifungal compounds such as carbendazim, benomyl, thiabendazole, thiophanate-methyl and the like, proc
  • the present compounds may be used by mixing with or in combination with insecticide, acaricide, nematicide, herbicide, plant growth regulator, fertilizer or the like.
  • examples of the vegetable disease which can be controlled by the present compound are as follows: blast (Pyricularia orvzae) , leaf spot (Cochliobolus miyabeanus) and sheath blight (Rhizoctonia solani) of rice plant, powdery mildew (Ervsiphe ⁇ raminis) , scab (Gibberella zeae) , rust (Puccinia striiformis, P. ⁇ raminis, P. recondita. P.
  • powdery mildew (Sphaerotheca fuli ⁇ inea) , gummy stem blight (Mvcosphaerella elonis) , stem rot (Fusarium oxysporum) , downy mildew ( Pseudoperonospora cubensis) , late blight (Phvtophthora sp. ) and da ping-off (Pvthium SP.
  • the present compound When used as an active ingredient for insecticidal and/or acaricidal agent, they may be used as such without addition of any other ingredients. However, it is usually used by formulating into oil solution, emulsifiable concentrate, water dispersible powder, flowable agent, granule, dust, aerosol, fumigant (fogging agent or the like) , poisonbait or the like, by mixing with solid carrier, liquid carrier, gaseous carrier, bait or the like and, if necessary, adding surfactant, or other auxiliaries for formulation.
  • These preparations contain the present compound as an active ingredient, usually, in a ratio by weight of 0.01% to 95%.
  • the solid carrier used for such formulation are fine powders or granules of clay (such as caolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, Fubasami clay, acid clay and the like) , talcs, ceramic, other inorganic minerals (such as cericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica and the like) , chemical fertilizer (such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride and the like) .
  • clay such as caolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, Fubasami clay, acid clay and the like
  • talcs ceramic
  • other inorganic minerals such as cericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica and the like
  • liquid carrier examples include water, alcohols (such as methanol, ethanol and the like) , ketones (such as acetone, methyl ethyl ketone and the like) , aromatic hydrocarbons (such as benzene, toluene, xylene, ethylbenzene, methylnaphthalene and the like) , aliphatic hydrocarbons (such as hexane, cyclohexane, kerosine, light oil and the like) , esters (such as ethyl acetate, butyl acetate and the like) , nitriles (such as acetonitrile, isobutyronitrile and the like) , ethers (such as diisopropyl ether, dioxane and the like) , acid amides (such as N,N-dimethylformamide, N,N-dimethylacetamide and the like) , halogenated hydrocarbons (such as
  • surfactant examples include alkylsulfate salt, alkylsulfonate salt, alkylarylsulfonate salt, alkyl aryl ether and its polyoxyethylene compound, polyethylene glycol ether, polyhydric alcohol ester, sugar alcohol derivative and the like.
  • auxiliary for formulation such as adhesive agent and dispersing agent
  • polysaccharides such as starch powder, gum arabic, cellulose derivative, alginic acid and the like
  • lignin derivatives such as starch powder, gum arabic, cellulose derivative, alginic acid and the like
  • bentonite such as lignin derivatives
  • sugars such as polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid and the like
  • synthetic water-soluble polymer such as polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid and the like
  • the stabilizing agent examples include PAP (acid isopropyl phosphate), BHT (2, 6-di-tert-butyl-4- ethylphenol) , BHA (mixture of 2-tert-butyl-4-methoxyphenol and3-tert-butyl-4-methoxyphenol) , vegetable oil, mineral oil, surfactant, and fatty acid or ester thereof and the like.
  • PAP acid isopropyl phosphate
  • BHT 2, 6-di-tert-butyl-4- ethylphenol
  • BHA mixture of 2-tert-butyl-4-methoxyphenol and3-tert-butyl-4-methoxyphenol
  • vegetable oil mineral oil
  • surfactant and fatty acid or ester thereof and the like.
  • Examples of the base material for poison bait are components for bait such as cereal powder, vegetable oil, sugar, crystalline cellulose and the like, antioxidant such as dibutylhydroxytoluene, nordihydroguaiaretic acid and the like, preservative such as dehydroacetic acid and the like, substance for preventing erroneous eating such as red pepper powder, attractant flavor such as cheese flavor, onion flavor and the like.
  • the preparations thus prepared are used as they are or after diluted with water or the like.
  • the preparations may be used by mixing with or in combination with other insecticide, nematicide, acaricide, antifungal agent, herbicide, plant growth regulator, synergist, fertilizer, soil conditioner, animal feed, and the like.
  • the insecticide and/or nematocide and/or acaricide may include, for example, organophosphorus compounds such as
  • the application dosage is usually 0.1 g to 100 g/10 are.
  • the application concentration is usually 0.1 ppm to 5000 ppm.
  • Granule, dust and the like are applied as preparations themselves without any dilution.
  • emulsifiable concentrate, water dispersible powder, flowable agent and the like are usually applied after diluted with water to 0.1 ppm to 5000 ppm, and oil solution, aerosol, fumigant, poison bait and the like are applied as such.
  • application dosage and application concentration may vary depending upon kind of preparations, application timing, application place, application method, kind of insect pest, degree of damage and the like and they may be increased or decreased beyond the above range.
  • the harmful insects and harmful ticks and mites , against which the present compounds exhibit controlling activity may include, for example, the following: Hemiptera:
  • Planthoppers such as small brown planthopper (Laodelphax striatellus) , brown rice planthopper
  • Leafhoppers such as green rice leafhopper (Nephotettix cincticeos) and green rice leafhopper (Nephotettix virescense) ; aphids (Aphididae) , stink bugs (Pentatomidae) , whiteflies (Aleyrodidae) , scales
  • Pyralid moths such as rice stem borer (Chilo suppressalis) , rice leafroller (Cnaphalocrocis medinalis) and Indian meal moth (Plodia interpunctella) ; owlet moths (Noctuidae) such as common cutworm (Soodoptera litura) , rice armyworm (Pseudaletia separata) and cabbage armyworm (Mamestra brassicae) , white and sulfer butterflies (Pieridae) such as common cabbageworm (Pieris rapae crucivora) , tortricid moths
  • Trotricidae such as Adoxophyes spp . ; Carposinidae; lyonetiid moths (Lyonetiidae) ; tussock moth (Lymantriidae) ; Plusiae;
  • Agrothis spp. such as cutworm (A ⁇ rothis se ⁇ etum) and black cutworm (A ⁇ rothis ipsilon) : Heliothis spp.; diamondblack
  • Mosquitos (Calicidae) such as common mosquito (Culex pipiens pallens) and Culex tritaeniorhvnchus; Aedes spp. such as Aedes ae ⁇ vpti and Aedes albopictus; Anopheles spp. such as
  • Corn rootworm such as western corn rootworm (Diabrotica vir ⁇ ifora) and southern corn root worm (Diabrotica undecimpunctata) ; scarabs (Scarabaeidae) such as cupreous chafer (Anomala cuprea) and soybean beetle (Anomala rufocuprea) ; weevils (Cureulionidae) such as maize weevil (Sitophilus zeamalis) , rice water weevil (Lissorhoptrus orvzophilus) and adzuki bean weevil (Callosobruchys chineneis) ; darkling beetles (Tenebrionidae) such as yellow mealworm (Tenebrio moliter) and red flour beetles (Tribolium astaneum) ; leaf beetles (Chrysomelidae) such as striped flea beetles (Phyllotrata stroilata) and cucurbit leaf beet
  • German cockroach (Blattella ⁇ ermanica) , smokybrown cockroach (Periplaneta fuli ⁇ inosa) , American cockroch (Periolaneta americana) , brown cockroach (Periplaneta brunnea) and oriental cockroach (Blatta orientalis) Thysanoptera:
  • Thrips palmi and flower thrips (Thrips hawaiiensis) Hymenoptera:
  • Ants Formidae
  • Vespidae Vespidae
  • Bethylidae sawflies
  • Enthredinidae such as cabbage sawfly
  • cabbage sawfly Athalia rosae -iaponensis
  • Mole crickets (Gryllotalpidae; grasshoppers (Acrididae) Aphaniptera : Purex irritans Anoplura :
  • Phthirus pubis Isoptera Phthirus pubis Isoptera
  • Reticulitermes speratus Reticulitermes speratus .
  • Formosan subterrauean termite (Coptotermes formosanus) Acarina plant parasitic mites such as Tetranvchus urticae. Panonvchus citri, Tetranvchus cinnabarinus and Panonvchus ulmi . animal parasitic Ixodes such as Boophilus microphus . and house dust mites
  • the present compound is also effective for the control of insect pests with resistance to conventional insecticides or acaricides.
  • the organic layer was washed with dilute hydrochloric acid once and extracted twice with 300 ml of an aqueous solution of sodium carbonate.
  • the resulting sodium carbonate solution was made weakly acidic with concentrated hydrochloric acid to precipitate the desired material as crystals.
  • This mixture was extracted twice with 500 ml of ethyl acetate to obtain the organic layer, which was washed once with water, dried with magnesium sulfate and concentrated to obtain 1.1 g (3.7 mmol) of the desired methyl 3-hydroxy-2- (N-methyl-3-acetylanilino) acrylate.
  • N,N-dimethylformamide was stirred at room temperature overnight.
  • the resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate.
  • the organic layer was washed once with dilute hydrochloric acid and extracted twice with an aqueous solution of sodium carbonate.
  • the resulting aqueous alkaline layer was adjusted to around pH
  • the resulting mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate.
  • the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate and dried with magnesium sulfate.
  • To the residue obtained by concentration were added 8.3 g (60mmol) of potassium carbonate, 100 ml of methanol and 10 ml of water, which was heated to reflux for 1 hour and allowed to cool to room temperature.
  • the resulting reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water .
  • the organic layer was dried with magnesium sulfate and concentrated to obtain the residue, and to this were added 0.20 liter of methanol and 0.30 g (1.6 mmol) of p-toluenesulfonic acid monohydrate, followed by heating to reflux for 3 hours. The mixture was allowed to cool to room temperature, and 1 ml (7.2 mmol) of triethylamine was added thereto, followed by concentration. The residue was partitioned between ethyl acetate and water and the organic layer was dried with magnesium sulfate and concentrated to obtain 3.5 g (19 mmol) of the desired N-methyl-3- (dimethoxymethyl) aniline .
  • the aqueous layer was made acidic by the addition of concentrated hydrochloric acid and the precipitates were extracted twice with ethyl acetate.
  • the organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 1.8 g (7.2 mmol) of the desired methyl 2- (3-acetylphenylthio) -3 -hydroxyacrylate .
  • reaction solution was poured into dilute hydrochloric acid, extracted with 20ml of ethyl acetate, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodiumbicarbonate, dried with magnesium sulfate and concentrated to obtain 593 mg (2.08 mmol) of the desired 2- ⁇ 3-(N- methyltrifluoroacetoamino) phenyl ⁇ -2- methoxyiminoacetonitrile .
  • the resulting reaction solution was poured into dilute hydrochloric acid, extracted with 20 ml of ethyl acetate, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodiumbicarbonate, dried with magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 192 mg (0.736 mmol) of the desired 2- ⁇ 3- (N-methyl-N-methoxycarbonylmethylamino) phenyl ⁇ -2- methoxyiminoacetonitrile (intermediate for preparing present compound) .
  • the organic layer was washed once with dilute hydrochloric acid, extracted twice with an aqueous solution of sodium carbonate, the combined aqueous sodium carbonate layers were made weakly acidic with concentrated hydrochloric acid, the precipitates were extracted with 20 ml of ethyl acetate, and the organic layer was washed once with water, dried with magnesium sulfate and concentrated to obtain 119 mg (0.412 mmol) of the desired 2- [3- ⁇ N-methyl-N- (methyl 3-hydroxyacrylate-2- y1) amino ⁇ phenyl] -2-methoxyiminoacetonitrile (intermediate for preparing present compound) .
  • the resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate .
  • the organic layer was washed once with dilute hydrochloric acid and extracted twice with an aqueous solution of sodium carbonate.
  • the resulting aqueous alkaline layer was adjusted to around pH 6 using concentrated hydrochloric acid, and the precipitates were extracted with ethyl acetate.
  • the organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 0.40 g (about 1.6 mol) of the crude product of the desired methyl 2- (5- acetyl-2-methylphenoxy) -3-hydroxyacrylate.
  • the aqueous layer was made acidic by the addition of concentrated hydrochloric acid, and the precipitates were extracted twice with ethyl acetate.
  • the ethyl acetate layers were combined, washed with water, dried with magnesium sulfate and concentrated to obtain 450 mg (1.69 mmol) of the desired methyl 2- (5-acetyl-2-methyl- phenylthio) -3-hydroxyacrylate .
  • the residue (17.90 g) obtained by concentration was dissolved in 50 ml of 95% ethanol, and to this was added 17.5 g of potassium hydroxide in portions at a bath temperature of 100 °C, followed by heating to reflux for 5 hours and 30 minutes. After ethanol was distilled off from the reaction mixture, water and diethyl ether were added to the residue, the layers were separated, and the aqueous layer was washed with diethyl ether three times.
  • Me represents methyl group
  • Et represents ethyl group
  • n-Pr represents propyl group
  • i-Pr represents isopropyl group
  • n-Bu represents butyl group
  • t- Bu represents tert-butyl group
  • Am represents amyl group
  • Bz represents benzyl group
  • F 5 BZ represents 2,3,4,5,6- pentafluorobenzyl group
  • Ph represents phenyl group
  • 4-CF 3 - PhCH(CH 3 ) represents 1- (4-trifluoromethylphenyl) ethyl group
  • Py represents pyridyl group
  • c represents cyclo
  • sec represents secondary
  • SUIM represents succinimid-1-yl group
  • (A) represents 3-Cl-5-CF 3 -Py-2-yl group
  • (B) represents 5- CF 3 -Py-2-yl group, respectively.
  • Each 2 parts of the present compounds 1-493 and 1001- 1078, 88 parts of caolin clay and 10 parts of talc are sufficiently ground and mixed to obtain each dust.
  • Formulation Example 4 Each 20 parts of the present compounds 1-493 and 1001-1078 , 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecyl benzenesulfonate and 60 parts of xylene are sufficiently mixed to obtain each emulsifiable concentrate.
  • Each 0.2 part of the present compounds 1-493 and 1001-1078 , 0.2 part of d-allethrin, 0.2 part of d-phenothrin, 5 parts of xylene, 3.4 parts of deodorized kerosine and 1 part of an emulsifier ⁇ ATMOS 300 (registered trade name by Atlas Chemical Co.) ⁇ is mixed to dissolve, and this solution and 50 parts of pure water are filled into an aerosol container, a valve part is attached thereto, and 40 parts of a propellant (liquefied petroleum gas) is filled under pressure through the valve part to obtain each aqueous aerosol .
  • a propellant liquefied petroleum gas
  • 0.3 g of d-allethrin is added to each 0.3 g of the present compounds 1-493 and 1001-1078, the mixture is dissolved in 20 ml of acetone, mixed with 99.4 g of a carrier for a mosquito coil (prepared by mixing Tabu powder, pyrethrum marc powder and wood flour in the ratio of 4:3:3) uniformly by stirring, 120 ml of water is added and sufficiently kneaded, molded and dried to obtain each mosquito coil.
  • Formulation Example 11 Acetone is added to each 0.4 g of the present compounds 1-493 and 1001-1078 , 0.4 g of d-allethrin and 0.4 g of piperonyl butoxide to dissolve to a total volume of 10 ml.
  • Each 10 mg of the present compounds 1-493 and 1001-1078 is dissolved in 0.5 ml of acetone, this solution is added to 5 g of solid bait powder for animals (Breeding Solid Feed CE-2; trade name by Japan Clea Co. , Ltd. ) and mixed uniformly. Then, acetone is removed by air-drying to obtain each 0.5% poison bait.
  • Test Examples indicate that the present compounds are useful as a microbicidal agent for agriculture and/or horticulture, and an insecticidal and/or acaricidal agent.
  • the present compounds are indicated by referring to chemical Nos . in Table 1 and Table 2.
  • the efficacy of the present compounds was assessed by the rate of disease area on tested plants in a case of agricultural and/or horticultural antifungal use, or calculating mortality of the test worms in a case of insecticidal or acaricidal use.
  • Test Example 1 Efficacy of invented compounds against rice blast (preventive effect)
  • a predetermined concentration 500 or 200 ppm
  • Test Example 4 The efficacy of the invented compounds against brown leaf rust of wheat (preventive effect)
  • the plants were air-dried and spores of brown leaf rust of wheat were inoculated on the wheats . After inoculation, the plants were first placed at 23 °C in the darkness under high humidity for one day and further under illumination for 6 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of brown leaf rust of wheat. The rate of desease area on the treated plants was less than 30 %.
  • Test Example 5 Efficacy of the invented compounds against leaf blight of wheat (preventive effect)
  • Test Example 6 The efficacy of the invented compound against glume blotch of wheat (preventive effect)
  • the plants were air-dried and PDA medium containing spores of eyespot of wheat was placed at the wheat foot. After inoculation, the plants were first placed at 15 °C in the darkness under high humidity for 7 days and further under illumination for 4 days, and the efficacy of the tested compound assessed. As a result, all the compounds inhibited development of eyespot of wheat.
  • the disease area on the treated plant was less than 3/10 times as much as that on the non-treated plant.
  • Test Example 8 The efficacy of the invented compounds on downy mildew of cucumber (preventive effect)
  • Nos. 1, 2, 4, 115, 116, 163, 174, 215, 216, 217, 252, 272 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500 ppm) , and these were sprayed onto foliage of cucumbers sufficiently. After the treatment, the plants were air-dried and spores of downy mildew of cucumber were inoculated on the cucumbers. After inoculation, the plants were first placed at 23 °C under high humidity for 1 day and further in a greenhouse for 10 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of downy mildew of cucumber.
  • Test Example 9 The efficacy of the invented compounds on gray mold of cucumber (preventive effect)
  • the plants were air-dried and PDA medium containing hyphae of gray mold of cucumber was placed on the cucumber leaves. After inoculation, the plants were placed at 10 °C under high humidity for 4 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of gray mold of cucumber. The percentage of the treated plant was less than 30%.
  • Test Example 10 The efficacy of the invented compounds on powdery mildew of cucumber (preventive effect)
  • the plants were air-dried and spores of powdery mildew of cucumber were inoculated on the cucumbers . After inoculation, the plants were placed at 23 °C for 12 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of powdery mildew of cucumber. The rate of disease area on the treated plant was less than 30%.
  • Test Example 11 The efficacy of the invented compounds on downy mildew of grape (preventive effect)
  • the plants were air-dried and zoosporangia of downy mildew of grape were inoculated on the grapes . After inoculation, the plants were placed first at 23 °C under high humidity for 1 day and further in a greenhouse for 6 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of powdery mildew of grape. The rate of disease area on the treated plant was less than 30%.
  • Test Example 12 Insecticidal test against larva of common cutworm (Spodoptera litura) Each of the compounds Nos. 4, 9 and 13 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain 2 ml of a diluted solution, which was soaked into 13 g of an artificial feed for Spodoptera litura which had been prepared in a polyethylene cup having the diameter of 11 cm. 5 larvae of 4 week-age Spodoptera litura were released in the cup and, after 6 days, the death or survival thereof was investigated to obtain mortality. As a result, all the test compounds showed mortality of 80%. Test Example 13 : Insecticidal test against larva of brown planthopper (Nilaparvata lugens)
  • each of the compounds Nos .2, 4-6, 8-10 and 14 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500 ppm) , and this was sprayed to foliage so as to sufficiently attach to rice leavee. After spray, the plants were air-dried, and about 30 larvae of
  • Nilaparvata lugens were released thereon. After release of larvas, the plants were left in a greenhouse for 6 days, the death or survival thereof was investigated to obtain mortality.
  • Test Example 14 Insecticidal test against larva of southern corn root worm (Diabrotica undecimpunctata)
  • Each of the compounds Nos. 2 and 4-10 was prepared into emulsifiable concentrate according to the procedures in Formulation Example 4 and diluted with water to a predetermined concentration (50 ppm) to obtain 1 ml of the diluted solution, whichwas added dropwise on the filter. About 30 eggs of southern corn root worm were placed on the filter, and one budding of corn was placed thereon as a feed. After 8 days, the death or survival of hatched larvae was investigated to obtain mortality. As a result, all the compounds showed mortality of 80% or more.
  • Test Example 15 Application test against cotton aphid (Aphid gossypii)
  • each of the present compounds 5, 6, 8 and 10 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain the diluted solution, which was sprayed at an amount of 20 ml/pot. 6 days after drug solution spray, the controlling value was obtained according to the following equation. As a result, the above compounds showed the controlling effect of 90% or more, respectively.
  • Controlling value ⁇ 1- (Cb»Tai) / (Tb»Cai) ⁇ x 100
  • Cb Number of worms in non-treated plot before treatment
  • Cai Number of worms in non-treated plot at observation
  • Tb Number of worms in test plot before treatment
  • Tai number of worms in test plot at observation
  • Example 16 Spraying test against Tetranychus urticae Bush bean (Phaseolus vulgaris L.var. humilis Alef.) (primordial leaf stage) planted in a polyethylene cup was made parasitic with 20 female adults of Tetranychus urticae per leaf and was placed in a constant temperature room.
  • each of the present compounds 5 , 6, 7, 8, 9, 10 and 13 was prepared into emulsifiable concentrate according to the procedures in Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain the diluted solution, which was sprayed to the pot at an amount of 20 ml/pot. 8 days after the spray, degree of damage by Tetranychus urticae was investigated. As a result, in plots treated with the above test compounds, damage was hardly observed.
  • Test Example 17 Insecticidal test against house-fly (Musca domestica) The bottom of a polyethylene cup having a diameter of 5.5 cm was covered with a filter paper having the same diameter of that of the bottom. Each of the present compounds 1, 2, 4, 5, 7, 8, 9, 10 and 13 was prepared into emulsifiable concentrate, diluted with water to a predetermined concentration (500 ppm) to obtain 0.7 ml of diluted solution, which was added dropwise on the filter, and 30 mg of sucrose as a feed was placed uniformly in the cup. 10 female adults of Musca domestica were released in the cup, the cup was capped and, after 24 hours, the survival or death thereof was investigated to obtain mortality. As a result, the above test compounds showedmortality of 80% or more, respectively.
  • Test Example 18 Insecticidal test against common mosquito (Culex pipens pallens)
  • Each of the present compounds 1, 4, 6, 8, 10, 12 and 13 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain 0.7ml of a diluted solution, which was added to 100 ml of ion-exchanged water (concentration of an active ingredient: 3.5 ppm). 20 larvae of one week-age Culex pipens pallens were released therein and, 8 days after treatment, adult eclosion inhibiting rate was investigated. As a result, the above test compounds showed adult eclosion inhibiting rate of 80% or more, respectively.
  • the present compounds have excellent antifungal effect for agriculture and/or horticulture as well as excellent insecticidal and/or acaricidal effect.

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Abstract

According to the present invention, there are provided oxime ether compounds represented by general formula (I). These compounds have excellent antifungal effect for agriculture and/or horticulture as well as excellent insecticidal and/or acaricidal effect.

Description

DESCRIPTION OXIME ETHER COMPOUNDS, THEIR USE AND INTERMEDIATES FOR PREPARATIONS OF THE SAME
Technical Field
The present invention relates to oxime ether compounds, their use and intermediates for preparation of the same . More particularly, the present invention provides compounds having excellent antifungal effects for agriculture and/or horticulture, and excellent insecticidal and/or acaricidal effects .
Disclosure of Invention
The present inventors studies hard and, as a result, found that oxime ether compounds represented by the general formula
4 below have excellent antifungal effects for agriculture and/or horticulture, and insecticidal and/or acaricidal effects, which resulted in completion of the present invention.
That is, the present invention provides oxime ether compounds (hereinafter referred to as present compound) represented by the general formula 4 :
wherein R1 represents hydrogen atom, alkyl group, cycloalkyl group, alkoxyalkyl group, haloalkyl group, cyano group, nitro group or alkoxycarbonyl group, one of T, U and V represents CR2 group, the other one represents CH group or nitrogen atom and the rest one represents CR3 group or nitrogen atom, W represents CR33 group or nitrogen atom,
R2, R3 and R33 are the same or different and represent hydrogen atom, halogen atom, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, nitro group, alkoxycarbonyl group, alkylthio group or haloalkylthio group, R4 represents hydrogen atom, alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group or heterocyclic group, wherein the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group or the heterocyclic group may have one or more substituents,
R5 and R6 are the same or different and represent alkyl group,
X represents NR7 group, oxygen atom or sulfur atom, R7 represents alkyl group optionally having one or more substituents,
Y represents CH group or nitrogen group,
Z represents oxygen atom or NH group, provided that when
Y is CH group, then Z is oxygen atom, as well as antifungal agents for agriculture and/or horticulture, and insecticidal and/or acaricidal agents containing the same as an active ingredient.
The present invention further provides compounds represented by the general formula 5 : [compound 5]
wherein R1, R4, R6, T, U, V, , X and Y are as defined above, compounds represented by the general formula 6 :
[compound 6]
wherein R1 , R4 , R6 , T, U, V, W and X are as defined above, compounds represented by the general formula 7 :
wherein R1, R5, R6, T, U, V, W, X and Z are as defined above, and compounds represented by the general formula 8 :
[Compound 8] wherein R5 and R6 are as defined above, which are useful as an intermediate for preparing the present compound.
Detailed Description of the Invention
In the present invention, examples of the alkyl group representedby R1 include C1-C10 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, hexyl group, decyl group and the like. Examples of the cycloalkyl group represented by R1 include C3-C10 cycloalkyl group such as cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclodecyl group and the like.
Examples of the alkoxyalkyl group represented by R1 include C2-C10 alkoxyalkyl group such as methoxymethyl group, 2-ethoxyethyl group, 4-methoxybutyl group, 5-pentyloxypentyl group and the like.
Examples of the haloalkyl group represented by R1 include C1-C5 haloalkyl group such as trifluoromethyl group, chloromethyl group, 2-fluoroethyl group and the like. Examples of the alkoxycarbonyl group represented by R1 include C2-C5 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, n- butoxycarbony1 group, i-propoxycarbonyl group, i- butoxycarbonyl group, t-butoxycarbonyl group and the like. Examples of the halogen atom represented by R2, R3 or R33 include chlorine atom, bromine atom, fluorine atom and the like. Examples of the alkyl group represented by R2, R3 or R33 include C1-C5 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group and the like.
Examples of the alkoxy group represented by R2, R3 or R33 include C1-C5 alkoxy group such as methoxy group, ethoxy group, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group, pentyloxy group and the like. Examples of the haloalkyl group represented by R2, R3 or R33 include C1-C5 haloalkyl group such as trifluoromethyl group and the like.
Examples of the haloalkoxy group represented by R2, R3 or R33 include C1-C5 haloalkoxy group such as trifluoromethoxy group, difluoromethoxy group, bromodifluoromethoxy group, chlorodifluoromethoxy group, 1, 1, 2 , 2 , -tetrafluoroethoxy group, 2, 2, 2-trifluoroethoxy group and the like.
Examples of the alkoxycarbonyl group represented by R2, R3 or R33 include C2-C5 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, n- propoxycarbonyl group, n-butoxycarbonyl group, i- propoxycarbonyl group, i-butoxycarbonyl group, t- butoxycarbonyl group and the like. Examples of the alkylthio group represented by R2, R3 or R33 include C1-C5 alkylthio group such as methylthio group, ethylthio group, n-propylthio group, n-butylthio group, n- pentylthio group, i-propylthio group, i-butylthio group, t- butylthio group and the like. Examples of the haloalkylthio group represented by R2, R3 or R33 include C1-C5 haloalkylthio group such as trifluoromethylthio group, difluoromethylthio group, bromodifluoromethylthio group, chlorodifluoromethylthio group, 1, 1, 2,2, -tetrafluoroethylthio group, 2,2,2- trifluoroethylthio group and the like.
