WO2018015797A1 - Novel benzylamide compound, method for producing the same, and miticide - Google Patents

Novel benzylamide compound, method for producing the same, and miticide Download PDF

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Publication number
WO2018015797A1
WO2018015797A1 PCT/IB2016/055523 IB2016055523W WO2018015797A1 WO 2018015797 A1 WO2018015797 A1 WO 2018015797A1 IB 2016055523 W IB2016055523 W IB 2016055523W WO 2018015797 A1 WO2018015797 A1 WO 2018015797A1
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compound
alkyl
cdci
reaction
formula
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PCT/IB2016/055523
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French (fr)
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Tetsuya Imai
Surendra Kumar KUMAWAT
Manish Kumar SINGH
Pramod Kumar CHAUHAN
Amol Vasant SHELKE
Rajesh Kumar Singh
Ram Kishore
Ashish BHATT
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Insecticides (India) Limited
Oat Agrio Co., Ltd.
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Priority to TW106123632A priority Critical patent/TWI739860B/en
Publication of WO2018015797A1 publication Critical patent/WO2018015797A1/en

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    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine 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
    • A01N37/18—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 the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues 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
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • 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
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/10—Sulfones; Sulfoxides
    • 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
    • C07C323/23—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 nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/31—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 nitrogen atoms, not being part of nitro or nitroso 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
    • C07C323/33—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 nitrogen atoms, not being part of nitro or nitroso 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 having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D213/24—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
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/56—Amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—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
    • 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim

Definitions

  • the present invention relates to a novel benzylamide compound, method for producing the same, and miticide containing the compound.
  • Patent Literature (PTL) 1) discloses a compound represented by following Formula (A) :
  • R 5 represents substituted or unsubstituted Ci-20 alkyl, substituted or unsubstituted amino, N-containing heterocycles, or the like, and reports that this compound exhibits miticidal activity.
  • PTL 1 mainly, urea compounds are produced, and although the amide compounds where R 5 is alkyl, haloalkyl, aryl, or cycloalkyl are also produced, no amide compounds where R 5 is benzyl is disclosed. In addition, PTL 1 nowhere discloses that the above compound (A) exhibits ovicidal activity.
  • An object of the present invention is to provide a novel benzylamide compound or a salt thereof that exhibits miticidal activity.
  • Another object of the present invention is to provide a method for producing the benzylamide compound or the salt thereof.
  • a further object of the present invention is to provide a new type of miticide containing the benzylamide compound or the salt thereof.
  • the present inventors conducted extensive research to achieve the above objects, and succeeded in synthesizing a compound represented by the following Formula (1) or a salt thereof that has miticidal activity.
  • the present inventors have conducted further research based on the above findings .
  • the present invention has thereby been accomplished.
  • the present invention includes the following embodiments:
  • R 1 represents Ci_6 alkyl or Ci-6 haloalkyl
  • R 2 and R 3 are identical or different and each represent hydrogen, halogen, cyano, nitro, Ci- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl or C 3 - 8 cycloalkyl Ci- 6 alkyl;
  • R 4 represents hydrogen, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkoxy Ci- 6 alkyl, Ci- 6 haloalkoxy Ci- 6 alkyl, C 3 - 8 cycloalkyl, C 3 - 8 cycloalkyl Ci- 6 alkyl, Ci- 6 alkylcarbonyl, Ci- 6 haloalkylcarbonyl, Ci- 6 alkoxycarbonyl, Ci- 6 haloalkoxycarbonyl, arylcarbonyl, aryloxycarbonyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -e alkynyl, C 2 -e haloalkynyl, Ci- 6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkyl
  • R 7 , R 8 , R 9 , R 10 , and R 11 are identical or different and each represent hydrogen, halogen, nitro, cyano, hydroxyl, formyl, Ci-6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkoxy Ci- 6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C 3 - 8 cycloalkyl Ci-6 alkyl, Ci- 6 alkylcarbonyl, Ci- 6 haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, Ci- 6 alkoxycarbonyl, Ci- 6 haloalkoxycarbonyl, Ci- 6 cyanoalkyl, Ci-6 cyanoalkoxy, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C 2 -e haloalkyny
  • R 7 and R 8 , R 8 and R 9 , R 9 and R 10 , or R 10 and R 11 , taken together with the benzene ring to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom;
  • X represents oxygen or sulfur
  • n an integer of 0 to 2.
  • R 7 , R 8 , R 9 , R 10 , and R 11 are identical or different and each represent hydrogen, halogen, nitro, Ci-6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci_6 haloalkylthio, substituted or unsubstituted amino, aryl, or heterocyclic.
  • step (d) obtaining a sulfide compound represented by Formula (1-1) by reacting a thiol compound represented by Formula (6) with an alkylating reagent represented by Formula (7) : wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above and G represents a leaving group; and
  • step (e) obtaining a benzylamide compound represented by Formula (1-2) by reacting the sulfide compound represented by Formula (1-1) with an oxidizing agent:
  • step (c) obtaining a thiol compound represented by Formula (6) by reacting a sulfonylchloride compound represented b Formula (5) with a reducing agent:
  • step (b) obtaining the sulfonylchloride compound represented by Formula (5) by chlorosulfonylating an amide com ound represented by Formula (4) :
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above.
  • step (a) obtaining the amide compound represented by Formula (4) by reacting an aniline compound represented by Formula (2) with a benzylcarbonyl compound represented by Formula (3) :
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above, and Y represents a leaving group or hydroxyl group Item 10:
  • the benzylamide compound or the salt thereof according to the present invention achieves an excellent miticidal effect with a small amount thereof.
  • the benzylamide compound and the salt thereof can simply be produced with an excellent yield.
  • a new type of miticide containing the benzylamide compound or the salt thereof according to the present invention can be provided.
  • the present invention is directed to a compound represented by Formula (1) :
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , X and n are as defined above.
  • halogen examples include, but are not particularly limited to, fluorine, chlorine, bromine, iodine, and the like.
  • Ci_6 alkyl examples include, but are not particularly limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and like Ci_6 straight- chain or branched-chain alkyl.
  • Ci_6 haloalkyl examples include, but are not particularly limited to, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, trifluoromethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3, 3, 3-trifluoropropyl, 4, 4, 4-trifluorobutyl, heptafluoroisobutyl, and like Ci-6 straight-chain or branched- chain alkyl substituted with 1 to 9, and preferably 1 to 5, halogen atoms .
  • Ci_6 alkoxy examples include, but are not particularly limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and like Ci-6 straight-chain or branched-chain alkoxy.
  • Ci-6 haloalkoxy examples include, but are not particularly limited to, fluoromethoxy, chloromethoxy, bromomethoxy, iodomethoxy, difluoromethoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, pentafluoroethoxy, 3, 3, 3-trifluoropropoxy, 4, 4, 4-trifluorobutoxy, heptafluoroisobutoxy, and like Ci-6 straight-chain or branched-chain alkoxy substituted with 1 to 9, preferably 1 to 5, halogen atoms.
  • Ci-6 alkoxy Ci-6 alkyl examples include, but are not particularly limited to, methoxymethyl, ethoxymethyl, n- propoxymethyl, isopropoxymethyl, n-butoxymethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, methoxyethyl, ethoxyethyl, methoxy-n-propyl, methoxy-n-butyl, and like alkoxyalkyl in which Ci-6 straight-chain or branched-chain alkyl is substituted with Ci_ 6 straight-chain or branched-chain alkoxy.
  • Ci-6 haloalkoxy Ci-6 alkyl examples include, but are not particularly limited to, fluoromethoxymethyl, chloromethoxymethyl, bromomethoxymethyl, iodomethoxymethyl, difluoromethoxymethyl, trifluoromethoxymethyl, 2,2,2- trifluoroethoxymethyl, and like straight-chain or branched-chain alkoxyalkyl substituted with 1 to 9, preferably 1 to 5, halogen atoms .
  • C3-8 cycloalkyl examples include, but are not particularly limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.
  • C 3 - 8 cycloalkyl Ci- 6 alkyl examples include, but are not particularly limited to, cyclopropylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, and the like.
  • Ci-6 alkylcarbonyl examples include, but are not particularly limited to, methylcarbonyl (acetyl) , ethylcarbonyl (propionyl) , n-propylcarbonyl (butyryl) , isopropylcarbonyl (isobutyryl) , n-butylcarbonyl (valeryl) , isobutylcarbonyl (isovaleryl) , sec-butylcarbonyl, tert-butylcarbonyl, and like Ci- 6 straight-chain or branched-chain alkylcarbonyl groups.
  • Ci-6 haloalkylcarbonyl examples include, but are not particularly limited to, fluoromethylcarbonyl, chloromethylcarbonyl, bromomethylcarbonyl, iodomethylcarbonyl, dichloromethylcarbonyl, trichloromethylcarbonyl, difluoromethylcarbonyl, trifluoromethylcarbonyl, chlorodifluoromethylcarbonyl, bromodifluoromethylcarbonyl, dichlorofluoromethylcarbonyl, 2,2, 2-trichloroethylcarbonyl,
  • arylcarbonyl examples include, but are not particularly limited to, benzoyl, tert-butylbenzoyl, and like substituted or unsubstituted benzoyl group; 1-naphthoyl, 2- naphthoyl, and the like substituted or unsubstituted naphthoyl group .
  • aryloxycarbonyl examples include, but are not particularly limited to, phenoxycarbonyl, 4- diaminophenoxycarbonyl, 4-fluorophenoxycarbonyl, 4-tert- butylphenoxycarbonyl, and like substituted or unsubstituted phenoxycarbonyl group; 1-naphthoxycarbonyl, 2-naphthoxycarbonyl, and the like substituted or unsubstituted naphthoxycarbonyl group
  • Ci_6 alkoxycarbonyl examples include, but are not particularly limited to, methoxycarbonyl, ethoxycarbonyl, n- propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, and like Ci-6 straight-chain or branched-chain alkoxycarbonyl groups.
  • Ci_6 haloalkoxycarbonyl examples include, but are not particularly limited to, fluoromethoxycarbonyl, chloromethoxycarbonyl , bromomethoxycarbonyl , iodomethoxycarbonyl, dichloromethoxycarbonyl, trichloromethoxycarbonyl, difluoromethoxycarbonyl, trifluoromethoxycarbonyl, 2,2,2- trifluoroethoxymethyl, pentafluoroethoxycarbonyl, 3,3,3- trifluoropropoxycarbonyl, 4,4, 4-trifluorobutoxycarbonyl, heptafluoroisopropoxycarbonyl, and like Ci_6 straight-chain or branched-chain alkoxycarbonyl substituted with 1 to 9, preferably 1 to 5, halogen atoms.
  • cyano Ci_6 alkyl examples include, but are not particularly limited to, cyanomethyl, cyanoethyl, cyano-n-propyl, cyano-isopropyl, cyano-n-butyl, cyano-isobutyl, cyano-sec-butyl, cyano-tert-butyl, cyano-n-hexyl, and like Ci-6 straight-chain or branched-chain alkyl substituted with a cyano group.
  • cyano Ci-6 alkoxy examples include cyanomethoxy, cyanoethoxy, cyano-n-propoxy, cyano-isopropoxy, cyano-n-butoxy, cyano-iso-butoxy, cyano-sec-butoxy, cyano-tert-butoxy, cyano- hexyloxy, and like Ci_6 straight-chain or branched-chain alkoxy substituted with a cyano group.
  • C2-6 alkenyl examples include, but are not particularly limited to, vinyl, allyl, 2-butenyl, 3-butenyl, 1- methylallyl, and the like.
  • C 2 -6 haloalkenyl examples include, but are not particularly limited to, 2, 2-dichlorovinyl, 2, 2-dibromovinyl, 2, 2-difluorovinyl, 2, 2-dibromovinyl, 3, 3-difluoro-2-allyl, 4,4- difluoro-3-butenyl, 4, 4, 4-trifluoro-2-butenyl, and the like.
  • C2-6 alkynyl examples include, but are not particularly limited to, ethynyl, 2-propynyl (propargyl) , 1- methyl-2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and the like.
  • C 2 -6 haloalkynyl examples include, but are not particularly limited to, fluoroethynyl, bromoethynyl, chloroethynyl, iodoethynyl, 3, 3, 3-trifluoro-l-propynyl, and the like.
  • Ci-6 alkylsulfonyl examples include, but are not particularly limited to, methylsulfonyl, ethylsulfonyl, n- propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, and like Ci-6 straight-chain or branched-chain alkylsulfonyl groups.
  • Ci_6 haloalkylsulfonyl examples include, but are not particularly limited to, fluoromethylsulfonyl, chloromethylsulfonyl, bromomethylsulfonyl, iodomethylsulfonyl, dichloromethylsulfonyl, trichloromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, chlorodifluoromethylsulfonyl, bromodifluoromethylsulfonyl, dichlorofluoromethylsulfonyl, 2,2, 2-trichloroethylsulfonyl,
  • Ci_6 alkylsulfinyl examples include, but are not particularly limited to, methylsulfinyl, ethylsulfinyl, n- propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, and like Ci-6 straight-chain or branched-chain alkylsulfinyl groups.
  • Ci_6 haloalkylsulfinyl examples include, but are not particularly limited to, fluoromethylsulfinyl, chloromethylsulfinyl, bromomethylsulfinyl, iodomethylsulfinyl, dichloromethylsulfinyl, trichloromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, chlorodifluoromethylsulfinyl, bromodifluoromethylsulfinyl, dichlorofluoromethylsulfinyl, 2,2, 2-trichloroethylsulfinyl,
  • Ci-6 alkylthio examples include, but are not particularly limited to, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert- butylthio, and like Ci-6 straight-chain or branched-chain alkylthio.
  • Ci-6 haloalkylthio examples include, but are not particularly limited to, fluoromethylthio, chloromethylthio, bromomethylthio, iodomethylthio, dichloromethylthio, trichloromethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, bromodifluoromethylthio, dichlorofluoromethylthio, 2, 2, 2-trichloroethylthio, 2,2,2- trifluoroethylthio, pentafluoroethylthio, and like Ci-6 straight- chain or branched-chain alkylthio substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
  • C3-8 cycloalkylsulfonyl examples include, but are not particularly limited to, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl, and the like.
  • C3-8 cycloalkylsulfinyl examples include, but are not particularly limited to, cyclopropylsulfinyl, cyclobutylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl, and the like.
  • C3-8 cycloalkylthio examples include, but are not particularly limited to, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio, and the like.
  • Ci-6 alkylsulfonyl examples include, but are not particularly limited to, cyclopropylmethylsulfonyl, 2-cyclopropylethylsulfonyl, 3-cyclopropylpropylsulfonyl, cyclohexylmethylsulfonyl, and the like.
  • Ci-6 alkylsulfinyl examples include, but are not particularly limited to, cyclopropylmethylsulfinyl, 2-cyclopropylethylsulfinyl, 3-cyclopropylpropylsulfinyl, cyclohexylmethylsulfinyl, and the like.
  • Ci-6 alkylthio examples include, but are not particularly limited to, cyclopropylmethylthio, 2- cyclopropylethylthio, 3-cyclopropylpropylthio, cyclohexylmethylthio, and the like.
  • Ci-6 alkoxy Ci-6 alkylsulfonyl examples include, but are not particularly limited to, methoxymethylsulfonyl, ethoxymethylsulfonyl , n-propoxymethylsulfonyl , isopropoxymethylsulfonyl, n-butoxymethylsulfonyl, sec- butoxymethylsulfonyl, tert-butoxymethylsulfonyl, methoxyethylsulfonyl, and like alkoxyalkylsulfonyl in which Ci-6 straight-chain or branched-chain alkylsulfonyl is substituted with Ci-6 straight-chain or branched-chain alkoxy.
  • Ci-6 alkoxy Ci-6 alkyl sulfinyl examples include, but are not particularly limited to, methoxymethylsulfinyl, ethoxymethylsulfinyl, n-propoxymethylsulfinyl, isopropoxymethylsulfinyl, n-butoxymethylsulfinyl, sec- butoxymethylsulfinyl, tert-butoxymethylsulfinyl, 2- methoxyethylsulfinyl, and like alkoxyalkylsulfinyl in which Ci-6 straight-chain or branched-chain alkylsulfinyl is substituted with Ci-6 straight-chain or branched-chain alkoxy.
  • Ci_6 alkoxy Ci_6 alkylthio examples include, but are not particularly limited to, methoxymethylthio, ethoxymethylthio, n-propoxymethylthio, isopropoxymethylthio, n-butoxymethylthio, sec-butoxymethylthio, tert-butoxymethylthio, 2-methoxyethylthio, and like alkoxyalkylthio in which Ci-6 straight-chain or branched- chain alkylthio is substituted with Ci-6 straight-chain or branched-chain alkoxy.
  • C2-6 alkenyloxy examples include, but are not particularly limited to, vinyloxy, 1-propenyloxy, isopropenyloxy, allyloxy, 2-butenyloxy, 3-butenyloxy, 1-methylallyloxy, and the like .
  • C2-6 haloalkenyloxy examples include, but are not particularly limited to, 2, 2-dichlorovinyloxy, 2,2- dibromovinyloxy, 2, 2-difluorovinyloxy, 2, 2-dibromovinyloxy, 3,3- difluoro-2-allyloxy, 4, 4-difluoro-3-butenyloxy, 4,4, 4-trifluoro- 2-butenyloxy, and the like.
  • C2-6 alkynyloxy examples include, but are not particularly limited to, ethynyloxy, 2-propynyloxy, l-methyl-2- propynyloxy, 1, l-dimethyl-2-propynyloxy, 1-butynyloxy, 2- butynyloxy, 3-butynyloxy, and the like.
  • C2-6 haloalkynyloxy examples include, but are not particularly limited to, fluoroethynyloxy, bromoethynyloxy, chloroethynyloxy, iodoethynyloxy, 3, 3, 3-trifluoro-l-propynyloxy, and the like.
  • Ci-6 alkylsulfonyloxy examples include, but are not particularly limited to, methylsulfonyloxy, ethylsulfonyloxy, n- propylsulfonyloxy, isopropylsulfonyloxy, n-butylsulfonyloxy, isobutylsulfonyloxy, sec-butylsulfonyloxy, tert-butylsulfonyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfonyl groups .
  • Ci_6 haloalkylsulfonyloxy examples include, but are not particularly limited to, fluoromethylsulfonyloxy, chloromethylsulfonyloxy, bromomethylsulfonyloxy, iodomethylsulfonyloxy, dichloromethylsulfonyloxy, trichloromethylsulfonyloxy, difluoromethylsulfonyloxy, trifluoromethylsulfonyloxy, chlorodifluoromethylsulfonyloxy, bromodifluoromethylsulfonyloxy, dichlorofluoromethylsulfonyloxy, 2,2, 2-trichloroethylsulfonyloxy, 2,2, 2-trifluoroethylsulfonyloxy, pentafluoroethylsulfonyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfonyloxy substitute
  • Ci-6 alkylsulfinyloxy examples include, but are not particularly limited to, methylsulfinyloxy, ethylsulfinyloxy, n- propylsulfinyloxy, isopropylsulfinyloxy, n-butylsulfinyloxy, isobutylsulfinyloxy, sec-butylsulfinyloxy, tert-butylsulfinyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfinyloxy groups .
  • Ci_6 haloalkylsulfinyloxy examples include, but are not particularly limited to, fluoromethylsulfinyloxy, chloromethylsulfinyloxy, bromomethylsulfinyloxy, iodomethylsulfinyloxy, dichloromethylsulfinyoxy, trichloromethylsulfinyloxy, difluoromethylsulfinyloxy, trifluoromethylsulfinyloxy, chlorodifluoromethylsulfinyloxy, bromodifluoromethylsulfinyloxy, dichlorofluoromethylsulfinyloxy, 2,2, 2-trichloroethylsulfinyloxy, 2,2, 2-trifluoroethylsulfinyloxy, pentafluoroethylsulfinyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfinyloxy substituted
  • substituted or unsubstituted amino examples include, but are not particularly limited to, amino, monoalkylamino, dialkylamino, monoacylamino, and the like.
  • alkyl examples include Ci_6 alkyl mentioned above, and the like.
  • acyl examples include Ci-6 alkoxycarbonyl, haloalkoxycarbonyl, arylcarbonyl mentioned above, and the like.
  • aryl examples include, but are not particularly limited to, phenyl, 1-naphthyl, 2-naphthyl, and the like.
  • aryl Ci-6 alkyl examples include, but are not particularly limited to, benzyl, phenylethyl, phenyl-n-propyl, and the like.
  • aryloxy examples include, but are not particularly limited to, phenoxy, 1-naphthyloxy, 2-naphthyloxy, and the like.
  • aryl Ci-6 alkoxy examples include, but are not particularly limited to, benzyloxy, phenoxyethoxy, phenoxy-n- propoxy, phenyl-n-butoxy, 1-naphthylmethoxy, 2-naphthylmethoxy, and like.
  • arylsulfonyl examples include, but are not particularly limited to, phenylsulfonyl, 1-naphthylsulfonyl, 2- naphthylsulfonyl, and the like.
  • arylsulfinyl examples include, but are not particularly limited to, phenylsulfinyl, 1-naphthylsulfinyl, 2- naphthylsulfinyl, and the like.
  • arylthio examples include, but are not particularly limited to, phenylthio, 1-naphthylthio, 2-naphthylthio, and the like .
  • aryl Ci-6 alkylsulfonyl examples include, but are not particularly limited to, benzylsulfonyl, phenylethylsulfonyl, phenyl-n-propylsulfonyl, phenyl-n-butylsulfonyl, 1- naphthylmethylsulfonyl, 2-naphthylmethylsulfonyl, and the like.
  • aryl Ci-6 alkylsulfinyl examples include, but are not particularly limited to, benzylsulfinyl, phenylethylsulfinyl, phenyl-n-propylsulfinyl, phenyl-n-butylsulfinyl, 1- naphthylmethylsulfinyl, 2-naphthylmethylsulfinyl, and the like.
  • aryl Ci-6 alkylthio examples include, but are not particularly limited to, benzylthio, phenylethylthio, phenyl-n- propylthio, phenyl-n-butylthio, 1-naphthylmethylthio, 2- naphthylmethylthio, and the like.
  • All the Aryls mentioned above may optionally be further substituted.
  • Examples of the number of substituents include, but are not particularly limited to, 1 to 20 (preferably 1 to 10, and more preferably 1 to 5) .
  • heterocyclic group examples include, but are not particularly limited to, thienyl, furyl, tetrahydrofuryl, dioxolanyl, dioxanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, oxazolyl, isoxazolyl, oxazolinyl, oxazolidinyl, isoxazolinyl, thiazolyl, isothiazolyl, thiazolinyl, thiazolidinyl, isothiazolinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxadiazolyl, oxadiazolinyl, thiadiazolinyl, triazolyl, triazolinyl, triazolidinyl, tetrazolyl, tetrazolinyl, pyridyl, dihydrox
  • heterocyclic groups include those substituted at any substitutable position with an oxo or thioketone group.
  • heterocyclic Ci_6 alkyl include, but are not particularly limited to, 2-pyridylmethyl, 3-pyridylmethyl, 2- pyrazinylmethyl, pyrimidinylmethyl, 2-quinolinylmethyl, and the like .
  • heterocyclicoxy examples include, but are not particularly limited to, 2-pyridyloxy, 3-pyridyloxy, 2- pyrazinyloxy, pyrimidinyloxy, 2-quinolinylmethyloxy, and the like
  • heterocyclics mentioned above may optionally be further substituted.
  • substituents include, but are not particularly limited to, 1 to 20 (preferably 1 to 10, and more preferably 1 to 5) .
  • R 5 and R 6 taken together with the carbon atom to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom.
  • hetero atom in the specification include, but are not particularly limited to, an oxygen atom, a sulfur atom, a nitrogen atom, and the like.
  • 3- to 8-membered ring include: but are not particularly limited to, cyclopropane, cycloheptane, and the like C3-8 cycloalkyl; tetrahydropyran, piperidine, and the like heterocyclic.
  • R 7 and R 8 , R 8 and R 9 , R 9 and R 10 , or R 10 and R 11 , taken together with the benzene ring to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom.
  • Examples of the 3- to 8-membered ring include: C3-8 cycloalkyl, aryl, heterocyclic, and the like. The C3-8 cycloalkyl, the aryl, and the heterocyclic are as defined above .
  • substituted groups include: but are not particularly limited to, the halogen, nitro, cyano, hydroxyl, formyl, Ci- 6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C 3 - 8 cycloalkyl, C 3 - 8 cycloalkyl Ci- 6 alkyl, Ci- 6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, Ci- 6 alkoxycarbonyl, Ci- 6 haloalkoxycarbonyl, Ci- 6 cyanoalkyl, Ci-6 cyanoalkoxy, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C 2 -6 haloalkynyl, Ci-
  • substituents are halogen, nitro, Ci-6 alkyl, Ci- 6 haloalkyl, Ci- 6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci- 6 alkylthio, Ci- 6 haloalkylthio, substituted or unsubstituted amino, aryl, and heterocyclic , and more preferable substituents are fluorine, chlorine, nitro, methyl, ethyl, trifluoromethyl, methoxy, and trifluoromethoxy.
  • Preferable substituted aryl groups are halogen- substituted aryl, Ci- 6 alkyl-substituted aryl, Ci- 6 haloalkyl- substituted aryl, halogen and Ci- 6 haloalkyl—substituted aryl, Ci- 6 alkoxy-substituted aryl, Ci- 6 haloalkoxy-substituted aryl, and Ci- 6 alkylthio-substituted aryl.
  • More preferable substituted aryl groups are chlorine-substituted aryl, fluorine-substituted aryl, trifluoromethyl-substituted aryl, chlorine- and trifluoromethyl- substituted aryl, trifluoromethoxy-substituted aryl, and methoxy- substituted aryl, and methylthio-substituted aryl.
