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WO2014029708A1 - Methods of controlling insects - Google Patents

Methods of controlling insects Download PDF

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Publication number
WO2014029708A1
WO2014029708A1 PCT/EP2013/067184 EP2013067184W WO2014029708A1 WO 2014029708 A1 WO2014029708 A1 WO 2014029708A1 EP 2013067184 W EP2013067184 W EP 2013067184W WO 2014029708 A1 WO2014029708 A1 WO 2014029708A1
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WO
WIPO (PCT)
Prior art keywords
trifluoromethyl
alkyl
chloro
formula
phenyl
Prior art date
Application number
PCT/EP2013/067184
Other languages
French (fr)
Inventor
Myriem El Qacemi
Jérôme Yves CASSAYRE
Original Assignee
Syngenta Participations Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Syngenta Participations Ag filed Critical Syngenta Participations Ag
Publication of WO2014029708A1 publication Critical patent/WO2014029708A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2

Definitions

  • the present invention relates to a method of controlling insects, in particular diamondblack moth
  • GABA gamma-aminobutyric acid
  • GABA gamma- aminobutyric acid
  • the invention provides a method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula I
  • R 1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl
  • R is group X
  • X 2 is C-X 6 or nitrogen
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X 1 , X 3 and X 6 is not hydrogen;
  • A is selected from Al to A5
  • Y 1 is C-R 6 , CH or nitrogen
  • Y 2 and Y 3 are independently CH or nitrogen;
  • R 5 is hydrogen, halogen, cyano, nitro, NH 2 , Ci-C 4 alkyl, Ci-C 4 haloalkyl, C3-C 5 cycloalkyl, C 3 - C 5 halocycloalkyl, Ci-C 2 alkoxy, or Ci-C 2 haloalkoxy, preferably provided that when A is A3 or A4 R 5 is not hydrogen;
  • R 7 is C r C 4 alkyl
  • R 8 is Ci-C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkoxy(Ci-C 4 )alkyl, Ci-C 4 alkylthio(C r C 4 )alkyl, C r
  • R 9 is Ci-C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkyl-0-CH 2 -, Ci-C 4 haloalkyl-0-CH 2 -,C 3 -C 6 cycloalkyl, C 3 -
  • each Z is independently halogen, Ci-Ci 2 alkyl or Ci-Ci 2 alkyl substituted by one to five R 12 , nitro, Cp
  • Ci-Ci 2 haloalkylsulfinyl Ci-Ci 2 haloalkylsulfonyl, hydroxyl or thiol;
  • each R 12 is halogen, cyano, nitro, hydroxy, CpCgalkoxy-, Ci-Cghaloalkoxy-, mercapto, CpCgalkylthio-, or
  • k 0, 1,2 or 3.
  • the invention provides use of a compound of formula I for controlling and/or preventing insects from the genus Plutella in useful plants.
  • the insects may be resistant to other insecticides.
  • the invention provides a method for obtaining regulatory approval for the use of one or more of a compound of formula I to control insects from the genus Plutella, comprising at least one step of referring to, submitting or relying on biological data showing that said active ingredient reduces insect pressure.
  • a preferred species is Plutella xylostella.
  • the compounds of formula I are used to control insects from the genus Plutella in brassica crops.
  • Preventing insects in useful plants means for example preventing infestation of insects in useful plants.
  • the compounds of the invention may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
  • the compounds of the invention may contain one or more asymmetric carbon atoms, and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such. Reference to compounds of the invention also includes reference to salts and N-oxides.
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. Preferably at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • R 2 is 3,5-dichlorophenyl, 3,5-dichloro-4-fluorophenyl- or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
  • R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, most preferably R 5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl.
  • R 8 is C r C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 -
  • R 9 is C r C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 - Cgcycloalkyl, C 3 -C 6 cycloalkyl-CH 2 -, C r C 4 alkyl-S(0)-CH 2 -, Ci-C 4 alkyl-S(0 2 )-CH 2 -, more preferably C r Qalkyl, C r C 4 haloalkyl, C r C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl- CH 2 -, more preferably Ci-C 4 alkyl, Ci-C 4 haloalkyl or C 3 -C 4 cycloalkyl, more preferably methyl,
  • each Z is independently halogen, cyano, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy, or Ci-C 4 haloalkoxy, most preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
  • Each R 12 is preferably bromo, chloro, fluoro, methoxy, or methylthio, most preferably chloro, fluoro, or methoxy.
  • k is 0 or 1.
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. Preferably at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • R 2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is N
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is N
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH.
  • R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, more preferably R 5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, even more preferably hydrogen, chloro, bromo, methyl or trifluoromethyl, most preferably chloro, bromo, fluoro or methyl.
  • R 8 is C r C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 - Cgcycloalkyl, C 3 -C 6 cycloalkyl-CH 2 -, C r C 4 alkyl-S(0)-CH 2 -, Ci-C 4 alkyl-S(0 2 )-CH 2 -, more preferably C r C 4 alkyl, C r C 4 alkyl-0-CH 2 -, C r C 4 alkyl-S-CH 2 -, C r C 4 alkyl-SO-CH 2 -, C r C 4 alkyl-S0 2 -CH 2 -, C 3 - C 4 cycloalkyl, or C3-C 4 cycloalkyl-CH 2 -, more preferably R 8 is methyl, ethyl, n-propyl,
  • CH and R 1 is CF 3 .
  • Y 3 is CH.
  • R 8 methyl, ethyl, n-propyl, isopropyl, CH 3 -0-CH 2 -, CH 3 -S-CH 2 -, CH 3 -S(0)-CH 2 -, CH 3 -S0 2 -CH 2 -, cyclobutyl, cyclopropyl or cyclopropyl-CH 2 -, preferably n-propyl or cyclopropyl.
  • R 5 is chloro, bromo, fluoro or methyl
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. Preferably at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is N
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is N
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH.
  • R 7 is methyl
  • R 8 is C r C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 -
  • R 1 is CF 3 and R 7 is methyl.
  • R 7 is methyl and R 8 is methyl, ethyl, n-propyl, isopropyl, CH 3 -0-CH 2 -, CH 3 -S-CH 2 -, CH 3 -S(0)- CH 2 -, CH 3 -S0 2 -CH 2 -, cyclobutyl, cyclopropyl or cyclopropyl-CH 2 -, preferably n-propyl or cyclopropyl.
  • R 7 is methyl
  • R 8 is methyl, ethyl, n-propyl, isopropyl, CH 3 -0-CH 2 -, CH 3 -S-CH 2 -, CH 3 -S(0)-CH 2 -, CH 3 -S0 2 -CH 2 -, cyclobutyl, cyclopropyl or cyclopropyl-CH 2 -, preferably n-propyl or cyclopropyl
  • R 1 is CF 3
  • -C N-CH 2 - or - N-CH 2 -CH 2 -
  • Y 1 , Y 2 and Y 3 are CH.
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. Preferably at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is N
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is N
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH.
  • R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R 5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
  • R 5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R 5 is cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
  • each Z is independently halogen, cyano, Ci-C 4 alkyl, Ci-C 4 alkoxy, or Ci-C ihaloalkoxy, more preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
  • k is 0 or 1.
  • R 1 is CF 3
  • R 5 is cyano and k is 0 or k is 1
  • Z is cyano or trifluoromethyl.
  • Y 3 is CH, R 1 is CF 3 , and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
  • R 5 is cyano, k is 0 or 1 and Z is cyano or trifluoromethyl.
  • R 5 is cyano
  • R 1 is CF 3
  • Y 1 , Y 2 and Y 3 are CH
  • k is 0.
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. Preferably at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is N
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is N
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH.
  • R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R 5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
  • R 5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R 5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R 5 is cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
  • each Z is independently halogen, cyano, Ci-C 4 alkyl, Ci-C 4 alkoxy, or Ci-C ihaloalkoxy, more preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
  • k is 0 or 1 , more preferably 1.
  • Z is attached to the 4 position of the imidazole moiety as indicated below:
  • CH and R 1 is CF 3 .
  • Y 3 is CH and R 1 is CF 3 .
  • Y 3 is CH, R 1 is CF 3 , R 5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl and R 2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, and when k is 1, Z is attached to the 4 position of the imi
  • R 5 In another group of compounds of formula ID R 5 is cyano, k is 0 or 1 and Z is cyano or trifluoromethyl.
  • R 5 In another group of compounds of formula ID R 5 is cyano, k is 0 or 1 , preferably 1 , and Z is cyano or trifluoromethyl, and when k is 1 , Z is attached to the 4 position of the imidazole moiety.
  • the compound of formula I is a compound of formula IE
  • R 1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
  • X 1 , X 3 and X 6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen. More preferably X 1 , X 3 and X 6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X 1 , X 3 and X 6 are not hydrogen.
  • at least two of X 1 , X 3 and X 6 are chloro, bromo or trifluoromethyl.
  • R 2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyr
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is N
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is N
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is N
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH
  • Y 1 is CH
  • Y 2 is CH
  • Y 3 is CH.
  • R 9 is C r C 4 alkyl, C r C 4 haloalkyl, Ci-C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 - Cgcycloalkyl, C 3 -C 6 cycloalkyl-CH 2 -, C r C 4 alkyl-S(0)-CH 2 -, Ci-C 4 alkyl-S(0 2 )-CH 2 -, more preferably C r C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkyl-0-CH 2 -, C r C 4 haloalkyl-0-CH 2 -,C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl- CH 2 -, more preferably Ci-C 4 alkyl, Ci-C 4 haloalkyl or C 3 -C 4 cycloalkyl, more preferably methyl,
  • Y 1 is CH, Y 2 is CH, Y 3 is CH, or Y 1 is N, Y 2 is CH, Y 3 is CH, or Y 1 is N, Y 2 is N, Y 3 is CH, or Y 1 is CH, Y 2 is N, Y 3 is CH, or Y 1 is CH, Y 2 is CH, Y 3 is N.
  • Y 1 is CH, Y 2 is CH, and Y 3 is CH.
  • CH and R 1 is CF 3 .
  • Table 11 provides 304 compounds of formula la wherein R5 is hydrogen, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
  • Table 12 provides 304 compounds of formula la wherein R5 is methyl, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
  • Table 13 provides 304 compounds of formula la wherein R5 is trifluoromethyl, B1-B2-B3 is N-CH2- CH2, and R2 and R8 are as defined in Table P.
  • Table 14 provides 304 compounds of formula la wherein R5 is chloro, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
  • Table 15 provides 304 compounds of formula la wherein R5 is bromo, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
  • Table 18 provides 304 compounds of formula lb wherein B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
  • Table 21 provides 19 compounds of formula Ic wherein B 1-B2-B3 is N-CH2-CH2, and R2 is as defined in Table Q.
  • Table 26 provides 19 compounds of formula Id wherein k is CN, B1-B2-B3 is N-CH2-CH2 and R2 is as defined in Table Q.
  • Table 27 provides 19 compounds of formula Id wherein k is CF3, B1-B2-B3 is N-CH2-CH2 and R2 is as defined in Table Q.
  • Table 30 provides 114 compounds of formula le wherein B1-B2-B3 is N-CH2-CH2, and R2 and R9 are as defined in Table S.
  • the invention includes mixtures of compounds I* and I** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio.
  • the molar proportion of compound I** compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • the molar proportion of the compound of formula I* compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • Enantiomerically (or epimerically) enriched mixtures of formula I** are preferred.
  • Each compound disclosed in Tables 1 to 30 represents a disclosure of a compound according to the compound of formula I* and a compound according to the compound of formula I**.
  • group A2 may be group A2* or A2**.
  • the invention includes mixtures of compounds of formula I with A2 as A2* and A2** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio.
  • the molar proportion of formula I with A2 as A2* compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • the molar proportion of the compound of formula I with A2 as A2**, compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • Enantiomerically (or epimerically) enriched mixtures of formula I with A2 as A2** are preferred.
  • Each compound disclosed in Tables 16 to 18 represents a disclosure of I with A2 as A2* and a compound I with A2 as A2**.
  • Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I* with A2 as A2*.
  • Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I** with A2 as A2*.
  • Each compound 5 disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I* with A2 as A2**.
  • Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I** with A2 as A2**.
  • Enantiomerically (or epimerically) enriched mixtures of formula I** with A2 as A2** are preferred.
  • group A5 may be A5* or A5**
  • the invention includes mixtures of compounds of formula I with A5 as A5* and A5** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1 , e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio.
  • a molar ratio of 1 :99 to 99: 1 e.g. 10: 1 to 1 : 10
  • a substantially 50:50 molar ratio e.g. in an enantiomerically (or epimerically) enriched mixture of formula I with A5 as A5*
  • the molar proportion of formula I with A5 as A5* compared to the total amount of both enantiomers (or epimers) is for example
  • the molar proportion of the compound of formula I with A5 as A5**, compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%.
  • Compounds of formula A5* are preferred.
  • Each compound disclosed in Tables 28 to 30 represents a disclosure of I with A5 as A5* and a compound I with A5 as A5**.
  • Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I* with A5 as A5*.
  • Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I** with A5 as A5*.
  • Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I* with A5 as
  • Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I** with A5 as A5**.
  • Reference to compounds of the invention also includes reference to salts and N-oxides.
  • the compounds of formula I may be prepared as described in WO 2008/12871 1 , WO 2010/043315, WO 201 1/051455, WO 2007/105814, WO 2008/122375, WO 2009/035004, WO
  • locus of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil.
  • An example for such a locus is a field, on which crop plants are growing.
  • plant propagation material is understood to denote generative parts of a plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material” is understood to denote seeds.
  • Application may be before infestation or when the pest is present.
  • Application of the compounds of the invention can be performed according to any of the usual modes of application, e.g. foliar, drench, soil, in furrow etc.
  • control of Anthonomus grandis s is usually achieved by foliar application, which is the preferred mode of application according to the invention.
  • Application of the compounds of the invention is preferably to a crop of cotton plants, the locus thereof or propagation material thereof.
  • Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.
  • the plant parts also include harvested material, and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, offshoots and seeds.
  • Treatment according to the invention of the plants and plant parts with the active compounds can be carried out directly or by allowing the compounds to act on their surroundings, habitat or storage space by the customary treatment methods, for example by immersion, spraying, evaporation, fogging, scattering, painting on, injecting and, in the case of propagation material, in particular in the case of seed, also by applying one or more coats.
  • the compounds of the invention are suitable for use on any plant (preferably cotton plant), including those that have been genetically modified to be resistant to active ingredients such as herbicides, or to produce biologically active compounds that control infestation by plant pests.
  • plants as used herein includes seedlings, bushes and trees. Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering.
  • herbicides or classes of herbicides e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and
  • Compounds of formula I may be used on transgenic plants (including cultivars) obtained by genetic engineering methods and/or by conventional methods. These are understood as meaning plants having novel properties ("traits") which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive "synergistic") effects.
  • the preferred transgenic plants or plant cultivars which are to be treated according to the invention include all plants which, by virtue of the genetic modification, received genetic material which imparts particularly advantageous, useful traits to these plants. Examples of such traits are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products.
  • transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice), maize, soybean, potatoes, sugar beet, tomatoes, peas and other vegetable varieties, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes).
  • Transgenic cotton is of particular interest.
  • Pesticidal proteins may be used on transgenic plants that are capable of producing one or more pesticidal proteins which confer upon the transgenic plant tolerance or resistance to harmful pests, e.g. insect pests, nematode pests and the like.
  • pesticidal proteins include, without limitation, Cry proteins from Bacillus thuringiensis CrylAb, CrylAc, CrylF, Cry2Ab, Cry2Ae, Cry3A, Cry3Bb, or Cry9C; engineered proteins such as modified Cry3A ( US Patent 7,030,295) or CrylA.105; or vegetative insecticidal proteins such as Vipl, Vip2 or Vip3.
  • Bt Cry proteins and VIPs useful in the invention can be found on the worldwide web at Bacillus thuringiensis Toxin Nomenclature Database maintained by the University of Hampshire (see also, Crickmore et al. (1998) Microbiol. Mol. Biol. Rev. 62:807-813).
  • Other pesticidal proteins useful in the invention include proteins of bacteria colonizing nematodes, e.g. Photorhabdus spp.
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins, or other insect-specific neurotoxins
  • toxins produced by fungi such Streptomycetes toxins, plant lectins, such as pea or barley lectins; agglutinins
  • proteinase inhibitors such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin or papain inhibitors
  • ribosome- inactivating proteins (RIP) such as ricin, maize-RIP, abrin, luffin, saporin or bryodin
  • steroid metabolism enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-IDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase
  • ion channel blockers such as blockers of sodium or calcium channels
  • pesticidal proteins or transgenic plants capable of synthesizing such proteins are disclosed, e.g., in EP-A 374753, WO 93/007278, WO 95/34656, EP-A 427529, EP-A 451878, WO 03/18810 and WO 03/52073.
  • Agrisure®CB (PI) (corn producing CrylAb), Agrisure®RW (P2) (corn producing mCry3A), Agrisure® Viptera (P3) (corn hybrids producing Vip3Aa); Agrisure300GT (P4) (corn hybrids producing CrylAb and mCry3A); YieldGard® (P5) (corn hybrids producing the CrylAb protein), YieldGard® Plus (P6) (corn hybrids producing CrylAb and Cry3Bbl), Genuity® SmartStax® (P7) (corn hybrids with CrylA.105, Cry2Ab2, CrylF, Cry34/35, Cry3Bb) ; Herculex® I (P8) (corn hybrids producing CrylFa) and Herculex®RW (P9) (corn hybrids producing Cry34Abl, Cry35Abl and the enzyme Phosphinothricin-N-
  • transgenic crops are:
  • Btl76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 7). Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ⁇ Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylA(b) toxin. Btl 76 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St.
  • MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/DE/02/9 (P19). MON 863 expresses a CrylllB(bl) toxin and has resistance to certain Coleoptera insects.
  • NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren,
  • NK603 ⁇ MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • CP4 EPSPS obtained from Agrobacterium sp. strain CP4
  • Roundup® contains glyphosate
  • CrylA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • transgenic plants and of very high interest, are those carrying traits conferring resistance to 2.4D (e.g. Enlist®) (e.g. WO 2011066384) (, glyphosate (e.g. Roundup Ready® (P24), Roundup Ready 2 Yield® (P25)), sulfonylurea (e.g. STS®) (P26), glufosinate (e.g. Liberty Link® (P27), Ignite® (P28)), Dicamba (P29) (Monsanto), HPPD tolerance (P30) (e.g. isoxaflutole herbicide) (Bayer CropScience, Syngenta).
  • Enlist® e.g. WO 2011066384
  • glyphosate e.g. Roundup Ready® (P24), Roundup Ready 2 Yield® (P25)
  • sulfonylurea e.g. STS®
  • P26 glufosinate
  • P27 glufos
  • Double or triple stacks of any of the traits described here are also of interest, including glyphosate and sulfonyl-urea tolerance ((e.g. Optimum GAT®) (P31), plants stacked with STS® and Roundup Ready® (P32) or plants stacked with STS® and Roundup Ready 2 Yield® (P33)), dicamba and glyphosate tolerance (P34) (Monsanto).
  • glyphosate and sulfonyl-urea tolerance (e.g. Optimum GAT®) (P31), plants stacked with STS® and Roundup Ready® (P32) or plants stacked with STS® and Roundup Ready 2 Yield® (P33)), dicamba and glyphosate tolerance (P34) (Monsanto).
  • soybean plants carrying trains conferring resistance to 2.4D e.g. Enlist®
  • glyphosate e.g. Roundup Ready®, Roundup Ready 2 Yield®
  • HPPD tolerance e.g. isoxaflutole herbicide
  • cotton transgenic events include MON 531 / 757 / 1076 (Bollgard I ® - Monsanto), MON1445 (Roundup ready cotton ®- Monsanto), MON531 x MON1445 (Bollgard I + RR ®- Monsanto), MON15985 (Genuity Bollgard II cotton ®- Monsanto), MON88913 (Genuity RR FLEX cotton ®- Monsanto), MON15985 x MON1445 (Genuity Bollgard II + RR FELX cotton ®- Monsanto), MON15983 x MON88913 (Genuity Bollgard II + RR FLEX cotton ® - Monsanto), MON15985
  • MON88913 x MON15985 (FibreMax LL GlyTol Bollgard II cotton ® - Monsanto), MON88913 (FibreMax RR Flex cotton ® - Monsanto), GHB119 + T304-40 (Twinlink ® - BCS Stoneville), GHB119 + T304-40 x LL25 x GHB614 (Twinlink LL GT ® - BCS Stoneville), 3006-210-23 x 281-24-236
  • Soy transgenic events include MON87701 x MON89788 (Genuity Roundup ready 2 Yield soybeans® - Monsanto), MON89788 (Roundup Ready2Yield®, RR2Y® - Monsanto), MON87708 (Monsanto), 40-3-2 (Roundup Ready®, RRl® - Monsanto), MON87701 (Monsanto), DAS-68416 (Enlist Weed Control System® - Dow), DP356043 (Optimum GAT® - Pioneer), A5547-127 (LibertyLink soybean® - Bayercropscience), A2704-12 (Bayercropscience), GU262 (Bayercropscience), W62 W98 (Bayercropscience), CRV127 (Cultivance® - BASF / EMBRAPA), SYHT0H2 (WO2012/082548).
  • Maize transgenic events include T25 (LibertyLink®, LL® - Bayerscropscience), DHT-1 (Dow), TCI 507 (Herculex I® - Dow), DAS59122-7 (Herculex RW® - Dow), TCI 507 + DAS59122-7 - Herculex Xtra® - Dow), TCI 507 x DAS-59122-7 x NK603 (Herculex Xtra + RR® - Dow), TC1507 x DAS-59122- x MON88017 x MON89034 (Genuity Smartstax corn®, Genuity
  • Herbicide-resistant plants plants bred in a conventional manner for herbicide tolerance
  • plants bred in a conventional manner for herbicide tolerance include the varieties sold under the name Clearfield(®) (for example maize).
  • the compounds of the invention are suitable for use on any cotton plant, including those that have been genetically modified to be resistant to active ingredients such as herbicides, or to produce biologically active compounds that control infestation by plant pests, e.g. BT cotton.
  • a compound of the invention may be used in mixtures with fertilizers (for example nitrogen-, potassium- or phosphorus-containing fertilizers).
  • Suitable formulation types include granules of fertilizer.
  • the mixtures preferably contain up to 25% by weight of the compound of the invention.
  • the invention therefore also provides a fertilizer composition comprising a fertilizer and a compound of the invention.
  • compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
  • compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
  • the compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, e.g. a insecticide, fungicide or herbicide, or a synergist or plant growth regulator where appropriate.
  • a pesticide e.g. a insecticide, fungicide or herbicide, or a synergist or plant growth regulator where appropriate.
  • An additional active ingredient may provide a composition having a broader spectrum of activity or increased persistence at a locus; synergize the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components.
  • suitable pesticides include the following:
  • a) Pyrethroids such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin and gamma cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, S-bioallethrin, fenfluthrin, prallethrin, acrinathirin, etofenprox or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate;
  • Organophosphates such as profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, al
  • Benzoyl ureas such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron, diafenthiuron, lufeneron, novaluron, noviflumuron or chlorfluazuron;
  • Organic tin compounds such as cyhexatin, fenbutatin oxide or azocyclotin;
  • Pyrazoles such as tebufenpyrad, tolfenpyrad, ethiprole, pyriprole, fipronil, and fenpyroximate;
  • Macrolides such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad, azadirachtin, milbemectin, lepimectin or spinetoram;
  • Organochlorine compounds such as endosulfan (in particular alpha-endosulfan), benzene hexachloride, DDT, chlordane or dieldrin;
  • Amidines such as chlordimeform or amitraz
  • Fumigant agents such as chloropicrin, dichloropropane, methyl bromide or metam
  • Neonicotinoid compounds such as imidacloprid, thiacloprid, acetamiprid, nitenpyram, dinotefuran, thiamethoxam, clothianidin, or nithiazine;
  • Diacylhydrazines such as tebufenozide, chromafenozide or methoxyfenozide
  • Diphenyl ethers such as diofenolan or pyriproxifen
  • Ketoenols such as Spirotetramat, spirodiclofen or spiromesifen
  • Diamides such as flubendiamide, chlorantraniliprole (Rynaxypyr®) or cyantraniliprole;
  • Essential oils such as Bugoil® - (Plantlmpact); or
  • a comopund selected from buprofezine, flonicamid, acequinocyl, bifenazate, cyenopyrafen, cyflumetofen, etoxazole, flometoquin, fluacrypyrim, fluensulfone, flufenerim, flupyradifuone, harpin, iodomethane, dodecadienol, pyridaben, pyridalyl, pyrimidifen, flupyradifurone, 4-[(6-Chloro-pyridin-3- ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one (DE 102006015467), CAS: 915972-17-7
  • pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition.
