WO2007134799A1 - Novel microbiocides - Google Patents

Novel microbiocides Download PDF

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Publication number
WO2007134799A1
WO2007134799A1 PCT/EP2007/004425 EP2007004425W WO2007134799A1 WO 2007134799 A1 WO2007134799 A1 WO 2007134799A1 EP 2007004425 W EP2007004425 W EP 2007004425W WO 2007134799 A1 WO2007134799 A1 WO 2007134799A1
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Prior art keywords
formula
substituted
alkyl
hydrogen
halogen
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PCT/EP2007/004425
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French (fr)
Inventor
Daniel Stierli
John J. Taylor
Harald Walter
Paul Anthony Worthington
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Syngenta Participations Ag
Syngenta Limited,
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Priority to AT07764538T priority Critical patent/ATE449068T1/en
Priority to CA002650795A priority patent/CA2650795A1/en
Priority to JP2009510362A priority patent/JP5155303B2/en
Priority to CN2007800211443A priority patent/CN101466671B/en
Priority to MX2008014534A priority patent/MX2008014534A/en
Priority to EP07764538A priority patent/EP2018367B1/en
Priority to BRPI0712027A priority patent/BRPI0712027B1/en
Priority to US12/301,080 priority patent/US8618023B2/en
Priority to DE602007003343T priority patent/DE602007003343D1/en
Priority to KR1020087030887A priority patent/KR101380139B1/en
Publication of WO2007134799A1 publication Critical patent/WO2007134799A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • 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
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
    • C07D327/06—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D411/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to novel microbiocidally active, in particular f ungicidally active, cyclopropyl amides. It further relates to intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
  • N-[2-(2-pyridinyl)cycloalkyl]-carboxamide derivatives and their use as fungicides are described in WO 05/103006 and WO 05/103004.
  • 2,6-Di-chloro-isonicotinic acid phenethyl- amide derivatives and their use as pesticides are described in JP-09-165-374.
  • X is oxygen or sulfur
  • A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R 6 , R 7 and R 8 ;
  • R 6 , R 7 and R 8 are each, independently, hydrogen, halogen, cyano, nitro, C 1-4 alkyl,
  • Ri. R ⁇ . R 3 and R 4 independently of each other stand for hydrogen, halogen, cyano, nitro, Ci-
  • each R a independently of each other stand for halogen, cyano, nitro, d-C 6 alkoxy, C 1 -
  • R c is Ci-C 6 alkyl
  • R 53 and R 5b are each, independently, hydrogen, C r C 6 alkyl, d-C 6 halogenalkyl, C 2 -C 6 alkenyl,
  • R 5C is hydrogen, d-C 6 alkyl, Ci-C 6 halogenalkyl, d-Cealkoxy-d-C ⁇ alkyl, d-C 6 halogenalkoxy- d-C 6 alkyl, d.C 6 alkylthio, d-C 6 halogenalkylthio, d-C 6 alkoxy, d-C 6 halogenalkoxy, C 3 -
  • B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents
  • each substituent R 9 independently of each other stands for halogen, cyano, nitro, -
  • each R J is independently of each other hydrogen or d-C 6 alkyl; each R k is independently of each other d-C 6 alkyl; and tautomers/isomers/enantiomers of these compounds.
  • alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, ⁇ -propyl, n-butyl, n-pentyl, ⁇ -hexyl, /sopropyl, ⁇ -butyl, sec-butyl, /sobutyl or fert-butyl.
  • Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned.
  • the alkenyl and alkynyl groups can be mono- or di- unsaturated.
  • the cycloalkyl groups occuring in the definitions of the substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • bicycloalkyl groups occuring in the definitions of the substituents are, depending on the ring size, bicyclo[2.1.1 ]hexane, bicyclo[2.2.1 ]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, bicyclo[4.2.2]decane, bicyclo[4.3.2]undecane, adamantane and the like.
  • Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy.
  • Halogenalkyl groups preferably have a chain length of from 1 to 4 carbon atoms.
  • Halogenalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 ,1 -difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2- trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
  • Suitable halogenalkenyl groups are alkenyl groups which are mono- or polysubstituted by halogen, halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-i -methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut-2-en- 1 -yl.
  • Suitable halogenalkynyl groups are, for example, alkynyl groups which are mono- or polysubstituted by halogen, halogen being bromine, iodine and in particular fluorine and chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoro- propynyl and 4,4,4-trifluorobut-2-yn-1 -yl.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy.
  • Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2- trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec- butylthio or tert-butylthio, preferably methylthio and ethylthio.
  • Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
  • substituted by one or more substituents in the definition of substituents R 1 , R 2 , R3, R 4 and R f , means typically, depending on the chemical structure of substituents Ri, R 2 , R 3 , R 4 and R f , monosubstituted to nine-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.
  • substituted by one or more substituents in the definition of substituent B, means typically, depending on the chemical structure of substituent B, monosubstituted to seven-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.
  • a "5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur” preferably means pyrazolyl (especially pyrazol-4-yl), thiazolyl (especially thiazol-5-yl), pyrrolyl (especially pyrrol-3-yl), 1 ,2,3 triazolyl, oxazolyl (especially oxazol-5-yl), pyridyl (especially pyrid-3-yl) or 2,3 dihydro-[1 ,4]oxathiinyl (especially 2,3 dihydro-[1 ,4]oxathiin-5-yl).
  • heteroaryl is preferably understood to be an aromatic 5- or 6-membered heteroaryl group bonded via a carbon atom or an nitrogen atom, which group may be interrupted once by oxygen, once by sulfur and/or once, twice or three times by nitrogen.
  • Said groups bonded via a carbon atom are, for example, pyrazol-3-yl, pyrazol-4-yl, 3-isoxazolyl, pyrrol-2-yl, pyrrol-3-yl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, imidazol- 2-yl, imidazol-4-yl, imidazol-5-yl, 2-oxazolyl, 5-oxazolyl, 4-oxazolyl, 2-thiazolyl, 5-thiazolyl, 4- thiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-isothiazolyl, 1 ,2,3-triazol-4-yl, 1 ,2,3-triazol-2-yl, 1 ,2,4- triazol-3-yl, 1 ,2,3-oxadiazol-4-yl, 1 ,2,4-oxadiazol-5-yl, 1 ,2,4-oxadiazol-3
  • Said groups bonded via a nitrogen atom are, for example, 1 H-pyrrol-1 -yl, 1 H-pyrazol-1 -yl, 1 H-1 ,2,4- triazol-1 -yl or 4H-1 ,2,4-triazol-4-yl.
  • the invention covers all those isomers and mixtures thereof.
  • the compounds of the formula I may occur in different tautomeric forms.
  • compounds of formula I, wherein X is oxygen and R 2 is hydrogen exist in the tautomeric forms I
  • the invention covers all those tautomeric forms and mixtures thereof.
  • a prefered group of compounds A is a 5-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the heterocyclic ring being substituted by the groups R 6 , R 7 and R 8 .
  • A is A 1
  • R 17 is d-C 4 alkyl, d-C 4 halogenalkyl, d-C 4 halogenalkoxy, d-C 4 alkoxy-d-C 4 alkyl or C 1 - C 4 halogenalkoxy-d-C 4 alkyl;
  • R 18 is hydrogen, halogen or cyano; or A is A 2
  • R 26 is halogen, cyano, nitro, C r C 4 alkyl, d-C 4 halogenalkyl, d-C 4 halogenalkoxy, C 1 -
  • R 27 is d-C 4 alkyl, d ⁇ halogenalkyl, d-C ⁇ alogenalkoxy, CrC ⁇ alkoxy-CrC ⁇ alkyl or C 1 - dhalogenalkoxy-C T -dalkyl; or A is A 3
  • R 36 is halogen, cyano, nitro, d-C 4 alkyl, Crdhalogenalkyl, d-C 4 halogenalkoxy, C 1 -
  • R 37 is d-C 4 alkyl, d-C 4 halogenalkyl, CrC-shalogenalkoxy, C 1 -C 4 BIkOXy-C 1 -C 4 alkyl or C 1 -
  • R 38 is hydrogen, halogen or cyano; or A is A 4
  • R 46 and R 47 independently of one another are halogen, cyano, nitro, CrC 4 alkyl, d- C 4 halogenalkyl, C 1 -C 4 halogenalkoxy, d-C 4 alkoxy- C r C 4 alkyl or d-C 4 halogenalkoxy-d- C 4 alkyl.
  • A is A 1 .
  • A is A 2 .
  • A is A 3 .
  • group of compounds A is a phenyl ring or a 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the phenyl ring or the heterocyclic ring being substituted by the groups R 6 , R 7 and R 8 .
  • A is A 5
  • R 56 is halogen, d-C 4 halogenalkyl, Ci-C 4 halogenalkoxy or d-C 4 halogenalkoxy-d-dalkyl; or A is A 6
  • R 66 is halogen, cyano, nitro, d-C 4 alkyl, Ci-C 4 halogenalkyl, d-C 4 alkoxy- d-C 4 alkyl or C 1 -
  • R 76 is Ci-C 4 alkyl or d-C 4 halogenalkyl.
  • A is A 5 .
  • A is A 6 .
  • A is A 7 .
  • R 18 is hydrogen.
  • R 16 is C 1 -C 4 alkyl or CrC 4 haloalkyl, preferably C 1 -C 4 haloalkyl;
  • R 17 is C 1 -C 4 alkyl; and
  • R 18 is hydrogen or halogen, preferably hydrogen.
  • R 27 is d-C 4 alkyl.
  • R 37 is d-C 4 alkyl
  • R 38 is hydrogen or halogen.
  • R 46 halomethyl preferably R 46 is selected from CF 3 , CF 2 H and CFH 2 ; and R 47 is d-C 4 alkyl.
  • One embodiment of the invention is represented by compounds, wherein X is oxygen.
  • Another embodiment of the invention is represented by compounds, wherein X is sulfur.
  • Compounds, wherein X is oxygen are prefered.
  • R 5 is hydrogen
  • R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, cyano or d-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, d-C 6 alkoxy and T -C ⁇ halogenalkoxy; more preferably R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, cyano or Ci-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C 6 alkoxy; most preferably R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, or d-C 6 alkyl.
  • R 1 is hydrogen, halogen, d-C 6 alkyl, d-C 6 halogenalkyl or d-C 6 alkoxy-d-C 6 alkyl;
  • R 2 is hydrogen, halogen, d-C 6 alkyl, d-C 6 halogenalkyl or d-Cealkoxy-d-Cealkyl;
  • R 3 is hydrogen, halogen, d-C 6 alkyl, d-C 6 halogenalkyl or d-Cealkoxy-d-Cealkyl; and R 4 is hydrogen, halogen, d-C 6 alkyl, d-C 6 halogenalkyl or d-C 6 alkoxy-d-C 6 alkyl.
  • R 1 is hydrogen, halogen or d-C 6 alkyl; and R 2 , R 3 and
  • R 4 are each independently selected from hydrogen and d-C 6 alkyl. Within said embodiment, more preferably R 3 and R 4 are hydrogen. In one embodiment R 2 , R 3 and R 4 are hydrogen. In another embodiment, R 1 , R 2 , R 3 and R 4 are hydrogen.
  • One embodiment of the invention is represented by compounds, wherein B is a phenyl group, which is substituted by one or more substituents R 9 .
  • B is a phenyl group, which is substituted by one, two or three substituents R 9 ; more preferably B is a phenyl group, which is substituted by one or two substituents R 9 .
  • B is a phenyl group, that is substituted by at least one substituent R 9 in the para-position.
  • each L independently of each other is a bond or -O-.
  • each substituent R f independently of each other stands for d-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C 6 alkoxy; C 2 - C 6 alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C 6 alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
  • B is B 1 in which
  • R 19a is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, CrC 6 alkoxy, d-C 6 halogenalkyl, d-C ⁇ halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
  • R 19b is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, d-C 6 alkoxy, CrC 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
  • R 19c is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, C r C 6 alkoxy, d-C 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
  • R 19d is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, d-C 6 alkoxy, d-C 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
  • R 19e is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, d-C 6 alkoxy, d-C 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R 193 , Ri 9b , Ri 9c , Ri 9d and R 19e is not hydrogen.
  • R 19b and R 19d is hydrogen; and R 19a , R 19c and R 19e independently of one another are selected from hydrogen, halogen, cynao, C 2 -C 6 alkynyl, C 1 -
  • Another embodiment of the invention is represented by compounds, wherein B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R 9 .
  • Another embodiment of the invention is represented by compounds, wherein B is a naphthyl group, which is substituted by one or more substituents R 9 .
  • B is a naphthyl group, which is substituted by one or two substituents R 9 .
  • each substituent R 6 independently of each other stands for halogen
  • -C(R d ) N(OR e ) or -L-R f
  • each substituent R 6 independently of each other stands for halogen or -L-R f .
  • each L independently of each other is a bond or -O-.
  • each substituent R f independently of each other stands for C 1 - C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC 6 alkoxy; C 2 -C 6 alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C 6 alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
  • Another embodiment of the invention is represented by compounds, wherein B is a quinolinyl group, which is substituted by one or more substituents R 9 .
  • B is a quinolinyl group, which is substituted by one or two substituents R 9 .
  • each L independently of each other is a bond or -O-.
  • each substituent R f independently of each other stands for C 1 - C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from
  • halogen and d-C ⁇ alkoxy C 2 -C 6 alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC 6 alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
  • A is as defined under formula I, and R * is halogen, hydroxy or C 1-6 alkoxy, preferably chloro, in the presence of a base, such as triethylamine, Hunig base, sodium bicarbonate, sodium carbonate, potassium carbonate, pyridine or quinoline, but preferably triethylamine, and in a solvent, such as diethylether, TBME, THF, dichloromethane, chloroform, DMF or NMP, for between 10 minutes and 48 hours, preferably 12 to 24 hours, and between 0 0 C and reflux, preferably 20 to 25 0 C.