  • Preferable substituted heterocyclic groups are halogen- substituted heterocyclic, Ci- 6 alkyl-substituted heterocyclic, Ci- 6 haloalkyl-substituted heterocyclic, Ci-6 alkoxy-substituted heterocyclic, Ci- 6 haloalkoxy-substituted heterocyclic, and Ci- 6 alkylthio-substituted heterocyclic.
  • More preferable substituted heterocyclic groups are chlorine-substituted heterocyclic, fluorine-substituted heterocyclic, trifluoromethyl-substituted heterocyclic, trifluoromethoxy-substituted heterocyclic, methoxy- substituted heterocyclic, and methylthio-substituted heterocyclic.
  • the salts of the compounds represented by Formula (1) may be any type of salts as long as they are agriculturally acceptable.
  • the salts include a hydrochloride salt, a sulfate salt, a nitrate salt, and like inorganic acid salts; an acetate salt, a methanesulfonic acid salt, and like organic acid salts; a sodium salt, a potassium salt, and like alkali metal salts; a magnesium salt, a calcium salt, and like alkaline earth metal salts; dimethylammonium, triethylammonium, and like quaternary ammonium salts; and the like.
  • X represents oxygen or sulfur.
  • n an integer of 0 to 2.
  • a preferable compound is a compound in which R 1 is Ci-6 haloalkyl, and a more preferable compound (1) is a compound in which R 1 is trifluoromethyl or trifluoroethyl .
  • a preferable compound is a compound in which R 2 is hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R 2 is fluorine, chlorine, bromine, or methyl.
  • a preferable compound is a compound in which R 3 is hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R 3 is fluorine, chlorine, bromine, methyl or trifluoromethyl .
  • a preferable compound is a compound in which R 4 is hydrogen, Ci-6 alkyl, C 2 -e alkenyl, C 2 -6 alkynyl, or Ci- 6 haloalkyl
  • a more preferable compound (1) is a compound in which R 4 is hydrogen, methyl, ethyl, n-propyl, n-butyl, 3, 3, 3-trifluoro-n-propyl, heptafluoroisopropyl, or propargyl .
  • a preferable compound is a compound in which R 5 and R 6 are identical or different and each represent hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R 5 and R 6 are hydrogen, fluorine, methyl, isopropyl, or tert-butyl .
  • a preferable compound is a compound in which R 7 , R 8 , R 9 , R 10 , and R 11 are hydrogen, halogen, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkylsulfonyl, Ci- 6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, substituted or unsubstituted amino, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic, and a more preferable compound (1) is a compound in which R 7 , R 8 , R 9 , R 10 , and R 11 are hydrogen, fluorine, chlorine, bromine, nitro, methyl, ethyl, n-propy
  • the compound (1) has isomers such as optical isomers, stereoisomers, regioisomers, and the like,
  • any of the isomers and mixtures thereof are included within the scope of the compound (1) .
  • the compound (1) has optical isomers
  • the optical isomer separated from a racemic body is also included within the scope of the compound (1) .
  • Each of such isomers may be obtained as a single compound by known synthesis and separation means (e.g., concentration, solvent extraction, column chromatography, recrystallization, etc.).
  • Method for producing a benzylamide compound and a salt thereof No limitations are placed on the method for producing a benzylamide compound (1) (compound (1-1) and compound (1-2) ) according to the present invention, and the benzylamide compound (1) can be produced by Steps 1 to 5 represented by Reaction Scheme 1 below:
  • Compound (4) An amide compound represented by Formula (4) can be produced by reacting an aniline compound (hereinafter may be referred to as “compound (2)”) represented by Formula (2)) with a benzylcarbonyl compound (hereinafter may be referred to as "compound (3)”) represented by Formula (3) (Reaction Scheme 2) :
  • Y represents a leaving group or a hydroxyl group
  • the leaving group include: halogen such as chlorine, bromine, and iodine; substituted or unsubstituted Ci-6 alkyl sulfonate; and substituted or unsubstituted aryl sulfonate.
  • the substituent include the aforementioned substituents such as the halogen and the Ci_6 haloalkyl.
  • Step 1A (when Y is a leaving group)
  • a phenylacetamide compound (hereinafter may be referred to as "compound (4)") represented by Formula (4) can be produced by reacting the aniline compound (hereinafter may be referred to as “compound (2) ) represented by Formula (2) ) with a benzylcarbonyl compound (hereinafter may be referred to as "compound (3A) represented by Formula (3A) (Reaction Scheme 3) : [Reaction Scheme 3]
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above.
  • Y' represents a leaving group.
  • benzylcarbonyl compound (3A) examples include, but are not particularly limited to, phenylacetyl chloride, phenylacetyl bromide, and the like substituted or unsubstituted phenylacetyl halide; and ethyl phenylacetate, methyl phenylacetate, and the like substituted or unsubstituted phenylacetic acid esters.
  • a used ratio of the aniline compound (2) and the benzylcarbonyl compound (3A) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the aniline compound (2), typically approximately 1 to 5 moles of the benzylcarbonyl compound (3A) and preferably approximately equimolar to 1.2 moles thereof is used.
  • the aforementioned reaction can be performed under absence or presence of a base.
  • the reaction is performed preferably under the presence of the base.
  • a conventionally known base can widely be used, and examples of the base include: sodium carbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, and the like alkali metal carbonates; sodium hydroxide, potassium hydroxide, and the like alkali metal hydroxides; alkali metal hydrides such as sodium hydride and potassium hydride, and the like inorganic bases; sodium methoxide, sodium ethoxide, potassium tert-butoxide, and the like alkali metal alkoxides; pyridine, triethylamine, diethylamin, dimethylamine, methylamine, imidazole, benzimidazole, diisopropylethylamine, 4-dimethylamine pyridine, piperidine, and the like organic bases; and the like. Any separate one of these bases or a combination of
  • Relative to 1 mole of the aniline compound (2) typically approximately 1 to 10 moles of the base and preferably approximately 1 to 5 moles thereof may excessively be used.
  • triethylamine, pyridine, or like an organic base it can be used in large excess to serve also as a reaction solvent.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • a solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1,2- dichloroethane, chloroform, and carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, tetrahydrofuran (THF) , 1,4-dioxane, and the like ether-based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; N, N-diofurane, and the like ether-based solvents; methyl acetate, ethyl acetate, and the like esters solvent
  • Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -10°C and a boiling point of the solvent used and preferably 0 to 25°C. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.5 to 24 hours.
  • Step IB (when Y is a hydroxyl group)
  • the compound (4) can be produced by reacting the aniline compound (2) with a phenylacetic acid compound
  • a used ratio of the aniline compound (2) and the phenylacetic acid compound (3B) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the aniline compound (2), typically approximately 1 to 5 moles of the phenylacetic acid compound (3B) and preferably approximately equimolar to 1.2 moles thereof is used.
  • the aforementioned reaction can be performed under absence or presence of a condensing agent.
  • the aforementioned reaction is preferably performed under the presence of the condensing agent.
  • the condensing agent a conventionally known condensing agent can be used, and examples of the condensing agent include l-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDCI HC1) , 1-hydroxybenzotriazole (HOBT) , 1- [bis (dimethylamino) methylene] -lH-1, 2, 3-triazolo [4, 5-b] pyridinium-3-oxide hexafluorophosphate (HATU) , bis (2-oxo-3- oxazolidinyl) phosphine acid chloride (BOP-C1) , propylphosphonic acid anhydride (T3P) , and the like. Any separate one of these condensing agents or a combination of two or more types thereof is
  • Relative to 1 mole of the aniline compound (2) typically 1 to 10 moles of the condensing agent and preferably approximately 1 to 3 moles thereof can excessively be used.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • a solvent include: fatty n-hexane, cyclohexane, n-heptane, and the like acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1,2- dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, and 1,4-dioxane, and the like ether-based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF and the like amide solvents; and dimethyl sulfate, 1,2-dioxane, and the like ether-based solvents; diethyl ether, THF, and 1,4-d
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
  • a phenylacetic acid halide compound (3C) obtained by reacting the phenylacetic acid compound (3B) with a halogenation reagent can be used as a raw material.
  • the aforementioned reaction can be performed under presence of a base.
  • a base any of the same bases as those described above can be used, and preferable examples of the base include triethylamine, pyridine, di-isopropylamine, 4- diisopropylethylamine, 4-dimethylamine pyridine, lutidine, and the like organic bases, and this base can also much excessively be used to be also used as a reaction solvent.
  • halogenation reagent includes, but are not particularly limited to, P0C1 3 , POBr 3 , S0C1 2 , S0 2 C1 2 , oxalyl chloride .
  • Relative to 1 mole of the aniline compound (2) typically 1 to 10 moles of the halogenation reagent and preferably approximately 1 to 5 moles thereof can be used.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction.
  • the aforementioned solvents are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
  • the aniline compound (2), the benzylcarbonyl compound (3A) , the phenylacetic acid compound (3B) , and phenylacetic acid halide compound (3C) in Step 1 used as starting materials in Step 1 are known compounds or compounds that can easily be produced by a known method.
  • the compound (4) obtained by the method shown in Step 1 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the compound (4) can be provided for next reaction without being isolated from the reaction system.
  • a sulfonyl chloride compound (hereinafter may be referred to as "compound (5)") represented by Formula (5) can be produced by chlorosulfonating the amide compound (4) (Reaction Scheme 5) :
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above.
  • a reagent used for the chlorosulfonation is not particularly limited, and for example, include chlorosulfonic acid, and the like.
  • the step can be carried out in one step.
  • a two-step method including sulfonation and then chlorination can be used.
  • the sulfonyl chloride compound (5) can be produced by reacting the amide compound with a sulfonation reagent to produce an HOSO 2 - substituted amide compound and then reacting the HOS0 2 -containing amide compound with a chlorination agent.
  • the reagent used for the sulfation is not particularly limited, and for example, chlorosulfonic acid, sulfuric acid are provided.
  • Examples of the chlorinating agent used for the chlorination include, but are not particularly limited to, chlorine, P0C1 3 , S0C1 2 , S0 2 C1 2 , and oxalyl chloride.
  • a used ratio between the amide compound (4) and the chlorosulfonic acid in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the amide compound (4) , typically approximately 1 to 50 moles of chlorosulfonic acid and preferably approximately 1 to 20 moles thereof is used.
  • a used ratio between the sulfonation reagent and the chlorinating agent in the reaction between the amide compound (4) and the sulfonation reagent is not particularly limited and can appropriately be selected from a wide range.
  • Relative to 1 mole of the amide compound (4) typically approximately 1 to 50 moles of the sulfonation reagent and preferably approximately 1 to 20 moles thereof is used.
  • a used ratio between the two in the reaction between the amide compound (4) and the chlorinating agent is not particularly limited, and can appropriately be selected from a wide range.
  • Relative to 1 mol of the amide compound (1) typically approximately 1 to 50 moles of the sulfuric acid and preferably 1 to 20 moles thereof is used.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • the solvent no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction.
  • the same solvents as those described above are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 150°C, and more preferably 0 to 100°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
  • the sulfonyl chloride compound (5) obtained by the method shown in Step 2 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfonyl chloride compound (5) can be provided for next reaction without being isolated from the reaction system.
  • a thiol compound (hereinafter may be referred to as "compound (6)") represented by Formula (6) can be produced by reacting the sulfonyl chloride compound (5) with a reducing agent (Reaction Scheme 6) :
  • a used ratio between the sulfonyl chloride compound (5) and the reducing agent in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the sulfonyl chloride compound (5) , typically approximately 1 to 50 moles of the reducing agent and more preferably approximately 1 to 20 moles thereof is used.
  • any of conventionally known reducing agents can widely be used, and examples of the reducing agent include: triphenylphosphine and the like phosphorous compounds; reducing agents containing metal and acid such as zinc and acid, tin (II) and acid, and iron and acid; and reducing agentred phosphorus, iodine, dichlorodimethylsilane-zinc- dimethylacetamide, lithium aluminum hydride, and the like specific reducing agents.
  • the acid include acetic acid and the like organic acids; and hydrochloric acid, sulfuric acid, and the like inorganic acids.
  • the aforementioned reaction is performed in an appropriate solvent. No limitations are placed on the solvent as long as the solvent is inactive with respect to the reaction.
  • the same solvents as those described above are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 150°C, and more preferably 20 to 120°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
  • the thiol compound (6) obtained by the method shown in Step 3 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the thiol compound (6) can be provided for next reaction without being isolated from the reaction system.
  • Examples of the method for producing the sulfide compound represented by Formula (1-1) include, but are not limited to, a production route 1, a production route 2, a production route 3, a production route 4, described below, and the like.
  • a sulfide compound (1-1) can be produced by reacting the thiol compound (6) with an alkyl reagent (hereinafter may be referred to as "alkyl reagent (7) ) represented by Formula (7) (Reaction Scheme 7) :
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above, and G represents a leaving group.
  • a used ratio between the thiol compound (6) and the alkyl reagent (7) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the thiol compound (6), typically approximately 1 to 10 moles of the alkyl reagent (7) and preferably approximately 1 to 5 moles thereof is used.
  • alkyl reagent (7) examples include, but are not particularly limited to, methyl iodide, ethyl bromide, and the like Ci_6 alkyl halides; trifluoromethyl iodide, trifluoromethyl bromide, trifluoroethyl iodide, trifluoroethyl bromide, and the like Ci-6 haloaklyl halides; and the like.
  • the aforementioned reaction can be performed under presence of a base.
  • the aforementioned reaction is preferably performed under the presence of the base.
  • the base conventionally known bases can widely be used, and any of the same bases as those described above can be used.
  • the aforementioned reaction can be performed by further adding a radical starting agent.
  • a radical starting agent include, but are not particularly limited to, sulfurous acid, a sulfurous acid salt, Rongalit (product name, sodium- formaldehyde-sulfoxylate) , and the like sulfurous acid adducts .
  • the base and the radical starting agent can be used in combination.
  • radical starting agent when used, as an additive amount thereof, relative to 1 mole of the thiol compound (6), typically 0.1 to 10 moles of the radical starting agent and preferably approximately 0.1 to 5 moles thereof can be used.
  • the aforementioned reaction is performed in an appropriate solvent.
  • the solvent include: n-hexane, cyclohexane n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like ester-based solvents; acetonitrile; DMF, N, N-dimethylacetamide, N-methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-
  • Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60 °C, and more preferably 0 to 50 °C.
  • Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
  • the sulfide compound (1-1) obtained by the method shown in Step 4 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfide compound (1-1) can be provided for next reaction without being isolated from the reaction system.
  • a sulfide compound (hereinafter may be referred to as "compound (1-lb)”) represented by Formula (1-lb) can be produced by reacting a sulfide compound (hereinafter may be referred to as "compound (1-la)”) represented by Formula (1-la) with a compound (hereinafter may be referred to as "compound (7') represented by Formula (7' ) : R4'-G (Reaction Scheme 8) :
  • R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X are as defined above, and R 4 ' represents formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci- 6 haloalkoxy, Ci- 6 alkoxy Ci- 6 alkyl, Ci- 6 haloalkoxy Ci- 6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkyl carbonyl, Ci- 6 haloalkyl carbonyl, Ci- 6 alkoxycarbonyl, Ci- 6 haloalkoxycarbonyl, arylcarbonyl, aryloxy carbonyl, C2-6 alkenyl, C 2 -6 haloalkenyl, C 2 -e alkynyl, C 2 -e haloalkynyl, Ci- 6 alkyls
  • a used ratio between the sulfide compound (1-la) and the compound (7' ) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
  • the aforementioned reaction can be performed under presence of a base.
  • the aforementioned reaction is preferably performed under the presence of the base.
  • the base conventionally known bases can be used and any of the same bases as those described above can be used.
  • a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can be used.
  • triethylamine, pyridine, or like an organic base it can be used in large excess to serve also as a reaction solvent.
  • the aforementioned reaction is performed in an appropriate solvent.
  • the solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF, N, N-dimethylacetamide, N- methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60°C, and more preferably 20 to 50°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
  • the sulfide compound (1-lb) obtained by the method shown in Step 4 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfide compound (1-lb) can be provided for next reaction without being isolated from the reaction system.
  • the sulfide compound (1-1) can be produced in accordance with not only what have been mentioned above but also production routes 3, 4, and 5.
  • the sulfide compound (1-la) can be produced by reacting an aniline compound (hereinafter may be referred to as "compound (8)") with a phenylacetic acid compound (3) (Reaction Scheme 9) : [Reaction Scheme 9]
  • the sulfide compound (1-la) can be produced by reacting the aniline compound (2) with a benzylcarbonyl compound (3A) (Reaction Scheme 10) :
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above, and Y' represents a leaving group.
  • Examples of the benzylcarbonyl compound (3A) include, but are not particularly limited to, the same compounds as those of Step 1A.
  • the aniline compound (8) used as a starting material can be produced according to methods described in WO2007/131680.
  • a used ratio between the aniline compound (8) and the benzylcarbonyl compound (3A) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the former, typically aproximately 1 to 5 moles of the latter and preferably approximately equimolar to 1.2 moles thereof is used.
  • the aforementioned reaction can be performed under absence or presence of a base.
  • the aforementioned reaction is preferably performed under the presence of the base.
  • the base any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
  • a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can excessively be used.
  • the base Preferably one to five times of the base may excessively be used.
  • triethylamine, pyridine, or like an organic base it can be used in large excess to serve also as a reaction solvent.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • any of the same solvents as those shown in Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used and preferably 0 to 50°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
  • the aniline compound (8) used as a starting material is a known compound or a compound that can easily be produced by a known method.
  • the sulfide compound (1-la) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfide compound (1-la) can be provided for next reaction without being isolated from the reaction system.
  • Step 3B (when Y is a hydroxyl group)
  • the compound (1-la) can be produced by reacting the aniline compound (8) with a phenylacetic acid compound (3B) (Reaction Scheme 11) :
  • R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above.
  • a used ratio between the aniline compound (8) and the phenylacetic acid compound (3B) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 5 moles of the latter and preferably equimolar to 1.2 moles thereof is used.
  • the aforementioned reaction can be performed under absence or presence of a condensing agent. Among the above, the aforementioned reaction is preferably performed under the presence of the condensing agent.
  • the condensing agent the same condensing agents as those shown in Step IB are listed. Any separate one of these condensing agents or a combination of two or more types thereof is used.
  • a stoichiometric amount of the condensing agent or an excessive amount thereof over the aforementioned amount can be used.
  • the aforementioned reaction can be performed under absence or presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base.
  • the base any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
  • a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can be used.
  • Preferably approximately 1 to 5 times of the base can excessively be used.
  • triethylamine, pyridine, or like an organic base it can be used in large excess to serve also as a reaction solvent.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • any of the same solvents as those shown in Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used and preferably 0 to 25°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
  • a phenylacetic acid halide compound (3C) obtained by reacting the phenylacetic acid compound (3B) with a halogenation reagent can be used as a material.
  • the aforementioned reaction can be performed under presence of a base.
  • a base any of the same bases as those described above can be used, and preferable examples of the base include triethylamine, pyridine, di-isopropylamine, 4- diisopropylethylamine, 4-dimethylamine pyridine, lutidine, and the like organic bases.
  • the bases can much excessively be used to be also used as reaction solvents.
  • halogen reagent examples include, but are not particularly limited to, P0C1 3 , POBr 3 , S0C1 2 , S0 2 C1 2 , and oxalyl chloride.
  • Relative to 1 mole of the aniline compound (2) typically 1 to 10 moles of the halogenation reagent and preferably approximately 1 to 5 moles thereof can be used.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction.
  • the aforementioned solvents are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between 10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
  • the sulfide compound (1-la) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfide compound (1-la) can be provided for next reaction without being isolated from the reaction system.
  • the sulfide compound (1-1) can be produced by reacting a sulfide compound (hereinafter may be referred to as "compound (9)”) with an amide compound (hereinafter may be referred to as “compound (10)”) represented by Formula (10) (Reaction Scheme 12) :
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and X are as defined above, and Z represents a leaving group.
  • a used ratio between the sulfide compound (9) and the amide compound (10) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
  • the aforementioned reaction can be performed under absence or presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base.
  • the base any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
  • the aforementioned reaction is performed in an appropriate solvent or without any solvent.
  • any of the same solvents as those shown in the Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
  • Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably between -0°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
  • the sulfide compound (9) used as a starting material can be produced according to methods described in EP3002279 and WO2012/176856.
  • the sulfide compound (1-1) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
  • the sulfide compound (1-1) can be provided for next reaction without being isolated from the reaction system.
  • a benzylamide compound (hereinafter may be referred to as "compound (1-2)") represented by Formula (1-2) can be produced by reacting a sulfide compound represented by Formula (1-1) with an oxidizing agent (Reaction Scheme 13) :
  • a used ratio between the benzylamide compound (1-1) and the oxidizing agent in the reaction therebetweeen is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
  • the aforementioned reaction can be performed under presence of the oxidizing agent.
  • the oxidizing agent any of known oxidizing agents can be used as long as the oxidizing agent can achieve oxidization of sulfide into sulfoxide, and examples of the oxidizing agent include a combination of: performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m- chloroperbenzoic acid (mCPBA) , o-carbonylperbenzoic acid, and the like peracids; hydrogen peroxide, t-butylhydroperoxide, cumene hydroperoxide, and the like alkyl hydroperoxides; and titanium tetraisopropoxide and the like titanium tetraalkoxides ⁇ dichromate, sodium bichromate, patassium bichromate, and the like dichromate salts; and permanganic acid, sodium permanganate, potassium permanganate, and the like permanganates; and the like. Any
  • a stoichiometric amount of the oxidizing agent or an excessive amount thereof over the aforementioned amount can excessively be used.
  • the aforementioned reaction can further be performed by adding a catalyst.
  • the aforementioned reaction is performed in an appropriate solvent.
  • the solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF, N, N-dimethylacetamide, N- methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-
  • Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60°C, and more preferably 20 to 50°C.
  • Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
  • the sulfide compound (1-2) obtained by the method shown in Step 5 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, chromatography, etc.
  • Each compound (1) obtained after the completion of the reactions shown in Reaction Scheme 1 to Reaction Scheme 13 may be easily isolated from the reaction mixture and purified by known isolation and purification techniques, such as filtration, solvent extraction, distillation, recrystallization, and column chromatography.
  • each regioisomer may be separated by a usual separation step, such as silica gel chromatography.
  • Compound (1) of the present invention may be used as an active ingredient of a pest-controlling agent.
  • pest- controlling agents include agents (agricultural and horticultural insecticide, miticides, nematicides, or soil insecticides) for controlling pests, mites, nematode, or soil pests that all cause problems in the agricultural and horticultural fields; animal- ectoparasite-controlling agents (e.g., pulicide, ixodicide, and pedivulicideon) , and the like.
  • compound (1) of the present invention For use as an active ingredient of a pest-controlling agent, it is possible to use compound (1) of the present invention as is with no additional components. However, it is usually preferable to use the compound by combining with a solid carrier, liquid carrier, or gaseous carrier (propellant) , and optionally with a surfactant and other adjuvants for pharmaceutical preparation, and formulating the resulting mixture into various forms such as oil solutions, emulsions, wettable powders, flowable preparations, granules, dusts, aerosols, fumigants, or the like, according to known preparation methods.
  • a solid carrier liquid carrier, or gaseous carrier (propellant)
  • surfactant and other adjuvants for pharmaceutical preparation, and formulating the resulting mixture into various forms such as oil solutions, emulsions, wettable powders, flowable preparations, granules, dusts, aerosols, fumigants, or the like, according to known preparation methods.
  • Compound (1) of the present invention is usually contained in these formulations in a proportion of 0.01 to 95 wt%, and preferably 0.1 to 50 wt%.
  • solid carriers usable in the formulations include solid carriers in a fine powder or granular form, such as clay (e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon dioxide, bentonite, Fubasami clay, and acid clay) , talc, ceramic, other inorganic minerals (e.g., celite, quartz, sulfur, active carbon, calcium carbonate, and hydrated silica) , and chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, and ammonium chloride); and the like.
  • clay e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon dioxide, bentonite, Fubasami clay, and acid clay
  • talc ceramic
  • other inorganic minerals e.g., celite, quartz, sulfur, active carbon, calcium carbonate, and hydrated silica
  • chemical fertilizers e.g., ammonium sulfate, ammonium
  • liquid carriers examples include water, alcohols (e.g., methanol and ethanol) , ketones (e.g., acetone and methylethylketone) , aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene, and methylnaphthalene) , aliphatic hydrocarbons (e.g., hexane, cyclohexane, kerosene, and light oil), esters (e.g., ethyl acetate and butyl acetate), nitriles (e.g., acetonitrile and isobutyronitrile) , ethers (e.g., diisopropyl ether and dioxane) , acid amides (e.g., N, iV-dimethylformamide and N, IV-dimethylacetamide) , halogenated hydrocarbons (e.g.
  • gaseous carriers examples include butane gas, LPG (liquefied petroleum gas) , dimethyl ether, carbon dioxide gas, and the like.
  • surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, alkyl aryl ethers, polyoxyethylene adducts thereof, polyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives, and the like.
  • adjuvants for pharmaceutical preparation include fixing agents, dispersants, stabilizers, and the like.
  • fixing agents and dispersants examples include casein, gelatin, polysaccharides (e.g., starch, gum arabic, cellulose derivatives, and alginic acid) , lignin derivatives, bentonite, sugars, and water-soluble synthetic polymers (e.g., polyvinyl alcohol, polyvinyl pyrrolidone, and polyacrylic acids) .
  • stabilizers examples include PAP (acidic isopropyl phosphate), BHT (2, 6-di- tert-butyl-4-methylphenol) , BHA (mixture of 2- ert-butyl-4-methoxyphenol and 3- ert-butyl-4-methoxyphenol) , vegetable oils, mineral oils, fatty acids, and fatty acid esters, and the like.