  • selective insecticides for particular crops for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed.
  • insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
  • acaricidal ovo-larvicides such as clofentezine, flubenzimine, hexythiazox or tetradifon
  • acaricidal motilicides such as dicofol or propargite
  • acaricides such as bromopropylate or chlorobenzilate
  • growth regulators such
  • fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l -sulfonamide,
  • acibenzolar-S-methyl alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, bixafen, blasticidin S, boscalid, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture, cyclufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide
  • OjO-di-wo-propyl-S-benzyl thiophosphate dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl-(Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino- oxycarbonyl)amino]thio)- -alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph,
  • fluoxastrobin fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, fluxapyroxad, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, mandipropamid, maneb, mefenoxam, metalaxyl, mepanipyrim, me
  • biological agents may be included in the composition of the invention e.g. Baciullus species such as Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria species such as Pasteuria penetrans and Pasteuria nishizawae.
  • Bacillus firmus strain is strain CNCM 1-1582 which is commercially available as BioNemTM.
  • a suitable Bacillus cereus strain is strain CNCM 1-1562. Of both Bacillus strains more details can be found in US 6,406,690.
  • Other biological organisms that may be included in the compositions of the invention are bacteria such as Streptomyces spp. such as S.
  • avermitilis and fungi such as Pochonia spp. such as P. chlamydosporia.
  • Pochonia spp. such as P. chlamydosporia.
  • Metarhizium spp. such as M. anisopliae
  • Pochonia spp. such as P. chlamydosporia.
  • the compounds of the invention may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
  • synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
  • Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
  • An example of a rice selective herbicide which may be included is propanil.
  • An example of a plant growth regulator for use in cotton is PIXTM.
  • Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type.
  • other formulation types may be prepared.
  • one active ingredient is a water insoluble solid and the other a water insoluble liquid
  • the resultant composition is a suspoemulsion (SE) formulation.
  • weight ratio of the compound of I with an additional active ingredient may generally be between 1000 : 1 and 1 : 1000.
  • that weight ratio of the compound of formula I to the additional active ingredient may be between 500 : 1 to 1 : 500, for example between 100 : 1 to 1 : 100, for example between 1 : 50 to 50 : 1, for example 1 : 20 to 20 : 1, for example 1 : 10 to 10: 1, for example 1 :5 to 5: 1, for example 1 : 1, 1 :2, 1 :3, 1 :4, 1 :5, 2: 1, 3: 1, 4: 1, or 5:1.
  • Mixtures with pyrethroids, in particular pymetrozine, are of particular interest for the present invention.
  • compositions of the invention include those prepared by premixing prior to application, e.g. as a readymix or tankmix, or by simultaneous application or sequential application to the plant.
  • compounds of the invention is usually formulated into a composition which includes, in addition to the compound of the invention, a suitable inert diluent or carrier and, optionally, a surface active agent (SFA).
  • SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting).
  • compositions both solid and liquid formulations
  • the composition is generally used for the control of pests such that a compound of the invention is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
  • the compounds of the invention are used for pest control on cotton at 1 :500 g/ha, for example 10-70g/ha.
  • sprays are often very intense and at very low threshold levels and can be down to almost zero tolerance.
  • a compound of the invention When used in a seed dressing, a compound of the invention is used at a rate of 0.000 lg to lOg (for example O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
  • Compositions comprising a compound of the invention can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro- emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations.
  • the formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of the invention.
  • Dustable powders may be prepared by mixing a compound of the invention with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
  • solid diluents for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers
  • Soluble powders may be prepared by mixing a compound of the invention with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water
  • water-soluble inorganic salts such as sodium bicarbonate, sodium carbonate or magnesium sulfate
  • water-soluble organic solids such as a polysaccharide
  • compositions may also be granulated to form water soluble granules (SG).
  • WP Wettable powders
  • WG Water dispersible granules
  • Granules may be formed either by granulating a mixture of a compound of the invention and one or more powdered solid diluents or carriers, or from pre- formed blank granules by absorbing a compound of the invention (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of the invention (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulfates or phosphates) and drying if necessary.
  • a hard core material such as sands, silicates, mineral carbonates, sulfates or phosphates
  • Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils).
  • solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters
  • sticking agents such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils.
  • One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
  • DC Dispersible Concentrates
  • a compound of the invention may be prepared by dissolving a compound of the invention in water or an organic solvent, such as a ketone, alcohol or glycol ether.
  • organic solvent such as a ketone, alcohol or glycol ether.
  • surface active agent for example to improve water dilution or prevent crystallization in a spray tank.
  • Emulsifiable concentrates or oil- in- water emulsions (EW) may be prepared by dissolving a compound of the invention in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents).
  • Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cg-Cio fatty acid dimethylamide) and chlorinated hydrocarbons.
  • aromatic hydrocarbons such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark
  • ketones such as cycl
  • An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.
  • Preparation of an EW involves obtaining a compound of the invention either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion.
  • Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
  • Microemulsions may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation.
  • a compound of the invention is present initially in either the water or the solvent/SFA blend.
  • Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs.
  • An ME may be either an oil- in- water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation.
  • An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in- water emulsion.
  • SC Suspension concentrates
  • SCs may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of the invention.
  • SCs may be prepared by ball or bead milling the solid compound of the invention in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound.
  • One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle.
  • a compound of the invention may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
  • Aerosol formulations comprise a compound of the invention and a suitable propellant (for example n-butane).
  • a compound of the invention may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non- pressurized, hand-actuated spray pumps.
  • a compound of the invention may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
  • Capsule suspensions may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerization stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of the invention and, optionally, a carrier or diluent therefor.
  • the polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure.
  • the compositions may provide for controlled release of the compound of the invention and they may be used for seed treatment.
  • a compound of the invention may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
  • a composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of the invention).
  • additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of the invention).
  • a compound of the invention may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS).
  • DS powder for dry seed treatment
  • SS water soluble powder
  • WS water dispersible powder for slurry treatment
  • CS capsule suspension
  • compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
  • Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
  • Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
  • Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (for example sodium lauryl sulfate), salts of sulfonated aromatic compounds (for example sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalene sulfonate and mixtures of sodium di-z ' opropyl- and tri-wopropyl-naphthalene sulfonates), ether sulfates, alcohol ether sulfates (for example sodium laureth-3-sulfate), ether carboxylates (for example sodium laureth-3- carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and
  • Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
  • Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide);
  • alkylene oxides such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof
  • fatty alcohols such as oleyl alcohol or cetyl alcohol
  • alkylphenols such as octylphenol, nonylphenol or octylcresol
  • partial esters derived from long chain fatty acids or hexitol anhydrides condensation products of said partial esters with ethylene oxide
  • alkanolamides alkanolamides
  • simple esters for example fatty acid polyethylene glycol esters
  • amine oxides for example lauryl dimethyl amine oxide
  • lecithins alkanolamides
  • simple esters for example fatty acid polyethylene glycol esters
  • amine oxides for example lauryl dimethyl amine oxide
  • lecithins lecithins
  • Suitable suspending agents include hydrophilic colloids (such as polysaccharides,
  • polyvinylpyrrolidone or sodium carboxymethylcellulose and swelling clays (such as bentonite or attapulgite).
  • a compound of the invention may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapor or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water- soluble bag) in soil or an aqueous environment.
  • a locus of the pests such as a habitat of the pests, or a growing plant liable to infestation by the pests
  • a compound of the invention may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
  • compositions for use as aqueous preparations are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use.
  • These concentrates which may include DCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • Such aqueous preparations may contain varying amounts of a compound of the invention (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
  • Example 1 Preparation of N-r(l S)-l -r4-r3-r3,5-bis(trifluoromethyl)phenyll-3- (trifluorometh l)pyrrolidin-l -yllphenyllethyllcyclopropanecarboxamide
  • Tris(dibenzylideneacetone)dipalladium(0) 32 mg
  • 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene 61 mg
  • sodium tert-butoxide 190 mg
  • 3-(3,5-dichlorophenyl)-3- (trifluoromethyl)pyrrolidine 520 mg, prepared as described in WO 2008/128711
  • N-[(lS)-l-(4- bromophenyl)ethyl]cyclopropanecarboxamide prepared as described in WO 2012/001107, 520 mg
  • toluene 15 mL
  • Step 1
  • benzenecarboximidothioate (4 g, 14.27 mmol) and l,2,3-trichloro-5-[l-(trifluoromethyl)vinyl]benzene (3.97g., 14.41 mmol) in tetrahydrofuran (5 mL) was slowly added tetrabutylammonium hydrofluoride (7.13 mL, 7.133 mmol, 1 mol/L) .
  • the reaction was stirred at -5°C for 30 mins, then allowed to come to room temperature, and stirred at room temperature for 2 hours under nitrogen atmosphere.
  • the reaction was diluted with water (50 mL) and extracted with ethylacetate (3 x 100 mL).
  • Step 5 Preparation of 2-(l ,2,4-triazol-l-yl)-5-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dih dropyrrol-5-yl]benzonitrile
  • the reaction mass was quenched with water (50 mL) and the compound was extracted with ethylacetate (30 mL x 2) in order to remove debromo compound.
  • the aqueous layer was acidified with ammonium chloride and extracted with ethylacetate (30 mL x 2).
  • the combined organic layers were dried with sodium sulfate and evaporated off under vacuum and dried under vacuum. Weight: 0.61 g
  • Step 3 Preparation of tert-butyl N-[(lS)-l-[4-(trimethylsilylmethylcarbamoyl)phenyl]ethyl]carbamate
  • Step 4 Preparation of tert-butyl N-[(lS)-l-[4(trimethylsilylmethylcarbamothioyl)phenyl]ethyl]carbamate
  • reaction mass was taken into THF (25 mL) and l,2,3-trichloro-5-[l -(trifluoromethyl)vinyl] benzene (1 eq., 1 mmol) was added into it.
  • the mixture was cooled to 0°C, TBAF (1 eq, 1 mmol) was added and stirring was continued for 3 hours at room temperature.
  • the solvent was evaporated off under vacuum and the reaction mass was diluted with ethylacetate and washed with water (30 mL x 2) and dried with sodium sulphate and evaporated off under vacuum.
  • the compound was purified by combiflash, (25-30% EtOAC-hexane). Weight: 0.1 lg
  • Step 6 Preparation of N-[(lS)-l-[4-[5-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-3- yl]phenyl]ethyl]cyclopropanecarboxamide
  • reaction mass was diluted with DCM (20 mL) and washed with water (20 mL). The organic layer was then dried over anhydrous sodium sulphate, and the solvent was removed under vacuum. The compound was purified by Combiflash (35 % EtOAC- hexane). Weight: 0.2 g, melting point: 80-82°C.
  • Step 1 Bromination of 3-bromo-4-methyl benzoic acid.
  • Step 2 Preparation of 3-bromo-4-(dibromomethyl)-N-[(trimethylsilyl)methyl]benzamide.
  • Step 4 Preparation of 3-bromo-4-hydroxymethyl-N-[trimethylsilaylmethyl] benzamide.
  • Step 5 Preparation of Acetic acid 2-bromo-4- (trimethylsilanylmethyl-carbamoyl)-benzylester.
  • Step 6 Preparation of 3-bromo-4-(2-oxo-propyl)-N-trimethylsilanylmethyl-thiobenzamide.
  • Step 8 Preparation of 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]- phenyl-methanol.
  • Step 9 Preparation of Methanesulfonic acid-2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5- dih dro-3H-pyrrol-2yl]-benzylester.
  • methanesulfonyl chloride (0.35 g, 3.0 mmol) gradually. The mixture was stirred for 1 hour at room temperature. The reaction mixture was washed with water. The organic layer was separated and dried using sodium sulphate. The organic layer was evaporated to obtain the solid compound methanesulfonic acid-2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]-benzylester (0.9 g).
  • Step 10 Preparation of2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol- 2yl] -benzylamine.
  • Step 11 Preparation of N- ⁇ 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H- pyrrol-2yl] -benzyl ⁇ acetamide.

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Abstract

The present invention provides provides a method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula (I), wherein -B1-Β2-Β3- is -C=N-O-, -C=N-CH2-, or -N-CH2-CH2-; R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl; R2 is group X X2 is C-X6 or nitrogen; X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen; A is selected from A1 to A5 Y1 is C-R6, CH or nitrogen; Y2 and Y3 are independently CH or nitrogen; wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; R5 is hydrogen, halogen, cyano, nitro, NH2, C1-C4alkyl, C1C4aloalkyl, C3-C5cycloalkyl, C3- C5halocycloalkyl, C1-C2alkoxy, or C1-C2haloalkoxy, preferably provided that when A is A3 or A4 R5 is not hydrogen; R6 when present together with R5 forms a -CH=CH-CH=CH- bridge; R7 is C1C4alkyl; R8 is C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy(C1-C4)alkyl, C1-C4alkylthio(C1-C4)alkyl, C1- C4alkylsulfinyl(C1-C4)alkyl, C1-C4alkylsulfonyl(C1-C4)alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl(C1-C4)alkyl-, or tetrahydrofuranyl; R9 is C1-C4alkyl, C1-C4haloalkyl, C1-C4alkyl-O-CH2-, C1-C4haloalkyl-O-CH2-,C3-C6cycloalkyl, C3-C6cycloalkyl-CH2-, C1-C4alkyl-S-CH2-, C1-C4alkyl-S(O)-CH2-, or C1-C4alkyl-S(O2)-CH2; each Z is independently halogen, C1-C12alkyl or C1-C12alkyl substituted by one to five R12, nitro, C1-C12alkoxy or C1-C12alkoxy substituted by one to five R12 cyano, C1-C12alkylsulfinyl, C1-C12alkylsulfonyl, C1-C12haloalkylsulfinyl, C1-C12haloalkylsulfonyl, hydroxyl or thiol; each R12 is halogen, cyano, nitro, hydroxy, C1-C8alkoxy-, C1-C8haloalkoxy-, mercapto, C1-C8alkylthio-, or C1-C8haloalkylthio; and k is 0, 1,2 or 3.

Description

METHODS OF CONTROLLING INSECTS
The present invention relates to a method of controlling insects, in particular diamondblack moth
(Plutella).
Compounds that are insecticidally, acaricidally, nematicidally and/or moluscicidally active by antagnonism of the gamma-aminobutyric acid (GABA)-gated chloride channel, and which comprise a partially saturated heterocycle that is substituted by a haloalkyl substituent and one or two optionally substituted aromatic or heteroaromatic rings, represent a new class of pesticides that are described for example in Ozoe et al. Biochemical and Biophysical Research Communications, 391 (2010) 744-749. Compounds from this class are broadly described in WO 2005/085216 (EP1731512), WO 2007/123853, WO 2007/075459, WO 2009/002809, WO 2008/019760, WO 2008/122375, WO 2008/128711, WO 2009/097992, WO 2010/072781, WO 2010/072781, WO 2008/126665, WO 2007/125984, WO
2008/130651, JP2008110971, JP2008133273, JP2009108046, WO 2009/022746, WO 2009/022746, WO 2010/032437, WO 2009/080250, WO 2010/020521, WO 2010/025998, WO 2010/020522, WO
2010/084067, WO 2010/086225, WO 2010/149506 and WO 2010/108733.
It has now surprisingly been found that particular insecticides from this new class of gamma- aminobutyric acid (GABA)-gated chloride channel antagonists (disclosed in e.g. WO 2009/080250, WO 2010/020522, WO 2010/149506, WO 2011/101229 and WO 2012/045700) are highly effective at controlling Plutella. These compounds therefore represent an important new solution for safeguarding crops of useful plants, from the genus Plutella, particularly where the insects are resistant to current methods.
In a first aspect the invention provides a method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula I
Figure imgf000003_0001
wherein -B'-B^B3- is -C=N-0-, -C=N-CH2- , or -N-CH2-CH2
R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R is group X
Figure imgf000003_0002
X2 is C-X6 or nitrogen;
X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen; A is selected from Al to A5
Figure imgf000004_0001
Y1 is C-R6, CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; R5 is hydrogen, halogen, cyano, nitro, NH2, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5cycloalkyl, C3- C5halocycloalkyl, Ci-C2alkoxy, or Ci-C2haloalkoxy, preferably provided that when A is A3 or A4 R5 is not hydrogen;
R6 when present together with R5 forms a -CH=CH-CH=CH- bridge;
R7 is CrC4alkyl;
R8 is Ci-C4alkyl, CrC4haloalkyl, Ci-C4alkoxy(Ci-C4)alkyl, Ci-C4alkylthio(CrC4)alkyl, Cr
C4alkylsulfmyl(Ci-C4)alkyl, Ci-C4alkylsulfonyl(Ci-C4)alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl(Cr
C4)alkyl-, or tetrahydrofuranyl;
R9 is Ci-C4alkyl, CrC4haloalkyl, CrC4alkyl-0-CH2-, Ci-C4haloalkyl-0-CH2-,C3-C6cycloalkyl, C3-
C6cycloalkyl-CH2-, CrC4alkyl-S-CH2-, CrC4alkyl-S(0)-CH2-, or CrC4alkyl-S(02)-CH2;
each Z is independently halogen, Ci-Ci2alkyl or Ci-Ci2alkyl substituted by one to five R12, nitro, Cp
Ci2alkoxy or Ci-Ci2alkoxy substituted by one to five R12 cyano, Ci-Ci2alkylsulfinyl, Ci-Ci2alkylsulfonyl,
Ci-Ci2haloalkylsulfinyl, Ci-Ci2haloalkylsulfonyl, hydroxyl or thiol;
each R12 is halogen, cyano, nitro, hydroxy, CpCgalkoxy-, Ci-Cghaloalkoxy-, mercapto, CpCgalkylthio-, or
CpCghaloalkylthio; and
k is 0, 1,2 or 3.
In a further embodiment the invention provides use of a compound of formula I for controlling and/or preventing insects from the genus Plutella in useful plants. The insects may be resistant to other insecticides.
In a further aspect the invention provides a method for obtaining regulatory approval for the use of one or more of a compound of formula I to control insects from the genus Plutella, comprising at least one step of referring to, submitting or relying on biological data showing that said active ingredient reduces insect pressure. An example of a preferred species is Plutella xylostella. Preferably the compounds of formula I are used to control insects from the genus Plutella in brassica crops.
Preventing insects in useful plants means for example preventing infestation of insects in useful plants.
The compounds of the invention may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. The compounds of the invention may contain one or more asymmetric carbon atoms, and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such. Reference to compounds of the invention also includes reference to salts and N-oxides.
The preferences for B1, B2, B3, R1, R2, Y1, Y2, Y3, R5, R6 R7, R8, R9, R12, X1 X2, X3, X6, Z and k are, in any combination, as described below.
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-
(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichlorophenyl, 3,5-dichloro-4-fluorophenyl- or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
Preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, most preferably R5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl.
Preferably R8 is CrC4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3-
Cgcycloalkyl, C3-C6cycloalkyl-CH2-, CrC4alkyl-S(0)-CH2-, Ci-C4alkyl-S(02)-CH2-, more preferably Cr Qalkyl, CrC4alkyl-0-CH2-, CrC4alkyl-S-CH2-, CrC4alkyl-SO-CH2-, CrC4alkyl-S02-CH2-, C3- C4cycloalkyl, or C3-C4cycloalkyl-CH2-, most preferably R8 is methyl, ethyl, n-propyl, isopropyl, CH3-O- CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-SO2-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-.
Preferably R9 is CrC4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3- Cgcycloalkyl, C3-C6cycloalkyl-CH2-, CrC4alkyl-S(0)-CH2-, Ci-C4alkyl-S(02)-CH2-, more preferably Cr Qalkyl, CrC4haloalkyl, CrC4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-, C3-C6cycloalkyl, C3-C6cycloalkyl- CH2-, more preferably Ci-C4alkyl, Ci-C4haloalkyl or C3-C4cycloalkyl, more preferably methyl, ethyl, n- propyl, CF3CH2- or cyclopropyl, even more preferably ethyl, CF3CH2- or cyclopropyl.
Preferably each Z is independently halogen, cyano, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, or Ci-C4haloalkoxy, most preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
Each R12 is preferably bromo, chloro, fluoro, methoxy, or methylthio, most preferably chloro, fluoro, or methoxy.
Preferably k is 0 or 1.
In one group of compounds -B1-B2-B3- is -C=N-0-.
In another group of compounds -B1-B2-B3- is -C=N-CH2-.
In another group of compounds -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds Y1 is C-R6 and R6 together with R5 forms a -CH=CH-CH=CH- bridge.
In one embodiment the compound of formula I is a compound of formula IA
Figure imgf000006_0001
wherein B 1 ,
Figure imgf000006_0002
R5D and R 8° are as defined for a compound of formula I.
In compounds of formula IA preferred definitions of B1, B2, B3, R1, R2, Y1, Y2, Y3, R5 and R8 are, in any combination, as set out below:
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-
(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
Preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, more preferably R5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, even more preferably hydrogen, chloro, bromo, methyl or trifluoromethyl, most preferably chloro, bromo, fluoro or methyl.
Preferably R8 is CrC4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3- Cgcycloalkyl, C3-C6cycloalkyl-CH2-, CrC4alkyl-S(0)-CH2-, Ci-C4alkyl-S(02)-CH2-, more preferably Cr C4alkyl, CrC4alkyl-0-CH2-, CrC4alkyl-S-CH2-, CrC4alkyl-SO-CH2-, CrC4alkyl-S02-CH2-, C3- C4cycloalkyl, or C3-C4cycloalkyl-CH2-, more preferably R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0- CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, most preferably n-propyl or cyclopropyl.
In one group of compounds of formula IA -B1-B2-B3- is -C=N-0-.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is
CH and R1 is CF3.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is chloro, bromo, fluoro or methyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0- CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0- CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-SO2-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5- (trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)- 4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IA -B1-B2-B3- is -C=N-CH2-.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IA -B 1-B2-B3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is chloro, bromo, fluoro or methyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2- , CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3- 0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3- 0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5- (trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)- 4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3 ,4-dichlorophenyl-
In one group of compounds of formula IA -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds of formula IA -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH,
Y3 is CH.
In another group of compounds of formula IA -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IA -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is chloro, bromo, fluoro or methyl . In another group of compounds of formula IA -B'-B^B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)- CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B'-B^B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2- , preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is chloro, bromo, fluoro or methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3- O-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2- and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl- In another group of compounds of formula IA R5 is chloro, bromo, fluoro or methyl and
R8 methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IA R5 is chloro, bromo, fluoro or methyl;
R8 methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl, R1 is CF3, -B1-B2-B3 is -C=N-0- or -C=N-CH2-, Y1, Y2 and Y3 are CH, and R5 is chloro or methyl.
In a further preferred embodiment of compounds of formula IA -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, Y1, Y2 and Y3 are CH, R5 is chloro, and R8 is n-propyl.
In a further preferred embodiment of compounds of formula IA -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, Y1, Y2 and Y3 are CH, R5 is chloro, and R8 is n-propyl.
In a further preferred embodiment of compounds of formula IA -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R2 is 3-bromo-5-trifluoromethylphenyl, Y1, Y2 and Y3 are CH and R8 is n-propyl.
In a further preferred embodiment of compounds of formula IA -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R2 is 3-bromo-5-trifluoromethylphenyl, Y1, Y2 and Y3 are CH and R5 is chloro.