  • a base such as triethylamine, Hunig base, sodium bicarbonate, sodium carbonate, potassium carbonate, pyridine or quinoline, but preferably triethylamine
  • a solvent such as diethylether, TBME, THF, dichloromethane, chloroform, DMF or NMP, for between 10 minutes and 48 hours, preferably 12 to 24 hours, and
  • a coupling agent such as benzotriazol-i -yloxytris(dimethylamino) phosphoniumhexafluorophosphate, bis-(2-oxo-3-oxazolidinyl)-phosphinic acid chloride (BOP- Cl), N.N'-dicyclohexylcarbodiimide (DCC) or 1 ,1 '-carbonyl-diimidazole (CDI), may be used.
  • BOP- Cl bis-(2-oxo-3-oxazolidinyl)-phosphinic acid chloride
  • DCC N.N'-dicyclohexylcarbodiimide
  • CDI 1 ,1 '-carbonyl-diimidazole
  • R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, cyano or d-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, d-C 6 alkoxy and ⁇ Cehalogenalkoxy; more preferably R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, cyano or d-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C 6 alkoxy; most preferably R 1 , R 2 , R 3 and R 4 indepedently of each other stands for hydrogen, halogen, or d-C 6 alkyl.
  • R 1 is hydrogen, halogen, d-C 6 alkyl, C 1 - C 6 halogenalkyl or d-C 6 alkoxy-d-C 6 alkyl
  • R 2 is hydrogen, halogen, d-C 6 alkyl, C 1 - C 6 halogenalkyl or d-Cealkoxy-d-Cealkyl
  • R 3 is hydrogen, halogen, d-C 6 alkyl, C 1 - C 6 halogenalkyl or d-C 6 alkoxy-d-C 6 alkyl
  • R 4 is hydrogen, halogen, d-C 6 alkyl, C 1 - C 6 halogenalkyl or d-C 6 alkoxy-d-C 6 alkyl.
  • R 1 is hydrogen, halogen or d-C 6 alkyl; and R 2 , R 3 and R 4 are each independently selected from hydrogen and d-C 6 alkyl. Within said embodiment, more preferably R 3 and R 4 are hydrogen. In one embodiment R 2 , R 3 and R 4 are hydrogen.
  • R 2 , R 3 and R 4 are hydrogen.
  • In preferred intermediates of formula Il B is a phenyl group, which is substituted by one or more substituents R 9 .
  • preferably B is a phenyl group, which is substituted by one, two or three substituents R 9 ; more preferably B is a phenyl group, which is substituted by one or two substituents R 9 .
  • Also preferably, in intermediates of formula Il B is a phenyl group, that is substituted by at least one substituent R 9 in the para-position.
  • each L independently of each other is a bond or -O-.
  • each substituent R f independently of each other stands for d-C 6 alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C 1 -C 6 BIkOXy; C 2 - C 6 alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC 6 alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
  • R 19a is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, d-Cealkoxy, C 1 - C 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens
  • R 19b is hydrogen, halogen, cyano, d-C ⁇ alkyl, C 2 -C 6 alkynyl, d-C 6 alkoxy, d-C 6 halogenalkyl, d-C 6 halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens
  • R 19c is hydrogen, halogen, cyano, d-C 6 alkyl, C 2 -C 6 alkynyl, C 1 - C 6 alkoxy, d-C ⁇ halogenalkyl, d-C 6 halogenal
  • Ri9c, Ri9d and R 19e is not hydrogen.
  • R 19b and R 19d is hydrogen; and R 193 , Ri 9c and R 19e independently of one another are selected from hydrogen, halogen, cynao, C 2 -C 6 alkynyl, Ci-C 6 halogenalkyl, d-C ⁇ halogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R 193 , Ri 9c and R 19e is not hydrogen.
  • intermediates of formula Il B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R 9 .
  • B is as defined under formula I (intermediates of formula II, in which R 1 , R 2 , R 3 and R 4 are hydrogen and B is as defined under formula I) may be prepared by reaction scheme 1.
  • N-vinylphthalimide (V) to afford phthalimides of the formula IV, wherein B is as defined under formula I, and following hydrazinolysis to afford the cis-2-arylcyclopropylamines of the formula MB, wherein B is as defined under formula I.
  • the reactions are carried out at temperatures of between 0 - 5O 0 C in a convenient organic solvent such as methanol, ethanol, chloroform, dichloromethane or dioxane.
  • a convenient organic solvent such as methanol, ethanol, chloroform, dichloromethane or dioxane.
  • a range of metal catalysts such as the ones derived from copper, palladium, iron or rhodium can be used for the cyclopropanation reaction.
  • the preferred catalyst is rhodium acetate which reacts with the sodium or lithium salt of the tosylhydrazone and N-vinylphthalimide (V) in the presence of a phase transfer catalyst such as benzyltriethylammonium chloride to give phthalimides of the formula IV.
  • the phthalimides of the formula IV are converted to the amines of formula MB with hydrazine hydrate in a convenient solvent such as ethanol.
  • 2-arylcyclopropylamines of the formula MB wherein B is as defined under formula I 1 can be prepared with a moderate trans-selectivity.
  • the cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I can be prepared by metal catalyzed cyclopropanation of an alkyl-diazoacetate of the formula N 2 CHCO 2 R 1 wherein R is d-C 6 alkyl, with an olefin of the formula X, wherein B is as defined under formula I.
  • Suitable solvents for this process include ether, CH 2 CI 2 and CICH2CH 2 CI, preferably ether.
  • Reaction temperatures range from room temperature to 60 0 C, preferably 40 0 C.
  • Suitable catalysts for the cyclopropanation are Cu(acac) 2 or Pd(OAc) 2 .
  • the 2-arylcyclopropylamines trans/cis-(IIB) are then prepared from the cyclopropyl-esters trans/cis-(IX) using a three-step sequence: basic hydrolysis of the ester (J. Vallgarda et al, J.Chem, Soc. Perkin Trans. 1 1994), Curtius rearrangement, and finally hydrolysis of the isocyanate (P.A.S. Smith, Org. Reactions, III, 3371946).
  • trans-2-arylcyclopropylamines of formula trans-(IIB) can be purified by recrystallisation of the corresponding D-and L- tartrates from aqueous 2-propanol according to known methods.
  • 2-arylcyclopropylesters trans/cis-(IX) can selectively hydrolyzed by a modification of the method of H. M Walborsky and L. Plonsker, J. Am. Soc, 83, 2138 (1961).
  • cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I can be prepared by the reaction of diazomethane with an alkyl cinnamate of formula Xl, wherein B is as defined under formula I, in the presence of Pd(OAc) 2 as described by U. Mende et al. THL No.9,629-632, 1975.
  • Pd(OAc) 2 as described by U. Mende et al. THL No.9,629-632, 1975.
  • Such cyclopropanations with diazomethane and chiral palladium(ll)complexes are also described by Scott E. Denmark et al. J. Org. Chem. 1997,62,3375-3389.
  • the trans-2-arylcyclopropylamines of formula trans-(IIB) can then be prepared from the cyclopropyl-esters trans/cis-(IX) as described above.
  • R 1 is hydrogen, halogen, cyano, CrC 6 alkyl, which is unsubstituted or substituted by one or more substituents R a , or C 3 -C 6 cycloalkyl, which is unsubstituted or substituted by one or more substituents R a , wherein each R a independently of each other stand for halogen, cyano, nitro, Ci-C 6 alkoxy, d-C 6 halogenalkoxy, C 3 -C 6 cycloalkyl, d-C 6 alkylthio or d-
  • R 2 is hydrogen, cyano, nitro, Ci-C 6 alkyl, which is unsubstituted or substituted by one or more substituents R a , or C 3 -C 6 cycloalkyl, which is unsubstituted or substituted by one or more substituents R a ; wherein each R a independently of each other stand for halogen, cyano, nitro, CrC 6 alkoxy, d-C 6 halogenalkoxy, C 3 -C 6 cycloalkyl, d-C 6 alkylthio or C 1 - C 6 halogenalkylthio;
  • R 3 and R 4 independently of each other stand for hydrogen, cyano, nitro, Ci-C 6 alkyl, which is unsubstituted or substituted by one or more substituents R a , or CV-Cecycloalkyl, which is unsubstituted or substituted by one or more substituents R a ; wherein each R a independently of each other stand for halogen, cyano, nitro, d-C 6 alkoxy, Ci-C 6 halogenalkoxy, C 3 - C 6 cycloalkyl, Ci-C 6 alkylthio or C,-C 6 halogenalkylthio; may be prepared by reaction scheme 2.
  • reaction of compounds of formula XVI, wherein R 1 , R 3 , R 4 and B are as defined under formula HC, with alkyldiazoacetate derivatives of formula XV, wherein R 2 is as defined under formula MC and R' is d-C 6 alkyl, and Vitamin B 12 a as catalyst gives a diastereomeric mixture of cyclop ropylcarboxylates of formula XIV, wherein R 1 , R 2 , R 3 , R 4 and B are as defined under formula MC.
  • the diastereomers can be separated either chromatographically or, after saponification, by recrystallisation of the corresponding carboxylic acids of formula XIII, wherein R 1 , R 2 , R 3 , R 4 and B are as defined under formula HC Curtius degradation to the BOC-protected amines of formula XII, wherein R 1 , R 2 , R 3 , R 4 and B are as defined under formula HC, and deprotection with hydrogen chloride produces the compounds of formula MC in the form of hydrochlorides (see PCT/US2004/021505 and G. Haufe et al, J. Med. Chem. 2004, 47, 5860-5871 ).
  • the cis and trans isomers of (XIV) or (XII) may be separated by chromatography.
  • the reactions are carried out at temperatures of between 0 - 100°C in a convenient organic solvent such as methanol, ethanol, tert-butanol, trifluoroethanol, chloroform, dichloromethane or dioxane.
  • a convenient organic solvent such as methanol, ethanol, tert-butanol, trifluoroethanol, chloroform, dichloromethane or dioxane.
  • Curtius rearrangement of the carboxylic acids of formula XIII to the BOC-protected amines of formula XII can be carried out using diphenylphosphoryl azide with a convenient base such as triethylamine followed by treatment with di-tert-butyl carbonate (D. Kim and S.
  • the BOC protecting group can be removed by sequential acid and base treatment.
  • R 9 is as defined under formula I; n is 1 , 2, 3, 4, 5, 6 or 7, preferably 1 or 2; R 1 is hydrogen, cyano, CrC 6 alkyl, which is unsubstituted or substituted by one or more substituents R a , or C 3 -C 6 cycloalkyl, which is unsubstituted or substituted by one or more substituents R a , wherein each R a independently of each other stand for halogen, cyano, nitro, d-C 6 alkoxy, Ci-C 6 halogenalkoxy, C 3 -C 6 cycloalkyl, d-C 6 alkylthio or C 1 - C 6 halogenalkylthio; and R 3 and R 4 independently of each other stand for hydrogen, cyano, nitro, d-C ⁇ alkyl, which is unsubstituted or substituted by one or more substituents R a , or C 3 - C 6 cycl
  • Said compounds of formula XVII correspond to compounds of formula X or XVI, wherein B is a naphthyl group, which is substituted by one or more substituents R 9 , with the exception of compounds according to formula XVI, wherein R 1 is halogen.
  • compounds of the formula XVII wherein R 9 , n, R 1 , R 3 and R 4 are as defined above, can be prepared from compounds of formula XVIII, wherein R 9 , n, R 1 , R 3 and R 4 are as defined under formula XVII, or from compounds of formula XIX, wherein R 9 , n, R 1 , R 3 and R 4 are as defined under formula XVII, by alcohol-dehydration over KHSO 4 according to Charles C. Price et al. J Org Chem (1949), 14 111-117.
  • Monohalogen-vinylnaphtalenes of formula XX wherein Hal is F or Cl
  • R 5a and R 5b are each, independently, hydrogen, d-C 6 alkyl, d-C 6 halogenalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, COOd-C 4 alkyl, COOC 3 -C 6 alkenyl, COOC 3 -C 6 alkynyl or CN ;
  • R 5c is hydrogen, Ci-C 6 alkyl, CrC 6 halogenalkyl, d-Cealkoxy-d-Cealkyl, d-C 6 halogenalkoxy- d-C 6 alkyl, d-C 6 alkylthio, d-C 6 halogenalkylthio, d-C 6 alk
  • R 1 , R 2 , R 3 , R 4 and R 5 are as defined under formula HD.
  • Compounds of formula I, wherein X is sulfur can be prepared from compounds of formula I, wherein X is oxygen, for example by reaction with P 2 S 5 in an inert solvent, such as benzene, toluene, tetrahydrofurane, dioxane or mixtures thereof.
  • the compounds of the formula III are known and partially commercially available. They can be prepared analogously as described, for example, in WO 00/09482 , WO 02/38542, WO 04/018438, EP-0-589-301 , WO 93/11 117 and Arch. Pharm. Res. 2000, 23(4), 315-323.
  • aprotic inert organic solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone.
  • hydrocarbons such as benzene, toluene, xylene or cyclohexane
  • chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene
  • ethers such as diethyl
  • the reaction temperatures are advantageously between -20 0 C and +120 0 C.
  • the reactions are slightly exothermic and, as a rule, they can be carried out at room temperature.
  • the mixture may be heated briefly to the boiling point of the reaction mixture.
  • the reaction times can also be shortened by adding a few drops of base as reaction catalyst.
  • Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1 ,4-diazabicyclo[2.2.2]octane, 1 ,5-diazabicyclo[4.3.0]non-5-ene or 1 ,5-diazabicyclo- [5.4.0]undec-7-ene.
  • inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, or hydrogen carbonates such as potassium hydrogen carbonate and sodium hydrogen carbonate may also be used as bases.
  • the bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
  • a phase-transfer catalyst for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
  • the compounds of formula I can be isolated in the customary manner by concentrating and/or by evaporating the solvent and purified by recrystallization or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons.