  • PAP acidic isopropyl phosphate
  • BHT 2, 6-di- tert-butyl-4-methylphenol
  • BHA mixture of 2- ert-butyl-4-methoxyphenol and 3- ert-butyl-4-methoxyphenol
  • vegetable oils mineral oils, fatty acids, and fatty acid esters, and the like.
  • the pest-controlling agent of the present invention it is preferable to use compound (1) as is, or by diluting it with water or the like.
  • the pest-controlling agent of the present invention may be used by mixing with, for example, other pest- controlling agents, such as known insecticides, nematicides, acaricides, fungicides, herbicides, plant-growth-controlling agents, synergists, soil conditioners, animal feeds, and the like, or it may be used simultaneously with these agents without mixing.
  • the amount of the pest-controlling agent of the invention is not limited, and may be suitably selected from a wide range according to various conditions such as the concentration of active ingredient, the form of preparation, type of disease or pest to be treated, type of plant, severity of disease, time for application, method for application, chemicals to be used in combination (insecticide, nematicide, miticide, fungicide, herbicide, plant growth control agent, synergist, soil conditioner, etc.), and amount and type of fertilizer.
  • compound (1) of the present invention When used as a pesticide, compound (1) of the present invention is usually used in an amount of 0.01 to 500 g/100 m 2 , and preferably 1 to 200 g/100 m 2 .
  • compound (1) of the present invention When used as a miticide, compound (1) of the present invention is usually used in an amount of 0.1 to 500 g/100 m 2 , and preferably 1 to 200 g/100 m 2 .
  • concentration When the emulsion, wettable powder, flowable preparation, or the like is used by diluting with water, the concentration is 0.1 to 1, 000 ppm, and preferably 1 to 500 ppm.
  • the granules, dusts, or the like can be used as is without dilution.
  • Compound (1) of the present invention is characterized by having a particularly excellent miticidal activity and a broad spectrum of activity.
  • Compound (1) of the present invention is effectively used as an agricultural and horticultural insecticide, miticide, nematicide, or a soil insecticide. Specifically, compound (1) of the present invention is effective for controlling
  • pests such as green peach aphids, cotton aphids, and like aphids; diamondback moths, cabbage armyworms, common cutworms, codling moths, bollworms, tobacco budworms, gypsy moths, rice leafrollers, smaller tea tortrix moths, Colorado potato beetles, cucurbit leaf beetles, boll weevils, plant hoppers, leafhoppers, scales, bugs, whiteflies, thrips, grasshoppers, anthomyiid flies, scarabs, black cutworms, cutworms, ants, and agricultural pest insects; slugs, snails, and like gastropods; rat mite, cockroaches, houseflies, house mosquitoes, and like hygiene- harming insects; angoumois grain moths, adzuki bean weevils, red flour beetles, mealworms, and like stored-grain insects; casemaking clothes moths, black
  • mites such as two-spotted spider mites, carmine spider mites, citrus red mites, Kanzawa spider mites, European red mites (fruit tree spider mites) , broad mites, pink citrus rust mites, bulb mites, and like plant-parasitic mites; Tyrophagus putrescentiae, Dermatophagoides farinae, Chelacaropsis moorei, and like house dust mites; and the like, and
  • soil pests such as root-knot nematodes, cyst nematodes, root- lesion nematodes, white-tip nematode, strawberry bud nematode, pine wood nematode, and like plant parasitic nematodes; pill bugs, sow bugs, and like isopods; and the like.
  • the pest-controlling agent of the present invention is also effective for controlling various pests resistant to chemicals such as organophosphorus agents, carbamate agents, synthetic pyrethroid agents, and neonicotinoid agent.
  • the crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 1.0 g of the title compound 6-14 as an off white solid.
  • the reaction mixture was then poured into distilled water and extracted with dichloromethane .
  • the combined organic layer was washed with distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude product.
  • the crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 2.90 g of the title compound as an off white solid.
  • Tables 2 show ⁇ -NMR data of the thus obtained compounds of the present invention.
  • F fluoro
  • CI chloro
  • Br bromo
  • Me methyl
  • Et ethyl
  • n-Pr normal-propyl
  • i-Pr isopropyl
  • n-Bu normal-butyl
  • t-Bu tert- butyl
  • n-Pent normal-pentyl
  • CF 3 trifluoromethyl
  • OMe methoxy
  • OEt ethoxy
  • OCF 3 trifluoromethoxy
  • SCF 3 trifluoromethylthio
  • SMe methylthio
  • N3 ⁇ 4 amino, NO 2 : nitro
  • Ph phenyl
  • S sulfur atom
  • 0 oxygen atom.
  • A-56 CDCI 3 ⁇ 7.39 (s, 1 H), 7.30 (s, 1 H), 7.11 -7.05 (m, 4H), 3.42-3.25 (m, 4H), 3.19 (s, 3H), 2.48 (s, 3H).
  • A-97 CDCI 3 ⁇ 7.45-7.53 (m, 2H), 7.29 (s, 1 H), 7.18-7.06 (m, 3H), 6.90-6.72 (m, 1 H), 5.06-4.84 (m, 1 H), 3.59- 3.37 (m, 1 H), 3.01-2.87 (m, 2H), 2.49 (s, 3H), 2.18-1.90 (m, 2H).
  • A-119 CDCI 3 ⁇ 7.37-7.32 (m, 5H), 7.19-7.12 (m, 2H), 7.09-7.06 (m, 2H), 7.04 (s, 1 H), 3.55-3.44 (m, 2H), 3.30- 3.19 (m, 5H), 2.51 (s, 3H).
  • A-124 CDCI 3 ⁇ 7.43-7.38 (m, 3H), 7.33-7.27 (m, 2H), 7.14-7.06 (m, 5H), 3.52-3.44 (m, 2H), 3.24-3.17 (m, 5H), 2.48 (s, 3H).
  • A-125 CDCI 3 ⁇ 7.40-7.32 (m, 5H), 7.19-7.12 (m, 2H), 7.09-7.04 (m, 3H), 3.55-3.44 (m, 2H), 3.28-3.21 (m, 5H), 2.51 (s, 3H).
  • A-135 CDCI 3 ⁇ 8.05 (s, 1 H), 7.82-7.76 (m, 2H), 7.18-7.16 (m, 1 H), 7.16-7.12 (m, 1 H), 6.94-6.89 (m, 1 H), 3.73- 3.58 (m, 2H), 3.40-3.36 (m, 2H), 3.22 (s, 3H), 3.10-2.98 (m, 3H), 2.47 (s, 3H).
  • each compound of the invention was added to a mixture of 2 parts of sodium lauryl sulfate, 4 parts of sodiumlignin sulfonate, 20 parts of fine powder of synthetic hydrated silicon dioxide, and 54 parts of clay.
  • the mixtures were mixed by stirring with a juice mixer to give 20% wettable powders
  • each compound of the invention was mixed with 20 parts of water containing 3 parts of polyoxyethylene tristyrylphenyl ether phosphoric acid ester triethanolamine and 0.2 parts of Rhodorsil 426R.
  • the mixtures were subjected to wet pulverization with a DYNO-Mill, and mixed with 60 parts of water containing 8 parts of propylene glycol and 0.32 parts of xanthan gum to give 20% suspensions in water.
  • Test Examples are given below to demonstrate that the compounds of the invention are useful as an active ingredient for miticides .
  • Test Example 1 Mitsubishi test on Two-Spotted Spider Mites
  • a piece of non-woven fabric (4.5x5.5cm) was suspended inside a plastic cup through an incision made in the lid of the plastic cup. After water was poured into the cup, the cup was covered with the lid.
  • a kidney bean leaf (about 3.5x4.5 cm) was then placed on the sufficiently soaked, non-woven fabric.
  • Another kidney bean leaf with two-spotted spider mites (about 30 mite samples) was placed on top of the first leaf, and the fabric and leaves were placed in a thermostatic chamber having a temperature of 25 ⁇ 2° C and a humidity of 40%.
  • Miticidal formulations containing the compound of the invention were prepared by adding an aqueous solution (100 ppm) of Sorpol 355 (manufactured by Tobo Kagaku Co. Ltd.) to a methanol solution of the compound of the invention.
  • the compounds that exhibited the mortality rate of 50% or more are as follows:
  • a piece of non-woven fabric (4.5x5.5cm) was suspended inside a plastic cup through an incision made in the lid of the plastic cup. After water was poured into the cup, the cup was covered with the lid. A kidney bean leaf (about 3.5x4.5 cm) was then placed on the sufficiently soaked, non-woven fabric. Twenty female adults of two-spotted spider mite were placed on the top of the leaf, and the fabric and leaf were placed in a thermostatic chamber having a temperature of 25 ⁇ 2° C and a humidity of 40% and 16L8D.

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Abstract

An object of the present invention is to provide a benzylamide compound or a salt thereof that controls a mite. The present invention provides a benzylamide compound represented by Formula (1): or a salt thereof, wherein R1 represents C1-6 alkyl or C1-6 haloalkyl; R2 and R3 are identical or different and each represent hydrogen, halogen, cyano, nitro, C1-6 alkyl, or the like; R4 represents hydrogen, formyl, C1-6 alkyl, or the like; R5 and R6 are identical or different and each represent hydrogen, halogen, or C1-6 alkyl, or the like; R7, R8, R9, R10, and R11 are identical or different and each 5 represent hydrogen, halogen, or the like; X represents oxygen or sulfur; and n represents an integer of 0 to 2.

Description

DESCRIPTION
Title of Invention: NOVEL BENZYLAMIDE COMPOUND, METHOD FOR PRODUCING THE SAME, AND MITICIDE Technical Field
The present invention relates to a novel benzylamide compound, method for producing the same, and miticide containing the compound. Background Art
Due to the emergence of mites resistant to miticides in recent years as a result of long-term use of miticides, it has become difficult to accomplish control by use of known miticides.
Under such circumstances, there has been an urgent demand for the development of new types of miticides that are expected to achieve excellent miticidal activity.
For example, Patent Literature (PTL) 1) discloses a compound represented by following Formula (A) :
R3 R4
/S(0)n(X)m
R1
wherein R5 represents substituted or unsubstituted Ci-20 alkyl, substituted or unsubstituted amino, N-containing heterocycles, or the like, and reports that this compound exhibits miticidal activity.
However, in PTL 1, mainly, urea compounds are produced, and although the amide compounds where R5 is alkyl, haloalkyl, aryl, or cycloalkyl are also produced, no amide compounds where R5 is benzyl is disclosed. In addition, PTL 1 nowhere discloses that the above compound (A) exhibits ovicidal activity.
Citation List
Patent Literature
PTL 1: Japanese Patent Application Laid-open No. 2011-042611 Summary of Invention
Technical Problem
An object of the present invention is to provide a novel benzylamide compound or a salt thereof that exhibits miticidal activity.
Another object of the present invention is to provide a method for producing the benzylamide compound or the salt thereof.
A further object of the present invention is to provide a new type of miticide containing the benzylamide compound or the salt thereof.
Solution to Problem
The present inventors conducted extensive research to achieve the above objects, and succeeded in synthesizing a compound represented by the following Formula (1) or a salt thereof that has miticidal activity. The present inventors have conducted further research based on the above findings . The present invention has thereby been accomplished.
More specifically, the present invention includes the following embodiments:
Item 1:
A benzylamide compound represented by Formula
Figure imgf000003_0001
or a salt thereof,
wherein R1 represents Ci_6 alkyl or Ci-6 haloalkyl;
R2 and R3 are identical or different and each represent hydrogen, halogen, cyano, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl or C3-8 cycloalkyl Ci-6 alkyl;
R4 represents hydrogen, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, arylcarbonyl, aryloxycarbonyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-e haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, aryl, aryl Ci-6 alkyl, arylsulfonyl, arylsulfinyl, arylthio, or heterocyclic, all the substituents defined as R4 may optionally be further substituted; R5 and R6 are identical or different and each represent hydrogen, halogen, Ci-6 alkyl, or Ci-6 haloalkyl; R5 and R6, taken together with the carbon atom, may bond to each other to form a 3- to 8- membered ring, via or not via at least one heteroatom;
R7, R8, R9, R10, and R11 are identical or different and each represent hydrogen, halogen, nitro, cyano, hydroxyl, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, Ci-6 cyanoalkyl, Ci-6 cyanoalkoxy, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-e haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, C3-8 cycloalkylsulfonyl, C3-8 cycloalkylsulfinyl, C3-8 cycloalkylthio, C3-8 cycloalkyl Ci-6 alkylsulfonyl, C3-8 cycloalkyl Ci-6 alkylsulfinyl, C3-8 cycloalkyl Ci-6 alkylthio, Ci-6 alkoxy Ci-6 alkylsulfonyl, Ci-6 alkoxy Ci-6 alkylsulfinyl, Ci-6 alkoxy Ci-6 alkylthio, 2-6 alkenyloxy, 2-6 haloalkenyloxy, C2-6 alkynyloxy, C2-6 haloalkynyloxy, Ci-6 alkylsulfonyloxy, Ci-6 haloalkylsulfonyloxy, Ci-6 alkylsulfinyloxy, Ci-6 haloalkylsulfinyloxy, carboxyl, OCN, SCN, SF5, substituted or unsubstituted amino, aryl, aryl Ci-6 alkyl, aryloxy, aryl Ci-6 alkoxy, arylsulfonyl, arylsulfinyl, arylthio, aryl Ci-6 alkylsulfonyl, aryl Ci-6 alkylsulfiny I , aryl Ci-6 alkylthio, heterocyclic, heterocyclic Ci-6 alkyl, or heterocyclic oxy, all of which may optionally be further substituted;
R7 and R8, R8 and R9, R9 and R10, or R10 and R11, taken together with the benzene ring to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom;
X represents oxygen or sulfur; and
n represents an integer of 0 to 2.
Item 2:
The benzylamide compound or the salt thereof according to Item 1, wherein R1 is Ci_6 haloalkyl.
Item 3:
The benzylamide compound or the salt thereof according to Item 1 or 2, wherein R2 and R3 are identical or different and each represent halogen, cyano, or Ci-6 alkyl.
Item 4:
The benzylamide compound or the salt thereof according to any one of Items 1 to 3, wherein R4 is hydrogen, or Ci-6 alkyl. Item 5:
The benzylamide compound or the salt thereof according to any one of Items 1 to 4, wherein R7, R8, R9, R10, and R11 are identical or different and each represent hydrogen, halogen, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci_6 haloalkylthio, substituted or unsubstituted amino, aryl, or heterocyclic.
Item 6:
A method for producing the benzylamide compound or the salt thereof according to any one of Items 1 to 5, comprising at least one step selected from the group consisting of following steps (d) and (e) :
step (d) : obtaining a sulfide compound represented by Formula (1-1) by reacting a thiol compound represented by Formula (6) with an alkylating reagent represented by Formula (7) :
Figure imgf000006_0001
wherein, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above and G represents a leaving group; and
step (e) : obtaining a benzylamide compound represented by Formula (1-2) by reacting the sulfide compound represented by Formula (1-1) with an oxidizing agent:
Figure imgf000006_0002
(1-1 ) (1-2) wherein, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, n' represents 1 or 2.
Item 7:
The method for producing the benzylamide compound and the salt thereof according to Item 6, further comprising the following step (c) :
step (c) : obtaining a thiol compound represented by Formula (6) by reacting a sulfonylchloride compound represented b Formula (5) with a reducing agent:
Figure imgf000006_0003
defined above.
Item 8:
The method for producing the benzylamide compound and the salt thereof according to Item 7, further comprising the following step (b) : step (b) : obtaining the sulfonylchloride compound represented by Formula (5) by chlorosulfonylating an amide com ound represented by Formula (4) :
Figure imgf000007_0001
wherein, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above.
Item 9:
The method for producing the benzylamide compound and the salt thereof according to Item 8, further comprising the following step (a) :
step (a) : obtaining the amide compound represented by Formula (4) by reacting an aniline compound represented by Formula (2) with a benzylcarbonyl compound represented by Formula (3) :
Figure imgf000007_0002
wherein, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, and Y represents a leaving group or hydroxyl group Item 10:
A pesticide containing the benzylamide compound or the salt thereof of according to any one of Items 1 to 5.
Item 11:
A miticide containing the benzylamide compound or the salt thereof of according to any one of Items 1 to 5. Advantageous Effects of Invention
The benzylamide compound or the salt thereof according to the present invention achieves an excellent miticidal effect with a small amount thereof.
With the present invention, the benzylamide compound and the salt thereof can simply be produced with an excellent yield.
Additionally, with the present invention, a new type of miticide containing the benzylamide compound or the salt thereof according to the present invention can be provided.
Description of Embodiments
1. benzylamide compound or a salt thereof
The present invention is directed to a compound represented by Formula (1) :
Figure imgf000008_0001
or a salt thereof (hereinafter sometimes referred to as "benzylamide compound (1) of the present invention" or "compound (1)") ,
Wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, X and n are as defined above.
The following shows specific examples of each group as used in this specification.
Examples of halogen include, but are not particularly limited to, fluorine, chlorine, bromine, iodine, and the like.
Examples of Ci_6 alkyl include, but are not particularly limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and like Ci_6 straight- chain or branched-chain alkyl.
Examples of Ci_6 haloalkyl include, but are not particularly limited to, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, trifluoromethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 3, 3, 3-trifluoropropyl, 4, 4, 4-trifluorobutyl, heptafluoroisobutyl, and like Ci-6 straight-chain or branched- chain alkyl substituted with 1 to 9, and preferably 1 to 5, halogen atoms .
Examples of Ci_6 alkoxy include, but are not particularly limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and like Ci-6 straight-chain or branched-chain alkoxy.
Examples of Ci-6 haloalkoxy include, but are not particularly limited to, fluoromethoxy, chloromethoxy, bromomethoxy, iodomethoxy, difluoromethoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, pentafluoroethoxy, 3, 3, 3-trifluoropropoxy, 4, 4, 4-trifluorobutoxy, heptafluoroisobutoxy, and like Ci-6 straight-chain or branched-chain alkoxy substituted with 1 to 9, preferably 1 to 5, halogen atoms.
Examples of Ci-6 alkoxy Ci-6 alkyl include, but are not particularly limited to, methoxymethyl, ethoxymethyl, n- propoxymethyl, isopropoxymethyl, n-butoxymethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, methoxyethyl, ethoxyethyl, methoxy-n-propyl, methoxy-n-butyl, and like alkoxyalkyl in which Ci-6 straight-chain or branched-chain alkyl is substituted with Ci_ 6 straight-chain or branched-chain alkoxy.
Examples of Ci-6 haloalkoxy Ci-6 alkyl include, but are not particularly limited to, fluoromethoxymethyl, chloromethoxymethyl, bromomethoxymethyl, iodomethoxymethyl, difluoromethoxymethyl, trifluoromethoxymethyl, 2,2,2- trifluoroethoxymethyl, and like straight-chain or branched-chain alkoxyalkyl substituted with 1 to 9, preferably 1 to 5, halogen atoms .
Examples of C3-8 cycloalkyl include, but are not particularly limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.
Examples of C3-8 cycloalkyl Ci-6 alkyl include, but are not particularly limited to, cyclopropylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, and the like.
Examples of Ci-6 alkylcarbonyl include, but are not particularly limited to, methylcarbonyl (acetyl) , ethylcarbonyl (propionyl) , n-propylcarbonyl (butyryl) , isopropylcarbonyl (isobutyryl) , n-butylcarbonyl (valeryl) , isobutylcarbonyl (isovaleryl) , sec-butylcarbonyl, tert-butylcarbonyl, and like Ci-6 straight-chain or branched-chain alkylcarbonyl groups.
Examples of Ci-6 haloalkylcarbonyl include, but are not particularly limited to, fluoromethylcarbonyl, chloromethylcarbonyl, bromomethylcarbonyl, iodomethylcarbonyl, dichloromethylcarbonyl, trichloromethylcarbonyl, difluoromethylcarbonyl, trifluoromethylcarbonyl, chlorodifluoromethylcarbonyl, bromodifluoromethylcarbonyl, dichlorofluoromethylcarbonyl, 2,2, 2-trichloroethylcarbonyl,
2, 2, 2-trifluoroethylcarbonyl, pentafluoroethylcarbonyl, and like Ci-6 straight-chain or branched-chain alkylcarbonyl substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of arylcarbonyl include, but are not particularly limited to, benzoyl, tert-butylbenzoyl, and like substituted or unsubstituted benzoyl group; 1-naphthoyl, 2- naphthoyl, and the like substituted or unsubstituted naphthoyl group .
Examples of aryloxycarbonyl include, but are not particularly limited to, phenoxycarbonyl, 4- diaminophenoxycarbonyl, 4-fluorophenoxycarbonyl, 4-tert- butylphenoxycarbonyl, and like substituted or unsubstituted phenoxycarbonyl group; 1-naphthoxycarbonyl, 2-naphthoxycarbonyl, and the like substituted or unsubstituted naphthoxycarbonyl group
Examples of Ci_6 alkoxycarbonyl include, but are not particularly limited to, methoxycarbonyl, ethoxycarbonyl, n- propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, and like Ci-6 straight-chain or branched-chain alkoxycarbonyl groups.
Examples of Ci_6 haloalkoxycarbonyl include, but are not particularly limited to, fluoromethoxycarbonyl, chloromethoxycarbonyl , bromomethoxycarbonyl , iodomethoxycarbonyl, dichloromethoxycarbonyl, trichloromethoxycarbonyl, difluoromethoxycarbonyl, trifluoromethoxycarbonyl, 2,2,2- trifluoroethoxymethyl, pentafluoroethoxycarbonyl, 3,3,3- trifluoropropoxycarbonyl, 4,4, 4-trifluorobutoxycarbonyl, heptafluoroisopropoxycarbonyl, and like Ci_6 straight-chain or branched-chain alkoxycarbonyl substituted with 1 to 9, preferably 1 to 5, halogen atoms.
Examples of cyano Ci_6 alkyl include, but are not particularly limited to, cyanomethyl, cyanoethyl, cyano-n-propyl, cyano-isopropyl, cyano-n-butyl, cyano-isobutyl, cyano-sec-butyl, cyano-tert-butyl, cyano-n-hexyl, and like Ci-6 straight-chain or branched-chain alkyl substituted with a cyano group.
Examples of cyano Ci-6 alkoxy include cyanomethoxy, cyanoethoxy, cyano-n-propoxy, cyano-isopropoxy, cyano-n-butoxy, cyano-iso-butoxy, cyano-sec-butoxy, cyano-tert-butoxy, cyano- hexyloxy, and like Ci_6 straight-chain or branched-chain alkoxy substituted with a cyano group.
Examples of C2-6 alkenyl include, but are not particularly limited to, vinyl, allyl, 2-butenyl, 3-butenyl, 1- methylallyl, and the like.
Examples of C2-6 haloalkenyl include, but are not particularly limited to, 2, 2-dichlorovinyl, 2, 2-dibromovinyl, 2, 2-difluorovinyl, 2, 2-dibromovinyl, 3, 3-difluoro-2-allyl, 4,4- difluoro-3-butenyl, 4, 4, 4-trifluoro-2-butenyl, and the like.
Examples of C2-6 alkynyl include, but are not particularly limited to, ethynyl, 2-propynyl (propargyl) , 1- methyl-2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and the like.
Examples of C2-6 haloalkynyl include, but are not particularly limited to, fluoroethynyl, bromoethynyl, chloroethynyl, iodoethynyl, 3, 3, 3-trifluoro-l-propynyl, and the like.
Examples of Ci-6 alkylsulfonyl include, but are not particularly limited to, methylsulfonyl, ethylsulfonyl, n- propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, and like Ci-6 straight-chain or branched-chain alkylsulfonyl groups. Examples of Ci_6 haloalkylsulfonyl include, but are not particularly limited to, fluoromethylsulfonyl, chloromethylsulfonyl, bromomethylsulfonyl, iodomethylsulfonyl, dichloromethylsulfonyl, trichloromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, chlorodifluoromethylsulfonyl, bromodifluoromethylsulfonyl, dichlorofluoromethylsulfonyl, 2,2, 2-trichloroethylsulfonyl,
2, 2, 2-trifluoroethylsulfonyl, pentafluoroethylsulfonyl, and like Ci-6 straight-chain or branched-chain alkylsulfonyl substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of Ci_6 alkylsulfinyl include, but are not particularly limited to, methylsulfinyl, ethylsulfinyl, n- propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, and like Ci-6 straight-chain or branched-chain alkylsulfinyl groups.
Examples of Ci_6 haloalkylsulfinyl include, but are not particularly limited to, fluoromethylsulfinyl, chloromethylsulfinyl, bromomethylsulfinyl, iodomethylsulfinyl, dichloromethylsulfinyl, trichloromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, chlorodifluoromethylsulfinyl, bromodifluoromethylsulfinyl, dichlorofluoromethylsulfinyl, 2,2, 2-trichloroethylsulfinyl,
2, 2, 2-trifluoroethylsulfinyl, pentafluoroethylsulfinyl, and like Ci-6 straight-chain or branched-chain alkylsulfinyl substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of Ci-6 alkylthio include, but are not particularly limited to, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert- butylthio, and like Ci-6 straight-chain or branched-chain alkylthio.
Examples of Ci-6 haloalkylthio include, but are not particularly limited to, fluoromethylthio, chloromethylthio, bromomethylthio, iodomethylthio, dichloromethylthio, trichloromethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, bromodifluoromethylthio, dichlorofluoromethylthio, 2, 2, 2-trichloroethylthio, 2,2,2- trifluoroethylthio, pentafluoroethylthio, and like Ci-6 straight- chain or branched-chain alkylthio substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of C3-8 cycloalkylsulfonyl include, but are not particularly limited to, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl, and the like.
Examples of C3-8 cycloalkylsulfinyl include, but are not particularly limited to, cyclopropylsulfinyl, cyclobutylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl, and the like.
