WO1999032464A1 - Thiazole-, isothiazole- and thiadiazole-derivatives having microbicidal and plant immunizing activities - Google Patents

Thiazole-, isothiazole- and thiadiazole-derivatives having microbicidal and plant immunizing activities Download PDF

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Publication number
WO1999032464A1
WO1999032464A1 PCT/EP1998/008335 EP9808335W WO9932464A1 WO 1999032464 A1 WO1999032464 A1 WO 1999032464A1 EP 9808335 W EP9808335 W EP 9808335W WO 9932464 A1 WO9932464 A1 WO 9932464A1
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Prior art keywords
alkyl
alkoxy
unsubstituted
substituted
halo
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PCT/EP1998/008335
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French (fr)
Inventor
Philippe Chemla
Thomas Maetzke
Peter Ertl
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Novartis Ag
Novartis-Erfindungen Verwaltungsgesellschaft Mbh
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Application filed by Novartis Ag, Novartis-Erfindungen Verwaltungsgesellschaft Mbh filed Critical Novartis Ag
Priority to IL13658998A priority Critical patent/IL136589A0/en
Priority to JP2000525401A priority patent/JP2001526277A/en
Priority to PL98341290A priority patent/PL341290A1/en
Priority to AU20546/99A priority patent/AU2054699A/en
Priority to HU0100619A priority patent/HUP0100619A3/en
Priority to BR9814394-8A priority patent/BR9814394A/en
Priority to EP98965285A priority patent/EP1042306A1/en
Priority to CA002309973A priority patent/CA2309973A1/en
Publication of WO1999032464A1 publication Critical patent/WO1999032464A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
    • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • 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
    • C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • C07D277/22—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • 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

  • Thiazole-, isothiazole- and thiadiazole-derivatives having microbicidal and plant immunizing activities having microbicidal and plant immunizing activities.
  • the invention relates to a method for protecting and immunizing plants against attack by phytopathogenic microorganisms by applying to the plants, to parts of the plants and/or to the locus of the plants a compound of formula I
  • Z is a d-group to which 1-3 halogen atoms or 1 -3 unsubstituted or substituted hetero atoms selected from the group O, S and N are bonded;
  • Ri and R 2 are independently H, OH, SH, CN, COOH, N0 2 , NH 2 , halogen, C C 6 alkyl, haloC C 6 alkyl, alkoxyC ⁇ -C 6 alkyl, aminoCrC 6 alkyl, alkoxaminoCrC ⁇ alkyl, C ⁇ -C 6 alkoxy, halo- C ⁇ -C 6 alkoxy, CrC 6 alkanoyloxy, aroyloxy, C ⁇ -C 6 alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, C C 6 alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, C ⁇ -C 6 alkylaminocarbonyl, C ⁇ -C 6 dialkylaminocarbonyl, C ⁇ .C 6 alkylthio, haloCrC 6 alkylthio, CrC 6 alkylsulfinyl, haloCrC
  • Ri and R 2 together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 8 membered isocyclic or heterocyclic ring; or
  • R 2 and Z together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 7 membered lactone, lactame, thiolactone or thiolactame, which ring may have 1 to 2 additional hetero atoms selected from the group O, S and N;
  • R 3 , R 4 and R 5 are independently H, OH, SH, CN, NO 2 , NH 2 , halogen, C C 6 alkyl, haloCrC 6 alkyl, hydroxyCrC 6 alkyl, alkoxyCrC 6 alkyl, aminoCrC 6 alkyl, alkoxaminod-C 6 alkyl, C ⁇ -C 6 alkoxy, d-C 6 alkylthio, haloC ⁇ -C 6 alkylthio, d-C 6 alkylsulfinyl, haloC ⁇ -C 6 alkylsulfinyl, d-Cealkylsul
  • the invention relates also to new compounds of formula I, to the preparation of those compounds, to new intermediates and to agrochemical compositions comprising at least one of those compounds as active ingredient.
  • compounds of formula I can be used for protecting and immunizing plants against attack by microorganisms, such as phytopathogenic fungi, bacteria and viruses and for improving the qualities of the plants.