Examples of the alkyl group represented by R4 include C1-C10 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 1- methylpropyl group, pentyl group, 1-methylbutyl group, 1- ethylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 2 , 2-dimethylpropyl group, 1,2-dimethylpropyl group, 1,1- dimethylpropyl group, hexyl group, 1-methylpentyl group, 1- ethylpentyl group, 3 , 3-dimethylbutyl group, heptyl group, 3 , 7-dimethyloctyl group and the like.
Examples of the alkenyl group represented by R4 include
C3-C10 alkenyl group such as allyl group, l-methyl-2-propenyl group, 2-methyl-2-propenyl group, 3-methyl-2-propenyl group,
2-butenyl group, 2-pentenyl group, 3-methyl-2-butenyl group, geranyl group and the like.
Examples of the alkynyl group represented by R4 include C3-C10 alkynyl group such as propargyl group, 1-methyl-2- propynyl, 3-methyl-2-propynyl group and the like.
Examples of the cycloalkyl group representedby R4 include C5-C10 cycloalkyl group such as cyclopentyl group, cyclohexyl group and the like.
Examples of the cycloalkenyl group represented by R4 include C5-C10 cycloalkenyl group such as cyclopentenyl group, cyclohexenyl group and the like. Examples of the aryl group represented by R4 include phenyl group, a -naphthyl group, β -naphthyl group and the like.
Examples of the heterocyclic group represented by R4 include 2-pyridyl group, 4-pyridyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 3-pyrazolyl group, 2-thiazolyl group, 2-imidazolyl group, 3- (1, 2 , 4-triazolyl group) and the like. Examples of the substituent ofthe alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group and the heterocyclic group as R4 include :
(1) halogen atom (chlorine atom, bromine atom, fluorine atom and the like) ;
(2) OR8 group {wherein R8 represents hydrogen atom, C1-C10 alkyl group [such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group and the like] , C1-C5 haloalkyl group
[such as trifluoromethyl group, difluoromethyl group, bromodifluoromethyl group, 1, 1, 2, 2 , -tetrafluoroethyl group, 2, 2, 2 -trifluoroethyl group and the like], C3-C6 cycloalkyl group [such as cyclopropyl group, cyclopentyl group, cyclohexyl group an the like] , C2-C10 alkoxyalkyl group [such as 2- methoxyethyl group and the like] , C1-C10 acyl group [such as formyl group, acetyl group, propanoyl group, pivaloyl group, C1-C10 alkanoyl group optionally substituted with halogen atom (chlorine atom, bromine atom, fluorine atom and the like) such as chloroacetyl group and the like, benzoyl group and the like] , C2-C11 alkoxycarbonyl group [such as methoxycarbonyl group, ethoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group and the like] , N-(C1-C10 alkyl) carbamoyl group [such as N-methylcarbamoyl group, N-ethylcarbamoyl group and the like], N-N-di (C1-C10 alkyl ) carbamoyl group [such as N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group and the like] , or phenyl group [the phenyl group may be substituted with halogen atom (such as chlorine atom, bromine atom, fluorine atom and the like) , C1-C5 alkyl group (such as methyl group, ethyl group, tert-butyl group and the like) or trifluoromethyl group; such as 4-chlorophenyl group, 4-
( trifluoromethyl) phenyl group, 3 , 4-dichlorophenyl group, 4- ethylphenyl group, 2 , 3-dimethylphenyl group, 2-chloro-4- (trifluoromethyl) phenyl group, 4-fluorophenyl group, 3,5- dichlorophenyl group, 4-tert-butyl phenyl group, 2-chloro- 6-fluorophenyl group and the like] ; (3) group represented by N(R9)R10 {wherein R9 and R10 are the same or different and represent hydrogen atom, C1-C10 alkyl group [such as methyl group, ethyl group, butyl group and the like] , C5-C6 cycloalkyl group [such as cyclopentyl group or cyclohexyl group] , C1-C10 acyl group [such as acetyl group, propanoyl group, butanoyl group, C1-C10 alkanoyl group optionally substituted with halogen atom (chlorine atom, bromine atom, fluorine atom and the like) such as trifluoroacetyl group and the like, benzoyl group and the like] , C2-C11 alkoxycarbonyl group, N-(C1-C10 alkyl) carbamoyl group [such as N-methylcarbamoyl group, N-ethylcarbamoyl group and the like], N,N-di (C1-C10 alkyl) carbamoyl group [such as N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group and the like] , C1-C5 alkylsulfonyl group [such as methylsulfonyl group and the like], C6-C10 aryl (ex. phenyl, a -naphthyl or β -naphthyl) sulfonyl group [such as p-toluenesulfonyl group and the like] , C1-C5 haloalkylsulfonyl group and the like [such as trifluoromethanesulfonyl group, trichloromethanesulfonyl group, 2,2,2, -trifluoroethanesulfonyl group and the like], C1-C5 alkylsulfinyl group [such as methylsulfinyl group and the like] or C1-C5 haloalkylsulfinyl group [such as trifluoromethanesulfinyl group and the like] , or phenyl group [the phenyl group may be substituted with halogen atom (ex. chlorine atom, bromine atom, fluorine atom and the like) , C1-C5 alkyl group (such as methyl group, ethyl group, tert-butyl group and the like) or trifluoromethyl group; such as 4-chlorophenyl group, 4-trifluoromethylphenyl group, 4-ethylphenyl group, 3 , 4-dichlorophenyl group, 3 , 5-dichlorophenyl group, 2- chloro-6-fluorophenyl group, 4-fluorophenyl group and the like] , or R9 and R10 are taken together to represent tetramethylene group, pentamethylene group or 3- oxapentamethylene group} ;
(4) group represented by C (R13) =NOR14 {wherein R13 and R14 are the same or different and represent hydrogen atom, C1-C10 alkyl group [such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group and the like] , C3-C6 cycloalkyl group
[such as cyclopropyl group, cyclopentyl group and cyclohexyl group] , or phenyl group [the phenyl group may be substituted with halogen atom (ex. chlorine atom, bromine atom, fluorine atom and the like) , C1-C5 alkyl group (such as methyl group, ethyl group, tert-butyl group and the like) , trifluoromethyl group, cyano group or nitro group; such as 4-chlorophenyl group, 4-trifluoromethylphenyl group, 4-ethylphenyl group, 3,4- dichlorophenyl group, 3 , 5-dichlorophenyl group, 2-chloro-6- fluorophenyl group, 4-fluorophenyl group, 4-cyanophenyl group, 4-nitrophenyl group and the like] } :
(5) C1-C5 alkylthio group [such as methylthio group, ethylthio group, propylthio group, isopropylthio group, pentylthio group and the like] ;
(6) C1-C5 haloalkylthio group [such as 2,2,2- trifluoroethylthio group, 4-chlorobutylthio group and the like] ;
(7) C1-C10 acyl group [such as C1-C10 alkanoyl group (ex. formyl group, acetyl group, propanoyl group, butanoyl group, pentanoyl group, isobutanoyl group and the like) optionally substituted with halogen atom (ex. chlorine atom, bromine atom, fluorine atom and the like) , benzoyl group and the like] ; (8) C2-C11 alkoxycarbonyl group [such as methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butyloxycarbonyl group, octyloxycarbonyl group and the like;
(9) N-(C1-C10 alkyl) carbamoyl group [such as N- methylcarbamoyl group, N-ethylcarbamoyl group and the like] ;
(10) N,N-di(Cl-C10 alkyl ) carbamoyl group [such as N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group and the like] ;
(11) cyano group; (12) nitro group;
(13) aryl group {such as phenyl group, a -naphthyl group, β -naphthyl group and the like ; the aryl group may be substituted with halogen atom [such as chlorine atom, bromine atom, fluorine atom and the like] , C1-C10 alkyl group [such as methyl group, ethyl group, tert-butyl group and the like] , C3-C10 cycloalkyl group [such as cyclopropyl group, cyclopentyl group, cyclohexyl group and the like] , C1-C5 haloalkyl group [such as trifluoromethyl group and the like] , hydroxy group, C1-C10 alkoxy group [such as methoxy group, ethoxy group, propyloxy group, isopropyloxy group and the like] , C1-C5 haloalkoxy group [such as trifluoromethoxy group, difluoromethoxy group and the like] , amino group, cyano group, nitro group, C2-C6 alkoxycarbonyl group [such as methoxycarbonyl group, ethoxycarbonyl group and the like] , C3-C8 cycloalkoxy group [such as cyclopentyloxy group, cyclohexyloxy group and the like], N-(C1-C5 alkyl) carbamoyl group [such as N- methylcarbamoyl group, N-ethylcarbamoyl group and the like] , N,N-di(Cl-C5 alkyl) carbamoyl group [such as N,N- dimethylcarbamoyl group, N,N-diethylcarbamoyl group and the like], C1-C10 acyl group [such as C1-C10 alkanoyl group (ex. acetyl group and the like) , benzoyl group and the like] , phenoxy group optionally substituted with one or more halogen atom, C1-C3 alkyl group, C1-C3 haloalkyl group or C1-C3 alkylthio group [such as phenoxy group, 4-chlorophenoxy group] , phenyl group optionally substituted with one or more cyano group, 2-pyridyloxy group [the 2-pyridyloxy group may be substituted with one or more trifluoromethyl group or halogen atom; such as 5-trifluoromethylpyridin-2-yloxy group, 3-chloro-5- trifluoromethylpyridin-2-yloxy group and the like] , morpholin-4-yl group, benzyloxy group, benzoyloxy group, C1-C5 alkylsulfonyloxy group [such as methylsulfonyloxy group and the like] , C1-C5 haloalkylsulfonyloxy group [such as trifluoromethylsulfonyloxy group and the like] , trifluoromethanesulfonylamino group, R11OC(0)0 group,
Rn(R12)NC(0)0 group, RnC(0)N(R12) group, Rn0C(0)NH group, R11(R12)NC(0)NH group (wherein R11 and R12 are the same or different and represent C1-C5 alkyl group such as methyl group, ethyl group and the like} or C1-C10 alkylthio group [such as methylthio group, ethylthio group and the like]}; and
(14) heterocyclic group {such as 2-pyridyl group, 3- pyridyl group, 4-pyridyl group, 2-pyrimidinyl group, 4- pyrimidinyl group, 5-pyrimidinyl group, 1-pyrazolyl group, 3-pyrazolyl group, 4-pyrazolyl group, 5-pyrazolyl group, 2- thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 4- isoxazolyl group, 1- (1, 2, 4-triazolyl) group, 3-(l,2,4- triazolyl) group, 3-oxolanyl, succinimid-1-yl group, maleinimid-1-yl group, phthalimid-1-yl group and the like; the heterocyclic group may be substituted with one or more halogen atom [ex. chlorine atom, bromine atom, fluorine atom and the like] , C1-C10 alkyl group [such as methyl group, ethyl group, tert-butyl group and the like] , C3-C10 cycloalkyl group [such as cyclopropyl group, cyclopentyl group, cyclohexyl group and the like] , C1-C5 haloalkyl group [such as trifluoromethyl group and the like] , hydroxy group, C1-C10 alkoxy group [such as methoxy group, ethoxy group and the like] , amino group or C1-C10 alkylthio group [such as methylthio group, ethylthio group and the like] } . Examples of the alkyl group represented by R5 or R6 include C1-C5 alkyl group such as methyl group, ethyl group, propyl group and the like. Inter alia, methyl group is preferable from a viewpoint of antifungal effect for agriculture and horticulture. Examples of the alkyl group represented by R7 include C1-C5 alkyl group such as methyl group, ethyl group, propyl group and the like. Examples of the substituent of R7 are halogen atom [such as chlorine atom, bromine atom, fluorine atom and the like] , C1-C5 alkoxy group [such as methoxy group, ethoxy group and the like] , C2-C5 alkoxycarbonyl group [such as methoxycarbonyl group, ethoxycarbonyl group and the like] , N-(C1-C5 alkyl) carbamoyl group [such as N-methylcarbamoyl group, N-ethylcarbamoyl group and the like], N,N-di(Cl-C5 alkyl) carbamoyl group [such as N,N-dimethylcarbamoyl group) , N,N-diethylcarbamoyl group and the like] , cyano group and the like.
Examples of 6-membered cyclic aromatic ring containing T, U, V and W include benzene ring, pyridine ring, pyrimidine ring and the like.
From the view point of the antifungal effect for agriculture and/or horticulture, the present compounds wherein RI is methyl group, T is C-CH3, U is CH, V is CH, W is CH, R5 is methyl group, R6 is methyl group, X is oxygen atom, Y is CH and Z is oxygen atom are preferred. Examples of the preferred compound include methyl 2-{5- (1-benzyloxyiminoethyl) -2- methylphenoxy}-3-methoxyacrylate, methyl 3- [5-{l- (2 , 4- dichlorobenzyloxyimino) ethyl}-2-methylphenoxy] -3- methoxyacrylate, methyl 2-{5- (1-propargyloxyiminoethyl) -2- methylphenoxy}-3-methoxyacrylate, methyl 2-{5-(l-n- propyloxyiminoethyl) -2-methylphenoxy} -3-methoxyacrylate, and the like. In the present compound, that is, compounds represented by the general formula 5 and compounds represented by the general formula 6, there may be (E) and (Z) isomers resulting from C=N linkage and/or C=C linkage and any of such isomers and a mixture thereof are included in the present invention (Terms (E) and (Z) used herein are defined according to Cahn-Ingold-Prelog rule which is widely used for designating geometrical isomers) . The present compound can be prepared according to synthetic scheme shown in the following Scheme 7, Scheme 8, Scheme 9 or Scheme 10. Scheme 7
Compound 4( R4 ≠H)
wherein R44 represents R4 except for hydrogen, R1, R5, R6, T, U, V, W, X, Y and Z are as defined above, and L1 represents a leaving group such as halogen atom (such as chlorine atom, bromine atom, iodine atom and the like) , sulfonate ester group (such as mesyloxy group, tosyloxy group and the like) , sulfate ester group (methoxysulfonyloxy group, ethoxysulfonyloxy group and the like) . Scheme 8
Compound 6
wherein R1, R4, R5, R6, T, U, V, , X, Y and L1 are as defined above, and L2 is alkoxy group (ex. C1-C5 alkoxy group such as methoxy group, ethoxy group and the like) , aryloxy group (phenoxy group and the like) or acyloxy group (ex. C1-C5 acyloxy group such as acetoxy group and the like) when Y is CH group, and L2 is alkoxy group (ex. C1-C5 alkoxy group such as methoxy, group, ethoxy group, isoamyloxy group, butoxy group, tert- butoxy group and the like) or chlorine atom when Y is nitrogen.
Scheme 9
wherein R1, R44, R5, R6, T, U, V, W, X and 1 are as defined above,
Scheme 10
Compound 4 (Y=N, Z=0) Compound 4 (Y=N, Z=NH) wherein R1, R4, R5, R6, T, U, V, W and X are as defined above. A raw material compound [I] in the above Scheme 7 can be prepared, for example, according to the following Scheme 11. Scheme 11
[I] (Y=N, Z=0) [I] (Y=N) z=NH)
wherein R1, R5, R6, T, U, V, W, X, Y, L1 and L2 are as defined above, and R11 represents alkyl group (ex. C1-C5 alkyl group such as methyl group, ethyl group, propyl group, butyl group and the like) or two R11 ' s are taken together to represent alkylene group (ex. C2-C5 alkylene group such as ethylene group, 1, 2-dimethylethylene group, propylene group and the like). A raw material compound 6 in the above Scheme 8 and a raw material compound [X] in the above Scheme 11 can be prepared, for example, according to the following Scheme 12
Scheme 12
Process 12c L11— CH2C02R6 Process 12 b L11— CH2C02R6
wherein R1, R4, R6, X, T, U, V and W are as defined above, L1 represents halogen atom (such as chlorine atom, bromine atom, iodine atom and the like) or sulfonate ester group (such as mesyloxy group, tosyloxy group and the like) .
When R1 is cyano group, alkoxycarbonyl group or nitro group, the intermediate compound [XIII] in the above Scheme 12 can be also prepared, for example, according to the following
Scheme 13.
Scheme 13
wherein R11 represents cyano group, alkoxycarbonyl group or nitro group, R44, L1, L2, X, T, U, V and W are as defined above, and X' represents a group which can be synthetic-chemically derived into X-H group in process 13c, when X represents oxygen atom, then X' represents an oxygen ether group such as benzyloxy group, methoxymethyloxy group, methylthiomethyloxy group, benzyloxymethyloxy group, tetrahydropyran-2-yloxy group and the like, when X represents sulfur atom, then X' represents sulfur ether group such as methoxymethylthio group, isobutoxymethylthio group, tetrahydropyran-2-ylmethylthio group and the like, when X represents NR7 group (wherein R7 is as defined above) , X' represents nitro group or N(R7)R20 group (wherein R7 is as defined above and R20 represents acyl group such as t-butoxycarbonyl group, formyl group, acetyl group and the like) .
In a reaction of a carbonyl compound { [I] , [IV] , [II] or [X]} with a hydroxylamine derivative {HONH2, R4ONH2 or R44ONH2} in process 7a and 7c of the above Scheme 7, process 9c, process 9d, process 9f and process 9i of Scheme 9, and process 12a and process 12d of Scheme 12, a reaction temperature is usually in a range of 0 to 150 2C, a reaction time is usually in a range of 1 to 24 hours, and a molar ratio of the hydroxylamine derivative relative to the carbonyl compound is usually in a range of 1 to 5. Hydroxylamine derivative may be used as a salt with an acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid or the like.
If necessary, an acid catalyst or base catalyst may be used in the reaction. A molar ratio of the catalyst relative to the hydroxylamine derivative is usually in a range of 0.01 to 100. Examples of the acid catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, carboxylic acids such as acetic acid, trifluoroacetic acid, oxalic acid, benzoic acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like and a mixture thereof . The acid catalyst may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like. Examples of the base catalyst include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, potassium carbonate and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2- picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N, -diethylaniline and the like and a mixture thereof . The base catalyst may form a salt with mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like. Examples thereof include sodium acetate and the like. If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane, water and the like and a mixture thereof .
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
In a nucleophilic substitution reaction in process 7b of the above Scheme 7, process 8b of Scheme 8, process 9b, process 9e, process 9h and process 9j of Scheme 9, process lie of Scheme
11, process 12b and process 12c of Scheme 12, and process 13b of Scheme 13, a reaction temperature is in a range of 0 to 150 aC, a reaction time is usually in a range of 1 to 24 hours, and a molar ratio of the electrophilic reagent {R44-L1, R5-Lx or Lu-CH2C02R6} relative to the nucleophilic reagent {Compound 4
(R4=H) , Compound 5, [III], [VI], [VIII], [IX], [XII], [XIII] or [II]} is usually in a range of 1 to 10.
The reaction is usually carried out in the presence of a base, and a molar ratio of the base relative to the electrophilic reagent is usually in a range of 1 to 10. Examples of the base include inorganic salts such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, potassium carbonate, sodium hydride, potassium hydride, silver oxide and the like, alkali metal alkoxides such as potassium-tert-butoxide, sodium methoxide, sodium ethoxide, and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2- picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N, N-diethylaniline, and the line and a mixture thereof.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N, N-diethylaniline and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane, water and the like and a mixture thereof .
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
In an acetalization reaction in process 11a of Scheme 11, a reaction temperature is usually in a range of 0 to 150 aC, and a reaction time is usually in a range of 1 to 24 hours.
When compounds wherein R11 is alkyl group (ex. C1-C5 alkyl group such as methyl group, ethyl group, propyl group, butyl group and the like) in compound [XI] are prepared, a reaction reagent used for acetalizing carbonyl compound [X] is an alcohol compound represented by R11OH, which is usually used at two or more moles excessive amount relative to carbonyl compound [X] . The alcohol compound may be used also as a reaction solvent. When compounds wherein two R11 ' s are taken together to represent alkylene group (ex. C2-C5 alkylene group such as ethylene group, 1, 2-dimethylethylene group, propylene group and the like) in compound [XI] are prepared, a reaction reagent used for acetalizing carbonyl compound [X] is an alkylenediol compound which is corresponding to an acetal moiety, which is usually used at one mole or more excessive amount relative to carbonyl compound [X] .
The reaction is usually carried out in the presence of an acid catalyst and a molar ratio of the acid catalyst relative to carbonyl compound [X] is usually in a range of 0.01 to 100. Examples of the acid catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, carboxylic acids such as acetic acid, trifluoroacetic acid, oxalic acid, benzoic acid and the like, sulfonic acids such as p- toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethane sulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof. The acid catalyst may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like. Orthoesters as a reaction reagent can be further added to the reaction to accelerate the reaction and a molar ratio of the orthoesters to be used relative to carbonyl compound [X] is in a range of 1 to an amount useable as a solvent. Examples of the orthoesters include methyl orthoformate, ethyl orthoformate and the like.
If necessary, a solvent may be used in the reaction. Examples of the solvent include ether solvents such as 1,4- dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, N,N- dimethyl-2-imidazolidone, sulfolane, and the like and a mixture thereof .
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound. In a reaction in process 8a of Scheme 8, process lib of Scheme 11, and process 13a of Scheme 13, a reaction temperature is usually in a range of 0 to 150 aC, a reaction time is usually in a range of 1 to 24 hours, and a molar ratio of the reagent {0=Y-L2} to be used for the reaction relative to the reagent {Compound 6, [XI] or [XIV]} is usually in a range of 1 to 100.
The reaction is usually carried out in the presence of a base. Examples of the base include inorganic bases such as sodium hydride, potassium hydride and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, and alkali metal amides such as sodium amide, lithium amide, lithium diisopropylamide, sodium hexamethyldisilazide, lithium hexamethyldisilazide and the like and a mixture thereof. If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N-dimethylaniline, N, N-diethylaniline and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, N,N- dimethyl-2-imidazolidone, sulfolane and the like and a mixture thereof . After completion of the reaction, the reaction solution can be treated with an aqueous acidic solution such as dilute hydrochloric acid, subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. In a reaction of process 10 of Scheme 10, and process lid of Scheme 11, a reaction temperature is usually in a range of 0 to 150 2C, a reaction time is usually in a range of 1 to 24 hours, and a molar ratio of alkylamine represented by R6-NH2 relative to alkylester {Compound 4, (Y=N, Z=0) or [I] (Y=N, Z=0) } is usually in a range of 1 to 100.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as dichloroethane, carbon tetrachloride, monochlorobenzene and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane and the like and a mixture thereof. After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. In a reaction in process 9a and process 9g of Scheme 9, a reaction temperature is usually in a range of 0 to 150 aC, a reaction time is usually in a range of 1 to 24 hours. A molar ratio of 2-chloro-2- (hydroxyimino) acetate ester to be used for the reaction relative to compound [II] or [VII] is usually in a range of 1 to 10. A method of preparing 2-chloro-2- (hydroxyimino) acetate ester is described, for example, in U.S. P. No. 3584032.
The reaction is usually carried out in the presence of a base and a molar ratio of the base relative to compound [II] or [VII] is usually in a range of 1 to 100. Examples of the base include inorganic beses such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4- dimethylaminopyridine , quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and a mixture thereof.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane, water and the like and a mixture thereof.
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound.
In process 13c of Scheme 13 , when X represents oxygen atom and X' represents oxygen ether group, when X represents sulfur atom and X' represents sulfur ether group, or when X represents NR7 group (wherein R7 group is as defined above) , X' represents N(R7)R20 group and R20 group represents acyl group such as t-butoxycarbonyl group, formyl group or acetyl group, then the reaction is usually carried out in the presence of an acid. A reaction temperature is usually in a range of 0 to 150 aC, a reaction time is usually in a range of 1 to 100 hours, and a molar ratio of the acid relative to compound [XVI] is usually in a range of 0.001 to an amount useable as a solvent. Examples of the acid to be used in the reaction include carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid, benzoic acid and the like, sulfonic acids such as methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid and the like, mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, perchloric acid and the like, Lewis acids such as zinc chloride, aluminium chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride, trimethylsilyl iodide and the like, and a mixture thereof.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane, water and the like and a mixture thereof.
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. When X represents N-R7group (wherein R7 group is as defined above) and X1 represents nitro group, process 13c comprises a process represented by the following Scheme 14:
Scheme 14
Process 14a
[XIX] [XX]
Process 14d
[XXI](X=N-R7) wherein R11, R44, R7, T, U, V, W and L1 are as defined above, and R21 represents hydrogen atom, alkyl group such as methyl group, or haloalkyl group such as chloromethyl group, trichloromethyl group and trifluoromethyl group.
Process 14a is a reducing reaction carried out using zinc , iron, tin or tin (II) chloride usually in the presence of an acid. A reaction temperature is usually in a range of 0 to 150 aC, and a reaction time is usually in a range of 1 to 100 hours. A molar ratio of the acid relative to compound [XVII] is usually in a range of 1 to an amount useable as a solvent. Examples of the acid to be used in the reaction include carboxylic acids such as acetic acid, propionic acid, butyric acid, trifluoroacetic acid, pentafluoropropionic acid and the like, sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid and the like, mineral acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid and the like, and a mixture thereof .
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, organic acid solvents such as acetic acid and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, and a mixture thereof. After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. An acylation reaction represented by process 14b is carried out using an acylating reagent such as R21COOH itself, or ester, acid halide or anhydride thereof. A molar ratio of the acylating reagent relative to compound [XVIII] is usually in a range of 1 to an amount useable as a solvent. A reaction temperature is usually in a range of 0 to 200 aC, and a reaction time is usually in a range of 1 to 200 hours. The reaction may be carried out in the presence of an acid or base catalyst as necessary. A molar ratio of the catalyst relative to raw material compound [XVIII] is in a range of 0.0001 to 100.
Examples of the acid catalyst include mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof. The acid catalyst may form a salt with alkali metal such as sodium, potassium and the like, or organic base such as pyridine, triethylamine, N,N- di ethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
Examples of the base catalyst include inorganic bases such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, barium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, alkali metal amides such as sodium amide, lithium amide, lithium diisopropylamide, sodium hexamethyldisilazide, lithium hexamethyldisilazide and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and a mixture thereof. The base catalyst may form a salt with mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as acetic acid, benzoic acid and the like, Lewis acids such as zinc chloride and the like. One example thereof is sodium acetate. If necessary, a solvent may be used in the reaction. Examples of the solvent include ether solvents such as 1,4- dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, N,N- dimethyl-2-imidazolidone, sulfolane, water and the like, and a mixture thereof.
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, distillation, chromatography or the like to isolate the desired compound.
In process 14c, a reaction temperature is usually in a range of 0 to 150 aC, and a reaction time is usually in a range of 1 to 24 hours. A molar ratio of compound R7-L1 relative to compound [XIX] is usually in a range of 1 to 10.
The reaction is usually carried out in the presence of a base and a molar.ratio of the base relative to compound R7-L1 is usually in a range of 1 to 10. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate, sodium hydride, potassium hydride, silver oxide and the like, alkali metal alkoxides such as potassium-tert-butoxide, sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, organic bases such as pyridine, 2-picoline, 4-picoline, 4- dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N,N-dimethylaniline, N,N- diethylaniline and the like, and a mixture thereof.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- di ethylaniline, N, N-diethylaniline and the like, ester solvents such as ethyl formate, butyl acetate, ethyl acetate, diethyl carbonate and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N- dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2- imidazolidone, sulfolane, water and the like, and a mixture thereof .