In a further preferred embodiment of compounds of formula IA -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R 2 is 3-bromo-5-trifluoromethylphenyl, Y 1 , Y 2 and Y 3 are CH, R 5 is chloro, and R 8 is n- propyl.
In one embodiment the compound of formula I is a compound of formula IB
Figure imgf000010_0001
(IB)
1 2 3 1 2 1 2 3 V 8
wherein B , B , B\ R , R Y , Y% YJ, R' and R° are as defined for a compound of formula I
In compounds of formula IB preferred definitions of B1, B2, B3, R1, R2, Y1, Y2, Y3, R7 and R8 are, in any combination, as set out below
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
Preferably R7 is methyl.
Preferably R8 is CrC4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3-
Cgcycloalkyl, C3-C6cycloalkyl-CH2-, CrC4alkyl-S(0)-CH2-, Ci-C4alkyl-S(02)-CH2-, more preferably Cr Qalkyl, CrC4alkyl-0-CH2-, CrC4alkyl-S-CH2-, CrC4alkyl-SO-CH2-, CrC4alkyl-S02-CH2-, C3- C4cycloalkyl, or C3-C4cycloalkyl-CH2-, more preferably R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0- CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, most preferably n-propyl or cyclopropyl.
In one group of compounds of formula IB -B1-B2-B3- is -C=N-0-. In another group of compounds of formula IB -B'-B^B3- is -C=N-0- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IB -B'-B^B3- is -C=N-0- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IB -B'-B^B3- is -C=N-0- , Y1 is CH, Y2 is CH, Y3 is
CH, R1 is CF3 and R7 is methyl.
In another group of compounds of formula IB -B'-B^B3- is -C=N-0- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of -B1-B2-B3- is -C=N-0- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is
CF3, R7 is methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)- CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-0- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R7 is methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3- S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4- fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IB -B1-B2-B3- is -C=N-CH2-.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R7 is methyl.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2- , CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R7 is methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R7 is methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3- S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4- fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds of formula IB -B'-B^B3- is -N-CH2-CH2- and Y1 is CH, Y2 is
CH, Y3 is CH.
In another group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R7 is methyl.
In another group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)- CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R7 is methyl and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R7 is methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4- fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl- In another group of compounds of formula IB R7 is methyl, and R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl.
In another group of compounds of formula IB R7 is methyl, R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-, preferably n-propyl or cyclopropyl, R1 is CF3, -B1-B2-B3- is -C=N-0-, -C=N-CH2- or - N-CH2-CH2-, and Y1, Y2 and Y3 are CH.
In a further preferred embodiment of compounds of formula IB -B1-B2-B3- is -C=N-0-, R1 is
1 2 3 5 1 8
trifluoromethyl, Y , Y and Y are CH; R is chloro, R is methyl and R is n-propyl.
In a further preferred embodiment of compounds of formula IB -B1-B2-B3- is -C=N-0-, R1 is
1 2 3 5 1 8
trifluoromethyl, Y , Y and Y are CH; R is chloro, R is methyl and R is n-propyl. In a further preferred embodiment of compounds of formula IB -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R 2 is 3-bromo-5-trifluoromethylphenyl, Y 1 , Y2 and Y 3 are CH, RV is methyl and R 8 is n- propyl.
In a further preferred embodiment of compounds of formula IB -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R 2 is 3-bromo-5-trifluoromethylphenyl, Y 1 , Y 2 and Y 3 are CH, R 5 is chloro and R V is methyl.
In a further preferred embodiment of compounds of formula IB -B1-B2-B3- is -C=N-0-, R1 is trifluoromethyl, R 2 is 3-bromo-5-trifluoromethylphenyl, Y 1 , Y 2 and Y 3 are CH, R 5 is chloro, R V is methyl and R8 is n-propyl.
In one embodiment the compound of formula I is a compound of formula IC
Figure imgf000013_0001
wherein B 1 , B2,
Figure imgf000013_0002
R5D Z and k are as defined for a compound of formula I
In compounds of formula IC preferred definitions of B1, B2, B3, R1, R2, Y1, Y2, Y3, R5, Z and k are, in any combination, as set out below
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl. Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
In one embodiment, preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
In a further more preferred embodiment, preferably R5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R5 is cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
Preferably each Z is independently halogen, cyano, Ci-C4alkyl,
Figure imgf000014_0001
Ci-C4alkoxy, or Ci-C ihaloalkoxy, more preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
Preferably k is 0 or 1.
In one group of compounds of formula IC -B1-B2-B3- is -C=N-0-.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is
CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro-5- bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5- dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IC -B1-B2-B3- is -C=N-CH2-.
In another group of compounds of formula IC -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IC -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3. In another group of compounds of formula IC -B'-B^B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula IC -B'-B^B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B'-B^B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B'-B^B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro-5- bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5- dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH,
Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro- 5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In another group of compounds of formula IC R5 is cyano, k is 0 or 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula IC R5 is cyano, R1 is CF3, -B1-B2-B3- is -C=N-0- or - C=N-CH2-, Y1, Y2 and Y3 are CH, and k is 0.
In one embodiment the compound of formula I is a compound of formula ID
Figure imgf000016_0001
wherein B 1 , B2,
Figure imgf000016_0002
R5D Z and k are as defined for a compound of formula I
In compounds of formula ID preferred definitions of B1, B2, B3, R1, R2, Y1, Y2, Y3, R5 Z and k are, in any combination, as set out below
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl.
Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
In one embodiment, preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is hydrogen, chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R5 is hydrogen, cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano.
In a further more preferred embodiment, preferably R5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, methoxy, nitro, trifluoromethoxy, cyano, cyclopropyl, more preferably R5 is chloro, bromo, fluoro, trifluoromethyl, methyl, ethyl, nitro, cyano, cyclopropyl, even more preferably R5 is cyano, chloro, bromo, fluoro, methyl, or trifluoromethyl, most preferably cyano. Preferably each Z is independently halogen, cyano, Ci-C4alkyl,
Figure imgf000017_0001
Ci-C4alkoxy, or Ci-C ihaloalkoxy, more preferably each Z is independently hydrogen, cyano, halogen, methyl, halomethyl, methoxy or halomethoxy, most preferably cyano or trifluoromethyl.
Preferably k is 0 or 1 , more preferably 1. When k is 1 preferably Z is attached to the 4 position of the imidazole moiety as indicated below:
Figure imgf000017_0002
In one group of compounds of formula ID -B1-B2-B3- is -C=N-0-.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is
CH and R1 is CF3.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl, and when k is 1 , Z is attached to the 4 position of the imidazole moiety.
In another group of compounds of formula ID -B'-B^B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro-5- bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-,
3.5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5- dibromophenyl-, or 3,4-dichlorophenyl-.
In another group of compounds of formula ID -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or 1 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-,
2.6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, and when k is 1, Z is attached to the 4 position of the imidazole moiety.
In one group of compounds of formula ID -B1-B2-B3- is -C=N-CH2-. In another group of compounds of formula ID -B'-B^B3- is -C=N-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl, and when k is 1 , Z is attached to the 4 position of the imidazole moiety.
In another group of compounds of formula ID -β'-Β^Β3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro-5- bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-,
3.5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5- dibromophenyl-, or 3,4-dichlorophenyl-.
In another group of compounds of formula ID -B1-B2-B3- is -C=N-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-,
2.6- bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, and when k is 1, Z is attached to the 4 position of the imidazole moiety.
In one group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH,
Y3 is CH and R1 is CF3.
In another group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R5 is cyano.
In another group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and k is 0 or k is 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID -B1-B2-B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl. In another group of compounds of formula ID -B'-B^B3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl, and when k is 1, Z is attached to the 4 position of the imidazole moiety.In another group of compounds of formula ID -β'-Β^Β3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 and Z is cyano or trifluoromethyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5- (trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)- 4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In another group of compounds of formula ID -β'-Β^Β3- is -N-CH2-CH2- , Y1 is CH, Y2 is CH,
Y3 is CH, R1 is CF3, R5 is cyano and k is 0 or k is 1 , preferably 1 , and Z is cyano or trifluoromethyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, and when k is 1, Z is attached to the 4 position of the imidazole moiety.
In another group of compounds of formula ID R5 is cyano, k is 0 or 1 and Z is cyano or trifluoromethyl.
In another group of compounds of formula ID R5 is cyano, k is 0 or 1 , preferably 1 , and Z is cyano or trifluoromethyl, and when k is 1 , Z is attached to the 4 position of the imidazole moiety.
In another group of compounds of formula ID R5 is cyano, k is 0 or 1 and Z is cyano or trifluoromethyl, R1 is CF3, -B1-B2-B3- is -C=N-0- or -C=N-CH2-, Y1, Y2 and Y3 are CH.
In another group of compounds of formula ID R5 is cyano, k is 0 or 1 , preferably 1 , and Z is cyano or trifluoromethyl, R1 is CF3, -B1-B2-B3- is -C=N-0- or -C=N-CH2-, Y1, Y2 and Y3 are CH, and when k is 1, Z is attached to the 4 position of the imidazole moiety.In one embodiment the compound of formula I is a compound of formula IE
Figure imgf000019_0001
wherein B 1 , 3
Figure imgf000019_0002
and YJ are as defined for a compound of formula I.
In compounds of formula ID preferred definitions of B 1, B2, B3, R 1, R2, R9, Y1, Y2, Y3, are, in any combination, as set out below
Preferably R1 is trifluoromethyl, or chlorodifluoromethyl, most preferably trifluoromethyl. Preferably X1, X3 and X6 are independently hydrogen, halogen or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. More preferably X1, X3 and X6 are independently hydrogen, chloro, bromo or trifluoromethyl, wherein at least two of X1, X3 and X6 are not hydrogen. Preferably at least two of X1, X3 and X6 are chloro, bromo or trifluoromethyl.
In one group of compounds R2 is 3,5-dichlorophenyl-, 3-chloro-4-fluorophenyl-, 3-fluoro-4- chlorophenyl-, 3,4-dichlorophenyl-, 3-chloro-4-bromophenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5- trichlorophenyl-, 3,5-dichloro-4-iodophenyl-, 3,4,5-trifluorophenyl-, 3-chloro-5-bromophenyl-, 3-chloro- 5-fluorophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,4-dichloro-5-(trifluoromethyl)phenyl-, 3,5- bis(trifluoromethyl)phenyl-, 4-chloro-3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6- dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3-bromo-5-(trifluoromethyl)phenyl-, more preferably 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5-bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4- pyridyl-, 2,6-bis(trifluoromethyl)-4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5- (trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-, more preferably R2 is 3,5-dichloro- phenyl or 3,4,5-trichloro-phenyl, most preferably 3,5-dichloro-phenyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Most preferably Y1 is CH, Y2 is CH, and Y3 is CH.
Preferably R9 is CrC4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3- Cgcycloalkyl, C3-C6cycloalkyl-CH2-, CrC4alkyl-S(0)-CH2-, Ci-C4alkyl-S(02)-CH2-, more preferably Cr C4alkyl, CrC4haloalkyl, CrC4alkyl-0-CH2-, CrC4haloalkyl-0-CH2-,C3-C6cycloalkyl, C3-C6cycloalkyl- CH2-, more preferably Ci-C4alkyl, Ci-C4haloalkyl or C3-C4cycloalkyl, more preferably methyl, ethyl, propyl, CF3CH2- or cyclopropyl, even more preferably ethyl, CF3CH2- or cyclopropyl.
Preferably Y1 is CH, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is CH, Y3 is CH, or Y1 is N, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is N, Y3 is CH, or Y1 is CH, Y2 is CH, Y3 is N. Preferably Y1 is CH, Y2 is CH, and Y3 is CH.
In one group of compounds of formula IE -B1-B2-B3- is -C=N-0-.
In another group of compounds of formula IE -B1-B2-B3- is -C=N-0-and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IE -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is
CH and R1 is CF3.
In another group of compounds of formula IE -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R9 is CrC4alkyl.
In another group of compounds of formula IE -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R9 is CrC4haloalkyl.
In another group of compounds of formula IE -B1-B2-B3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is C3-C4cycloalkyl. In another group of compounds of formula IE -β'-Β^Β3- is -C=N-0-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is Ci-C4alkyl, Ci-C4haloalkyl or C3-C4cycloalkyl and R2 is 3-chloro-5-bromophenyl-,
3- chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)- 4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IE -B1-B2-B3- is -C=N-CH2-.
In another group of compounds of formula IE -B'-B^B3- is -C=N-CH2- and Y1 is CH, Y2 is CH, Y3 is CH.
In another group of compounds of formula IE -β'-Β^Β3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IE -β'-Β^Β3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R9 is CrC4alkyl.
In another group of compounds of formula IE -β'-Β^Β3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R9 is CrC4haloalkyl.
In another group of compounds of formula IE -β'-Β^Β3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is C3-C4cycloalkyl.
In another group of compounds of formula IE -β'-Β^Β3- is -C=N-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is Ci-C4alkyl, Ci-C4haloalkyl or C3-C4cycloalkyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)-
4- pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
In one group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2- and Y1 is CH, Y2 is
CH, Y3 is CH.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH and R1 is CF3.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3 and R9 is CrC4alkyl.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, and R9 is CrC4haloalkyl.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is C3-C4cycloalkyl.
In another group of compounds of formula IE -B1-B2-B3- is -N-CH2-CH2-, Y1 is CH, Y2 is CH, Y3 is CH, R1 is CF3, R9 is Ci-C4alkyl, Ci-C4haloalkyl or C3-C4cycloalkyl and R2 is 3-chloro-5-bromophenyl-, 3-chloro-5-(trifluoromethyl)phenyl-, 3,5-dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl-, 3,5- bis(trifluoromethyl)phenyl-, 3-(trifluoromethyl)phenyl-, 2,6-dichloro-4-pyridyl-, 2,6-bis(trifluoromethyl)- 4-pyridyl-, 3,5-dichloro-4-bromophenyl-, 3-bromo-5-(trifluoromethyl)phenyl-, 3,5-dibromophenyl-, or 3,4-dichlorophenyl-.
The following compounds of formula 1-1, 1-2 and 1-3 illustrate the compounds of formula I when -B'-B^B3- is -C=N-0-, -C=N-CH2- , or -N-CH2-CH2- respectively.
Figure imgf000022_0001
(1-1 ) (I-2) (I-3)
Tables 1 to 30 below illustrate compounds of the invention.
Figure imgf000022_0002
Table 1
Table 1 provides 304 compounds of formula la wherein R5 is hydrogen, B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 2
Table 2 provides 304 compounds of formula la wherein R5 is methyl, B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 3
Table 3 provides 304 compounds of formula la wherein R5 is trifluoromethyl, B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 4
Table 4 provides 304 compounds of formula la wherein R5 is chloro, B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 5
Table 5 provides 304 compounds of formula la wherein R5 is bromo, B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 6
Table 6 provides 304 compounds of formula la wherein R5 is hydrogen, B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 7
Table 7 provides 304 compounds of formula la wherein R5 is methyl, B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 8
Table 8 provides 304 compounds of formula la wherein R5 is trifluoromethyl, B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 9
Table 9 provides 304 compounds of formula la wherein R5 is chloro, B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 10
Table 10 provides 304 compounds of formula la wherein R5 is bromo, B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 11
Table 11 provides 304 compounds of formula la wherein R5 is hydrogen, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
Table 12
Table 12 provides 304 compounds of formula la wherein R5 is methyl, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
Table 13
Table 13 provides 304 compounds of formula la wherein R5 is trifluoromethyl, B1-B2-B3 is N-CH2- CH2, and R2 and R8 are as defined in Table P.
Table 14
Table 14 provides 304 compounds of formula la wherein R5 is chloro, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
Table 15
Table 15 provides 304 compounds of formula la wherein R5 is bromo, B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
Table P
R2 R8
1 3,5- dichloropheny 1 methyl
2 3 -chloro-4-fluorophenyl methyl
3 3-fluoro-4-chlorophenyl methyl
4 3 ,4-dichlorophenyl methyl
5 3 -chloro-4-bromophenyl methyl
6 3,5-dichloro-4-fluorophenyl methyl
7 3,4,5-trichlorophenyl methyl
8 3,5-dichloro-4-iodophenyl methyl
9 3,4,5-trifluorophenyl methyl
10 3-chloro-5-bromophenyl methyl
11 3-chloro-5-fluorophenyl methyl
12 3-chloro-5-(trifluoromethyl)phenyl methyl
13 3,4-dichloro-5-(trifluoromethyl)phenyl methyl
14 3 , 5 -bis(trifluoromethyl)phenyl methyl
15 4-chloro-3,5-bis(trifluoromethyl)phenyl methyl
16 3 -(trifluoromethyl)phenyl methyl
17 2,6-dichloro-4-pyridyl methyl
18 2,6-bis(trifluoromethyl)-4-pyridyl methyl
19 3-bromo-5-trifluoromethylphenyl methyl
20 3,5- dichloropheny 1 ethyl
21 3 -chloro-4-fluorophenyl ethyl
22 3-fluoro-4-chlorophenyl ethyl