Examples of C3-8 cycloalkylthio include, but are not particularly limited to, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio, and the like.
Examples of C3-8 cycloalkyl Ci-6 alkylsulfonyl include, but are not particularly limited to, cyclopropylmethylsulfonyl, 2-cyclopropylethylsulfonyl, 3-cyclopropylpropylsulfonyl, cyclohexylmethylsulfonyl, and the like.
Examples of C3-8 cycloalkyl Ci-6 alkylsulfinyl include, but are not particularly limited to, cyclopropylmethylsulfinyl, 2-cyclopropylethylsulfinyl, 3-cyclopropylpropylsulfinyl, cyclohexylmethylsulfinyl, and the like.
Examples of C3-8 cycloalkyl Ci-6 alkylthio include, but are not particularly limited to, cyclopropylmethylthio, 2- cyclopropylethylthio, 3-cyclopropylpropylthio, cyclohexylmethylthio, and the like.
Examples of Ci-6 alkoxy Ci-6 alkylsulfonyl include, but are not particularly limited to, methoxymethylsulfonyl, ethoxymethylsulfonyl , n-propoxymethylsulfonyl , isopropoxymethylsulfonyl, n-butoxymethylsulfonyl, sec- butoxymethylsulfonyl, tert-butoxymethylsulfonyl, methoxyethylsulfonyl, and like alkoxyalkylsulfonyl in which Ci-6 straight-chain or branched-chain alkylsulfonyl is substituted with Ci-6 straight-chain or branched-chain alkoxy.
Examples of Ci-6 alkoxy Ci-6 alkyl sulfinyl include, but are not particularly limited to, methoxymethylsulfinyl, ethoxymethylsulfinyl, n-propoxymethylsulfinyl, isopropoxymethylsulfinyl, n-butoxymethylsulfinyl, sec- butoxymethylsulfinyl, tert-butoxymethylsulfinyl, 2- methoxyethylsulfinyl, and like alkoxyalkylsulfinyl in which Ci-6 straight-chain or branched-chain alkylsulfinyl is substituted with Ci-6 straight-chain or branched-chain alkoxy.
Examples of Ci_6 alkoxy Ci_6 alkylthio include, but are not particularly limited to, methoxymethylthio, ethoxymethylthio, n-propoxymethylthio, isopropoxymethylthio, n-butoxymethylthio, sec-butoxymethylthio, tert-butoxymethylthio, 2-methoxyethylthio, and like alkoxyalkylthio in which Ci-6 straight-chain or branched- chain alkylthio is substituted with Ci-6 straight-chain or branched-chain alkoxy.
Examples of C2-6 alkenyloxy include, but are not particularly limited to, vinyloxy, 1-propenyloxy, isopropenyloxy, allyloxy, 2-butenyloxy, 3-butenyloxy, 1-methylallyloxy, and the like .
Examples of C2-6 haloalkenyloxy include, but are not particularly limited to, 2, 2-dichlorovinyloxy, 2,2- dibromovinyloxy, 2, 2-difluorovinyloxy, 2, 2-dibromovinyloxy, 3,3- difluoro-2-allyloxy, 4, 4-difluoro-3-butenyloxy, 4,4, 4-trifluoro- 2-butenyloxy, and the like.
Examples of C2-6 alkynyloxy include, but are not particularly limited to, ethynyloxy, 2-propynyloxy, l-methyl-2- propynyloxy, 1, l-dimethyl-2-propynyloxy, 1-butynyloxy, 2- butynyloxy, 3-butynyloxy, and the like.
Examples of C2-6 haloalkynyloxy include, but are not particularly limited to, fluoroethynyloxy, bromoethynyloxy, chloroethynyloxy, iodoethynyloxy, 3, 3, 3-trifluoro-l-propynyloxy, and the like.
Examples of Ci-6 alkylsulfonyloxy include, but are not particularly limited to, methylsulfonyloxy, ethylsulfonyloxy, n- propylsulfonyloxy, isopropylsulfonyloxy, n-butylsulfonyloxy, isobutylsulfonyloxy, sec-butylsulfonyloxy, tert-butylsulfonyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfonyl groups .
Examples of Ci_6 haloalkylsulfonyloxy include, but are not particularly limited to, fluoromethylsulfonyloxy, chloromethylsulfonyloxy, bromomethylsulfonyloxy, iodomethylsulfonyloxy, dichloromethylsulfonyloxy, trichloromethylsulfonyloxy, difluoromethylsulfonyloxy, trifluoromethylsulfonyloxy, chlorodifluoromethylsulfonyloxy, bromodifluoromethylsulfonyloxy, dichlorofluoromethylsulfonyloxy, 2,2, 2-trichloroethylsulfonyloxy, 2,2, 2-trifluoroethylsulfonyloxy, pentafluoroethylsulfonyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfonyloxy substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of Ci-6 alkylsulfinyloxy include, but are not particularly limited to, methylsulfinyloxy, ethylsulfinyloxy, n- propylsulfinyloxy, isopropylsulfinyloxy, n-butylsulfinyloxy, isobutylsulfinyloxy, sec-butylsulfinyloxy, tert-butylsulfinyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfinyloxy groups .
Examples of Ci_6 haloalkylsulfinyloxy include, but are not particularly limited to, fluoromethylsulfinyloxy, chloromethylsulfinyloxy, bromomethylsulfinyloxy, iodomethylsulfinyloxy, dichloromethylsulfinyoxy, trichloromethylsulfinyloxy, difluoromethylsulfinyloxy, trifluoromethylsulfinyloxy, chlorodifluoromethylsulfinyloxy, bromodifluoromethylsulfinyloxy, dichlorofluoromethylsulfinyloxy, 2,2, 2-trichloroethylsulfinyloxy, 2,2, 2-trifluoroethylsulfinyloxy, pentafluoroethylsulfinyloxy, and like Ci_6 straight-chain or branched-chain alkylsulfinyloxy substituted with 1 to 9, and preferably 1 to 5, halogen atoms.
Examples of substituted or unsubstituted amino include, but are not particularly limited to, amino, monoalkylamino, dialkylamino, monoacylamino, and the like. Examples of the alkyl include Ci_6 alkyl mentioned above, and the like. Examples of the acyl include Ci-6 alkoxycarbonyl, haloalkoxycarbonyl, arylcarbonyl mentioned above, and the like.
Examples of aryl include, but are not particularly limited to, phenyl, 1-naphthyl, 2-naphthyl, and the like.
Examples of aryl Ci-6 alkyl include, but are not particularly limited to, benzyl, phenylethyl, phenyl-n-propyl, and the like.
Examples of aryloxy include, but are not particularly limited to, phenoxy, 1-naphthyloxy, 2-naphthyloxy, and the like.
Examples of aryl Ci-6 alkoxy include, but are not particularly limited to, benzyloxy, phenoxyethoxy, phenoxy-n- propoxy, phenyl-n-butoxy, 1-naphthylmethoxy, 2-naphthylmethoxy, and like.
Examples of arylsulfonyl include, but are not particularly limited to, phenylsulfonyl, 1-naphthylsulfonyl, 2- naphthylsulfonyl, and the like.
Examples of arylsulfinyl include, but are not particularly limited to, phenylsulfinyl, 1-naphthylsulfinyl, 2- naphthylsulfinyl, and the like.
Examples of arylthio include, but are not particularly limited to, phenylthio, 1-naphthylthio, 2-naphthylthio, and the like .
Examples of aryl Ci-6 alkylsulfonyl include, but are not particularly limited to, benzylsulfonyl, phenylethylsulfonyl, phenyl-n-propylsulfonyl, phenyl-n-butylsulfonyl, 1- naphthylmethylsulfonyl, 2-naphthylmethylsulfonyl, and the like.
Examples of aryl Ci-6 alkylsulfinyl include, but are not particularly limited to, benzylsulfinyl, phenylethylsulfinyl, phenyl-n-propylsulfinyl, phenyl-n-butylsulfinyl, 1- naphthylmethylsulfinyl, 2-naphthylmethylsulfinyl, and the like.
Examples of aryl Ci-6 alkylthio include, but are not particularly limited to, benzylthio, phenylethylthio, phenyl-n- propylthio, phenyl-n-butylthio, 1-naphthylmethylthio, 2- naphthylmethylthio, and the like.
All the Aryls mentioned above may optionally be further substituted. Examples of the number of substituents include, but are not particularly limited to, 1 to 20 (preferably 1 to 10, and more preferably 1 to 5) .
Examples of a heterocyclic group include, but are not particularly limited to, thienyl, furyl, tetrahydrofuryl, dioxolanyl, dioxanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, oxazolyl, isoxazolyl, oxazolinyl, oxazolidinyl, isoxazolinyl, thiazolyl, isothiazolyl, thiazolinyl, thiazolidinyl, isothiazolinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxadiazolyl, oxadiazolinyl, thiadiazolinyl, triazolyl, triazolinyl, triazolidinyl, tetrazolyl, tetrazolinyl, pyridyl, dihydropyridyl, tetrahydropyridyl, piperidyl, oxazinyl, dihydroxazinyl, morpholino, thiazinyl, dihydrothiazinyl, thiamorpholino, pyridazinyl, dihydropyridazinyl, tetrahydropyridazinyl, hexahydropyridazinyl, oxadiazinyl, dihydrooxadiazinyl, tetrahydrooxadiazinyl, thiadiazolyl, thiadiazinyl, dihydrothiadiazinyl, tetrahydrothiadiazinyl, pyrimidinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, hexahydropyrimidinyl, pyrazinyl, dihydropyrazinyl, tetrahydropyrazinyl, piperazinyl, triazinyl, dihydrotriazinyl, tetrahydrotriazinyl, hexahydrotriazinyl, tetrazinyl, dihydrotetrazinyl, indolyl, indolinyl, isoindolyl, indazolyl, quinazolinyl, dihydroquinazolyl, tetrahydroquinazolyl, carbazolyl, benzoxazolyl, benzoxazolinyl, benzisoxazolyl, benzisoxazolinyl, benzothiazolyl, benzisothiazolyl, benzisothiazolinyl, benzimidazolyl, indazolinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, pyridoindolyl, dihydrobenzoxazinyl, cinnolinyl, dihydrocinnolinyl, tetrahydrocinnolinyl, phthalazinyl, dihydrophthalazinyl, tetrahydrophthalazinyl, quinoxalinyl, dihydroquinoxalinyl, tetrahydroquinoxalinyl, purinyl, dihydrobenzotriazinyl, dihydrobenzotetrazinyl, phenothiazinylfuranyl, benzofuranyl, chromanyl, benzothienyl, and the like.
These heterocyclic groups include those substituted at any substitutable position with an oxo or thioketone group. Examples of heterocyclic Ci_6 alkyl include, but are not particularly limited to, 2-pyridylmethyl, 3-pyridylmethyl, 2- pyrazinylmethyl, pyrimidinylmethyl, 2-quinolinylmethyl, and the like .
Examples of heterocyclicoxy include, but are not particularly limited to, 2-pyridyloxy, 3-pyridyloxy, 2- pyrazinyloxy, pyrimidinyloxy, 2-quinolinylmethyloxy, and the like
All the heterocyclics mentioned above may optionally be further substituted. Examples of the number of substituents include, but are not particularly limited to, 1 to 20 (preferably 1 to 10, and more preferably 1 to 5) .
R5 and R6, taken together with the carbon atom to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom.
Examples of hetero atom in the specification include, but are not particularly limited to, an oxygen atom, a sulfur atom, a nitrogen atom, and the like. Examples of 3- to 8-membered ring include: but are not particularly limited to, cyclopropane, cycloheptane, and the like C3-8 cycloalkyl; tetrahydropyran, piperidine, and the like heterocyclic.
R7 and R8, R8 and R9, R9 and R10, or R10 and R11, taken together with the benzene ring to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom. Examples of the 3- to 8-membered ring include: C3-8 cycloalkyl, aryl, heterocyclic, and the like. The C3-8 cycloalkyl, the aryl, and the heterocyclic are as defined above .
Examples of "substituents" for the above substituted groups include: but are not particularly limited to, the halogen, nitro, cyano, hydroxyl, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, Ci-6 cyanoalkyl, Ci-6 cyanoalkoxy, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, C3-8 cycloalkylsulfonyl, C3-8 cycloalkylsulfinyl, C3-8 cycloalkylthio, C3-8 cycloalkyl Ci-6 alkylsulfonyl, C3-8 cycloalkyl Ci-6 alkylsulfinyl, C3-8 cycloalkyl Ci-6 alkylthio, Ci-6 alkoxy Ci-6 alkylsulfonyl, Ci-6 alkoxy Ci-6 alkylsulfinyl, Ci-6 alkoxy Ci-6 alkylthio, C2-6 alkenyloxy, C2-6 haloalkenyloxy, C2-6 alkynyloxy, C2-6 haloalkynyloxy, Ci-6 alkylsulfonyloxy, Ci-6 haloalkylsulfonyloxy, Ci-6 alkylsulfinyloxy, Ci-6 haloalkylsulfinyloxy, carboxyl, OCN, SCN, SF5, substituted or unsubstituted amino, aryl, aryl Ci-6 alkyl, aryloxy, aryl Ci-6 alkoxy, arylsulfonyl, arylsulfinyl, arylthio, aryl Ci-6 alkylsulfonyl, aryl Ci-6 alkylsulfiny I , aryl Ci-6 alkylthio, heterocyclic, heterocyclic Ci-6 alkyl, heterocyclic oxy, and the like. Of these, preferable substituents are halogen, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, substituted or unsubstituted amino, aryl, and heterocyclic , and more preferable substituents are fluorine, chlorine, nitro, methyl, ethyl, trifluoromethyl, methoxy, and trifluoromethoxy.
Preferable substituted aryl groups are halogen- substituted aryl, Ci-6 alkyl-substituted aryl, Ci-6 haloalkyl- substituted aryl, halogen and Ci-6 haloalkyl—substituted aryl, Ci-6 alkoxy-substituted aryl, Ci-6 haloalkoxy-substituted aryl, and Ci-6 alkylthio-substituted aryl. More preferable substituted aryl groups are chlorine-substituted aryl, fluorine-substituted aryl, trifluoromethyl-substituted aryl, chlorine- and trifluoromethyl- substituted aryl, trifluoromethoxy-substituted aryl, and methoxy- substituted aryl, and methylthio-substituted aryl.
Preferable substituted heterocyclic groups are halogen- substituted heterocyclic, Ci-6 alkyl-substituted heterocyclic, Ci-6 haloalkyl-substituted heterocyclic, Ci-6 alkoxy-substituted heterocyclic, Ci-6 haloalkoxy-substituted heterocyclic, and Ci-6 alkylthio-substituted heterocyclic. More preferable substituted heterocyclic groups are chlorine-substituted heterocyclic, fluorine-substituted heterocyclic, trifluoromethyl-substituted heterocyclic, trifluoromethoxy-substituted heterocyclic, methoxy- substituted heterocyclic, and methylthio-substituted heterocyclic.
The salts of the compounds represented by Formula (1) may be any type of salts as long as they are agriculturally acceptable. Examples of the salts include a hydrochloride salt, a sulfate salt, a nitrate salt, and like inorganic acid salts; an acetate salt, a methanesulfonic acid salt, and like organic acid salts; a sodium salt, a potassium salt, and like alkali metal salts; a magnesium salt, a calcium salt, and like alkaline earth metal salts; dimethylammonium, triethylammonium, and like quaternary ammonium salts; and the like.
X represents oxygen or sulfur.
Symbol n represents an integer of 0 to 2.
Among compounds (1) of the present invention, a preferable compound is a compound in which R1 is Ci-6 haloalkyl, and a more preferable compound (1) is a compound in which R1 is trifluoromethyl or trifluoroethyl .
Among compounds (1) of the present invention, a preferable compound is a compound in which R2 is hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R2 is fluorine, chlorine, bromine, or methyl.
Among compounds (1) of the present invention, a preferable compound is a compound in which R3 is hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R3 is fluorine, chlorine, bromine, methyl or trifluoromethyl .
Among compounds (1) of the present invention, a preferable compound is a compound in which R4 is hydrogen, Ci-6 alkyl, C2-e alkenyl, C2-6 alkynyl, or Ci-6 haloalkyl, and a more preferable compound (1) is a compound in which R4 is hydrogen, methyl, ethyl, n-propyl, n-butyl, 3, 3, 3-trifluoro-n-propyl, heptafluoroisopropyl, or propargyl .
Among compounds (1) of the present invention, a preferable compound is a compound in which R5 and R6 are identical or different and each represent hydrogen, halogen, or Ci-6 alkyl, and a more preferable compound (1) is a compound in which R5 and R6 are hydrogen, fluorine, methyl, isopropyl, or tert-butyl .
Among compounds (1) of the present invention, a preferable compound is a compound in which R7, R8, R9, R10, and R11 are hydrogen, halogen, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, substituted or unsubstituted amino, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic, and a more preferable compound (1) is a compound in which R7, R8, R9, R10, and R11 are hydrogen, fluorine, chlorine, bromine, nitro, methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl, trifluoromethyl, methoxy, ethoxy, n-propoxy, trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio, methylsulfonyl, methylthio, NH2, phenyl, 2-chlorophenyl, 4-chlorophenyl, 3,4- dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3, 5-difluorophenyl, 2-chloro-4-fluorophenyl, 2- trifluoromethylphenyl, 3-trifluoromethylphenyl, 4- trifluoromethylphenyl, 3-chloro-5-trifluoromethylphenyl, 4- chloro-3-trifluoromethylphenyl, 2-trifluoromethoxylphenyl, 3- trifluoromethoxylphenyl, 4-trifluoromethoxylphenyl, 4- methoxylphenyl, 2-methylthiophenyl, 5-trifluoromethyl-2-pyridyl, or 5-pyrimidyl .
When the compound (1) has isomers such as optical isomers, stereoisomers, regioisomers, and the like,
any of the isomers and mixtures thereof are included within the scope of the compound (1) . For example, when the compound (1) has optical isomers, the optical isomer separated from a racemic body is also included within the scope of the compound (1) . Each of such isomers may be obtained as a single compound by known synthesis and separation means (e.g., concentration, solvent extraction, column chromatography, recrystallization, etc.). 2. Method for producing a benzylamide compound and a salt thereof No limitations are placed on the method for producing a benzylamide compound (1) (compound (1-1) and compound (1-2) ) according to the present invention, and the benzylamide compound (1) can be produced by Steps 1 to 5 represented by Reaction Scheme 1 below:
[Reaction Scheme 1]
Figure imgf000022_0001
defined above.
Step 1
An amide compound (hereinafter may be referred to as "compound (4)") represented by Formula (4) can be produced by reacting an aniline compound (hereinafter may be referred to as "compound (2)") represented by Formula (2)) with a benzylcarbonyl compound (hereinafter may be referred to as "compound (3)") represented by Formula (3) (Reaction Scheme 2) :
[Reaction Scheme 2]
Figure imgf000023_0001
above .
Y represents a leaving group or a hydroxyl group, and examples of the leaving group include: halogen such as chlorine, bromine, and iodine; substituted or unsubstituted Ci-6 alkyl sulfonate; and substituted or unsubstituted aryl sulfonate. Examples of the substituent include the aforementioned substituents such as the halogen and the Ci_6 haloalkyl.
Step 1A (when Y is a leaving group)
A phenylacetamide compound (hereinafter may be referred to as "compound (4)") represented by Formula (4) can be produced by reacting the aniline compound (hereinafter may be referred to as "compound (2) ) represented by Formula (2) ) with a benzylcarbonyl compound (hereinafter may be referred to as "compound (3A) represented by Formula (3A) (Reaction Scheme 3) : [Reaction Scheme 3]
Figure imgf000023_0002
(2) (3A) (4)
wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above. Y' represents a leaving group.
Examples of the benzylcarbonyl compound (3A) include, but are not particularly limited to, phenylacetyl chloride, phenylacetyl bromide, and the like substituted or unsubstituted phenylacetyl halide; and ethyl phenylacetate, methyl phenylacetate, and the like substituted or unsubstituted phenylacetic acid esters.
A used ratio of the aniline compound (2) and the benzylcarbonyl compound (3A) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the aniline compound (2), typically approximately 1 to 5 moles of the benzylcarbonyl compound (3A) and preferably approximately equimolar to 1.2 moles thereof is used.
The aforementioned reaction can be performed under absence or presence of a base. Among the above, the reaction is performed preferably under the presence of the base. As the base, a conventionally known base can widely be used, and examples of the base include: sodium carbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, and the like alkali metal carbonates; sodium hydroxide, potassium hydroxide, and the like alkali metal hydroxides; alkali metal hydrides such as sodium hydride and potassium hydride, and the like inorganic bases; sodium methoxide, sodium ethoxide, potassium tert-butoxide, and the like alkali metal alkoxides; pyridine, triethylamine, diethylamin, dimethylamine, methylamine, imidazole, benzimidazole, diisopropylethylamine, 4-dimethylamine pyridine, piperidine, and the like organic bases; and the like. Any separate one of these bases or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (2), typically approximately 1 to 10 moles of the base and preferably approximately 1 to 5 moles thereof may excessively be used. When triethylamine, pyridine, or like an organic base is used, it can be used in large excess to serve also as a reaction solvent.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction. Examples of such a solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1,2- dichloroethane, chloroform, and carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, tetrahydrofuran (THF) , 1,4-dioxane, and the like ether-based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; N, N-dimethylformamide (DMF) and the like amide-based solvents; and dimethyl sulfoxide and the like sulfoxide-based solvents. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -10°C and a boiling point of the solvent used and preferably 0 to 25°C. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.5 to 24 hours.
Step IB (when Y is a hydroxyl group)
As another method for obtaining the phenylacetamide compound (4), the compound (4) can be produced by reacting the aniline compound (2) with a phenylacetic acid compound
(hereinafter may be referred to as "compound (3B)") represented by Formula (3B) (Reaction Scheme 4) :
[Reaction Scheme 4]
Figure imgf000025_0001
defined above.
A used ratio of the aniline compound (2) and the phenylacetic acid compound (3B) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the aniline compound (2), typically approximately 1 to 5 moles of the phenylacetic acid compound (3B) and preferably approximately equimolar to 1.2 moles thereof is used.
The aforementioned reaction can be performed under absence or presence of a condensing agent. Among the above, the aforementioned reaction is preferably performed under the presence of the condensing agent. As the condensing agent, a conventionally known condensing agent can be used, and examples of the condensing agent include l-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDCI HC1) , 1-hydroxybenzotriazole (HOBT) , 1- [bis (dimethylamino) methylene] -lH-1, 2, 3-triazolo [4, 5-b] pyridinium-3-oxide hexafluorophosphate (HATU) , bis (2-oxo-3- oxazolidinyl) phosphine acid chloride (BOP-C1) , propylphosphonic acid anhydride (T3P) , and the like. Any separate one of these condensing agents or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (2), typically 1 to 10 moles of the condensing agent and preferably approximately 1 to 3 moles thereof can excessively be used.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction. Examples of such a solvent include: fatty n-hexane, cyclohexane, n-heptane, and the like acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1,2- dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, and 1,4-dioxane, and the like ether-based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF and the like amide solvents; and dimethyl sulfoxide and the like sulfoxide-based solvents. Any one of these solvents can be used alone or a combination of two or more types of the solvents can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
Step 1C
Note that as a method for producing the phenylacetamide compound (4) , a phenylacetic acid halide compound (3C) obtained by reacting the phenylacetic acid compound (3B) with a halogenation reagent can be used as a raw material.
The aforementioned reaction can be performed under presence of a base. As the base, any of the same bases as those described above can be used, and preferable examples of the base include triethylamine, pyridine, di-isopropylamine, 4- diisopropylethylamine, 4-dimethylamine pyridine, lutidine, and the like organic bases, and this base can also much excessively be used to be also used as a reaction solvent.
Examples of the halogenation reagent includes, but are not particularly limited to, P0C13, POBr3, S0C12, S02C12, oxalyl chloride .
Relative to 1 mole of the aniline compound (2), typically 1 to 10 moles of the halogenation reagent and preferably approximately 1 to 5 moles thereof can be used.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction. As such a solvent, the aforementioned solvents are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
The aniline compound (2), the benzylcarbonyl compound (3A) , the phenylacetic acid compound (3B) , and phenylacetic acid halide compound (3C) in Step 1 used as starting materials in Step 1 are known compounds or compounds that can easily be produced by a known method.
The compound (4) obtained by the method shown in Step 1 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the compound (4) can be provided for next reaction without being isolated from the reaction system.
Step 2
A sulfonyl chloride compound (hereinafter may be referred to as "compound (5)") represented by Formula (5) can be produced by chlorosulfonating the amide compound (4) (Reaction Scheme 5) :
Reaction Scheme 5]
Figure imgf000028_0001
wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above.
A reagent used for the chlorosulfonation is not particularly limited, and for example, include chlorosulfonic acid, and the like. When using chlorosulfonic acid, the step can be carried out in one step. For the chlorosulfonation, a two-step method including sulfonation and then chlorination can be used. The sulfonyl chloride compound (5) can be produced by reacting the amide compound with a sulfonation reagent to produce an HOSO2- substituted amide compound and then reacting the HOS02-containing amide compound with a chlorination agent.
The reagent used for the sulfation is not particularly limited, and for example, chlorosulfonic acid, sulfuric acid are provided. Examples of the chlorinating agent used for the chlorination include, but are not particularly limited to, chlorine, P0C13, S0C12, S02C12, and oxalyl chloride.
When the chlorosulfonic acid is used, a used ratio between the amide compound (4) and the chlorosulfonic acid in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the amide compound (4) , typically approximately 1 to 50 moles of chlorosulfonic acid and preferably approximately 1 to 20 moles thereof is used.