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. In process 14d which is a hydrolysis reaction, a reaction temperature is usually in a range of 0 to 150 aC, and a reaction time is usually in a range of 1 to 24 hours. The reaction is carried out usually in the presence of a base or an acid and a molar ratio of the base or the acid relative to compound [XX] is usually in a range of 0.001 to 1000. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, barium carbonate, calcium carbonate and the like, alkali metal alkoxides such as potassium-t-butoxide, sodium methoxide, sodium ethoxide and the like, alkaline earth metal alkoxides such as magnesium ethoxide and the like, and a mixture thereof. Examples of the acid include mineral acids such as hydrochloric acid, perchloric acid, hydrobromic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, polyphosphoric acid and the like, sulfonic acids such as p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like, Lewis acids such as zinc chloride, boron trifluoride diethyl ether complex, trimethylsilyl chloride and the like, and a mixture thereof. The acid may form a salt with alkali metals such as sodium, potassium and the like, organic bases such as pyridine, triethylamine, N,N-dimethylaniline and the like. Examples thereof are pyridinium p-toluenesulfonate and the like.
If necessary, a solvent may be used in the reaction. Examples of the solvent include alcohol solvents such as methanol, ethanol, propanol, butanol, isopropanol and the like, ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tert-butyl methyl ether and the like, aliphatic hydrocarbon solvents such as hexane, heptane, ligroin, petroleum ether and the like, aromatic hydrocarbon solvents such as toluene, xylene and the like, halogenated hydrocarbon solvents such as chloroform, dichloroethane, carbon tetrachloride, monochlorobenzene and the like, organic base solvents such as pyridine, triethylamine, N-methylaniline, N,N- dimethylaniline, N,N-diethylaniline and the like, nitro compound solvents such as nitroethane, nitrobenzene and the like, nitrile solvents such as acetonitrile, isobutyronitrile and the like, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethyl-2-imidazolidone, sulfolane, water and the like, and a mixture thereof.
After completion of the reaction, the reaction solution can be subjected to conventional post-treatment such as extraction with organic solvents, concentration and the like and, if necessary, further purified by recrystallization, chromatography or the like to isolate the desired compound. In Scheme 11, when X represents sulfur atom, compound [X] can be also prepared, for example, by reacting diazonium compound [XXII] and thiolate salt [XXIII] according to the following Scheme 15. Diazonium salt [XXII] can be prepared by the known methods . Scheme 15
[xxπ] [xxπη pq ( x=s, z=o )
wherein R1, R6, T, U, V and W are as defined above, and L" represents halogen ion such as chlorine ion, bromine ion, or monoanion of strong acid such as sulfuric acid ion, nitric acid ion and the like. When the present compound is used as an active ingredient for agricultural and/or horticultural antifungal agent, it is usually used by formulating into emulsifiable concentrate, water dispersible powder, suspension, dust or granule by mixing with solid carrier, liquid carrier, surfactant or other adjuvants for formulation although it may be used as it is without addition of any other ingredients. These formulations contain as an active ingredient the present compound usually at a weight ratio of 0.1 to 99.9%, preferably 1 to 90%.
Examples of the solid carrier used for such formulation include fine powders or granules of caolin clay, attapulgite, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, maize rachis powder, walnut shell powder, urea, ammonium sulfate, synthetic hydrated silicon oxide and the like, and examples of the liquid carrier include aromatic hydrocarbons such as xylene, methylnaphthalene and the like, alcohols such as isopropanol, ethylene glycol, cellosolve and the like, ketones such as acetone, cyclohexanone, isophorone and the like, vegetable oils such as soybean oil, cotton seed oil and the like, dimethyl sulfoxide, acetonitrile, water and the like. Examples of the surfactant include anionic surfactants such as alkylsulfate salt, alkyl (aryl) sulfonate salt, dialkylsulfosuccinate salt, polyoxyethylene alkyl aryl ether phosphate salt, naphthalenesulfonate formalin condensate and the like, nonionic surfactant such as polyoxyethylene alkyl ether, polyoxyethylene alkyl polyoxypropylene block copolymer, sorbi an fatty acid ester and the like.
Examples of the adjuvant for formulation include lignin sulfonate salt, alginate salt, polyvinyl alcohol, gum arabic, CMC (carboxylmethyl cellulose) , PAP (isopropyl acid phosphate) and the like.
The present compound is applied by, for example, foliage application, soil treatment, seed disinfection although they can be usually used by any application method known to those skilled in the art. When the present compound is used as an active ingredient for an agricultural and/or horticultural antifungal agent, an amount of the present compound to be applied may vary depending upon kind of subject plant (crop and the like) , kind of subject disease, occurrence degree of disease, formulation form, application method, application time, weather conditions and may be usually 0.01 to 50 g/are, preferably 0.05 to 10 g/are. When emulsifiable concentrate, water dispersible powder, suspension and the like are applied after diluted with water, the application concentration of the present compound is usually 0.0001 to 0.5%, preferably 0.0005 to 0.2%, and dust, granule or the like is applied as it is without any dilution. The present compound may be used as an agricultural and/or horticultural antifungal agent for farmland, paddy field, orchard, tea plantation, pasture, lawn area and potentiated antifungal effect can be expected by using by mixing with other agricultural and/or horticultural antifungal agent. Example of the other agricultural and horticultural antifungal agent include azole antifungal compound such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromoconazole, epoxyconazole, difenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, myclobutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole (RPA 400727), bitertanol, imazalil, flutriafol and the like, cyclic amine antifungal compound such as fenpropimorph, tridemorph, fenpropidin and the like, benzimidazole antifungal compounds such as carbendazim, benomyl, thiabendazole, thiophanate-methyl and the like, procymidone, cyprodinil, pyrimethanil, diethofencarb, thiuram, fluazinam, mancozeb, iprodione, vinclozolin, chlorothalonil, captan, mepanipyrim, fenpiclonil, fludiozonil, dichlofluanid, folpet, kresoxim-methyl (or methyl methoxyimino- a -(o- tolyloxy) -o-tolylacetate, or BAS490F) , azoxystrobin (or methyl (E) -{2- [6- (2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}- 3-methoxyacrylate, or ICIA5504) , N-methyl- a -methoxyimino- 2-[ (2, 5-dimethylphenoxy) methyl]phenylacetamide and the like. Further, the present compounds may be used by mixing with or in combination with insecticide, acaricide, nematicide, herbicide, plant growth regulator, fertilizer or the like. Examples of the vegetable disease which can be controlled by the present compound are as follows: blast (Pyricularia orvzae) , leaf spot (Cochliobolus miyabeanus) and sheath blight (Rhizoctonia solani) of rice plant, powdery mildew (Ervsiphe σraminis) , scab (Gibberella zeae) , rust (Puccinia striiformis, P. σraminis, P. recondita. P. hordei) , snow blight (Typhula sp. , Micronectriella nivalis ) , loose smut (Ustilaσo tritici. U. nuda) , bunt (Tilletia caries) , eyespot ( Pseudocercosporella herpotrichoides ) , leaf blotch (Rhvnchosporium secalis) , leaf blight (Septoria tritici) and glume blotch (Leptosphaeria nodorum) of cereal, melanose (Diaporthe citri) , scab (Elsinoe fawcetti) and blue mold (Penicillium diσitatum, P. italicum) of oranges, blossom blight (Sclerotinia mali) , canker (Valsa mali) , powdery mildew (Podosphaera leucotricha) , alternaria blotch (Alternaria mali) and scab (Venturia inaeσualis) of apple, scab (Venturia nashicola, V. pirina) , black spot (Alternaria kikuchiana) and rust (Gvmnosporandium haraeanum) of pear, brown rot (Sclerotinia cinerea) , scab (Cladosporium carpophilum) and phomopsis rot (Phomoosis sp. ) of peach, anthracnose (Elsinoe ampelina) , ripe rot (Glomerella cinσulata) , powdery mildew (Uncinula necator) , rust (Phakopsora amelopsidis) , black rot (Guiσnardia biwellii) and downy mildew (Plasmopara viticola) of grape anthracnose (Gloeosporium kaki) and angular leaf spot (Cercospora kaki . Mvcosphaerelle nawae) of persimmon, anthracnose (Colletotrichum laσenarium) . powdery mildew (Sphaerotheca fuliσinea) , gummy stem blight (Mvcosphaerella elonis) , stem rot (Fusarium oxysporum) , downy mildew ( Pseudoperonospora cubensis) , late blight (Phvtophthora sp. ) and da ping-off (Pvthium SP. ) of Cucurbit, early blight (Alternaria solani) , leaf mold (Cladosporium fulvum) and late blight (Phvtophthora infestans) of tomato, brown spot (Phomopsis vexans ) and powdery mildew (Ervsiphe cichoracearum) of egg plant, alternaria leaf spot (Alternaria iaponica) and white spot (Cercosporella brassicae) of Crucifer, rust (Puccinia allii) of Welsh onion, purple stain (Cercospora kikuchii) , sphaceloma scab (Elsinoe σlycines) and melanose (Diaoorthe phaseolorum var . saiae) of soybean, anthracnose (Collectotrichum lindemthianum) of kidney bean, early leaf spot (Cercospora personata) and late leaf spot (Cercospora arachidocola) of peanut, powdery mildew (Ervsiphe pisi) of garden pea, early blight (Alternaria solani) and late light (Phytophthora infestans) of potato, powdery mildew (Sphaerotheca humuli) of strawberry, net blister blight (Exobasidium reticulatum) and white scab (Elsinoe leucospila) of tea, brown spot (Alternaria lonσipes) , powdery mildew (Ervsiphe cichoracearum) , anthracnose (Collectotrichum tabacum) , downy mildew (Peronospora tabacina) and late blight (Phvtophthora nicotianae. of tobacco, cercospora leaf spot (Cercospora beticola) of beat, black spot (Diplocaroon rosae) and powdery mildew (Sphaerotheca pannosa) of rose, leaf blight (Septoria chrvsanthemiindici) and white rust (Puccinia horiana) of chrysanthemum, and gray mold (Botrvtis cinerea) and sclerotinia rot (Sclerotinia sclerotiorum) of various crops.
When the present compound is used as an active ingredient for insecticidal and/or acaricidal agent, they may be used as such without addition of any other ingredients. However, it is usually used by formulating into oil solution, emulsifiable concentrate, water dispersible powder, flowable agent, granule, dust, aerosol, fumigant (fogging agent or the like) , poisonbait or the like, by mixing with solid carrier, liquid carrier, gaseous carrier, bait or the like and, if necessary, adding surfactant, or other auxiliaries for formulation.
These preparations contain the present compound as an active ingredient, usually, in a ratio by weight of 0.01% to 95%. Examples of the solid carrier used for such formulation are fine powders or granules of clay (such as caolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, Fubasami clay, acid clay and the like) , talcs, ceramic, other inorganic minerals (such as cericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica and the like) , chemical fertilizer (such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride and the like) . Examples of the liquid carrier are water, alcohols (such as methanol, ethanol and the like) , ketones (such as acetone, methyl ethyl ketone and the like) , aromatic hydrocarbons (such as benzene, toluene, xylene, ethylbenzene, methylnaphthalene and the like) , aliphatic hydrocarbons (such as hexane, cyclohexane, kerosine, light oil and the like) , esters (such as ethyl acetate, butyl acetate and the like) , nitriles (such as acetonitrile, isobutyronitrile and the like) , ethers (such as diisopropyl ether, dioxane and the like) , acid amides (such as N,N-dimethylformamide, N,N-dimethylacetamide and the like) , halogenated hydrocarbons (such as dichloromethane, trichloroethane, carbon tetrachloride and the like) , dimethyl sulfoxide, vegetable oils such as soy bean oil, cotton seed oil and the like. Examples of the gaseous carrier, that is, propellant are flon gas, butane gas, LPG (liquefied petroleum gas) , dimethyl ether, carbonic acid gas and the like.
Examples of the surfactant are alkylsulfate salt, alkylsulfonate salt, alkylarylsulfonate salt, alkyl aryl ether and its polyoxyethylene compound, polyethylene glycol ether, polyhydric alcohol ester, sugar alcohol derivative and the like.
Examples of the auxiliary for formulation such as adhesive agent and dispersing agent are casein, gelatin, polysaccharides (such as starch powder, gum arabic, cellulose derivative, alginic acid and the like) , lignin derivatives, bentonite, sugars, synthetic water-soluble polymer (such as polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid and the like) and the like. Examples of the stabilizing agent are PAP (acid isopropyl phosphate), BHT (2, 6-di-tert-butyl-4- ethylphenol) , BHA (mixture of 2-tert-butyl-4-methoxyphenol and3-tert-butyl-4-methoxyphenol) , vegetable oil, mineral oil, surfactant, and fatty acid or ester thereof and the like.
Examples of the base material for poison bait are components for bait such as cereal powder, vegetable oil, sugar, crystalline cellulose and the like, antioxidant such as dibutylhydroxytoluene, nordihydroguaiaretic acid and the like, preservative such as dehydroacetic acid and the like, substance for preventing erroneous eating such as red pepper powder, attractant flavor such as cheese flavor, onion flavor and the like.
The preparations thus prepared are used as they are or after diluted with water or the like. Alternatively, the preparations may be used by mixing with or in combination with other insecticide, nematicide, acaricide, antifungal agent, herbicide, plant growth regulator, synergist, fertilizer, soil conditioner, animal feed, and the like.
The insecticide and/or nematocide and/or acaricide may include, for example, organophosphorus compounds such as
Fenitrothion [O, O-dimethyl 0- (3-methyl-4- nitrophenyl)phosphorothioate] , Fenthion [0, O-dimethyl 0-(3- methyl-4- (methylthio) phenyl) phophorothioate] , Diazinon
[0, O-diethyl -0-2 -isopropyl -6 -methylpyrimidin-4- ylphosphorothioate] , Chlorpyrifos [0, O-diethyl-0-3 , 5 , 6- trichloro-2-pyridylphosphorothioate] , Acephate [0,S- dimethylacetylphosphoramidothioate] , Methidathion [S-2,3- dihydro-5-methoxy-2-oxo-l , 3 , 4-thiadiazol-3-ylmethyl 0, 0- dimethylphosphorodithioate] , Disulfoton [0, 0-diethyl S-2- e t hy 1 thi o e t hy lpho sphor o thi oa t e ] , DDVP [2,2- dichlorovinyldimethylphosphate] , Sulprofos [0-ethyl 0-4- (methylthio) phenyl S-propyl phosphorodithioate] , Cyanophos [ 0- 4 -cyanophenyl 0 , 0-dime thy lphosphor o thioa t e ] , Dioxabenzofos [2-methoxy-4H-l, 3 , 2-benzodioxaphosphinine-2- sul f ide ] , Dimethoate [ 0 , O-dimethyl -S- ( N- methylcarbamoylmethyDdithiophosphate] , Phenthoate [ethyl 2-dimethoxyphosphinothioylthio (phenyl) acetate] , Malathion [diethyl (dimethoxyphosphinothioylthio ) succinate] , Trichlorf on [ dimethyl 2 , 2 , 2 -trichloro-1 - hydroxyethylphosphonate] , Azinphos -methyl [S-3 , 4-dihydro-4- oxo - l , 2 , 3 -benz o triaz in - 3 -ylme thyl 0 , 0 - di ethylphosphorodithioate] , Monocrotophos [dimethyl (E)-l- methyl-2 - (methylcarbamoyl ) vinylphosphate ] , Ethion
[ 0 , 0 , 0 ' , 0 ' - t e t r a e t h y l S , S ' - methylenebis (phosphorodithioate) ] , and phosphothiazate [N- (0-methyl-S-sec-butyl) phosphorylthiazolidine-2 -one) ; carbamate compounds such as BPMC (2-sec- butylphenylmethylcarbamate) , Benfuracarb [ethyl N-[2,3- d i hydr o - 2 , 2 - d i me t hy l b e n z o f u r a n - 7 - yloxycarbonyl (methyl) aminothio] -N-isopropyl- β -alaninate] , Propoxur [2-isopropoxyphenyl N-methylcarbamate] , Carbosulfan
[2 , 3-dihydro-2 , 2-dimethyl-7-benzo [b] furanyl N- dibutylaminothio-N-methylcarbamate] , Carbaril [1 -naphthyl -
N-methylcarbamate] , Methomyl [S-methyl-N-
[ (methylcarbamoyl) oxy] thioacetimidate] , Ethiofencarb [2- (ethylthiomethyl)phenylmethylcarbamate] , Aldicarb [2- methyl-2- (methylthio) propionaldehyde 0 - me thy lcarbamoy loxime ] , Oxamyl [ N , N- dime thy 1 - 2 - methylcarbamoyloxyimino-2- (methylthio) acetamide] , and Fenothiocarb [S-4-phenoxybutyl-N,N-dimethylthiocarbamate] ; pyrethroid compounds such as Etofenprox [2-(4- ethoxyphenyl ) -2 -methylpropyl-3 -phenoxybenzylether ] , Fenvalerate [ (RS )- a -cyano-3 -phenoxybenzyl (RS)-2-(4- chlorophenyl) -3-methylbutyrate] , Esf envalerate [(S)-α- cyano-3 -phenoxybenzyl ( S ) - 2 - ( 4 -chlor opheny 1 ) - 3 - me thylbutyrate ] , Fenpr opa thr in [ ( RS ) - a - cyano- 3 - phenoxybenzyl 2,2,3, 3-tetramethylcyclopropanecarboxylate] , Cypermethrin [ (RS) - -cyano-3 -phenoxybenzyl (1RS,3RS)- 3- (2, 2-dichlorovinyl) -2 , 2-dimethylcyclopropanecarboxylate] , Permethrin [ 3 -phenoxybenzyl (IRS, 3RS)- 3-(2,2- dichlorovinyl) -2 , 2 -dimethylcyclopropanecarboxylate] , Cyhalothrin [ (RS) - a -cyano-3 -phenoxybenzyl (Z) - (IRS, 3RS) -3- (2-chloro-3 , 3 , 3 -trif luoropropenyl) -2 , 2 - dimethylcyclopropanecarboxylate] , Deltamethrin [ (S) - a - cyano-m-phenoxybenzyl (IR, 3R) -3- (2 , 2-dibromovinyl) -2 , 2- dimethylcyclopropanecarboxylate] , Cycloprothrin [(RS)-α- cyano-3-phenoxybenzyl (RS) -2 , 2-dichloro-l- ( 4 - ethoxyphenyl) cyclopropanecarboxylate] , Fluvalinate ( a - cyano-3 -phenoxybenzyl N- (2-chloro- a , a, a -trif luoro-p- tolyl) -D-valinate) , Bifenthrin [2-methylbiphenyl-3-ylmethyl (Z) - (IRS) -cis-3- (2-chloro-3 , 3 , 3-trif luoroprop-1-enyl) -2,2- dimethylcyclopropanecarboxylate) , Acrinathrin [cyano- (3- phenoxyphenyl) methyl [1R-{1 a (S*),3 a (Z) } ] -2 , 2-dimethyl-3- [3-oxo-3- (2,2, 2-trif luoro-1- ( trif luoromethyl ) ethoxy- 1- propenyl ) cyclopropanecarboxylate ] , 2 -methyl -2 -( 4 - bromodif luoromethoxyphenyl) propyl ( 3 -phenoxybenzyl ) ether, Tralomethrin [ (S) - a -cyano-3-phenoxylbenzyl (lR)-cis-3- ( l , 2 , 2 , 2 - t e t r a b r o m o e t h y l ) - 2 , 2 - dimethylcyclopropanecarboxylate] , and Silafluofen [4- e t h o x y l p h e n y l [3- (4-f luoro-3-phenoxyphenyl) propyl] dimethyls i lane] ; thiadiazine derivatives such as Buprofezin (2-tert- butylimino-3-isopropyl-5-phenyl-l, 3, 5-triaziazinane-4-one; nitroimidazolidine derivatives such as Imidacloprid [l-(6- chloro-3-pyridylmethyl) -N-nitroimidazolidin-2-ylidenamine] ; Nereistoxin derivatives such as Cartap [S, S' - (2- dimethylaminotrimethylene)bis (thiocarbamate) ] , Thiocyclam [N,N-dimethyl-l, 2 , 3 -trithian-5-ylamine] , and Bensultap [ S , S ' - 2 - d i m e t h y l a m i n o t r i m e t h y l e n e di (benzene thiosulfonate) ] ; N-cyanoamidine derivatives such as N-cyano-N' -methyl-N' - (6-chloro-3-pyridylmethyl) acetamidine; chlorinated hydrocarbon compounds such as Endosulfan [6,7,8,9,10, 10-hexachloro-l, 5, 5a, 6, 9, 9a-hexahydro-6 , 9- methano-2 , 4 , 3 -benzodioxathiepinoxide ] , gamma-BHC [ 1 , 2 , 3 , 4 , 5 , 6 -hexachlorocyc lohexane ] , and 1, 1- bis (chlorophenyl) -2,2, 2-trichloroethanol; benzoylphenylurea compounds such as Chlorf luazuron [ 1- (3 , 5-dichloro-4- (3- chloro-5-trif luoromethylpyridin-2-yloxy) phenyl) -3- (2 , 6- dif luorobenzoyl) urea] , Tef lubenzuron [1- (3 , 5-dichloro-2 , 4- di fluorophenyl ) -3- (2 , 6-dif luorobenzoyl) urea] , and Fulphenoxron [1- (4- (2-chloro-4-trif luoromethylphenoxy) -2- f luorophenyl) -3- (2 , 6-dif luorobenzoyl) -urea] ; formamidine d e r i v a t i v e s s u c h a s Am i t r a z [ N , N ' - [ (methylimino) dimethylidine ] -di-2 , 4-xylidine] , and Chlordimeform [ ' - (4-chloro-2-methylphenyl) -N,N- dimethylmethinimidamide] ; thiourea derivatives such as Diafenthiuron. [N- (2, 6-diisopropyl-4-phenoxyphenyl) -N' -tert- butylcarbodiimide] , phenylpyrazole compounds, Tebfenozide [ N- t ert -butyl -N ' - ( 4 - ethylben z oyl ) - 3 , 5 - dimethylbenzohydrazide] , 4-bromo-2- (4-chlorophenyl ) -1- ethoxymethyl-5-trif luoromethylpyrrole-3 -carbonitrile ; Bromopropylate [isopropyl 4, 4 ' -dibromobenzylate] , Tetradifon [ 4 - chlor opheny 1 2 , 4 , 5 - t r i chlor opheny 1 sul f one ] , Quinomethionate [S, S-6-methylquinoxaline-2 , 3 - diy ldi thi oc arbona t e ] , Propargate [2- (4-tert- butylphenoxy) cyclohexyl prop-2-yl sulfite] , Fenbutatin oxide [bis [tris (2-methyl-2-phenylpropyl) tin] oxide] , Hexythiazox [ (4RS, 5RS) -5- (4-chlorophenyl) -N-chlorohexyl-4-methyl-2-oxo- 1, 3-thiazolidine-3-carboxamide] , Chlof entezine [3,6-bis(2- chlorophenyl) -1, 2 , 4, 5-tetrazine] , Pyridathioben [2-tert- butyl-5- (4-tert-butylbenzylthio) -4-chloropyridazine-3 (2H) - one], Fenpyroximate [tert-butyl (E) -4- [ ( 1 , 3-dimethyl-5- phenoxypyr az o 1 - 4 -y 1 ) me thy 1 eneami nooxyme thy 1 ] - benzoate] , Tebfenpyrad [N-4-tert-butylbenzyl] -4-chloro-3- ethyl-1 -methyl- 5 -pyrazolecarboxamide] , polynactin complexes [e.g., tetranactin, dinactin, trinactin] , Milbemectin, Avermectin, Ivermectin, Azadilactin [AZAD] , Pyrimidifen [5- chloro-N- [2- {4- (2-ethoxyethyl) -2 , 3-dimethylphenoxy}ethyl] - 6-ethylpyrimidine-4-amine] , pymetrozine [2,3,4,5- tetrahydro-3-oxo-4- [ (pyridin-3-yl)methyleneamino] -6-methyl- 1,2, 4-triazine.
When the present compounds are used as an agricultural insecticidal and/or acaricidal agent, the application dosage is usually 0.1 g to 100 g/10 are. When emulsif iable concentrate, water dispersible powder, f lowable and the like are used after diluted with water, the application concentration is usually 0.1 ppm to 5000 ppm. Granule, dust and the like are applied as preparations themselves without any dilution. When the present compound is used as epidemic preventive insecticidal and/or acaricidal agent, emulsifiable concentrate, water dispersible powder, flowable agent and the like are usually applied after diluted with water to 0.1 ppm to 5000 ppm, and oil solution, aerosol, fumigant, poison bait and the like are applied as such.
These application dosage and application concentration may vary depending upon kind of preparations, application timing, application place, application method, kind of insect pest, degree of damage and the like and they may be increased or decreased beyond the above range.
The harmful insects and harmful ticks and mites , against which the present compounds exhibit controlling activity, may include, for example, the following: Hemiptera:
Planthoppers (Delphacidae) such as small brown planthopper (Laodelphax striatellus) , brown rice planthopper
(Nilaoarvata luσens) , white-backed rice planthopper (Soσatella furcifera) ; leafhoppers (Deltocephalidae) such as green rice leafhopper (Nephotettix cincticeos) and green rice leafhopper (Nephotettix virescense) ; aphids (Aphididae) , stink bugs (Pentatomidae) , whiteflies (Aleyrodidae) , scales
(Coccidae) , lace bugs (Tingidae) , psyllids (Psyllidae) Lepidoptera:
Pyralid moths (Pyralidae) such as rice stem borer (Chilo suppressalis) , rice leafroller (Cnaphalocrocis medinalis) and Indian meal moth (Plodia interpunctella) ; owlet moths (Noctuidae) such as common cutworm (Soodoptera litura) , rice armyworm (Pseudaletia separata) and cabbage armyworm (Mamestra brassicae) , white and sulfer butterflies (Pieridae) such as common cabbageworm (Pieris rapae crucivora) , tortricid moths
(Tortricidae) such as Adoxophyes spp . ; Carposinidae; lyonetiid moths (Lyonetiidae) ; tussock moth (Lymantriidae) ; Plusiae;
Agrothis spp. such as cutworm (Aσrothis seσetum) and black cutworm (Aσrothis ipsilon) : Heliothis spp.; diamondblack
(Plutella xylostella) ; casemaking clothes moth (Tinea pellionella) ; webbing clothes moth (Tineola bisselliella) Diptera:
Mosquitos (Calicidae) such as common mosquito (Culex pipiens pallens) and Culex tritaeniorhvnchus; Aedes spp. such as Aedes aeσvpti and Aedes albopictus; Anopheles spp. such as
Anopheles sinensis ; midges (Chironomidae) ; house flies (Muscidae) such as housefly (Musca domestica) and false stablefly (Muscina stabulans) ; Calliphoridae; Sarcophagidae; anthomyiid flies (Anthornyiidae) such as lesser housefly (Fannia canicularis) , seedcorn maggot (Hylemya platura) and onion maggot (Delia antiσue) ; fruit flies (Tephritidae) ; small fruit flies (Drosophilidae) ; moth flies (Psychodidiae) ; black flies
(Simuliidae) ; Tabanidae; stable flies (Stomoxyidae)
Celeoptera:
Corn rootworm such as western corn rootworm (Diabrotica virσifora) and southern corn root worm (Diabrotica undecimpunctata) ; scarabs (Scarabaeidae) such as cupreous chafer (Anomala cuprea) and soybean beetle (Anomala rufocuprea) ; weevils (Cureulionidae) such as maize weevil (Sitophilus zeamalis) , rice water weevil (Lissorhoptrus orvzophilus) and adzuki bean weevil (Callosobruchys chineneis) ; darkling beetles (Tenebrionidae) such as yellow mealworm (Tenebrio moliter) and red flour beetles (Tribolium astaneum) ; leaf beetles (Chrysomelidae) such as striped flea beetles (Phyllotrata stroilata) and cucurbit leaf beetle (Aulacophora femoralis) ; drugstore beetles (Anobiidae) ; Epilachna spp. such as twenty-eight-spotted ladybirds (Epilachna viσintioctopunctata) ; powder post beetles (Lyctidae) ; false powder post beetles (Bostrychidae) ; longhorn beetles (Ceramysidae) , Paederus fuscioes Dictyoptera:
German cockroach (Blattella σermanica) , smokybrown cockroach (Periplaneta fuliσinosa) , American cockroch (Periolaneta americana) , brown cockroach (Periplaneta brunnea) and oriental cockroach (Blatta orientalis) Thysanoptera:
Thrips palmi and flower thrips (Thrips hawaiiensis) Hymenoptera:
Ants (Formicidae) ; Vespidae; Bethylidae; sawflies (Tenthredinidae) such as cabbage sawfly (Athalia rosae -iaponensis)
Orthoptera :
Mole crickets (Gryllotalpidae; grasshoppers (Acrididae) Aphaniptera : Purex irritans Anoplura :
Pediculus humanus caoitis. Phthirus pubis Isoptera:
Reticulitermes speratus . Formosan subterrauean termite (Coptotermes formosanus) Acarina : plant parasitic mites such as Tetranvchus urticae. Panonvchus citri, Tetranvchus cinnabarinus and Panonvchus ulmi . animal parasitic Ixodes such as Boophilus microphus . and house dust mites
The present compound is also effective for the control of insect pests with resistance to conventional insecticides or acaricides.