23 3 ,4-dichlorophenyl ethyl
24 3 -chloro-4-bromophenyl ethyl
25 3,5-dichloro-4-fluorophenyl ethyl
26 3,4,5-trichlorophenyl ethyl
27 3,5-dichloro-4-iodophenyl ethyl
28 3,4,5-trifluorophenyl ethyl 3-chloro-5-bromophenyl ethyl
3-chloro-5-fluorophenyl ethyl
3-chloro-5-(trifluoromethyl)phenyl ethyl
3,4-dichloro-5-(trifluoromethyl)phenyl ethyl
3 , 5 -bis(trifluoromethyl)phenyl ethyl
4-chloro-3,5-bis(trifluoromethyl)phenyl ethyl
3 -(trifluoromethyl)phenyl ethyl
2,6-dichloro-4-pyridyl ethyl
2,6-bis(trifluoromethyl)-4-pyridyl ethyl
3-bromo-5-trifluoromethylphenyl ethyl
3,5- dichloropheny 1 propyl
3 -chloro-4-fluorophenyl propyl
3-fluoro-4-chlorophenyl propyl
3 ,4-dichlorophenyl propyl
3 -chloro-4-bromophenyl propyl
3,5-dichloro-4-fluorophenyl propyl
3,4,5-trichlorophenyl propyl
3,5-dichloro-4-iodophenyl propyl
3,4,5-trifluorophenyl propyl
3-chloro-5-bromophenyl propyl
3-chloro-5-fluorophenyl propyl
3-chloro-5-(trifluoromethyl)phenyl propyl
3,4-dichloro-5-(trifluoromethyl)phenyl propyl
3 , 5 -bis(trifluoromethyl)phenyl propyl
4-chloro-3,5-bis(trifluoromethyl)phenyl propyl
3 -(trifluoromethyl)phenyl propyl
2,6-dichloro-4-pyridyl propyl
2,6-bis(trifluoromethyl)-4-pyridyl propyl
3-bromo-5-trifluoromethylphenyl propyl
3,5- dichloropheny 1 isopropyl
3 -chloro-4-fluorophenyl isopropyl
3-fluoro-4-chlorophenyl isopropyl
3 ,4-dichlorophenyl isopropyl
3 -chloro-4-bromophenyl isopropyl
3,5-dichloro-4-fluorophenyl isopropyl
3,4,5-trichlorophenyl isopropyl
3,5-dichloro-4-iodophenyl isopropyl
3,4,5-trifluorophenyl isopropyl
3-chloro-5-bromophenyl isopropyl
3-chloro-5-fluorophenyl isopropyl
3-chloro-5-(trifluoromethyl)phenyl isopropyl
3,4-dichloro-5-(trifluoromethyl)phenyl isopropyl
3 , 5 -bis(trifluoromethyl)phenyl isopropyl
4-chloro-3,5-bis(trifluoromethyl)phenyl isopropyl
3 -(trifluoromethyl)phenyl isopropyl
2,6-dichloro-4-pyridyl isopropyl 75 2,6-bis(trifluoromethyl)-4-pyridyl isopropyl
76 3-bromo-5-trifluoromethylphenyl isopropyl
77 3,5- dichloropheny 1 CH3CH2CH(CH3)-
78 3 -chloro-4-fluorophenyl CH3CH2CH(CH3)-
79 3-fluoro-4-chlorophenyl CH3CH2CH(CH3)-
80 3 ,4-dichlorophenyl CH3CH2CH(CH3)-
81 3 -chloro-4-bromophenyl CH3CH2CH(CH3)-
82 3,5-dichloro-4-fluorophenyl CH3CH2CH(CH3)-
83 3,4,5-trichlorophenyl CH3CH2CH(CH3)-
84 3,5-dichloro-4-iodophenyl CH3CH2CH(CH3)-
85 3,4,5-trifluorophenyl CH3CH2CH(CH3)-
86 3-chloro-5-bromophenyl CH3CH2CH(CH3)-
87 3-chloro-5-fluorophenyl CH3CH2CH(CH3)-
88 3-chloro-5-(trifluoromethyl)phenyl CH3CH2CH(CH3)-
89 3,4-dichloro-5-(trifluoromethyl)phenyl CH3CH2CH(CH3)-
90 3 , 5 -bis(trifluoromethyl)phenyl CH3CH2CH(CH3)-
91 4-chloro-3,5-bis(trifluoromethyl)phenyl CH3CH2CH(CH3)-
92 3 -(trifluoromethyl)phenyl CH3CH2CH(CH3)-
93 2,6-dichloro-4-pyridyl CH3CH2CH(CH3)-
94 2,6-bis(trifluoromethyl)-4-pyridyl CH3CH2CH(CH3)-
95 3-bromo-5-trifluoromethylphenyl CH3CH2CH(CH3)-
96 3,5- dichloropheny 1 CH30CH2-
97 3 -chloro-4-fluorophenyl CH30CH2-
98 3-fluoro-4-chlorophenyl CH30CH2-
99 3 ,4-dichlorophenyl CH30CH2-
100 3 -chloro-4-bromophenyl CH30CH2-
101 3,5-dichloro-4-fluorophenyl CH30CH2-
102 3,4,5-trichlorophenyl CH30CH2-
103 3,5-dichloro-4-iodophenyl CH30CH2-
104 3,4,5-trifluorophenyl CH30CH2-
105 3-chloro-5-bromophenyl CH30CH2-
106 3-chloro-5-fluorophenyl CH30CH2-
107 3-chloro-5-(trifluoromethyl)phenyl CH30CH2-
108 3,4-dichloro-5-(trifluoromethyl)phenyl CH30CH2-
109 3 , 5 -bis(trifluoromethyl)phenyl CH30CH2-
110 4-chloro-3,5-bis(trifluoromethyl)phenyl CH30CH2-
111 3 -(trifluoromethyl)phenyl CH30CH2-
112 2,6-dichloro-4-pyridyl CH30CH2-
113 2,6-bis(trifluoromethyl)-4-pyridyl CH30CH2-
114 3-bromo-5-trifluoromethylphenyl CH30CH2-
115 3,5- dichloropheny 1 CH30CH2CH2-
116 3 -chloro-4-fluorophenyl CH30CH2CH2-
117 3-fluoro-4-chlorophenyl CH30CH2CH2-
118 3 ,4-dichlorophenyl CH30CH2CH2-
119 3 -chloro-4-bromophenyl CH30CH2CH2-
120 3,5-dichloro-4-fluorophenyl CH30CH2CH2- 121 3,4,5-trichlorophenyl CH30CH2CH2-
122 3,5-dichloro-4-iodophenyl CH30CH2CH2-
123 3,4,5-trifluorophenyl CH30CH2CH2-
124 3-chloro-5-bromophenyl CH30CH2CH2-
125 3-chloro-5-fluorophenyl CH30CH2CH2-
126 3-chloro-5-(trifluoromethyl)phenyl CH30CH2CH2-
127 3,4-dichloro-5-(trifluoromethyl)phenyl CH30CH2CH2-
128 3 , 5 -bis(trifluoromethyl)phenyl CH30CH2CH2-
129 4-chloro-3,5-bis(trifluoromethyl)phenyl CH30CH2CH2-
130 3 -(trifluoromethyl)phenyl CH30CH2CH2-
131 2,6-dichloro-4-pyridyl CH30CH2CH2-
132 2,6-bis(trifluoromethyl)-4-pyridyl CH30CH2CH2-
133 3-bromo-5-trifluoromethylphenyl CH30CH2CH2-
134 3,5- dichloropheny 1 CH30CH(CH3)CH2-
135 3 -chloro-4-fluorophenyl CH30CH(CH3)CH2-
136 3-fluoro-4-chlorophenyl CH30CH(CH3)CH2-
137 3 ,4-dichlorophenyl CH30CH(CH3)CH2-
138 3 -chloro-4-bromophenyl CH30CH(CH3)CH2-
139 3,5-dichloro-4-fluorophenyl CH30CH(CH3)CH2-
140 3,4,5-trichlorophenyl CH30CH(CH3)CH2-
141 3,5-dichloro-4-iodophenyl CH30CH(CH3)CH2-
142 3,4,5-trifluorophenyl CH30CH(CH3)CH2-
143 3-chloro-5-bromophenyl CH30CH(CH3)CH2-
144 3-chloro-5-fluorophenyl CH30CH(CH3)CH2-
145 3-chloro-5-(trifluoromethyl)phenyl CH30CH(CH3)CH2-
146 3,4-dichloro-5-(trifluoromethyl)phenyl CH30CH(CH3)CH2-
147 3 , 5 -bis(trifluoromethyl)phenyl CH30CH(CH3)CH2-
148 4-chloro-3,5-bis(trifluoromethyl)phenyl CH30CH(CH3)CH2-
149 3 -(trifluoromethyl)phenyl CH30CH(CH3)CH2-
150 2,6-dichloro-4-pyridyl CH30CH(CH3)CH2-
151 2,6-bis(trifluoromethyl)-4-pyridyl CH30CH(CH3)CH2-
152 3-bromo-5-trifluoromethylphenyl CH30CH(CH3)CH2-
153 3,5- dichloropheny 1 cyclopropyl
154 3 -chloro-4-fluorophenyl cyclopropyl
155 3-fluoro-4-chlorophenyl cyclopropyl
156 3 ,4-dichlorophenyl cyclopropyl
157 3 -chloro-4-bromophenyl cyclopropyl
158 3,5-dichloro-4-fluorophenyl cyclopropyl
159 3,4,5-trichlorophenyl cyclopropyl
160 3,5-dichloro-4-iodophenyl cyclopropyl
161 3,4,5-trifluorophenyl cyclopropyl
162 3-chloro-5-bromophenyl cyclopropyl
163 3-chloro-5-fluorophenyl cyclopropyl
164 3-chloro-5-(trifluoromethyl)phenyl cyclopropyl
165 3,4-dichloro-5-(trifluoromethyl)phenyl cyclopropyl
166 3 , 5 -bis(trifluoromethyl)phenyl cyclopropyl 167 4-chloro-3,5-bis(trifluoromethyl)phenyl cyclopropyl
168 3 -(trifluoromethyl)phenyl cyclopropyl
169 2,6-dichloro-4-pyridyl cyclopropyl
170 2,6-bis(trifluoromethyl)-4-pyridyl cyclopropyl
171 3-bromo-5-trifluoromethylphenyl cyclopropyl
172 3,5- dichloropheny 1 Cyclopropyl-CH2-
173 3 -chloro-4-fluorophenyl Cyclopropyl-CH2-
174 3-fluoro-4-chlorophenyl Cyclopropyl-CH2-
175 3 ,4-dichlorophenyl Cyclopropyl-CH2-
176 3 -chloro-4-bromophenyl Cyclopropyl-CH2-
177 3,5-dichloro-4-fluorophenyl Cyclopropyl-CH2-
178 3,4,5-trichlorophenyl Cyclopropyl-CH2-
179 3,5-dichloro-4-iodophenyl Cyclopropyl-CH2-
180 3,4,5-trifluorophenyl Cyclopropyl-CH2-
181 3-chloro-5-bromophenyl Cyclopropyl-CH2-
182 3-chloro-5-fluorophenyl Cyclopropyl-CH2-
183 3-chloro-5-(trifluoromethyl)phenyl Cyclopropyl-CH2-
184 3,4-dichloro-5-(trifluoromethyl)phenyl Cyclopropyl-CH2-
185 3 , 5 -bis(trifluoromethyl)phenyl Cyclopropyl-CH2-
186 4-chloro-3,5-bis(trifluoromethyl)phenyl Cyclopropyl-CH2-
187 3 -(trifluoromethyl)phenyl Cyclopropyl-CH2-
188 2,6-dichloro-4-pyridyl Cyclopropyl-CH2-
189 2,6-bis(trifluoromethyl)-4-pyridyl Cyclopropyl-CH2-
190 3-bromo-5-trifluoromethylphenyl Cyclopropyl-CH2-
191 3,5- dichloropheny 1 cyclobutyl
192 3 -chloro-4-fluorophenyl cyclobutyl
193 3-fluoro-4-chlorophenyl cyclobutyl
194 3 ,4-dichlorophenyl cyclobutyl
195 3 -chloro-4-bromophenyl cyclobutyl
196 3,5-dichloro-4-fluorophenyl cyclobutyl
197 3,4,5-trichlorophenyl cyclobutyl
198 3,5-dichloro-4-iodophenyl cyclobutyl
199 3,4,5-trifluorophenyl cyclobutyl
200 3-chloro-5-bromophenyl cyclobutyl
201 3-chloro-5-fluorophenyl cyclobutyl
202 3-chloro-5-(trifluoromethyl)phenyl cyclobutyl
203 3,4-dichloro-5-(trifluoromethyl)phenyl cyclobutyl
204 3 , 5 -bis(trifluoromethyl)phenyl cyclobutyl
205 4-chloro-3,5-bis(trifluoromethyl)phenyl cyclobutyl
206 3 -(trifluoromethyl)phenyl cyclobutyl
207 2,6-dichloro-4-pyridyl cyclobutyl
208 2,6-bis(trifluoromethyl)-4-pyridyl cyclobutyl
209 3-bromo-5-trifluoromethylphenyl cyclobutyl
210 3,5- dichloropheny 1 CH3-S-CH2-
211 3 -chloro-4-fluorophenyl CH3-S-CH2-
212 3-fluoro-4-chlorophenyl CH3-S-CH2- 213 3 ,4-dichlorophenyl CH3-S-CH2-
214 3 -chloro-4-bromophenyl CH3-S-CH2-
215 3,5-dichloro-4-fluorophenyl CH3-S-CH2-
216 3,4,5-trichlorophenyl CH3-S-CH2-
217 3,5-dichloro-4-iodophenyl CH3-S-CH2-
218 3,4,5-trifluorophenyl CH3-S-CH2-
219 3-chloro-5-bromophenyl CH3-S-CH2-
220 3-chloro-5-fluorophenyl CH3-S-CH2-
221 3-chloro-5-(trifluoromethyl)phenyl CH3-S-CH2-
222 3,4-dichloro-5-(trifluoromethyl)phenyl CH3-S-CH2-
223 3 , 5 -bis(trifluoromethyl)phenyl CH3-S-CH2-
224 4-chloro-3,5-bis(trifluoromethyl)phenyl CH3-S-CH2-
225 3 -(trifluoromethyl)phenyl CH3-S-CH2-
226 2,6-dichloro-4-pyridyl CH3-S-CH2-
227 2,6-bis(trifluoromethyl)-4-pyridyl CH3-S-CH2-
228 3-bromo-5-trifluoromethylphenyl CH3-S-CH2-
229 3,5- dichloropheny 1 CH3-S(0)-CH2-
230 3 -chloro-4-fluorophenyl CH3-S(0)-CH2-
231 3-fluoro-4-chlorophenyl CH3-S(0)-CH2-
232 3 ,4-dichlorophenyl CH3-S(0)-CH2-
233 3 -chloro-4-bromophenyl CH3-S(0)-CH2-
234 3,5-dichloro-4-fluorophenyl CH3-S(0)-CH2-
235 3,4,5-trichlorophenyl CH3-S(0)-CH2-
236 3,5-dichloro-4-iodophenyl CH3-S(0)-CH2-
237 3,4,5-trifluorophenyl CH3-S(0)-CH2-
238 3-chloro-5-bromophenyl CH3-S(0)-CH2-
239 3-chloro-5-fluorophenyl CH3-S(0)-CH2-
240 3-chloro-5-(trifluoromethyl)phenyl CH3-S(0)-CH2-
241 3,4-dichloro-5-(trifluoromethyl)phenyl CH3-S(0)-CH2-
242 3 , 5 -bis(trifluoromethyl)phenyl CH3-S(0)-CH2-
243 4-chloro-3,5-bis(trifluoromethyl)phenyl CH3-S(0)-CH2-
244 3 -(trifluoromethyl)phenyl CH3-S(0)-CH2-
245 2,6-dichloro-4-pyridyl CH3-S(0)-CH2-
246 2,6-bis(trifluoromethyl)-4-pyridyl CH3-S(0)-CH2-
247 3-bromo-5-trifluoromethylphenyl CH3-S(0)-CH2-
248 3,5- dichloropheny 1 CH3-S(02)-CH2-
249 3 -chloro-4-fluorophenyl CH3-S(02)-CH2-
250 3-fluoro-4-chlorophenyl CH3-S(02)-CH2-
251 3 ,4-dichlorophenyl CH3-S(02)-CH2-
252 3 -chloro-4-bromophenyl CH3-S(02)-CH2-
253 3,5-dichloro-4-fluorophenyl CH3-S(02)-CH2-
254 3,4,5-trichlorophenyl CH3-S(02)-CH2-
255 3,5-dichloro-4-iodophenyl CH3-S(02)-CH2-
256 3,4,5-trifluorophenyl CH3-S(02)-CH2-
257 3-chloro-5-bromophenyl CH3-S(02)-CH2-
258 3-chloro-5-fluorophenyl CH3-S(02)-CH2- 259 3-chloro-5-(trifluoromethyl)phenyl CH3-S(02)-CH2-
260 3,4-dichloro-5-(trifluoromethyl)phenyl CH3-S(02)-CH2-
261 3 , 5 -bis(trifluoromethyl)phenyl CH3-S(02)-CH2-
262 4-chloro-3,5-bis(trifluoromethyl)phenyl CH3-S(02)-CH2-
263 3 -(trifluoromethyl)phenyl CH3-S(02)-CH2-
264 2,6-dichloro-4-pyridyl CH3-S(02)-CH2-
265 2,6-bis(trifluoromethyl)-4-pyridyl CH3-S(02)-CH2-
266 3-bromo-5-trifluoromethylphenyl CH3-S(02)-CH2-
267 3,5- dichloropheny 1 tetrahydrofuran-2-yl
268 3 -chloro-4-fluorophenyl tetrahydrofuran-2-yl
269 3-fluoro-4-chlorophenyl tetrahydrofuran-2-yl
270 3 ,4-dichlorophenyl tetrahydrofuran-2-yl
271 3 -chloro-4-bromophenyl tetrahydrofuran-2-yl
272 3,5-dichloro-4-fluorophenyl tetrahydrofuran-2-yl
273 3,4,5-trichlorophenyl tetrahydrofuran-2-yl
274 3,5-dichloro-4-iodophenyl tetrahydrofuran-2-yl
275 3,4,5-trifluorophenyl tetrahydrofuran-2-yl
276 3-chloro-5-bromophenyl tetrahydrofuran-2-yl
277 3-chloro-5-fluorophenyl tetrahydrofuran-2-yl
278 3-chloro-5-(trifluoromethyl)phenyl tetrahydrofuran-2-yl
279 3,4-dichloro-5-(trifluoromethyl)phenyl tetrahydrofuran-2-yl
280 3 , 5 -bis(trifluoromethyl)phenyl tetrahydrofuran-2-yl
281 4-chloro-3,5-bis(trifluoromethyl)phenyl tetrahydrofuran-2-yl
282 3 -(trifluoromethyl)phenyl tetrahydrofuran-2-yl
283 2,6-dichloro-4-pyridyl tetrahydrofuran-2-yl
284 2,6-bis(trifluoromethyl)-4-pyridyl tetrahydrofuran-2-yl
285 3-bromo-5-trifluoromethylphenyl tetrahydrofuran-2-yl
286 3,5- dichloropheny 1 tetrahydrofuran-3 -yl
287 3 -chloro-4-fluorophenyl tetrahydrofuran-3 -yl
288 3-fluoro-4-chlorophenyl tetrahydrofuran-3 -yl
289 3 ,4-dichlorophenyl tetrahydrofuran-3 -yl
290 3 -chloro-4-bromophenyl tetrahydrofuran-3 -yl
291 3,5-dichloro-4-fluorophenyl tetrahydrofuran-3 -yl
292 3,4,5-trichlorophenyl tetrahydrofuran-3 -yl
293 3,5-dichloro-4-iodophenyl tetrahydrofuran-3 -yl
294 3,4,5-trifluorophenyl tetrahydrofuran-3 -yl
295 3-chloro-5-bromophenyl tetrahydrofuran-3 -yl
296 3-chloro-5-fluorophenyl tetrahydrofuran-3 -yl
297 3-chloro-5-(trifluoromethyl)phenyl tetrahydrofuran-3 -yl
298 3,4-dichloro-5-(trifluoromethyl)phenyl tetrahydrofuran-3 -yl
299 3 , 5 -bis(trifluoromethyl)phenyl tetrahydrofuran-3 -yl
300 4-chloro-3,5-bis(trifluoromethyl)phenyl tetrahydrofuran-3 -yl
301 3 -(trifluoromethyl)phenyl tetrahydrofuran-3 -yl
302 2,6-dichloro-4-pyridyl tetrahydrofuran-3 -yl
303 2,6-bis(trifluoromethyl)-4-pyridyl tetrahydrofuran-3 -yl
304 3-bromo-5-trifluoromethylphenyl tetrahydrofuran-3 -yl
Figure imgf000030_0001
Table 16
Table 16 provides 304 compounds of formula lb wherein B1-B2-B3 is C=N-0, and R2 and R8 are as defined in Table P.
Table 17
Table 17 provides 304 compounds of formula lb wherein B1-B2-B3 is C=N-CH2, and R2 and R8 are as defined in Table P.
Table 18
Table 18 provides 304 compounds of formula lb wherein B1-B2-B3 is N-CH2-CH2, and R2 and R8 are as defined in Table P.
Figure imgf000030_0002
Table 19
Table 19 provides 19 compounds of formula Ic wherein B1-B2-B3 is C=N-0, and R2 is as defined in Table Q.
Table 20
Table 20 provides 19 compounds of formula Ic wherein B1-B2-B3 is C=N-CH2, and R2 is as defined in Table Q.
Table 21
Table 21 provides 19 compounds of formula Ic wherein B 1-B2-B3 is N-CH2-CH2, and R2 is as defined in Table Q.
Figure imgf000030_0003
Table 22 provides 19 compounds of formula Id wherein k is CN, B1-B2-B3 is C=N-0 and R2 is as defined in Table Q.
Table 23
Table 23 provides 19 compounds of formula Id wherein k is CF3, B1-B2-B3 is C=N-0 and R2 is as defined in Table Q.
Table 24
Table 24 provides 19 compounds of formula Id wherein k is CN, B1-B2-B3 is C=N-CH2 and R2 is as defined in Table Q.
Table 25
Table 25 provides 19 compounds of formula Id wherein k is CF3, B1-B2-B3 is C=N-CH2 and R2 is as defined in Table Q.
Table 26
Table 26 provides 19 compounds of formula Id wherein k is CN, B1-B2-B3 is N-CH2-CH2 and R2 is as defined in Table Q.
Table 27
Table 27 provides 19 compounds of formula Id wherein k is CF3, B1-B2-B3 is N-CH2-CH2 and R2 is as defined in Table Q.
Table 0
R2
1 3,5- dichloropheny 1
2 3 -chloro-4-fluorophenyl
3 3-fluoro-4-chlorophenyl
4 3 ,4-dichlorophenyl
5 3 -chloro-4-bromophenyl
6 3,5-dichloro-4-fluorophenyl
7 3,4,5-trichlorophenyl
8 3,5-dichloro-4-iodophenyl
9 3,4,5-trifluorophenyl
10 3-chloro-5-bromophenyl
11 3-chloro-5-fluorophenyl
12 3-chloro-5-(trifluoromethyl)phenyl
13 3,4-dichloro-5-(trifluoromethyl)phenyl
14 3 , 5 -bis(trifluoromethyl)phenyl
15 4-chloro-3,5-bis(trifluoromethyl)phenyl
16 3 -(trifluoromethyl)phenyl
17 2,6-dichloro-4-pyridyl
18 2,6-bis(trifluoromethyl)-4-pyridyl
19 3-bromo-5-trifluoromethylphenyl
Figure imgf000032_0001
Table 28
Table 28 provides 114 compounds of formula le wherein B1-B2-B3 is C=N-0, and R2 and R9 are as defined in Table S.
Table 29
Table 29 provides 114 compounds of formula le wherein B1-B2-B3 is C=N-CH2, and R2 and R9 are as defined in Table S.
Table 30
Table 30 provides 114 compounds of formula le wherein B1-B2-B3 is N-CH2-CH2, and R2 and R9 are as defined in Table S.
Table S
R2 R9
1 3,5- dichloropheny 1 methyl
2 3 -chloro-4-fluorophenyl methyl
3 3-fluoro-4-chlorophenyl methyl
4 3 ,4-dichlorophenyl methyl
5 3 -chloro-4-bromophenyl methyl
6 3,5-dichloro-4-fluorophenyl methyl
7 3,4,5-trichlorophenyl methyl
8 3,5-dichloro-4-iodophenyl methyl
9 3,4,5-trifluorophenyl methyl
10 3-chloro-5-bromophenyl methyl
11 3-chloro-5-fluorophenyl methyl
12 3-chloro-5-(trifluoromethyl)phenyl methyl
13 3,4-dichloro-5-(trifluoromethyl)phenyl methyl
14 3 , 5 -bis(trifluoromethyl)phenyl methyl
15 4-chloro-3,5-bis(trifluoromethyl)phenyl methyl
16 3 -(trifluoromethyl)phenyl methyl
17 2,6-dichloro-4-pyridyl methyl
18 2,6-bis(trifluoromethyl)-4-pyridyl methyl
19 3-bromo-5-trifluoromethylphenyl methyl
20 3,5- dichloropheny 1 ethyl
21 3 -chloro-4-fluorophenyl ethyl
22 3-fluoro-4-chlorophenyl ethyl
23 3 ,4-dichlorophenyl ethyl
24 3 -chloro-4-bromophenyl ethyl
25 3,5-dichloro-4-fluorophenyl ethyl 3,4,5-trichlorophenyl ethyl
3,5-dichloro-4-iodophenyl ethyl
3,4,5-trifluorophenyl ethyl
3-chloro-5-bromophenyl ethyl
3-chloro-5-fluorophenyl ethyl
3-chloro-5-(trifluoromethyl)phenyl ethyl
3,4-dichloro-5-(trifluoromethyl)phenyl ethyl
3 , 5 -bis(trifluoromethyl)phenyl ethyl
4-chloro-3,5-bis(trifluoromethyl)phenyl ethyl
3 -(trifluoromethyl)phenyl ethyl
2,6-dichloro-4-pyridyl ethyl
2,6-bis(trifluoromethyl)-4-pyridyl ethyl
3-bromo-5-trifluoromethylphenyl ethyl
3,5- dichloropheny 1 cyclopropyl
3 -chloro-4-fluorophenyl cyclopropyl
3-fluoro-4-chlorophenyl cyclopropyl
3 ,4-dichlorophenyl cyclopropyl
3 -chloro-4-bromophenyl cyclopropyl
3,5-dichloro-4-fluorophenyl cyclopropyl
3,4,5-trichlorophenyl cyclopropyl
3,5-dichloro-4-iodophenyl cyclopropyl
3,4,5-trifluorophenyl cyclopropyl
3-chloro-5-bromophenyl cyclopropyl
3-chloro-5-fluorophenyl cyclopropyl
3-chloro-5-(trifluoromethyl)phenyl cyclopropyl
3,4-dichloro-5-(trifluoromethyl)phenyl cyclopropyl
3 , 5 -bis(trifluoromethyl)phenyl cyclopropyl
4-chloro-3,5-bis(trifluoromethyl)phenyl cyclopropyl
3 -(trifluoromethyl)phenyl cyclopropyl
2,6-dichloro-4-pyridyl cyclopropyl
2,6-bis(trifluoromethyl)-4-pyridyl cyclopropyl
3-bromo-5-trifluoromethylphenyl cyclopropyl
3,5- dichloropheny 1 CF3CH2-
3 -chloro-4-fluorophenyl CF3CH2-
3-fluoro-4-chlorophenyl CF3CH2-
3 ,4-dichlorophenyl CF3CH2-
3 -chloro-4-bromophenyl CF3CH2-
3,5-dichloro-4-fluorophenyl CF3CH2-
3,4,5-trichlorophenyl CF3CH2-
3,5-dichloro-4-iodophenyl CF3CH2-
3,4,5-trifluorophenyl CF3CH2-
3-chloro-5-bromophenyl CF3CH2-
3-chloro-5-fluorophenyl CF3CH2-
3-chloro-5-(trifluoromethyl)phenyl CF3CH2-
3,4-dichloro-5-(trifluoromethyl)phenyl CF3CH2-
3 , 5 -bis(trifluoromethyl)phenyl CF3CH2- 72 4-chloro-3,5-bis(trifluoromethyl)phenyl CF3CH2-
73 3 -(trifluoromethyl)phenyl CF3CH2-
74 2,6-dichloro-4-pyridyl CF3CH2-
75 2,6-bis(trifluoromethyl)-4-pyridyl CF3CH2-
76 3-bromo-5-trifluoromethylphenyl CF3CH2-
77 3,5- dichloropheny 1 cyclopropyl-CH2-
78 3 -chloro-4-fluorophenyl cyclopropyl-CH2-
79 3-fluoro-4-chlorophenyl cyclopropyl-CH2-
80 3 ,4-dichlorophenyl cyclopropyl-CH2-
81 3 -chloro-4-bromophenyl cyclopropyl-CH2-
82 3,5-dichloro-4-fluorophenyl cyclopropyl-CH2-
83 3,4,5-trichlorophenyl cyclopropyl-CH2-
84 3,5-dichloro-4-iodophenyl cyclopropyl-CH2-
85 3,4,5-trifluorophenyl cyclopropyl-CH2-
86 3-chloro-5-bromophenyl cyclopropyl-CH2-
87 3-chloro-5-fluorophenyl cyclopropyl-CH2-
88 3-chloro-5-(trifluoromethyl)phenyl cyclopropyl-CH2-
89 3,4-dichloro-5-(trifluoromethyl)phenyl cyclopropyl-CH2-
90 3 , 5 -bis(trifluoromethyl)phenyl cyclopropyl-CH2-
91 4-chloro-3,5-bis(trifluoromethyl)phenyl cyclopropyl-CH2-
92 3 -(trifluoromethyl)phenyl cyclopropyl-CH2-
93 2,6-dichloro-4-pyridyl cyclopropyl-CH2-
94 2,6-bis(trifluoromethyl)-4-pyridyl cyclopropyl-CH2-
95 3-bromo-5-trifluoromethylphenyl cyclopropyl-CH2-
96 3,5- dichloropheny 1 isopropyl
97 3 -chloro-4-fluorophenyl isopropyl
98 3-fluoro-4-chlorophenyl isopropyl
99 3 ,4-dichlorophenyl isopropyl
100 3 -chloro-4-bromophenyl isopropyl
101 3,5-dichloro-4-fluorophenyl isopropyl
102 3,4,5-trichlorophenyl isopropyl
103 3,5-dichloro-4-iodophenyl isopropyl
104 3,4,5-trifluorophenyl isopropyl
105 3-chloro-5-bromophenyl isopropyl
106 3-chloro-5-fluorophenyl isopropyl
107 3-chloro-5-(trifluoromethyl)phenyl isopropyl
108 3,4-dichloro-5-(trifluoromethyl)phenyl isopropyl
109 3 , 5 -bis(trifluoromethyl)phenyl isopropyl
110 4-chloro-3,5-bis(trifluoromethyl)phenyl isopropyl
111 3 -(trifluoromethyl)phenyl isopropyl
112 2,6-dichloro-4-pyridyl isopropyl
113 2,6-bis(trifluoromethyl)-4-pyridyl isopropyl
114 3-bromo-5-trifluoromethylphenyl isopropyl Compounds of formula I include at least one chiral centre and may exist as compounds of formula I* or compounds of formula I**. Compounds I* and I** are enantiomers if there is no other chiral center or epimers otherwise.