  • the compounds I and, where appropriate, the tautomers thereof can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.
  • Diastereomer mixtures or racemate mixtures of compounds I which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
  • Enantiomer mixtures such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high- performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is com- plexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities
  • Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereose- lective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.
  • the compounds I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
  • the invention relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as acitve ingredient to the plants, to parts thereof or the locus thereof.
  • the compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants.
  • the compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
  • compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
  • the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
  • the compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara).
  • Fungi imperfecti e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria
  • Basidiomycetes e.g. Rhizoctonia, Hemileia, Puccinia
  • novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). Good activity has been observed against Asian soybean rust (Phakopsora pachyrhizi).
  • useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco
  • useful plants is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • imazamox by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
  • useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-O 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-O 392 225, WO 95/33818, and EP-A-O 353 191.
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • 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 the 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.
  • the compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
  • the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
  • compositions are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.
  • the methods of application such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.
  • the compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
  • the compounds of formula I or compositions comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds.
  • further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • a preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • extenders for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • the agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 2Og to 60Og a.i./ha.
  • convenient rates of application are from 10mg to 1 g of active substance per kg of seeds.
  • the rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
  • the compounds of formula I can also be used in methods of protecting crops of useful plants against attack by phytopathogenic organisms as well as the treatment of crops of useful plants infested by phytopathogenic organisms comprising administering a combination of glyphosate and at least one compound of formula I to the plant or locus thereof, wherein the plant is resistant or sensitive to glyphosate.
  • Said methods may provide unexpectedly improved control of diseases compared to using the compounds of formula I in the absence of glyphosate. Said methods may be effective at enhancing the control of disease by compounds of formula I. While the mixture of glyphosate and at least one compound of formula I may increase the disease spectrum controlled, at least in part, by the compound of formula I, an increase in the activity of the compound of formula I on disease species already known to be controlled to some degree by the compound of formula I can also be the effect observed.
  • Said methods are particularly effective against the phytopathogenic organisms of the kingdom Fungi, phylum Basidiomycot, class Uredinomycetes, subclass Urediniomycetidae and the order Uredinales (commonly referred to as rusts).
  • Species of rusts having a particularly large impact on agriculture include those of the family Phakopsoraceae, particularly those of the genus Phakopsora, for example Phakopsora pachyrhizi, which is also referred to as Asian soybean rust, and those of the family Pucciniaceae, particularly those of the genus P ⁇ ccinia such as Puccinia graminis, also known as stem rust or black rust, which is a problem disease in cereal crops and P ⁇ ccinia recondita, also known as brown rust.
  • An embodiment of said method is a method of protecting crops of useful plants against attack by a phytopathogenic organism and/or the treatment of crops of useful plants infested by a phytopathogenic organism, said method comprising simultaneously applying glyphosate, including salts or esters thereof, and at least one compound of formula I, which has activity against the phytopathogenic organism to at least one member selected from the group consisting of the plant, a part of the plant and the locus of the plant.
  • the compounds of formula I, or a pharmaceutical salt thereof, described above have also an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal.
  • Animal can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human.
  • Treatment means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection.
  • prevention means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
  • a compound of formula I in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal.
  • a compound of formula I as a pharmaceutical agent.
  • a compound of formula I as an antimicrobial agent in the treatment of an animal.
  • a pharmaceutical composition comprising as an active ingredient a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal.
  • This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs.
  • this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion.
  • this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection.
  • this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
  • the compounds of formula I are effective against various microbial species able to cause a microbial infection in an animal.
  • microbial species are those causing Aspergillosis such as Aspergillus f ⁇ migatus, A. flavus, A. terms, A. nidulans and A. niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C.
  • Aspergillosis such as Aspergillus f ⁇ migatus, A. flavus, A. terms, A. nidulans and A. niger
  • Blastomycosis such as Blastomyces dermatitidis
  • Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C
  • Microsporum Spp Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and Histoplasma Spp.
  • Example PI Preparation of S-difluoromethyl-i-methyl-I H-pyrazole ⁇ -carboxylic acid f2-(4-chlorophenvO-cyclopropyn-amide (compound no. 1.001):
  • Example P2 Preparation of S-difluoromethyl-i-methyl-I H-pyrazole ⁇ -carboxylic acid (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-amide (compound no. 1.004):
  • Example P3 Preparation of N-rd R ⁇ SV ⁇ -r ⁇ -chlorophenvD- ⁇ -fluoro-cyclopropy ⁇ - trifluoromethyl-benzamide (compound no. 6.004):
  • the dichloromethane soluble material consisted of a 1 :1 mixture of cis/trans isomers.
  • a 1 M sodium methoxyde solution was prepared by adding sodium (423mg, 18.39mmol) to anhydrous methanol (19ml) with external cooling. Once all of the metal was dissolved, 4- chlorobenzaldehyde tosyl hydrazone (5.39g, 17.51 mmol) was added and the mixture was stirred until the solid was dissolved. After stirring for a further 15 min at room temperature the methanol was removed under reduced pressure at room temperature. 5.73g of 4- chlorobenzaldehyde tosyl hydrazone sodium salt was obtained in the form of a white powder (99% of theory).
  • Example P5 Preparation of 2-(4-chlorophenyl)-2-fluoro-cvclopropylamine (compound no. Z1.004): a) Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropane carboxylic acid ethyl ester
  • Vitamin B12a (LOOg ; 0.723mmol) was dissolved in dry trifluoroethanol (70ml) and 1 -chloro- 4-(1-fluoro-vinyl)-benzene (6.5Og ; 41.5mmol) and ethyl diazoacetate (6.3Og; 50mmol; 90% purity) was added. The solution was stirred, under reflux, under nitrogen atmosphere for 18h. After cooling the solvent was evaporated and the residue purified by flash chromatography using 9:1 hexane/ethyl acetate.
  • the carboxylic acid from example P5b) (5.09g; 23.7mmol) was dissolved in a mixture of cyclohexane (150ml) and tert-butanol (17.7Og; 0.237m). Triethylamine (2.86g; 0.0284m) and diphenylphosphoryl azide (7.3Og; 0.0262m) were added and the solution stirred under reflux under nitrogen for 18h. After cooling, di-tert-butyl carbonate (7.86g ; 0.0359m) was added and the mixture stirred under reflux for 2h.
  • Tables 1 to 8 which follow the Table Y below, comprises 274 compounds of the formula (IA) in which R 1 , R 2 , R 3 , R 4 , R 9a , R 9 b and R 9c have the values given in Table Y and A has the value given in the relevant Table 1 to 8.
  • Table 1 corresponds to Table Y when Y is 1 and A has the value given under the Table 1 heading
  • Table 2 corresponds to Table Y when Y is 2 and A has the value given under the Table 2 heading
  • Table 1 provides 274 compounds of formula (IA), wherein A is wherein the broken lines indicate the point of attachment of the group A to the amide group, and R 1 , R 2 , R3, R 4 , R9a > R ⁇ b and R 9c are as defined in Table Y.
  • compound 1.001 has the following structure:
  • Table 2 provides 274 compounds of formula (IA) wherein A is
  • R 1 , R 2 , R3, R 4 , Rg a , R ⁇ b and R 9c are as defined in Table Y.
  • Table 3 provides 274 compounds of formula (IA) wherein A is
  • R 1 , R 2 , R 3 , R 4 , Rga, R 9b and R 9c are as defined in Table Y.
  • Table 4 provides 274 compounds of formula (IA) wherein A is
  • Table 5 provides 274 compounds of formula (IA) wherein A is
  • R 1 , R 2 , R 3 , R 4 , R 9a , Rg b and R 9c are as defined in Table Y.
  • Table 6 provides 274 compounds of formula (IA) wherein A is
  • R 1 , R 2 , R 3 , R 4 , R 9a , R 9b and R 90 are as defined in Table Y.
  • Table 7 provides 274 compounds of formula (IA) wherein A is
  • R 1 , R 2 , R 3 , R 4 , R 9a , R 9b and R 90 are as defined in Table Y.
  • Table 8 provides 274 compounds of formula (IA) wherein A is
  • Tables 9 to 16 which follow the Table W below, comprises 872 compounds of the formula (IB) in which B, R 1 , R 2 , R 3 and R 4 have the values given in Table W and A has the value given in the relevant Table 9 to 16.
  • Table 9 corresponds to Table W when W is 9 and A has the value given under the Table 9 heading
  • Table 10 corresponds to Table W when W is 10 and A has the value given under the Table 10 heading
  • Table W In Table W the group B stands for the group B 1 , B 2 , B 3 or B 4 :
  • Table 9 provides 872 compounds of formula (IB), wherein A is wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R 1 , R 2 , R 3 , R 4 , R 9a and R 9b are as defined in Table W.
  • compound 9.001 has the following structure:
  • Table 10 provides 872 compounds of formula (IB) wherein A is
  • Table 11 provides 872 compounds of formula (IB) wherein A is
  • Table 12 provides 872 compounds of formula (IB) wherein A is wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R 1 , R 2 , R 3 , R 4 , R 9a and R 9b are as defined in Table W.
  • Table 13 provides 872 compounds of formula (IB) wherein A is
  • Table 14 provides 872 compounds of formula (IB) wherein A is
  • Table 15 provides 872 compounds of formula (IB) wherein A is
  • Table 16 provides 872 compounds of formula (IB) wherein A is
  • Table 18 shows selected melting point and selected NMR data for compounds of Tables 1 to 17.
  • CDCI 3 was used as the solvent for NMR measurements, unless otherwise stated. If a mixture of solvents was present, this is indicated as, for example: CDCI 3 Zd 6 - DMSO). No attempt is made to list all characterising data in all cases.
  • Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
  • Example F-2 Emulsifiable concentrate
  • Emulsions of any desired concentration can be prepared. by diluting such concentrates with water.
  • the solutions are suitable for use in the form of microdrops.
  • Example F7 Flowable concentrate for seed treatment compound of Tables 1 to 16 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % tristyrenephenole with 10-20 moles EO 2 %
  • Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • Example B-1 Action against Podosphaera leucotricha I apple (Powdery mildew on apple) 5 week old apple seedlings cv. Mclntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by shaking plants infected with apple powdery mildew above the test plants. After an incubation period of 12 days at 22 0 C and 60%r.h. under a light regime of 14/10hours (light/dark) the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test ( ⁇ 20% infestation).
  • Example B-2 Action against Venturia inaepualis I apple (Scab on apple) 4 week old apple seedlings cv. Mclntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber.
  • One day after application apple plants are inoculated by spraying a spore suspension (4x10 5 conidia/ml) on the test plants. After an incubation period of 4 days at 21 0 C and 95%r.h. the plants are placed for 4 days at 21 0 C and 60%r.h. in a greenhouse. After another 4 day incubation period at 21 0 C and 95%r.h. the disease incidence is assessed.
  • Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test ( ⁇ 20% infestation).
  • Example B-3 Action against Ervsiphe graminis / barley (Powdery mildew on barley) 1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application barley plants are inoculated by shaking powdery mildew infected plants above the test plants. After an incubation period of 6 days at 20 0 C / 18 0 C (day/night) and 60%r. h. in a greenhouse the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079,1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test ( ⁇ 20% infestation).
  • Example B-4 Action against Botrytis cinerea I apple (Botrvtis on apple fruits) In an apple fruit cv. Golden Delicious 3 holes are drilled and each filled with 30 ⁇ l droplets of the formulated test compound (0.02% active ingredient). Two hours after application 50 ⁇ l of a spore suspension of B. cinerea (4x10 5 conidia/ml) are pipetted on the application sites. After an incubation period of 7 days at 22 0 C in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test ( ⁇ 20% infestation).
  • Example B-5 Action against Botrvtis cinerea I grape (Botrvtis on grapes) 5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application grape plants are inoculated by spraying a spore suspension (1x10 6 conidia/ml) on the test plants. After an incubation period of 4 days at 21 0 C and 95%r.h. in a greenhouse the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test ( ⁇ 20% infestation).
  • Example B-6 Action against Botrvtis cinerea I tomato (Botrvtis on tomatoes) 4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application tomato plants are inoculated by spraying a spore suspension (1x10 5 conidia/ml) on the test plants. After an incubation period of 4 days at 2O 0 C and 95%r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test ( ⁇ 20% infestation).
  • Example B-7 Action against Pyrenophora teres I barley (Net blotch on barley)
  • Example B-8 Action against Septoria fr/f/ ' c/ /wheat (Septoria leaf spot on wheat)
  • Example B-9 Action against Uncinula necator/ grape (powdery mildew on grape) 5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application, the grape plants are inoculated by shaking plants infected with grape powdery mildew above the test plants. After an incubation period of 7 days at 26°C and 60%r.h. under a light regime of 14/10hours (light/dark) the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test ( ⁇ 20% infestation).
  • Example B-10 Action against Alternaria solani/ tomato (early blight on tomatoes) 4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application, the tomato plants are inoculated by spraying a spore suspension (2x10 5 conidia/ml) on the test plants. After an incubation period of 3 days at 20 0 C and 95%r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test ( ⁇ 20% infestation).

Abstract

Compounds of the formula (I) in which the substituents are as defined in claim 1 are suitable for use as microbiocides. Formula (I), wherein X is oxygen or sulfur; A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R<SUB>6</SUB>, R<SUB>7</SUB> and R<SUB>8</SUB>; R<SUB>6</SUB>, R<SUB>7</SUB> and R<SUB>8</SUB> are each, independently, hydrogen, halogen, cyano, nitro, C<SUB>1</SUB>

Description

Novel Microbiocides
The present invention relates to novel microbiocidally active, in particular f ungicidally active, cyclopropyl amides. It further relates to intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
N-[2-(2-pyridinyl)cycloalkyl]-carboxamide derivatives and their use as fungicides are described in WO 05/103006 and WO 05/103004. 2,6-Di-chloro-isonicotinic acid phenethyl- amide derivatives and their use as pesticides are described in JP-09-165-374.