The following Preparations, Formulation Examples and Test Examples illustrate the present invention in detail but are not to be construed to limit the scope thereof.
Preparation 1 [Example of process 7c of the above Scheme 7]
0.2 g (0.76 mmol) of methyl 2- (N-methyl-3- acetylanilino) -3-methoxyacrylate (prepared according to
Reference Preparation 1 below), 0.07 g (0.84 mmol) of methoxylamine hydrochloride, 0.1ml (1.2 mmol) of pyridine and
2 ml of methanol were mixed at room temperature and the mixture was stirred for 3 hours . The reaction mixture was concentrated under reduced pressure, and the resulting residue was partitioned between 10 ml of ethyl acetate and 10 ml of dilute hydrochloric acid. The organic layer was successively washed with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and concentrated under reduced pressure to obtain the residue, which was subjected to silica gel column chromatography to obtain 0.2 g (0.68 mmol) of the desired methyl
2-{N-methyl-3- (1-methoxyiminoethyl) anilino}-3- ethoxyacrylate (present compound 2) .
Preparation 2 [Example of process 7a of the above Scheme 7]
0.4 g (1.5 mmol) of methyl 2- (N-methyl-3- acetylanilino) -3-methoxyacrylate (prepared according to Reference Preparation 1 below), 0.12 g (1.7 mmol) of hydroxylamine hydrochloride, 0.15 ml (1.9 mmol) of pyridine and 5 ml of methanol were mixed at room temperature and the mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the resulting residue was partitioned between 30 ml of ethyl acetate and 30 ml of dilute hydrochloric acid. The organic layer was successively washed with dilute hydrochloric acid once and water once and concentrated under reduced pressure to obtain 0.4 g (1.4 mmol) of the desired methyl 2-{N-methyl-3- (1- hydroxyiminoethyl)anilino}-3-methoxyacrylate (present compound 3 )
Preparation 3 [Example of process 7b of the above Scheme
7]
A mixture of 24 mg (1.0 mmol) of sodium hydride and 2 ml of N,N-dimethylformamide was added at once to a solution of 0.2 g (0.72 mmol) of methyl 2-{N-methyl-3- (1- hydroxyiminoethyl) anilino} -3-methoxyacrylate (present compound 3: prepared in Preparation 2) in 0.5 ml of N,N- di ethylformamide while stirring at room temperature, followed by stirring at room temperature for 1 hour. Then, 0.1 ml (0.84 mmol) of benzyl bromide was added thereto at once at room temperature, followed by stirring at room temperature for 3 hours. The reaction mixture was poured into 10ml of a mixture of ice and dilute hydrochloric acid and extracted with 10 ml of ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried over magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 0.2 g (0.54 mmol) of the desired methyl 2- {N-methyl-3- (1- benzyloxyiminoethyl) anilino}-3-methoxyacrylate (present compound 4) .
Preparation 4 [Example of process 7c of the above Scheme
7] A mixture of 0.10 g (0.39 mmol) of N-methyl-2- (N- methyl-3-acetylanilino) -2-methoxyiminoacetamide (prepared in Reference Preparation 2 below), 40 mg (0.48 mmol) of methoxylamine hydrochloride, 0.063 ml (0.78 mmol) of pyridine and 2.0 ml of methanol was stirred at room temperature overnight . The resulting mixture was concentrated and the residue was partitioned between ethyl acetate and dilute hydrochloric acid. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodiumbicarbonate, dried with magnesium sulfate and concentrated to obtain 0.11 g (0.38 mmol) of the desired N-methyl-2-{N-methyl-3- (1- methoxyiminoethyl) anilino}-2-methoxyiminoacetamide (present compound 31) .
Preparation 5 [Example of process 7c of the above Scheme 7] A mixture of 0.20 g (0.80 mmol) of methyl 2- (3- acetylphenoxy) -3-methoxyacrylate (prepared in Reference Preparation 3 below) , 0.20 g (1.3 mmol) of O-benzylhydroxyamine hydrochloride, 0.080 ml (1.0 mmol) of pyridine and 1 ml of methanol was stirred at room temperature overnight. The resulting reaction mixture was concentrated, and the resulting residue was partitioned between ethyl acetate and water. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 0.25 g (0.70mmol) of the desired methyl 2- {3- (1-benzyloxyiminoethyl) phenoxy} - 3-methoxyacrylate (present compound 12) .
Preparation 6 (Example of process 12d of the above Scheme 12 and examples of process 8a and process 8b of Scheme 8) (i) [Example of process 12d of the above Scheme 12]
A mixture of 0.50 g (2.4 mmol) of methyl 2- (N-methyl- 3-formylanilino) acetate (prepared in Reference Preparation 4 below), 0.40 g (2.5 mmol) of O-benzylhydroxylamine hydrochloride, 0.20 ml (2.5 mmol) of pyridine and 5 ml of methanol was stirred at room temperature overnight and concentrated. The residue was partitioned between ethyl acetate and dilute hydrochloric acid, and the organic layer was washed with an aqueous solution of sodium bicarbonate and dried with magnesium sulfate. Concentration afforded 0.74 g (2.4 mmol) of the desired methyl 2-{N-methyl-3- (benzyloxyiminomethyl)anilino}acetate (example of the intermediate represented by the above Compound 6) . 1H-N R (CDC13, TMS)
§ (ppm) : 8.09 (IH, s) , 7.1-7.5 (7H) , 6.9-7.0 (2H) , 6.69 (IH, br.d), 5.21 (2H, s) , 4.08 (2H, s) , 3.71 (3H, s) , 3.07 (3H, s) (ii) [Example of process 8a of the above Scheme 8] A mixture of 0.74 g (2.4 mmol) of methyl 2- {N-methyl- 3- (benzyloxyiminomethyl)anilino}acetate, 1.0ml (16 mmol) of methyl formate, 0.10 g (4.2 mmol) of sodium hydride and 8 ml of N,N-dimethylformamide was stirred at room temperature for 2 hours . The resulting mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid and extracted twice with an aqueous solution of sodium carbonate. The resulting aqueous basic solution was adjusted to pH 6 using concentrated hydrochloric acid. The precipitated organic material was extracted with ethyl acetate. The organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 50 mg (0.13 mmol) of the desired methyl 3 -hydroxy-2- {N-methyl-3 -
(benzyloxyiminomethyl)anilino}acrylate (example of the intermediate represented by the above Compound 5) .
(iii) [Example of process 8b of the above Scheme 8] 1.0 ml (16 mmol) of methyl iodide, 1.0 g (7.2 mmol) of potassium carbonate and 4 ml of N,N-dimethylformamide were added to 50 mg (0.13 mmol) of methyl 3 -hydroxy-2- {N-methyl- 3- (benzyloxyiminomethyl)anilino}acrylate, followed by stirring at room temperature overnight. The resulting mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 50 mg (0.13 mmol) of the desired methyl 2-{N-methyl-3- (benzyloxyiminomethyl) anilino) }-3- methoxyacrylate (present compound 1) .
Preparation 7 [Example of process 7c of the above Scheme 7 (process 9c of the above Scheme 9)] A mixture of 0.18 g (0.67mmol) of methyl 2-(N-methyl- 3-acetylanilino) -2-methoxyiminoacetate [prepared ■ in Reference Preparation 2 (ii) below], 0.13 g (0.81 mmol) of hydroxylamine-O-benzyl ether hydrochloride, 0.11 ml (1.4 mmol) of pyridine and 2.0 ml of methanol was stirred at room temperature overnight . The resulting mixture was concentrated and the residue was partitioned between ethyl acetate and dilute hydrochloric acid. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once, dried with magnesium sulfate and concentrated to obtain 0.24 g (0.65 mmol) of the desired methyl 2-{N-methyl-3- (1-benzyloxyiminoethyl) anilino}-2- methoxyiminoacetate (present compound 199) .
Preparation 8 [Example of process 7c of the above Scheme 7]
A mixture of 0.20 g (0.75 mmol) of methyl 2- (3- acetylphenylthio) -3-methoxyacrylate [prepared in Reference Preparation 5 below], 0.13 g (0.81 mmol) of 0- benzylhydroxylamine hydrochloride, 0.073 ml (0.9 mmol) of pyridine and 2.0 ml of methanol was stirred at room temperature overnight. The resulting reaction mixture was concentrated, and the resulting residue was partitioned between ethyl acetate and dilute hydrochloric acid. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 0.23 g (0.65 mmol) of the desired methyl 2-{3- (l-benzyloxyiminoethyl)phenylthio}-3- methoxyacrylate (present compound 209) .
Preparation 9 [Examples of process 8a and process 8b of the above Scheme 8]
The same manner as that in Preparation 6 (ii) and (iii) except that methyl 2-{3- (1-benzyloxyiminoethyl) -6- chlorophenoxy}acetate [prepared in Reference Preparation 6 below] was used instead of methyl 2-{N-methyl-3- (benzyloxyiminomethyl)anilino}acetate as a starting material afforded the desired methyl 2-{3- (1-benzyloxyiminoethyl) -6- chlorophenoxy} -3 -methoxyacrylate (present compound 132) .
Preparation 10 [Example of process 8b of the above Scheme 8]
A mixture of 119 mg (0.412 mmol) of 2- [3- {N-methyl-N-
(methyl 3 -hydroxyacrylate-2-yl ) amino}phenyl] -2- methoxyiminoacetonitrile (prepared in Reference Preparation 7 below), 100 mg (0.724 mmol) of potassium carbonate, 0.05 ml (0.8 mmol) of methyl iodide and 1 ml of dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid, extracted with ethyl acetate, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried over magnesium sulfate and concentrated to obtain 120 mg (0.396 mmol) of the desired 2- [3-{N-methyl-N-
(methyl 3-methoxylacrylate-2-yl) amino}phenyl] -2- methoxyiminoacetonitrile (present compound 272) .
Preparation 11 [Example of process 7b of the above Scheme 7]
A mixture of 500 mg (1.89 mmol) of methyl 2-{3-(l- hydroxyiminoethyl ) phenoxy} -3-methoxyacrylate [prepared in Reference Preparation 8 below], 408 mg (1.89 mmol) of 2,3- dichloro-5-trifluoromethylpyridine, 300 mg (2.17 mmol) of potassium carbonate and 3 ml of N,N-dimethylformamide was stirred for 2 hours while heating to 100 aC to obtain the mixture which was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate and concentrated to obtain the residue, which was purified by silica gel column chromatography to obtain 800 mg
(1.80 mmol) of the desired methyl 2- [3-{l- (3-chloro-5- trifluoromethylpyridine-2-yl) oxyiminoethyl}phenoxy] -3- methoxyacrylate (present compound 116) .
Preparation 12 [Example of process 7b of the above Scheme 7]
A mixture of 500 mg (1.80 mmol) of methyl 2-{N- methyl-3- (1-hydroxyiminoethyl) anilino} -3-methoxyacrylate [prepared in the above Preparation 2 (present compound 3) ] , 389 mg (1.80 mmol) of 2 , 3-dichloro-5-trifluoromethylpyridine, 300 mg (2.17 mmol) of potassium carbonate and 3 ml of N,N- dimethylformamide was stirred for 2 hours while heating to 100 aC to obtain the mixture, which was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate and concentrated to obtain the residue, whichwas purified by silica gel column chromatography to obtain 800 mg (1.75 mmol) of the desired methyl 2- [N-methyl-3-{l- (3-chloro-5- trifluoromethylpyridin-2-yl)oxyiminoethyl}anilino] -3- methoxyacrylate (present compound 252) .
Preparation 13 [Example of process 8b of the above Scheme 8] A mixture of 15 g (about 41 mmol) of crude product of methyl 2- {5- (1-benzyloxyiminoethyl) -2-methylphenoxy}-3- hydroxyacrylate [prepared in Reference Preparation 9 below] , 8.8 g (62 mmol) of methyl iodide, 9.7 g (70 mmol) of potassium carbonate and 100 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate. Concentration gave the crude crystals, which were washed with hexane, filtered and dried to obtain 9.8 g (27 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2- methylphenoxy} -3 -methoxyacrylate (present compound 215) . Preparation 14 [Example of process 7c of the above Scheme 7]
A mixture of 0.12 g (0.47 mmol) of methyl 2- (5- acetyl-2-methylphenoxy) -3-methoxyacrylate [prepared in Reference Preparation 10 below], 0.12 g (0.76 mmol) of 0- benzylhydroxyamine hydrochloride, 0.046 ml (0.58 mmol) of pyridine and 0.6 ml of methanol was stirred at room temperature for 5 hours. The resulting reaction mixture was concentrated, and the resulting residue was partitioned between ethyl acetate and water. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once , dried with magnesium sulfate and concentrated to obtain 0.15 g (0.41 mmol) of the desired methyl 2-{5-(l- benzyloxyiminoethyl ) -2-methylphenoxy} -3 -methoxyacrylate (present compound 215) . Preparation 15
A mixture of 1.0 g (about 2.7 mmol) of crude product of methyl 2-{5- (1-benzyloxyiminoethyl) -2-ethylphenoxy}-3- hydroxyacrylate [prepared in Reference Preparation 11 below] , 0.59 g (4. lmmol) of methyl iodide, 0.64 g (4.6 mmol) of potassium carbonate and 6 ml of N,N-dimethylformamide was stirred at room temperature for 1 hour. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate.
Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 0.36 g (1.0 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2- ethylphenoxy} -3-methoxyacrylate (present compound 216) .
Preparation 16
A mixture of 0.28 g (1.0 mmol) of methyl 2-(5-acetyl- 2-methyl-phenylthio) -3-methoxyacrylate [prepared in Reference Preparation 12 below], 0.17 g (1.1 mmol) of 0- benzylhydroxyamine hydrochloride, 0.10 g (1.2 mmol) of pyridine and 6 ml of methanol was stirred at room temperature overnight. The resulting reaction mixture was concentrated and the resulting residue was partitioned between ethyl acetate and dilute hydrochloric acid. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 0.35 g (0.91 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2-methyl-phenylthio} -3- methoxyacrylate (present compound 217) . Preparation 17
A mixture of 0.70 g (2.5 mmol) of methyl 2-(5-acetyl- 2-methyl-phenylthio) -2- (methoxyimino) acetate [prepared in Reference Preparation 13 below], 0.65 g (4.0 mmol) of 0- benzylhydroxyamine hydrochloride, 0.25 g (3.1 mmol) of pyridine and 4 ml of methanol was stirred at room temperature for 1 hour. The resulting reaction mixture was concentrated and the resulting residue was partitioned between ethyl acetate anddilute hydrochloric acid. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 0.88 g (2.3 mmol) of the desired methyl 2- {5- (1-benzyloxyiminoethyl) -2-methyl-phenylthio}-2- (methoxyimino) acetate (present compound 232). Preparation 18
A mixture of 0.40 g (1.0 mmol) of methyl 2-{5-(l- benzyloxyiminoethyl ) -2-methyl-phenylthio}-2- (methoxyimino) acetate [prepared in the above Preparation 17 (present compound 232)], 3 ml of methanol and 2.3 g (29 mmol) of a 40% solution of methylamine in methanol was stirred at room temperature for 1 hour. The resulting reaction mixture was filtered, and the filtrate was concentrated to obtain 0.40 g (1.0 mmol) of the desired N-methyl-2-{5- (1- benzyloxyiminoethyl) -2-methyl-phenylthio} -2- (methoxyimino) aceta ide (present compound 233). Preparation 19
A mixture of 24 mg (0.091 mmol) of methyl 2- (5- acetyl-2-methylphenoxy) -2- (methoxyimino) acetate [prepared in Reference Preparation 14 below], 16 mg (0.10 mmol) of O- benzylhydroxyamine hydrochloride, 9 mg (0.11 mmol) of pyridine and 2 ml of methanol was stirred at room temperature for 3 hours . The resulting reaction mixture was concentrated and the resulting residue was partitioned between ethyl acetate and dilute hydrochloric acid. The organic layer was washed successivelywith dilute hydrochloric acid, an aqueous solution of sodium bicarbonate and water, dried with magnesium sulfate and concentrated to obtain 29 mg (0.078 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2-methylphenoxy} -2- (methoxyimino) acetate (present compound 256) . Preparation 20
A solution of 29 mg (0.078 mmol) of methyl 2-{5-(l- benzyloxyi inoethyl) -2-methylphenoxy} -2-
(methoxyimino) acetate [prepared in the above Preparation 19 (present compound 256) ] , 2 ml of methanol and 100 mg (1.3 mmol) of a 40% solution of methylamine in methanol was allowed to stand at room temperature overnight, and to this was added 100 mg (1.3 mmol) of a 40% solution of methylamine in methanol, followed by stirring for 3 hours. The resulting reaction solution was subjected as it was to silica gel thin layer chromatography to obtain 23 mg (0.062 mmol) of the desired N-methyl-2-{5- (1- benzyloxyiminoethyl) -2-methylphenoxy} -2- (methoxyimino) acetamide (present compound 257). Preparation 21 A mixture of 200mg (0.717 mmol) of methyl 2-{5-(l- hydroxyiminoethyl) -2-methylphenoxy} -3-methoxyacrylate [prepared in Reference Preparation 16 below] , 20 mg (0.83 mmol) of sodium hydride and 2 ml of N,N-dimethylformamide was stirred at room temperature for 20 minutes and 105 mg of 1-chloro- 2-methoxyiminopropane was added thereto . Stirring was further continued for 1 hour and the resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate.
Concentration gave an oil which was purified by silica gel column chromatography to obtain 150 mg (0.412 mmol) of the desired methyl 2-{5- (1- (2-methoxyiminopropoxy) iminoethyl) - 2-methylphenoxy} -3-methoxyacrylate (present compound 446) .
Reference Preparation 1
(i) [Example of process 12c of the above Scheme 12] A mixture of 25 g (0.17 mol) of N-methyl-3-acetylaniline, 24 g (0.17 mol) of potassium carbonate, 16 ml (0.17 mol) of methyl bromoacetate and 300 ml of N,N-dimethylformamide was stirred overnight, the mixture was poured into 500 ml of a mixture of ice and dilute hydrochloric and extracted with 500 ml of ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once, dried with magnesium sulfate and concentrated to obtain 24 g (0.11 mmol) of the desired methyl 2-(N- methyl-3-acetylanilino) acetate. ^-NMR (CDC13, TMS) δ (ppm) : 7.2-7.4 (3H) , 6.89 (IH, m) , 4.14 (2H, s) , 3.73 (3H, s), 3.12 (3H, s) , 2.59 (3H, s)
(ii) [Example of process 11a of the above Scheme 11] A mixture of 23.8 g (0.10 mmol) of methyl 2-(N- methyl-3-acetylanilino) acetate, 1.0 g (5.3 mmol) of p- toluenesulfonic acid monohydrate, 20 ml (0.18 mmol) of trimethyl orthoformate and 300 ml of methanol was heated to reflux for 3 hours while stirring. After allowing to stand at room temperature and addition of 1 ml (7.2 mmol) of triethylamine, concentration under reduced pressure gave the residue, which was partitioned between ethyl acetate and water . The organic layer was dried with magnesium sulfate and concentrated to obtain 28 g (0.10 mol) of the desired methyl 2-{N-methyl-3- (1, 1-dimethoxyethyl) anilino}acetate. XH-NMR (CDC13, TMS) δ (ppm) : 7.21 (IH, t) , 6.8-7.0 (2H) , 6.60 (IH, br.d) , 4.09 (2H, s), 3.72 (3H, s) , 3.18 (6H, s) , 3.07 (3H, s) , 1.52 (3H, s)
(iii) [Example of process lib of the above Scheme 11] A mixture of 10 g (37 mmol) of methyl 2-{N-methyl-3- (1, 1-dimethoxyethyDanilino}acetate and 20 ml (0.32 mol) of methyl formate was added to a mixture of 2.5 g (0.10 mol) of sodium hydride and 200 ml of N,N-dimethylformamide at once while stirring at room temperature. Stirring was further continued at room temperature for 3 hours , and the mixture was poured into 300 ml of a mixture of ice and dilute hydrochloric acid and extracted with 500 ml of ethyl acetate. The organic layer was washed with dilute hydrochloric acid once and extracted twice with 300 ml of an aqueous solution of sodium carbonate. The resulting sodium carbonate solution was made weakly acidic with concentrated hydrochloric acid to precipitate the desired material as crystals. This mixture was extracted twice with 500 ml of ethyl acetate to obtain the organic layer, which was washed once with water, dried with magnesium sulfate and concentrated to obtain 1.1 g (3.7 mmol) of the desired methyl 3-hydroxy-2- (N-methyl-3-acetylanilino) acrylate.
XH-NMR (CDCI3, TMS) (2:1 mixture of isomers) δ (ppm) : 7.23 (1HX1/3, s) , 7.1-7.4 (3H + 1HX2/3) , 6.36 (IH, ), 3.69 (3HX1/3, s) , 3.64 (3HX2/3, s) , 3.12 (3HX1/3, s), 3.09 (3HX2/3, s) , 2.53 (3HX1/3, s) , 2.40 (3HX2/3, s) (iv) [Example of process lie of the above Scheme 11] A mixture of 1.1 g (4.4 mmol) of methyl 3-hydroxy-2- (N-methyl-3-acetylanilino)acrylate, 1 g (7.2 mmol) of potassium carbonate, 0.5 ml (8.02 mmol) of methyl iodide and 15 ml of N,N-dimethylformamide was stirred at room temperature overnight, poured into 30 ml of a mixture of ice and dilute hydrochloric acid and extracted with 30 ml of ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once, driedwithmagnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain l.Og (3.2 mmol) of the desired methyl 3-methoxy-2- (N-methyl-3-acetylanilino) acrylate. ^-NMR (CDC13, TMS) δ (ppm) : 7.43 (IH, s) , 7.2-7.4 (3H) , 6.83 (IH, br.d) , 3.88 (3H, s), 3.67 (3H, s) , 3.10 (3H, s) , 2.53 (3H, s) Reference Preparation 2
(i) [Example of process 9a of the above Scheme 9] After a solution of 1.9 g (13 mmol) of methyl 2- chloro-2-hydroxyiminoacetate in 2 ml of toluene was added dropwise to a mixture of 2.0 g (13 mmol) of N-methyl-3- acetylaniline, 1.9 ml (13 mmol) of triethylamine and 15 ml of toluene while stirring under ice-cooling, stirring was continued for 12 hours while raising a temperature gradually to room temperature. The resulting reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with water once and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain l.Og (4.0 mmol) of the desired methyl 2- (N-methyl-3-acetylanilino) -2- hydroxyiminoacetate .
XH-NMR (TMS, CDC13.) δ (ppm) : 7.53 (IH, d) , 7.41 (IH, br.s), 7.35 (IH, t, ) , 6.94 (IH, br.d), 3.77 (3H, s) , 3.31 (3H, s) , 2.57 (3H, s) (ii) [Example of process 9b of the above Scheme 9] After a mixture of 0.84 g (3.4 mmol) of methyl 2-(N- methyl-3-acetylanilino) -2-hydroxyiminoacetate, 0.10 g (4.2 mmol) of sodium hydride and 10 ml of tetrahydrofuran was stirred at room temperature for 20 minutes, the mixture was ice-cooled, 0.46 ml (3.4 mmol) of dimethyl sulfate was added thereto dropwise, and stirring was continued for 2 hours while raising a temperature to room temperature. The resulting mixture was poured into a mixture of ice and an aqueous solution of sodium chloride and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and concentrated to obtain the residue which was subjected to silica gel column chromatography to obtain 0.36 g (1.4 mmol) of the desired methyl 2-(N- methyl-3-acetylanilino) -2-methoxyiminoacetate. ^Η-NMR (TMS, CDC13) δ (ppm) : 7.52 (IH, d) , 7.3-7.4 (2H) , 6.93 (IH, br.d) , 4.04 (3H, s) , 3.80 (3H, s), 3.27 (3H, s) , 2.58 (3H, s)
(iii) [Example of process lid of the above Scheme 11] A mixture of 0.25 g (0.95 mmol) of methyl 2- (N- methyl-3-acetylanilino) -2-methoxyiminoacetate, 3 ml of methanol and 3 g (27 mmol) of a 28% solution of methylamine in methanol was stirred at 50 C for 2 hours. Concentration gave the residue, which was dissolved in ethyl acetate, and washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate. The organic layer was dried with magnesium sulfate and concentrated to obtain the 0.20 g
(0.76 mmol) of the desired N-methyl-2- (N-methyl-3- acetylanilino) -2-methoxyiminoactamide. XH-NMR (CDC13, TMS) (2:1 mixture of isomers) δ (ppm) : 7.3-7.8 (3H) , 6.6-7.1 (2H) , {3.83 (3Hx2/3) , 3.40 (3Hxl/3) ,eachs}, {3.27 (3Hx2/3), 3.24 (3Hxl/3), eachs}, {2.89 (3Hx2/3) , 2.75 (3Hxl/3) , eachd}, {2.58 (3Hx2/3) , 2.56 (3Hxl/3) , each s} Reference Preparation 3
(i) [Example of process 12c of the above Scheme 12] A mixture of 4.4 g (32 mmol) of 3-hydroxyacetophenone, 3.3 ml (35 mmol) of methyl bromoacetate, 5.3 g (38 mmol) of potassium carbonate and 60 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 6.2 g (30 mmol) of the desired methyl 2- (3-acetylphenoxy) acetate. ^- MR (TMS, CDC13) δ (ppm) : 7.60 (IH, d) , 7.49 (IH, br.s) , 7.40 (IH, t) , 7.14 ( IH, br . d) , 4 .71 ( 2H, s ) , 3 . 83 ( 3H, s ) , 2 . 58 ( 3H, s )
(ii) [Example of process 11a of the above Scheme 11] A mixture of 6.2 g (30 mmol) of methyl 2- (3- acetylphenoxy) acetate, 0.60 g (3.1 mmol) of p-toluenesulfonic acid monohydrate, 30 ml (270 mmol) of trimethyl orthoformate and 20ml of methanol was heated to reflux for 12 hours. The reaction solution was allowed cool to room temperature, and to this was added 1 ml (7.2 mmol) of triethylamine, followed by stirring for 15 minutes . Concentration gave the residue, which was partitioned between ethyl acetate andwater, and the organic layer was dried with magnesium sulfate and concentrated to obtain 7.4 g (29 mmol) of the desired methyl 2-{3-(1,1- dimethoxyethyl)phenoxy}acetate . δ (ppm) : 7.27 (IH, t) , 7.13 (IH, br.d), 7.08 (IH, br.s), 6.83 (IH, br.d), 4.65 (2H, s) , 3.81 (3H, s) , 3.18 (6H, s) , 1.52 (3H, s)
(iii) [Example of process lib of the above Scheme 11]
A mixture of 7.4 g (29 mmol) of methyl 2-{3-(l,l- dimethoxyethyl)phenoxy}acetate, 10 ml (170 mmol) of methyl formate, 1.5 g (63 mmol) of sodium hydride and 100ml of
N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed once with dilute hydrochloric acid and extracted twice with an aqueous solution of sodium carbonate.