When the sulfonation reagent and the chlorinating agent are used, a used ratio between the sulfonation reagent and the chlorinating agent in the reaction between the amide compound (4) and the sulfonation reagent is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the amide compound (4) , typically approximately 1 to 50 moles of the sulfonation reagent and preferably approximately 1 to 20 moles thereof is used. A used ratio between the two in the reaction between the amide compound (4) and the chlorinating agent is not particularly limited, and can appropriately be selected from a wide range. Relative to 1 mol of the amide compound (1) , typically approximately 1 to 50 moles of the sulfuric acid and preferably 1 to 20 moles thereof is used.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction. As examples of such a solvent, the same solvents as those described above are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 150°C, and more preferably 0 to 100°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
The sulfonyl chloride compound (5) obtained by the method shown in Step 2 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfonyl chloride compound (5) can be provided for next reaction without being isolated from the reaction system.
Step 3
A thiol compound (hereinafter may be referred to as "compound (6)") represented by Formula (6) can be produced by reacting the sulfonyl chloride compound (5) with a reducing agent (Reaction Scheme 6) :
Reaction Scheme 6]
Figure imgf000030_0001
defined above.
A used ratio between the sulfonyl chloride compound (5) and the reducing agent in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the sulfonyl chloride compound (5) , typically approximately 1 to 50 moles of the reducing agent and more preferably approximately 1 to 20 moles thereof is used.
As the reducing agent, any of conventionally known reducing agents can widely be used, and examples of the reducing agent include: triphenylphosphine and the like phosphorous compounds; reducing agents containing metal and acid such as zinc and acid, tin (II) and acid, and iron and acid; and reducing agentred phosphorus, iodine, dichlorodimethylsilane-zinc- dimethylacetamide, lithium aluminum hydride, and the like specific reducing agents. Examples of the acid include acetic acid and the like organic acids; and hydrochloric acid, sulfuric acid, and the like inorganic acids.
The aforementioned reaction is performed in an appropriate solvent. No limitations are placed on the solvent as long as the solvent is inactive with respect to the reaction. As examples of such a solvent, the same solvents as those described above are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 150°C, and more preferably 20 to 120°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
The thiol compound (6) obtained by the method shown in Step 3 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the thiol compound (6) can be provided for next reaction without being isolated from the reaction system.
Method for producing a sulfide compound represented by Formula (1-1) or a salt thereof
Examples of the method for producing the sulfide compound represented by Formula (1-1) include, but are not limited to, a production route 1, a production route 2, a production route 3, a production route 4, described below, and the like.
Production route 1 (Step 4)
A sulfide compound (1-1) can be produced by reacting the thiol compound (6) with an alkyl reagent (hereinafter may be referred to as "alkyl reagent (7) ) represented by Formula (7) (Reaction Scheme 7) :
[Reaction Scheme 7
Figure imgf000032_0001
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, and G represents a leaving group.
As examples of the leaving group, the same leaving groups as those described above are listed.
A used ratio between the thiol compound (6) and the alkyl reagent (7) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the thiol compound (6), typically approximately 1 to 10 moles of the alkyl reagent (7) and preferably approximately 1 to 5 moles thereof is used.
Examples of the alkyl reagent (7) include, but are not particularly limited to, methyl iodide, ethyl bromide, and the like Ci_6 alkyl halides; trifluoromethyl iodide, trifluoromethyl bromide, trifluoroethyl iodide, trifluoroethyl bromide, and the like Ci-6 haloaklyl halides; and the like.
The aforementioned reaction can be performed under presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base. As examples of the base, conventionally known bases can widely be used, and any of the same bases as those described above can be used.
Relative to 1 mole of the thiol compound (6), typically
1 to 10 moles of the base and preferably approximately 1 to 3 moles thereof can be used. When triethylamine, pyridine, or like an organic base is used, it can be used in large excess to serve also as a reaction solvent.
The aforementioned reaction can be performed by further adding a radical starting agent. Examples of the radical starting agent include, but are not particularly limited to, sulfurous acid, a sulfurous acid salt, Rongalit (product name, sodium- formaldehyde-sulfoxylate) , and the like sulfurous acid adducts .
The base and the radical starting agent can be used in combination.
When the radical starting agent is used, as an additive amount thereof, relative to 1 mole of the thiol compound (6), typically 0.1 to 10 moles of the radical starting agent and preferably approximately 0.1 to 5 moles thereof can be used.
The aforementioned reaction is performed in an appropriate solvent. Examples of the solvent include: n-hexane, cyclohexane n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like ester-based solvents; acetonitrile; DMF, N, N-dimethylacetamide, N-methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-based solvents such as sulfolane, methanol, ethanol, isopropyl alcohol, and the like aprotic polar solvents; water; and the like. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60 °C, and more preferably 0 to 50 °C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
The sulfide compound (1-1) obtained by the method shown in Step 4 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfide compound (1-1) can be provided for next reaction without being isolated from the reaction system.
Production Route 2
A sulfide compound (hereinafter may be referred to as "compound (1-lb)") represented by Formula (1-lb) can be produced by reacting a sulfide compound (hereinafter may be referred to as "compound (1-la)") represented by Formula (1-la) with a compound (hereinafter may be referred to as "compound (7') represented by Formula (7' ) : R4'-G (Reaction Scheme 8) :
[Reaction Scheme 8]
Figure imgf000034_0001
wherein R1, R2, R3, R5, R6, R7, R8, R9, R10, R11 and X are as defined above, and R4' represents formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkyl carbonyl, Ci-6 haloalkyl carbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, arylcarbonyl, aryloxy carbonyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-e haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, aryl, aryl Ci-6 alkyl, arylsulfonyl, arylsulfinyl, arylthio, and heterocyclic, and these groups may optionally be further substituted. G represents a leaving group.
As examples of the leaving group, the leaving groups as those described above are listed.
A used ratio between the sulfide compound (1-la) and the compound (7' ) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
The aforementioned reaction can be performed under presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base. As the base, conventionally known bases can be used and any of the same bases as those described above can be used.
Relative to 1 mole of the sulfide compound (1-la) , a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can be used. Preferably one to ten times of the base and more preferably one to five times thereof may excessively be used. When triethylamine, pyridine, or like an organic base is used, it can be used in large excess to serve also as a reaction solvent.
The aforementioned reaction is performed in an appropriate solvent. Examples of the solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF, N, N-dimethylacetamide, N- methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-based solvents such as sulfolane, methanol, ethanol, and isopropyl alcohol and the like aprotic polar solvents; and water. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60°C, and more preferably 20 to 50°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.25 to 24 hours.
The sulfide compound (1-lb) obtained by the method shown in Step 4 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfide compound (1-lb) can be provided for next reaction without being isolated from the reaction system.
The sulfide compound (1-1) can be produced in accordance with not only what have been mentioned above but also production routes 3, 4, and 5.
Production Route 3
The sulfide compound (1-la) can be produced by reacting an aniline compound (hereinafter may be referred to as "compound (8)") with a phenylacetic acid compound (3) (Reaction Scheme 9) : [Reaction Scheme 9]
Figure imgf000037_0001
(8) (3) (1-1 a)
wherein R1, R2, R3, R5, R6, R7, R8, R9, R10, R11, X, and Y are as defined above. Production Route 3A (when Y is a leaving group)
The sulfide compound (1-la) can be produced by reacting the aniline compound (2) with a benzylcarbonyl compound (3A) (Reaction Scheme 10) :
[Reaction Scheme 10]
Figure imgf000037_0002
(8) (3A) (1-1 a)
wherein R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, and Y' represents a leaving group.
Examples of the benzylcarbonyl compound (3A) include, but are not particularly limited to, the same compounds as those of Step 1A.
The aniline compound (8) used as a starting material can be produced according to methods described in WO2007/131680.
A used ratio between the aniline compound (8) and the benzylcarbonyl compound (3A) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the former, typically aproximately 1 to 5 moles of the latter and preferably approximately equimolar to 1.2 moles thereof is used.
The aforementioned reaction can be performed under absence or presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base. As examples of the base, any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (8) , a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can excessively be used.
Preferably one to five times of the base may excessively be used. When triethylamine, pyridine, or like an organic base is used, it can be used in large excess to serve also as a reaction solvent.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, any of the same solvents as those shown in Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used and preferably 0 to 50°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
The aniline compound (8) used as a starting material is a known compound or a compound that can easily be produced by a known method.
The sulfide compound (1-la) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfide compound (1-la) can be provided for next reaction without being isolated from the reaction system. Step 3B (when Y is a hydroxyl group) As another method for obtaining the phenylacetamide compound (1-la) , the compound (1-la) can be produced by reacting the aniline compound (8) with a phenylacetic acid compound (3B) (Reaction Scheme 11) :
[Reaction Scheme 11
Figure imgf000039_0001
wherein R1, R2, R3, R5, R6, R7, R8, R9, R10, R11, and X are as defined above.
A used ratio between the aniline compound (8) and the phenylacetic acid compound (3B) in the reaction therebetween is not particularly limited and thus can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 5 moles of the latter and preferably equimolar to 1.2 moles thereof is used.
The aforementioned reaction can be performed under absence or presence of a condensing agent. Among the above, the aforementioned reaction is preferably performed under the presence of the condensing agent. As examples of the condensing agent, the same condensing agents as those shown in Step IB are listed. Any separate one of these condensing agents or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (8) , a stoichiometric amount of the condensing agent or an excessive amount thereof over the aforementioned amount can be used. Preferably approximately one to five times of the condensing agent may excessively be used.
The aforementioned reaction can be performed under absence or presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base. As the base, any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (8) , a stoichiometric amount of the base or an excessive amount thereof over the aforementioned amount can be used. Preferably approximately 1 to 5 times of the base can excessively be used. When triethylamine, pyridine, or like an organic base is used, it can be used in large excess to serve also as a reaction solvent.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, any of the same solvents as those shown in Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -20°C and a boiling point of the solvent used and preferably 0 to 25°C. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
Production Route 3C
Note that as a method for producing the phenylacetamide compound (1-la), a phenylacetic acid halide compound (3C) obtained by reacting the phenylacetic acid compound (3B) with a halogenation reagent can be used as a material.
The aforementioned reaction can be performed under presence of a base. As the base, any of the same bases as those described above can be used, and preferable examples of the base include triethylamine, pyridine, di-isopropylamine, 4- diisopropylethylamine, 4-dimethylamine pyridine, lutidine, and the like organic bases. The bases can much excessively be used to be also used as reaction solvents.
Examples of the halogen reagent include, but are not particularly limited to, P0C13, POBr3, S0C12, S02C12, and oxalyl chloride. Relative to 1 mole of the aniline compound (2), typically 1 to 10 moles of the halogenation reagent and preferably approximately 1 to 5 moles thereof can be used.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, no limitations are placed on the solvent as long as the solvent is inactive with respect to the aforementioned reaction. As examples of such a solvent, the aforementioned solvents are listed. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between 10°C and a boiling point of the solvent used and preferably within a range between -5°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
The sulfide compound (1-la) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfide compound (1-la) can be provided for next reaction without being isolated from the reaction system.
Production Route 4
The sulfide compound (1-1) can be produced by reacting a sulfide compound (hereinafter may be referred to as "compound (9)") with an amide compound (hereinafter may be referred to as "compound (10)") represented by Formula (10) (Reaction Scheme 12) :
[Reaction Scheme 12]
Figure imgf000042_0001
(9) (10)
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, and Z represents a leaving group.
A used ratio between the sulfide compound (9) and the amide compound (10) in the reaction therebetween is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
The aforementioned reaction can be performed under absence or presence of a base. Among the above, the aforementioned reaction is preferably performed under the presence of the base. As the base, any of the same bases as those shown in Step 1 above can be used. Any separate one of these bases or a combination of two or more types thereof is used.
Relative to 1 mole of the aniline compound (9), typically 1 to 10 moles of the base and preferably approximately 1 to 5 moles thereof is used.
The aforementioned reaction is performed in an appropriate solvent or without any solvent. When the aforementioned reaction is carried out in the solvent, any of the same solvents as those shown in the Step 1 above can be used. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited and is typically within a range between -10°C and a boiling point of the solvent used and preferably between -0°C and the boiling point of the solvent. Reaction time varies depending on, for example, the reaction temperature and the reaction typically ends in approximately 0.5 to 24 hours.
The sulfide compound (9) used as a starting material can be produced according to methods described in EP3002279 and WO2012/176856.
The sulfide compound (1-1) is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, column chromatography, etc.
After end of the reaction, the sulfide compound (1-1) can be provided for next reaction without being isolated from the reaction system.
Step 5
A benzylamide compound (hereinafter may be referred to as "compound (1-2)") represented by Formula (1-2) can be produced by reacting a sulfide compound represented by Formula (1-1) with an oxidizing agent (Reaction Scheme 13) :
[Reaction Scheme 13]
Figure imgf000043_0001
(1 -1 ) (1 -2) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, X, and n' are as described above.
A used ratio between the benzylamide compound (1-1) and the oxidizing agent in the reaction therebetweeen is not particularly limited and can appropriately be selected from a wide range. Relative to 1 mole of the former, typically approximately 1 to 10 moles of the latter and preferably approximately equimolar to 5 moles thereof is used.
The aforementioned reaction can be performed under presence of the oxidizing agent. As the oxidizing agent, any of known oxidizing agents can be used as long as the oxidizing agent can achieve oxidization of sulfide into sulfoxide, and examples of the oxidizing agent include a combination of: performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m- chloroperbenzoic acid (mCPBA) , o-carbonylperbenzoic acid, and the like peracids; hydrogen peroxide, t-butylhydroperoxide, cumene hydroperoxide, and the like alkyl hydroperoxides; and titanium tetraisopropoxide and the like titanium tetraalkoxides^ dichromate, sodium bichromate, patassium bichromate, and the like dichromate salts; and permanganic acid, sodium permanganate, potassium permanganate, and the like permanganates; and the like. Any separate one of these oxidizing agents or a combination of two or more types thereof is used.
Relative to 1 mole of the benzylamide compound (1-1) , a stoichiometric amount of the oxidizing agent or an excessive amount thereof over the aforementioned amount can excessively be used. Preferably one to ten times of the oxidizing agent and more preferably approximately one to five times thereof may be used.
The aforementioned reaction can further be performed by adding a catalyst.
The aforementioned reaction is performed in an appropriate solvent. Examples of the solvent include: n-hexane, cyclohexane, n-heptane, and the like fatty acid or alicyclic hydrocarbon-based solvents; benzene, chlorobenzene, toluene, xylene, and the like aromatic hydrocarbon-based solvents; methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, and the like halogenated hydrocarbon-based solvents; diethyl ether, THF, 1,4-dioxane, and the like ether- based solvents; methyl acetate, ethyl acetate, and the like esters solvents; acetonitrile; DMF, N, N-dimethylacetamide, N- methyl-2-pyrolidone, and the like amide-based solvents; dimethyl sulfoxide and the like sulfoxide-based solvents; alcohol-based solvents such as sulfolane, methanol, ethanol, isopropyl alcohol, and the like aprotic polar solvents. Any one of these solvents can be used alone or a combination of two or more types thereof can be used when necessary.
Reaction temperature for the aforementioned reaction is not particularly limited, and is typically within a range between -20°C and a boiling point of the solvent used, preferably -10°C to 60°C, and more preferably 20 to 50°C. Reaction time varies depending on, for example, the reaction temperature, and the reaction typically ends in approximately 0.25 to 24 hours.
The sulfide compound (1-2) obtained by the method shown in Step 5 is easily isolated from a reaction mixture to be purified by use of typical isolation means and purification means, for example, filtration, solvent extraction, distillation, recrystallization, chromatography, etc.
Each compound (1) obtained after the completion of the reactions shown in Reaction Scheme 1 to Reaction Scheme 13 may be easily isolated from the reaction mixture and purified by known isolation and purification techniques, such as filtration, solvent extraction, distillation, recrystallization, and column chromatography.
When compound (1) has regioisomers, each regioisomer may be separated by a usual separation step, such as silica gel chromatography.
Pest-Controlling Agent
Compound (1) of the present invention may be used as an active ingredient of a pest-controlling agent. Examples of pest- controlling agents include agents (agricultural and horticultural insecticide, miticides, nematicides, or soil insecticides) for controlling pests, mites, nematode, or soil pests that all cause problems in the agricultural and horticultural fields; animal- ectoparasite-controlling agents (e.g., pulicide, ixodicide, and pedivulicideon) , and the like.
For use as an active ingredient of a pest-controlling agent, it is possible to use compound (1) of the present invention as is with no additional components. However, it is usually preferable to use the compound by combining with a solid carrier, liquid carrier, or gaseous carrier (propellant) , and optionally with a surfactant and other adjuvants for pharmaceutical preparation, and formulating the resulting mixture into various forms such as oil solutions, emulsions, wettable powders, flowable preparations, granules, dusts, aerosols, fumigants, or the like, according to known preparation methods.
Compound (1) of the present invention is usually contained in these formulations in a proportion of 0.01 to 95 wt%, and preferably 0.1 to 50 wt%.
Examples of solid carriers usable in the formulations include solid carriers in a fine powder or granular form, such as clay (e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon dioxide, bentonite, Fubasami clay, and acid clay) , talc, ceramic, other inorganic minerals (e.g., celite, quartz, sulfur, active carbon, calcium carbonate, and hydrated silica) , and chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, and ammonium chloride); and the like.
Examples of liquid carriers include water, alcohols (e.g., methanol and ethanol) , ketones (e.g., acetone and methylethylketone) , aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene, and methylnaphthalene) , aliphatic hydrocarbons (e.g., hexane, cyclohexane, kerosene, and light oil), esters (e.g., ethyl acetate and butyl acetate), nitriles (e.g., acetonitrile and isobutyronitrile) , ethers (e.g., diisopropyl ether and dioxane) , acid amides (e.g., N, iV-dimethylformamide and N, IV-dimethylacetamide) , halogenated hydrocarbons (e.g., dichloromethane, trichloroethane, and carbon tetrachloride) , dimethylsulfoxide, soybean oil, cottonseed oil, and like vegetable oils, and the like.
Examples of gaseous carriers include butane gas, LPG (liquefied petroleum gas) , dimethyl ether, carbon dioxide gas, and the like.
Examples of surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, alkyl aryl ethers, polyoxyethylene adducts thereof, polyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives, and the like. Examples of adjuvants for pharmaceutical preparation include fixing agents, dispersants, stabilizers, and the like.
Examples of the fixing agents and dispersants include casein, gelatin, polysaccharides (e.g., starch, gum arabic, cellulose derivatives, and alginic acid) , lignin derivatives, bentonite, sugars, and water-soluble synthetic polymers (e.g., polyvinyl alcohol, polyvinyl pyrrolidone, and polyacrylic acids) .
Examples of stabilizers include PAP (acidic isopropyl phosphate), BHT (2, 6-di- tert-butyl-4-methylphenol) , BHA (mixture of 2- ert-butyl-4-methoxyphenol and 3- ert-butyl-4-methoxyphenol) , vegetable oils, mineral oils, fatty acids, and fatty acid esters, and the like.
For the pest-controlling agent of the present invention, it is preferable to use compound (1) as is, or by diluting it with water or the like. The pest-controlling agent of the present invention may be used by mixing with, for example, other pest- controlling agents, such as known insecticides, nematicides, acaricides, fungicides, herbicides, plant-growth-controlling agents, synergists, soil conditioners, animal feeds, and the like, or it may be used simultaneously with these agents without mixing.
The amount of the pest-controlling agent of the invention is not limited, and may be suitably selected from a wide range according to various conditions such as the concentration of active ingredient, the form of preparation, type of disease or pest to be treated, type of plant, severity of disease, time for application, method for application, chemicals to be used in combination (insecticide, nematicide, miticide, fungicide, herbicide, plant growth control agent, synergist, soil conditioner, etc.), and amount and type of fertilizer.
When used as a pesticide, compound (1) of the present invention is usually used in an amount of 0.01 to 500 g/100 m2, and preferably 1 to 200 g/100 m2.
When used as a miticide, compound (1) of the present invention is usually used in an amount of 0.1 to 500 g/100 m2, and preferably 1 to 200 g/100 m2. When the emulsion, wettable powder, flowable preparation, or the like is used by diluting with water, the concentration is 0.1 to 1, 000 ppm, and preferably 1 to 500 ppm. The granules, dusts, or the like can be used as is without dilution.
Compound (1) of the present invention is characterized by having a particularly excellent miticidal activity and a broad spectrum of activity.
Compound (1) of the present invention is effectively used as an agricultural and horticultural insecticide, miticide, nematicide, or a soil insecticide. Specifically, compound (1) of the present invention is effective for controlling
pests, such as green peach aphids, cotton aphids, and like aphids; diamondback moths, cabbage armyworms, common cutworms, codling moths, bollworms, tobacco budworms, gypsy moths, rice leafrollers, smaller tea tortrix moths, Colorado potato beetles, cucurbit leaf beetles, boll weevils, plant hoppers, leafhoppers, scales, bugs, whiteflies, thrips, grasshoppers, anthomyiid flies, scarabs, black cutworms, cutworms, ants, and agricultural pest insects; slugs, snails, and like gastropods; rat mite, cockroaches, houseflies, house mosquitoes, and like hygiene- harming insects; angoumois grain moths, adzuki bean weevils, red flour beetles, mealworms, and like stored-grain insects; casemaking clothes moths, black carpet beetles, subterranean termites, and like clothes-harming insects and house- and household-harming insects; and the like,
mites, such as two-spotted spider mites, carmine spider mites, citrus red mites, Kanzawa spider mites, European red mites (fruit tree spider mites) , broad mites, pink citrus rust mites, bulb mites, and like plant-parasitic mites; Tyrophagus putrescentiae, Dermatophagoides farinae, Chelacaropsis moorei, and like house dust mites; and the like, and
soil pests, such as root-knot nematodes, cyst nematodes, root- lesion nematodes, white-tip nematode, strawberry bud nematode, pine wood nematode, and like plant parasitic nematodes; pill bugs, sow bugs, and like isopods; and the like.
The pest-controlling agent of the present invention is also effective for controlling various pests resistant to chemicals such as organophosphorus agents, carbamate agents, synthetic pyrethroid agents, and neonicotinoid agent.
Examples
The present invention is described in more detail with reference to the following Production Examples and Examples; however, the present invention is not limited to these Examples.
Production Example 1 :
Preparation of N- (2-fluoro-4-methylphenyl) -2- (4-
(trifluoromethoxy) phenyl) acetamide (4-14)
To a solution of 2-fluoro-4-methylbenzenamine (2-14;
1.1 g, 8.79 mmol, 1 equiv.) and 2- (4- (trifluoromethoxy) phenyl) acetic acid (3b-14; 2.12 g, 9.67 mmol, 1.1 equiv.) in pyridine (10 ml) slowly added P0C13 (1.6 ml, 17.58 mmol, 2 equiv.) at 0 °C. The reaction was further maintained at the same temperature for 15 minutes. The reaction mixture was then quenched into ice and the product was then extracted with ethyl acetate. The combined organic layer was washed by IN HC1 solution followed by brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to get 2.20 g of the crude product 4-14 as yellow solid. The crude product thus obtained was further used as such without any purification.
1H NMR (CDC13) : 8.10 (t, J = 8.6 Hz, 1H) , 7.39-7.37 (m, 2H) , 7.25- 7.23 (m, 3H) , 6.92-6.85 (m, 2H) , 3.75 (s, 2H) , 2.29 (s, 3H) . Production Example 2 :
Preparation of 5- (2- (4- (trifluoromethoxy) phenyl) acetamide) -4- fluoro-2-methylbenzene-l-sulfonyl chloride (5-14)
Chlorosulfonic acid (14.0 g, 120 mmol, 18 equiv.) was added to N- (2-fluoro-4-methylphenyl) -2- (4- (trifluoromethoxy) phenyl) acetamide (4-14; 2.20 g, 6.72 mmol, 1 equiv.) at a temperature below 50 °C. The reaction mixture was then stirred at room temperature overnight. The reaction mixture was then quenched into ice, the product was then extracted with ethyl acetate. The combined organic layer was washed by distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get 2.60 g of the crude product 5-14 as black viscous oil. The crude product thus obtained was further used as such without any purification.
1H NMR (CDC13) : 9.08 (d, J = 7.6 Hz, 1H) , 7.39-7.36 (m, 2H) , 7.25- 7.24 (m, 3H) , 7.12 (d, J = 10.8 Hz, 1H) , 3.79 (s, 2H) , 2.71 (s, 3H) .
Production Example 3 :
Preparation of N- (2-fluoro-5-mercapto-4-methylphenyl) -2- (4- (trifluoromethoxy) phenyl) acetamide (6-14)
To a mixture of 5- (2- (4- (trifluoromethoxy) phenyl) acetamide) -4-fluoro-2-methylbenzene-l-sulfonyl chloride (5-14; 2.60 g, 6.11 mmol, 1 equiv.) in toluene (20 ml) was added triphenyl phosphine (4.8 g, 18.35 mmol, 3 equiv.) at room temperature. The reaction was then heated to 100 °C for 3 hours. The reaction mixture was cooled to room temperature and all the volatiles were distilled out by rotary evaporator. The crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 1.0 g of the title compound 6-14 as an off white solid.
¾ NMR (CDCI3) : 8.26 (d, J = 7.6 Hz, 1H) , 7.38-7.36 (m, 2H) , 7.25- 7.21 (m, 3H) , 6.87 (d, J = 10.8 Hz, 1H) , 3.74 (s, 2H) , 3.30 (s, 1H) , 2.25 (s, 3H) .