It has been found that novel cyclopropyl amides have microbiocidal activity.
The present invention thus provides compounds of the formula I
Figure imgf000002_0001
wherein
X is oxygen or sulfur;
A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R6, R7 and R8;
R6, R7 and R8 are each, independently, hydrogen, halogen, cyano, nitro, C1-4alkyl,
Ci.4 halogenalkyl, Ci.4 halogenalkoxy, Ci.4alkoxy(Ci.4)alkyl or
Figure imgf000002_0002
halogenalkoxy(C1^)alkyl, provided that at least one of R6, R7 and R8 is not hydrogen;
Ri. R≥. R3 and R4 independently of each other stand for hydrogen, halogen, cyano, nitro, Ci-
C6alkyl, which is unsubstituted or substituted by one or more substituents Ra, C3-
C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra, C2-
C6alkenyl, which is unsubstituted or substituted by one or more substituents Ra or C2-
C6alkynyl, which is unsubstituted or substituted by one or more substituents Ra; each Ra independently of each other stand for halogen, cyano, nitro, d-C6alkoxy, C1-
C6halogenalkoxy, C3-C6cycloalkyl, Ci-C6alkylthio, CrC6halogenalkylthio or -C(Rb)=N(ORc); Rb is hydrogen or Ci-C6alkyl;
Rc is Ci-C6alkyl;
R5 is hydrogen, d.4 alkyl, CH2CH=CHR53, CH2C≡ CR5b or COR50;
R53 and R5b are each, independently, hydrogen, CrC6alkyl, d-C6halogenalkyl, C2-C6alkenyl,
C2-C6alkynyl, C3-C7cycloalkyl, COOC1-C4alkyl, COOC3-C6alkenyl, COOC3-C6alkynyl or CN ;
R5C is hydrogen, d-C6alkyl, Ci-C6halogenalkyl, d-Cealkoxy-d-Cβalkyl, d-C6halogenalkoxy- d-C6alkyl, d.C6alkylthio, d-C6halogenalkylthio, d-C6alkoxy, d-C6halogenalkoxy, C3-
C6alkenyloxy, C3.C6halogenalkenyloxy, C3-C6alkynyloxy or C3-C6halogenalkynyloxy;
B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents
R9; each substituent R9 independently of each other stands for halogen, cyano, nitro, -
C(Rd)=N(ORe) or a group -L-Rf; each Rd is independently of each other hydrogen or d-C6alkyl; each Re is independently of each other d-C6alkyl; each L is independently of each other a bond, -O- or -S-; each Rf is independently of each other d-C6alkyl, which is unsubstituted or substituted by one or more substituents Rh, C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Rh, C6-C14bicycloalkyl, which is unsubstituted or substituted by one or more substituents Rh, C2-C6alkenyl, which is unsubstituted or substituted by one or more substituents Rh, C2-C6alkynyl, which is unsubstituted or substituted by one or more substituents Rh, phenyl, which is unsubstituted or substituted by one or more substituents Rh or heteroaryl, which is unsubstituted or substituted by one or more substituents Rh; each Rh is independently of each other halogen, cyano, nitro, d-C6alkoxy, C1-
C6halogenalkoxy, d.C6alkylthio, d-C6halogenalkylthio, C3-C6alkenyloxy, C3-C6alkynyloxy or
-C(R')=N(ORk); each RJ is independently of each other hydrogen or d-C6alkyl; each Rk is independently of each other d-C6alkyl; and tautomers/isomers/enantiomers of these compounds.
The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, π-propyl, n-butyl, n-pentyl, π-hexyl, /sopropyl, π-butyl, sec-butyl, /sobutyl or fert-butyl. Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or di- unsaturated. The cycloalkyl groups occuring in the definitions of the substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The bicycloalkyl groups occuring in the definitions of the substituents are, depending on the ring size, bicyclo[2.1.1 ]hexane, bicyclo[2.2.1 ]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, bicyclo[4.2.2]decane, bicyclo[4.3.2]undecane, adamantane and the like.
Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy.
Halogenalkyl groups preferably have a chain length of from 1 to 4 carbon atoms. Halogenalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 ,1 -difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2- trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
Suitable halogenalkenyl groups are alkenyl groups which are mono- or polysubstituted by halogen, halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-i -methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut-2-en- 1 -yl.
Suitable halogenalkynyl groups are, for example, alkynyl groups which are mono- or polysubstituted by halogen, halogen being bromine, iodine and in particular fluorine and chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoro- propynyl and 4,4,4-trifluorobut-2-yn-1 -yl.
Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy. Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2- trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec- butylthio or tert-butylthio, preferably methylthio and ethylthio.
Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
In the context of the present invention "substituted by one or more substituents" in the definition of substituents R1, R2, R3, R4 and Rf, means typically, depending on the chemical structure of substituents Ri, R2, R3, R4 and Rf, monosubstituted to nine-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.
In the context of the present invention "substituted by one or more substituents" in the definition of substituent B, means typically, depending on the chemical structure of substituent B, monosubstituted to seven-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.
In the context of the present invention a "5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur" preferably means pyrazolyl (especially pyrazol-4-yl), thiazolyl (especially thiazol-5-yl), pyrrolyl (especially pyrrol-3-yl), 1 ,2,3 triazolyl, oxazolyl (especially oxazol-5-yl), pyridyl (especially pyrid-3-yl) or 2,3 dihydro-[1 ,4]oxathiinyl (especially 2,3 dihydro-[1 ,4]oxathiin-5-yl).
In the context of the present invention "heteroaryl" is preferably understood to be an aromatic 5- or 6-membered heteroaryl group bonded via a carbon atom or an nitrogen atom, which group may be interrupted once by oxygen, once by sulfur and/or once, twice or three times by nitrogen. Said groups bonded via a carbon atom are, for example, pyrazol-3-yl, pyrazol-4-yl, 3-isoxazolyl, pyrrol-2-yl, pyrrol-3-yl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, imidazol- 2-yl, imidazol-4-yl, imidazol-5-yl, 2-oxazolyl, 5-oxazolyl, 4-oxazolyl, 2-thiazolyl, 5-thiazolyl, 4- thiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-isothiazolyl, 1 ,2,3-triazol-4-yl, 1 ,2,3-triazol-2-yl, 1 ,2,4- triazol-3-yl, 1 ,2,3-oxadiazol-4-yl, 1 ,2,4-oxadiazol-5-yl, 1 ,2,4-oxadiazol-3-yl, 1 ,2,3-thiadiazol-4- yl, 1 ,2,4-thiadiazol-5-yl, 1 ,2,4-thiadiazol-3-yl, 1 ,2,5-thiadiazol-3-yl, 1 ,3,4-thiadiazol-2-yl, 2- pyridyl, 4-pyridyl, 3-pyridyl, 3-pyridazinyl, 3-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 2-pyrazinyl, 1 ,3,5-triazin-2-yl, 1 ,2,4-triazin-5-yl or 1 ,2,4-triazin-6-yl. Said groups bonded via a nitrogen atom are, for example, 1 H-pyrrol-1 -yl, 1 H-pyrazol-1 -yl, 1 H-1 ,2,4- triazol-1 -yl or 4H-1 ,2,4-triazol-4-yl.
All compounds of formula I occur in at least two different isomeric forms: Ii (cis) and 1» (trans):
Figure imgf000006_0001
I1 >..
The invention covers all those isomers and mixtures thereof.
The compounds of the formula I may occur in different tautomeric forms. For example, compounds of formula I, wherein X is oxygen and R2 is hydrogen, exist in the tautomeric forms I|M and J|V-
Figure imgf000006_0002
l,v
The invention covers all those tautomeric forms and mixtures thereof.
In a prefered group of compounds A is a 5-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the heterocyclic ring being substituted by the groups R6, R7 and R8.
Within said prefered group of compounds, further preferably A is A1
Figure imgf000006_0003
R17 in which R16 is halogen, cyano, nitro, d-C4alkyl, d-C4halogenalkyl, Ci-C4halogenalkoxy, C1- C4BIkOXy-C1-C4BlRyI or C1-C4halogenalkoxy-C1-C4alkyl;
R17 is d-C4alkyl, d-C4halogenalkyl, d-C4halogenalkoxy, d-C4alkoxy-d-C4alkyl or C1- C4halogenalkoxy-d-C4alkyl; and
R18 is hydrogen, halogen or cyano; or A is A2
Figure imgf000007_0001
27 in which
R26 is halogen, cyano, nitro, CrC4alkyl, d-C4halogenalkyl, d-C4halogenalkoxy, C1-
C4BIkOXy-C1 -C4alkyl or C1-C4halogenalkoxy-C1-C4alkyl; and
R27 is d-C4alkyl, d^halogenalkyl, d-C^alogenalkoxy, CrC^alkoxy-CrC^alkyl or C1- dhalogenalkoxy-CT-dalkyl; or A is A3
Figure imgf000007_0002
R37 in which
R36 is halogen, cyano, nitro, d-C4alkyl, Crdhalogenalkyl, d-C4halogenalkoxy, C1-
C4alkoxy-d-C4alkyl or d-dhalogenalkoxy-Crdalkyl;
R37 is d-C4alkyl, d-C4halogenalkyl, CrC-shalogenalkoxy, C1 -C4BIkOXy-C1 -C4alkyl or C1-
C4halogenalkoxy-d-C4alkyl; and
R38 is hydrogen, halogen or cyano; or A is A4
R46
N R M.7 in which R46 and R47 independently of one another are halogen, cyano, nitro, CrC4alkyl, d- C4halogenalkyl, C1-C4halogenalkoxy, d-C4alkoxy- CrC4alkyl or d-C4halogenalkoxy-d- C4alkyl.
Within said prefered group of compounds, further preferably A is A1. Within said prefered group of compounds, further preferably A is A2. Within said prefered group of compounds, further preferably A is A3. Within said prefered group of compounds, further preferably A is A4.
In another prefered group of compounds A is a phenyl ring or a 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the phenyl ring or the heterocyclic ring being substituted by the groups R6, R7 and R8.
Within said prefered group of compounds, further preferably A is A5
Figure imgf000008_0001
in which
R56 is halogen, d-C4halogenalkyl, Ci-C4halogenalkoxy or d-C4halogenalkoxy-d-dalkyl; or A is A6
Figure imgf000008_0002
in which
R66 is halogen, cyano, nitro, d-C4alkyl, Ci-C4halogenalkyl, d-C4alkoxy- d-C4alkyl or C1-
C4halogenalkoxy-C1-C4alkyl; or A is A7
Figure imgf000008_0003
in which
R76 is Ci-C4alkyl or d-C4halogenalkyl. Within said prefered group of compounds, further preferably A is A5. Within said prefered group of compounds, further preferably A is A6. Within said prefered group of compounds, further preferably A is A7.
In a particular preferred group of compounds A is A1, wherein R18 is hydrogen. In another particular preferred group of compounds A is A1, wherein R16 is C1-C4alkyl or CrC4haloalkyl, preferably C1-C4haloalkyl; R17 is C1-C4alkyl; and R18 is hydrogen or halogen, preferably hydrogen.
In another particular preferred group of compounds A is A2, wherein R26 is d-C4alkyl or C1-
C4haloalkyl; and R27 is d-C4alkyl.
In yet another particular preferred group of compounds A is A3, wherein R36 is d-C4alkyl or
CrC4haloalkyl; R37 is d-C4alkyl; and R38 is hydrogen or halogen.
In yet another particular preferred group of compounds A is A4, wherein R46 is d-C4alkyl or
CrC4haloalkyl; and R47 is d-C4alkyl.
In yet another particular preferred group of compounds A is A4, wherein R46 halomethyl, preferably R46 is selected from CF3, CF2H and CFH2; and R47 is d-C4alkyl.
In yet another particular preferred group of compounds A is A5, wherein R56 is halogen or C1-
C4haloalkyl.
In yet another particular preferred group of compounds A is A6, wherein R66 is halogen or C1-
C4haloalkyl.
In yet another particular preferred group of compounds A is A7, wherein R76 is Ci-C4alkyl or d-C4haloalkyl.
One embodiment of the invention is represented by compounds, wherein X is oxygen. Another embodiment of the invention is represented by compounds, wherein X is sulfur. Compounds, wherein X is oxygen are prefered.
In a prefered group of compounds R5 is hydrogen.
In a prefered group of compounds R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, d-C6alkoxy and T-Cβhalogenalkoxy; more preferably R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or Ci-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy; most preferably R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, or d-C6alkyl.
In a prefered group of compounds
R1 is hydrogen, halogen, d-C6alkyl, d-C6halogenalkyl or d-C6alkoxy-d-C6alkyl;
R2 is hydrogen, halogen, d-C6alkyl, d-C6halogenalkyl or d-Cealkoxy-d-Cealkyl;
R3 is hydrogen, halogen, d-C6alkyl, d-C6halogenalkyl or d-Cealkoxy-d-Cealkyl; and R4 is hydrogen, halogen, d-C6alkyl, d-C6halogenalkyl or d-C6alkoxy-d-C6alkyl.
Within said embodiment, preferably, R1 is hydrogen, halogen or d-C6alkyl; and R2, R3 and
R4 are each independently selected from hydrogen and d-C6alkyl. Within said embodiment, more preferably R3 and R4 are hydrogen. In one embodiment R2, R3 and R4 are hydrogen. In another embodiment, R1, R2, R3 and R4 are hydrogen.
One embodiment of the invention is represented by compounds, wherein B is a phenyl group, which is substituted by one or more substituents R9.
Within said embodiment, preferably B is a phenyl group, which is substituted by one, two or three substituents R9; more preferably B is a phenyl group, which is substituted by one or two substituents R9.
Also preferably, B is a phenyl group, that is substituted by at least one substituent R9 in the para-position.