The resulting aqueous alkaline layer was adjusted to around pH
6 with concentrated hydrochloric acid and the precipitates were extractedwith ethyl acetate . The organic layer was washedwith water, dried with magnesium sulfate and concentrated to obtain 5.0 g (21 mmol) of the crude product of desired methyl 2- (3-acetylphenoxy) -3-hydroxyacrylate.
(iv) [Example of process lie of the above Scheme 11] A mixture of 5.0 g (21 mmol) of the crude product of methyl 2- (3-acetylphenoxy) -3-hydroxyacrylate, 2 ml (32 mmol) of methyl iodide, 5 g (36 mmol) of potassium carbonate and 50 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 2.7 g (11 mmol) of the desired methyl 2- (3- acetylphenoxy) -3-methoxyacrylate. XH-NMR (TMS, CDC13) δ (ppm) : 7.59 (IH, d) , 7.51 (IH, br.s) , 7.37 (IH, t) , 7.35 (IH, s) , 7.18 (IH, br.d), 3.87 (3H, s) , 3.71 (3H, s) , 2.58 (3H, s)
Reference Preparation 4
(i) A mixture of 10 g (66 mmol) of 3-nitrobenzaldehyde, 0.30 g (1.6 mmol) of p-toluenesulfonic acid monohydrate and 0.20 liter of methanol was heated to reflux for 3 hours, followed by allowing to cool to room temperature. 1.0 ml (7.2 mmol) of triethylamine was added to the resulting mixture and concentrated to obtain the residue, which was partitioned between 200 ml of ethyl acetate and water. The organic layer was dried with magnesium sulfate and filtered to obtain an ethyl acetate solution, and to this was added 0.50 g (2.2 mmol) of platinum dioxide, followed by shaking at room temperature for 3 hours under hydrogen gas atmosphere. Filtration gave the solution, which was concentrated to obtain 11 g (66 mmol) of the desired 3- (dimethoxymethyl) aniline. XH-NMR (CDC13 , TMS) δ (ppm) : 7.14 (IH, t) , 6.7-6.9 (2H) , 6.64 (IH, br.d) , 5.29 (IH, s), 3.67 (2H, br) , 3.32 (6H, s)
(ii) After 12 ml (85 mmol) of trifluoroacetic anhydride was added dropwise to a mixture of 11 g (66 mmol) of 3- (dimethoxymethyl) aniline, 14 ml (lOOmmol) of triethylamine and 0.20 liter of methylene chloride over 30 minutes while stirring under ice-cooling, a temperature was raised to room temperature over 1 hour. The resulting mixture was concentrated, and to the residue were added 14 g (100 mmol) of potassium carbonate, 6.4 ml (100 mmol) of methyl iodide and 100 ml of N,N- dimethylformamide, followed by stirring at room temperature overnight. The resulting mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate and dried with magnesium sulfate. To the residue obtained by concentration were added 8.3 g (60mmol) of potassium carbonate, 100 ml of methanol and 10 ml of water, which was heated to reflux for 1 hour and allowed to cool to room temperature. The resulting reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water . The organic layer was dried with magnesium sulfate and concentrated to obtain the residue, and to this were added 0.20 liter of methanol and 0.30 g (1.6 mmol) of p-toluenesulfonic acid monohydrate, followed by heating to reflux for 3 hours. The mixture was allowed to cool to room temperature, and 1 ml (7.2 mmol) of triethylamine was added thereto, followed by concentration. The residue was partitioned between ethyl acetate and water and the organic layer was dried with magnesium sulfate and concentrated to obtain 3.5 g (19 mmol) of the desired N-methyl-3- (dimethoxymethyl) aniline . XH-NMR (CDC13, TMS) δ (ppm) : 7.19 (IH, t) , 6.78 (IH, d) , 6.72 (IH, br.s) , 6.59 (IH, br.d), 5.32 (IH, s) , 3.33 (6H, s) , 2.84 (3H, s)
(iii) A mixture of 3.5 g (19 mmol) of N-methyl-3- (dimethoxymethyl) aniline, 2.0 ml (21 mmol) of methyl bromoacetate, 3.0 g (22 mmol) of potassium carbonate and 40 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 3.5 g (17 mmol) of the desired methyl 2- (N-methyl-3- formylanilino) acetate .
XH-NMR (CDC13, TMS) δ (ppm) : 9.96 (IH, s) , 7.39 (IH, t) , 7.24 (IH, d) , 7.17 (IH, br.s), 6.94 (IH, br.d), 4.15 (2H, s) , 3.73 (3H, s) , 3.12 (3H, s)
Reference Preparation 5 (i) [Example of process 12c of the above Scheme 12] A mixture of 2.84 g (19 mmol) of 3-acetylbenzenethiol, 2.0 ml (21 mmol) of methyl bromoacetate, 4.0 g (29 mmol) of potassium carbonate and 40 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 2.7 g (12 mmol) of the desired methyl 2- (3-acetylphenylthio) acetate. XH-NMR (TMS, CDC13) δ (ppm) : 8.00 (IH, s), 7.81 (IH, d) , 7.61 (IH, d) , 7.41 (IH, t) , 3.73 (3H, s), 3.70 (2H, s) , 2.59 (3H, s) (ii) [Example of process 11a of the above Scheme 11] A mixture of 2.7 g (12 mmol) of methyl 2- (3- acetylphenylthio) acetate, 0.11 g (0.53 mmol) of p- toluenesulfonic acid monohydrate, 10 ml (92 mmol) of trimethyl orthoformate and 30 ml of methanol was heated to reflux for 4 hours. The reaction solution was allowed to cool to room temperature, and to this was added 0.50 ml (3.6 mmol) of triethylamine, followed by stirring for 15 minutes. Concentration gave the residue, which was partitioned between ethyl acetate and water, and the organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 2.6 g (9.6 mmol) of the desired methyl 2-{3-(l,l- dimethoxyethyl) phenylthio}acetate. ^- MR (TMS, CDC13) δ (ppm) : 7.54 (IH, s), 7.3-7.4 (3H) , 3.72 (3H, s) , 3.66 ( 2H , s ) , 3 . 17 ( 6H , s ) , 1 . 51 ( 3H , s )
(iii) [Example of process lib of the above Scheme 11] A solution of 2.1 g (7.7 mmol) of methyl 2-{3-(l,l- dimethoxyethyl) phenylthio}acetate in 10 ml (170 mmol) of methyl formate was added dropwise to a mixture of 1.0 g (17 mmol) of potassium hydride and 30 ml of 1, 2-dimethoxyethane under argon atmosphere while stirring, followed by further stirring at room temperature for 2 hours. The resulting reaction mixture was poured into ice-water, the aqueous layer was washed twice with diethyl ether. The aqueous layer was made acidic by the addition of concentrated hydrochloric acid and the precipitates were extracted twice with ethyl acetate. The organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 1.8 g (7.2 mmol) of the desired methyl 2- (3-acetylphenylthio) -3 -hydroxyacrylate .
XH-NMR (TMS, CDC13) (2:1 mixture of isomers) δ (ppm) : 7.7-8.3 (3H) , 7.3-7.5 (2H) , 3.77 (2/3X3H, s) , 3.76 (1/3X3H, s), 2.57 (3H, s)
(iv) [Example of process lie of the above Scheme 11] A mixture of 1.8 g (7.2 mmol) of methyl 2- (3- acetylphenylthio) -3 -hydroxyacrylate, 0.5 ml (8.0 mmol) of methyl iodide, 1.0 g (7.2 mmol) of potassium carbonate and 14 ml of N,N-dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 1.8 g (6.8 mmol) of the desired methyl 2- (3- acetylphenylthio) -3-methoxyacrylate. XH-NMR (TMS, CDC13) δ (ppm) : 8.02 (IH, s) , 7.79 (IH, s) , 7.70 (IH, d) , 7.3-7.5 (2H), 4.01 (3H, s) , 3.73 (3H, s) , 2.56 (3H, s)
Reference Preparation 6 : Preparation of intermediate of compound No. 132
(i) [Example of process 12c of the above Scheme 12] The same manner as that in Reference Preparation 3 (i) except that 200 mg (1.17 mmol) of 3-hydroxy-4- chloroacetophenone was used instead of 3-hydroxyacetophenone afforded 192 mg (0.79 mmol) of methyl-2- (3-acetyl-6- chlorophenoxy) acetate .
Hϊ-NMR (CDC13, TMS) δ (ppm) : 7.4-7.6 (3H) , 4.79 (2H, s) , 3.81 (3H, s) , 2.57 (3H, s)
(ii) [Example of process 12d of the above Scheme 12] The same manner as that in Preparation 6 (i) except that 192 mg (0.792 mmol) of methyl-2- (3-acetyl-6- chlorophenoxy) acetate was used instead of methyl 2-(N- methyl-3-formylanilino) acetate afforded 182 mg (0.751 mmol) of methyl 2-{3- (1-benzyloxyiminoethyl) -6-chlorophenoxy}acetate (intermediate for preparing the present compound) . XH-NMR (CDC13, TMS) δ (ppm) : 7.1-7.4 (8H), 5.22 (2H, s) , 4.74 (2H, s) , 3.80 (3H, s), 2.32 (3H, s)
Reference Preparation 7 (Preparation of intermediate for present compound 272)
(i) [Example of process 13a of the above Scheme 13] 2.34 g (14.4mmol) of 2- (3-nitropheny1) acetonitrile was added to a mixture of 380 mg (15.8 mmol) of sodium hydride and 25 ml of dimethylformamide at room temperature while stirring the mixture. After vigorous evolution of hydrogen gas ceased, 2.23 g (21.6 mmol) of tert-butyl nitrite was added thereto at room temperature, followed by continuing to stir overnight. The reaction solution was poured into 100 ml of dilute hydrochloric acid and extracted with 100 ml of ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate. Concentration gave the residue, which was subjected to silica gel column chromatography to obtain 647 mg (2.29 mmol) of the desired 2- (3-nitropheny1) -2-hydroxyiminoacetatonitrile. (ϋ) [Example of process 13b of the above Scheme 13] 647 mg (2.29 mmol) of 2- (3-nitrophenyl) -2- hydroxyiminoacetonitrile was added to a mixture of 8 ml of tetrahydrofuran and 70 mg (2.9 mmol) of sodium hydride at room temperature while stirring the mixture. After vigorous evolution of hydrogen gas ceased, 0.3 ml (3.17 mmol) of dimethyl sulfate was added thereto while ice-cooling the reaction solution, and stirring was continued for 1 hour while allowing to warm to room temperature. The resulting reaction solution was diluted with 30 ml of diethyl ether, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 527 mg (2.57 mmol) of the desired 2- (3-nitrophenyl) -2- methoxyiminoacetonitrile . XH-NMR (CDCI3, TMS) δ (ppm) : 8.68 (IH, br.s) , 8.33 (IH, br.d) , 8.11 (IH, br.d) , 7.68 (IH, t), 4.28 (3H, s)
(iii) [Example of process 14a of the above Scheme 14] A mixture of 0.87 g (16 mmol) of iron powder and 1.5 ml of 10% aqueous solution of acetic acid was stirred at 100 °C for 1 hour. To the reaction solution was added a mixture of
527 mg (2.57 mmol) of 2- (3-nitrophenyl) -2- methoxyiminoacetonitrile, 2.5 ml of acetic acid and 2.5 ml of ethyl acetate, which was heated to reflux for 20 minutes and allowed to cool. The reaction solution was poured into 25 ml of an aqueous solution of sodium bicarbonate, extracted twice with ethyl acetate, the combined organic layers were further washed twice with an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 438 mg
(2.50 mmol) of the desired 2- (3-aminophenyl) -2- methoxyiminoacetonitrile .
XH-NMR (CDCI3. TMS) δ (ppm) : 7.1-7.3 (2H) , 7.10 (IH, br.s), 6.78 (IH, br.d), 4.20 (3H, s) , 3.81 (2H, br.)
(iv) [Example of process 14b of the above Scheme 14] Trifluoroacetic anhydride was added dropwise to a mixture of 438 mg (2.50 mmol) of 2- (3-aminophenyl) -2- methoxyiminoacetonitrile and ethyl acetate under ice-cooling while stirring the mixture. After the ice bath was removed and stirring was continued for 1 hour, the reaction solution was concentrated under reduced pressure to obtain 664 mg (2.45 mmol) of the desired 2- (3-trifluoroacetoaminophenyl) -2- methoxyiminoacetonitrile . XH-NMR (CDCI3. TMS) δ (ppm) : 7.97 (IH, br.s) , 7.94 (IH, br.) , 7.81 (IH, br.d) , 7.67 (IH, br.d) , 7.52 (IH, t) , 4.24 (3H, s)
(v) [Example of process 14c of the above Scheme 14] A suspension of 70 mg (2.9 mmol) of sodium hydride in 1 ml of dimethylformamide was added to a mixture of an all amount of 2- (3-trifluoroacetoaminophenyl) -2- methoxyiminoacetonitrile obtained in the above (iv) , 0.3 ml (4.82 mmol) of methyl iodide and 5 ml of dimethylformamide while stirring the mixture under ice-cooling. The ice bath was removed and stirring was continued at room temperature for 1 hour. The reaction solution was poured into dilute hydrochloric acid, extracted with 20ml of ethyl acetate, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodiumbicarbonate, dried with magnesium sulfate and concentrated to obtain 593 mg (2.08 mmol) of the desired 2-{3-(N- methyltrifluoroacetoamino) phenyl} -2- methoxyiminoacetonitrile . XH-NMR (CDCI3, TMS) δ (ppm) : 7.83 (IH, br.d), 7.73 (IH, br.s), 7.54 (IH, t) , 7.38 (IH, br.d), 4.24 (3H, s) , 3.41 (3H, s)
(vi) [Example of process 14d of the above Scheme 14] A mixture of an all amount of 2-{3-(N- methyltrifluoroacetamino) phenyl} -2-methoxyiminoacetonitrile obtained in the above (v) , 1.0 g (7.2 mmol) of potassium carbonate, 5 ml of methanol and 3 ml of water was heated to reflux for 30 minutes and allowed to cool to room temperature, methanol was distilled off under reduced pressure, the resulting mixture was partitioned between 20 ml of water and 20 ml of ethyl acetate, and the organic layer was dried with magnesium sulfate and concentrated to obtain 316 mg (1.67 mmol) of the desired 2- {3- (N-methylamino) phenyl} -2-methoxyiminoactonitrile. h-I-NMR (CDC13, TMS) δ (ppm) : 7.24 (IH, t) , 7.12 (IH, br.d), 7.00 (IH, br.s), 6.72 (IH, br.d), 4.20 (3H, s) , 2.88 (3H, s)
(vii) [Example of process 12b of the above Scheme 12] A mixture of an all amount of 2-{3-(N- methylamino) phenyl} -2-methoxyiminoacetonitrile obtained in the above (vi) , 400mg (2.89 mmol) of potassium carbonate, 0.24 ml (2.53 mmol) of methyl bromoacetate and 5 ml of dimethylformamide was stirred at room temperature overnight. The resulting reaction solution was poured into dilute hydrochloric acid, extracted with 20 ml of ethyl acetate, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodiumbicarbonate, dried with magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 192 mg (0.736 mmol) of the desired 2- {3- (N-methyl-N-methoxycarbonylmethylamino) phenyl} -2- methoxyiminoacetonitrile (intermediate for preparing present compound) .
XH-NMR (CDCI3, TMS) δ (ppm) : 7.29 (IH, t) , 7.18 (IH, br.d) , 7.07 (IH, br.s) , 6.78 (IH, br.d), 4.20 (3H, s) , 4.13 (2H, s), 3.74 (3H, s) , 3.12 (3H, s)
(viii) [Example of process 8a of the above Scheme 8] A solution of 192 mg (0.736 mmol) of 2- {3- (N-methyl- N-methoxycarbonylmethylamino)phenyl} -2- methoxyiminoacetonitrile in 1 ml (16 mmol) of methyl formate was added dropwise to a mixture of 35 mg (1.5 mmol) of sodium hydride and 4 ml of dimethylformamide at room temperature while stirring the mixture . After stirring was continued for 3 hours , the reaction solution was poured into dilute hydrochloric acid and extracted with 20 ml of ethyl acetate. The organic layer was washed once with dilute hydrochloric acid, extracted twice with an aqueous solution of sodium carbonate, the combined aqueous sodium carbonate layers were made weakly acidic with concentrated hydrochloric acid, the precipitates were extracted with 20 ml of ethyl acetate, and the organic layer was washed once with water, dried with magnesium sulfate and concentrated to obtain 119 mg (0.412 mmol) of the desired 2- [3-{N-methyl-N- (methyl 3-hydroxyacrylate-2- y1) amino}phenyl] -2-methoxyiminoacetonitrile (intermediate for preparing present compound) .
^-NMR (CDC13, TMS) (3:1 mixture of isomers) δ (ppm) : 7.70 (IH, br.s), 7.0-7.4 (3H) , 6.80 (IH), 4.20 (3HX3/4, s), 4.19 (3HX1/4, s) , 3.72 (3HX1/4, s) , 3.67 (3H X3/4, s), 3.12 (3HX1/4, s) , 3.09 (3HX3/4, s)
Reference Preparation 8 [Example of process 7a of the above Scheme 7] (intermediate for present compound 116)
After a mixture of 3.0 g (12 mmol) of methyl 2- (3- acetylphenoxy) -3-methoxyacrylate [prepared in the above Reference Preparation 3], 1.0 g (14 mmol) of hydroxyamine hydrochloride, 1.2 ml (15 mmol) of pyridine and 30 ml of methanol was stirred at room temperature for 5 hours, the residue obtained by concentration was partitioned between ethyl acetate and water. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 3.2 g (12 mmol) of the desired methyl 2-{3-(l- hydroxyiminoethyl) phenoxy} -3 -methoxyacrylate (present compound 351) .
XH-NMR (CDC13, TMS) δ (ppm) :7.35(1H, s) , 7.2-7.3 (3H) , 6.97 (IH, m) , 3.87 (3H, s), 3.73 (3H, s), 2.25 (3H, s) Reference Preparation 9 [Preparation of intermediate for present compound 215, (1)]
(i) [Example of process 12c of the above Scheme 12] 21.88 g (0.136 mol) of methyl bromoacetate was added dropwise to a mixture of 19.58g (0.130 mol) of 3-hydroxy-4- methylacetophenone, 21.53 g (0.156 mol) of potassium carbonate and 100 ml of N,N-dimethylformamide at 20-25 °C, followed by stirring at room temperature for 5 hours. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with an aqueous solution of sodium bicarbonate once and water once, dried with magnesium sulfate and concentrated to obtain 27.87 g (0.125 mol) of the desired methyl 2- (5-acetyl-2-methylphenoxy) acetate. XH-NMR (TMS, CDCI3) δ (ppm) : 7.48 (IH, dd) , 7.33 (IH, d) , 7.23 (IH, d) , 4.72 (2H, s), 3.80 (3H, s) , 2.55 (3H, s) , 2.34 (3H, s)
(ii) [Example of process 12d of the above Scheme 12] A mixture of 11 g (50 mmol) of methyl 2- (5-acetyl-2- methylphenoxy) acetate, 13 g (81 mmol) of O-benzylhydroxyamine hydrochloride, 4.9 g (63 mmol) of pyridine and 60 ml of methanol was stirred at room temperature for 3 hours. The resulting reaction mixture was concentrated, and the resulting residue was partitioned between ethyl acetate and water. The organic layer was washed successively with dilute hydrochloric acid and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 16 g (49 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2-methylphenoxy}acetate
(intermediate for preparing present compound) . XH-NMR (TMS, CDC13) δ (ppm) : 7.1-7.45 (8H, m) , 5.22 (2H, s) , 4.68 (2H, s) , 3.79 (3H, s), 2.29 (3H, s) , 2.22 (3H, s)
(iii) [Example of process 8a of the above Scheme 8] After a solution of 16 g (49 mmol) of methyl 2-{5-(l- benzyloxyiminoethyl) -2-methylphenoxy}acetate, 29 g (490 mmol) of methyl formate and 10 ml of 1, 2-dimethoxyethane was added dropwise to a mixture of 12 g (108 mmol) of potassium hydride (35% oil dispersion) and 160 ml of 1, 2-dimethoxyethane under argon atmosphere while stirring under ice-cooling, stirring was continued for 3 hours while raising a temperature to room temperature gradually. The resulting reaction mixture was poured into water, washed with twice with diethyl ether, and the aqueous layer was poured into dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried with magnesium sulfate and concentrated to obtain 15 g (about 41 mmol) of the crude product of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2- methylphenoxy} -3-hydroxyacrylate (intermediate for preparing present compound) . XH-NMR (TMS, CDC13) δ (ppm) : 8.01 (lHxl/2,s), 7.55 (lHxl/3, s) , 7.28-7.5 ( ) , 7.1-7.2 (2H, m) , 5.23 (2H x 1/2, s) , 5.20 (2H x 1/2, s) , 4.72 (3Hxl/3, s) , 3.68 (3Hxl/2, s) , 3.55 (3Hxl/2, s) , 3.40 (3HX2/3, s), 2.35 (3Hxl/2, s) , 2.29 (3Hxl/2,s), 2.23 (3H x 1/2) , 2.16 (3H x 1/2, s)
Reference Preparation 10 (Preparation of present compound 215, (2))
(i) [Example of process 11a of the above Scheme 11] A mixture of 5.0 g (22 mmol) of methyl 2- (5-acetyl-2- methylphenoxy) acetate, 0.43 g (2.2 mmol) of p-toluenesulfonic acid monohydrate, 21.5 g (200 mmol) of tri ethyl orthoformate and 15 ml of methanol was heated to reflux for 7 hours . The reaction solution was allowed to cool to room temperature, and to this was added 0.55 g (5.4 mmol) of triethylamine, followed by stirring for 15 minutes . The residue obtained by concentration was partitioned between ethyl acetate and water, and the organic layer was dried with magnesium sulfate and concentrated to obtain 2.7 g (about 10 mmol) of the crude product of the desired methyl 2-{5- (1, 1-dimethoxyethyl) -2- methylphenoxy}acetate .
H-I-NMR (TMS, CDC13) δ (ppm) : 6.8-7.2 (3H, m) , 4.68 (2H, s) , 3.79 (3H, s) , 3.18 (6H, s), 2.28 (3H, s) , 1.50 (3H, s) (ii) [Example of process lib of the above Scheme 11] A mixture of 1.0 g (about 3.7 mmol) of the crude product of methyl 2-{5- (1, 1-dimethoxyethyl) -2-methylphenoxy}acetate, 1.3 g (22 mmol) of methyl formate, 0.32 g (8.1 mmol) of sodium hydride (60% oil dispersion) and 13 ml of N,N-dimethylformamide was stirred at room temperature for 2 hours . The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed once with dilute hydrochloric acid and extracted twice with an aqueous solution of sodium carbonate. The resulting aqueous alkaline layer was adjusted to around pH 6 using concentrated hydrochloric acid, and the precipitates were extracted with ethyl acetate. The organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 0.40 g (about 1.6 mol) of the crude product of the desired methyl 2- (5- acetyl-2-methylphenoxy) -3-hydroxyacrylate.
(iii) [Example of process lie of the above Scheme 11] A mixture of 0.4 g (about 1.6 mmol) of the crude product of methyl 2- (5-acetyl-2-methylphenoxy) -3-hydroxyacrylate, 0.35 g (2.4 mmol) of methyl iodide, 0.38 g (2.7 mmol) of potassium carbonate and 40 ml of N,N-dimethylformamide was stirred at room temperature for 4 hours . The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate . The residue obtained by concentration was subjected to silica gel column chromatography to obtain 0.12 g (0.65 mmol) of the desired methyl 2- (5-acetyl-2-methylphenoxy) -3-methoxyacrylate. XH-NMR (TMS, CDCl3) δ (ppm) : 7.2-7.5 (4H, m) , 3.90 (3H,s) , 3.71 (3H, s) , 2.54 (3H, s), 2.41 (3H, s)
Reference Preparation 11 (preparation of intermediate for present compound 216) (i) [Example of process 12c of the above Scheme 12] A mixture of 5.0 g (30 mmol) of 3-hydroxy-4- ethylacetophenone, 5.1 g (33 mmol) of methyl bromoacetate, 5.1 g (37 mmol) of potassium carbonate and 60 ml of N,N- dimethylformamide was stirred at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once, and dried with magnesium sulfate to obtain 6.6 g (28 mmol) of the desired methyl 2- (5-acetyl-2-ethylphenoxy) acetate. XH-NMR (TMS, CDC13) δ (ppm) : 7.53 (IH, dd) , 7.35 (IH, d) , 7.27 (IH, d) , 4.74 (2H, s), 3.81 (3H, s), 2.78 (2H, q) , 2.58 (3H, s) , 1.25 (3H, t)
(ii) [Example of process 12d of the above Scheme 12] A mixture of 6.6 g (28 mmol) of methyl 2- (5-acetyl-2- ethylphenoxy) acetate, 7.2 g (45 mmol) of O-benzylhydroxyamine hydrochloride, 2.7 g (35 mmol) of pyridine and 35 ml of methanol was stirred at room temperature overnight. The resulting reaction mixture was concentrated to obtain the residue, which was partitioned between ethyl acetate and water. The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated to obtain 9.2 g (27 mmol) of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2- ethylphenoxy}acetate (Intermediate for preparing present compound) .
^- MR (TMS, CDC13) δ (ppm) : 7 . 1-7 . 45 ( 8H , m) , 5 . 22 ( 2H , s ) , 4 . 68 ( 2H , s ) , 3 .79 ( 3H, s ) , 2 .71 ( 2H, q) , 2 . 22 ( 3H, s ) , 1 . 21 ( 3H, t )
(iii) [Example of process 8b of the above Scheme 8]
5.3 g (88 mmol) of methyl formate was added to a mixture of 0.78 g (19 mmol) of potassium hydride and 30 ml of 1,2- dimethoxyethane under argon atmosphere, followed by the addition of 3.00 g (8.8 mmol) of methyl 2-{5-(l- benzyloxyiminoethyl) -2-ethylphenoxy}acetate and stirring at room temperature for 3 hours . The resulting reaction mixture was poured into ice-water, washed twice with diethyl ether, and the aqueous layer was poured into dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried with magnesium sulfate and concentrated to obtain l.Og (about 2.8 mol) of the crude product of the desired methyl 2-{5- (1-benzyloxyiminoethyl) -2- ethylphenoxy} -3-hydroxyacrylate (intermediate for preparing present compound) .