  • the formula I embraces all stereoisomeric forms and mixtures thereof, such as enantiomeric and diastereomeric pure forms and mixtures thereof.
  • the compounds of formula I and, where appropriate, their tautomers can be in the form of salts.
  • Compounds of formula I that have at least one basic centre can form acid addition salts.
  • compounds of formula I having at least one acid group can form salts with bases. Preference is given to agrochemically advantageous salts.
  • Z is a d-group which means that no additional carbon atoms are directly attached to this group.
  • Examples for the group Z are trihalomethyl, dihalomethyl or halomethyl as chloromethyl; formyl or an acetal or thioacetal thereof; a carboxyiic acid or derivatives thereof, as nitrile, esters, anhydrides, thioesters, amides, amidines, imidic-.hydrazonic- and hydroxamic-acids or derivatives thereof; or heterocyclyl, as 2-imidazolyl, 2-pyrimidinyl and 2- thiazolyl.
  • Hydrocarbon radicals may be saturated or unsaturated, open-chained or cyclic, or mixed open-chained and cyclic, for example cyclopropylmethyl or benzyl.
  • Alkyl groups are straight-chained or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, sec-amyl, tert-amyl, 1-hexyl or 3-hexyl.
  • Unsaturated hydrocarbon radicals are alkenyl, alkynyl or alkenynyl groups having not more than three multiple bonds, for example butadienyl, hexatrienyl or 2-penten-4-ynyl.
  • Alkenyl is straight-chained or branched alkenyl, for example allyl, methallyl, 1 -methylvinyl or but-2-en-1-yl. Preference is given to alkenyl radicals having a chain length of 2 to 4 carbon atoms.
  • Alkynyl may be straight-chained or branched, for example propargyl, but-1-yn-1-yl or but-1 - yn-3-yl. Propargyl is preferred.
  • Cyclic unsaturated hydrocarbon radicals may be aromatic, for example phenyl and naphthyl, or non-aromatic, for example cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctadienyl, or partially aromatic, for example tetrahydronaphthyl and indanyl.
  • Halogen, or halo is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
  • Haloalkyi may contain identical or different halogen atoms, for example fluoromethyl, difiuoromethyl, difluorochloromethyl, trifluoromethyl, chloromethyi, dichloromethyl, trichloro- methyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl, 3,3,3-trifluoro- propyl.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec- butoxy and tert-butoxy, preferably methoxy and ethoxy.
  • Haloalkoxy is, for example, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy and 2,2-difluoroethoxy.
  • Cycloalkyl is cyclopropyl, cyciobutyl, cyclopentyl or cyclohexyl.
  • Alkanoyi is either straight-chained or branched. Examples are formyl, acetyl, propionyl, butyryl, pivaloyl and octanoyl.
  • a heterocyclyl radical is to be understood as being a 3 to 7-membered, aromatic or non- aromatic ring having hetero atoms N, O and/or S. Furthermore, an unsubstituted or substituted benzo group may be fused onto such a heterocyclyl radical bonded to the rest of the molecule.
  • heterocyclyl groups are pyridyl, pyrimidinyl, imidazolyl, thiazolyl, 1 ,3,4-thiadiazolyl, triazolyl, thienyl, furanyl, pyrrolyl, morpholinyl, oxazolyl and the corresponding partially or completely hydrogenated rings.
  • heterocyclyl groups to which a benzo group is fused are quinolyl, isoquinolyl, benzoxazolyl, quinoxalinyl, benzothiazolyl, benzimidazolyl, indolyl and indolinyl.
  • Aryl is phenyl, naphthyl, phenanthryl or fluorenyl, in particular phenyl.
  • hydrocarbyl groups as alkyl, alkenyl, alkynyl, and the haloalkyi, haloalkenyl, haloalkoxy and alkanoyi groups mentioned hereinabove and hereinbelow can be substituted by aryl, hetaryl, aryloxy, hetaryloxy, arylsulfenyl, arylsulfinyl, arylsulfonyl, heterarylsulfenyl, hetarylsulfinyl or heterarylsulfonyl, each of which is unsubstituted or additionally substituted.