In a prefered group of compounds each substituent R9 independently of each other stands for halogen, -C(Rd)=N(ORΘ) or -L-R*; more preferably each substituent R9 independently of each other stands for halogen or -L-R*. In a prefered group of compounds each L independently of each other is a bond or -O-. In a prefered group of compounds each substituent Rf independently of each other stands for d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy; C2- C6alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
Within said embodiment, further preferably B is B1
Figure imgf000011_0001
in which
R19a is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, CrC6alkoxy, d-C6halogenalkyl, d-Cεhalogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
R19b is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-C6alkoxy, CrC6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
R19c is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, CrC6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
R19d is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens;
R19e is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R193, Ri9b, Ri9c, Ri9d and R19e is not hydrogen.
In one embodiment of the invention, R19b and R19d is hydrogen; and R19a, R19c and R19e independently of one another are selected from hydrogen, halogen, cynao, C2-C6alkynyl, C1-
C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R193, R19c and R19θ is not hydrogen.
Another embodiment of the invention is represented by compounds, wherein B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R9.
Another embodiment of the invention is represented by compounds, wherein B is a naphthyl group, which is substituted by one or more substituents R9.
Within said embodiment, preferably B is a naphthyl group, which is substituted by one or two substituents R9. Within said embodiment, in a prefered group of compounds each substituent R6 independently of each other stands for halogen, -C(Rd)=N(ORe) or -L-Rf; more preferably each substituent R6 independently of each other stands for halogen or -L-Rf. In a prefered group of compounds each L independently of each other is a bond or -O-. In a prefered group of compounds each substituent Rf independently of each other stands for C1- C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC6alkoxy; C2-C6alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
Another embodiment of the invention is represented by compounds, wherein B is a quinolinyl group, which is substituted by one or more substituents R9.
Within said embodiment, preferably B is a quinolinyl group, which is substituted by one or two substituents R9. Within said embodiment, in a prefered group of compounds each substituent R6 independently of each other stands for halogen, -C(Rd)=N(ORe) or -L-Rf; more preferably each substituent R6 independently of each other stands for halogen or -L-Rf. In a prefered group of compounds each L independently of each other is a bond or -O-. In a prefered group of compounds each substituent Rf independently of each other stands for C1- C6alkyl, which is unsubstituted or substituted by one or more substituents selected from
halogen and d-Cεalkoxy; C2-C6alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC6alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
Compounds of formula I, wherein R5 is hydrogen and X is oxygen, may be prepared by reacting a compound of formula Il
Figure imgf000012_0001
in which B, R1, R2, R3 and R4 are as defined under formula I; with a compound of formula III
A-C(=O)-R* (III),
in which A is as defined under formula I, and R* is halogen, hydroxy or C1-6 alkoxy, preferably chloro, in the presence of a base, such as triethylamine, Hunig base, sodium bicarbonate, sodium carbonate, potassium carbonate, pyridine or quinoline, but preferably triethylamine, and in a solvent, such as diethylether, TBME, THF, dichloromethane, chloroform, DMF or NMP, for between 10 minutes and 48 hours, preferably 12 to 24 hours, and between 00C and reflux, preferably 20 to 25 0C.
When R* is hydroxy, a coupling agent, such as benzotriazol-i -yloxytris(dimethylamino) phosphoniumhexafluorophosphate, bis-(2-oxo-3-oxazolidinyl)-phosphinic acid chloride (BOP- Cl), N.N'-dicyclohexylcarbodiimide (DCC) or 1 ,1 '-carbonyl-diimidazole (CDI), may be used.
The intermediates of the formula Il
Figure imgf000013_0001
in which B, R1, R2, R3 and R4 are as defined under formula I; are novel and were developed specifically for the preparation of the compounds of the formula I. Accordingly, they also form part of the subject-matter of the present invention.
In preferred intermediates of formula II, R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, d-C6alkoxy and ^Cehalogenalkoxy; more preferably R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy; most preferably R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, or d-C6alkyl.
In a prefered group of intermediates of formula II, R1 is hydrogen, halogen, d-C6alkyl, C1- C6halogenalkyl or d-C6alkoxy-d-C6alkyl; R2 is hydrogen, halogen, d-C6alkyl, C1- C6halogenalkyl or d-Cealkoxy-d-Cealkyl; R3 is hydrogen, halogen, d-C6alkyl, C1- C6halogenalkyl or d-C6alkoxy-d-C6alkyl; and R4 is hydrogen, halogen, d-C6alkyl, C1- C6halogenalkyl or d-C6alkoxy-d-C6alkyl. Within said embodiment, preferably, R1 is hydrogen, halogen or d-C6alkyl; and R2, R3 and R4 are each independently selected from hydrogen and d-C6alkyl. Within said embodiment, more preferably R3 and R4 are hydrogen. In one embodiment R2, R3 and R4 are hydrogen. In preferred intermediates of formula Il B is a phenyl group, which is substituted by one or more substituents R9. Within said embodiment, preferably B is a phenyl group, which is substituted by one, two or three substituents R9; more preferably B is a phenyl group, which is substituted by one or two substituents R9. Also preferably, in intermediates of formula Il B is a phenyl group, that is substituted by at least one substituent R9 in the para-position.
In a prefered group of intermediates of formula Il each substituent R9 independently of each other stands for halogen, -C(Rd)=N(ORe) or -L-Rf; more preferably each substituent R9 independently of each other stands for halogen or -L-Rf. In a prefered group of compounds each L independently of each other is a bond or -O-. In a prefered group of compounds each substituent Rf independently of each other stands for d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C1-C6BIkOXy; C2- C6alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and CrC6alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.
Within said embodiment, further preferably in intermediates of formula Il B is B1
Figure imgf000014_0001
in which R19a is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-Cealkoxy, C1- C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19b is hydrogen, halogen, cyano, d-Cβalkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19c is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, C1- C6alkoxy, d-Cεhalogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19d is hydrogen, halogen, cyano, d-Cβalkyl, C2- C6alkynyl, d-C6alkoxy, CrC6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19β is hydrogen, halogen, cyano, C1- C6alkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R19a, Risb. Ri9c, Ri9d and R19e is not hydrogen. In one embodiment of the invention, in intermediates of formula Il R19b and R19d is hydrogen; and R193, Ri9c and R19e independently of one another are selected from hydrogen, halogen, cynao, C2-C6alkynyl, Ci-C6halogenalkyl, d-Cβhalogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R193, Ri9c and R19e is not hydrogen.
In another embodiment of the invention, in intermediates of formula Il B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R9.
Intermediates of the formula II, in which B, R1, R2, R3 and R4 are as defined under formula I; may be prepared according to the following reaction schemes (scheme 1 and 2) or in analogy to those reaction schemes.
Intermediates of the formula MB
Figure imgf000015_0001
in which B is as defined under formula I (intermediates of formula II, in which R1, R2, R3 and R4 are hydrogen and B is as defined under formula I) may be prepared by reaction scheme 1.
Scheme 1 :
Figure imgf000016_0001
route b
(IIB)
Figure imgf000016_0002
(XI)
Scheme 1 , route a (cis-selective synthesis):
According to the procedure of Varinder K. Aggarwal et al, Organic Lett. 2001, Vol. 3, No.17,
2785-2788, aldehydes of formula VIII, wherein B is as defined under formula I, are reacted with compounds of formula VII to give tosylhydrazones of formula Vl, wherein B is as defined under formula I. These diazo-precursors of formula Vl can be induced to react directly with
N-vinylphthalimide (V) to afford phthalimides of the formula IV, wherein B is as defined under formula I, and following hydrazinolysis to afford the cis-2-arylcyclopropylamines of the formula MB, wherein B is as defined under formula I.
The reactions are carried out at temperatures of between 0 - 5O0C in a convenient organic solvent such as methanol, ethanol, chloroform, dichloromethane or dioxane.
A range of metal catalysts such as the ones derived from copper, palladium, iron or rhodium can be used for the cyclopropanation reaction. The preferred catalyst is rhodium acetate which reacts with the sodium or lithium salt of the tosylhydrazone and N-vinylphthalimide (V) in the presence of a phase transfer catalyst such as benzyltriethylammonium chloride to give phthalimides of the formula IV.
The phthalimides of the formula IV are converted to the amines of formula MB with hydrazine hydrate in a convenient solvent such as ethanol.
Scheme 1. route b: synthesis of trans-compounds
According to the procedure of A. Burger et al, J. Am. Soc, 70, 2198 (1948), J. of Med.
Chem. 1962, 5, 1243-1265, 2-arylcyclopropylamines of the formula MB, wherein B is as defined under formula I1 can be prepared with a moderate trans-selectivity. The cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I, can be prepared by metal catalyzed cyclopropanation of an alkyl-diazoacetate of the formula N2CHCO2R1 wherein R is d-C6alkyl, with an olefin of the formula X, wherein B is as defined under formula I. Suitable solvents for this process include ether, CH2CI2 and CICH2CH2CI, preferably ether. Reaction temperatures range from room temperature to 600C, preferably 400C. Suitable catalysts for the cyclopropanation are Cu(acac)2 or Pd(OAc)2. The 2-arylcyclopropylamines trans/cis-(IIB) are then prepared from the cyclopropyl-esters trans/cis-(IX) using a three-step sequence: basic hydrolysis of the ester (J. Vallgarda et al, J.Chem, Soc. Perkin Trans. 1 1994), Curtius rearrangement, and finally hydrolysis of the isocyanate (P.A.S. Smith, Org. Reactions, III, 3371946). The trans-2-arylcyclopropylamines of formula trans-(IIB) can be purified by recrystallisation of the corresponding D-and L- tartrates from aqueous 2-propanol according to known methods. 2-arylcyclopropylesters trans/cis-(IX) can selectively hydrolyzed by a modification of the method of H. M Walborsky and L. Plonsker, J. Am. Soc, 83, 2138 (1961).
Alternatively, cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I, can be prepared by the reaction of diazomethane with an alkyl cinnamate of formula Xl, wherein B is as defined under formula I, in the presence of Pd(OAc)2 as described by U. Mende et al. THL No.9,629-632, 1975. Such cyclopropanations with diazomethane and chiral palladium(ll)complexes are also described by Scott E. Denmark et al. J. Org. Chem. 1997,62,3375-3389. The trans-2-arylcyclopropylamines of formula trans-(IIB) can then be prepared from the cyclopropyl-esters trans/cis-(IX) as described above.
Intermediates of the formula HC
Figure imgf000017_0001
in which B is as defined under formula I and (||),
R1 is hydrogen, halogen, cyano, CrC6alkyl, which is unsubstituted or substituted by one or more substituents Ra, or C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra, wherein each Ra independently of each other stand for halogen, cyano, nitro, Ci-C6alkoxy, d-C6halogenalkoxy, C3-C6cycloalkyl, d-C6alkylthio or d-
C6halogenalkylthio; R2 is hydrogen, cyano, nitro, Ci-C6alkyl, which is unsubstituted or substituted by one or more substituents Ra, or C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra; wherein each Ra independently of each other stand for halogen, cyano, nitro, CrC6alkoxy, d-C6halogenalkoxy, C3-C6cycloalkyl, d-C6alkylthio or C1- C6halogenalkylthio;
R3 and R4 independently of each other stand for hydrogen, cyano, nitro, Ci-C6alkyl, which is unsubstituted or substituted by one or more substituents Ra, or CV-Cecycloalkyl, which is unsubstituted or substituted by one or more substituents Ra; wherein each Ra independently of each other stand for halogen, cyano, nitro, d-C6alkoxy, Ci-C6halogenalkoxy, C3- C6cycloalkyl, Ci-C6alkylthio or C,-C6halogenalkylthio; may be prepared by reaction scheme 2.
Scheme 2:
Figure imgf000018_0001
H R NH,
Figure imgf000018_0002
(XII) (UC)
According to scheme 2, reaction of compounds of formula XVI, wherein R1, R3, R4 and B are as defined under formula HC, with alkyldiazoacetate derivatives of formula XV, wherein R2 is as defined under formula MC and R' is d-C6alkyl, and Vitamin B12a as catalyst (Y. Chen and X. P. Zhang, J. Org. Chem. 2004, 69, 2431 -2435), gives a diastereomeric mixture of cyclop ropylcarboxylates of formula XIV, wherein R1, R2, R3, R4 and B are as defined under formula MC. The diastereomers can be separated either chromatographically or, after saponification, by recrystallisation of the corresponding carboxylic acids of formula XIII, wherein R1, R2, R3, R4 and B are as defined under formula HC Curtius degradation to the BOC-protected amines of formula XII, wherein R1, R2, R3, R4 and B are as defined under formula HC, and deprotection with hydrogen chloride produces the compounds of formula MC in the form of hydrochlorides (see PCT/US2004/021505 and G. Haufe et al, J. Med. Chem. 2004, 47, 5860-5871 ). The cis and trans isomers of (XIV) or (XII) may be separated by chromatography.
The reactions are carried out at temperatures of between 0 - 100°C in a convenient organic solvent such as methanol, ethanol, tert-butanol, trifluoroethanol, chloroform, dichloromethane or dioxane.
Other catalysts such as copper acetate can be used as an alternative to Vitamin B12a for the cyclopropanation reaction.
The Curtius rearrangement of the carboxylic acids of formula XIII to the BOC-protected amines of formula XII can be carried out using diphenylphosphoryl azide with a convenient base such as triethylamine followed by treatment with di-tert-butyl carbonate (D. Kim and S.
M. Weinreb, J. Org. Chem. 1978, 43, 125-131). The BOC protecting group can be removed by sequential acid and base treatment.
Compounds of the formulae VIII, X, Xl or XVI, all wherein B is a phenyl group, which is substituted by one or more substituents R9, are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.
Compounds of the formula III are known and partially commercially available. They can be prepared analogously as described, for example, in WO 00/09482 , WO 02/38542, WO 04/018438, EP-0-589-301 , WO 93/11117 and Arch. Pharm. Res. 2000, 23(4), 315-323.