Reference Preparation 12 (Preparation of intermediate for present compound 217) (i) [Example of process 15 of the above Scheme 15]
1.49 g (10 mmol) of 3-amino-4-methylacetophenone was suspended in 8 ml of 10% sulfuric acid, and a solution obtained by dissolving 0.71 g (10 mmol) of sodium nitrite in 4 ml of water was added dropwise at about 5 °C. To this was added a copper salt of methyl thioglycolate (the copper salt was prepared by adding 1.07 ml of methyl thioglycolate dropwise to a solution obtained by dissolving 1.49 g of copper sulfate pentahydrate in 10 ml of water to give yellow precipitates which were isolated by filtration) in portions at the same temperature. After stirring at room temperature for 3 hours, diethyl ether was added to the reaction mixture, followed by filtration. The filtrate was separated, and the organic layer was washed successively with dilute hydrochloric acid and an aqueous dilute solution of sodium hydroxide (twice), washed with water and dried with magnesium sulfate. The residue obtained by concentration was subjected to silica gel column chromatography to obtain 0.53 g (2.22 mmol) of the desired methyl 2- (5- acetyl-2-methyl-phenylthio) acetate. XH-NMR (TMS, CDC13) δ (ppm) : 7.95 (IH, d) , 7.71 (IH, dd) , 7.27 (IH, d) , 3.73 (3H, s), 3.70 (2H, s) , 2.58 (3H, s) , 2.45 (3H, s)
(ii) [Example of process 11a of the above Scheme 11] A mixture of 0.52 g (2.18 mmol) of methyl 2- (5- acetyl-2-methyl-phenylthio) acetate, 40 mg (0.21 mmol) of p- toluenesulfonic acid monohydrate, 2.36 g (21.8 mmol) of trimethyl orthoformate and 10 ml of methanol was heated to reflux for 4 hours . To the reaction mixture were added further 40 mg (0.21 mmol) of p-toluenesulfonic acid monohydrate, 2.36 g (21.8 mmol) of trimethyl orthoformate and 10 ml of methanol, followed by further heating to reflux for 5 hours . The reaction solution was allowed to cool to room temperature, and to this was added 0.36 g (3.53 mmol) of triethylamine to stir for 15 minutes. The residue obtained by concentration was partitioned between ethyl acetate and water, and the organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain 0.61 g (2.14 mmol) of the desired methyl 2-{5- (1, 1-dimethoxyethyl) -2-methyl-phenylthio}acetate. αH-NMR (TMS, CDC13) δ (ppm) : 7 .47 ( IH, d) , 7 .25 ( IH, dd) , 7 . 17 ( IH , d) , 3 .71 ( 3H, s ) , 3 . 65 ( 2H, s ) , 3 . 17 ( 6H, s ) , 2 . 41 ( 3H, s ) , 1 . 51 ( 3H, s )
(iii) [Example of process lib of the above Scheme 11] A solution of 600 mg (2.11 mmol) of methyl 2-{5-(l,l- dimethoxyethyl) -2-methyl-phenylthio}acetate in 3.07 g (46 mmol) of methyl formate was added dropwise to a mixture of 274 mg (6.86 mmol) of potassium hydride and 7 ml of 1,2- dimethoxyethane at room temperature under argon atmosphere while stirring, followed by stirring at room temperature for 2 hours and 30 minutes. The resulting reaction mixture was poured into ice-water, and the aqueous layer was washed twice with diethyl ether. The aqueous layer was made acidic by the addition of concentrated hydrochloric acid, and the precipitates were extracted twice with ethyl acetate. The ethyl acetate layers were combined, washed with water, dried with magnesium sulfate and concentrated to obtain 450 mg (1.69 mmol) of the desired methyl 2- (5-acetyl-2-methyl- phenylthio) -3-hydroxyacrylate . XH-NMR (TMS, CDCl3) δ (ppm) : 7.73 (IH, br.d), 7.63 (IH, dd) , 7.60 (IH, s) , 7.22 (IH, d) , 3.77 (3H, s) , 2.53 (3H, s) , 2.44 (3H, s)
(iv) [Example of process 11c of the above Scheme 11] A mixture of 0.44 g (1.65 mmol) of methyl 2- (5- acetyl-2-methyl-phenylthio) -3-hydroxyacrylate, 0.26 g (1.82 mmol) of methyl iodide, 0.25 g (1.82 mmol) of potassium carbonate and 6 ml of N,N-dimethylformamide was stirred at room temperature for 3 hours. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate . The organic layer was washed successively with dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once and dried with magnesium sulfate . The residue obtainedby concentration was subjected to silica gel thin layer chromatography to obtain 0.28 g (1.0 mmol) of the desired methyl 2- (5-acetyl-2-methyl-phenylthio) -3-methoxyacrylate. XH-NMR (TMS, CDC13) δ (ppm) : 8.05 (IH, s) , 7.55-7.7 (2H, m) , 7.19 (IH, d) , 3.99 (3H, s), 3.71 (3H, s) , 2.51 (3H, s) , 2.45 (3H, s) Reference Preparation 13 (Preparation of intermediate for present compounds 232 and 233)
(i) [Example of starting material [II] in Scheme 9 and Scheme 12]
11.19 g (75 mmol) of 3-amino-4-methylacetophenone was suspended in 15 ml of concentrated hydrochloric acid and 15 g of ice, and a solution obtained by dissolving 5.52 g (80 mmol) of sodium nitrite in 12.5 ml of water was added dropwise at about 5 °C thereto. This was added dropwise to a solution obtained by dissolving 14.00 g (87 mmol) of potassium xanthate (potassium O-ethyl dithiocarbonate) in 18 ml of water while maintaining a temperature of the solution at 40 to 45 °C, followed by further stirring at the same temperature for 30 minutes. Diethyl ether was added to the reaction solution, layers were separated and the aqueous layer was further extracted twice with diethyl ether . The organic layers were combined, washed successively with an aqueous dilute solution of sodium hydroxide and water and dried with magnesium sulfate.
The residue (17.90 g) obtained by concentration was dissolved in 50 ml of 95% ethanol, and to this was added 17.5 g of potassium hydroxide in portions at a bath temperature of 100 °C, followed by heating to reflux for 5 hours and 30 minutes. After ethanol was distilled off from the reaction mixture, water and diethyl ether were added to the residue, the layers were separated, and the aqueous layer was washed with diethyl ether three times. 65 ml of 6N sulfuric acid and 0.2 g of zinc were added to the aqueous layer, extracted with diethyl ether, the diethyl ether layer was dried with magnesium sulfate and concentrated to obtain 9.33 g of the crude product of 5- acetyl-2-methyl-thiophenol. ^-N R (TMS, CDC13) δ (ppm) : 7.86 (IH, d) , 7.64 (IH, dd) , 7.24 (IH, d) , 3.42 (IH, s), 2.56 (3H, s) , 2.38 (3H, s)
(ii) [Example of process 9a of the above Scheme 9] After a solution obtained by dissolving 1.01 g (10 mmol) of triethylamine in 10 ml of tetrahydrofuran was added dropwise to a solution obtained by dissolving 1.66 g (about 10 mmol) of the crude product of 5-acetyl-2-methyl-thiophenol and 1.38 g (10 mmol) of methyl 2-chloro-2- (hydroxyimino) acetate while stirring the solution, stirring was continued at room temperature for 4 hours. The resulting reaction mixture was filtered and the filtrate was concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 1.91 g (7.1 mmol) of the desired methyl 2-(5-acetyl- 2-methyl-phenylthio) -2- (hydroxyimino) acetate. XH-NMR (TMS, CDC13) δ (ppm) : 8.04 (IH, d) , 7.87 (IH, dd) , 7.36 (IH, d) , 3.53 (3H, s) , 2.58 (3H, s) , 2.54 (3H, s)
(iii) [Example of process 9b of the above Scheme 9] A mixture of 1.90 g (7.1 mmol) of methyl 2-(5-acetyl- 2-methyl-phenylthio) -2-hydroxyiminoacetate, 1.18 g (1.2 mmol) of potassium carbonate, 1.07 g (1.2 mmol) of dimethyl sulfate and 22 ml of tetrahydrofuran was stirred at room temperature overnight. The resulting reaction mixture was filtered, and the filtrate was concentrated to obtain the residue, which was subjected to silica gel column chromatography to obtain 1.42 g (5.1 mmol) of the desired methyl 2- (5-acetyl-2-methyl- phenylthio) -2-methoxyiminoacetate . ^-N R (TMS, CDC13) δ (ppm) : 8.02 (IH, d) , 7.86 (IH, dd) , 7.36 (IH, d) , 4.12 (3H,s), 3.50 (3H, s) , 2.57 (3H, s) , 2.53 (3H, s)
Reference Preparation 14 (Preparation of intermediate for present compounds 256 and 257) (i)-l [Example of process 9b of the above Scheme 9]
90 mg (2.25 mmol) of sodium hydride (60% oil dispersion) was suspended in 3 ml of tetrahydrofuran, and to this was added dropwise 300 mg (2.0 mmol) of 3-hydroxy-4-methylacetophenone at 5 to 10 °C under nitrogen atmosphere. After evolution of hydrogen gas ceased, to this was added dropwise a solution of
275 mg (2.0 mmol) of methyl 2-chloro-2-hydroxyiminoacetate at the same temperature. To this was added dropwise 408 mg (4.0 mmol) of triethylamine and stirring was continued at room temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted twice with diethyl ether. The organic layers were combined, washed with water three times, dried with magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel thin layer chromatography (developing solvent; hexane:ethyl acetate=l : 1) to obtain 27 mg (about 0.11 mmol) of the crude product of the desired methyl 2- (5-acetyl-2- methylphenoxy) -2-hydroxyiminoacetate . XH-NMR (TMS, CDC13) δ (ppm) : 7.62 (IH, dd) , 7.32 (IH, d) , 7.31 (IH, d) , 3.82 (3H, s), 2.55 (3H, s) , 2.43 (3H, s)
(i)-2 [Example of process 9a of the above Scheme 9] 148 mg (2.55 mmol) of powdered potassium hydroxide was suspended in 3 ml of N,N-dimethylformamide, 300 mg (2.0 mmol) of 3-hydroxy-4-methylacetophenone was added thereto at about 5 °C and, then, to this was added dropwise a solution obtained by dissolving 275 mg (2.0 mmol) of methyl 2-chloro-2- hydroxyiminoacetate in 2 ml of N,N-dimethylformamide at 5-10 °C. After stirred at room temperature for 1 hour, 408 mg (4.0 mmol) of triethylamine was added dropwise thereto at the same temperature and stirring was continued at the same temperature overnight. The resulting reaction mixture was poured into dilute hydrochloric acid and extracted twice with diethyl ether. The organic layers were combined, washed with water, dried with magnesium sulfate and concentrated to obtain the residue, which was subjected to silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate=l:l) to obtain 17 mg (about 0.068 mmol) of the crude product of the desired methyl 2- (5-acetyl-2-methylphenoxy) -2-hydroxyiminoacetate. (ii) [Example of process 9b of the above Scheme 9]
A mixture of 44 mg (about 0.18 mmol) of the crude product of methyl 2- (5-acetyl-2-methylphenoxy) -2-hydroxyiminoacetate {synthesized in the above (i)-l and (i)-2}, 28 mg (0.20 mmol) of potassium carbonate, 26 mg (0.20 mmol) of dimethyl sulfate and 3 ml of tetrahydrofuran was stirred at room temperature for
6 hours. The resulting reaction mixture was subjected as it was to silica gel thin layer chromatography to obtain 24 mg
(0.091 mmol) of the desired methyl 2- (5-acetyl-2- methylphenoxy) -2-methoxyiminoacetate.
XH-NMR (TMS, CDC13) δ (ppm) : 7.61 (IH, dd) , 7.25-7.35 (2H, m) , 4.04 (3H, s) , 3.83 (3H, s), 2.54 (3H, s) , 2.41 (3H, s) Reference Preparation 15 133.27 ml (133.26 mmol) of IN dilute sulfuric acid was added to a mixture of 273.51 g (740.38 mmol) of methyl 2- {5- (1-benzyloxyiminoethyl) -2-methylphenoxy} -3- methoxyacrylate, 82.25 g (2.379 mol) of paraformaldehyde and 2.7 liter of acetonitrile at room temperature while stirring, followed by stirring at 25 °C for 15 hours and at 30 °C for 3 hours. To the resulting reaction mixture was added 7.54 ml (54. lmmol) of triethylamine at room temperature while stirring, followed by concentration under reduced pressure. The resulting residue was dissolved in 8 liter of ethyl acetate, washed with 8 liter of 2N dilute hydrochloric acid twice and 8 liter of a 5% aqueous solution of sodium bicarbonate once, dried with anhydrous magnesium sulfate and concentrated to obtain the residue, which was purified by silica gel column chromatography to obtain 154.83 g (633.10 mmol) of the desired methyl 2- (5-acetyl-2-methylphenoxy) -3-methoxyacrylate. ^-NMR (TMS, CDC13) δ (ppm) : 7.2-7.5 (4H, ) , 3.90 (3H, s) , 3.71 (3H, s) , 2.54 (3H, s), 2.41 (3H, s)
Reference Preparation 16 A mixture of 15.0 g (56.8 mmol) of methyl 2- (5- acetyl-2-methylphenoxy) -3-methoxyacrylate, 6.00 g (86.3 mmol) of hydroxylamine hydrochloride, 5.00 ml (61.8 mmol) of pyridine and 200 ml of methanol was stirred at room temperature for 1 hour. The resulting reaction mixture was concentrated to obtain the residue which was partitioned between ethyl acetate andwater, the organic layer was washed successivelywith dilute hydrochloric acid once and an aqueous solution of sodium bicarbonate once, dried with anhydrous magnesium sulfate and concentrated to obtain 14.5 g (52.0 mmol) of the desired methyl 2-{5- (1-hydroxyiminoethyl) -2-methylphenoxy} -3- methoxyacrylate (present compound 463) . XH-NMR (TMS, CDC13) δ (ppm) : 7.35 (IH, s) , 7.17 (IH, d) , 7.12 (IH, d) , 7.03 (IH, s), 3.87 (3H, s) , 3.71 (3H, s) , 2.36 (3H, s) , 2.23 (3H, s)
Examples of the present compounds together with compound Nos . are shown in Table 1 and Table 2.
Compounds represented by
[Table 1]
No. R R' R' R' X Y
277 CO2Me H H Bz NMe CH O
278 CO2Me H H Bz NMe N O
279 CO2Me H H Bz NMe N NH
280 CO2Me H H Bz O CH O
281 CO2Me H H Bz O N O
282 CO2Me H H Bz O N NH
283 CO2Me H H Bz s CH O
284 CO2Me H H Bz s N O
285 CO2 e H H Bz s N NH
286 CO2Et H H Bz NMe CH O
287 CO2Et H H Bz NMe N O
288 CO2Et H H Bz NMe N NH
289 CO2Et H H Bz O CH O
290 CO2Et H H Bz O N O
291 CO2Et H H Bz O N NH
292 CO2Et H 4-Me Bz NMe CH O
293 CO2Et H 4-Me Bz NMe N O
294 CO2Et H 4-Me Bz NMe N NH
295 CO2Et H 4-Me Bz O CH O
296 CO2Et H 4-Me Bz O N O
297 CO2Et H 4- e Bz O N NH
298 CO2Et H 4-Me Bz s CH O
299 CO2Et H 4-Me Bz s N O
300 CO2Et H 4-Me Bz s N NH
301 Me H 4-Me (A) O CH O
Compounds represented by
In Tables land 2, Me represents methyl group, Et represents ethyl group, n-Pr represents propyl group, i-Pr represents isopropyl group, n-Bu represents butyl group, t- Bu represents tert-butyl group, Am represents amyl group, Bz represents benzyl group, F5BZ represents 2,3,4,5,6- pentafluorobenzyl group, Ph represents phenyl group, 4-CF3- PhCH(CH3) represents 1- (4-trifluoromethylphenyl) ethyl group, Py represents pyridyl group, c represents cyclo, sec represents secondary, SUIM represents succinimid-1-yl group, (A) represents 3-Cl-5-CF3-Py-2-yl group, and (B) represents 5- CF3-Py-2-yl group, respectively.
Then, physical properties [1H-NMR (CDC13, TMS, δ (ppm) ) data] of some embodiments of the present compounds are shown below. The present compounds are represented by chemical No.s shown in Table 1 and Table 2. Present compound 1 :
8.07 (IH, s) , 7.2-7.5 (6H) , 7.17 (IH, dd) , 6.94 (IH, br.d) , 6.87 (IH, br.s), 6.65 (IH, br.d), 5.20 (2H, s) , 3.84 (3H, 3), 3.67 (3H, s), 3.08 (3H, s) Present compound 2 : 7.40 (IH, s), 7.16 (IH, t) , 6.98 (IH, d) , 6.91 (IH, br.s), 6.64 (IH, br.d), 3.99 (3H, s) , 3.87 (3H, s) , 3.66 (3H, s) , 3.10 (3H, s), 2.18 (3H, s)
Present compound 3 : 7.41 (IH, s) , 7.19 (IH, t) , 6.9-7.0 (2H) , 6.66 (IH, br.d) , 3.84 (3H, s), 3.67 (3H, s) , 3.08 (3H, s) , 2.23 (3H, s)
Present compound 4 :
7.2-7.5 (6H) , 7.16 (IH, t) , 6.97 (IH, d) , 6.93 (IH, br.s) , 6.63 (IH, br.d), 5.23 (2H, s) , 3.83 (3H, s) , 3.67 (3H, s) , 3.09 (3H, s), 2.23 (3H, s)
Present compound 5 :
7.40 (IH, s), 7.17 (IH, t) , 6.99 (IH, br.d), 6.93 (IH, br.s), 6.64 (IH, br.d), 4.22 (2H, q) , 3.86 (3H, s) , 3.67 (3H, s), 3.09 (3H, s), 2.19 (3H, s) , 1.31 (3H, t) Present compound 6 :
7.39 (IH, s) , 7.16 (IH, t) , 6.99 (IH, br.d), 6.93 (IH, br.s), 6.63 (IH, br.d), 4.13 (2H, t) , 3.86 (3H, s) , 3.67 (3H, s), 3.09 (3H, s), 2.20 (3H, s) , 1.73 (2H, sex.), 0.97 (3H, t)
Present compound 7 : 7.40 (IH, s) , 7.18 (IH, dd) , 6.9-7.1 (2H) , 6.62 (IH, br.d) , 3.86 (3H, s), 3.67 (3H, s) , 3.09 (3H, s) , 2.16 (3H, s) , 1.34 (9H, s)
Present compound 8 :
7.40 (IH, s), 7.17 (IH, t) , 6.99 (IH, br.d), 6.93 (IH, br.s), 6.64 (IH, br.d), 6.07 (IH, ddt), 5.34 (IH, br.d), 5.23
(IH, br.d), 4.69 (2H, br.d), 3.86 (3H, s) , 3.67 (3H, s) , 3.09 (3H, s), 2.05 (3H, s)
Present compound 9 :
7.42 (IH, s) , 7.17 (IH, t) , 6.9-7.0 (2H) , 6.65 (IH, br.d) , 5 . 26 (2H, s ) , 3 . 87 ( 3H, s ) , 3 . 67 ( 3H, s ) , 3 . 08 ( 3H, s ) , 2 . 15 ( 3H, s )
Present compound 10:
7.41 (IH, s), 7.18 (IH, t) , 6.9-7.0 (2H) , 6.67 (IH, br.d), 6.20 (IH, t), 4.76 (2H, d) , 3.87 (3H, s) , 3.68 (3H, s) , 3.09 (3H, s), 2.19 (3H, s)
Present compound 11 :
7.33 (IH, s), 7.2-7.3 (3H) , 6.93 (IH, br.d), 3.98 (3H, s), 3.87 (3H, s), 3.72 (3H, s) , 2.19(3H, s) Present compound 12 :
7.2-7.5 (9H) , 6.93 (IH, br.d), 5.23 (2H, s) , 3.85 (3H, s), 3.72 (3H, s), 2.23 (3H, s) Present compound 13 :
7.60 (2H, d) , 7.46 (2H, d) , 7.1-7.6 (4H) , 6.89 (IH, m) , 5.39 (IH, q) , 3.82 (3H, s) , 3.70 (3H, s) , 2.69 (3H, s) , 1.60 (3H, d)
Present compound 14
7.60 (2H, d) , 7.48 (2H, d) , 7.36 (IH, s) , 7.14 (IH, t) , 6.91 (IH, br.d), 6.83 (IH, br.d), 6.62 (IH, br.d), 5.40 (IH, q) , 3.82 (3H, s) , 3.65 (3H, s) , 3.04 (3H, s) , 2.26 (3H, s) , 1.60 (3H, d)
Present compound 30
7.4-7.5 (2H), 7.31 (IH, t) , 7.17 (IH, br.d), 4.00 (3H, s), 3.80 (3H, s), 3.63 (3H, s) , 3.26 (3H, s) , 2.19 (3H, s) Present compound 31
7.13-7.25 (2H), 7.06 (IH, br.s), 6.75 (IH, br.d), 6.68 (IH, br) , 3.97 (3H, s) , 3.89 (3H, s) , 3.27 (3H, s) , 2.88 (3H, d) , 2.18 (3H, s)
Present compound 55 8.00 (IH, s), 7.52 (IH, s), 7.43 (IH, d) , 7.1-7.3 (2H) , 3.99 (3H, s), 3.98 (3H, s) , 3.73 (3H, s) , 2.17 (3H, s) Present compound 115 :
8.56 (IH, s), 7.95 (IH, dd) , 7.52 (IH, d) , 7.3-7.5 (4H) , 7.02 (IH, dd) , 3.90 (3H, s) , 3.74 (3H, s) , 2.52 (3H, s) Present compound 116:
8.46 (IH, br.s) , 7.95 (IH, br.s) , 7.44 (IH, br.d) , 7.3-7.4 (3H), 7.02 (IH, br.d), 3.88 (3H, s), 3.73 (3H, s) , 2.54 (3H, s) Present compound 122 :
7.33 (IH, s), 7.2-7.3 (3H) , 6.95 (lH,m) , 4.74 (2H, s) , 3.86 (3H, s), 3.77 (3H, s) , 3.72 (3H, s) , 2.28 (3H, s) Present compound 132:
7.0-7.5 (9H), 5.21 (2H, s) , 3.86 (3H, s) , 3.72 (3H, s) , 2.18 (3H, s)
Present compound 163 :
8.55 (IH, br.s), 7.94 (IH, br.d), 7.52 (IH, d) , 7.43 (IH, s), 7.27 (IH, m) , 7.10 (IH, br.d), 7.02 (IH, br.s), 6.74 (IH, br.d), 3.89 (3H, s) , 3.70 (3H, s) , 3.13 (3H, s) , 2.51 (3H, s) Present compound 174
7.41 (IH, s), 7.19 (IH, t) , 6.9-7.0 (2H) , 6.67 (IH, t) , 4.81 (2H, s), 3.88 (3H, s) , 3.68 (3H, s) , 3.06 (3H,s), 2.23 (3H, s)
Present compound 199: 7.1-7.5 (7H), 7.06 (IH, br.s), 6.77 (IH, br.d), 5.23 (2H, s) 4.02 (3H, s), 3.74 (3H, s) , 3.26 (3H, s) , 2.23 (3H, s) Present compound 200:
7.1-7.5 (7H), 7.05 (IH, br.s), 6.75 (IH, br.d), 6.66 (IH, br) , 5.22 (2H, s) , 3.87 (3H, s) , 3.25 (3H, s),2.86 (3H, d) , 2.21 ( 3H, s )
Present compound 201:
6.9-7.5 (10H), 3.88 (3H, s) , 3.73 (3H, s) , 2.42 (3H, s) Present compound 202: 8.43 (IH, s), 7.72 (IH, d) , 7.2-7.4 (5H) , 6.94 (IH, m) , 5.19 (2H, s), 3.87 (3H, s) , 3.72 (3H, s) , 2.21 (3H, s) Present compound 203:
7.1-7.4 (8H), 6.93 (IH, d) , 4.86 (2H, t) , 3.88 (3H, s) , 3.73 (3H, s), 3.01 (2H, t) , 2.17 (3H, s) Present compound 204:
7.2-7.4 (6H), 6.9-7.0 (4H) , 4.53 (2H, t) , 4.28(2H, t) ,
3.86 (3H, s), 3.72 (3H, s) , 2.21 (3H, s)
Present compound 205:
7.2-7.4 (6H), 6.9-7.0 (4H) , 4.38 (2H, t) , 4.11 (2H, t) , 3.87 (3H, s), 3.72 (3H, s) , 2.20 (3H, s) , 2.1-2.3 (2H, )
Present compound 206: 7.33 (IH, s), 7.2-7.3 (3H) , 6.95 (lH,m) , 4.95 (2H, s) ,
3.87 (3H, s), 3.73 (3H, s) , 2.44 (3H, s) , 2.32 (3H, s) , 2.15 (3H,s) Present compound 207:
7.33 (IH, s), 7.2-7.3 (3H) , 6.93 (IH, d) , 3.7-4.4 (6H) , 3.86 (3H, s), 3.72(3H, s) , 2.22 (3H, s) , 1.6-2.1 (3H)
Present compound 208:
7.2-7.4 (6H), 6.8-7.0 (3H) , 5.16 (2H, s) , 3.87 (3H, s) , 3.83 (3H, s) , 3.73 (3H, s) , 2.20 (3H, s)
Present compound 209:
7.99 (IH, s), 7.51 (IH, s) , 7.1-7.5 (8H) , 5.23 (2H, s) , 3.97 (3H, s), 3.73 (3H,s), 2.23 (3H, s)
Present compound 210: 7.2-7.5 (8H), 6.93 (IH, m) , 5.34 (2H, s) , 3.85 (3H, s) ,
3.71 (3H, s), 2.27 (3H, s)
Present compound 211:
7.2-7.4 (8H), 6.94 (IH, m) , 5.19 (2H, s) , 3.85 (3H, s) , 3.72 (3H, s), 2.24 (3H, s) Present compound 212: 7.2-7.4 (8H), 6.94 (IH, m) , 5.17 (2H, s) , 3.85 (3H, s) ,
3.72 (3H, s), 2.22 (3H, s)
Present compound 213 : 7.2-7.4 (6H), 7.02 (IH, m) , 6.94 (IH, m) , 5.37 (2H, s) , 3.86 (3H, s), 3.72 (3H, s) , 2.17 (3H, s) Present compound 214:
8.59 (2H, d), 7.2-7.4 (6H), 6.94 (IH, m) , 5.24 (2H, s) , 3.86 (3H, s), 3.73 (3H, s) , 2.29 (3H, s) Present compound 215:
7.0-7.45 (9H, m) , 5.20 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s), 2.35 (3H, s), 2.19 (3H, s) Present compound 216:
7.0-7.45 (9H, ) , 5.20 (2H, s) , 3.83 (3H, s) , 3.70 (3H, s), 2.76 (2H, q) , 2.19 (3H, s) , 1.26 (3H, t) Present compound 217:
7.98 (IH, s), 7.25-7.45 (7H, m) , 7.10 (IH, s) , 5.20 (2H, s), 3.93 (3H, s), 3.70 (3H, s) , 2.41 (3H, s) , 2.19 (3H, s) Present compound 220: 6.85-7.5{9H), 5.19 (2H, s) , 3.91 (3H, s) , 3.83 (3H, s) , 3.71 (3H, s), 2.18 (3H, s)
Present compound 232: (14:1 mixture of isomers) 7.71 (IH, d) , 7.58 (IH, dd) , 7.2-7.45 (6H, m) , {5.22 (2H X14/15), 5.10 (2HX1/15), each s}, 4.10 (3H, s) , {3.43 (3H X14/15), 3.35 (3HX1/15), each s}, 2.46 (3H, s) , {2.21 (3H X14/15), 2.15 (3HX1/15), each s} Present compound 233:
7.69 (IH, d) , 7.52 (IH, dd) , 7.2-7.45 (6H, m) , 6.25 (IH, br) , 5.21 (2H, s) , 3.99 (3H, s) , 2.66 (3H, d) , 2.47 (3H, s) , 2.21 (3H, s)
Present compound 237:
7.0-7.5 (9H), 5.37 (2H, s) , 3.85 (3H, s) , 3.71 (3H, s) , 2.37 (3H, s) Present compound 247:
7.2-7.5 (6H) , 7.17 (IH, t) , 6.96 (IH, d) , 6.91 (IH, br.s) , 6.63 (IH, dd) , 5.21 (2H, s) , 3.85 (3H, s) , 3.67 (3H, s), 3.08 (3H, s), 2.74 (2H, q) , 1.11 (3H, t) Present compound 250: 7.2-7.4 (4H), 6.93 (IH, m) , 3.96 (3H, s) , 3.87 (3H, s) , 3.72 (3H, s), 2.70 (2H, dd) , 1.2-1.7 (4H) , 0.91 (3H, t) Present compound 251:
7.47 (IH, s) , 7.15 (IH, t) , 6.9-7.0 (2H) , 6.64 (IH, br.d) , 3.97(3H,s), 3.85(3H,s), 3.67(3H,s), 3.49 (2H, q) , 2.18 (3H, s) , 1.19 (3H, t)
Present compound 252:
8.46 (IH, br.s), 7.93 (IH, br.s), 7.41 (IH, s) , 7.22 (IH, t) , 7.09 (IH, br.d) , 6.99 (IH, br.d) , 6.71 (IH, br.d) , 3.88 (3H, s), 3.68 (3H, s), 3.11 (3H, s) , 2.52 (3H, s) Present compound 253:
7.33 (IH, s), 7.15 (2H, dd(AB)), 7.02 (IH, s) , 3.96 (3H, s), 3.88 (3H, s), 3.70 (3H, s) , 2.35 (3H, s),2.15 (3H, s) Present compound 254: 8.63 (2H, d) , 7.41 (IH, s) , 7.18 (IH, t) , 7.10 (IH, br.d), 7.07 (IH, t), 6.99 (IH, br.s) , 6.69 (br.s), 3.87 (3H, s) , 3.68 (3H, s), 3.11 (3H, s), 2.51 (3H, s)
Present compound 256: (8:1 mixture of isomers) 7.0-7.45 (8H, m) , {5.20 (2HX8/9), 5.08 (2HX1/9), each s}, {4.03 (3HX8/9), 3.97 (3HX1/9), eachs}, {3.79 (3HX8/9), 3.73 (3HX1/9), each s}, {2.34 (3HX8/9), 2.22 (3HX 1/9) , each s}, {2.18 (3HX8/9), 2.14 (3HX1/9), each s}
Present compound 257: (10:1 mixture of isomers)
7.0-7.45 (8H, m), {6.63 and 6.33 , combined IH, each br} , {5.20 (2HX10/11), 5.08 (2HX1/11), eachs}, {3.92 (3HX10/11),
3.88 (3HX1/11), each s}, {2.84 (3HX10/11), 2.73 (3HX1/11), eachs}, {2.35 and 2.36, combined 3H, eachs}, {2.18 (3HX 10/11) ,
2.15 (3HX1/11) , each s}
Present compound 272: 7.44 (IH, s), 7.23 (IH, dd) , 7.14 (IH, br.d), 7.03 (IH, br.s), 6.73 (IH, br.d), 4.17 (3H, s) , 3.89 (3H, s) , 3.69 (3H, s), 3.10 (3H, s)
Present compound 301:
8.67 (IH, s), 7.39 (IH, s), 7.38 (IH, s), 7.1-7.3 (3H) , 3.92 (3H,s), 3.74 (3H, s) , 2.47 (3H, s) , 2.41 (3H, s) Present compound 302:
8.56 (IH, br.s), 7.94 (IH, br.d), 7.46 (IH, d) , 7.0-7.4 (4H), 3.90 (3H, s), 3.73 (3H, s) , 2.48 (3H, s) , 2.40 (3H, s) Present compound 321: 7.0-7.4 (8H), 5.14 (2H, s), 3.81 (3H, s) , 3.68 (3H, s) , 2.34 (3H, s), 2.16 (3H, s) Present compound 322:
7.61 (2H, d) , 7.50 (2H, d) , 7.31 (IH, s) , 7.14 (2H, s) , 6.99 (IH, s), 5.24 (2H, s) , 3.83 (3H, s) , 3.69 (3H, s) , 2.34 ( 3H , s ) , 2 .20 ( 3H, s )
Present compound 324:
7.64 (2H, d), 7.48 (2H, d) , 7.31 (IH, s) , 7.14 (2H, s) , 6.97 (IH, s), 5.24 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s), 2.21 (3H, s)
Present compound 326:
7.0-7.4 (8H), 5.15 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.35 (6H, s), 2.17 (3H, s) Present compound 329: 7.34 (2H, d) , 7.33 (IH, s) , 7.15 (IH, d) , 7.13 (IH, d) , 7.03 (IH, s), 6.89 (2H, s) , 5.12 (2H, s) , 3.86 (3H, s) , 3.81 (3H, s), 3.70 (3H, s) , 2.35 (3H, s) , 2.16 (3H, s) Present compound 332:
7.48 (2H, d) , 7.32 (IH, s) , 7.27 (2H, d) , 7.13 (2H, s) , 6.99 (IH, s), 5.13 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.34 (3H, s), 2.18 (3H, s)
Present compound 333 :
7.0-7.4 (8H), 5.18 (2H, s) , 3.83 (3H, s) , 3.69 (3H, s) , 2.35 (3H, s), 2.19 (3H, s) Present compound 336:
7.0-7.6 (8H), 5.15 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s), 2.20 (3H, s) Present compound 351:
7.2-7.4 (5H), 6.97 (IH, m) , 3.87 (3H, s) , 3.73 (3H, s) , 2.25 (3H, s)
Present compound 353:
7.0-7.4 (9H), 4.19 (2H, t) , 3.84 (3H, s) , 3.70 (3H, s) , 2.74 (2H, dd) , 2.35 (3H, s) , 2.16 (3H, s) , 2.03 (2H, m) Present compound 356: 7.0-7.5 (8H), 5.26 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s), 2.34 (3H, s), 2.18 (3H, s) Present compound 357
7.0-7.5 (8H), 5.32 (2H, s) , 3.86 (3H, s) , 3.71 (3H, s) , 2.36 (3H, s), 2.24 (3H, s) Present compound 359:
7.0-7.5 (8H), 5.21 (2H, s) , 3.86 (3H, s) , 3.70 (3H, s) , 2.40 (3H, s), 2.35 (3H, s) , 2.17 (3H, s) Present compound 360: 7.33 (IH, s), 7.0-7.2 (6H), 5.18 (2H, s) , 3.86 (3H, s) , 3.70 (3H, s), 2.36 (3H, s) , 2.35 (3H, s) , 2.32 (3H, s), 2.17 (3H, s)
Present compound 362:
7.65 (IH, br.s), 7.57 (2H, br.t), 7.48 (IH, br.d), 7.31 (IH, s), 7.14 (2H, s) , 7.00 (IH, s) , 5.24 (2H, s) , 3.84 (3H, s), 3.69 (3H, s), 2.35 (3H, s) , 2.20 (3H, s) Present compound 366:
7.68 (IH, s), 7.60 (2H, t) , 7.46 (IH, dd) , 7.34 (IH, s) , 7.14 (2H, s), 6.99 (IH, s) , 5.21 (2H, s) , 3.86 (3H, s) , 3.70 (3H, s), 2.35 (3H, s) , 2.21 (3H, s) Present compound 371:
7.0-7.4 (8H), 5.17 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s), 2.18 (3H, s) , 1.30 (9H, s) Present compound 373: 6.9-7.4 (7H), 5.34 (2H, s) 3.87 (3H, s) , 3.70 (3H, s) , 2.34 (3H, s), 2.13 (3H, s) Present compound 374:
7.1-7.4 (7H) , 5.46 (2H, s) , 3.87 (3H, s) , 3.70 (3H, s) , 2.34 (3H, s), 2.14 (3H, s) Present compound 377:
6.9-7.4 (7H), 5.12 (2H, s) , 3.86 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) 2.18 (3H, s)
Present compound 383: (2:1 mixture of isomers) 7.0-7.4 (7H), {5.23 (2HX1/3), 5.13 (2HX2/3), eachs}, {3.86 (3HX1/3), 3.86 (3HX2/3), each s}, 3.70 (3H, s) , 2.35 (3H, s), {2.31 (3HX1/3), 2.60 (3HX2/3), each s}, {2.30 (3H Xl/3), 2.70 (3HX2/3), each s}, 2.17 (3H, s) Present compound 393: 8.17 (IH, d) , 7.85 (2H, dd) , 7.4-7.6 (4H, ) , 7.32 (IH, s), 7.18 (IH, d) , 7.13 (IH, d) , 7.04 (IH, s) , 5.66 (2H, s) , 3.84 (3H, s), 3.71 (3H, s) , 2.35 (3H, s) , 2.16 (3H, s) Present compound 414:
8.66 (IH, s), 7.39 (IH, s) , 7.38 (IH, s) , 7.29 (IH, d) , 7.24 (IH, d) , 7.13 (IH, s) , 3.92 (3H, s) , 3.74 (3H, s) , 2.47 (3H, s), 2.41 (3H, s)
Present compound 417:
7.33 (IH, s), 7.18 (IH, dd) , 7.12 (IH, d) , 7.02 (IH, d) , 4.21 (2H, q) , 3.87 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) , 2.15 (3H, s), 1.30 (3H, t)
Present compound 418:
7.32 (IH, s) , 7.18 (IH, dd) , 7.13 (IH, d) , 7.02 (IH, d) , 4.12 (2H, t), 3.87 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) , 2.16 (3H, s), 1.65-1.8 (2H, m) , 0.97 (3H, t) Present compound 419:
7.32 (IH, s), 7.18 (IH, dd) , 7.13 (IH, d) , 7.03 (IH, d) , 4.35-4.5 (IH, m) , 3.87 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) , 2.14 (3H, s), 1.28 (6H, d)
Present compound 421: 7.32 (IH, s), 7.18 (IH, dd) , 7.12 (IH, d) , 7.03 (IH, d) , 4.15-4.3 (IH, m) , 3.87 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) , 2.14 (3H,s), 1.5-1.8 (2H, m) , 1.25 (3H,d), 0.94 (3H, t)
Present compound 422 : 7.32 (IH, s), 7.0-7.2 (3H, ) , 3.93 (2H, d) , 3.87 (3H, s), 3.70 (3H, s), 2.33 (3H, s) , 2.16 (3H, s) , 1.95-2.1 (IH, m) , 0.95 (6H, d)
Present compound 423:
7.33 (IH, s), 7.20 (IH, dd) , 7.12 (IH, d) , 7.08 (IH, d) , 3.87 (3H, s), 3.70 (3H, s) , 2.35 (3H, s) , 2.13 (3H, s) , 1.33
(9H,s)
Present compound 430:
7.32 (IH, s), 7.16 (IH, d) , 7.13 (IH, d) , 6.99 (IH, s) , 4.70 (2H, s), 4.23 (2H, q) , 3.87 (3H, s) , 3.70 (3H, s), 2.35 (3H, s), 2.24 (3H, s) , 1.28 (3H, t) Present compound 433:
7.33 (IH, s), 7.19 (IH, d) , 7.14 (IH, d) , 7.03 (IH, s) , 4.76 (2H, d) , 3.88 (3H, s) , 3.71 (3H, s) , 2.46 (IH, t) , 2.41 (3H, s), 2.19 (3H, s) Present compound 434:
7.32 (IH, s), 7.15 (IH, d) , 7.13 (IH, d) , 7.02 (IH, s) , 6.06 (IH, ) , 5.32 (IH, d) , 5.21 (IH, d) , 4.67 (2H, d) , 3.87 (3H, s), 3.70 (3H, s) , 2.35 (3H, s) , 2.18 (3H, s)
Present compound 435: 7.34 (IH, d) , 7.15 (2H,s), 7.06 (IH, s) , 6.18 (IH, s) , 4.74 (2H, d) , 3.88 (3H, s), 3.71 (3H, s) , 2.36 (3H, s) , 2.15 (3H, s)
Present compound 436:
7.31 (IH, s), 7.14 (2H, s) , 7.00 (IH, s) , 4.60 (2H, s) , 3 . 86 ( 3H, s ) , 3 .70 ( 3H, s ) , 2 . 53 ( 3H, s ) , 2 . 23 ( 3H s ) , 1 . 48 ( 9H, s )
Present compound 438:
6.6-7.5 (13H), 5.17 (2H, s) , 3.85 (3H, s) , 3.67 (3H, s) , 3.09 (3H, s), 2.21 (3H, s) Present compound 439:
6.4-7.5 (14H), 5.14 (2H,s), 5.06 (2H, s) , 3.83 (3H, s) , 3.66 (3H, s), 3.08 (3H, s) , 2.19 (3H, s) Present compound 440: 8.19 (IH, d) , 7.8-7.9 (2H) , 7.4-7.6 (4H) , 7.40 (IH, s) , 7.18 (IH, t), 7.00 (IH, br.d), 6.96 (IH, br.s), 6.65 (IH, br.d), 5.69 (2H, s), 3.85 (3H, s) , 3.68 (3H, s) , 3.10 (3H, s) , 2.22 (3H, s)
Present compound 441: 6.6-7.4 (13H), 5.16 (2H, s) , 3.84 (3H, s) , 3.66 (3H, s) ,
3.08 (3H, s), 2.24 (3H, s) , 2.21 (3H, s)
Present compound 442 :
6.6-7.7 (14H), 5.26 (2H, s), 3.84 (3H, s) , 3.66 (3H, s) ,
3.09 (3H, s), 2.24 (3H, s) Present compound 443 :
7.76 (IH, d) , 7.64 (IH, dd) , 7.5-7.6 (5H) , 7.43 (IH, t) , 7.40 (IH, s), 7.17 (IH, t) , 6.99 (IH, d) , 6.95 (IH, s) , 6.64 (IH, d) , 5.29 (2H, s) , 3.85 (3H, s) , 3.66 (3H, s) , 3.09 (3H, s) , 2.26 (3H, s) Present compound 444:
7.32 (IH, s), 7.17 (IH, d) , 7.13 (IH, d) , 7.03 (IH, s) , 4.99 (IH, s), 4.91 (IH, s), 4.59 (2H, s) , 3.87 (3H, s) , 3.70 (3H, s), 2.35 (3H, s) , 2.19 (3H, s) , 1.79 (3H, s)
Present compound 445: (5:1 mixture of isomers) 7.32 (IH, s), 7.2-7.3 (3H) , 6.94 (IH, m) , {5.00 (2HX 1/6) , 4.68 (2HX5/6) , each s}, {3.98 (3HX1/6) , 3.85 (3HX5/6) , each s}, {3.89 (3HX5/6) , 3.84 (3HX1/6) , each s}, 3.71 (3H, s), {2.21 (3HX5/6), 2.18 (3HX1/6), each s}, {2.23 (3HX1/6), 1.92 (3HX5/6) , each s}
Present compound 446: (5:1 mixture of isomers)
7.33 (IH, s), 7.17 (IH, d) , 7.14 (IH, d) , 7.03 (IH, s) , {4.98 (2HX1/6), 4.66 (2HX5/6), each s}, {3.89 (3HX5/6), 3.84 (3HX1/6), each s}, 3.87 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s) , {2.19 (3HX1/6), 2.17 (3HX5/6), each s}, 1.91 (3H, s) Present compound 447: (5:1 mixture of isomers) 7.40 (IH, s), 7.17 (IH, t) , 6.97 (IH, d) , 6.92 (IH, br.s),
6.66 (IH, br.d), {5.00 (2HX1/6), 4.68 (2HX5/6), eachs}, {3.89
(3HX5/6), 3.83 (3HX1/6), each s}, 3.87 (3H, s) , 3.67 (3H, s) , 3.09 (3H, s), {2.22 (3HX1/6,), 2.21 (3HX5/6), each s}, 1.93
(3H, s)
Present compound 448: (5:1 mixture of isomers) 7.2-7.3 (2H) , 7.05 (IH, m) , 6.78 (IH, m) , {5.00 (2HX
1/6), 4.68 (2HX5/6), each s}, 4.02 (3H,s), {3.89 (3HX5/6), 3.84 (3HX1/6), eachs}, 3.76 (3H, s) , 3.25 (3H, s) , {2.22 (3H
Xl/6), 2.21 (3HX5/6) , each s}, 1.92 (3H, s)
Present compound 449: (5:1 mixture of isomers) 7.1-7.4 (2H), 7.05 (IH, m) , 6.80 (IH, m) , 6.70 (IH, br.),
{5.00 (2HX1/6), 4.67 (2HX5/6), each s}, 3.90 (3H, s) , {3.89 (3HX5/6), 3.84 (3HX1/6), eachs}, 3.27 (3H, s) , 2.88 (3H, d) ,
{2.22 (3HX1/6), 2.20 (3HX5/6), each s}, 1.91 (3H, s) Present compound 450: 7.32 (IH, s), 7.18 (IH, d) , 7.15 (IH, d) , 7.02 (IH, s) ,
5.42 (IH, s), 5.36 (IH, s) , 4.70 (2H, s) , 3.85 (3H, s) , 3.69 ( 3H, s ) , 2 . 35 ( 3H, s ) , 2 . 21 ( 3H , s )
Present compound 451:
7.33 (IH, s), 7.0-7.3 (3H) , 5.11 (lH,d), 4.65 (2H, d) , 3.87 (3H,s), 3.71 (3H,s), 2.35 (3H, s) , 2.17 (3H, s) , 1.25 (9H, s)
Present compound 452:
7.0-7.4 (8H), 5.17 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.36 (3H, s), 2.34 (3H, s) , 2.19 (3H, s)
Present compound 453 : 6.9-7.4 (9H), 5.34 (IH, q) , 3.81 (3H, s), 3.68 (3H, s) , 2.33 (3H,s), 2.20 (3H,s), 1.59 (3H,d)
Present compound 454:
7.39 (IH, s), 7.38 (lH,d), 7.32 (IH, s) , 7.24 (IH, dd) ,
7.14 (2H, s), 7.01 (IH, s) , 3.85 (3H, s) , 3.70 (3H, s), 2.34 (3H, s), 2.21 (3H,s)
Present compound 455:
7.0-7.5 (7H), 5.26 (2H, s) , 3.85 (3H, s) , 3.70 (3H, s) , 2.35 (3H, s), 2.24 (3H, s) Present compound 456: 7.75 (IH, s), 7.63 (IH, d) , 7.37 (IH, d) , 7.33 (IH, s) ,
7.15 (IH, d), 7.14 (IH, d) , 7.09 (IH, t) , 7.01 (IH, s) , 5.13 (2H, s), 3.85 (3H,s), 3.70 (3H, s) , 2.35 (3H, s) , 2.19 (3H, s)
Present compound 457 :
7.34 (IH, s), 7.16 (IH, d) , 7.12 (IH, d) , 7.04 (IH, s) , 6.92 (IH, s), 6.84 (IH, s) , 5.97 (2H, s) , 5.20 (2H, s) , 3.87 (3H, s), 3.70 (3H, s) , 2.35 (3H, s) , 2.20 (3H, s) Present compound 458:
7.0-7.5 (9H), 6.66 (IH, d) , 6.42 (IH, dt) , 4.83 (2H, d) , 3.81 (3H, s), 3.69 (3H, s) , 2.35 (3H, s) , 2.20 (3H, s) Present compound 459:
7.31 (IH, s), 7.16 (IH, d) , 7.14 (IH, d) , 6.98 (IH, s) , 5.92 (IH, m) , 5.33 (lH,d), 5.24 (IH, d) , 4.74 (2H, s) , 4.62 (2H, d) , 3.87 (3H, s), 3.70 (3H, s) , 2.35 (3H, s) , 2.24 (3H, s) Present compound 460:
6.95-7.4 (9H, ) , 3.89 (3H, s) , 3.72 (3H, s) , 2.39 (3H, s), 2.38 (3H, s)
Present compound 461:
8.19 (2H, d), 7.52 (2H, d) , 7.31 (IH, s) , 7.13 (2H, s) , 6.98 (IH, s) , 5.27 (2H, s) , 3.83 (3H, s) , 3.68 (3H, s), 2.34 (3H, s), 2.22 (3H, s)
Present compound 462:
7.36 (IH, s), 7.05-7.2 (3H, m) , 5.23 (2H, s) , 3.89 (3H, s), 3.71 (3H, s), 2.35 (3H, s) , 2.12 (3H, s) Present compound 463:
7.35 (IH, s), 7.17 (IH, d) , 7.12 (IH, d) , 7.03 (IH, s) , 3.87 (3H, s), 3.71 (3H, s) , 2.36 (3H, s) , 2.23 (3H, s)
Then, Formulation Examples are described. Part means part by weight and the present compounds are represented by chemical Nos . shown in Table 1 and Table 2.
Formulation Example 1
Each 50 parts of the present compounds 1-493 and 1001-1078 ,
3 parts of calcium lignin sulfonate, 2 parts of sodium laurylsulfate and 45 parts of synthetic hydrated silicon oxide are sufficiently ground and mixed to obtain each water dispersible powder.
Formulation Example 2
Each 25 parts of the present compounds 1-493 and 1001-1078 , 3 parts of polyoxyethylene sorbitan monooleate, 3 parts of CMC and 69 parts of water are mixed and wet-ground until particle size of the active ingredients becomes 5 micron or less, to obtain each flowable. Formulation Example 3
Each 2 parts of the present compounds 1-493 and 1001- 1078, 88 parts of caolin clay and 10 parts of talc are sufficiently ground and mixed to obtain each dust. Formulation Example 4 Each 20 parts of the present compounds 1-493 and 1001-1078 , 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecyl benzenesulfonate and 60 parts of xylene are sufficiently mixed to obtain each emulsifiable concentrate. Formulation Example 5 Each 2 parts of the present compounds 1-493 and 1001- 1078, 1 part of synthetic hydrated silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of caolin clay are sufficiently ground and mixed, water was added to well knead and granulated to dry, to obtain each granule.
Formulation Example 6
Each 20 parts of the present compound 1-493 and 1001- 1078, 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and the mixture is finely-ground (particle size 3 μ or less) with a sand grinder . 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and 10 parts of propylene glycol is further added, followed by stirring and mixing to obtain each 20% suspensionconcentrate. Formulation Example 7
Each 0.1 part of the present compounds 1-493 and 1001-1078 is dissolved in 5 parts of xylene and 5 parts of trichloroethane and the solution is mixed with 89.9 parts of deodorized kerosine to obtain each 0.1% oil solution. Formulation Example 8
Each 0.1 part of the present compounds 1-493 and 1001-1078, 0.2 part of tetramethrin, 0.1 part of d-phenothrin, 10 parts of trichloroethane and 59.6 parts of deodorized kerosine are mixed to dissolve, the solution is filled into an aerosol container, a valve part is attached thereto, and 30 parts of propellant (liquefied petroleum gas) is filled under pressure through the valve part to obtain each oily aerosol. Formulation Example 9
Each 0.2 part of the present compounds 1-493 and 1001-1078 , 0.2 part of d-allethrin, 0.2 part of d-phenothrin, 5 parts of xylene, 3.4 parts of deodorized kerosine and 1 part of an emulsifier {ATMOS 300 (registered trade name by Atlas Chemical Co.)} is mixed to dissolve, and this solution and 50 parts of pure water are filled into an aerosol container, a valve part is attached thereto, and 40 parts of a propellant (liquefied petroleum gas) is filled under pressure through the valve part to obtain each aqueous aerosol . Formulation Example 10
0.3 g of d-allethrin is added to each 0.3 g of the present compounds 1-493 and 1001-1078, the mixture is dissolved in 20 ml of acetone, mixed with 99.4 g of a carrier for a mosquito coil (prepared by mixing Tabu powder, pyrethrum marc powder and wood flour in the ratio of 4:3:3) uniformly by stirring, 120 ml of water is added and sufficiently kneaded, molded and dried to obtain each mosquito coil. Formulation Example 11 Acetone is added to each 0.4 g of the present compounds 1-493 and 1001-1078 , 0.4 g of d-allethrin and 0.4 g of piperonyl butoxide to dissolve to a total volume of 10 ml. 0.5 ml of this solution is impregnated into a base material for an electric mosquito mat (2.5 cm X 1.5 cm, thickness 0.3 cm) (prepared by forming a fibrillated mixture of cotton linter and pulp into a sheet) uniformly to obtain each electric mosquito mat. Formulation Example 12
Each 100 mg of the present compounds 1-493 and 1001-1078 is dissolved in an appropriate amount of acetone, and the solution is impregnated into a porous ceramic plate (4.0 cm X 4.0 cm, thickness 1.2 cm) to obtain each heat fumigant. Formulation Example 13
Each 10 mg of the present compounds 1-493 and 1001-1078 is dissolved in 0.5 ml of acetone, this solution is added to 5 g of solid bait powder for animals (Breeding Solid Feed CE-2; trade name by Japan Clea Co. , Ltd. ) and mixed uniformly. Then, acetone is removed by air-drying to obtain each 0.5% poison bait.
Then, the following Test Examples indicate that the present compounds are useful as a microbicidal agent for agriculture and/or horticulture, and an insecticidal and/or acaricidal agent. The present compounds are indicated by referring to chemical Nos . in Table 1 and Table 2.
The efficacy of the present compounds was assessed by the rate of disease area on tested plants in a case of agricultural and/or horticultural antifungal use, or calculating mortality of the test worms in a case of insecticidal or acaricidal use.
Test Example 1: Efficacy of invented compounds against rice blast (preventive effect)
Sandy loam was packed into a plastic pot, and rice (variety: Nihonbare) was seeded thereon and grown in a greenhouse for 20 days. Thereafter, each of the compounds having chemical Nos . 1, 2, 4-14, 30, 31,115, 116, 163, 174, 199, 200, 215, 216, 217, 220, 231, 232, 233, 237, 247, 250, 251, 252, 253, 255, 257, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 414, 417, 418, 419, 421, 422, 423, 430, 433-436, 438-462 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed onto the rice plants. After treatment, the plants were air-dried, and spores of rice blast were inoculated onto the rice plants. After inoculation, the plants were placed at 28 °C under high humidity for 6 days, and the efficacy of the tested compound was assesed. As a result, all the compounds inhibited development of rice blast. The rate of the disease area on the treated plant was less than 30%. Test Example 2 : Efficacy of the invented compounds against sheath blight of rice (preventive effect)
Sandy loam was packed into a plastic pot, and rice (variety: Nihonbare) was seeded thereon and grown in a greenhouse for 20 days. Thereafter, each of the compounds having chemical Nos. 1, 2, 4-14, 31, 116, 199, 200, 216, 220, 231, 237, 255, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 414, 417, 418, 419, 421, 422, 423, 430, 433-436, 438-462 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500-200 ppm) , and these were sprayed to foliage of rice plants sufficiency. After the treatment, the plants were air-dried, and hyphae of sheath blight were inoculated on rice plant. After inoculation, the plants were placed at 28 °C for under high humidity for 6 days, and the efficacy of the tested compound was assesed. As a result, all the compounds inhibited development of sheath blight . The desease area on the treated plant was less than 3/10 times as much as that on non-treated plant. Test Example 3 : The efficacy of the invented compound against powdery mildew of wheat, (curative effect)
Sandy loam was packed into a plastic pot, and wheat (variety: Norin 73 ) was seeded thereon and grown in a greenhouse for 10 days. Spores of powdery mildew of wheat were inoculated on wheats. After inoculation, the plants were placed in a greenhouse at 23 °C for 2 days. Each of the compounds having chemical Nos. 1, 2, 4-14, 30, 31, 115, 116, 163, 174, 199, 200, 215, 216, 217, 220, 232, 237, 247, 251, 252, 253, 255, 256, 257, 272, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 417, 418, 419, 421, 422, 423, 430, 433-436, 438-462 was prepared into suspension according to the procedures of Formulation Example 2 , diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed onto the inoculated wheats . After the treatment, the plants were left under illumination for 7 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of powdery mildew of wheat. The rate of the desease area on the treated plant was less than 30%.