Example 1 :
Preparation of N- (5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylphenyl) -2- (4- (trifluoromethoxy) phenyl) acetamide (1A-14)
To a cooled mixture of N- (2-fluoro-5-mercapto-4- methylphenyl) -2- (4- (trifluoromethoxy) phenyl) acetamide (6-14; 1.00 g, 2.78 mmol, 1 equiv.) in DMF (10 ml) was added cesium carbonate (0.90 g, 2.78 mmol, 1 equiv.) followed by sodium formaldehyde sulfoxylate (0.33 g, 2.78 mmol, 1 equiv.). To this mixture was then added slowly trifluoroethyl iodide (0.639 g, 3.06 mmol, 1.1 equiv.) at 0 °C and the resulting mixture was then stirred at room temperature for 6 hours . The reaction mixture was then poured into distilled water and extracted with dichloromethane . The combined organic layer was washed with distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. The crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 0.95 g of the title compound 1A- 14 as a pale yellow solid.
Production Example 4 :
Preparation of N- (2-fluoro-4-methylphenyl) acetamide
To a mixture of 2-fluoro-4-methylaniline (5.50 g, 43.95 mmol, 1 equiv.) in chloroform (30 ml), a solution of acetic anhydride (4.49 g, 43.95 mmol, 1 equiv.) in chloroform (20 ml) was slowly added at 0 °C. The reaction mixture was then stirred at room temperature for 3 hours. The reaction mixture was then quenched into sodium bicarbonate solution and the product was extracted with dichloromethane. The combined organic layer was washed by sodium bicarbonate solution followed by distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get 5.92 g of the crude product as white solid. The crude product thus obtained was further used as such without any purification.
¾ NMR (CDC13) : δ 8.14-8.10 (m, 1H) , 7.25 (bs, 1H) , 6.93-6.88 (m, 2H) , 2.31 (s, 3H) , 2.20 (s, 3H) .
Production Example 5:
Preparation of 5-acetamido-4-fluoro-2-methylbenzene-l-sulfonyl chloride Chlorosulfonic acid (20.56 g, 176.46 mmol, 5 equiv.) was slowly added to N- (2-fluoro-4-methylphenyl) acetamide (5.90 g, 35.29 mmol, 1 equiv.) keeping the temperature of the reaction mixture below 50 °C. The resulting mixture was then heated to 70 °C for 4 hours. After cooling to room temperature, the reaction mixture was then poured carefully into ice, the precipitate was filtered, washed well with distilled water and dried to get 7.3 g of crude product as light brown solid. The crude product thus obtained was further used as such without any purification.
¾ NMR (CDC13) : δ 9.09 (d, J = 7.6 Hz, 1H) , 7.48 (bs, 1H) , 7.14 (d, J = 10.8 Hz, 1H) , 2.72 (s, 3H) , 2.25 (s, 3H) .
Production Example 6:
Preparation of N- (2-fluoro-5-mercapto-4-methylphenyl) acetamide
To a mixture of 5-acetamido-4-fluoro-2-methylbenzene-l- sulfonyl chloride (7.00 g, 26.34 mmol, 1 equiv.) in glacial acetic acid (60 ml) was portion-wise added zinc dust (34.44 g, 526.80 mmol, 20 equiv.) at room temperature. The resulting mixture was then refluxed for 4 hours. After cooling to room temperature, the reaction mixture was diluted with distilled water and ethyl acetate and filtered through celite bed. The organic layer was washed well by distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get 3.64 g of the crude product as pale yellow solid. The crude product thus obtained was further used as such without any purification.
¾ NMR (CDCI3) : δ 8.25 (d, J = 7.6 Hz, 1H) , 7.29 (bs, 1H) , 6.89 (d, J = 11.6 Hz, 1H) , 3.34 (bs, 1H) , 2.26 (s, 3H) , 2.20 (s, 3H) .
Production Example 7 :
Preparation of N- (5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylphenyl) acetamide
To a cooled mixture of N- (2-fluoro-5-mercapto-4- methylphenyl) acetamide (3.10 g, 15.56 mmol, 1 equiv.) in DMF (30 ml) was added cesium carbonate (5.07 g, 15.56 mmol, 1 equiv.) followed by sodium formaldehyde sulfoxylate (1.84 g, 15.56 mmol, 1 equiv.) . To this mixture was then added slowly trifluoroethyl iodide (3.27 g, 15.56 mmol, 1 equiv.) and the resulting mixture was then stirred at room temperature for 6 hours . The reaction mixture was then poured into distilled water and extracted with dichloromethane . The combined organic layer was washed with distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude product. The crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 2.90 g of the title compound as an off white solid.
¾ NMR (CDC13) : δ 8.49 (d, J = 8.0 Hz, 1H) , 7.29 (bs, 1H) , 6.96 (d, J = 11.6 Hz, 1H) , 3.42-3.35 (q, J = 9.6 Hz, 2H) , 2.41 (s, 3H) , 2.21 (s, 3H) .
Production Example 8 :
Preparation of 5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylbenzenamine
To a mixture of N- (5- (2, 2, 2-trifluoroethylthio) -2- fluoro-4-methylphenyl) acetamide (2.20 g, 7.82 mmol, 1 equiv.) in ethanol/water (30 ml/4 ml) was added concentrated HC1 (30 ml) . The resulting mixture was then refluxed for 6 hours. After cooling to room temperature, all volatiles were removed by vacuum distillation and pH of the residue was then made basic by slow addition of IN NaOH solution. The product was then extracted with ethyl acetate. The combined organic layer was then washed with distilled water followed by brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude product as a brown oil . The crude product thus obtained was further used as such without any purification.
¾ NMR (CDCI3) : δ 6.98 (d, J = 9.2 Hz, 1H) , 6.86 (d, J = 11.6 Hz, 1H) , 3.64 (bs, 2H) , 3.32-3.25 (q, J = 9.6 Hz, 2H) , 2.36 (s, 3H) . Example 2 : Preparation of N- (5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylphenyl) -2-phenylacetamide (lA-1)
To a cooled solution of 5- (2, 2, 2-trifluoroethylthio) -2- fluoro-4-methylbenzenamine (0.10 g, 0.42 mmol, 1 equi . ) in chloroform (10 ml), triethylamine (0.046 g, 0.46 mmol, 1.1 equiv.) was added followed by slow addition of 2-phenylacetyl chloride (0.068 g, 0.44 mmol, 1.05 equiv.). The resulting mixture was then stirred at room temperature for 14 hours. The reaction mixture was then poured into NaHCC>3 solution and the product was extracted by dichloromethane . The combined organic layer was then washed with distilled water followed by brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to get 0.125 g of title product as an off white solid. Example 3 :
Preparation of N- (5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylphenyl) -2- (2-chlorophenyl) acetamide (1A-3)
To a cooled solution of 5- (2, 2, 2-trifluoroethylthio) -2- fluoro-4-methylbenzenamine (0.05 g, 0.21 mmol, 1 equiv.) in dichloromethane (10 ml), triethylamine (0.042 g, 0.42 mmol, 2.0 equiv.) was added followed by slow addition of 2- (2-chlorophenyl) acetyl chloride (0.04 g, 0.21 mmol, 1 equiv.) . The resulting mixture was then stirred at room temperature for 14 hours. The reaction mixture was then poured into NaHC03 solution and the product was extracted by dichloromethane. The combined organic layer was then washed with distilled water followed by brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude product. The crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 0.07 g of the title compound as a brown solid.
Example 4 :
Preparation of N- (5- (2, 2, 2-trifluoroethylthio) -2-fluoro-4- methylphenyl) -2- (2, 5-dichlorophenyl) acetamide (1A-4) To a cooled mixture of 5- (2, 2, 2-trifluoroethylthio) -2- fluoro-4-methylbenzenamine (0.05 g, 0.21 mmol, 1 equiv.) and 2- (2, 5-dichlorophenyl) acetic acid (0.05 g, 0.25 mmol, 1.2 equiv.) in pyridine (3 ml), POCI3 (0.08 g, 0.52 mmol, 2.5 equiv.) was added very slowly. After few minutes, the reaction mixture was poured into ice and the product was extracted with ethyl acetate. The combined organic layer was then washed with IN HC1 followed with distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude product. The crude product thus obtained was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane as an eluent to obtain 0.023 g of the title compound as a light yellow solid. Example 5:
The compounds shown in Tables 1 and 2, other than the compounds obtained in Examples 1 to 4, were produced by methods similar to the methods described in Examples 1 to 4 or methods described in the description.
Tables 2 show ^-NMR data of the thus obtained compounds of the present invention.
The abbreviations in Tables 1 and 2 are as indicated below.
F: fluoro, CI: chloro, Br: bromo, Me: methyl, Et: ethyl, n-Pr: normal-propyl, i-Pr: isopropyl, n-Bu: normal-butyl, t-Bu: tert- butyl, n-Pent: normal-pentyl, CF3: trifluoromethyl, OMe: methoxy, OEt: ethoxy, OCF3: trifluoromethoxy, SCF3: trifluoromethylthio, SMe: methylthio, N¾: amino, NO2: nitro, Ph: phenyl, S: sulfur atom, 0: oxygen atom. Table 1
Figure imgf000056_0001
S. No. R2 R3 R* R5 R3 R7 R8 R9 R10 R1 X n
1A-1 Me F H H H H H H H H 0 0
1A-2 Me F H H H H H CI H H 0 0
1A-3 Me F H H H CI H H H H 0 0
1A-4 Me F H H H CI H H CI H 0 0
1A-5 Me F H H H H CI CI H H 0 0
1A-6 Me F H H H H CI H CI H 0 0
1A-7 Me F H H H CI CI H H H 0 0
1A-8 Me F H H H CI H CI H H 0 0
1A-9 Me F H H H H CI H H H 0 0
1A-10 Me F H H H H H t-Bu H H 0 0
1A-11 Me F H H H CI H H H CI 0 0
1A-12 Me F H H H H H CF3 H H 0 0
1A-13 Me F H H H H H F H H 0 0
1A-14 Me F H H H H H OCF3 H H 0 0
1A-15 Me F H H H F H F H F 0 0
1A-16 Me F H H H Br H OMe H H 0 0
1A-17 Me F H H H H F H H H 0 0
1A-18 Me F H H H F H H H H 0 0
1A-19 Me F H H H H OCF3 H H H 0 0
1A-20 Me F H H H F H H H F 0 0
1A-21 Me F H H H Me H H H H 0 0
1A-22 Me F H H H Me H Me H Me 0 0
1A-23 Me F H H H H H Br H H 0 0
1A-24 Me F H H H H H OMe H H 0 0
1A-25 Me F H H H H H OEt H H 0 0
1A-26 Me F H H H H H O-n-Pr H H 0 0
1A-27 Me F H H H H H 3,4-CI2-Ph H H 0 0
1A-28 Me F H H H H H 4-OCF3-Ph H H 0 0
1A-29 Me F H H H H H 4-CF3-Ph H H 0 0
1A-30 Me F H H H H H rPr H H 0 0
1A-31 Me F H H H H H NH2 H H 0 0
1A-32 Me F H H H H H N02 H H 0 0
1A-33 Me F H H rPr H H CI H H 0 0
1A-34 Me F H Me Me H H CI H H 0 0
1A-35 Me F H H H H H CI H H 0 1
1A-36 Me F H H H H H CI H H 0 2
1A-37 Me F H H H H H OCF3 H H 0 1
1A-38 Me F H H H H H OCF3 H H 0 2
1A-39 Me F H H H H H CF3 H H 0 1 A- 0 Me F H H H H H CF3 H H 0 2A-41 Me F Me H H H H CI H H 0 0A-42 Me F Me H H H H OCF3 H H 0 0A-43 Me F Me H H H H CF3 H H 0 0A-44 Me Br H H H H H CI H H 0 0A-45 Me F Et H H H H CI H H 0 0A-46 Me F H H H H H n-Pr H H 0 0A-47 Me F H H H H H SCF3 H H 0 0A-48 Me F Et H H H H OCF3 H H 0 0A-49 Me F Me H H H H SCF3 H H 0 0A-50 Me Br Me H H H H CI H H 0 0A-51 Me Br Me H H H H OCF3 H H 0 0A-52 Me Br Me H H H H CF3 H H 0 0A-53 Me Br H H H H H CF3 H H 0 0A-54 Me Br H H H H H OCF3 H H 0 0A-55 Me CI Et H H H H CI H H 0 0A-56 Me CI Me H H H H OCF3 H H 0 0A-57 Me CI Me H H H H CI H H 0 0A-58 Me CI Et H H H H OCF3 H H 0 0A-59 Me CI H H H H H OCF3 H H 0 0A-60 Me CI H H H H H CF3 H H 0 0A-61 Me CI H H H H H CI H H 0 0A-62 Me CI H H H H H SCF3 H H 0 0A-63 Me F H H H H H 4-CI-Ph H H 0 0A-64 Me F H H H H H 5-CF3-2-FV H H 0 0A-65 Me F H H H H H Ph H H 0 0A-66 Me F H H H H H 3,5-F2-Ph H H 0 0A-67 Me F H H H H H 2-SMe-Ph H H 0 0A-68 Me F H H H H H 2-CI-Ph H H 0 0A-69 Me F H H H H H Me H H 0 0A-70 Me F H H H H H Et H H 0 0A-71 Me F H H H H H n-pent H H 0 0A-72 Me F Me H H H H SMe H H 0 0A-73 Me Br Me H H H H SCF3 H H 0 0A-74 Me Br Me H H H H SMe H H 0 0A-75 Me Br H H H H H SCF3 H H 0 0A-76 Me F H H H H H SMe H H 0 0A-77 Me Br H H H H H SMe H H 0 0A-78 Me F Et H H H H SMe H H 0 0A-79 F Me H H H H H CI H H 0 0A-80 F Me H H H H H OCF3 H H 0 0A-81 F Me H H H H H CF3 H H 0 0A-82 Me CI Me H H H H CF3 H H 0 0A-83 Me CI Et H H H H CF3 H H 0 0A-84 F Me H H H H H SCF3 H H 0 0A-85 Me Br Et Me H H H CI H H 0 0A-86 Me F Me Me H H H CI H H 0 0 A-87 Me F Et Me H H H CI H H 0 0A-88 Me Br Me Me H H H CI H H 0 0A-89 Me Br H Me H H H CI H H 0 0A-90 Me F H Me H H H CI H H 0 0A-91 Me F n-Pr H H H H CF3 H H 0 0A-92 Me F n-Bu H H H H CF3 H H 0 0A-93 Me F Me H H H H 3,4-CI2-Ph H H 0 0A-94 Me F Et H H H H 3,4-CI2-Ph H H 0 0A-95 Me F Me H H H H Ph H H 0 0A-96 Me F Et H H H H Ph H H 0 0A-97 Me F Propargyl H H H H CF3 H H 0 0A-98 Me F rPr H H H H CF3 H H 0 0A-99 F Me H H H H H 4-OCF3-Ph H H 0 0A-100 F Me H H H H H 4-CF3-Ph H H 0 0A-101 Me F Heptafluoro-rPr H H H H CF3 H H 0 0A-102 Me F H H H H H 4-F-Ph H H 0 0A-103 Me F H H H H H 4-OMe-Ph H H 0 0A-104 Me F H H H H H 3-OCF3-Ph H H 0 0A-105 Me F H H H H H 3-CI, 5-CF3- H H 0 0
Ph
A-106 Me F H H H H H 2-OCF3-Ph H H 0 0A-107 Me F H H H H H 3-CF3-Ph H H 0 0A-108 Me F H H H H H 3-F-Ph H H 0 0A-109 Me F H H H H H 2-F-Ph H H 0 0A-110 Me F Me H H H H 4-CI, 3-CF3- H H 0 0
Ph
A-111 Me F Me H H H H 2-CI, 4-F-Ph H H 0 0A-112 Me F 3,3,3-trifluoro- H H H H CF3 H H 0 0 n-Pr
A-113 Me F H H H H H 2-CI, 4-F-Ph H H 0 0A-114 Me F H H H H H 4-CI, 3-CF3- H H 0 0
Ph
A-115 Me F H H H H H 5-Pyrimidyl H H 0 0A-116 Me F H H H H H CF3 H H s 0A-117 Me F Me H H H H CF3 H H s 0A-118 Me F Me H H H H 3-F-Ph H H 0 0A-119 Me F Me H H H H 3-CF3-Ph H H 0 0A-120 Me F Me H H H H 3-CI, 5-CF3- H H 0 0
Ph
A-121 Me F Me H H H H 3-OCF3-Ph H H 0 0A-122 Me F Me H H H H 4-OMe-Ph H H 0 0A-123 Me F Me H H H H 4-F-Ph H H 0 0A-124 Me F Me H H H H 2-F-Ph H H 0 0A-125 Me F Me H H H H 2-OCF3-Ph H H 0 0A-126 Me F H F F H H CI H H 0 0A-127 Me F Me H H H H 4-CI-Ph H H 0 0A-128 Me F Me H H H H 2-CI-Ph H H 0 0 1A-129 Me F Me F F H H CI H H 0 0
1A-130 Me F Me H H H H n-Pr H H 0 0
1A-131 Me F Me H H H CI CI H H 0 0
1A-132 Me F Me H H F H H H F 0 0
1A-133 Me F Me H H H H Et H H 0 0
1A-134 Me F Et H H H H S02Me H H 0 0
1A-135 Me F Me H H H H S02Me H H 0 0
1A-136 Me F H H H H H S02Me H H 0 0
1A-137 Me F H F F H H CF3 H H 0 0
1A-138 Me F Me F F H H CF3 H H 0 0
1A-139 Me F Me H H H H CN H H 0 0
1A-140 Me F H H H H H 2,4-CI2-Ph H H 0 0
1A-141 Me F H H H H H 3,4,5-F3-Ph H H 0 0
1A-142 Me F H H H H H 4-Br-Ph H H 0 0
1A-143 Me F H H H H H 3,5-CI2-Ph H H 0 0
1A-144 Me F H H H H H 4-SMe-Ph H H 0 0
1A-145 Me F H H H H H 4-Me-Ph H H 0 0
1A-146 Me F Me H H H H 4-SMe-Ph H H 0 0
1A-147 Me F Me H H H H 3,5-CI2-Ph H H 0 0
1A-148 Me F Me H H H H 4-Br-Ph H H 0 0
1A-149 Me F Me H H H H 4-Me-Ph H H 0 0
Table 2
S. No. 'H NMR
1A-1 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.43-7.40 (m, 2H), 7.37-7.33 (m, 3H), 7.27-7.24 (bs, 1 H), 6.90 (d, J = 11.2 Hz, 1 H), 3.77 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H).
1A-2 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.39-7.37 (m, 2H), 7.29-7.27 (m, 2H), 7.24 (bs, 1 H), 6.93 (d, J = 11.6 Hz, 1 H), 3.73 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
1A-3 CDCI3: δ 8.59 (d, J = 8.0 Hz, 1 H), 7.47-7.41 (m, 3H), 7.33-7.28 (m, 2H), 6.92 (d, J = 11.6 Hz, 1 H), 3.89 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.40 (s, 3H).
1A-4 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.42-6.42 (m, 2H), 7.28-7.26 (m, 2H), 6.95 (d, J = 11.6 Hz, 1 H), 3.84 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
1A-5 DMSO-d6: δ 10.02 (s, 1 H), 8.06 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 4.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 1 H), 7.25 (d, J = 11.6 Hz, 1 H), 3.82-3.76 (m, 4H), 2.37 (s, 3H).
1A-6 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.34 (s, 1 H), 7.26-7.25 (m, 3H), 7.96 (d, J = 11.6 Hz, 1 H), 3.70 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.42 (s, 3H).
1A-7 CDCI3: δ 8.47 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 9.2 Hz, 1 H), 7.39 (bs, 1 H), 7.33 (d, J = 6.8 Hz, 1 H), 7.27-7.23 (m, 1 H), 6.95 (d, J = 11.2 Hz, 1 H), 3.93 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
1A-8 CDCI3: δ 8.47 (d, J= 8.0 Hz, 1 H), 7.47 (d, J = 2.0 Hz, 1 H), 7.38 (bs, 1 H), 7.36 (d, J = 8.6 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 1 H), 6.95 (d, J = 11.6 Hz, 1 H), 3.85 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
1A-9 CDCI3: δ 8.48 (d, J = 8.0 Hz, 1 H), 7.32 (m, 3H), 7.26-7.23 (m, 2H), 6.93 (d, J = 11.6 Hz, 1 H), 3.73 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.41 (s, 3H).
1A-10 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.4 Hz, 2H), 7.28-7.25 (m, 3H), 6.90 (d, J = 11.2 Hz, 1 H), 3.73 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.39 (s, 3H), 1.33 (s, 9H).
1A-11 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.40 (d, J = 8.0 Hz, 2H), 7.37 (bs, 1 H), 7.22 (d, J = 8.4 Hz, 1 H), 6.94 (d, J = 11.6 Hz, 1 H), 4.14 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.41 (s, 3H). A-12 CDCI3: δ 8.47 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.27 (bs, 1 H), 6.94 (d, J = 11.2 Hz, 1 H), 3.82 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-13 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.33-7.29 (m, 2H), 7.23 (bs, 1 H), 7.10 (t, J = 8.6 Hz, 2H), 6.92 (d, J = 11.6 Hz, 1 H), 3.74 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-14 CDCI3: δ 8.48 (d, J = 8.0 Hz, 1 H), 7.38 (d, J = 8.4 Hz, 2H), 7.27-7.24 (m, 3H), 6.94 (d, J = 11.6 Hz, 1 H), 3.76 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-15 CDCI3: δ 8.49 (d, J= 7.6 Hz, 1 H), 7.40 (bs, 1 H), 6.97 (d, J = 11.6 Hz, 1 H), 6.75 (t, J = 7.8 Hz, 2H), 3.77 (s, 2H), 3.36 (q, J = 9.6 Hz, 2H), 2.42 (s, 3H).
A-16 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.38 (bs, 1 H), 7.32 (d, J = 8.4 Hz, 1 H), 7.18 (d, J = 2.8 Hz, 1 H), 6.94-6.89 (m, 2H), 3.83 (s, 2H), 3.81 (s, 3H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-17 CDCI3: δ 8.48 (d, J = 7.6 Hz, 1 H), 7.38 (q, J = 7.0 Hz, 1 H), 7.12 (d, J = 7.6 Hz, 2H), 7.07-7.03 (m, 2H), 6.92 (d, J = 11.6 Hz, 1 H), 3.76 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-18 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.40-7.31 (m, 3H), 7.20-7.11 (m, 2H), 6.93 (d, J = 11.6 Hz, 1 H), 3.78 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-19 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.43 (bs, 1 H), 7.32-7.28 (m, 2H), 6.99-6.94 (m, 3H), 3.83 (s, 2H), 3.36 (q, J= 9.6 Hz, 2H), 2.41 (s, 3H).
A-20 CDCI3: δ 8.48 (d, J = 8.0 Hz, 1 H), 7.44 (t, J = 8.4 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.22-7.20 (m, 2H), 6.93 (d, J = 11.6 Hz, 1 H), 3.78 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.41 (s, 3H).
A-21 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.28-7.26 (m, 4H), 7.18 (bs, 1 H), 6.88 (d, J = 11.2 Hz, 1 H), 3.78 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H).
A-22 CDCI3: δ 8.43 (d, J = 7.6 Hz, 1 H), 7.18 (bs, 1 H), 6.95 (s, 2H), 6.87 (d, J = 11.2 Hz, 1 H), 3.77 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H), 2.31-2.30 (m, 9H).
A-23 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.53 (d, J = 8.0 Hz, 2H), 7.26-7.21 (m, 3H), 6.93 (d, J = 11.6 Hz, 1 H), 3.71 (s, 2H), 3.37 (q, J = 9.7 Hz, 2H), 2.40 (s, 3H).
A-24 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.27-7.24 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 11.6 Hz, 1 H), 3.83 (s, 3H), 3.70 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H).
A-25 CDCI3: δ 8.49 (d, J = 8.0 Hz, 1 H), 7.28-7.22 (m, 3H), 6.94-6.88 (m, 3H), 4.07^.02 (m, 2H), 3.70 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H), 1.43 (t, J = 8.0 Hz, 3H).
A-26 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.28-7.22 (m, 3H), 6.94-6.88 (m, 3H), 3.93 (t, J = 6.6 Hz, 2H), 3.70 (s, 2H), 3.38 (q, J = 8.8 Hz, 2H), 2.39 (s, 3H), 1.86-1.17 (m, 2H), 1.04 (s, 3H).
A-27 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.68 (d, J = 1.6 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 1 H), 7.44-7.41 (m, 3H), 7.29 (bs, 1 H), 6.92 (d, J = 11.2 Hz, 1 H), 3.81 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).A-28 CDCI3: δ 8.51 (d, J = 7.6 Hz, 1 H), 7.62-7.59 (m, 4H), 7.42 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 3H), 6.92 (d, J = 11.6 Hz, 1 H), 3.81 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-29 CDCI3: δ 8.51 (d, J = 7.6 Hz, 1 H), 7.70 (bs, 4H), 7.65 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.32 (bs, 1 H), 6.92 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-30 CDCI3: δ 8.48 (d, J = 8.0 Hz, 1 H), 7.00-6.73 (m, 5H), 6.89 (d, J = 7.6 Hz, 1 H), 3.73 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.96-2.89 (m, 1 H), 2.39 (s, 3H), 1.26 (d, J = 6.8 Hz, 6H).
A-31 CDCI3: δ 8.49 (d, J = 8.0 Hz, 1 H), 7.31 (bs, 1 H), 7.10 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 11.6 Hz, 1 H), 6.72 (d, J = 8.4 Hz, 2H), 3.72 (bs, 2H), 3.65 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H).
A-32 CDCI3: δ 8.46 (d, J = 8.0 Hz, 1 H), 8.26 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.31 (bs, 1 H), 6.96 (d, J = 11.6 Hz, 1 H), 3.86 (s, 2H), 3.36 (q, J = 9.6 Hz, 2H), 2.42 (s, 3H).
A-33 CDCI3: δ 8.49 (d, J = 8.0 Hz, 1 H), 7.35-7.28 (m, 5H), 6.93 (d, J = 11.2 Hz, 1 H), 3.37 (q, J = 9.6 Hz, 2H), 2.99 (d, J = 10.0 Hz, 1 H), 2.48-2.40 (m, 4H), 1.10 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz, 3H).