Figure imgf000035_0001
(I*) (I**)
Generally compounds of formula I** are more biologically active than compounds of formula I*.
The invention includes mixtures of compounds I* and I** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio. In an enantiomerically (or epimerically) enriched mixture of formula I**, the molar proportion of compound I** compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (or epimerically) enriched mixtures of formula I*, the molar proportion of the compound of formula I* compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Enantiomerically (or epimerically) enriched mixtures of formula I** are preferred. Each compound disclosed in Tables 1 to 30 represents a disclosure of a compound according to the compound of formula I* and a compound according to the compound of formula I**.
Likewise, group A2 may be group A2* or A2**.
Figure imgf000035_0002
(A2*) (A2**)
The invention includes mixtures of compounds of formula I with A2 as A2* and A2** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1, e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio. In an enantiomerically (or epimerically) enriched mixture of formula I with A2 as A2*, the molar proportion of formula I with A2 as A2* compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (or epimerically) enriched mixture of formula I with A2 as A2**, the molar proportion of the compound of formula I with A2 as A2**, compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Enantiomerically (or epimerically) enriched mixtures of formula I with A2 as A2** are preferred. Each compound disclosed in Tables 16 to 18 represents a disclosure of I with A2 as A2* and a compound I with A2 as A2**. Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I* with A2 as A2*. Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I** with A2 as A2*. Each compound 5 disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I* with A2 as A2**. Each compound disclosed in Tables 16 to 18 represents a disclosure of a compound according to formula I** with A2 as A2**. Enantiomerically (or epimerically) enriched mixtures of formula I** with A2 as A2** are preferred.
Likewise, group A5 may be A5* or A5**
Figure imgf000036_0001
10 (A5*) (A5**)
The invention includes mixtures of compounds of formula I with A5 as A5* and A5** in any ratio e.g. in a molar ratio of 1 :99 to 99: 1 , e.g. 10: 1 to 1 : 10, e.g. a substantially 50:50 molar ratio. In an enantiomerically (or epimerically) enriched mixture of formula I with A5 as A5*, the molar proportion of formula I with A5 as A5* compared to the total amount of both enantiomers (or epimers) is for example
15 greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (or epimerically) enriched mixture of formula I with A5 as A5**, the molar proportion of the compound of formula I with A5 as A5**, compared to the total amount of both enantiomers (or epimers) is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99%. Compounds of formula A5* are preferred.
20 Each compound disclosed in Tables 28 to 30 represents a disclosure of I with A5 as A5* and a compound I with A5 as A5**. Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I* with A5 as A5*. Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I** with A5 as A5*. Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I* with A5 as
25 A5**. Each compound disclosed in Tables 28 to 30 represents a disclosure of a compound according to formula I** with A5 as A5**.
Reference to compounds of the invention also includes reference to salts and N-oxides. The compounds of formula I may be prepared as described in WO 2008/12871 1 , WO 2010/043315, WO 201 1/051455, WO 2007/105814, WO 2008/122375, WO 2009/035004, WO
30 2009/045999, WO 2009/072621 , WO 2009/097992, WO 2010/133336, WO 2010/043315, WO
201 1/051455, WO 201 1/08021 1 , JP2010235590, JP201 1037817, JP201 1 178724, CN102210317, CN102246777, WO 2009/07261, WO 2009/097992, WO 2009/051956, each of which is incorporated herein by reference.
The term "locus" of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.
The term "plant propagation material" is understood to denote generative parts of a plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
Application may be before infestation or when the pest is present. Application of the compounds of the invention can be performed according to any of the usual modes of application, e.g. foliar, drench, soil, in furrow etc. However, control of Anthonomus grandis s is usually achieved by foliar application, which is the preferred mode of application according to the invention.
Application of the compounds of the invention is preferably to a crop of cotton plants, the locus thereof or propagation material thereof.
The compounds of the invention may be applied to plant parts. Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. The plant parts also include harvested material, and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, offshoots and seeds. Treatment according to the invention of the plants and plant parts with the active compounds can be carried out directly or by allowing the compounds to act on their surroundings, habitat or storage space by the customary treatment methods, for example by immersion, spraying, evaporation, fogging, scattering, painting on, injecting and, in the case of propagation material, in particular in the case of seed, also by applying one or more coats.
The compounds of the invention are suitable for use on any plant (preferably cotton plant), including those that have been genetically modified to be resistant to active ingredients such as herbicides, or to produce biologically active compounds that control infestation by plant pests.
The term "plant" as used herein includes seedlings, bushes and trees. Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady® and
LibertyLink®.
Compounds of formula I may be used on transgenic plants (including cultivars) obtained by genetic engineering methods and/or by conventional methods. These are understood as meaning plants having novel properties ("traits") which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive "synergistic") effects.
Thus, for example, reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the substances and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products are possible, which exceed the effects which were actually to be expected.
The preferred transgenic plants or plant cultivars which are to be treated according to the invention include all plants which, by virtue of the genetic modification, received genetic material which imparts particularly advantageous, useful traits to these plants. Examples of such traits are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, higher quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products.
Further and particularly emphasized examples of such traits are a better defence of the plants against animal and microbial pests, such as against insects, mites, phytopathogenic fungi, bacteria and/or viruses, and also increased tolerance of the plants to certain herbicidally active compounds.
Examples of transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice), maize, soybean, potatoes, sugar beet, tomatoes, peas and other vegetable varieties, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes). Transgenic cotton is of particular interest.
Compounds of formula I may be used on transgenic plants that are capable of producing one or more pesticidal proteins which confer upon the transgenic plant tolerance or resistance to harmful pests, e.g. insect pests, nematode pests and the like. Such pesticidal proteins include, without limitation, Cry proteins from Bacillus thuringiensis CrylAb, CrylAc, CrylF, Cry2Ab, Cry2Ae, Cry3A, Cry3Bb, or Cry9C; engineered proteins such as modified Cry3A ( US Patent 7,030,295) or CrylA.105; or vegetative insecticidal proteins such as Vipl, Vip2 or Vip3. A full list of Bt Cry proteins and VIPs useful in the invention can be found on the worldwide web at Bacillus thuringiensis Toxin Nomenclature Database maintained by the University of Sussex (see also, Crickmore et al. (1998) Microbiol. Mol. Biol. Rev. 62:807-813). Other pesticidal proteins useful in the invention include proteins of bacteria colonizing nematodes, e.g. Photorhabdus spp. or Xenorhabdus spp.; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins, or other insect-specific neurotoxins; toxins produced by fungi, such Streptomycetes toxins, plant lectins, such as pea or barley lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin or papain inhibitors; ribosome- inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-IDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase; ion channel blockers, such as blockers of sodium or calcium channels; juvenile hormone esterase; diuretic hormone receptors (helicokinin receptors); stilben synthase, bibenzyl synthase, chitinases or glucanases. Further examples of such pesticidal proteins or transgenic plants capable of synthesizing such proteins are disclosed, e.g., in EP-A 374753, WO 93/007278, WO 95/34656, EP-A 427529, EP-A 451878, WO 03/18810 and WO 03/52073. The methods for producing such transgenic plants are generally known to the person skilled in the art and some of which are commercially available such as Agrisure®CB (PI) (corn producing CrylAb), Agrisure®RW (P2) (corn producing mCry3A), Agrisure® Viptera (P3) (corn hybrids producing Vip3Aa); Agrisure300GT (P4) (corn hybrids producing CrylAb and mCry3A); YieldGard® (P5) (corn hybrids producing the CrylAb protein), YieldGard® Plus (P6) (corn hybrids producing CrylAb and Cry3Bbl), Genuity® SmartStax® (P7) (corn hybrids with CrylA.105, Cry2Ab2, CrylF, Cry34/35, Cry3Bb) ; Herculex® I (P8) (corn hybrids producing CrylFa) and Herculex®RW (P9) (corn hybrids producing Cry34Abl, Cry35Abl and the enzyme Phosphinothricin-N-Acetyltransferase [PAT]) ; NuCOTN®33B (P10) (cotton cultivars producing CrylAc), Bollgard®I (PI 1) (cotton cultivars producing CrylAc), Bollgard®II (P12) (cotton cultivars producing CrylAc and Cry2Ab2) and VIPCOT® (PI 3) (cotton cultivars producing a Vip3Aa). Soybean Cyst Nematode resistance soybean (SCN® - Syngenta (PI 4)) and soybean with Aphid resistant trait (AMT® (PI 5)) are also of interest.
Further examples of such transgenic crops are:
1. Btll Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (P16). Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylA(b) toxin. Btl 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Btl76 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (PI 7). Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer {Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylA(b) toxin. Btl 76 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10 (P18). Maize which has been rendered insect-resistant by transgenic expression of a modified CrylllA toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-D-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/DE/02/9 (P19). MON 863 expresses a CrylllB(bl) toxin and has resistance to certain Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-l 150 Brussels, Belgium, registration number C/ES/96/02. (P20)
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-l 160 Brussels, Belgium, registration number C/NL/00/10. (P21) Genetically modified maize for the expression of the protein Cry IF for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren,
B-l 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 χ MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylA(b) toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
Further examples of transgenic plants, and of very high interest, are those carrying traits conferring resistance to 2.4D (e.g. Enlist®) (e.g. WO 2011066384) (, glyphosate (e.g. Roundup Ready® (P24), Roundup Ready 2 Yield® (P25)), sulfonylurea (e.g. STS®) (P26), glufosinate (e.g. Liberty Link® (P27), Ignite® (P28)), Dicamba (P29) (Monsanto), HPPD tolerance (P30) (e.g. isoxaflutole herbicide) (Bayer CropScience, Syngenta). Double or triple stacks of any of the traits described here are also of interest, including glyphosate and sulfonyl-urea tolerance ((e.g. Optimum GAT®) (P31), plants stacked with STS® and Roundup Ready® (P32) or plants stacked with STS® and Roundup Ready 2 Yield® (P33)), dicamba and glyphosate tolerance (P34) (Monsanto). Of particular interest are soybean plants carrying trains conferring resistance to 2.4D (e.g. Enlist®), glyphosate (e.g. Roundup Ready®, Roundup Ready 2 Yield®), sulfonylurea (e.g. STS®), glufosinate (e.g. Liberty Link®, Ignite®), Dicamba
(Monsanto) HPPD tolerance (e.g. isoxaflutole herbicide) (Bayer CropScience, Syngenta).
Transgenic crops of insect-resistant plants are also described in BATS (Zentrum fur Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003,
(http://bats.ch).
Examples of cotton transgenic events include MON 531 / 757 / 1076 (Bollgard I ® - Monsanto), MON1445 (Roundup ready cotton ®- Monsanto), MON531 x MON1445 (Bollgard I + RR ®- Monsanto), MON15985 (Genuity Bollgard II cotton ®- Monsanto), MON88913 (Genuity RR FLEX cotton ®- Monsanto), MON15985 x MON1445 (Genuity Bollgard II + RR FELX cotton ®- Monsanto), MON15983 x MON88913 (Genuity Bollgard II + RR FLEX cotton ® - Monsanto), MON15985
(FibreMax Bollgard II Cotton ® - Monsanto), LL25 (FibreMax LL cotton ® - BCS Stoneville), GHB614 (FibreMax GlyTol cotton ®- BCS Stoneville), LL25 x MON15985 (FibreMax LL Bollgard II cotton ® - BCS Stoneville / Monsanto), GHB614 x LL25 (FibreMax LL GlyTol cotton ® - BCS Stoneville), GHB614 x LL25 x MON15985 (FibreMax RR GlyTol Bollgard II cotton ® - BCS Stoneville),
MON88913 x MON15985 (FibreMax LL GlyTol Bollgard II cotton ® - Monsanto), MON88913 (FibreMax RR Flex cotton ® - Monsanto), GHB119 + T304-40 (Twinlink ® - BCS Stoneville), GHB119 + T304-40 x LL25 x GHB614 (Twinlink LL GT ® - BCS Stoneville), 3006-210-23 x 281-24-236
(PhytoGen Widestrike Insect Protection ® - Dow), 3006-210-23 x 281-24-236 x MON88913 (PhytoGen Widestrike Insect Protection + RR FLEX - ® Dow / Monsanto), 3006-210-23 x 281-24-236 x MON1445 ((PhytoGen Widestrike Insect Protection + RR ® - Dow / Monsanto), MON1445 (PhytoGen Roundup Ready ® - Monsanto), MON88913 (PhytoGen Roundup Ready FLEX ® - Monsanto), COT102 x COT67B (Vipcot ® - Syngenta), COT102 x COT67B x MON88913 (Vipcot RR FLEX ® - Syngenta / Monsanto), 281-24-236 (Dow), 3006-210-23 (Dow), COT102 (Syngenta), COT67B (Syngenta), T304-40 (BCS Stoneville).
Examples of Soy transgenic events include MON87701 x MON89788 (Genuity Roundup ready 2 Yield soybeans® - Monsanto), MON89788 (Roundup Ready2Yield®, RR2Y® - Monsanto), MON87708 (Monsanto), 40-3-2 (Roundup Ready®, RRl® - Monsanto), MON87701 (Monsanto), DAS-68416 (Enlist Weed Control System® - Dow), DP356043 (Optimum GAT® - Pioneer), A5547-127 (LibertyLink soybean® - Bayercropscience), A2704-12 (Bayercropscience), GU262 (Bayercropscience), W62 W98 (Bayercropscience), CRV127 (Cultivance® - BASF / EMBRAPA), SYHT0H2 (WO2012/082548).
Examples of Maize transgenic events include T25 (LibertyLink®, LL® - Bayerscropscience), DHT-1 (Dow), TCI 507 (Herculex I® - Dow), DAS59122-7 (Herculex RW® - Dow), TCI 507 + DAS59122-7 - Herculex Xtra® - Dow), TCI 507 x DAS-59122-7 x NK603 (Herculex Xtra + RR® - Dow), TC1507 x DAS-59122- x MON88017 x MON89034 (Genuity Smartstax corn®, Genuity
Smartstax RIB complete® - Monsanto / Dow), MON89034 x NK603 (Genuity VT double PRO® - Monsanto), MON89034 + MON88017 (Genuity VT Triple PRO® - Monsanto), NK603 (Roundup Ready 2®, RR2® - Monsanto), MON810 (YieldGard BT®, Yieldgard cornborer® - Monsanto), MON810 x NK603 (YieldGard cornborer RR Corn 2® - Monasnto), MON810 x MON863 (YieldGard Plus® - Monsanto), MON863 x MON810 x NK603 (YieldGard Plus + RR Corn2® / YieldGard RR Maize® - Monsanto), MON863 x NK603 (YieldGard Rotworm + RR Corn 2® - Monsanto), MON863 (YieldBard RW® - Monsanto), MON89034 (YieldGard RW® - Monsanto), MON88017 (YieldGard VT RW® - Monsanto), MON810 + MON88017 (YieldGard VT Triple® - Monsanto), MON88017 + MON89034 (YieldGard VT Triple Pro® - Monsanto), Btl 1 + MIR604 + GA21 (Agrisure 3000® - Syngenta), Btl 1 + TC1507 + MIR604 + 5307 + GA21 (Syngenta), Btl 1 + TC1507 + MIR604 + DAS59122 + GA21 (Agrisure 3122® - Syngenta), BTl 1 (Agrisure CB® - Syngenta), GA21 - (Agrisure GT® - Syngenta), MIR604 (Agrisure RW® - Syngenta), Btl 1 + MIR162 (Agrisure TL VIP® - Syngenta), BTl 1 + MIR162 + GA21 (Agrisure Viptra 3110® - Syngenta), BTl 1 + MIR162 + MIR604 (Agrisure TM 3100® - Syngenta), Event3272 + BTl 1 + MIR604 + GA21 (Syngenta), BTl 1 + MIR1692 + MIR604 + GA21 (Agrisure Viptera 3111® - Syngenta), BTl 1 + MIR 162 + TC1507 + GA21 (Agrisure Viptera 3220® - Syngenta), BTl 1 + MIR162 + TC1507 + MIR604 + 5307 + GA21 (Agrisure Viptera 3222® - Syngenta), MIR162 (Syngenta), BT11 + GA21 + MIR162 + MIR604 + 5307 (Syngenta), 5307 (Syngenta).
Herbicide-resistant plants (plants bred in a conventional manner for herbicide tolerance) which may be mentioned include the varieties sold under the name Clearfield(®) (for example maize).
These statements also apply to plant cultivars having these genetic traits or genetic traits still to be developed, which plant cultivars will be developed and/or marketed in the future.
The compounds of the invention are suitable for use on any cotton plant, including those that have been genetically modified to be resistant to active ingredients such as herbicides, or to produce biologically active compounds that control infestation by plant pests, e.g. BT cotton.
A compound of the invention may be used in mixtures with fertilizers (for example nitrogen-, potassium- or phosphorus-containing fertilizers). Suitable formulation types include granules of fertilizer. The mixtures preferably contain up to 25% by weight of the compound of the invention.
The invention therefore also provides a fertilizer composition comprising a fertilizer and a compound of the invention.
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.
The compound of formula (I) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, e.g. a insecticide, fungicide or herbicide, or a synergist or plant growth regulator where appropriate. An additional active ingredient may provide a composition having a broader spectrum of activity or increased persistence at a locus; synergize the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following:
a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin and gamma cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, S-bioallethrin, fenfluthrin, prallethrin, acrinathirin, etofenprox or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate;
b) Organophosphates, such as profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbamates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl;
d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron, diafenthiuron, lufeneron, novaluron, noviflumuron or chlorfluazuron;
e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin;
f) Pyrazoles, such as tebufenpyrad, tolfenpyrad, ethiprole, pyriprole, fipronil, and fenpyroximate;
g) Macrolides, such as avermectins or milbemycins, for example abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad, azadirachtin, milbemectin, lepimectin or spinetoram;
h) Hormones or pheromones;
i) Organochlorine compounds, such as endosulfan (in particular alpha-endosulfan), benzene hexachloride, DDT, chlordane or dieldrin;
j) Amidines, such as chlordimeform or amitraz;
k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metam;
1) Neonicotinoid compounds, such as imidacloprid, thiacloprid, acetamiprid, nitenpyram, dinotefuran, thiamethoxam, clothianidin, or nithiazine;
m) Diacylhydrazines, such as tebufenozide, chromafenozide or methoxyfenozide;
n) Diphenyl ethers, such as diofenolan or pyriproxifen;
o) Ureas such as Indoxacarb or metaflumizone;
p) Ketoenols, such as Spirotetramat, spirodiclofen or spiromesifen;
q) Diamides, such as flubendiamide, chlorantraniliprole (Rynaxypyr®) or cyantraniliprole;
r) Essential oils such as Bugoil® - (Plantlmpact); or
s) a comopund selected from buprofezine, flonicamid, acequinocyl, bifenazate, cyenopyrafen, cyflumetofen, etoxazole, flometoquin, fluacrypyrim, fluensulfone, flufenerim, flupyradifuone, harpin, iodomethane, dodecadienol, pyridaben, pyridalyl, pyrimidifen, flupyradifurone, 4-[(6-Chloro-pyridin-3- ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one (DE 102006015467), CAS: 915972-17-7
(WO 2006/129714; WO 2011/147953; WO2011/147952), CAS: 26914-55-8 (WO 2007/020986), chlorfenapyr, pymetrozine, sulfoxaflor and pyrifluqinazon.
In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example stemborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethylnon, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
Examples of fungicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide (SSF-129), 4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-l -sulfonamide,
a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-y-butyrolactone, 4-chloro-2-cyano-N,N-dimethyl-5-/ tolylimidazole- 1 -sulfonamide (IKF-916, cyamidazosulfamid), 3 -5-dichloro-N-(3 -chloro- 1 -ethyl- 1 -methyl-
2- oxopropyl)-4-methylbenzamide (RH-7281 , zoxamide), N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-
3- carboxamide (MON65500), N-(l-cyano-l,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide (AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, acibenzolar (CGA245704) (e.g. acibenzolar-S-methyl), alanycarb, aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, bixafen, blasticidin S, boscalid, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture, cyclufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide 1,1 '-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim,
OjO-di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl-(Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino- oxycarbonyl)amino]thio)- -alaninate, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, fluopyram,
fluoxastrobin, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, fluxapyroxad, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate, isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY248908, mancozeb, mandipropamid, maneb, mefenoxam, metalaxyl, mepanipyrim, mepronil, metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-wopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, penthiopyrad, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxinD, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, propionic acid, prothioconazole, pyrazophos, pyrifenox, pyrimethanil, pyraclostrobin, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, sedaxane, sipconazole (F-155), sodium pentachlorophenate, spiroxamine, streptomycin, sulfur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, zineb and ziram, N- [9-(dichloromethylene)- 1 ,2,3 ,4-tetrahydro- 1 ,4-methanonaphthalen-5-yl] -3 -(difluoromethyl)- 1 -methyl- 1 H-pyrazole-4-carboxamide [1072957-71-1], 1 -methyl-3 -difluoromethyl- 1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-l -methyl- indan-4-yl)-amide, and l-methyl-3-difluoromethyl-4H-pyrazole- 4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy- 1 -methyl-ethyl]-amide.
In addition, biological agents may be included in the composition of the invention e.g. Baciullus species such as Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria species such as Pasteuria penetrans and Pasteuria nishizawae. A suitable Bacillus firmus strain is strain CNCM 1-1582 which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain CNCM 1-1562. Of both Bacillus strains more details can be found in US 6,406,690. Other biological organisms that may be included in the compositions of the invention are bacteria such as Streptomyces spp. such as S.
avermitilis, and fungi such as Pochonia spp. such as P. chlamydosporia. Also of interest are Metarhizium spp. such as M. anisopliae; Pochonia spp. such as P. chlamydosporia.
The compounds of the invention may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
An example of a rice selective herbicide which may be included is propanil. An example of a plant growth regulator for use in cotton is PIX™.
Some mixtures may comprise active ingredients which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.
Unless otherwise stated the weight ratio of the compound of I with an additional active ingredient may generally be between 1000 : 1 and 1 : 1000. In other embodiments that weight ratio of the compound of formula I to the additional active ingredient may be between 500 : 1 to 1 : 500, for example between 100 : 1 to 1 : 100, for example between 1 : 50 to 50 : 1, for example 1 : 20 to 20 : 1, for example 1 : 10 to 10: 1, for example 1 :5 to 5: 1, for example 1 : 1, 1 :2, 1 :3, 1 :4, 1 :5, 2: 1, 3: 1, 4: 1, or 5:1.
Mixtures with pyrethroids, in particular pymetrozine, are of particular interest for the present invention.
Compositions of the invention include those prepared by premixing prior to application, e.g. as a readymix or tankmix, or by simultaneous application or sequential application to the plant.
In order to apply a compounds of the invention as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, compounds of the invention is usually formulated into a composition which includes, in addition to the compound of the invention, a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%>, of a compound of the invention. The composition is generally used for the control of pests such that a compound of the invention is applied at a rate of from O.lg to 10kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
In one embodiment the compounds of the invention are used for pest control on cotton at 1 :500 g/ha, for example 10-70g/ha. However, it should be noted that due to the very damaging effect of the Anthonomus grandis (quantity and quality on yield), sprays are often very intense and at very low threshold levels and can be down to almost zero tolerance.
When used in a seed dressing, a compound of the invention is used at a rate of 0.000 lg to lOg (for example O.OOlg or 0.05g), preferably 0.005g to lOg, more preferably 0.005g to 4g, per kilogram of seed.