Test Example 4: The efficacy of the invented compounds against brown leaf rust of wheat (preventive effect)
Sandy loam was packed into a plastic pot, and wheat (variety: Norin 73 ) was seeded thereon and grown in a greenhouse for 10 days. Each of the compounds having chemical Nos. 1, 2, 3, 4, 30, 31, 115, 116, 163, 174, 199, 200, 215, 216, 217, 220, 231, 237, 247, 251, 252, 253, 255, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 417, 418, 419, 421, 422, 423, 430, 433-436, 438-462 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed onto foliage of wheats sufficiently. After the treatment, the plants were air-dried and spores of brown leaf rust of wheat were inoculated on the wheats . After inoculation, the plants were first placed at 23 °C in the darkness under high humidity for one day and further under illumination for 6 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of brown leaf rust of wheat. The rate of desease area on the treated plants was less than 30 %.
Test Example 5 : Efficacy of the invented compounds against leaf blight of wheat (preventive effect)
Sandy loam was packed into a plastic pot, and wheat (variety: Norin 73) was seeded thereon and grown in a greenhouse for 10 days. Each of the compounds having chemical Nos. 1, 2, 4, 6-9, 12, 115, 116, 163, 215, 252, 255 and 272 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) , and these were sprayed onto foliage of wheats sufficiently. After the treatment, the plants were air-dried and spores of leaf blight of wheat were inoculated on the wheats . After inoculation, the plants were first placed at 15 °C in the darkness under high humidity for 3 days and further under illumination for 18 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of leaf blight of wheat. The rate of disease area on the treated plant was less than 10%. Test Example 6 : The efficacy of the invented compound against glume blotch of wheat (preventive effect)
Sandy loam was packed into a plastic pot, and wheat (variety: Norin 73 ) was seeded thereon and grown in a greenhouse for 10 days. Each of the compounds having chemical Nos. 1, 2, 4, 6-9, 12, 115, 116, 163, 215, 220, 233, 237, 252, 255, 257, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 374, 377, 383, 393, 414, 417, 418, 419, 421, 422, 423, 430, 433-436, 438-440, 442-448, 450-462 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed to foliage of wheat sufficiently. After the treatment, the plants were air-dried and spores of glume bloch of wheat were inoculated on the wheats. After inoculation, the plants were first placed at 15 °C in the darkness under high humidity for 4 days and further under illumination for 7 days, and the efficacy of the tested compound assessed. As a result, all the compounds inhibited development of glume blotch of wheat . The rate of disease area on the treated plant was less than 30 %. Test Example 7 : The efficacy of the invented compounds on eyespot of wheat (preventive effect)
Sandy loam was packed into a plastic pot, and wheat (variety: Norin 73 ) was seeded thereon and grown in a greenhouse for 10 days. Each of the compounds having chemical Nos. 1- 12, 116, 163, 174, 215, 220, 233, 237, 247, 252, 255, 272, 301, 322, 324, 326, 329, 336, 353, 357, 359, 360, 366, 371, 373, 374, 377, 383, 393, 414, 422, 430, 433, 434, 436, 438-443, 445, 446, 477, 449-456, 458 and 459 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, dilutedwith water to a predetermined concentration (500ppm), and these were sprayed onto foliage of wheats sufficiently. After the treatment, the plants were air-dried and PDA medium containing spores of eyespot of wheat was placed at the wheat foot. After inoculation, the plants were first placed at 15 °C in the darkness under high humidity for 7 days and further under illumination for 4 days, and the efficacy of the tested compound assessed. As a result, all the compounds inhibited development of eyespot of wheat. The disease area on the treated plant was less than 3/10 times as much as that on the non-treated plant.
Test Example 8 : The efficacy of the invented compounds on downy mildew of cucumber (preventive effect)
Sandy loam was packed into a plastic pot, and cucumber (variety: Sagamihanpaku) was seeded thereon and grown in a greenhouse for 20 days. Each of the compounds having chemical
Nos. 1, 2, 4, 115, 116, 163, 174, 215, 216, 217, 252, 272 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500 ppm) , and these were sprayed onto foliage of cucumbers sufficiently. After the treatment, the plants were air-dried and spores of downy mildew of cucumber were inoculated on the cucumbers. After inoculation, the plants were first placed at 23 °C under high humidity for 1 day and further in a greenhouse for 10 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of downy mildew of cucumber.
The rate of disease area on the treated plant was less than 10 % . Test Example 9 : The efficacy of the invented compounds on gray mold of cucumber (preventive effect)
Sandy loam was packed into a plastic pot, and cucumber (variety: Sagamihanpaku) was seeded thereon and grown in a greenhouse for 12 days . Each of the compounds having chemical Nos. 1, 2, 4-13, 30, 31, 116, 163, 174, 199, 200, 215, 220, 237, 247, 252, 255, 257, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 414, 417, 418, 419, 421, 422, 423, 430, 433-436, 439, 440, 442-447, and 450-462 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500-200 ppm) , and these were sprayed onto foliage of cucumbers sufficiently. After the treatment, the plants were air-dried and PDA medium containing hyphae of gray mold of cucumber was placed on the cucumber leaves. After inoculation, the plants were placed at 10 °C under high humidity for 4 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of gray mold of cucumber. The percentage of the treated plant was less than 30%.
Test Example 10 : The efficacy of the invented compounds on powdery mildew of cucumber (preventive effect)
Sandy loam was packed into a plastic pot, and cucumber (variety: Sagamihanpaku) was seeded thereon and grown in a greenhouse for 12 days . Each of the compounds having chemical Nos. 1, 2, 4-8, 11, 12, 14, 116, 215, 216, 217, 220, 257, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 414, 417, 418, 419, 421, 422, 423, 430, 433-436, 438, 440, 442, 444, 446, 447, and 450-462 was prepared into suspension according to the procedures of Formulation Example 2, diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed onto foliage of cucumbers sufficiently. After the tretment , the plants were air-dried and spores of powdery mildew of cucumber were inoculated on the cucumbers . After inoculation, the plants were placed at 23 °C for 12 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of powdery mildew of cucumber. The rate of disease area on the treated plant was less than 30%.
Test Example 11: The efficacy of the invented compounds on downy mildew of grape (preventive effect)
Sandy loam was packed into a plastic pot, and grape (variety: Berry A) was seeded thereon and grown in a greenhouse for 40 days. Each of the compounds having chemical Nos. 1, 2, 4, 115, 116, 163, 174, 215, 216, 217, 220, 230, 232, 233, 237, 252, 272, 301, 302, 321, 322, 324, 326, 329, 332, 333, 336, 353, 356, 357, 359, 360, 362, 366, 371, 373, 374, 377, 383, 393, 417, 418, 419, 421, 422, 423, 430, 433-436, 438, 440, 442-448, and 450-462 was prepared into suspension according to the procedures of Formulation Example 2, diluted with water to a predetermined concentration (500 or 200 ppm) , and these were sprayed onto foliage of grape sufficiently. After the treatment, the plants were air-dried and zoosporangia of downy mildew of grape were inoculated on the grapes . After inoculation, the plants were placed first at 23 °C under high humidity for 1 day and further in a greenhouse for 6 days, and the efficacy of the tested compound was assessed. As a result, all the compounds inhibited development of powdery mildew of grape. The rate of disease area on the treated plant was less than 30%.
Test Example 12 : Insecticidal test against larva of common cutworm (Spodoptera litura) Each of the compounds Nos. 4, 9 and 13 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain 2 ml of a diluted solution, which was soaked into 13 g of an artificial feed for Spodoptera litura which had been prepared in a polyethylene cup having the diameter of 11 cm. 5 larvae of 4 week-age Spodoptera litura were released in the cup and, after 6 days, the death or survival thereof was investigated to obtain mortality. As a result, all the test compounds showed mortality of 80%. Test Example 13 : Insecticidal test against larva of brown planthopper (Nilaparvata lugens)
Sandy loam was packed into a plastic pot, and rice
(variety: Nihonbare) was seeded thereon and grown in a greenhouse. Thereafter, each of the compounds Nos .2, 4-6, 8-10 and 14 was prepared into water dispersible powder according to the procedures of Formulation Example 1, diluted with water to a predetermined concentration (500 ppm) , and this was sprayed to foliage so as to sufficiently attach to rice leavee. After spray, the plants were air-dried, and about 30 larvae of
Nilaparvata lugens were released thereon. After release of larvas, the plants were left in a greenhouse for 6 days, the death or survival thereof was investigated to obtain mortality.
As a result, all the compounds showed mortality of 80% or more. Test Example 14: Insecticidal test against larva of southern corn root worm (Diabrotica undecimpunctata)
The bottom of a polyethylene cup having a diameter of 5.5 cm was covered with a filter paper having the same diameter as that of the bottom. Each of the compounds Nos. 2 and 4-10 was prepared into emulsifiable concentrate according to the procedures in Formulation Example 4 and diluted with water to a predetermined concentration (50 ppm) to obtain 1 ml of the diluted solution, whichwas added dropwise on the filter. About 30 eggs of southern corn root worm were placed on the filter, and one budding of corn was placed thereon as a feed. After 8 days, the death or survival of hatched larvae was investigated to obtain mortality. As a result, all the compounds showed mortality of 80% or more.
Test Example 15: Application test against cotton aphid (Aphid gossypii)
5 adults of test worms were released on true leaf plants of cucumber (first true leaf developed stage) planted in a polyethylene cup. One day after release, each of the present compounds 5, 6, 8 and 10 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain the diluted solution, which was sprayed at an amount of 20 ml/pot. 6 days after drug solution spray, the controlling value was obtained according to the following equation. As a result, the above compounds showed the controlling effect of 90% or more, respectively.
Controlling value = {1- (Cb»Tai) / (Tb»Cai) } x 100 Cb: Number of worms in non-treated plot before treatment Cai: Number of worms in non-treated plot at observation Tb: Number of worms in test plot before treatment Tai : number of worms in test plot at observation Test Example 16: Spraying test against Tetranychus urticae Bush bean (Phaseolus vulgaris L.var. humilis Alef.) (primordial leaf stage) planted in a polyethylene cup was made parasitic with 20 female adults of Tetranychus urticae per leaf and was placed in a constant temperature room. After 6 days, each of the present compounds 5 , 6, 7, 8, 9, 10 and 13 was prepared into emulsifiable concentrate according to the procedures in Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain the diluted solution, which was sprayed to the pot at an amount of 20 ml/pot. 8 days after the spray, degree of damage by Tetranychus urticae was investigated. As a result, in plots treated with the above test compounds, damage was hardly observed.
Test Example 17: Insecticidal test against house-fly (Musca domestica) The bottom of a polyethylene cup having a diameter of 5.5 cm was covered with a filter paper having the same diameter of that of the bottom. Each of the present compounds 1, 2, 4, 5, 7, 8, 9, 10 and 13 was prepared into emulsifiable concentrate, diluted with water to a predetermined concentration (500 ppm) to obtain 0.7 ml of diluted solution, which was added dropwise on the filter, and 30 mg of sucrose as a feed was placed uniformly in the cup. 10 female adults of Musca domestica were released in the cup, the cup was capped and, after 24 hours, the survival or death thereof was investigated to obtain mortality. As a result, the above test compounds showedmortality of 80% or more, respectively.
Test Example 18: Insecticidal test against common mosquito (Culex pipens pallens)
Each of the present compounds 1, 4, 6, 8, 10, 12 and 13 was prepared into emulsifiable concentrate according to the procedures of Formulation Example 4, diluted with water to a predetermined concentration (500 ppm) to obtain 0.7ml of a diluted solution, which was added to 100 ml of ion-exchanged water (concentration of an active ingredient: 3.5 ppm). 20 larvae of one week-age Culex pipens pallens were released therein and, 8 days after treatment, adult eclosion inhibiting rate was investigated. As a result, the above test compounds showed adult eclosion inhibiting rate of 80% or more, respectively. Industrial Applicability
The present compounds have excellent antifungal effect for agriculture and/or horticulture as well as excellent insecticidal and/or acaricidal effect.

Claims

Claims
1. An oxime ether compound represented by the general formula:
wherein R1 represents hydrogen atom, alkyl group, cycloalkyl group, alkoxyalkyl group, haloalkyl group, cyano group, nitro group or alkoxycarbonyl group, one of T, U and V represents CR2 group, the other one represents CH group or nitrogen atom and the rest one represents CR3 group or nitrogen atom,
W represents CR33 group or nitrogen atom, R2, R3 and R33 are the same or different and represent hydrogen atom, halogen atom, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, nitro group, alkoxycarbonyl group, alkylthio group or haloalkylthio group, R4 represents hydrogen atom, alkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, aryl group or heterocyclic group, wherein the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group and the heterocyclic group may have one or more substituents,
R5 and R6 are the same or different and represent alkyl group,
X represents NR7 group, oxygen atom or sulfur atom, R7 represents alkyl group optionally having one or more substituents,
Y represents CH group or nitrogen group, Z represents oxygen atom or NH group, provided that when Y is CH group, then Z is oxygen atom.
2. The oxime ether compound according to claim 1 , wherein the substituent in the definition of R4 is halogen atom; OR8 group; N(R)R10 group; C(R13)=NOR14 group; C1-C5 alkylthio group; C1-C5 haloalkylthio group; C1-C10 acyl group; C2-Cn alkoxycarbonyl group; N-(Cι-Cιo alkyl ) carbamoyl group; N, N- di(Cι-Cιo alkyl ) carbamoyl group; cyano group; nitro group; aryl group optionally having one or more substituents; or heterocyclic group optionally having one ore more substituents; in which R8 is hydrogen atom; Cι-Cι0 alkyl group; C1-C5 haloalkyl group; C3-Cβ cycloalkyl group; C2-Cχo alkoxyalkyl group; C1-C10 acyl group; C2-Cu alkoxycarbonyl group; N-(Cι-Cιo alkyl) carbamoyl group; N, N-di- (C1-C10 alkyl) carbamoyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C1-C5 alkyl group, and trifluoromethyl group;
R9 and R10 are same or different, and each is hydrogen atom; C1-C10 alkyl group; C5-C6 cycloalkyl group; C1-C10 acyl group; C2-C11 alkoxycarbonyl group; N-(C╬╣-C╬╣0 alkyl) carbamoyl group; N, N-di(C╬╣-C╬╣0 alkyl) carbamoyl group; C1-C5 alkylsulfonyl group; C╬▓-Cio arylsulfonyl group; C1-C5 haloalkylsulfonyl group; C1-C5 alkylsulfinyl group; C1-C5 haloalkylsulfinyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C1-C5 alkyl group and trifluoromethyl group; or R9 and R10 are taken together to form tetramethylene group, pentamethylene group, or CH2CH2OCH2CH2 group;
R13 and R14 are same or different, and each is hydrogen atom; C1-C10 alkyl group; C3-C6 cycloalkyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C1-C5 alkyl group, trifluoromethyl group, cyano group and nitro group; the sutstituent of the aryl group as R4 is halogen atom; C1-C10 alkyl group; C3-Cι0 cycloalkyl group; C1-C5 haloalkyl group; hydroxy group; Cχ-Cιo alkoxy group; C1-C5 haloalkoxy group; amino group; cyano group; nitro group; C2-Cδ alkoxycarbonyl group; C3-C8 cycloalkoxy group; N-(Cι-C5 alkyl ) carbamoyl group; N, N-di(Cι-C5 alkyl) carbamoyl group; C1-C10 acyl group; phenoxy group optionally having one or more substituents selected from the group consisting of halogen atom, Cι-C3 alkyl group, Cι-C3 haloalkyl group, and C1-C3 alkylthio group; phenyl group optionally having one or more cyano group; 2-pyridyloxy group optionally having one or more substituents selected from the group consisting of trifluoromethyl group and halogen atom; morpholine-1-yl group; benzyloxy group; benzoyloxy group; C_,-C5 alkylsulfonyloxy group; C1-C5 haloalkylsulfonyloxy group; trifluoromethanesulfonylamino group; R110C(0)0 group; Rn(R12)NC(0)0 group; RnC (O)N(R12) group; Rn0C(0)NH group; Rn(R12)NC(0)NH group; or C1-C10 alkylthio group; in which R11 and R12 are same or different, and each is C3.- C5 alkyl group; and the substituent of the heterocyclic group as R4 is halogen atom; Ci-Cio alkyl group; C3-Cι0 cycloalkyl group; C1-C5 haloalkyl group; hydroxy group; C1-C10 alkoxy group; amino group; or C1-C10 alkylthio group; and the substituent of the alkyl group as R7 is halogen atom; C1-C5 alkoxy group; C2-C5 alkoxycarbonyl group; N-(Cι-C5 alkyl ) carbamoyl group; N,N-di(Cι-C5 alkyl) carbamoyl group; or cyano group.
3. The oxime ether compound according to claim 1 or 2 , Wherein R1 is hydrogen atom; C1-C10 alkyl group; C3-C╬╣0 cycloalkyl group; C2-C╬╣o alkoxyalkyl group; C1-C5 haloalkyl group; cyano group; nitro group; or C2-C5 alkoxycarbonyl group;
R2, R3 and R33 are same or different, and each is hydrogen atom; halogen atom; C1-C5 alkyl group; C1-C5 alkoxy group; C1-C5 haloalkyl group; C1-C5 haloalkoxy group; cyano group; nitro group; C2-Cs alkoxycarbonyl group; C1-C5 alkylthio group; or
C1-C5 haloalkylthio group;
R4 is hydrogen atom; C1-C10 alkyl group; C3-C╬╣o alkenyl group; C3-C╬╣0 alkynyl group; C3-C╬╣0 cycloalkyl group; C5-C10 cycloalkenyl group; aryl group; or heterocyclic group; (in which the C1-C10 alkyl group, the C3-C╬╣o alkenyl group, the C3-C10 alkynyl group, the C3-C╬╣o cycloalkyl group, the C5-C10 cycloalkenyl group, the aryl group, and the heterocyclic group may have one or more substituents.); R5 and R6 are same or different, and each is C1-C5 alkyl group ; and
R7 is C1-C5 alkyl group optionally having one or more substituents.
4. The oxime ether compound according to any one of claims 1, 2 and 3, wherein
R4 is Ci-Cio alkyl group optionally having one or more substituents selected from the group consisting of OR8 group; N(R9)R10 group; C(R13)=NOR14 group; C1-C5 alkylthio group; Ci- C5 acyl group; C2-C5 alkoxycarbonyl group; N-(C╬╣-C5 alkyl) carbamoyl group; N, N-di(d-C5 alkyl) carbamoyl group; cyano group; nitro group; aryl group optionally having one or more substituents; and heterocyclic group optionally having one ore more substituents ; in which,
R8 is hydrogen atom; C1-C5 alkyl group; C2-C5 alkoxyalkyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C1-C5 alkyl group, and trifluoromethyl group; R9 and R10 are same or different, and each is hydrogen atom; C1-C5 alkyl group; C1-C5 acyl group; C2-C5 alkoxycarbonyl group; N- (C1-C5 alkyl) carbamoyl group; N, N-di (C1-C5 alkyl) carbamoyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C_,-C5 alkyl group and trifluoromethyl group; or R9 and R10 are taken together to form tetramethylene group, pentamethylene group, or CH2CH2OCH2CH2 group,
R13 and R14 are same or different, and each is hydrogen atom; C1-C10 alkyl group; C3-C6 cycloalkyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, C1-C5 alkyl group, trifluoromethyl group, cyano group and nitro group; the sutstituent of the aryl group as R4 is halogen atom; C1-C5 alkyl group; C3-C╬▓ cycloalkyl group; C1-C5 haloalkyl group, hydroxy group; C1-C5 alkoxy group; amino group; or C1-C5 alkylthio group; and the substituent of the heterocyclic group as R4 is halogen atom; C1-C5 alkyl group; C3-C6 cycloalkyl group; C1-C5 haloalkyl group; hydroxy grou ; C1-C5 alkoxy group; amino group; or C1-C5 alkylthio group.
5. The oxime ether compound according to any one of claims 1-4, wherein the aryl group is phenyl group; a -naphthyl group; or ╬▓ -naphthyl group; the heterocyclic group as R4 is 2-pyridyl group; 4-pyridyl group; 2-pyrimidinyl group; 4-pyrimidinyl group; 3-pyrazolyl group; 2-thiazolyl group; 2-imidazolyl group; or 3- (1,2,4- triazolyl) group; and the heterocyclic group as the substituent of the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group group, the cycloalkenyl group, the aryl group, or the heterocyclic group in the definition of R4 is 2-pyridyl group;
3 -pyridyl group; 4-pyridyl group; 2-pyrimidinyl group; 4- pyrimidinyl group; 5-pyrimidinyl group; 1-pyrazolyl group;
3-pyrazolyl group; 4-pyrazolyl group; 5-pyrazolyl group; 2- thiazolyl group; 4-thiazolyl group; 5-thiazolyl group; 1-
(1,2,4-triazolyl) group; 3- (1, 2 , 4-triazolyl) group; succinimido-1-yl group; maleinimido-1-yl group; or phthalimido-1-yl group.
6. The oxime ether compound according to any one of claims 1 to 3 , and 5, wherein
T, U, V, and W are not nitrogen atom; and
R4 is C1-C10 alkyl group optionally having one or more substituents, in which the substituent is C(R13)=NOR14 group; C2-C5 alkoxycarbonyl group; or phenyl group optionally having one or more substituents selected from the group consisting of halogen atom, Ci-Cio alkyl group, C1-C5 haloalkyl group, C1-C10 alkoxy group, cyano group, nitro group and C2-C6 alkoxycarbonyl group; in which
R13 and R14 are same or different, and each is hydrogen atom; C1-C10 alkyl group; C3-C6 cycloalkyl group; or phenyl group optionally having one or more halogen atom, C1-C5 alkyl group, triflluoromethyl group, cyano group or nitro group.
7. The oxime ether compound according to any one of claims 1 to 3 , and 5, wherein
T, U, V, and W are not nitrogen atom; and R4 is allyl group optionally having one or more substituents selected from the group consisting of halogen atom, C2-C5 alkoxycarbonyl group, cyano group and nitro group; 1- methyl-2-propenyl group; 2-methyl-2-propenyl group; 3- methyl-2-propenyl group; or 3-methyl-2-butenyl group.
8. The oxime ether compound according to any one of claims 1 to 3 , and 5, wherein
T, U, V, and W are not nitrogen atom; and R4 is propargyl group optionally having one or more substituents selected from the group consisting of halogen atom and C2-C5 alkoxycarbonyl group; l-methyl-2-propynyl group; or 2-butynyl group.
9. The oxime ether compound according to any one of claims 1 to 4, wherein the aryl group is phenyl; the heterocyclic group as R4 is 2-pyridyl group; or 4-pyridyl group; and the heterocyclic group as the substituent of the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the cycloalkenyl group, the aryl group, or the heterocyclic group in the definition of R4 is 2-pyridyl group; 3-pyridyl group; or 4-pyridyl group.
10. The oxime ether compound according to any one of claims 1-5, wherein one of T, U and V represents CH group, the other one represents CH group or nitrogen atom and the rest one represents CH group or nitrogen atom, and W represents CH group or nitrogen atom.
11. The oxime ether compound according to any one of claims 1-10, wherein R5, R6 and R7 are methyl group.
12. The oxime ether compound according to any one of claims 1-11, wherein none of T, U, V and W are nitrogen.
13. The oxime ether compound according to any one of claims 1-12, wherein X is NR7 group, wherein R7 is as defined above .
14. The oxime ether compound according to any one of claims 1-12, wherein X is oxygen atom.
15. The oxime ether compound according to any one of claims 1-12, wherein X is sulfur atom.
16. The oxime ether compound according to claim 14, wherein T represents CCH3 group, and U, V, W and Y represent CH group.
17. The oxime ether compound according to any one of claims 1-15, wherein Y is CH group.
18. The oxime ether compound according to any one of claims 1-15, wherein Y is nitrogen atom and Z is oxygen atom.
19. The oxime ether compound according to any one of claims 1-15, wherein Y is nitrogen atom and Z is NH group.
20.The oxime ether compound according to any one of claims 1-19, wherein R1 is methyl group.
21. An agricultural and/or horticultural antifungal agent, which comprises as an active ingredient the oxime ether compound according to any one of claims 1-20.
22. An insecticidal and/or acaricidal agent, which comprises as an active ingredient the oxime ether compound according to any one of claims 1-20.
23. A method for controlling plant disease, comprising applying an effective amount of the oxime ether compound according to any one of claims 1 to 20 to foliage of plant, soil or seed.
24. A method for controlling insect or acarine, comprising applying an effective amount of the oxime ether compound according to any one of claims 1 to 20 to foliage of plant, soil or seed.
25. Use of the oxime ether compound according to any one of claims 1-20 as agricultural and/or horticultural antifungal agent .
26. Use of the oxime ether compound according to any one of claims 1-20 as insecticidal and/or acaricidal agent.
27. A compound represented by the general formula:
wherein R1, R4, R6, T, U, V, W, X and Y are as defined in any one of claims 1-20.
28. A compound represented by the general formula:
wherein R1, R4, R6, T, U, V, W and X are as defined in any one of claims 1-20.
29. A compound represented by the general formula:
wherein R1, R5, R6, T, U, V, W, X and Z are as defined in any one of claims 1, 3, 10-16 and 18-20.
30. A compound represented by the general formula:
wherein R5 and R6 are defined in any one of 1, 3 and 11
EP98911069A 1997-04-01 1998-03-27 Oxime ether compounds, their use and intermediates for preparations of the same Withdrawn EP0975587A1 (en)

Applications Claiming Priority (7)

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JP8290097 1997-04-01
JP8290097 1997-04-01
JP31803197 1997-11-19
JP31803197 1997-11-19
JP2607498 1998-02-06
JP2607498 1998-02-06
PCT/JP1998/001408 WO1998043949A1 (en) 1997-04-01 1998-03-27 Oxime ether compounds, their use and intermediates for preparations of the same

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JP2000103772A (en) * 1998-09-30 2000-04-11 Sumitomo Chem Co Ltd Intermediate for manufacture of oxime ether compound
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CN102690246B (en) * 2012-05-30 2014-06-04 华中农业大学 Oxime ether amine compound or oxime ether amine salt, composition containing oxime ether amine compound or oxime ether amine salt and application thereof
CN102850246B (en) * 2012-07-10 2015-04-22 江西理工大学 Method for introducing mercapto group into aniline derivative
AR115870A1 (en) 2018-07-31 2021-03-10 Sumitomo Chemical Co METHOD FOR CONTROLLING SOYBEAN ROY FUNGUS THAT HAS RESISTANCE TO SITE INHIBITOR Qₒ
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