The compounds of formula VII, V, and XV are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.
Compounds of the formula XVII
Figure imgf000019_0001
(XVU), wherein R9 is as defined under formula I; n is 1 , 2, 3, 4, 5, 6 or 7, preferably 1 or 2; R1 is hydrogen, cyano, CrC6alkyl, which is unsubstituted or substituted by one or more substituents Ra, or C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra, wherein each Ra independently of each other stand for halogen, cyano, nitro, d-C6alkoxy, Ci-C6halogenalkoxy, C3-C6cycloalkyl, d-C6alkylthio or C1- C6halogenalkylthio; and R3 and R4 independently of each other stand for hydrogen, cyano, nitro, d-Cβalkyl, which is unsubstituted or substituted by one or more substituents Ra, or C3- C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra; wherein each Ra independently of each other stand for halogen, cyano, nitro, d-C6alkoxy, C1- C6halogenalkoxy, C3-C6cycloalkyl, d-C6alkylthio or d-C6halogenalkylthio; can be prepared according to reaction scheme 3 or in analogy to reaction scheme 3. Said compounds of formula XVII correspond to compounds of formula X or XVI, wherein B is a naphthyl group, which is substituted by one or more substituents R9, with the exception of compounds according to formula XVI, wherein R1 is halogen.
Scheme 3:
Figure imgf000020_0001
(XVII)
(XIX) (XVIII)
According to scheme 3, compounds of the formula XVII, wherein R9, n, R1, R3 and R4 are as defined above, can be prepared from compounds of formula XVIII, wherein R9, n, R1, R3 and R4 are as defined under formula XVII, or from compounds of formula XIX, wherein R9, n, R1, R3 and R4 are as defined under formula XVII, by alcohol-dehydration over KHSO4 according to Charles C. Price et al. J Org Chem (1949), 14 111-117.
Compounds of the formula XX
Figure imgf000020_0002
(XX), wherein Hal is F or Cl; can be prepared according to scheme 4. Compounds of formula XX form a sub-group of compounds of formula X or XVI.
Scheme 4:
Figure imgf000021_0001
Monohalogen-vinylnaphtalenes of formula XX, wherein Hal is F or Cl, can be prepared by a palladium-catalyzed vinylation of the naphthyl bromides of formula XXI, wherein Hal is F or Cl, using TBAF as activator and an inexpensive and non-toxic vinyl donor, such as 1 ,3,5,7- tetramethyl-1.S.δ.T-tetravinylcyclotetrasiloxane, as published by Scott E. Denmark Organic Letters 2006 Vol.8,No.1 63-66.
Furthermore, the synthesis of 6-chloro-2-vinylnaphthalene is known, see J. Am. Chem. Soc.,(1948), 70, 4265-4266.
Compounds of the formulae XIX, XVIII and XXI are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.
Compounds of the formula XXII or XXIII
Figure imgf000021_0002
(XXII) (xxiπ) wherein R9 is as defined under formula I; n is 1 , 2, 3, 4, 5 or 6, preferably 1 or 2; and R1, R3 and R4 are as defined under formula XVI, can be prepared according to reaction scheme 5 or in analogy to reaction scheme 5. Said compounds of formula XXII and XXIII correspond to compounds of formula X or XVI, wherein B is a quinolinyl group, which is substituted by one or more substituents R9.
Scheme 5:
Figure imgf000022_0001
Figure imgf000022_0002
(xxm)
According to scheme 5, compounds of the formula XXII and XXIII, wherein R9, n, R1, R3 and R4 are as defined above, can be prepared from compounds of formula XXIV and XXV, respectively via a Wittig-reaction with compounds of formula XXVI, wherein R2 is as defined under formula I.
Compounds of the formulae XXIV and XXV are known and are commercially available or can be prepared from known precursors according to methods known in the art. Especially, some monochloro-substituted 4-quinolinecarboxaldehydes and monochlorosubstituted 3- quinolinecarboxaldehydes are commercially available or known, for example, compounds XXIVa to XXIVj are registered under the following CAS-registry numbers.
XXlVa XXIVb
Figure imgf000022_0004
Figure imgf000022_0003
CAS 855613-24-0 CAS 491615-11-3 CAS 35839-88-4 CAS 35714-48-8 CAS482583-75-5
Figure imgf000022_0005
363135-55-1
Compounds according to formula ID
Figure imgf000023_0001
wherein A and B are as defined in R5 is C1-4 alkyl, CH2CH=CHR5a, CH2C≡ CR5b or COR5c; R5a and R5b are each, independently, hydrogen, d-C6alkyl, d-C6halogenalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, COOd-C4alkyl, COOC3-C6alkenyl, COOC3-C6alkynyl or CN ; R5c is hydrogen, Ci-C6alkyl, CrC6halogenalkyl, d-Cealkoxy-d-Cealkyl, d-C6halogenalkoxy- d-C6alkyl, d-C6alkylthio, d-C6halogenalkylthio, d-C6alkoxy, d-C6halogenalkoxy, C3- C6a!kenyloxy, C3.C6halogenalkenyloxy, C3-C6alkynyloxy or C3-C6halogenalkynyloxy; may be prepared according to reaction scheme 6.
Scheme 6: / / etc.)
1)
Figure imgf000023_0002
Figure imgf000023_0004
Figure imgf000023_0003
(H) (\ wherein X is O (X is a leaving group, (I, wnerein λ is U preferably halogen) (I, wherein X is O) and R5 is H) or
2)
Figure imgf000023_0005
(I. wherein X is O)
Figure imgf000023_0006
In compounds of formula XXVI B, R1, R2, R3, R4 and R5 are as defined under formula HD.
Compounds of formula I, wherein X is sulfur, can be prepared from compounds of formula I, wherein X is oxygen, for example by reaction with P2S5 in an inert solvent, such as benzene, toluene, tetrahydrofurane, dioxane or mixtures thereof. The compounds of the formula III are known and partially commercially available. They can be prepared analogously as described, for example, in WO 00/09482 , WO 02/38542, WO 04/018438, EP-0-589-301 , WO 93/11 117 and Arch. Pharm. Res. 2000, 23(4), 315-323.
The compounds of formula VII, V, Xl and XII are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.
For preparing all further compounds of the formula I functionalized according to the definitions of A, B, X, R1, R2, R3, R4 and R5, there are a large number of suitable known standard methods, such as alkylation, halogenation, acylation, amidation, oximation, oxidation and reduction. The choice of the preparation methods which are suitable are depending on the properties (reactivity) of the substituents in the intermediates.
The reactions to give compounds of the formula I are advantageously carried out in aprotic inert organic solvents. Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone. The reaction temperatures are advantageously between -200C and +1200C. In general, the reactions are slightly exothermic and, as a rule, they can be carried out at room temperature. To shorten the reaction time, or else to start the reaction, the mixture may be heated briefly to the boiling point of the reaction mixture. The reaction times can also be shortened by adding a few drops of base as reaction catalyst. Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1 ,4-diazabicyclo[2.2.2]octane, 1 ,5-diazabicyclo[4.3.0]non-5-ene or 1 ,5-diazabicyclo- [5.4.0]undec-7-ene. However, inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, or hydrogen carbonates such as potassium hydrogen carbonate and sodium hydrogen carbonate may also be used as bases. The bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt. The compounds of formula I can be isolated in the customary manner by concentrating and/or by evaporating the solvent and purified by recrystallization or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons.
The compounds I and, where appropriate, the tautomers thereof, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.
Diastereomer mixtures or racemate mixtures of compounds I, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high- performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is com- plexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents. Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereose- lective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.
It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity.
The compounds I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
It has now been found that the compounds of formula I according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisams, such as fungi, bacteria or viruses.
The invention relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as acitve ingredient to the plants, to parts thereof or the locus thereof. The compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants. The compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. Furthermore the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara). Outstanding activity has been observed against powdery mildew (Erysiphe spp.). Furthermore, the novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). Good activity has been observed against Asian soybean rust (Phakopsora pachyrhizi).
Within the scope of the invention, useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.
The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-O 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-O 392 225, WO 95/33818, and EP-A-O 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
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 the 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. The compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
To this end compounds of formula I and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
The compounds of formula I or compositions, comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation. A preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
The agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 2Og to 60Og a.i./ha. When used as seed drenching agent, convenient rates of application are from 10mg to 1 g of active substance per kg of seeds. The rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
Surprisingly, it has now been found that the compounds of formula I can also be used in methods of protecting crops of useful plants against attack by phytopathogenic organisms as well as the treatment of crops of useful plants infested by phytopathogenic organisms comprising administering a combination of glyphosate and at least one compound of formula I to the plant or locus thereof, wherein the plant is resistant or sensitive to glyphosate.
Said methods may provide unexpectedly improved control of diseases compared to using the compounds of formula I in the absence of glyphosate. Said methods may be effective at enhancing the control of disease by compounds of formula I. While the mixture of glyphosate and at least one compound of formula I may increase the disease spectrum controlled, at least in part, by the compound of formula I, an increase in the activity of the compound of formula I on disease species already known to be controlled to some degree by the compound of formula I can also be the effect observed.
Said methods are particularly effective against the phytopathogenic organisms of the kingdom Fungi, phylum Basidiomycot, class Uredinomycetes, subclass Urediniomycetidae and the order Uredinales (commonly referred to as rusts). Species of rusts having a particularly large impact on agriculture include those of the family Phakopsoraceae, particularly those of the genus Phakopsora, for example Phakopsora pachyrhizi, which is also referred to as Asian soybean rust, and those of the family Pucciniaceae, particularly those of the genus Pυccinia such as Puccinia graminis, also known as stem rust or black rust, which is a problem disease in cereal crops and Pυccinia recondita, also known as brown rust.
An embodiment of said method is a method of protecting crops of useful plants against attack by a phytopathogenic organism and/or the treatment of crops of useful plants infested by a phytopathogenic organism, said method comprising simultaneously applying glyphosate, including salts or esters thereof, and at least one compound of formula I, which has activity against the phytopathogenic organism to at least one member selected from the group consisting of the plant, a part of the plant and the locus of the plant.
Surprisingly, it has now been found that the compounds of formula I, or a pharmaceutical salt thereof, described above have also an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal. "Animal" can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human. "Treatment" means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection. "Prevention" means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
According to the present invention there is provided the use of a compound of formula I in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal. There is also provided the use of a compound of formula I as a pharmaceutical agent. There is also provided the use of a compound of formula I as an antimicrobial agent in the treatment of an animal. According to the present invention there is also provided a pharmaceutical composition comprising as an active ingredient a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal. This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs. Alternatively this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion. Alternatively this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection. Alternatively this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
The compounds of formula I are effective against various microbial species able to cause a microbial infection in an animal. Examples of such microbial species are those causing Aspergillosis such as Aspergillus fυmigatus, A. flavus, A. terms, A. nidulans and A. niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causing Coccidioidomycosis such as Coccidioides immitis; those causing Cryptococcosis such as Cryptococcus neoformans; those causing Histoplasmosis such as Histoplasma capsulatum and those causing Zygomycosis such as Absidia corymbifera, Rhizomucor pusillus and Rhizopυs arrhizus. Further examples are Fusarium Spp such as Fusariυm oxysporum and Fusarium solani and Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolificans. Still further examples are Microsporum Spp, Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and Histoplasma Spp.
The following non-limiting Examples illustrate the above-described invention in greater detail without limiting it.
Preparation examples:
Example PI : Preparation of S-difluoromethyl-i-methyl-I H-pyrazole^-carboxylic acid f2-(4-chlorophenvO-cyclopropyn-amide (compound no. 1.001):
Figure imgf000033_0001
The crude amine Z1.001 from Example P4 was suspended in dichloromethane (10ml) and triethylamine (250mg, 2.5mmol). To this suspension was added at 00C a solution of 3- difluoromethyl-1-methyl-1 H-pyrazole-4-carbonyl chloride (194mg, I .Ommol) in dichloromethane (2ml) and stirred for one hour. After removal of the solvent the residue was purified by flash chromatography over silica gel (eluant: hexane/ethyl acetate 1 :9). Yield: 92mg (28.2% of theory) of the cis-isomer of 3-difluoromethyl-1 -methyl-1 H-pyrazole-4- carboxylic acid [2-(4-chlorophenyl)-cyclopropyl]-amide (compound no. 1.001 ) in form of a solid m.p.127°C.
1H NMR (400MHz, CDCI3): 51.06-1.17(m,1 H,CHH),1.44(q,1 H,CHH),2.32- 2.38(q,1 H,CHAr),3.23-3.29(m,1 H,CHN),3.73(s,3H,NCH3),6.08(s,1 H,NH),6.48- 6.75(t,1 H,CHF2),7.14-7.17(d,2H,Ar-H), 7.20-7.23(d,2H,Ar-H),7.70(s,1 H,Pyrazol-H). MS [M+H]+ 326/328.
Example P2: Preparation of S-difluoromethyl-i-methyl-I H-pyrazole^-carboxylic acid (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-amide (compound no. 1.004):
Figure imgf000033_0002
A solution of S-difluoromethyl-i -methyl-I H-pyrazole^-carbonyl chloride (0.105g; 0.54mmol) in dichloromethane (2ml) was added dropwise to a stirred solution of the amine from example P5 (compound Z1.004; 2-(4-chlorophenyl)-2-fluoro-cycIopropylamine; 0.100g; 0.54mmol) and triethylamine (0.15ml; 1.08mmol) in dichloromethane (3ml). The reaction mixture was stirred for 1 hr at ambient temperature then allowed to stand for 18h. The reaction mixture was washed with 2M HCI (5ml) and with saturated NaHCO3 (5ml) and then dried over MgSO4. Evaporation of the solvent yielded 0.15g 3-difluoromethyl-1-methyl-1 H- pyrazole-4-carboxylic acid (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-amide in the form of a yellow solid (81 % of theory) as a 7:3 mixture of cis/trans isomers.