A-34 CDCI3: δ 7.38 (s, 1 H), 7.32 (d, J = 3.6 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 3.42-2.25 (m, 2H), 2.09 (s, 3H), 1.59 (s, 3H), 1.44 (s, 3H).
A-35 CDCI3: δ 8.77 (d, J = 7.6 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 2H), 7.32-7.21 (m, 3H), 6.98 (d, J = 11.2 Hz, 1 H), 3.75 (s, 2H), 3.61-3.50 (m, 1 H), 3.44-3.33 (m, 1 H), 2.37 (s, 3H).
A-36 CDCI3: δ 8.96 (d, J = 7.6 Hz, 1 H), 7.39 (d, J = 8.4 Hz, 2H), 7.29-7.26 (m, 3H), 7.07 (d, J = 11.2 Hz, 1 H), 3.91 (q, J = 8.8 Hz, 2H), 3.76 (s, 2H), 2.64 (s, 3H). A-37 CDCI3: δ 8.79 (d, J = 7.6 Hz, 1 H), 7.38 (d, J = 8.8 Hz, 2H), 7.32 (bs, 1 H), 7.26-7.24 (m, 2H), 6.98 (d, J = 10.8 Hz, 1 H), 3.78 (s, 2H), 3.58-3.50 (m, 1 H), 3.44-3.33 (m, 1 H), 2.38 (s, 3H).
A-38 CDCI3: δ 8.97 (d, J = 7.6 Hz, 1 H), 7.38 (d, J = 8.4 Hz, 2H), 7.29-7.25 (m, 3H), 7.07 (d, J = 10.8 Hz, 1 H), 3.90 (q, J = 8.9 Hz, 2H), 3.79 (s, 2H), 2.65 (s, 3H).
A-39 CDCI3: δ 8.78 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.35 (bs, 1 H), 6.99 (d, J = 11.2 Hz, 1 H), 3.84 (s, 2H), 3.60-3.49 (m, 1 H), 3.44-3.32 (m, 1 H), 2.38 (s, 3H).
A-40 CDCI3: δ 8.96 (d, J = 9.5 Hz, 1 H), 7.67 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.6 Hz, 2H), 7.31 (bs, 1 H), 7.08 (d, J = 11.2 Hz, 1 H), 3.90 (q, J = 8.9 Hz, 2H), 3.85 (s, 2H), 2.65 (s, 3H).
A-41 CDCI3: δ 7.26 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 10.0 Hz, 1 H), 6.96 (d, J = 8.4 Hz, 2H), 3.45-3.34 (m, 2H), 3.28-3.21 (m, 5H), 2.51 (s, 3H).
A-42 CDCI3: δ 7.30 (d, J = 7.6 Hz, 1 H), 7.10-7.04 (m, 5H), 3.48-3.38 (m, 2H), 3.29-3.17 (m, 5H), 2.51 (s, 3H).A-43 CDCI3: δ 7.53 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1 H), 7.19 (d, J = 7.6 Hz, 2H), 7.11 (d, J = 10.4 Hz, 1 H), 3.49 (q, J = 13.2 Hz, 2H), 3.30-3.23 (m, 5H), 2.54 (s, 3H).
A-44 CDCI3: δ 8.49 (s, 1 H), 7.53 (s, 1 H), 7.39 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 11.2 Hz, 2H), 7.26 (s, 1 H), 3.76 (s, 2H), 3.44 (q, J = 9.6 Hz, 2H), 2.35 (s, 3H).
A-45 CDCI3: δ 7.22-7.19 (m, 3H), 7.07 (d, J = 10.0 Hz, 1 H), 6.95 (d, J = 8.4 Hz, 2H), 3.74-3.66 (m, 2H), 3.42 (s, 2H), 3.26-3.19 (m, 2H), 2.51 (s, 3H), 0.84 (t, J = 8.8 Hz, 3H).
A-46 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.20-7.26 (m, 5H), 6.88 (d, J = 11.6 Hz, 1 H), 3.73 (s, 2H), 3.41-3.34 (m, 2H), 2.58 (t, J = 7.6 Hz, 2H), 2.39 (s, 3H), 1.68-1.60 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H).
A-47 CDCI3: δ 8.47 (d, J = 8.0 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.29 (bs, 1 H), 6.93 (d, J = 11.2 Hz, 1 H), 3.79 (s, 2H), 3.33 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-48 CDCI3: δ 7.26 (d, J = 6.4 Hz, 1 H), 7.09-7.04 (m, 5H), 3.77-3.63 (m, 2H), 3.44-3.34 (m, 2H), 3.29-3.20 (m, 2H), 2.48 (s, 3H), 0.86 (t, J = 9.6 Hz, 3H).
A-49 CDCI3: δ 7.51 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1 H), 7.08 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 14.4 Hz, 1 H), 3.48 (s, 2H), 3.29-3.22 (s, 5H), 2.51 (s, 3H).
A-50 CDCI3: δ 7.58 (s, 1 H), 7.51 (d, J = 8.0 Hz, 2H), 7.29 (s, 1 H), 7.19-7.18 (m, 2H), 3.46 (d, J = 14.8 Hz, 1 H), 3.37 (d, J = 14.8 Hz, 1 H), 3.29-3.22 (m, 2H), 3.19 (s, 3H), 2.48 (s, 3H).
A-51 CDCI3: δ 7.57 (s, 1 H), 7.21 (s, 1 H), 7.09 (s, 4H), 3.40 (d, J = 15.2 Hz, 1 H), 3.32-3.25 (m, 3H), 3.19 (s, 3H), 2.48 (s, 3H).
A-52 CDCI3: δ 7.57 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2H), 7.16 (s, 1 H), 6.98 (d, J = 8.4 Hz, 2H), 4.77 (d, J = 15.2 Hz, 1 H), 3.30-3.24 (m, 3H), 3.18 (s, 3H), 2.47 (s, 3H).
A-53 CDCI3: δ 8.48 (s, 1 H), 7.68 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 3H), 7.33 (s, 1 H), 3.84 (d, J = 8.0 Hz, 2H), 3.45 (q, J = 9.6 Hz, 2H), 2.36 (s, 3H).
A-54 CDCI3: δ 8.50 (s, 1 H), 7.52 (bs, 1 H), 7.40 (d, J = 8.4 Hz, 2H), 7.32-7.26 (m, 3H), 3.80 (s, 2H), 3.45 (q, J = 9.4 Hz, 2H), 2.35 (s, 3H).
A-55 CDCI3: δ 7.40 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2H), 7.11 (s, 1 H), 6.96 (d, J = 8.0 Hz, 2H), 4.04-3.95 (m, 1 H), 3.43-3.35 (m, 2H), 3.28-3.18 (m, 3H), 2.48 (s, 3H), 1.09 (t, J = 7.2 Hz, 3H).
A-56 CDCI3: δ 7.39 (s, 1 H), 7.30 (s, 1 H), 7.11 -7.05 (m, 4H), 3.42-3.25 (m, 4H), 3.19 (s, 3H), 2.48 (s, 3H).
A-57 CDCI3: δ 7.39 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2H), 7.17 (s, 1 H), 6.97 (d, J = 8.4 Hz, 2H), 3.38 (d, J = 15.2 Hz, 1 H), 3.27 (q, J = 9.6 Hz, 3H), 3.18 (s, 3H), 2.48 (s, 3H).
A-58 CDCI3: δ 7.40 (s, 1 H), 7.17 (s, 1 H), 7.10-7.05 (m, 4H), 4.01-3.99 (m, 1 H), 3.42-3.37 (m, 2H), 3.30-3.22 (m, 3H), 2.49 (s, 3H), 1.10 (t, J = 7.2 Hz, 3H).
A-59 CDCI3: δ 8.53 (s, 1 H), 7.54 (bs, 1 H), 7.40 (d, J = 8.4 Hz, 2H), 7.28-7.26 (m, 2H), 7.16 (s, 1 H), 3.80 (s, 2H), 3.44 (q, J = 9.6 Hz, 2H), 2.36 (s, 3H).
A-60 CDCI3: δ 8.51 (s, 1 H), 7.68 (d, J = 8.0 Hz, 2H), 7.54 (bs, 1 H), 7.49 (d, J = 8.4 Hz, 2H), 7.18 (s, 1 H), 3.85 (s, 2H), 3.44 (q, J = 9.6 Hz, 2H), 2.36 (s, 3H).
A-61 CDCI3: δ 8.52 (s, 1 H), 7.55 (bs, 1 H), 7.39 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.17 (s, 1 H), 3.76 (s, 2H), 3.44 (q, J = 9.6 Hz, 2H), 2.36 (s, 3H).
A-62 CDCI3: δ 8.53 (s, 1 H), 7.71 (d, J = 8.0 Hz, 2H), 7.52 (bs, 1 H), 7.43 (d, J = 8.0 Hz, 2H), 7.16 (s, 1 H), 3.82 (s, 2H), 3.44 (q, J = 9.6 Hz, 2H), 2.36 (s, 3H). A-63 CDCI3: δ 8.47 (d, J = 7.6 Hz, 1 H), 7.60-7.52 (m, 3H), 7.41 (d. J = 8.4 Hz, 2H), 7.26-7.21 (m, 4H), 6.95-6.90 (m, 1 H), 3.71 (s, 2H), 3.37 (q, J = 9.8 Hz, 2H), 2.40 (s, 3H).
A-64 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 8.44 (s, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 7.41 (d, J = 8.4 Hz, 2H), 7.31 (bs, 1 H), 7.20 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.8 Hz, 1 H), 6.94 (d, J = 11.6 Hz, 1 H), 3.79 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-65 CDCI3: δ 8.51 (d, J = 8.0 Hz, 1 H), 7.65-7.60 (m, 3H), 7.48-7.35 (m, 5H), 7.32 (bs, 1 H), 6.91 (d, J = 11.6 Hz, 2H), 3.81 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-66 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.30 (bs, 1 H), 7.11 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 11.2 Hz, 1 H), 6.82-6.78 (m, 1 H), 3.81 (s, 2H), 3.38 (q, J = 9.7 Hz, 2H), 2.40 (s, 3H).A-67 CDCI3: δ 8.52 (d, J = 8.0 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.41-7.21 (m, 5H), 6.92 (d, J = 11.2 Hz, 1 H), 3.82 (s, 2H), 3.39 (q, J = 9.7 Hz, 2H), 2.41 (s, 3H), 2.37 (s, 3H).
A-68 CDCI3: δ 8.52 (d, J = 8.0 Hz, 1 H), 7.50-7.47 (m, 3H), 7.41 (d, J = 8.0 Hz, 2H), 7.35-7.29 (m, 4H), 6.92 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-69 CDCI3: δ 8.49 (d, J = 7.6 Hz, 1 H), 7.26 (bs, 1 H), 7.22-7.51 (m, 4H), 6.89 (d, J = 11.6 Hz, 1 H), 3.72 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.39 (s, 3H), 2.38 (s, 3H).
A-70 CDCI3: δ 8.49 (d, J = 8.0 Hz, 1 H), 7.28-7.12 (m, 5H), 6.99 (d, J = 11.2 Hz, 1 H), 3.73 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.67 (q, J = 7.6 Hz, 2H), 2.39 (s, 3H), 1.25 (m, 3H).
A-71 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.28-7.22 (m, 5H), 6.89 (d, J = 11.6 Hz, 1 H), 3.73 (s, 2H), 3.38 (q, J = 9.7 Hz, 2H), 2.62 (t, J = 8.0 Hz, 2H), 2.39 (s, 3H), 1.66-1.58 (m, 2H), 1.28-1.36 (m, 4H), 0.91-0.80 (m, 3H).A-72 CDCI3: δ 7.23 (d, J = 7.6 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 10.4 Hz, 1 H), 6.94 (d, J = 8.4 Hz, 2H), 3.46-3.33 (m, 2H), 3.26-3.19 (m, 5H), 2.50 (s, 3H), 2.45 (s, 3H).
A-73 CDCI3: δ 7.57 (s, 1 H), 7.53 (d, J = 8.0 Hz, 2H), 7.22 (s, 1 H), 7.12 (d, J = 8.4 Hz, 2H), 3.45-3.26 (m, 4H), 3.19 (s, 3H), 2.48 (s, 3H).
A-74 CDCI3: δ 7.56 (s, 1 H), 7.13 (d, J = 8.4 Hz, 2H), 7.08 (s, 1 H), 6.95 (d, J = 8.4 Hz, 2H), 3.42-3.38 (m, 1 H), 3.27-3.19 (m, 3H), 3.17 (s, 3H), 2.46 (s, 3H), 2.45 (s, 3H).
A-75 CDCI3: δ 8.50 (s, 1 H), 7.72 (d, J = 8.0 Hz, 2H), 7.50 (bs, 1 H), 7.44 (d, J = 8.0 Hz, 2H), 7.32 (s, 1 H), 3.83 (s, 2H), 3.45 (q, J = 9.4 Hz, 2H), 2.35 (s, 3H).
A-76 CDCI3: δ 8.478 (d, J = 7.6 Hz, 1 H), 7.242-7.298 (m, 5H), 6.911 (d, J = 11.6 Hz, 1 H), 3.719 (s, 2H), 3.373 (q, J = 9.6 Hz, 2H), 2.497 (s, 3H), 2.398 (s, 3H).
A-77 CDCI3: δ 8.50 (s, 1 H), 7.58 (bs, 1 H), 7.32-7.29 (m, 5H), 3.74 (s, 2H), 3.46 (q, J = 9.6 Hz, 2H), 2.50 (s, 3H), 2.35 (s, 3H).
A-78 CDCI3: δ 7.16 (d, J = 7.6 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 10.0 Hz, 1 H), 6.93 (d, J = 8.0 Hz, 2H), 3.76-3.62 (m, 2H), 3.41 (d, J = 14.8 Hz, 1 H), 3.30 (d, J = 14.8 Hz, 1 H), 3.20 (q, J = 9.6 Hz, 2H), 2.51 (s, 3H), 2.45 (s, 3H), 1.08 (t, J = 7.2 Hz, 3H).
A-79 CDCI3: δ 7.95 (d, J = 7.6 Hz, 1 H), 7.40 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 8.90 (d, J = 9.2 Hz, 1 H), 8.75 (bs, 1 H), 3.75 (s, 2H), 3.50 (q, J = 9.6 Hz, 2H), 1.93 (s, 3H).
A-80 CDCI3: δ 7.98 (d, J = 7.6 Hz, 1 H), 7.40 (d, J = 8.4 Hz, 2H), 7.29-7.27 (m, 2H), 8.90 (d, J = 9.2 Hz, 1 H), 8.75 (bs, 1 H), 3.78 (s, 2H), 3.39 (q, J = 9.6 Hz, 2H), 1.98 (s, 3H).
A-81 CDCI3: δ 7.92 (d, J = 6.8 Hz, 1 H), 7.69 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 9.6 Hz, 1 H), 6.75 (bs, 1 H), 3.83 (s, 2H), 3.39 (q, J = 9.6 Hz, 2H), 2.02 (s, 3H).
A-82 CDCI3: δ 7.51 (d, J = 8.4 Hz, 2H), 7.40 (s, 1 H), 7.21 (s, 1 H), 7.17 (d, J = 8.4 Hz, 2H), 3.43 (d, J = 16.0 Hz, 1 H), 3.36 (d, J = 15.6 Hz, 1 H), 3.30-3.20 (m, 2H), 3.17 (s, 3H), 2.48 (s, 3H).
A-83 CDCI3: δ 7.50 (d, J = 8.0 Hz, 2H), 7.42 (s, 1 H), 7.16 (d, J = 8.4 Hz, 2H), 7.14 (s, 1 H), 4.05-3.96 (m, 1 H), 3.47-3.31 (m, 3H), 3.23 (q, J = 9.4 Hz, 2H), 2.49 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H).
A-84 CDCI3: δ 8.00 (d, J = 8.4 Hz, 1 H), 7.72 (d, J = 7.6 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 9.6 Hz, 1 H), 6.74 (bs, 1 H), 3.81 (s, 2H), 3.39 (q, J = 9.4 Hz, 2H), 1.96 (s, 3H).
A-85 CDCI3: δ 7.56 (s, 1 H), 7.20 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.56 (s, 1 H), 4.07-3.96 (m, 1 H), 3.25-3.37 (m, 2H), 3.08-2.97 (m, 2H), 2.46 (s, 3H), 1.37 (t, J = 6.8 Hz, 3H), 1.06 (t, J = 7.2 Hz, 3H). A-86 CDCI3: δ 7.83 (d, J = 8.0 Hz, 1 H), 7.27-7.24 (m, 3H), 6.98 (d, J = 8.4 Hz, 1 H), 6.86 (d, J = 8.0 Hz, 1 H), 4.14-3.97 (m, 1 H), 3.92-3.49 (m, 2H), 3.05 (s, 3H), 2.38 (s, 3H), 1.25 (d, J = 6.8 Hz, 3H).
A-87 CDCI3: δ 7.20-7.09 (m, 3H), 6.94-6.75 (m, 3H), 3.91-3.30 (m, 4H), 3.08-3.04 (m, 1 H), 3.52-3.49 (m, 3H), 1.37-1.35 (m, 3H), 1.05 (t, J = 6.8 Hz, 3H).
A-88 CDCI3: δ 7.56 (s, 1 H), 7.20 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H), 6.68 (s, 1 H), 3.34-3.29 (m, 1 H), 3.15 (s, 3H), 3.05 (q, J = 9.4 Hz, 2H), 2.44 (s, 3H), 1.38 (d, J = 6.8 Hz, 3H).
A-89 CDCI3: 8.48 (s, 1 H), 7.50 (bs, 1 H), 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.8 Hz, 3H), 3.71 (q, J = 7.2 Hz, 1 H), 3.46 (q, J = 9.6 Hz, 2H), 2.35 (s, 3H), 1.62 (d, J = 6.8 Hz, 3H).
A-90 CDCI3: δ 8.48 (d, J = 8.0 Hz, 1 H), 7.36 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.18 (bs, 1 H), 6.91 (d, J = 11.6 Hz, 1 H), 3.71 (q, J = 7.2 Hz, 1 H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H), 1.59 (d, J = 6.8 Hz, 3H).
A-91 CDCI3: δ 8.50 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.4 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 10.0 Hz, 1 H), 3.68-3.40 (m, 4H), 3.25-3.17 (m, 2H), 2.51 (s, 2H), 1.50-1.41 (m, 3H), 0.90-0.84 (m, 3H).
A-92 CDCI3: δ 7.49 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 10.0 Hz, 1 H), 3.73-3.66 (m, 2H), 3.62-3.54 (m, 2H), 3.25-3.18 (m, 2H), 2.52 (s, 3H). 1.46-1.41 (m, 2H) 1.32-1.22 (m, 2H), 0.862 (t, J = 7.6 Hz, 3H)
A-93 CDCI3: δ 7.63 (d, J = 3.0 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 2H), 7.36(s, 1 H), 7.30 (d, J = 7.2 Hz, 1 H), 7.13-7.08 (m, 3H), 3.53-3.42 (m, 2H), 3.26-3.20 (m, 5H), 2.52(s, 3H).
A-94 CDCI3: δ 7.63 (d, J = 2.4 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.40-7.36 (m, 3H), 7.24 (d, J = 8.4 Hz, 1 H), 7.12-7.09 (m, 3H), 3.78-3.65 (m, 2H), 3.50-3.37 (m, 2H), 3.25-3.17 (m, 2H), 2.52 (s, 3H). 1.10 (t, J = 7.2 Hz, 3H).
A-95 CDCI3: δ 7.55 (d, J = 7.6 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.42(t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1 H),7.28(s,1 H),7.14-7.06 (m, 3H), 3.55-3.42 (m, 2H), 3.24(s, 3H), 3.16 (s, 2H), 2.51 (s, 3H).
A-96 CDCI3: δ 7.56 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.42 (t, J = 7.2 Hz, 2H), 7.33 (d, J = 7.6 Hz, 1 H),7.20(d, J = 7.6 Hz, 1 H), 7.09(d, J = 8.4 Hz, 3H),3.80-3.65 (m, 2H), 3.51-3.37 (m, 2H), 3.22-3.14 (m, 2H), 2.51 (s, 3H). 1.10(t, J = 7.6 Hz, 3H).
A-97 CDCI3: δ 7.45-7.53 (m, 2H), 7.29 (s, 1 H), 7.18-7.06 (m, 3H), 6.90-6.72 (m, 1 H), 5.06-4.84 (m, 1 H), 3.59- 3.37 (m, 1 H), 3.01-2.87 (m, 2H), 2.49 (s, 3H), 2.18-1.90 (m, 2H).
A-98 CDCI3: δ 7.50 (d, J = 8.0 Hz, 2H), 7.15-7.10 (m, 4H), 4.97 (m, 1 H), 3.93-3.44 (m, 2H), 3.21-3.14 (m, 2H), 2.53 (s, 3H), 1.10 (d, J = 6.8 Hz, 3H), 0.98 (d, J = 6.8 Hz, 3H).
A-99 CDCI3: δ 7.99 (d, J = 7.2 Hz, 1 H), 7.62 (t, J = 7.2 Hz, 4H), 7.45 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 9.2 Hz, 1 H), 6.84 (s, 1 H), 3.83 (s, 2H), 3.43-3.36 (m, 2H), 1.98 (s, 3H).
A-100 CDCI3: δ 7.99 (d, J = 7.2 Hz, 1 H), 7.73 (s, 4H), 7.67 (d, J = 7.6 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 9.2 Hz, 1 H), 6.84 (bs, 1 H), 3.84 (s, 2H), 3.43-3.36 (m, 2H), 1.99 (s, 3H).
A-101 CDCI3: δ 8.51 (d, J = 9.2 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.53 (d, J = 7.6 Hz, 1 H), 7.32 (s, 1 H), 6.98 (d, J = 8.8 Hz, 1 H), 6.86(d, J = 12.0 Hz, 1 H), 3.64 (s, 2H), 3.36-3.25 (m, 2H), 2.37 (s, 3H).
A-102 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.59-7.54 (m, 4H), 7.41 (d, J = 8.0 Hz, 2H), 7.31 (bs, 1 H),7.14 (t, J = 8.8 Hz, 2H), 6.92 (d, J = 11.6 Hz, 1 H), 3.80 (s, 2H), 3.42-3.34 (m, 2H), 2.40 (s, 3H).
A-103 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.32 (bs, 1 H), 7.14 (t, J = 8.8 Hz, 2H), 6.92 (d, J = 11.6, 1 H), 3.86 (s, 3H), 3.79 (s, 2H), 3.15-3.34 (m, 2H) 2.40 (s , 3H) .
A-104 CDCI3: δ 7.61 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.4 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.44 (d, J = 7.6, 4H), 7.31 (bs, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.34-3.34 (m, 2H), 2.40 (s, 3H).A-105 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.73 (d, J = 14.4 Hz, 2H), 7.61 (d, J = 8.0 Hz, 3H), 7.46 (d, J = 8.0 Hz, 2H), 7.30 (bs, 1 H), 6.93 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.34-3.41 (m, 2H) 2.41 (s, 3H).
A-106 CDCI3: δ 8.53 (d, J = 8.0 Hz, 1 H), 7.51 (d, J = 8.0 Hz, 2H), 7.45-7.36 (m, 6H), 7.19-7.12 (m, 1 H), 6.92 (d, J = 11.2 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-107 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.84 (s, 1 H), 7.77 (d, J = 7.6 Hz, 1 H), 7.63 (t, J = 7.6 Hz, 3H), 7.57 (t, J = 7.6 Hz, 1 H),7.45 (d, J = 8.4 Hz, 2H), 7.33 (s, 1 H), 6.92 (d, J = 12.8 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.41 (s , 3H). A-108 CDCI3: δ 8.51 (d, J = 7.6 Hz, 1 H), 7.62 (d, J = 8.0 Hz, 2H), 7.44-7.36 (m, 4H), 7.31-7.26 (m, 2H), 7.07-7.04 (m, 1 H), 6.92 (d, J = 11.6 Hz, 1 H), 3.81 (s, 2H), 3.38 (q, J = 8.8 Hz, 2H), 2.40 (s, 3H).
A-109 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 6.8 Hz, 2H), 7.47-7.41 (m, 3H), 7.34-7.31 (m, 2H), 7.26-7.14 (m, 2H), 6.92 (d, J = 11.2 Hz, 1 H), 3.81 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-110 CDCI3: δ 7.85 (s, 1 H), 7.64 (d, J = 6.4 Hz, 1 H), 7.55 (d, J = 8.4 Hz, 1 H), 7.44 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 10.4 Hz, 1 H), 3.54-3.43 (m, 2H), 3.28-3.24 (m, 5H), 2.52 (s, 3H).
A-111 CDCI3: δ 7.69-7.65 (m, 2H), 7.57-7.53 (m, 1 H), 7.49-7.44 (m, 1 H), 7.32 (s, 1 H), 7.29 (s, 2H), 7.09 (d, J = 6.8 Hz, 2H), 3.57-3.48 (m, 2H), 3.29-3.22 (m, 5H), 2.51 (s, 3H).
A-112 CDCI3: δ 7.58 (d, J = 8.0 Hz, 2H), 7.19-7.11 (m, 4H), 3.75-3.83 (m, 1 H), 3.70-3.66 (m, 1 H), 3.52-3.40 (m, 2H), 3.27-3.20 (m, 2H), 2.53 (s, 3H), 2.15-2.09 (m, 2H), 1.79-1.71 (m, 2H).