  • All the aryl, hetaryl and heterocyclyl groups mentioned hereinabove and hereinbelow can be mono- or polysubstituted, for example by halogen, C ⁇ -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, d-dalkoxy, d-C 4 alkylthio, C ⁇ -C 4 haloalkyl, C 2 -C haloalkenyl, C 2 -C 4 -haloalkynyl, d-C 4 haloalkoxy, halogen, cyano, cyano-d-C 2 alkyl, cyano-d-C 2 alkoxy, OH, NO 2 , SCN, thiocyanomethyl, Si(CH 3 ) 3 , NH 2 , NH(d-C alkyl), N(d-C alkyl) 2 , d-C alkoxymethyl, C ⁇ -C 4 haloalky
  • Z is CN, CO-A, CS-A or CH(OR 10 ) 2 .
  • A is hydrogen, halogen, OR 6 , SR 7 , N(R 8 )R 9 , ON(R, ,)R 12 or N(R 13 )OR 14 ;
  • R 6 to R are independently hydrogen, an unsubstituted or substituted, open-chained, saturated or unsaturated hydrocarbon radical containing up to 8 carbon atoms, an unsubstituted or substituted, cyclic, saturated or unsaturated hydrocarbon radical containing up to 10 carbon atoms, unsubstituted or substituted benzyl or phenethyi, an unsubstituted or substituted acyl group containing up to 8 carbon atoms, an unsubstituted or substituted benzoyl group, or an unsubstituted or substituted heterocyclyl radical; or R 8 and R 9 , or Rn and R 1 , together with the nitrogen atom to which they are bonded, form a
  • R 10 are identical or different and are d-C 6 alkyl that is unsubstituted or substituted by phenyl, d-C 2 alkoxy, phenoxy or by benzyloxy; or two substituents OR ⁇ 0 , together with the carbon atom to which they are bonded, form a cyclic acetal group that is unsubstituted or substituted by d-C 3 alkyl, phenyl, benzyl, hydroxy or by C C 3 hydroxyalkyl.
  • A is OR 6 , SR 7 , N(R 8 )R 9 , ON(R desire)R 12 or N(R 13 )OR, 4 ;
  • R 6 to R, 4 are independently H, C ⁇ -C 6 alkyl, haloC ⁇ -C 6 alkyl, C C 4 alkoxycarbonyl, d-C 4 alkanoyld-C alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, phenyl, benzyl, phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 5 substituents independently selected from halogen, d-C 4 alkyl, halo-d-C 2 alkyl, d-C 2 alkoxy, halo- C ⁇ -C 2 alkoxy and d-C 2 alkylenedioxy.
  • R 3 is H, OH, d-C 6 alkyl, C 3 -C 6 cycloalkyl, halod-C 6 alkyl, d-C 6 alkoxy or halod-C 6 alkoxy.
  • R is H, OH, NH 2 , halogen, COOH, d-C 4 alkyl, halod-C 4 alkyi, d-C 4 alkoxy, d-C alkanoyloxy, aroylyloxy, d-C alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, d-C 4 alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, C ⁇ -C alkylaminocarbonyl, C,-C dialkylaminocarbonyl, alkanoyld-C alkyl, alkylcarbonyloxyCrC 4 alkyl, C 2 -C alkenyl, haloC 2 -C 4 alkenyl, C ⁇ -C 4 alkylamino, C ⁇ -C 4 dialkylamino, C ⁇ -C 4 alkanoylamino, d-C 4 alkoxycarbonylamino, benz
  • R 2 +Z together are a group selected from
  • R 17 , R i8 and R 19 are independently H or d-C 4 alkyl
  • R 3 is H, halogen, CrCealkyl, haloCrC 6 alkyl, C 3 -C 6 -cycloalkyl, C C 4 alkoxycarbonyl, phenyl which is unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C 4 alkyl, halo-d-C 2 alkyl, CrC 2 alkoxy, halo-CrC 2 alkoxy, amino, d-dalkylamino, d-C 4 dialkylamino, benzylamino, d-C alkanoylamino, benzoylamino, d-dalkoxycarbonylamino, formyl, or a 4-7-membered cyclic or d-C alkyl open-chained acetal or thioacetal thereof;
  • R 4 is H, OH, halogen, amino, d-C 6 alkyl, C ⁇ -C alkylamino, d-C 4 alkenylylamino, d-C 4 dialkylamino, benzylamino, d-C 4 alkanoylamino, benzoylamino, d-C 4 alkoxycarbonylamino.