1HNMR (400MHz, CDCI3): Cis isomer : 1.506 (m ; 1 H) : 1.926 (ddd ;1 H) : 3.626 (m ; 1 H) : 3.856 (s ; 3H) : 6.056 (br-s ; 1 H) : 6.606 (t ; 1 H) : 7.306-7.406 (m ; 4H) : 7.806 (s ; 1 H). Trans isomer : 1.576 (m ; 1 H) : 1.676 (ddd ; 1 H) : 3.326 (m ; 1 H) : 6.706 (br-s ; 1 H) : 6.856 (t ; 1 H) : 7.306-7.406 (m ; 4H) : 7.956 (s ; 1 H).
Example P3: Preparation of N-rd R^SV∑-rø-chlorophenvD-Σ-fluoro-cyclopropyπ^- trifluoromethyl-benzamide (compound no. 6.004):
Figure imgf000034_0001
A solution of 2-trifluoromethylbenzoyl chloride (0.10g; 0.54mmol) in dichloromethane (2ml) added dropwise to a stirred solution of the amine from example P5 (compound Z1.004; 2-(4- chlorophenyl)-2-fluoro-cyclopropylamine; 0.100g; 0.54mmol) and triethylamine (0.15ml;
1.08m) in dichloromethane (3ml). Stirred for 1 hr at room temperature then allowed to stand for 18hr. The white precipitate was filtered off, washed with 2M HCI, saturated NaHCO3 and water and air dried giving the pure cis isomer. 0.065g (34%).
1HNMR (400MHz1 CDCI3) : 1.606 (m ; 1 H) : 1.976 (ddd ; 1 H) : 3.676 (m ; 1 H) : 5.406 (br-s ;
1 H) : 7.106-7.656 (m ; 8H). MH+ 358. MP 204-206°.
The dichloromethane soluble material consisted of a 1 :1 mixture of cis/trans isomers.
Example P4: Preparation of (1 R,2R)-2-(4-chloro-phenyl)-cvclopropylamine (compound no. Z1.001):
Figure imgf000034_0002
To a stirred suspension of p-toluenesulfonyl hydrazide (5.Og, 26.8mmol) in methanol (20ml) 4-chloro-benzaldehyde (3.3g, 23.3mol) was added dropwise. After O.h hour the mixture was cooled to 00C and the product removed by filtration, washed with cold methanol (10ml) and then crystallized from hot methanol to give 5.5g (76.5% of theory) 4-chlorobenzaldehyde tosyl hydrazone in the form of a white solid.
1H NMR (400MHz, DMSO): δ 11.5(sbroad,1 H), 7.91 (S,1 H), 7.77(d,2H), 7.57(d,2H), 7.44(d,2H), 7.49(d,2H), 2.35(s,3H).
b) Preparation of 4-chlorobenzaldehyde tosyl hvdrazone sodium salt
Figure imgf000035_0001
A 1 M sodium methoxyde solution was prepared by adding sodium (423mg, 18.39mmol) to anhydrous methanol (19ml) with external cooling. Once all of the metal was dissolved, 4- chlorobenzaldehyde tosyl hydrazone (5.39g, 17.51 mmol) was added and the mixture was stirred until the solid was dissolved. After stirring for a further 15 min at room temperature the methanol was removed under reduced pressure at room temperature. 5.73g of 4- chlorobenzaldehyde tosyl hydrazone sodium salt was obtained in the form of a white powder (99% of theory).
c) Preparation of 2-f(1 R.2R)-2-(4-chloro-phenyl)-cvclopropyπ-isoindole-1.3-dione
Figure imgf000035_0002
A mixture of 4-chlorobenzaldehyde tosyl hydrazone sodium salt (1.67g, 5.05mmol), benzyltriethylammoniumchloride (1 15mg, O.δmmol), rhodium acetate (20mg, 0.05mmol) and N-vinylphtalimide (4.32g, 25.0mmol) in dry 1 ,4-dioxane (13ml) was stirred for one day under nitrogen at room temperature. Water (35ml) was added to the mixture and the aqueous phase was extracted three times with dichloromethane. The combined organic layers were dried over Na2SO4. Evaporation gave the crude material, which was purified by flash chromatography over silicagel (eluent: hexane/ethylacetate 1 :1 ). To afford 392mg (26.3% of theory) of 2-[2-(4-chloro-phenyl)-cyclopropyl]-isoindole-1 ,3-dione in the form of a solid. 1H NMR (400MHz1 CDCI3): δ 7.73-7.62(m,4H), 7.04-7.01 (m,4H), 3.08(td,1 H,CHN), 2.50(q,1 H1CHPh), 2.19(ddd,1 H,CHH), 1.63(q,1 H1CHH). MS [M+H]+ 298/300.
d) Preparation of (1 R.2R)-2-(4-chloro-phenvl)-cvclopropvlamine (compound no. Z1.001 ):
Figure imgf000036_0001
A mixture of 2-[2-(4-chloro-phenyl)-cyclopropyl]-isoindole-1 ,3-dione (320mg, 1.07mmol) and hydrazine hydrate (0.5ml) in ethanol (8ml) was stirred for 0.5 hour at 500C. The solution was evaporated under reduced pressure. The resulting amine (compound Z1.001 ) was used in example P1 without further purification.
Example P5: Preparation of 2-(4-chlorophenyl)-2-fluoro-cvclopropylamine (compound no. Z1.004): a) Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropane carboxylic acid ethyl ester
Figure imgf000036_0002
Vitamin B12a (LOOg ; 0.723mmol) was dissolved in dry trifluoroethanol (70ml) and 1 -chloro- 4-(1-fluoro-vinyl)-benzene (6.5Og ; 41.5mmol) and ethyl diazoacetate (6.3Og; 50mmol; 90% purity) was added. The solution was stirred, under reflux, under nitrogen atmosphere for 18h. After cooling the solvent was evaporated and the residue purified by flash chromatography using 9:1 hexane/ethyl acetate. 6.9g of 2-(4-chlorophenyl)-2-fluoro- cyclopropane carboxylic acid ethyl ester was obtained in the form of an oil (81% of theory) as a 7:3 mixture of cis/trans isomers.
1H NMR (400MHz, CDCI3): cis isomer : 1.055 (t ; 3H) : 1.825 (ddd ; 1 H) : 1.955 (ddd ; 1 H) : 2.575 (ddd ; 1 H) : 3.955 (m ; 2H) : 7.205-7.425 (m ; 4H). Trans isomer : 1.305 (t ; 3H) : 1.605 (ddd ; 1 H) : 2.175 (ddd ; 1 H) : 2.305 (ddd ; 1 H) : 4.255 (m ; 2H) : 7.205-7.425 (m ; 4H).
b) Preparation of 2-(4-chlorophenyl)-2-fluoro-cvclopropanecarboxylic acid
Figure imgf000036_0003
The ester from example P5a) (6.9Og; 28mmol) was added dropwise to a stirred solution of KOH in methanol (0.956M; 300ml; 0.28m) with ice/water cooling. The solution was then stirred at room temperature for 18h and concentrated under reduced pressure at room temperature. The residue was mixed with cold water and extracted with dichloromethane. The aqueous portion was acidified with concentrated HCI with ice cooling and extracted twice with dichloromethane. The extracts were dried (MgSO4) and evaporated. 5.1Og of 2-(4- chlorophenyl)-2-fluoro-cyclopropanecarboxylic acid was obtained in the form of a yellow solid (85% of theory) as a 7:3 mixture of cis/trans isomers.
1HNMR (400MHz, CDCI3): cis isomer : 1.85δ-2.00δ (m ; 2H) : 2.55δ (ddd ; 1 H) ; 7.20δ-7.40δ (m ; 4H). Trans isomer: 1.67δ (ddd ; 1 H) : 2.12δ (ddd ; 1 H) : 2.30δ (ddd ; 1 H) : 7.20δ-7.40δ (m ; 4H).
c) Preparation of (2-(4-chlorophenyl)-2-fluoro-cvclopropyl)-carbamic acid tert-butyl ester
Figure imgf000037_0001
The carboxylic acid from example P5b) (5.09g; 23.7mmol) was dissolved in a mixture of cyclohexane (150ml) and tert-butanol (17.7Og; 0.237m). Triethylamine (2.86g; 0.0284m) and diphenylphosphoryl azide (7.3Og; 0.0262m) were added and the solution stirred under reflux under nitrogen for 18h. After cooling, di-tert-butyl carbonate (7.86g ; 0.0359m) was added and the mixture stirred under reflux for 2h. After cooling the mixture was diluted with ethyl acetate (200ml) and washed with 5% citric acid solution (50ml) followed by saturated NaHCO3 solution. The extract was dried (MgSO4) and evaporated. The oily residue was triturated with pentane (50ml) and the white solid filtered off and recrystallized from hexane. 4.3g of (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-carbamic acid tert-butyl ester was obtained in the from of a white solid (63% of theory) as a 7:3 mixture of cis/trans isomers. 1HNMR (400MHz, CDCI3): cis isomer : 1.32δ (s ; 9H) : 1.42δ (m ; 1 H) : 1.80δ (ddd ; 1 H) : 3.30δ (m ; 1 H) : 4.25δ (br-s ; 1 H) : 7.30δ-7.40δ (m ; 4H). Trans isomer : 1.40δ (m ;1 H) : 1.50δ (s ; 9H) : 2.97δ (m ; 1 H) : 4.95δ (br-s ; 1 H) : 7.30δ-7.40δ (m ; 4H).
d) Preparation of 2-(4-chlorophenyl)-2-f luoro-cvclopropylamine (compound no. Z1.004)
Figure imgf000037_0002
(2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-carbamic acid tert-butyl ester from example P5c) (LOOg; 3.5mmol) was dissolved in methanol (10ml) and a saturated solution of HCI in ethanol (10ml) added. The solution was stirred at room temperature for 2h then evaporated leaving a white solid. Water (50ml) then added and mixture extracted twice with ethyl acetate. The aqueous phase was made alkaline with 2M NaOH and extracted twice with ethyl acetate. The extracts were dried (MgSO4) and evaporated. 0.6Og of 2-(4-chlorophenyl)- 2-fluoro-cyclopropylamine was obtained in the form of a yellow oil (92% of theory) as a 7:3 mixture of cis/trans isomers. 1HNMR (400MHz, CDCI3): cis isomer : 1.15δ (ddd ; 1 H) : 1.60δ (ddd ; 1 H) : 3.10δ (ddd ;1H) : 7.30δ-7.45δ (m ; 4H). Trans isomer : 1.27δ (ddd ; 1 H) : 1.40δ (m ; 1 H) : 2.57δ (ddd ; 1 H) : 7.10δ-7.30δ (m ; 4H).
Tables 1 to 8: Compounds of formula IA
The invention is further illustrated by the prefered individual compounds of formula (IA) listed below in Tables 1 to 8. Characterising data is given in Table 18.
Figure imgf000038_0001
Each of Tables 1 to 8, which follow the Table Y below, comprises 274 compounds of the formula (IA) in which R1, R2, R3, R4, R9a, R9b and R9c have the values given in Table Y and A has the value given in the relevant Table 1 to 8. Thus Table 1 corresponds to Table Y when Y is 1 and A has the value given under the Table 1 heading, Table 2 corresponds to Table Y when Y is 2 and A has the value given under the Table 2 heading, and so on for Tables 3 to 8. Table Y:
Figure imgf000038_0002
Figure imgf000039_0001
Figure imgf000040_0001
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Figure imgf000049_0001
Table 1 provides 274 compounds of formula (IA), wherein A is
Figure imgf000050_0001
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, R9a> Rθb and R9c are as defined in Table Y. For example, compound 1.001 has the following structure:
Figure imgf000050_0002
Table 2 provides 274 compounds of formula (IA) wherein A is
Figure imgf000050_0003
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1 , R2, R3, R4, Rga, Rθb and R9c are as defined in Table Y.
Table 3 provides 274 compounds of formula (IA) wherein A is
Figure imgf000050_0004
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, Rga, R9b and R9c are as defined in Table Y.
Table 4 provides 274 compounds of formula (IA) wherein A is
Figure imgf000050_0005
wherein the broken lines indicate the point of attachment of the group A to the amide group, and Ri, R2, R3, R4, R9a, R9b and R9c are as defined in Table Y.
Table 5 provides 274 compounds of formula (IA) wherein A is
CF2H ,
N. ,N N
CH3
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, R9a, Rgb and R9c are as defined in Table Y.
Table 6 provides 274 compounds of formula (IA) wherein A is
Figure imgf000051_0001
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, R9a, R9b and R90 are as defined in Table Y.
Table 7 provides 274 compounds of formula (IA) wherein A is
Figure imgf000051_0002
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, R9a, R9b and R90 are as defined in Table Y.
Table 8 provides 274 compounds of formula (IA) wherein A is
Figure imgf000051_0003
wherein the broken lines indicate the point of attachment of the group A to the amide group, and R1, R2, R3, R4, R9a, R9b and R9c are as defined in Table Y. Tables 9 to 16: Compounds of formula IB
The invention is further illustrated by the prefered individual compounds of formula (IB) listed below in Tables 9 to 16. Characterising data is given in Table 18.