Compositions comprising a compound of the invention can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro- emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of the invention.
Dustable powders (DP) may be prepared by mixing a compound of the invention with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of the invention with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water
dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of the invention with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of the invention and one or more powdered solid diluents or carriers, or from pre- formed blank granules by absorbing a compound of the invention (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of the invention (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulfates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of the invention in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallization in a spray tank).
Emulsifiable concentrates (EC) or oil- in- water emulsions (EW) may be prepared by dissolving a compound of the invention in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cg-Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of the invention either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifiying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of the invention is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs. An ME may be either an oil- in- water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in- water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of the invention. SCs may be prepared by ball or bead milling the solid compound of the invention in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of the invention may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
Aerosol formulations comprise a compound of the invention and a suitable propellant (for example n-butane). A compound of the invention may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non- pressurized, hand-actuated spray pumps.
A compound of the invention may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerization stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of the invention and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of the invention and they may be used for seed treatment. A compound of the invention may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of the invention). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of the invention).
A compound of the invention may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (for example sodium lauryl sulfate), salts of sulfonated aromatic compounds (for example sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalene sulfonate and mixtures of sodium di-z' opropyl- and tri-wopropyl-naphthalene sulfonates), ether sulfates, alcohol ether sulfates (for example sodium laureth-3-sulfate), ether carboxylates (for example sodium laureth-3- carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulfosuccinamates, paraffin or olefine sulfonates, taurates and lignosulfonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide);
alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides,
polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
A compound of the invention may be applied by any of the known means of applying pesticidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapor or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water- soluble bag) in soil or an aqueous environment.
A compound of the invention may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of the invention (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
The following Examples illustrate but do not limit the invention. Example 1 : Preparation of N-r(l S)-l -r4-r3-r3,5-bis(trifluoromethyl)phenyll-3- (trifluorometh l)pyrrolidin-l -yllphenyllethyllcyclopropanecarboxamide
Figure imgf000050_0001
To a solution of 3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine (0.15 g, 0.4271 mmol, prepared as described in WO 2008/12871 1) and N-[(l S)-l -(4- bromophenyl)ethyl]cyclopropanecarboxamide (0.134 g, 0.4997 mmol, prepared as described in WO 2012/001 107) in Toluene (6.03 mL), stirred under argon were added
tris(dibenzylideneacetone)dipalladium(0) (9 mg), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (18 mg) and sodium tert-butoxide (96 mg). The mixture was heated in a microwave at 130°C for 15 min. The reaction was then diluted with ethylacetate and water then brine and then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulphate, filtered then concentrated under reduced pressure to give a yellow oil which was purified by chromatography on a column (cyclohexane/EtOAc as solvent) to afford the desired product as a white foam (172 mg).
lH NMR (CDC13, 400MHz): d = 7.92 (s, 1 H), 7.86 (s, 2 H), 7.27 (m, 2 H), 6.63 (d, J=8.4 Hz, 2 H), 5.74 (d, J=7.7 Hz, 1 H), 5.09 (t, J=7.3 Hz, 1 H), 4.16 (d, J=10.3 Hz, 1 H), 3.85 (d, J=10.3 Hz, 1 H), 3.60 (d, J=8.1 Hz, 1 H), 3.51 (d, J=2.9 Hz, 1 H), 2.91 - 3.03 (m, 1 H), 2.61 (d, J=13.6 Hz, 1 H), 1.50 (d, J=7.0 Hz, 3 H), 1.17 - 1.34 (m, 1 H), 0.90 - 1.04 (m, 2 H), 0.63 - 0.80 ppm (m, 2 H) Example 2: Preparation of N-[(l S -l-r4-[3-(3,5-dichlorophenyl -3-(trifluoromethyl pyrrolidin-l - llphenyllethyllcyclopropanecarboxamide
Figure imgf000051_0001
Tris(dibenzylideneacetone)dipalladium(0) (32 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (61 mg) and sodium tert-butoxide (190 mg) were added to a solution of 3-(3,5-dichlorophenyl)-3- (trifluoromethyl)pyrrolidine (520 mg, prepared as described in WO 2008/128711) and N-[(lS)-l-(4- bromophenyl)ethyl]cyclopropanecarboxamide (prepared as described in WO 2012/001107, 520 mg) in toluene (15 mL) under argon atmosphere. The mixture was heated in a microwave at 130°C for 30 min. The reaction was then diluted with ethylacetate and water then brine and then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over sodium sulphate, filtered then concentrated under reduced pressure to give a yellow oil which was purified by chromatography on column (Heptane/EtOAc as solvent (10/0 to 0/10) to afford the desired product as a white foam (650 mg). lU NMR (CDC13, 400MHz): d = 7.40 (s, 1 H), 7.31 (s, 2 H), 7.26 (m, 2 H), 6.62 (d, 2 H), 5.73 (d, 1 H), 5.09 (t, 1 H), 4.06 (d, 1 H), 3.85 (d, 1 H), 3.57 (m, 1 H), 3.50 (m, 1 H), 2.84 (m, 1 H), 2.56 (m, 1 H), 1.50 (d, 3 H), 1.2 (m, 1 H), 0.99 (m, 2 H), 0.72 ppm (m, 2 H)
Example 3: Preparation of N-[(l S)-l-r4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3- yllphenyl] ethyl] acetamide
Step 1 :
Figure imgf000051_0002
To a suspension of N-[(lS)-l-(4-acetylphenyl)ethyl]acetamide (3 g) and l-(3,5-dichlorophenyl)-2,2,2- trifluoro-ethanone (3.6 g) in 1 ,2-dichloroethane (40 mL) was added triethylamine (0.2 mL) and potassium carbonate (1 g). The solution was stirred at 80°C. After 40 minutes more potassium carbonate (1 g) was added. The solution was heated at 80°C for another 20 minutes then more potassium carbonate (1 g) was added and the suspension was refluxed for 16 hours. The mixture was then cooled to room temperature, and water was added. The mixture was extracted with dichloromethane then washed with brine. The organic layers were combined and dried over magnesium sulphate, filtered then concentrated under reduced pressure to give a yellow oil which was purified by chromatography on column (Heptane/EtOAc as solvent (1/0 to 3/7) to afford the desired product as a yellow oil (5 g).
1H NMR (CDC13, 400MHz): d = 7.78 - 7.87 (m, 2 H), 7.42 - 7.40 (m, 2 H), 7.33 (m, 1 H), 7.16 (d, 2 H), 5.69 (d, 1 H), 5.02 - 5.26 (m, 1 H), 2.02 (s, 3 H), 1.48 - 1.51 ppm (d, 3 H)
Step 2:
Figure imgf000052_0001
To a solution of N-[(lS)-l-[4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-but-2-enoyl]phenyl]ethyl]acetamide (100 mg) in 1 ,2-dichloroethane (4 mL) was added tetrabutylammonium hydrobromide (40 mg), hydroxylamine (0.03 mL, 50% in water) and sodium hydroxide (0.46 mL, 1M) at room temperature. The solution was stirred at room temperature for 6 hours then a solution of saturated ammonium chloride was added. The mixture was extracted with DCM then washed with brine. The organic layers were combined and dried over magnesium sulphate, filtered then concentrated under reduced pressure to give a yellow oil which was purified by chromatography on column (Heptane/EtOAc as solvent (1/0 to 1/1) to afford the desired product as a yellow oil (77 mg).
lU NMR (CDC13, 400MHz): d = 7.59 - 7.69 (m, 2 H), 7.49 - 7.57 (m, 2 H), 7.43 (t, J=1.8 Hz, 1 H), 7.34 - 7.41 (m, J=8.4 Hz, 2 H), 5.65 (d, J=7.3 Hz, 1 H), 5.15 (t, J=7.2 Hz, 1 H), 4.01 - 4.13 (m, 1 H), 3.68 (d, J=17.2 Hz, 1 H), 2.01 (s, 3 H), 1.50 (d, J=7.0 Hz, 3 H), 1.27 ppm (t, J=7.2 Hz, 1 H). Example 4: Preparation of 2-(l ,2,4-triazol-l -yl)-5-r3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dihydropyrrol-5-yllbenzonitrile
Step 1 : Preparation of 3-bromo-4-fluoro-N-(trimethylsilylmethyl)benzamide
Figure imgf000052_0002
To a solution of 3-bromo-4-fluoro-benzoic acid (500 mg, 2.2830 mmol) in dichloromethane (15 mL) was added N,N-dimethylpyridin-4-amine (28mg, 0.22830 mmol) , EDCI HC1 (570mg, 2.9679 mmol). To this was added trimethylsilylmethanamine (260mg, 2.5113 mmol) and the reaction was stirred at room temperature under nitrogen atmosphere overnight and monitored by TLC. The reaction mass was diluted with water (10 mL) and extracted with DCM (3 x 50 mL). The combined organic layer was dried over sodium sulphate and concentrated under vacuum. Purification by chromatography (hexane/ethyl acetate) provided 3-bromo-4-fluoro-N-(trimethylsilylmethyl)benzamide (550 mg, ).
¾ NMR (400MHZ, CDC13): 7.94(dd,lH); 7.65(m,lH); 7.15(t, 1H); 5.9(brs, 1H); 2.94(d, 2H); 0.12(s, 9H), LCMS (methanol, ESI): retention time = 2.06, m/z = 302.0(M-H)
Ste 2: Preparation of 3-cyano-4-fluoro-N-(trimethylsilylmethyl)benzamide
Figure imgf000053_0001
In a sealed tube was taken a solution of 3-bromo-4-fluoro-N-(trimethylsilylmethyl)benzamide (10 g, 32.870 mmol) in N,N-dimethylformamide (60 mL) was added zinc formonitrile (7.85 g, 65.740 mmol) followed by palladium(0)tetrakis(triphenylphosphine) (7.61 g, 6.5740 mmol) . The reaction was degassed and purged with nitrogen and stirred at 100°C for 4-5 hours. The reaction was diluted with water (100 mL) extracted with ethylacetate (3 x 100 mL), and washed with sodium bicarbonate (50 mL) . The combined organic layer was dried over sodium sulphate and concentrated under vacuum. Purification by chromatography (hexane/ethyl acetate) provided 3-cyano-4-fluoro-N- (trimethylsilylmethyl)benzamide(6.7 g)
lU NMR (400MHz, CDC13): 7.98-8.02(m, 2H); 7.3(m, 1H); 5.94(brs, 1H); 2.95-2.98(m, 2H); 0.13(s, 9H). LCMS (methanol, APCI): retention time = 4.11, m/z = 249.09(M-H)
Step 3: Preparation of 3-cyano-4-fluoro-N-(trimethylsilylmethyl)benzenecarbothioamide
Figure imgf000053_0002
A solution of 3-cyano-4-fluoro-N-(trimethylsilylmethyl)benzamide (6.5 g, 26 mmol) and 2,4-bis(4- methoxyphenyl)-2,4-dithioxo-l,3,2,4-dithiadiphosphetane (1 lg, 26 mmol) in tetrahydrofuran (75 mL) was refluxed for 2 hours. The reaction mass was concentrated to remove THF, diluted with water (50 mL), and extracted with ethylacetate (3 x 100 mL). The combined organic layer was dried over sodium sulphate and concentrated under vacuum. Purification by chromatography (hexane/ethyl acetate) provided 3-cyano-4-fluoro-N-(trimethylsilylmethyl) benzenecarbothioamide (4.8g).
¾ NMR (400MHZ, CDC13): 8.2(m,lH); 7.93-7.99(m,lH); 7.64(brs, lH);7.22(m,lH); 3.52(d, 2H); 0.18(s, 9H), LCMS (methanol, APCI): retention time = 4.55, m/z = 265.45(M-H). Step 4: Preparation of 2-fluoro-5-[3-(3,4,5 richlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5- ljbenzonitrile
Figure imgf000054_0001
To a solution of 3-cyano-4-fluoro-N-(trimethylsilylmethyl)benzenecarbothioamide (4 g, 15.02 mmol) in N,N-dimethylformamide (40 mL) was added dipotassium carbonic acid (5.26 g, 37.54 mmol). To this was added iodomethane (21.31 g, 150.2 mmol). The reaction mass was stirred at room temperature for 3 hours and monitored by TLC. The reaction mass was quenched with water (10 mL) and extracted with ethylacetate (3 x 50mL). The combined organic layer was dried over sodium sulphate and concentrated under vacuum to give methyl-3-cyano-4-fluoro-N-(trimethylsilylmethyl) benzenecarboximidothioate.
To a -5°C cooled solution of methyl-3-cyano-4-fluoro-N-(trimethylsilylmethyl)
benzenecarboximidothioate (4 g, 14.27 mmol) and l,2,3-trichloro-5-[l-(trifluoromethyl)vinyl]benzene (3.97g., 14.41 mmol) in tetrahydrofuran (5 mL) was slowly added tetrabutylammonium hydrofluoride (7.13 mL, 7.133 mmol, 1 mol/L) . The reaction was stirred at -5°C for 30 mins, then allowed to come to room temperature, and stirred at room temperature for 2 hours under nitrogen atmosphere. The reaction was diluted with water (50 mL) and extracted with ethylacetate (3 x 100 mL). The combined organic layer was dried over sodium sulphate and concentrated under vacuum. Purification by chromatography (hexane/ethyl acetate) provided 2-fluoro-5-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dihydropyrrol-5-yl]benzonitrile (2.5 g).
lU NMR(400MHz, CDC13): 8.04-8.13(m, 2H); 7.37(s, 2H); 7.35(m, 1H); 4.82(dd, 1H); 4.36(d, 1H); 3.7(dd, 1H); 3.35(d, 1H) ,LCMS (methanol, APCI): retention time = 5.05, m/z = 434.88(M+H)
Step 5: Preparation of 2-(l ,2,4-triazol-l-yl)-5-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dih dropyrrol-5-yl]benzonitrile
Figure imgf000054_0002
A solution of 2-fluoro-5-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5- yljbenzonitrile (1.0 g, 2.3 mmol) , dipotassium carbonic acid (390 mg, 2.8 mmol) and lH-l,2,4-triazole (190mg, 2.8 mmol) were heated at 120 C for 2-3 hours and monitored by TLC. The reaction was diluted with water (10 mL) and extracted with ethylacetate (3 x 30 mL). The combined organic layer was dried over sodium sulphate and concentrated under vacuum. Purification by chromatography (hexane/ethyl acetate) provided 2-(l ,2,4-triazol-l-yl)-5-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dihydropyrrol-5-yl]benzonitrile as solid (950 mg). Melting point: 162-164 C.
'H NMR (400MHZ, CDC13): 8.9(S, lH), 8.29-8.34(m, 2H); 8.21(s, 1H); 7.93(d, 1H); 7.40(s, 2H); 4.94(d, 1H); 4.51(d, 1H); 3.84(d, 1H); 3.54(d, 1H);, LCMS (methanol, APCI): retention time =4.96, m/z = 483.94(M+H)
Example 5: Preparation of N-[(l S -l-r4-[5-(3,4,5-trichlorophenyl -3-(trifluoromethyl -2,4-dihydropyrrol- 3-yllphenyllethyllcyclopropanecarboxamide
Ste 1 : Preparation of tert-butyl N-[(lS)-l-(4-bromophenyl)ethyl"|carbamate
Figure imgf000055_0001
To a stirring solution of compound (l S)-l-(4-bromophenyl)ethanamine (50 mmol) in a 50 mL roundbottom flask and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20 min and stirring was continued vigorously, After 5 min solid was precipitated out from reaction mass and thus obtained solid was filtered and washed with hexane and dried under vacuum. Weight: 13 g
'H-NMR (400 MHz, CDC13): 7.45(2H, d), 7.18(2H, d), 4.74(1H, m), 1.40-1.48 (12H, m).
Step 2: Preparation of 4-[(lS)-l-(tert-butoxycarbonylamino)ethyl]benzoic acid
Figure imgf000055_0002
To a stirring solution of compound tert-butyl N-[(lS)-l-(4-bromophenyl)ethyl]carbamate (1 g, 3.331 mmol) in THF (30 mL) cooled to -78°C, methyl lithium (5.33 mmol, 1.6 eq.) was added drop wise under nitrogen atmosphere and stirring was continued for 15 mins followed by addition of butyllithium (5.33 mmol, 1.6 eq.) drop wise and stirring was continued for 30 mins. Dry carbon dioxide was added and stirring continued for 1 hour at -70 C to room temperature. The reaction mass was quenched with water (50 mL) and the compound was extracted with ethylacetate (30 mL x 2) in order to remove debromo compound. The aqueous layer was acidified with ammonium chloride and extracted with ethylacetate (30 mL x 2). The combined organic layers were dried with sodium sulfate and evaporated off under vacuum and dried under vacuum. Weight: 0.61 g
¾-NMR (400 MHz, CDC13): 7.86(2H, d), 7.37(2H, d), 4.64(1H, m), 1.28-1.31 (12H, m). LC-MS (methanol, ESI): m/z =264(M-H), RT 1.95-2.07.
Step 3: Preparation of tert-butyl N-[(lS)-l-[4-(trimethylsilylmethylcarbamoyl)phenyl]ethyl]carbamate
Figure imgf000056_0001
To a stirring solution of 4-[(lS)-l -(tert-butoxycarbonylamino)ethyl]benzoic acid (1 g, 3.769 mmol), 1- hydroxybenzotriazole hydrate (542 mg, 3.5mmol) in DMF (5 mL), in DCM (30 mL),
trimethylsilylmethanamine (0.38 g, 3.7 mmol), trimethylsilylmethanamine (0.38 g, 3.7 mmol) and the reaction mass was cooled to 0°C and 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-l-amine hydrochloride (848 mg, 4.4234 mmol) was added and the reaction was stirred at 0°C to room temperature overnight. TLC showed the reaction was completed. The reaction mass was quenched with water (30 mL) and extracted with DCM (35 mL x 2) and the combined organic layer was washed with water (20 mL x 2) and dried with sodium sulfate and evaporated of under reduced pressure and compound was purified by combiflash. Weight: 0.93 g
¾-NMR (400 MHz, CDC13): 7.68 (2H, d), 7.34(2H, d), 5.93(1H, m). 4.81 (2H, d), 2.95(2H, d), 1.40-1.45 (12H, m). LC-MS (methanol, ESI): m/z =349(M-H), RT 1.95-2.07 .
Step 4: Preparation of tert-butyl N-[(lS)-l-[4(trimethylsilylmethylcarbamothioyl)phenyl]ethyl]carbamate
Figure imgf000056_0002
To a solution of tert-butyl N-[(lS)-l-[4-(trimethylsilylmethylcarbamoyl)phenyl]ethyl]carbamate (1 g, 2.853 mmol) in THF (25 mL) was added 2,4-bis(4-methoxyphenyl)-l,3,2,4-dithiadiphosphetane-2,4- disulfide (1 eq, 2.853 mmol,) and reaction mass was stirred at 65 °C for 4hours. TLC showed the reaction was completed. The solvent was removed from the reaction mass on a rotary evaporator and the resultant reaction mass was diluted with ethylacetate and washed with water (twice). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude mass thus obtained was purified by combiflash (silica gel). Weight: 0.8 g
'H-NMR (400 MHz, CDC13): 7.65 (2H, d), 7.51-7.52 (1H, m), 7.30(2H, d), 4.76-4.81 (2H, m), 3.51 (2H, d), 1.40-1.45 (12H, m). LC-MS (methanol, ESI): m/z =365 (M-H), RT 2.51-2.57. Step 5: Preparation of tert-butyl N-[(lS)-l-[4-[5-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4- dihydropyrrol-3-yl]phenyl]ethyl]carbamate
Figure imgf000057_0001
To stirring solution of compound tert-butyl N-[(l S)-l-[4- (trimethylsilylcarbamothioyl)phenyl] ethyl] carbamate (0.5 g, 1 mmol) in DMF (25 mL), potassium carbonate (2 eq., 2 mmol) was added followed by addition of iodomethane (10 eq., 10 mmol) over period of 1 hour and stirring was continued for 3 ours. After completion of the reaction (monitored by TLC), the reaction mass was diluted with ethylacetate and washed with water (20 mL x 3) and dried with sodium sulphate and evaporated off under vacuum. The obtained reaction mass was taken into THF (25 mL) and l,2,3-trichloro-5-[l -(trifluoromethyl)vinyl] benzene (1 eq., 1 mmol) was added into it. The mixture was cooled to 0°C, TBAF (1 eq, 1 mmol) was added and stirring was continued for 3 hours at room temperature. After completion of the reaction (monitored by TLC), the solvent was evaporated off under vacuum and the reaction mass was diluted with ethylacetate and washed with water (30 mL x 2) and dried with sodium sulphate and evaporated off under vacuum. The compound was purified by combiflash, (25-30% EtOAC-hexane). Weight: 0.1 lg
'H-NMR (400 MHz, CDCI3): 7.97 (2H, d), 7.33-7.56 (4H, m), 4.85-4.92 (2H, m), 4.50 (1H, dd), 3.91 (1H, dd), 3.58 (1H, dd), 1.40-1.45 (12H, m). LC-MS (methanol, ESI): m/z = 533 (M-H), RT 2.51-2.57.
Step 6: Preparation of N-[(lS)-l-[4-[5-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-3- yl]phenyl]ethyl]cyclopropanecarboxamide
Figure imgf000057_0002
To a solution of tert-butyl N-[(lS)-l-[4-[5-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol- 3 -yl]phenyl] ethyl] carbamate (0.35 g) in DCM (20 mL) was added 2,2,2-trifluoroacetic acid (3 eq.) and the reaction mass was stirred for 5 hours at room temperature. After completion of the reaction, the solvent was removed under vacuum and the compound thus obtained was directly taken for the next step. A Solution of (l S)-l-[4-[5-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-3- yl]phenyl]ethanamine TFA salt ( 0.3 g, 0.7 mmol), in DCM (20 mL) was cooled at 0°C. To the cooled mixture was added triethylamine (2.2 eq, 1.54 mmol) followed by dropwise addition of cyclopropane carboxylic acid chloride (1 eq., 0.7 mmol) over period of 5 min and stirring was continued overnight. After completion of the reaction (monitored by TLC), the reaction mass was diluted with DCM (20 mL) and washed with water (20 mL). The organic layer was then dried over anhydrous sodium sulphate, and the solvent was removed under vacuum. The compound was purified by Combiflash (35 % EtOAC- hexane). Weight: 0.2 g, melting point: 80-82°C.
'H-NMR (400 MHz, CDC13): 7.82(2H, d), 7.35-7.41 (4H, m), 6.05 (1H, m), 5.13 (1H, m), 4.86 (1H, dd), 4.42 (1H, dd), 3.78 (1H, dd), 3.45 (1H, dd). 1.46-1.50 (4H, m), 0.93-0.96 (2H, m), 0.72-0.731 (2H, m) LC-MS (methanol, ESI): m/z = 501(M-H), RT 2.23-2.30.
Example 6: Preparation of N- {2-bromo-4- |"4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H- pyrrol-2yll -benzyl} acetamide.
Step 1 : Bromination of 3-bromo-4-methyl benzoic acid.
Figure imgf000058_0001
3-bromo-4-methyl benzoic acid (10 g, 46.72 mmol), NBS (8.7 g, 49.15 mmol)) and benzoylperoxide (0.5 g, 2 mmol)) were suspended in CCI4 and then heated to reflux for 5 hours. After completion of the reaction (TLC monitoring) water was added to the reaction mixture. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated in vaccuo. The crude mixture thus obtained containing 3-bromo-4-bromomethyl benzoic acid and the 3-bromo-4-dibromomethyl benzoic acid was taken directly into the next step.
LC-MS (methanol, ESI): m/z =291 (M-H) and 368 (M-H)
Step 2: Preparation of 3-bromo-4-(dibromomethyl)-N-[(trimethylsilyl)methyl]benzamide.