  • R 3 is H, OH, halogen, CrC 6 alkyl, halod-C 6 alkyl, C 3 -C 6 -cycloalkyl, CrC 6 alkoxy, alkoxycarbonylCrC 6 alkyl, phenyl, benzyl, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C 4 alkyl, halo- d-C 2 alkyl, d-C 2 alkoxy and halo-d-C 2 alkoxy; or formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof;
  • R 4 is H, OH, halogen, amino, CrC 6 alkyl, d-C 4 alkyiamino, d-dalkenylylamino,
  • A is hydrogen, halogen, OR 6 , SR 7 , N(R 8 )R 9 , ON(Rn)R 12 or N(R 13 )OR i4 ;
  • R 6 to R 9 and Rn to R are independently hydrogen, an unsubstituted or substituted, open- chained, saturated or unsaturated hydrocarbon radical containing up to 8 carbon atoms, an unsubstituted or substituted, cyclic, saturated or unsaturated hydrocarbon radical containing up to 10 carbon atoms, unsubstituted or substituted benzyl or phenethyi, an unsubstituted or substituted acyl group containing up to 8 carbon atoms, an unsubstituted or substituted benzoyl group, or an unsubstituted or substituted heterocyclyl radical; or R 8 and R 9 , or Rn and R 12 , together with the nitrogen atom to which they are bonded, form a 5- or 6-membered, unsubstituted
  • R 10 are identical or different and are d-C ⁇ alkyl that is unsubstituted or substituted by phenyl, d-C 2 alkoxy, phenoxy or by benzyloxy; or two substituents OR ⁇ 0 , together with the carbon atom to which they are bonded, form a cyclic acetal group that is unsubstituted or substituted by CrC 3 alkyl, phenyl, benzyl, hydroxy or by d-C 3 hydroxyalkyl.
  • R 6 , R 7 , R 8 R 9 are independently H, d-C 6 alkyl, haloC C 6 alkyl, C C alkoxycarbonyl, alkoxycarbonyld-C 6 alkyl, d-dalkanoyld-dalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C alkyl, halo-d-C 2 alkyl, d-C 2 alkoxy, halo-d-C 2 alkoxy.
  • A is OR 6 or N(R 8 )R 9 ;
  • R t is H, OH, halogen, d-C 4 alkyl, halod-dalkyl, d-dalkoxy, halo-C C 4 alkoxy, amino, d-dalkylamino, C C 4 dialkylamino, benzylamino; phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 2 substituents independently selected from halogen, halo-CrC 2 alkyl, C C 2 alkoxy, halo-d-C 2 alkoxy; R 2 is H, OH, halogen, d-dalkyl, halod-C 6 alkyl, or phenyl,
  • R 3 is H, OH, d-C 6 alkyl, C 3 -C 6 cycloalkyl, halod-C 6 alkyl, C C 6 alkoxy or haloC C 6 alkoxy,
  • R is H or Cl
  • R 6 , R 8 and R 9 are independently H, d-C 6 alkyl, haloCrC 6 alkyl, d-C 6 alkoxy, haloCrC 6 alkoxy, d-C alkoxycarbonyl, d-C alkanoylCrC alkyl, C -C 6 cycloalkyl,
  • R 2 is H.
  • R 3 is H, cyclopropyl or CF 3 ,
  • R 4 is Cl.
  • R 3 is H, halogen, d-C alkyl, haloC C 4 alkyl, C 3 -C 6 -cycloalkyl, C C alkoxycarbonyl, formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof.