Figure imgf000052_0001
Each of Tables 9 to 16, which follow the Table W below, comprises 872 compounds of the formula (IB) in which B, R1, R2, R3 and R4 have the values given in Table W and A has the value given in the relevant Table 9 to 16. Thus Table 9 corresponds to Table W when W is 9 and A has the value given under the Table 9 heading, Table 10 corresponds to Table W when W is 10 and A has the value given under the Table 10 heading, and so on for Tables 1 1 to 16. Table W: In Table W the group B stands for the group B1, B2, B3 or B4:
Figure imgf000052_0002
Figure imgf000052_0003
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Table 9 provides 872 compounds of formula (IB), wherein A is
Figure imgf000089_0001
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W. For example, compound 9.001 has the following structure:
Figure imgf000089_0002
Table 10 provides 872 compounds of formula (IB) wherein A is
Figure imgf000089_0003
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 11 provides 872 compounds of formula (IB) wherein A is
Figure imgf000089_0004
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 12 provides 872 compounds of formula (IB) wherein A is
Figure imgf000090_0001
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 13 provides 872 compounds of formula (IB) wherein A is
Figure imgf000090_0002
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 14 provides 872 compounds of formula (IB) wherein A is
Figure imgf000090_0003
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 15 provides 872 compounds of formula (IB) wherein A is
Figure imgf000090_0004
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 16 provides 872 compounds of formula (IB) wherein A is
Figure imgf000090_0005
wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R1, R2, R3, R4, R9a and R9b are as defined in Table W.
Table 17: Compounds of formula HA
Illustrative of the compounds of formula (MA) are the compounds listed in Table 17 below. Characterising data for these compounds are given in Table 18.
Figure imgf000091_0001
Figure imgf000091_0002
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Table 18: Characterising data
Table 18 shows selected melting point and selected NMR data for compounds of Tables 1 to 17. CDCI3 was used as the solvent for NMR measurements, unless otherwise stated. If a mixture of solvents was present, this is indicated as, for example: CDCI3Zd6- DMSO). No attempt is made to list all characterising data in all cases.
In Table 18 and throughout the description that follows, temperatures are given in degrees Celsius; "NMR" means nuclear magnetic resonance spectrum; MS stands for mass spectrum; "%" is percent by weight, unless corresponding concentrations are indicated in other units. The following abbreviations are used throughout this description:
m.p. = melting point b.p.= boiling point.
S = singlet br = broad d = doublet dd = doublet of doublets t = triplet q = quartet m = multiplet ppm = parts per million
Figure imgf000103_0001
Figure imgf000104_0001
FORMULATION EXAMPLES FOR COMPOUNDS OF FORMULA I: Example F-1.1 to F-1.2: Emulsifiable concentrates
Components F-1.1 F-1.2
compound of Tables 1 to 16 25% 50% calcium dodecylbenzenesulfonate 5% 6% castor oil polyethylene glycol ether (36 mol ethylenoxy units) 5% tributylphenolpolyethylene glycol ether (30 mol ethylenoxy units) 4% cyclohexanone 20% xylene mixture 65% 20%
Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
Example F-2: Emulsifiable concentrate
Components F-2
compound of Tables 1 to 16 10% octylphenolpolyethylene glycol ether
(4 to 5 mol ethylenoxy units) 3% calcium dodecylbenzenesulfonate 3% castor oil polyglycol ether
(36 mol ethylenoxy units) 4% cyclohexanone 30% xylene mixture 50%
Emulsions of any desired concentration can be prepared. by diluting such concentrates with water.
Examples F-3.1 to F-3.4: Solutions
Components F-3.1 F-3.2 F-3.3 F-3.4
compound of Tables 1 to 16 80% 10% 5% 95% propylene glycol monomethyl ether 20% - - polyethylene glycol (relative molecular mass: 400 atomic mass units) - 70% -
N-methylpyrrolid-2-one 20% - epoxidised coconut oil - 1% 5% benzin (boiling range: 160-190°) 94°/
The solutions are suitable for use in the form of microdrops.
Examples F-4.1 to F-4.4: Granulates
Components F-4.1 F-4.2 F-4.3 F-4.4
compound of Tables 1 to 16 5% 10% 8% 21 % kaolin 94% - 79% 54% highly dispersed silicic acid 1 % - 13% 7% attapulgite 90% - 18% The novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.
Examples F-5.1 and F-5.2: Dusts
Components F-5.1 F-5.2
compound of Tables 1 to 16 2% 5% highly dispersed silicic acid 1 % 5% talcum 97% kaolin - 90%
Ready for use dusts are obtained by intimately mixing all components.
Examples F-6.1 to F-6.3: Wettable powders
Components F-6.1 F-6.2 F-6.3
compound of Tables 1 to 16 25% 50% 75% sodium lignin sulfonate 5% 5% sodium lauryl sulfate 3% - 5% sodium diisobutylnaphthalene sulfonate - 6% 10% octylphenolpolyethylene glycol ether
(7 to 8 mol ethylenoxy units) - 2% highly dispersed silicic acid 5% 10% 10% kaolin 62% 27%
All components are mixed and the mixture is thoroughly ground in a suitable mill to give wettable powders which can be diluted with water to suspensions of any desired concentration.
Example F7: Flowable concentrate for seed treatment compound of Tables 1 to 16 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % tristyrenephenole with 10-20 moles EO 2 %
1 ,2-benzisothiazolin-3-one (in the form of a 20% solution in O .5 % water) monoazo-pigment calcium salt 5 %
Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
Water 45. 3 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
BIOLOGICAL EXAMPLES: FUNGICIDAL ACTIONS
Example B-1 : Action against Podosphaera leucotricha I apple (Powdery mildew on apple) 5 week old apple seedlings cv. Mclntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by shaking plants infected with apple powdery mildew above the test plants. After an incubation period of 12 days at 220C and 60%r.h. under a light regime of 14/10hours (light/dark) the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (< 20% infestation).
Example B-2: Action against Venturia inaepualis I apple (Scab on apple) 4 week old apple seedlings cv. Mclntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by spraying a spore suspension (4x105conidia/ml) on the test plants. After an incubation period of 4 days at 210C and 95%r.h. the plants are placed for 4 days at 210C and 60%r.h. in a greenhouse. After another 4 day incubation period at 210C and 95%r.h. the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).
Example B-3: Action against Ervsiphe graminis / barley (Powdery mildew on barley) 1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application barley plants are inoculated by shaking powdery mildew infected plants above the test plants. After an incubation period of 6 days at 200C / 180C (day/night) and 60%r. h. in a greenhouse the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079,1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).
Example B-4: Action against Botrytis cinerea I apple (Botrvtis on apple fruits) In an apple fruit cv. Golden Delicious 3 holes are drilled and each filled with 30μl droplets of the formulated test compound (0.02% active ingredient). Two hours after application 50 μl of a spore suspension of B. cinerea (4x105conidia/ml) are pipetted on the application sites. After an incubation period of 7 days at 220C in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test (<20% infestation).
Example B-5: Action against Botrvtis cinerea I grape (Botrvtis on grapes) 5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application grape plants are inoculated by spraying a spore suspension (1x106conidia/ml) on the test plants. After an incubation period of 4 days at 210C and 95%r.h. in a greenhouse the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test (<20% infestation).
Example B-6: Action against Botrvtis cinerea I tomato (Botrvtis on tomatoes) 4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application tomato plants are inoculated by spraying a spore suspension (1x105conidia/ml) on the test plants. After an incubation period of 4 days at 2O0C and 95%r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).
Example B-7: Action against Pyrenophora teres I barley (Net blotch on barley)
1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application barley plants are inoculated by spraying a spore suspension (3x104conidia/ml) on the test plants. After an incubation period of 2 days at 2O0C and 95%r.h. plants are kept for 2 days at 2O0C and 60%r.h. in a greenhouse. The disease incidence is assessed 4 days after inoculation. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).
Example B-8: Action against Septoria fr/f/'c/ /wheat (Septoria leaf spot on wheat)
2 week old wheat plants cv. Riband are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application, wheat plants are inoculated by spraying a spore suspension (10x105conidia/ml) on the test plants. After an incubation period of 1 day at 23°C and 95% r.h., the plants are kept for 16 days at 23°C and 60% r.h. in a greenhouse. The disease incidence is assessed 18 days after inoculation.
Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and
6.222show good activity in this test (<20% infestation).
Example B-9: Action against Uncinula necator/ grape (powdery mildew on grape) 5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application, the grape plants are inoculated by shaking plants infected with grape powdery mildew above the test plants. After an incubation period of 7 days at 26°C and 60%r.h. under a light regime of 14/10hours (light/dark) the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222show good activity in this test (< 20% infestation).
Example B-10: Action against Alternaria solani/ tomato (early blight on tomatoes) 4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application, the tomato plants are inoculated by spraying a spore suspension (2x105conidia/ml) on the test plants. After an incubation period of 3 days at 200C and 95%r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001 , 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Claims

WHAT IS CLAIMED IS:
1. A compound of the formula I
Figure imgf000110_0001
wherein
X is oxygen or sulfur;
A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R6, R7 and R8;
R6, R7 and R8 are each, independently, hydrogen, halogen, cyano, nitro, C1-4alkyl, d^halogenalkyl, C^ halogenalkoxy, C1-4alkoxy(C1.4)alkyl or C1^ halogenalkoxy(C1.4)alkyl, provided that at least one of R6, R7 and R8 is not hydrogen;
Ri, R2, R3 and R4 independently of each other stand for halogen, cyano, nitro, d-C6alkyl, which is unsubstituted or substituted by one or more substituents Ra, C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Ra, C2-C6alkenyl, which is unsubstituted or substituted by one or more substituents Ra or C2-C6alkynyl, which is unsubstituted or substituted by one or more substituents Ra; each Ra independently of each other stand for halogen, cyano, nitro, CrC6alkoxy, C1-
C6halogenalkoxy, C3-C6cycloalkyl, Ci-C6alkylthio, CrC6halogenalkylthio or -C(Rb)=N(ORc);
Rb is hydrogen or d-C6alkyl;
Rc is d-Cβalkyl; n is O, 1 , 2, 3 or 4;
R5 is hydrogen, d-4 alkyl, CH2CH=CHR53, CH2C= CR5b or COR5C;
R53 and R5b are each, independently, hydrogen, d-Cealkyl, d-C6halogenalkyl, C2-C6alkenyl,
C2-C6alkynyl, C3-C7cycloalkyl, COOCi-C4alkyl, COOC3-C6alkenyl, COOC3-C6alkynyl or CN ;
R5c is hydrogen, d-C6alkyl, d-C6halogenalkyl, d-Cealkoxy-d-Cealkyl, d-C6halogenalkoxy- d-C6alkyl, d.C6alkylthio, d-C6halogenalkylthio, d-C6alkoxy, d-C6halogenalkoxy, C3-
C6alkenyloxy, C3.C6halogenalkenyloxy, C3-C6alkynyloxy or C3-C6halogenalkynyloxy;
B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents
R9; each substituent R9 independently of each other stands for halogen, cyano, nitro, -
C(Rd)=N(ORe) or a group -L-Rf; each Rd is independently of each other hydrogen or d-C6alkyl; each Re is independently of each other Ci-C6alkyl; each L is independently of each other a bond, -O- or -S-; each Rf is independently of each other Ci-C6alkyl, which is unsubstituted or substituted by one or more substituents Rh, C3-C6cycloalkyl, which is unsubstituted or substituted by one or more substituents Rh, C6-C14bicycloalkyl, which is unsubstituted or substituted by one or more substituents Rh, C2-C6alkenyl, which is unsubstituted or substituted by one or more substituents Rh, C2-C6alkynyl, which is unsubstituted or substituted by one or more substituents Rh, phenyl, which is unsubstituted or substituted by one or more substituents Rh or heteroaryl, which is unsubstituted or substituted by one or more substituents Rh; each Rh is independently of each other halogen, cyano, nitro, d-C6alkoxy, d-
C6halogenalkoxy, d-C6alkylthio, Ci-C6halogenalkylthio, C3-C6alkenyloxy, C3-C6alkynyloxy or
- CTΛ(RRh')==.N(OR kK\); each R1 is independently of each other hydrogen or d-C6alkyl; each Rk is independently of each other d-C6alkyl; and tautomers/isomers/enantiomers of these compounds.
2. A compound of formula I according to claim 1 , wherein A is a 5-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the heterocyclic ring being substituted by the groups R6, R7 and R8.
3. A compound of formula I according to claim 1 , wherein A is a phenyl ring or a 6- membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the phenyl ring or the heterocyclic ring being substituted by the groups R6, R7 and R8.
4. A compound of formula I according to claim 1 , wherein X is oxygen.
5. A compound of formula I according to claim 1 , wherein R5 is hydrogen.
6. A compound of formula I according to claim 1 , wherein B is a phenyl group, which is substituted by one or more substituents R9.
7. A compound of formula I according to claim 1 , wherein B is B1
Figure imgf000112_0001
in which R19a is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-C6alkoxy, C1- C6halogenalkyl, CrC6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19b is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19c is hydrogen, halogen, cyano, d-C6alkyl, C2-C6alkynyl, C1- C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19d is hydrogen, halogen, cyano, d-C6alkyl, C2- C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R19e is hydrogen, halogen, cyano, C1- C6alkyl, C2-C6alkynyl, d-C6alkoxy, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R19a, Ri9b, Ri9c, Ri9d and R19θ is not hydrogen.
8. A compound of formula I according to claim 7, wherein R19b and R19d is hydrogen; and Riga, Ri9c and R19e independently of one another are selected from hydrogen, halogen, cynao, C2-C6alkynyl, d-C6halogenalkyl, d-C6halogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R19a, R19c and R19e is not hydrogen.
9. A compound of formula I according to claim 1 , wherein B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R9.
10. A compound of formula I according to claim 1 , wherein R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or d-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, d-C6alkoxy and C1- C6halogenalkoxy.
11. A compound of formula I according to claim 1 , wherein R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, cyano or Ci-C6alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and d-C6alkoxy.
12. A compound of formula I according to claim 1 , wherein R1, R2, R3 and R4 indepedently of each other stands for hydrogen, halogen, or CrCealkyl.
13. A compound of formula I according to claim 1 , wherein R1 is hydrogen, halogen or C1- C6alkyl; and R2, R3 and R4 are hydrogen.
14. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I according to claim 1 or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
15. A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I according to claim 1 and an inert carrier.
16. A compound of the formula Il
Figure imgf000113_0001
in which R1, R2, R3, R4 and B are as defined under formula I in claim 1.
(")■
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