Figure imgf000059_0001
A mixture of of 3-bromo-4-(bromomethyl)-N-[(trimethylsilyl)methyl]benzamide and 3-bromo-4- (dibromomethyl)-N-[(trimethylsilyl)methyl]benzamide (19 g, 51 mmol), 1 -(trimethylsilyl)methylamine (5.78 g, 56 mmol), N,N-dimethylaminopyridine (0.1 g) and N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide.HCl (12.74 g, 66 mmol) was dissolved in tetrahydroiuran solvent and stirred for 1 hour at room temperature. After completion of the reaction (TLC monitoring), the reaction mixture was concentrated on a rotary evaporator. Water was added to the reaction mixture, followed by extraction with ethylacetate. The organic layer was separated and dried using sodium sulphate. The residue was purified by silica gel chromatography to obtain 3-bromo-4-(dibromomethyl)-N-[(trimethylsilyl) methyl] benzamide (16 g).
LC-MS (methanol, ESI): m/z =456 (M+H).
IH-NMR (400 MHz, CDC13): 8.01 (1H, dd), 7.87(1H, d), 7.04(1H, dd), 6.13(lH,bs) , 3.51 (2H, d), 0.17 (9H,s). Step 3: Preparation of 3-bromo-4-formyl-N-[(trimethylsilyl)methyl]benzamide.
Figure imgf000059_0002
3-bromo-4-(dibromomethyl)-N-[(trimethylsilyl)methyl]benzamide (0.25 g, 0.69 mmol) was taken in acetone (5 mL) and water (2.5 mL). Silver nitrate (0.3 g, 1.7 mmol) was added to the reaction mixture. The reaction was stirred at room termperature for 6 hours. The reaction mass was then concentrated and extracted with ethylacetate. The organic layer was separated and dried using sodium sulphate. The organic layer was concentrated to obtain the product 3-bromo-4-formyl-N- [(trimethylsilyl)methyl]benzamide. (0.15 g).
LC-MS (methanol, ESI): m/z =314(M+H).
IH-NMR (400 MHz, CDC13): 10.33(lH,s),7.90 (1H, m), 7.60 (1H, dd), 7.56 (1H, m), 5.99(lH,s),2.99 (2H, d), 0.17 (9H,s).
Step 4: Preparation of 3-bromo-4-hydroxymethyl-N-[trimethylsilaylmethyl] benzamide.
Figure imgf000060_0001
3-bromo-4-formyl-N-[(trimethylsilyl)methyl]benzamide(0.1 g, 0.3 mmol) was dissolved in methanol and to this was added NaBH4 (0.014 g, 0.38 mmol). The reaction was stirred at room temperature for 1 hour. Methanol was removed under vaccuo and water was added to the reaction mass which was then extracted using ethyl acetate. The organic layer was separated and dried using sodium sulphate followed by concentration to get the product 3-bromo-4-hydroxymethyl-N-[trimethylsilaylmethyl] benzamide (0.05 g).
LC-MS (methanol, ESI): m/z =316 (M+H).
1H-NMR (400 MHz, CDC13): 7.90 (1H, m), 7.60 (1H, m), 7.53 (1H, m), 6.02(1H, s),4.75
(2H,s),2.99(2H,s), 0.17 (9H,s).
Step 5: Preparation of Acetic acid 2-bromo-4- (trimethylsilanylmethyl-carbamoyl)-benzylester.
Figure imgf000060_0002
3-bromo-4-hydroxymethyl-N-[trimethylsilaylmethyl] benzamide (0.25 g, 0.7 mmol) was dissolved in DMF solvent, triethyl amine (0.159 g, 1.5 mmol) and acetyl chloride (0.061 g, 0.8 mmol) were added to the reaction mixture at room temperature. The reaction was stirred at room temperature for 30 min. Water was added and the reaction mass was then extracted with ethyl acetate. The organic layer was separated, dried using sodium sulphate and concentrated to get the product: acetic acid 2-bromo-4- (trimethylsilanylmethyl-carbamoyl)-benzylester (0.15 g).
LC-MS (methanol): m/z =358 (M+H).
'H-NMR (400 MHz, CDC13): 7.90 (1H, m), 7.60 (1H, m), 7.38 (1H, m), 6.14(1H, bs), 5.11(2H, s), 2.99 (2H, d), 2.15 (3H, s), 0.17 (9H, s).
Step 6: Preparation of 3-bromo-4-(2-oxo-propyl)-N-trimethylsilanylmethyl-thiobenzamide.
Figure imgf000060_0003
Acetic acid 2-bromo-4- (trimethylsilanylmethyl-carbamoyl)-benzylester (2.4 g, 7.6 mmol) and Lawesson reagent (2.7 g,6.6 mmol) were suspended in THF. The mixture was heated to reflux for 3 hours, concentrated, washed with water and extracted with ethyl acetate. The organic layer was separated and dried using sodium sulphate. The residue was purified by silica gel chromatography to obtain 3-bromo-4- (2-oxo-propyl)-N-trimethylsilanylmethyl-thiobenzamide (1.8 g).
LC-MS (methanol, ESI): m/z =374(M+H).
'H-NMR (400 MHz, CDC13): 7.90 (1H, m), 7.60 (1H, m), 7.38 (1H, m), 6.01(1H, br s), 5.11 (2H, d), 2.99 (2H, d), 2.15 (3H, s), 0.17 (9H, s) Step 7: Preparation of Acetic acid 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro- 3H-pyrrol-2yl] -benzylester.
Figure imgf000061_0001
A mixed solution of methyliodide (0.69 g,4.8 mmol), potassium carbonate (0.80 g, 5.7 mmol) and 3- bromo-4-(2-oxo-propyl)-N-trimethylsilanylmethyl-thiobenzamide (1.8 g, 5.4 mmol) in DMF (25 mL) was stirred at 0°C for 4 hours.The reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The organic layer was separated, dried using sodium sulphate and concentrated to get the crude acetic acid 2-bromo-4 {methylsulfanyl-[(E)- trimethylsilanylmethylimino]-methyl} -benzyl ester.(0.95g) which was dissolved in THF and cooled to 0°C under nitrogen atmosphere. A solution of TBAF (1.0 M in THF) (0.56 mL) was added gradually into it and reaction mixture was stirred for 8 hours at room temperature. The reaction mass was then concentrated and extracted with ethylacetate. The organic layer was separated and dried using sodium sulphate. The resulting mixture was then purified by silica gel chromatography to obtain acetic acid 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro- 3H-pyrrol-2yl] -benzylester ( 1.1 g).
LC-MS (methanol, ESI): m/z =508 (M+H).
'H-NMR (400 MHz, CDC13): 8.07 (1H, m), 7.71 (1H, m), 7.47 (1H, m), 7.38 (1H, m), 7.24(2H, m), 5.23(2H, s), 4.90 (1H, m),4.43 (1H, d), 3.75 (1H, m), 3.43 (1H, d), 2.17 (3H, s).
Step 8: Preparation of 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]- phenyl-methanol.
Figure imgf000062_0001
To a solution of acetic acid 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H- pyrrol-2yl]-benzylester (1.1 g, 2.1 mmol) in methanol (20 mL) was added sodium methoxide (0.1 g, 1.85 mmol) and the solution was stirred for 1 hour at room temperature. The reaction mass was then concentrated and extracted with ethylacetate. The organic layer was separated and dried using sodium sulphate. The resulting mixture was then purified by silica gel chromatography to obtain 2-bromo-4- [4- (3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]-phenyl-methanol (0.95g).
LC-MS (methanol, ESI): m/z =466 (M+H).
'H-NMR (400 MHz, CDC13): 8.07 (1H, m), 7.78 (1H, m), 7.59 (1H, m), 7.38 (3H, m), 4.90 (3H, d),4.43 (1H, d), 3.75 (1H, m), 3.43 (1H, d).
Step 9: Preparation of Methanesulfonic acid-2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5- dih dro-3H-pyrrol-2yl]-benzylester.
Figure imgf000062_0002
To a solution of 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]- phenyl-methanol (0.95 g, 2 mmol) and triethylamine (0.4 g, 4.0 mmol) in THF was added
methanesulfonyl chloride (0.35 g, 3.0 mmol) gradually. The mixture was stirred for 1 hour at room temperature. The reaction mixture was washed with water. The organic layer was separated and dried using sodium sulphate. The organic layer was evaporated to obtain the solid compound methanesulfonic acid-2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]-benzylester (0.9 g).
LC-MS (methanol, ESI): m/z =544 (M+H).
'H-NMR (400 MHz, CDC13): 8.13 (1H, m), 7.81 (1H, m), 7.58 (1H, m), 7.38 (1H, m),
7.24(2H,m),5.36(2H, s), 4.90 (1H, m),4.43 (1H, d), 3.75 (1H, m), 3.43 (1H, d), 3.04 (3H,s).
Step 10: Preparation of2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol- 2yl] -benzylamine.
Figure imgf000063_0001
To a solution of methanesulfonic acid-2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5- dihydro-3H-pyrrol-2yl]-benzylester (1.0 g,1.8 mmol) in THF (30 mL) and MeOH (30 niL) was added dropwise to a mixed solution of aq. ammonia (30%), 30 mL, and the reaction was stirred for 12 hours at room temperature. The reaction mass was then concentrated and extracted with ethylacetate. The organic layer was separated and dried using sodium sulphate. The organic layer was evaporated to provide the gummy compound 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]- benzylamine.
LC-MS (methanol, ESI): m/z = 467(M+H).
'H-NMR (400 MHz, CDC13): 8.07 (1H, m), 7.71 (1H, m), 7.59 (1H, m), 7.38 (1H, m), 7.24(2H,m), 4.90 (1H, d),4.43 (3H, m), 3.75 (1H, m), 3.43 (1H, d).
Step 11 : Preparation of N- {2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H- pyrrol-2yl] -benzyl} acetamide.
Figure imgf000063_0002
To a solution of 2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]- benzylamine (0.15 g, 0.32 mmol) in THF was added acetic anhydride (0.04 g, 0.39 mmol) and the mixture was stirred at room temperature for 1 hour. The reaction mass was then concentrated under reduced pressure and extracted with ethylacetate. The organic layer was separated and dried using sodium sulphate. The resulting mixture was then purified by silica gel chromatography to obtain N- {2-bromo-4- [4-(3,5-dichlorophenyl )-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2yl]-benzyl} acetamide.
LC-MS (methanol,ESI): m/z = 509 (M+H).
'H-NMR (400 MHz, CDC13): 8.07 (1H, m), 7.71 (1H, m), 7.47 (1H, m), 7.38 (1H, m),
7.24(2H,m),5.98(lH, s), 4.90 (1H, d),4.43 (3H, m), 3.75 (1H, m), 3.43 (1H, d), 2.04 (3H,s).
Example 7: Preparation of N- {4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidinl -yll- 2-methyl- benzyPacetamide. Step 1 : Preparation of l-Benzyl-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine.
Figure imgf000064_0001
To a cooled solution of l,3-dichloro-5(l-trifluoromethyl)vinyl)benzene (0.5 g, 2.0 mmol) and N-benzyl- l-methoxy-N-9trimethylsilyl)methyl)methanamine (0.4 g, 2.0 mmol) in DCM (10 mL) was added dropwise a solution of TFA (0.024 g, 0.2 mmol) in DCM (1 mL). The reaction mixture was stirred for 3 hours at room temperature. The organic layer was washed with water (2 x 10 mL) and 10% aq sodium carbonate solution (10 mL). The organic layer was separated, dried with sodium sulphate and concentrated under reduced pressure The residue was purified by silica gel chromatography to yield 1 - Benzyl-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.5 g).
LC-MS (methanol, ESI): m/z = 374 (M+H).
'H-NMR (400 MHz, CDC13): 7.36 (4H, m), 7.30(2H, m), 7.23 (2H, m), 3.67 (2H, s), 3.08 (2H, dd), 2.69 (2H,m), 2.53 (1H, m), 2.27(lH,m).
Step 2: Preparation of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine.
Figure imgf000064_0002
To a solution of l-benzyl-3-( -(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.22 g, 0.59 mmol) and l-chloroethylchloroformate(0.17 g, 1.2 mmol) in DCM was heated for reflux for 3 hours. The mixture was cooled to room temperature and concentrated under reduced pressure. Methanol was added to the residue which was then heated with stirring for 3 hours at 60°C. The mixture was concentrated and water was added to it. The residue was extracted with ethylacetate (20 mL x 3) washed with brine, dried over sodium sulphate and concentrated under reduced pressure. Purification over silica gel yielded 3- (3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (4.2 g).
LC-MS (methanol, ESI): m/z = 284 (M+H).
'H-NMR (400 MHz, CDC13): 7.35 (1H, t), 7.25 (2H, d), 3.74 (1H, d), 3.19 (2H, m), 2.97(lH,m),2.53 (1H, m), 2.27(lH,m).
Step 3: Preparation of N-(4-bromo-2-methyl-benzyl)acetamide.
Figure imgf000065_0001
4-bromo-2-methyl benzonitrile (2.0 g, 0.01 mol) was taken in methanol along with Νί(¾ (2.41 g, 0.01 mol). In the same pot acetic anhydride was taken (2.0 g, 0.020 mol). The reaction was cooled to 0°C. NaBH4 (2.7 g, 0.07 mol) was added slowly to the reaction while stirring at the same temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and was extracted with ethylacetate. The organic layer was separated, dried using sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography to yield N-(4-bromo-2-methyl- benzyl)acetamide.(l .l g).
LC-MS (methanol, ESI): m/z = 242 (M+H).
1H-NMR (400 MHz, CDC13): 7.71 (1H, m), 7.47 (1H, m), 7.38 (1H, m), 5.98(1H, s), 3.75 (1H, m), 3.43 (1H, d), 2.31 (3H, s),2.04 (3H, s).
Step 4: Preparation of N- {4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidinl-yl]- 2-methyl- benz l)acetamide.
Figure imgf000065_0002
To the mixture of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.25 g, 0.88 mmol) and the N- (4-bromo-2-methyl-benzyl)acetamide (0.8 g, 0.7 mmol) in anhydrous toluene under nitrogen atmosphere was added tris(dibenzylidineacetone)dipalladium (0.02 g, 0.02 mmol) and the ligand xanthphos (0.03 g, 0.053 mmol) followed by the addition of sodium tertiary butoxide (0.127 g, 1.3 mmol). The reaction mixture was heated at 80°C for 3hours. After completion of the reaction (TLC monitoring), the reaction mass was filtered over celite. The filtrate was concentrated and purified using column chromatography. LC-MS (methanol, ESI): m/z = 445 (M+H).
1H-NMR (400 MHz, CDC13): 7.37 (1H, d), 7.29 (2H, m), 7.11 (1H, d), 6.41 (2H, m), 5.45(lH,b s), 4.35 (2H, s),4.01 (1H, d), 3.75 (1H, d), 3.43 (2H, m), 2.81 (lH,d),2.51 (lH,d),2.31 (3H,s),1.97 (3H,s).
The following examples were prepared according to methods described in US 2009/0156643 and were analysed by the LCMS methods described below:
Method A:
ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer) Instrument Parameter:
Ionization method: Electrospray
Polarity: positive and negative ions
Capillary: 3.00 kV
Cone: 30.00 V
Extractor: 2.00 V
Source Temperature: 100°C,
Desolvation Temperature: 250°C
Cone Gas Flow: 50 L/Hr
Desolvation Gas Flow: 400 L/Hr
Mass range: 100 to 900 Da
HP 1100 HPLC from Agilent:
Solvent degasser, quaternary pump, heated column compartment and diode-array detector.
Type of column: Phenomenex Gemini CI 8; Column length: 30 mm; Internal diameter of column: 3 mm;
Particle Size: 3 micron; Temperature: 60°C.
DAD Wavelength range (nm): 210 to 500
Solvent Gradient:
A = H20 + 5% MeOH + 0.05 % HCOOH
B= Acetonitril + 0.05 % HCOOH
Time A% B% Flow (mL/min)
0.00 100 0 1.700
2.00 0 100.0 1.700
2.80 0 100.0 1.700
2.90 100 0 1.700
3.00 100 0 1.700
Method B:
ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Ionisation method: Electrospray
Polarity: positive ions
Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700
Mass range: 100 to 800 Da
DAD Wavelength range (nm): 210 to 400 Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9: 1,0.1% formic acid and Solvent B: Acetonitrile,0.1%> formic acid ) Time (minutes) A (%) B (%) Flow rate (mL/min)
0 100 0 0.75
2.5 0 100 0.75
2.8 0 100 0.75
3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC BEH C18; Column length: 50 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.7 micron; Temperature: 60°C.
Example 8:
Figure imgf000067_0001
Method A, retention time 2.19 min, MH+ 493 Exam le 10:
Figure imgf000067_0002
Method B, retention time 1.98 min, MH+ 479
The following Example was prepared according to methods described in WO 2008/150393. Example 11 :
Figure imgf000068_0001
Method A, retention time 2.1 min, MH+ 470
The following Example was prepared according to methods described in WO 2009/051956.
Example 12:
Figure imgf000068_0002
1H NMR in CDC13: 3.73 ppm (d, 1H), 4.12 ppm (d, 1H), 7.58 ppm (d, 2H), 7.93 (m, 1H), 8.07-8.12 (m, 3H), 8.62 (s, 1H)
Example 13: Preparation of 5-bromo-N-hydroxyindan-l-imine:
Figure imgf000068_0003
A solution of 5-bromoindane-l-one (10.0 g, 47.38 mmol) in methanol (50 mL), treated with
hydroxylamine hydrochloride (3.65 g, 52.17 mmol) and sodium acetate (4.27 g, 52.17 mmol) and stirred at room temperature for 20 hours. The solvent was evaporated, and the residue was treated with water (25 mL) and extracted with ethylacetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated to give 5-bromo-N-hydroxyindan-l -imine (10 g). 'H-NMR (400 MHz, CDC13): 7.65 (1H d), 7.5 (1H, s), 7.4 (1H, d), 3.05 (2H, m), 3.10 (2H, m). LC-MS (methanol, ESI): m/z = 227 (M+H, retention time = 1.75).
Example 14: Preparation ofter-butyl (5-bromo-2,3-dihydro-lH-inde-l-yl)carbamate:
Figure imgf000068_0004
A solution of 5-bromo-N-hydroxyindan-l-imine (16 g, 70.77 mmol) in methanol (400 mL) and dioxane (200 mL) was treated with di-ter-butyl bicarbonate (31 g, 141.55mmol) and nickel chloride (4.68 g, 35.39 mmol). The reaction mixture was cooled to -20 C, sodium borohydride (10.7 g, 283.1 mmol) was added slowly and stirred for lhour. The reaction mixture was then treated with diethylenetriamine (16 mL), and stirred for 30 min. The reaction mixture was diluted by adding water, extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, concentrated and purified by column chromatography (hexane/ethylacetate 1 :9 as eluent) to give ter-butyl (5-bromo-2,3-dihydro-lH-inde-l- yl)carbamate (10.5 g). 'H-NMR (400 MHz, CDC13): 7.1 (1H, d), 7.2 (1H, s), 7.3 (1H, d), 5.15 (1H, m), 4.7 (1H, m), 2.9 (1H, m), 2.8 (1H, m), 2.5 (1H, m), 1.8 (1H, m), 1.45 (s, 9H).
Example 15: Preparation of l-(tert-butoxycarbonylamino)indane-5-carboxylic acid:
Figure imgf000069_0001
A solution of ter-butyl (5-bromo-2,3-dihydro-lH-inde-l-yl)carbamate (10 g, 32 mmol) in tetrahydrofuran (200 mL) was cooled to -78 °C, treated dropwise with methyl lithium (16 mL, 48 mmol) and stirred for 10 min, followed by addition of n-BuLi (29 mL, 64 mmol) and further stirred for 1 hour. The reaction mixture was treated with dry ice slowly and stirred for 30 min. It was then quenched with a saturated solution of ammonium chloride and extracted with ethylacetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate, concentrated under reduced pressure to afford crude solid material, and then triturated with hexane/diethyl ether to afford pure l-(tert-butoxycarbonylamino)indane-5-carboxylic acid (3.8 g). 'H-NMR (400 MHz, DMSO): 7.8 (1H, s), 7.3 (1H, m), 7.2 (1H, m), 5.00 (1H, m), 2.9 (1H, m), 2.8 (1H, m), 2.31 (1H, m), 1.8 (1H, m), 1.45 (s, 9H). LC-MS (methanol, ESI): m/z = 276 (M-H, retention time = 1.74). Example 16: Preparation of tert-butyl N-[5-(trimethylsilylmethylcarbamoyl)indan-l -yllcarbamate:
Figure imgf000069_0002
O A solution of l-(tert-butoxycarbonylamino)indane-5-carboxylic acid (2.1 g, 7.6 mmol) in dichloromethane (20 mL), was treated trimethylsilyl methylamine (0.88 g, 8.3 mmol), EDCI (1.4 g, 9.1 mmol) and a catalytic amount of DMAP (0.09 g, 0.76 mmol), and stirred for 20 hours. The reaction mixture was then treated with water (10 mL) and extracted with dichloromethane (2 x 25 mL). The combined organic layers were dried over sodium sulfate, concentrated, and purified by column chromatograph (hexane/ethylacetate as eluent) to afford tert-butyl N-[5-
(trimethylsilylmethylcarbamoyl)indan-l-yl]carbamate (1.9 g). 'H-NMR (400 MHz, CDC13): 7.6 (IH, s), 7.53 (IH, d), 7.33 (IH, d), 6.00 (IH, m), 5.2 (IH, m), 4.8 (IH, m), 3.0 (IH, m), 2.9 (2H, d), 2.8 (IH, m), 2.6 (IH, m), 1.8 (IH, m), 1.45 (s, 9H), 0.2 (s, 9H). LC-MS (methanol, ESI): m/z = 363 (M+H, retention time = 2.05).
Example 17: Preparation of tert-butyl N-[5-(trimethylsilylmethylcarbamothioyl indan-l-yllcarbamate:
Figure imgf000070_0001
A solution of tert-butyl N-[5-(trimethylsilylmethylcarbamoyl)indan-l-yl]carbamate (2.2 g, 6.1 mmol) in toluene (25 mL), was treated with lawessons reagent (2.8 g, 6.7 mmol), and heated at 120 C for 2 hours. The toluene was evaporated and the residue was treated with water (25 mL) and extracted with ethylacetate (25 mL). The combined organic layers were dried over sodium sulfate, concentrated, and purified by column chromatography (hexane/ethylacetate as eluent) to afford tert-butyl N-[5- (trimethylsilylmethylcarbamothioyl)indan-l -yl]carbamate (1.8 g). 'H-NMR (400 MHz, CDC13): 7.6 (IH, s), 7.53 (IH, brs), 7.45 (IH, d), 7.30 (IH, d), 5.2 (IH, brs), 4.7 (IH, brs), 3.5 (2H, d), 3.00 (IH, m), 2.8 (IH, m), 2.6 (IH, m), 1.8 (IH, m), 1.45 (s, 9H) 0.2 (s, 9H). LC-MS (methanol, ESI): m/z = 379 (M+H, retention time =2.27).
Example 18: Preparation of tert-butyl N-[5-r3-(3,5-dichlorophenyl -3-(trifluoromethyl -2,4- dihydropyrrol-5-yllindan- 1 -yl"|carbamate:
Figure imgf000071_0001
A solution of tert-butyl N-[5-(trimethylsilylmethylcarbamothioyl)indan-l-yl]carbamate (1.2 g, 3.2 mmol) in dimethyl formanide (10 mL) at 0 C, was treated with potassium carbonate (0.9 g, 6.3 mmol) and methyl iodide (4.5 g, 32 mmol) added in three portions, and stirred for 3 hours. To the reaction mixture water (10 mL) was added, followed by extraction with ethylacetate (2 x 25mL). The combined organic layers were dried over sodium sulfate, concentrated to afford crude material. The crude material was diluted with tetrahydroiuran (20 mL), cooled at 0 C, treated with l,3-dichloro-5-[l- (trifluoromethyl)vinyl]benzene and TBAB, and stirred for 20 hours. Tetrahydroiuran was removed under reduced pressure, diluted with water (25 mL), and extracted with ethylacetate (2 x 25mL). The combined organic layers were dried over sodium sulfate, concentrated and purified by column chromatography (hexane/ethyl acetate) gave tert-butyl N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4- dihydropyrrol-5-yl]indan-l-yl]carbamate (0.7 g). 'H-NMR (400 MHz, CDC13): 7.8 (2H, s), 7.7 (1H, m), 7.35 (2H, s), 7.25 (1H, d), 5.9 (1H, brs), 5.6 (1H, brs), 4.9 (1H, d), 4.4 (1H, d), 4.8 (1H, d), 3.40 (1H, d), 3.00 (1H, m), 2.90 (1H, m), 2.6 (1H, m), 2.00 (1H, m), 1.45 (s, 9H). LC-MS (methanol, ESI): m/z = 513 (M+H, retention time =2.50).