A-113 CDCI3: δ 8.52 (d, J = 8.0 Hz, 1 H), 7.46-7.40 (m, 4H), 7.34-7.30 (m, 2H), 7.25-7.22 (m, 1 H), 7.08-7.03 (m, 1 H), 6.93 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-114 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 1.6 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H), 7.57-7.61 (m, 3H), 7.45 (d, J = 8.0 Hz, 2H), 7.31 (bs, 1 H), 6.93 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).A-115 CDCI3: δ 9.22 (s, 1 H), 8.97 (s, 2H), 8.50 (d, J = 8.0 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.33 (bs, 1 H), 6.94 (d, J = 11.6 Hz, 1 H), 3.84 (s, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-116 CDCI3: δ 8.69 (d, J = 7.6 Hz, 1 H), 8.42 (bs, 1 H), 7.68 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 11.2 Hz, 1 H), 4.31 (s, 2H), 3.39 (q, J = 9.6 Hz, 2H), 2.44 (s, 3H).
A-117 CDCI3: δ 7.54 (d, J = 8.4 Hz, 2H), 7.13-7.10 (m, 3H), 7.03 (d, J = 10.0 Hz, 1 H), 4.14-3.95 (m, 2H), 3.66 (s, 3H), 3.19-3.05 (m, 2H), 2.49 (s, 3H).
A-118 CDCI3: δ 7.45 (d, J = 8.0 Hz, 2H), 7.41-7.30 (m, 3H), 7.28 (s, 1 H), 7.23 (s, 1 H), 7.11 (d, J = 8.0 Hz, 2H), 7.04-7.00 (m, 1 H), 3.54-3.42 (m, 2H), 3.29-3.18 (m, 5H), 2.49 (s, 3H).
A-119 CDCI3: δ 7.37-7.32 (m, 5H), 7.19-7.12 (m, 2H), 7.09-7.06 (m, 2H), 7.04 (s, 1 H), 3.55-3.44 (m, 2H), 3.30- 3.19 (m, 5H), 2.51 (s, 3H).
A-120 CDCI3: δ 7.68 (d, J = 14.0 Hz, 2H), 7.57 (s, 1 H), 7.45 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1 H), 7.15 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 10.0 Hz, 1 H), 3.49 (m, 2H), 3.33-3.19 (m, 5H), 2.52 (s, 3H).
A-121 CDCI3: δ 7.79 (s, 1 H), 7.73 (d, J = 7.6 Hz, 1 H), 7.60-7.52 (m, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.31-7.27 (m, 1 H), 7.19-7.10 (m, 3H), 3.55-3.43 (m, 2H), 3.27-3.19 (m, 5H), 2.50 (s, 3H).
A-122 CDCI3: δ 7.48 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.29-7.24 (m, 1 H), 7.19-7.14 (m, 1 H), 7.09-7.06 (m, 2H), 6.96 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H), 3.53-3.40 (m, 2H), 3.23-3.16 (m, 5H), 2.48 (s, 3H).
A-123 CDCI3: δ 7.52-7.48 (m, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.29-7.27 (m, 1 H), 7.14-7.07 (m, 5H), 3.53-3.41 (m, 2H), 3.23-3.20 (m, 5H), 2.51 (s, 3H).
A-124 CDCI3: δ 7.43-7.38 (m, 3H), 7.33-7.27 (m, 2H), 7.14-7.06 (m, 5H), 3.52-3.44 (m, 2H), 3.24-3.17 (m, 5H), 2.48 (s, 3H).
A-125 CDCI3: δ 7.40-7.32 (m, 5H), 7.19-7.12 (m, 2H), 7.09-7.04 (m, 3H), 3.55-3.44 (m, 2H), 3.28-3.21 (m, 5H), 2.51 (s, 3H).
A-126 CDCI3: δ 8.46 (d, J = 8.0 Hz, 1 H), 8.26 (bs, 1 H), 7.62 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 11.2 Hz, 1 H), 3.40-3.33 (m, 2H), 2.44 (s, 3H).
A-127 CDCI3: δ 7.49-7.35 (m, 4H), 7.29-7.28 (m, 2H), 7.11-7.06 (m, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.50-3.33 (m, 2H), 3.28-3.21 (m, 5H), 2.51 (s, 3H).
A-128 CDCI3: δ 7.45 (d, J = 6.8 Hz, 1 H), 7.33-7.27 (m, 6H), 7.10-7.06 (m, 3H), 3.56-3.44 (m, 2H), 3.24-3.20 (m, 5H), 2.51 (s, 3H).
A-129 CDCI3: δ 7.30 (d, J = 8.4 Hz, 2H), 7.18-7.14 (m, 3H), 6.89 (d, J = 10.4 Hz, 1 H), 3.28-3.21 (m, 5H), 2.47 (s, 3H).
A-130 CDCI3: δ 7.21 (d, J = 7.6 Hz, 1 H), 7.06-7.03 (m, 3H), 6.91 (d, J = 8.0 Hz, 2H), 3.48-3.34 (m, 2H), 3.25-3.14 (m, 5H), 3.54-2.49 (m, 5H), 1.62-1.50 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H).
A-131 CDCI3: δ 7.69-7.67 (m, 1 H), 7.35 (d, J = 7.6 Hz, 1 H), 7.12 (d, J = 11.2 Hz, 1 H), 6.94-6.83 (m, 2H), 3.56- 3.30 (m, 2H), 3.35-3.12 (m, 5H), 2.54 (s, 3H). A-132 CDCI3: δ 7.50 (d, J = 7.6 Hz, 1 H), 7.22-7.14 (m, 1 H), 7.11 (d, J = 10.0 Hz, 1 H), 6.83 (t, J = 9.4 Hz, 2H), 3.45 (s, 2H), 3.35 (q, J = 9.4 Hz, 2H), 3.25 (s, 3H), 2.51 (s, 3H).
A-133 CDCI3: δ 7.19 (d, J = 7.6 Hz, 1 H), 7.06 (d, J = 7.6 Hz, 3H), 6.92 (d, J = 8.0 Hz, 2H), 3.48-3.34 (m, 2H), 3.21-3.13 (m, 5H), 2.59 (q, J = 7.6 Hz, 2H), 2.50 (s, 3H), 1.24-1.14 (m, 3H).
A-134 CDCI3: δ 7.86-7.75 (m, 2H), 7.50-7.37 (m, 1 H), 7.22 (d, J = 8.0 Hz, 2H), 6.98-6.08 (m, 1 H), 3.37-3.25 (m, 2H), 3.21-3.17 (m, 5H), 2.55-2.41 (m, 5H), 1.17-1.13 (m, 3H).
A-135 CDCI3: δ 8.05 (s, 1 H), 7.82-7.76 (m, 2H), 7.18-7.16 (m, 1 H), 7.16-7.12 (m, 1 H), 6.94-6.89 (m, 1 H), 3.73- 3.58 (m, 2H), 3.40-3.36 (m, 2H), 3.22 (s, 3H), 3.10-2.98 (m, 3H), 2.47 (s, 3H).
A-136 CDCI3: δ 8.46 (d, J = 8.0 Hz, 1 H), 7.96 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.32 (s, 1 H), 6.95 (d, J = 11.6 Hz, 1 H), 3.85 (s, 2H), 3.40-3.32 (m, 2H), 3.06 (s, 3H), 2.42 (s, 3H).
A-137 CDCI3: δ 8.44 (d, J = 7.6 Hz, 1 H), 8.31 (s, 1 H), 7.82 (d, J = 8.4 Hz, 2H), 7.78 (s, 1 H), 7.76 (s, 1 H), 7.03 (d, J = 11.2 Hz, 1 H), 3.40-3.33 (m, 2H), 2.45 (s, 3H).
A-138 CDCI3: δ 7.58 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1 H), 6.84 (d, J = 10.0 Hz, 1 H), 3.32-3.20 (m, 5H), 2.47 (s, 3H).
A-139 CDCI3: δ 7.53 (d, J = 12.4 Hz, 1 H), 7.49 (d, J = 6.4 Hz, 1 H), 7.16-7.12 (m, 2H), 7.07 (d, J = 8.4 Hz, 1 H), 6.91 (d, J = 8.4 Hz, 1 H), 3.43-3.35 (m, 2H), 3.18 (d, J = 9.6 Hz, 2H), 2.40 (s, 3H), 1.41 (d, J = 6.4 Hz, 3H).A-140 CDCI3: δ 8.52 (d, J = 8.0 Hz, 1 H), 7.50 (d, J = 1.6 Hz, 1 H), 7.46-7.40 (m, 4H), 7.30 (d, J = 2.0 Hz, 1 H), 7.31 -7.26 (m, 2H), 6.93 (d, J = 11.6 Hz, 1 H), 3.82 (s, 2H), 3.38 (q, J = 10.0 Hz, 2H), 2.41 (s, 3H).
A-141 CDCI3: δ 8.50 (d, J = 8.0 Hz, 1 H), 7.54 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 7.6 Hz, 2H), 7.29 (bs, 1 H), 7.21-7.16 (m, 2H), 6.93 (d, J = 11.6 Hz, 1 H), 3.81 (d, J = 4.8 Hz, 2H), 3.37 (q, J = 9.6 Hz, 2H), 2.41 (s, 3H).
A-142 CDCI3: δ 8.49 (q, J = 4.8 Hz, 1 H), 7.69-7.40 (m, 5H), 7.30 (bs, 1 H), 7.26-7.21 (m, 3H), 6.99-6.90 (m, 1 H), 3.81 (d, J = 6.8 Hz, 2H), 3.41-3.27 (m, 2H), 2.40 (s, 3H).
A-143 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 1.6 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.35 (t, J = 1.6 Hz, 1 H), 7.29 (bs, 1 H), 6.92 (d, J = 11.6 Hz, 1 H), 3.81 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 3H).
A-144 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.61 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.34 (d, J = 8.4 Hz, 3H), 6.91 (d, J = 11.6 1 H), 3.80 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.53 (s, 3H), 2.40 (s, 3H).
A-145 CDCI3: δ 8.50 (d, J = 7.6 Hz, 1 H), 7.62 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.32 (bs, 1 H), 7.27-7.26 (m, 2H), 6.91 (d, J = 11.6 1 H), 3.80 (s, 2H), 3.38 (q, J = 9.6 Hz, 2H), 2.40 (s, 6H).A-146 CDCI3: δ 7.48 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.27 (s, 1 H), 7.08 (t J = 5.6 Hz, 3H), 3.50 (s, 1 H), 3.45 (s, 1 H), 3.23 (s, 3H), 3.20 (d, J = 10.0 Hz, 2H), 2.52 (s, 6H).
A-147 CDCI3: δ 7.42 (q, J = 6.5 Hz, 4H), 7.32 (s, 2H), 7.14 (s, 3H), 3.23 (m, 7H), 2.52 (s, 3H).
A-148 CDCI3: δ 7.56 (d, J = 6.0 Hz, 1 H), 7.44-7.40 (m, 2H), 7.37-7.32 (m, 2H), 7.29-7.26 (m, 1 H), 7.12-7.06 (m, 2H), 6.91 (d, J = 8.4 Hz, 2H), 3.49-3.28 (m, 2H), 3.28-3.18 (m, 5H), 2.51 (s, 3H).
A-149 CDCI3: δ 7.45 (d, J = 8.0 Hz, 4H), 7.23 (d, J = 8.4 Hz, 3H), 7.09-7.06 (m, 3H), 3.47 (m, 2H), 3.23 (s, 3H), 3.20-3.16 (m, 2H), 2.50 (s, 3H), 2.39 (s, 3H).
Below are Preparation Examples in which the "parts refers to "parts by weight." Preparation Example 1: Emulsions
10 parts of each compound of the invention was dissolved in 45 parts of Solvesso 150 and 35 parts of N- methylpyrrolidone . 10 parts of an emulsifier (trade name: Sorpol 3005X, produced by Toho Chemical Industry Co., Ltd.) was added thereto. The mixtures were mixed by stirring to give 10% emulsions .
Preparation Example 2 : Wettable powders
20 parts of each compound of the invention was added to a mixture of 2 parts of sodium lauryl sulfate, 4 parts of sodiumlignin sulfonate, 20 parts of fine powder of synthetic hydrated silicon dioxide, and 54 parts of clay. The mixtures were mixed by stirring with a juice mixer to give 20% wettable powders
Preparation Example 3 : Granules
2 parts of sodium dodecylbenzenesulfonate, 10 parts of bentonite, and 83 parts of clay were added to 5 parts of each compound of the invention, and each mixture was sufficiently mixed by stirring. An appropriate amount of water was added thereto. The resulting mixtures were further stirred and granulated with a granulator. The granules were air-dried to give 5% granules. Preparation Example 4 : Dusts
1 part of each compound of the invention was dissolved in an appropriate amount of acetone. 5 parts of fine powder of synthetic hydrated silicon dioxide, 0.3 parts of acidic isopropyl phosphate (PAP), and 93.7 parts of clay were added thereto. The mixtures were mixed by stirring with a juice mixer, and acetone was removed by evaporation to give 1% dust.
Preparation Example 5: Flowable preparations
20 parts of each compound of the invention was mixed with 20 parts of water containing 3 parts of polyoxyethylene tristyrylphenyl ether phosphoric acid ester triethanolamine and 0.2 parts of Rhodorsil 426R. The mixtures were subjected to wet pulverization with a DYNO-Mill, and mixed with 60 parts of water containing 8 parts of propylene glycol and 0.32 parts of xanthan gum to give 20% suspensions in water. Test Examples are given below to demonstrate that the compounds of the invention are useful as an active ingredient for miticides .
Test Example 1 (Miticidal test on Two-Spotted Spider Mites)
A piece of non-woven fabric (4.5x5.5cm) was suspended inside a plastic cup through an incision made in the lid of the plastic cup. After water was poured into the cup, the cup was covered with the lid. A kidney bean leaf (about 3.5x4.5 cm) was then placed on the sufficiently soaked, non-woven fabric. Another kidney bean leaf with two-spotted spider mites (about 30 mite samples) was placed on top of the first leaf, and the fabric and leaves were placed in a thermostatic chamber having a temperature of 25±2° C and a humidity of 40%.
Miticidal formulations containing the compound of the invention (200 ppm) were prepared by adding an aqueous solution (100 ppm) of Sorpol 355 (manufactured by Tobo Kagaku Co. Ltd.) to a methanol solution of the compound of the invention.
These miticidal formulations were sprayed onto the leaves, and the leaves were air-dried and placed in a thermostatic chamber (25±2° C and a humidity of 50%) . The mortality rate of the two- spotted spider mites was calculated after 2 days.
The compounds that exhibited the mortality rate of 50% or more are as follows:
Compound Nos.: 1A-2, 1A-5, 1A-8, 1A-12, 1A-13, 1A-14, 1A-15, 1A- 20, 1A-23, 1A-24, 1A-27, 1A-28, 1A-30, 1A-33, 1A-42, 1A-43, 1A-45, 1A-46, 1A-47, 1A-48, 1A-49, 1A-50, 1A-51, 1A-52, 1A-53, 1A-54, 1A-55, 1A-56, 1A-57, 1A-58, 1A-59, 1A-60, 1A-62, 1A-63, 1A-65, 1A-67, 1A-68, 1A-72, 1A-73, 1A-74, 1A-75, 1A-76, 1A-77, 1A-78, 1A-82, 1A-83, 1A-85, 1A-86, 1A-87, 1A-88, 1A-90, 1A-91, 1A-92, 1A-93, 1A-94, 1A-95, 1A-96, 1A-97, 1A-103, 1A-104, 1A-107, 1A-108, 1A-109, lA-111, 1A-112, 1A-113, 1A-114, 1A-116, 1A-117, 1A-118, 1A-119, 1A-120, 1A-121, 1A-122, 1A-123, 1A-126, 1A-127, 1A-128. Test Example 2 (Ovicidal test on Two-Spotted Spider Mites)
A piece of non-woven fabric (4.5x5.5cm) was suspended inside a plastic cup through an incision made in the lid of the plastic cup. After water was poured into the cup, the cup was covered with the lid. A kidney bean leaf (about 3.5x4.5 cm) was then placed on the sufficiently soaked, non-woven fabric. Twenty female adults of two-spotted spider mite were placed on the top of the leaf, and the fabric and leaf were placed in a thermostatic chamber having a temperature of 25±2° C and a humidity of 40% and 16L8D.
The next day, after the number of the female adults was adjusted once more to 20, 2 ml of a miticidal formulation containing the compound of the invention (200 ppm) prepared in the same manner as in test example 1 was sprayed onto the leaf, and the leaf was air-dried and placed in a thermostatic chamber (25±2° C and a humidity of 50%) . The ovicidal rate of the two-spotted spider mites was calculated 6 days after the spraying of the miticidal formulation. The compounds that exhibited a mortality of 50% or more at 500 ppm are as follows:
Compound Nos . : 1A-2, 1A-8, 1A-12, 1A-13, 1A-14, 1A-20, 1A-23, 1A- 27, 1A-33, 1A-42, 1A-43, 1A-47, 1A-48, 1A-49, 1A-50, 1A-51, 1A-52, 1A-53, 1A-54, 1A-55, 1A-56, 1A-57, 1A-58, 1A-59, 1A-60, 1A-61, 1A-63, 1A-65, 1A-67, 1A-68, 1A-69, 1A-70, 1A-71, 1A-72, 1A-73, 1A-74, 1A-76, 1A-77, 1A-78, 1A-82, 1A-83, 1A-85, 1A-86, 1A-87, 1A-88, 1A-90, 1A-91, 1A-93, 1A-94, 1A-95, 1A-96.

Claims

[Claim 1]
A benzylamide compound represented by Formula
Figure imgf000069_0001
or a salt thereof,
wherein R1 represents Ci_6 alkyl or Ci-6 haloalkyl;
R2 and R3 are identical or different and each represent hydrogen, halogen, cyano, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl or C3-8 cycloalkyl Ci-6 alkyl;
R4 represents hydrogen, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, arylcarbonyl, aryloxycarbonyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-e haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, aryl, aryl Ci-6 alkyl, arylsulfonyl, arylsulfinyl, arylthio, or heterocyclic, all the substituents defined as R4 may optionally be further substituted; R5 and R6 are identical or different and each represent hydrogen, halogen, Ci-6 alkyl, or Ci-6 haloalkyl; R5 and R6, taken together with the carbon atom to which they bond, may bond to each other to form a 3- to 8-membered ring, via or not via at least one heteroatom;
R7, R8, R9, R10, and R11 are identical or different and each represent hydrogen, halogen, nitro, cyano, hydroxyl, formyl, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkoxy Ci-6 alkyl, Ci-6 haloalkoxy Ci-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl Ci-6 alkyl, Ci-6 alkylcarbonyl, Ci-6 haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, Ci-6 alkoxycarbonyl, Ci-6 haloalkoxycarbonyl, Ci-6 cyanoalkyl, Ci-6 cyanoalkoxy, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-e haloalkynyl, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, C3-8 cycloalkylsulfonyl, C3-8 cycloalkylsulfinyl, C3-8 cycloalkylthio, C3-8 cycloalkyl Ci-6 alkylsulfonyl, C3-8 cycloalkyl Ci-6 alkylsulfinyl, C3-8 cycloalkyl Ci-6 alkylthio, Ci-6 alkoxy Ci-6 alkylsulfonyl, Ci-6 alkoxy Ci-6 alkylsulfinyl, Ci-6 alkoxy Ci-6 alkylthio, C2-6 alkenyloxy, C2-6 haloalkenyloxy, C2-6 alkynyloxy, C2-6 haloalkynyloxy, Ci-6 alkylsulfonyloxy, Ci-6 haloalkylsulfonyloxy, Ci-6 alkylsulfinyloxy, Ci-6 haloalkylsulfinyloxy, carboxyl, OCN, SCN, SF5, substituted or unsubstituted amino, aryl, aryl Ci-6 alkyl, aryloxy, aryl Ci-6 alkoxy, arylsulfonyl, arylsulfinyl, arylthio, aryl Ci-6 alkylsulfonyl, aryl Ci-6 alkylsulfiny I , aryl Ci-6 alkylthio, heterocyclic, heterocyclic Ci-6 alkyl, or heterocyclic oxy, all of which may optionally be further substituted;
R7 and R8, R8 and R9, R9 and R10, or R10 and R11, taken together with the benzene ring to which they bond, may bond to each other to form a 3- to 8-membered ring via or not via at least one heteroatom;
X represents oxygen or sulfur; and
n represents an integer of 0 to 2.
[Claim 2]
The benzylamide compound or the salt thereof according to claim 1, wherein R1 is Ci-6 haloalkyl.
[Claim 3]
The benzylamide compound or the salt thereof according to claim 1 or 2, wherein R2 and R3 are identical or different and each represent halogen, cyano, or Ci-6 alkyl.
[Claim 4]
The benzylamide compound or the salt thereof according to any one of claims 1 to 3, wherein R is hydrogen, or Ci-6 alkyl,
[Claim 5]
The benzylamide compound or the salt thereof according to any one of claims 1 to 4, wherein R7, R8 , R9, R10, and R11 are identical or different and each represent hydrogen, halogen, nitro, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, Ci-6 alkylsulfonyl, Ci-6 haloalkylsulfonyl, Ci-6 alkylsulfinyl, Ci-6 haloalkylsulfinyl, Ci-6 alkylthio, Ci-6 haloalkylthio, substituted or unsubstituted amino, aryl, or heterocyclic.
[Claim 6]
A method for producing the benzylamide compound or the salt thereof according to any one of claims 1 to 5, comprising at least one step selected from the group consisting of following steps (d) and (e) :
step (d) : obtaining a sulfide compound represented by Formula (1-1) by reacting a thiol compound represented by Formula (6) with an alkylating reagent represented by Formula (7) :
Figure imgf000071_0001
(6) (1-1 ) wherein, R1, R2 , R3, R4 , R5, R6, R7 , R8 , R9, R10, R11, and X are as defined above and G represents a leaving group; and
step (e) : obtaining a benzylamide compound represented by Formula (1-2) by reacting the sulfide compound represented by Formula (1-1) with an oxidizin a ent:
Figure imgf000071_0002
wherein, R1, R2 , R3, R4 , R5, R6, R7 , R8 , R9, R10, R11, and X are as defined above, n' represents 1 or 2.
[Claim 7]
The method for producing the benzylamide compound and the salt thereof according to claim 6, further comprising the following step (c) :
step (c) : obtaining a thiol compound represented by Formula (6) by reacting a sulfonylchloride compound represented b Formula (5) with a reducing agent:
Figure imgf000072_0001
defined above.
[Claim 8]
The method for producing the benzylamide compound and the salt thereof according to claim 7, further comprising the following step (b) :
step (b) : obtaining the sulfonylchloride compound represented by Formula (5) by chlorosulfonylating an amide com ound represented by Formula (4) :
Figure imgf000072_0002
wherein, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above.
[Claim 9]
The method for producing the benzylamide compound and the salt thereof according to claim 8, further comprising the following step (a) : step (a) : obtaining the amide compound represented by Formula (4) by reacting an aniline compound represented by Formula (2) with a benzylcarbonyl compound represented by Formula (3) :
Figure imgf000073_0001
wherein, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and X are as defined above, and Y represents a leaving group or hydroxyl group
[Claim 10]
A pesticide containing the benzylamide compound or the salt thereof of according to any one of claims 1 to 5.
[Claim 11]
A miticide containing the benzylamide compound or the salt thereof of according to any one of claims 1 to 5.
PCT/IB2016/055523 2016-07-18 2016-09-16 Novel benzylamide compound, method for producing the same, and miticide WO2018015797A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007131680A1 (en) 2006-05-16 2007-11-22 Bayer Cropscience Ag Insecticidal benzamidines
JP2011042611A (en) 2009-08-20 2011-03-03 Nippon Soda Co Ltd Acaricide and new urea compound
WO2012176856A2 (en) 2011-06-24 2012-12-27 Ishihara Sangyo Kaisha, Ltd. Pesticide
EP3002279A1 (en) 2014-10-02 2016-04-06 Bayer CropScience AG Method for the preparation of 3- (5-aminotriazolyl) sulfide derivatives

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007131680A1 (en) 2006-05-16 2007-11-22 Bayer Cropscience Ag Insecticidal benzamidines
JP2011042611A (en) 2009-08-20 2011-03-03 Nippon Soda Co Ltd Acaricide and new urea compound
WO2012176856A2 (en) 2011-06-24 2012-12-27 Ishihara Sangyo Kaisha, Ltd. Pesticide
EP3002279A1 (en) 2014-10-02 2016-04-06 Bayer CropScience AG Method for the preparation of 3- (5-aminotriazolyl) sulfide derivatives

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BORGNA P ET AL: "PHYTOTOXICITY AND INHIBITORY EFFECT ON THE HILL REACTION OF ALPHA SUBSTITUTED PHENYLACETANILIDES", IL FARMACO, vol. 28, no. 10, 1 January 1973 (1973-01-01), ELSEVIER FRANCE * EDITIONS SCIENTIFIQUES ET MEDICALES, FR, pages 800 - 810, XP009007676, ISSN: 0014-827X *
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1 January 1974 (1974-01-01), P. BORGNA ET AL.: "Phytotoxicity and inhibition of the Hill reaction by m-alkylthioanilides", XP002767841, Database accession no. 1974:14701 *
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1 January 1992 (1992-01-01), T. MODENA ET AL.: "Plant growth regulating activities of 2-[2-(arylamino)-2-oxoethyl]benzoic acids", XP002767842, Database accession no. 1992:2233 *
DATABASE CHEMCATS [online] 31 May 2016 (2016-05-31), UORSY STOCK SCREENING COMPOUNDS: "PB2032928669", XP002767840, retrieved from STN Database accession no. 0686357814 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 18 March 2014 (2014-03-18), FCH GROUP, XP002767843, Database accession no. 1569725-93-4 *
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 3 April 2014 (2014-04-03), XP002767844, Database accession no. 1580123-30-3 *
RAMOS-HUNTER SUSAN J ET AL: "Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 23, no. 18, 18 July 2013 (2013-07-18), pages 5195 - 5198, XP028694508, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2013.07.002 *

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