Example 19: General procedure for the preparation of N-[5-r3-(3,5-dichlorophenyl)-3-(trifluoromethyl)- 2.4-dihvdropyrrol-5-yl1indan-l-yl1amides: (a) R = Me. (b) R = Et. (c) R = cPr. (d) = CF3
Figure imgf000071_0002
A solution of tert-butyl N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indan-l- yl]carbamate (1 mmol) in dichloromethane (5 mL), was treated with TFA ( 4 eq.), and stirred for 5 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane (5 mL), and treated with triethylamine (5 eq.) and the appropriate carboxylic acid chloride (1.1 eq.) and stirred for 16 hours. The reaction mixture was concentrated and purified by column chromatography (hexane/ethyl acetate) to give:
(a) N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indan-l-yl]acetamide:
0.12 g, 'H-NMR (400 MHz, CDC13): 7.8 (1H, m), 7.7 (1H, m), 7.30 (1H, m), 7.20 (1H, m), 6.1 (1H, m), 5.5 (1H, m), 4.8 (1H, d), 4.4 (1H, d), 3.8 (1H, d), 3.45 (1H, d), 3.00 (1H, m), 2.90 (1H, m), 2.6 (1H, m), 2.00 (3H, s), 1.8 (1H, m). LC-MS (methanol, ESI): m/z = 455 (M+H, retention time = 2.11).
(b) N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indan-l- yl]propanamide: 0.12 g, 'H-NMR (400 MHz, CDC13): 7.9 (1H, m), 7.8 (1H, m), 7.40 (2H, m),
7.30 (2H, m), 5.70 (1H, m), 5.50 (1H, m), 4.90 (1H, d), 4.50 (1H, d), 3.90 (1H, d), 3.60 (1H, d), 3.00 (1H, m), 2.90 (1H, m), 2.6 (1H, m), 2.3 (2H, d), 1.8 (1H, m). 1.2 (3H, t) LC-MS (methanol, ESI): m/z = 469 (M+H, retention time = 2.17). (c) N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indan-l- yl]cyclopropanecarboxamide: 70 mg, 'H-NMR (400 MHz, CDC13): 7.8 (1H, m), 7.77 (1H, m), 7.40 (2H, m), 7.30 (2H, m), 5.90 (1H, m), 5.50 (1H, m), 4.90 (1H, d), 4.45 (1H, d), 3.85 (1H, d), 3.50 (1H, d), 3.00 (1H, m), 2.90 (1H, m), 2.6 (1H, m), 1.8 (1H, m). 1.0 (2H, m), 0.8 (2H, m), LC- MS (methanol, ESI): m/z = 481 (M+H, retention time = 2.22)
(d) N-[5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indan-l-yl]-2,2,2- trifluoro-acetamide: 120 mg, 'H-NMR (400 MHz, CDC13): 7.9 (1H, m), 7.8 (1H, m), 7.35 (2H, m), 7.25 (2H, m), 6.60 (1H, m), 5.50 (1H, m), 4.90 (1H, d), 4.50 (1H, d), 3.80 (1H, d), 3.50 (1H, d), 3.10 (1H, m), 3.00 (1H, m), 2.70 (1H, m), 2.00 (1H, m), LC-MS (methanol, ESI): m/z = 509 (M+H, retention time = 2.37)
Example 20: Preparation of 5-r3-r3.5-bis(trifluoromethyl)phenyll-3-(trifluoromethyl)pyrrolidin-l - yl"|indan- 1 -amine
Figure imgf000072_0001
To a solution of 3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine (0.260 g, prepared as described in WO 2008/128711) and tert-butyl N-(5-bromoindan-l-yl)carbamate (0.231 g) in toluene (5.2 mL) stirred under argon were added tris(dibenzylideneacetone)dipalladium(0) (13.6 mg), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (22.1 mg) and sodium tert-butoxide (147 mg).
The mixture was heated in the microwave at 130°C for 15 min. The reaction was then diluted with ethylacetate and water then brine and then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulphate, filtered then concentrated under reduced pressure to give a brown oil which was purified by chromatography on column (cyclohexane/EtOAc as solvent) to afford the desired product as a white foam (245 mg). 1H NMR (CDC13, 400MHz): d = 7.92 (s, 1 H), 7.86 (s, 2 H), 7.27 (m, 1 H), 6.47 - 6.58 (m, 2 H), 4.35 (m, 1 H), 4.05 - 4.23 (m, 1 H), 3.85 (m, 1 H), 3.60 (m, 1 H), 3.51 (m, 1 H), 2.90 - 3.03 (m, 2 H), 2.71 - 2.86 (m, 1 H), 2.55 - 2.66 (m, 1 H), 2.50 (dt, J=7.2, 4.3 Hz, 1 H), 1.83 - 2.13 (m, 2 H), 1.72 ppm (dd, J=12.5, 8.1 Hz, 1 H)
Example 21 : Preparation of N-[5-r3-r3,5-bis(trifluoromethyl)phenyll-3-(trifluoromethyl)pyrrolidin-l - yl"|indan- 1 -yl"|propanamide
Figure imgf000073_0001
To a solution of 5-[3-[3,5-bis(nifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-l-yl]indan-l -amine (100 mg), in dichloromethane (3.0 mL) and triethylamine (0.088 mL) stirred at room temperature, was added propanoyl chloride (0.027 mL) and the solution was stirred for 3 hours. The reaction was then diluted with ethylacetate and water and then the mixture was extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulphate, filtered then concentrated under reduced pressure to give a yellow solid which was purified by chromatography on column (cyclohexane/EtOAc as solvent) to afford the desired product as a beige solid (87 mg). 1H NMR (CDC13, 400MHz): d = 7.92 (s, 1 H), 7.86 (s, 2 H), 7.21 (d, J=8.1 Hz, 1 H), 6.45 - 6.58 (m, 2 H), 5.56 (d, J=8.1 Hz, 1 H), 5.37 - 5.49 (m, 1 H), 4.16 (d, J=9.2 Hz, 1 H), 3.85 (d, J=10.6 Hz, 1 H), 3.46 - 3.60 (m, 2 H), 2.91 - 3.04 (m, 2 H), 2.78 - 2.91 (m, 1 H), 2.52 - 2.70 (m, 2 H), 2.24 (q, J=7.7 Hz, 2 H), 1.76 - 1.87 (m, 1 H), 1.13 - 1.24 ppm (m, 3 H)
Example 22
Figure imgf000073_0002
The synthesis was as described in WO2009/112275. Melting point: 103-105 °C
LC-MS: retention time = 1.95, (M+H)+ = 471 (measured) (Method B)
Figure imgf000074_0001
To a solution of l-[4-(bromomethyl)-3-chloro-phenyl]ethanone (1 g, 4.04mmol) in N,N- dimethylformamide was added (1, 3-dioxoisoindolin-2-yl) potassium (823 mg, 4.44mmol). The reaction mixture was refluxed for 5-6 hours, while being monitored by Thin Layer Chromatography (TLC). The reaction mixture was then diluted with water (20 mL), extracted with ethylacetate (3 χ 30 niL). The combined organic layers were dried over sodium sulphate then concentrated under reduced pressure. The residue obtained was purified by column chromatography to afford the desired product 2-[(4-acetyl-2- chloro-phenyl)methyl]isoindoline-l,3-dione (870 mg)
ESI-MS: m/z = 313.9 [M+H]+.
lH NMR (400 MHz, CDC13): δ 7.85-7.90(m, 1H), 7.80-7.85 (m, 1H), 7.68-7.71 (m, 4H), 7.21-7.23 (m, 1H 4.96 (s, 2H), 2.50 (s, 3H)
Figure imgf000074_0002
To a solution of 2-[(4-acetyl-2-chloro-phenyl)methyl]isoindoline-l,3-dione (670 mg, 2.13 mmol) and 1- [3-bromo-5-(trifluoromethyl)phenyl]-2,2,2-trifluoro-ethanone (685 mg, 2.13 mmol) in acetonitrile (10 mL) was added potassium carbonate (150 mg, 1.06 mmol). The reaction mixture was refluxed at 120°C overnight. It was then diluted with water (10 mL) and extracted with ethylacetate (3 χ 30 mL). The combined organic layers were dried over sodium sulphate then concentrated under reduced pressure. The residue obtained was purified by column chromatography to afford the desired product 2-[[4-[(Z)-3-[3- bromo-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-but-2-enoyl]-2-chloro-phenyl]methyl]isoindoline-l,3- dione (550 mg)
ESI-MS: m/z = 614.76 [M-H]+.
lH NMR (400 MHz, CDC13): δ 7.87-7.93 (m, 3H), 7.73-7.83 (m, 4H), 7.52-7.65 (m, 2H), 7.38-7.42 (m, 1H), 7.27-7.31 (m, 1H), 5.00-5.02 (d, 2H)
Figure imgf000075_0001
To a solution of 2-[[4-[(Z)-3-[3-bromo-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-but-2-enoyl]-2-chloro- phenyl]methyl]isoindoline-l,3-dione (500 mg, 0.813 mmol) in isopropyl alcohol (5 mL) was added a solution of sodium hydroxide (98 mg, 2.44 mmol) in water (2 mL) followed by 50% hydroxylamine solution (322 mg, 4.88 mmol). The reaction mixture was refluxed for 6-7 hours, while being monitored by TLC. The reaction mixture was concentrated under reduced pressure, diluted with water (10 mL) and extracted with ethylacetate (3 x 30 mL). The combined organic layers were dried over sodium sulphate then concentrated under reduced pressure. The residue obtained was purified by column chromatography to afford the desired product [4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-isoxazol- 3-yl]-2-chloro-phenyl]methanamine (170 mg)
ESI-MS: m/z = 500.84 M+H]+.
Figure imgf000075_0002
To a solution of [4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2- chloro-phenyl]methanamine (100 mg, 0.2 mmol) in dichloromethane (4 mL) at 0°C was added triethylamine (0.05 mL, 0.3 mmol), followed by butyryl chloride (32 mg, 0.3 mmol). The reaction mixture was stirred at room temperature for lhour. It was then diluted with water (5 mL) and extracted with dichloromethane (3 x 20 mL). The combined organic layers were dried over sodium sulphate then concentrated under reduced pressure. The residue obtained was purified by column chromatography to afford the desired product N-[[4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H- isoxazol-3-yl]-2-chloro-phenyl]methyl]butanamide (50 mg)
ESI-MS: m/z = 570.88 [M+H]+.
lU NMR (400 MHz, CDC13): δ 7.88 (m, 1H), 7.77 (m, 1H), 7.72 (m, 1H), 7.62-7.63 (m, 1H), 7.38-7.46 (m, 2H), 5.89 (br s, 1H), 4.46-4.48 (d, 2H), 4.01-4.05 (d, 1H), 3.60-3.64 (d, 1H), 2.12-2.15 (m, 2H), 1.57- 1.65 (m, 2H), 0.85-0.89 (m, 3H)
Biological Examples
Table A
1 2 3 2 5 8
Tables A provides compounds of formula la wherein B , B , B , R , R , and R are as described below
Figure imgf000076_0001
Figure imgf000076_0002
Table B
Tables B provides compounds of formula lb* wherein B1, B2, B3, R2 and R8 are as described below
Figure imgf000077_0001
B1-B2-B3 R2 R8
Bl N-CH2-CH2 3,5- dichloropheny 1 cyclopropyl
B2 C=N-0 3,5- dichloropheny 1 -CH3
B3 C=N-CH2 3,4,5-trichlorophenyl cyclopropyl
B4 N-CH2-CH2 3,5-di- cyclopropyl
trifluoromethylphenyl
Table C
Tables C provides compounds of formula Ic wherein B1, B2, B3, R2 and R5 are as described below
Figure imgf000077_0002
Figure imgf000077_0003
Table D
1 2 3 2 5 1 2 3
Tables D provides compounds of formula Id wherein B,B,B,R,R,Z,Z and Z are as described below
Figure imgf000078_0001
B1-B2-B3 R2 R5 Zl Z2 Z3
3,5-dichloro-4-
Dl C=N-0 cyano H cyano H
fluorophenyl
3,5-dichloro-4-
D2 C=N-0 cyano H F H
fluorophenyl
D3 C=N-0 3,5- dichloropheny 1 cyano H H H
D4 C=N-0 3,5- dichloropheny 1 amino H H H
D5 C=N-0 3,5- dichloropheny 1 methyl H H H
3,5-dichloro-4-
D6 C=N-0 cyano H chloro H
fluorophenyl
3,5-dichloro-4-
D7 C=N-0 cyano H bromo H
fluorophenyl
3,5-dichloro-4-
D8 C=N-0 cyano H iodo H
fluorophenyl
3,5-dichloro-4-
D9 C=N-0 cyano H nitro H
fluorophenyl
3,5-dichloro-4-
D10 C=N-0 cyano CF3 H CF3 fluorophenyl
3,5-dichloro-4-
Dl l C=N-0 cyano CF3 H H
fluorophenyl
Table E
Tables E provides compounds of formula Ie wherein B1, B2, B3, R2, and R9 are as described below
Figure imgf000078_0002
Figure imgf000079_0001
Plutella xylostella (Diamond back moth):
larvicide, feeding/residual contact activity, preventive
A 24-well microtiter plate (MTP) with artificial diet is treated with test solutions by pipetting. After drying, the MTPs are infested with larvae (L2)(10-15 per well). After an incubation period of 5 days, the samples are checked for larval mortality.
The following compounds were tested and gave at least 80% control at 50ppm: Al, A2, A3, A4, A5, A6, A7, A19, A20, Bl, B2, B3, B4, CI, C2, C3, C4, Dl, El, E2, E3, E4, E5, E6, E7. A18 gave at least 50% control at 50ppm, No activity was found for D10 and Dl 1.
Comparative Example
Compounds are tested according to the above method. The results show that the compounds of the invention are significantly more active against Plutella xylostella than structurally similar compounds, particularly at low rates of application.
Compound of the invention Reference compound
Figure imgf000079_0002
Compound Test Application rate Control /
/ ppm %
Compound of the invention Plutella xylostella (Diamond 12.5 100
back moth)
3 100
0.8 100 Reference compound Plutella xylostella (Diamond 12.5 85
back moth)
3 0
0.8 0
The compound of the invention and reference compound are compounds 3-6 and 3-643 respectively from WO 2009/112275.

Claims

Claims
1. A method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula IE
Figure imgf000081_0001
wherein -β'-Β^Β3- is -C=N-0-, -C=N-CH2-, or -N-CH2-CH2-;
R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R2 is group X
Figure imgf000081_0002
X2 is C-X6 or nitrogen;
X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen;
Y1 is CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; and R9 is Ci-C4alkyl, CrC4haloalkyl, Ci-C4alkyl-0-CH2-, Ci-C4haloalkyl-0-CH2-, C3-C6cycloalkyl, C3- Cgcycloalkyl-CHr, CrC4alkyl-S-CH2-, CrC4alkyl-S(0)-CH2-, or CrC4alkyl-S(02)-CH2.
2. A method according to claim 1, wherein R9 is methyl, ethyl, propyl, CF3CH2- or cyclopropyl.
3. A method according to claim 1 or claim 2, wherein
R1 is CF3;
-B'-B^B3- is -C=N-0- or -C=N-CH2-; and
Y1, Y2 and Y3 are CH.
4. A method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula IC
Figure imgf000082_0001
wherein -β'-Β^Β3- is -C=N-0-, -C=N-CH2-, or -N-CH2-CH2-;
R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R2 is group X
Figure imgf000082_0002
X2 is C-X6 or nitrogen;
X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen;
Y1 is C-R6, CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; R5 is hydrogen, halogen, cyano, nitro, NH2, Ci-C4alkyl, C3-C5cycloalkyl, C3- C5halocycloalkyl, Ci-C2alkoxy, or Ci-C2haloalkoxy;
R6 when present together with R5 forms a -CH=CH-CH=CH- bridge;
each Z is independently halogen, Ci-Ci2alkyl or Ci-Ci2alkyl substituted by one to five R12, nitro, Cp Ci2alkoxy or Ci-Ci2alkoxy substituted by one to five R12 cyano, Ci-Ci2alkylsulfinyl, Ci-Ci2alkylsulfonyl, Ci-Ci2haloalkylsulfinyl, Ci-Ci2haloalkylsulfonyl, hydroxyl or thiol;
each R12 is halogen, cyano, nitro, hydroxy, CpCgalkoxy-, Ci-Cghaloalkoxy-, mercapto, CpCgalkylthio-, or CpCghaloalkylthio; and
k is 0, 1,2 or 3.
5. A method according to claim 4, wherein
R5 is cyano;
k is 0 or 1 ; and
Z is cyano or trifluoromethyl.
6. A method according to claim 4 or claim 5, wherein
R1 is CF3;
-B'-B^B3- is -C=N-0- or -C=N-CH2-;
Y1, Y2 and Y3 are CH; and
k is 0.
7. A method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula ID
Figure imgf000083_0001
wherein -β'-Β^Β3- is -C=N-0-, -C=N-CH2-, or -N-CH2-CH2-;
R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R2 is group X
Figure imgf000083_0002
X2 is C-X6 or nitrogen;
X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and
X6 is not hydrogen;
Y1 is C-R6, CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen;
R5 is hydrogen, halogen, cyano, nitro, NH2, Ci-C4alkyl,
Figure imgf000083_0003
C3-C5cycloalkyl, C3-
C5halocycloalkyl, Ci-C2alkoxy, or Ci-C2haloalkoxy;
R6 when present together with R5 forms a -CH=CH-CH=CH- bridge;
each Z is independently halogen, Ci-Ci2alkyl or Ci-Ci2alkyl substituted by one to five R12, nitro, Cp
Ci2alkoxy or Ci-Ci2alkoxy substituted by one to five R12 cyano, Ci-Ci2alkylsulfinyl, Ci-Ci2alkylsulfonyl,
Ci-Ci2haloalkylsulfinyl, Ci-Ci2haloalkylsulfonyl, hydroxyl or thiol; each R is halogen, cyano, nitro, hydroxy, CpCgalkoxy-, CpCghaloalkoxy-, mercapto, CpCgalkylthio-, or CpCghaloalkylthio; and
k is 0, 1,2 or 3.
5 8. A method according to claim 7, wherein
wherein
R5 is cyano;
k is 0 or 1 ; and
Z is cyano or trifluoromethyl;
10 and preferably when k is 1 , Z is attached to the 4 position of the imidazole moiety.
9. A method according to claim 7 or claim 8, wherein
R1 is CF3;
-B'-B^B3- is -C=N-0- or -C=N-CH2-;
15 Y1, Y2 and Y3 are CH;
k is 1 ; and
Z is cyano or trifluoromethyl;
and preferably Z is attached to the 4 position of the imidazole moiety.
20 10. A method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula IA
Figure imgf000084_0001
(IA)
wherein -β'-Β^Β3- is -C=N-0-, -C=N-CH2-, or -N-CH2-CH2- R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R2 is group X
Figure imgf000084_0002
X2 is C-X6 or nitrogen; X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen;
Y1 is C-R6, CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; R5 is hydrogen, halogen, cyano, nitro, NH2, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5cycloalkyl, C3- C5halocycloalkyl, Ci-C2alkoxy, or Ci-C2haloalkoxy;
R6 when present together with R5 forms a -CH=CH-CH=CH- bridge; and
R8 is Ci-C4alkyl, CrC4haloalkyl, Ci-C4alkoxy(Ci-C4)alkyl, CrC4alkylthio(Ci-C4)alkyl, Cr
C4alkylsulfinyl(Ci-C4)alkyl, Ci-C4alkylsulfonyl(CrC4)alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl(Cr C4)alkyl-, or tetrahydrofuranyl.
11. A method according to claim 10, wherein
R5 is chloro, bromo, fluoro or methyl; and
R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-.
12. A method or use according to claim 10 or claim 11, wherein
R1 is CF3;
-B'-B^B3- is -C=N-0- or -C=N-CH2-;
Y1, Y2 and Y3 are CH; and
R5 is chloro or methyl.
13. A method or use according to claim 10, wherein
-B'-B^B3- is -C=N-0-, R1 is trifluoromethyl, R2 is 3-bromo-5-trifluoromethylphenyl, Y1, Y2 and Y3 are CH; R5 is chloro, and R8 is n-propyl.
14. A method for controlling and/or preventing insects from the genus of Plutella in useful plants, comprising applying to a crop of useful plants, the locus thereof, or propagation material thereof, a compound of formula IB
Figure imgf000085_0001
wherein -β'-Β^Β3- is -C=N-0-, -C=N-CH2-, or -N-CH2-CH2-;
R1 is trifluoromethyl, difluoromethyl or chlorodifluoromethyl;
R2 is group X
Figure imgf000086_0001
X2 is C-X6 or nitrogen;
X1, X3 and X6 are independently hydrogen, halogen or trihalomethyl, wherein at least one of X1, X3 and X6 is not hydrogen;
Y1 is CH or nitrogen;
Y2 and Y3 are independently CH or nitrogen;
wherein no more than two of Y1, Y2 and Y3 are nitrogen and wherein Y2 and Y3 are not both nitrogen; R7 is CrC4alkyl; and
R8 is Ci-C4alkyl, CrC4haloalkyl, Ci-C4alkoxy(Ci-C4)alkyl, CrC4alkylthio(Ci-C4)alkyl, Cr
C4alkylsulfinyl(Ci-C4)alkyl, Ci-C4alkylsulfonyl(Ci-C4)alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl(Cr C4)alkyl-, or tetrahydrofuranyl.
15. A method according to claim 14, wherein
R7 is methyl; and
R8 is methyl, ethyl, n-propyl, isopropyl, CH3-0-CH2-, CH3-S-CH2-, CH3-S(0)-CH2-, CH3-S02-CH2-, cyclobutyl, cyclopropyl or cyclopropyl-CH2-.
16. A method according to claim 14 or claim 15, wherein
R1 is CF3;
-B'-B^B3- is -C=N-0-, -C=N-CH2- or -N-CH2-CH2-; and
Y1, Y2 and Y3 are CH.
17. A method according to any one of claims 1 to 16, wherein R2 is 3,5-dichlorophenyl-, 3,5- dichloro-4-fluorophenyl-, 3,4,5-trichlorophenyl- or 3,5-bis(trifluoromethyl)phenyl.
18. A method according to any one of claims 1 to 17, wherein the compound of formula I is a mixture of the compound of formula I* and the compound of formula I**
Figure imgf000087_0001
(I*) (I**)
wherein A represents Al, A2, A3 A4 or A5
Figure imgf000087_0002
and the remaining substituents are as defined in any one of claims 1 to 17, providing that R5 is hydrogen when A represents A2, and wherein said mixture is enriched for the compound of formula I**.
19. A method according to any one of claims 1 to 3 and 17 to 18, wherein the compound of formula IE is a mixture of compounds IE-a and IE-b
Figure imgf000087_0003
wherein the molar proportion of compound IE-a compared to the total amount of IE-a and IE-b is greater than 50%.
20. Use of a compound of formula I as defined in any one of claims 1 to 19 for control of insects from the genus Plutella in a crop of useful plants.
21. A method or use according to any one of claims 1 to 20, wherein the useful plant is brassica.
22. A method for obtaining regulatory approval for the use of one or more of a compound of formula I as defined in any one of claims 1 to 19 to control insects from the genus Plutella, in particular the species Plutella xylostella, comprising at least one step of referring to, submitting or relying on biological data showing that said active ingredient reduces insect pressure.
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