  • Z is CO-A
  • A is hydrogen, OR 6 , SR 7 , N(R 8 )R 9 ;
  • Ri is H, OH, halogen or d-dalkyl
  • R 2 is H
  • R 3 is H, OH, CrC 6 alkyl, C 3 -C 6 cycloalkyl, haloCrC 6 alkyl, CrC 6 alkoxy, halod-C 6 alkoxy, formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof;
  • R 4 is Cl
  • R 6 , R 7 , R 8 and R 9 are independently H, CrC 6 alkyl, halod-C 6 alkyl, CrC 6 alkoxy, haloCrC 6 alkoxy, C ⁇ -C alkoxycarbonyl, CrC alkanoylCrC alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-dalkyl, halo-CrC 2 alkyl, d-C 2 alkoxy, halo-d-C 2 alkoxy.
  • A is OR 6 or SR 7 ;
  • R, and R 2 are H;
  • R 3 is CrC 6 alkyl, C 3 -C 6 cycioalkyl, CF 3 or formyl;
  • R 4 is Cl
  • R 6 and R 7 are independently H, d-C 6 alkyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted with 1 to 2 substituents independently selected from halogen, d-dalkyl, halo-d-C 2 alkyl, d-C 2 alkoxy and halo-d-C 2 alkoxy.
  • the compounds of formula I may be prepared as outlined in the following reaction schemes.
  • L leaving group, preferably chlorine, bromine, mesylate or tosylate.
  • R a group which is inert under the reaction conditions
  • X, Y and R 3 are as defined for formula I, which comprises reaction of a compound of formula 11.1 with carbon monoxide under pressure of 2-20 bars, preferably 5-10 bars, in presence of a catalyst, for example cobalt carbonyl and optionally a phase transfer catalyst.
  • a catalyst for example cobalt carbonyl and optionally a phase transfer catalyst.
  • Th e functional groups of the compounds of formula I can be converted by known methods.
  • carboxylic acid derivatives can be converted as follows:
  • thionating agent reduction -H 2 0 e.g. H ⁇ cat e.g. Lawesson reagent e.g. SOCL
  • Suitable bases, leaving groups, solvents and catalysts are known to the skilled person.
  • thiazoles, isothiazoles and thiadiazoles can be synthesized by known methods or in analogy thereto according to the following references:
  • the compounds of the invention can be used in the agricultural sector and related fields preventively and/or curatively. Besides their microbicidal properties, the compounds exhibit plant immunizing properties, i.e. plants can be protected by activation and stimulation of the plant's own defense system (immunization) which is known as "Systemic Activated Resistance” (“SAR").
  • SAR Systemic Activated Resistance
  • the compounds and methods of the invention it is possible to control plant diseases on the one hand by strengthening the plant by activating its own defence system and on the other hand by additionally controlling the pathogens directly.
  • the compounds offer a long lasting protection against a variety of pathogenes in different crops.
  • the compounds I can also be used as dressings in the treatment of seed (fruit, tubers, grains) and plant cuttings to provide protection against fungus infections as well as against phytopathogenic fungi which occur in the soil.
  • the compounds I are effective, for example, against phytopathogenic fungi belonging to the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Moreover, they are effective against the classes of the Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and Oomycetes (e.g. Phyto- phthora, Pythium, Plasmopara).
  • Fungi imperfecti e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria
  • Basidiomycetes e.g. Rhizoctonia, Hemileia, Puccinia
  • Target crops to be protected within the scope of the present invention comprise e.g. the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, stone fruit 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 (marrows, cucumber, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocados, cinnamon, camphor); and plants such as tobacco, nuts, coffee
  • the compounds I are generally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession, with further compounds.
  • These further compounds can be, for example, fertilisers or micronutrient donors or other preparations that influence plant growth. 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 other application- promoting adjuvants customarily employed in formulation technology. Suitable solvents, carriers and adjuvants are known to the skilled person.
  • a preferred method of applying a compound of formula I, or an agrochemical composition comprising at least one of those compounds, is application to the leaves (foliar application).
  • the frequency and rate of application depend upon the risk of infestation by the corresponding pathogen.
  • the compounds I can, however, also penetrate the plant through the roots via the soil (systemic action) if the locus of the plant is impregnated with a liquid formulation or if the substances are introduced in solid form into the soil, e.g. in the form of granules (soil application). In paddy rice crops, such granules can be applied in metered amounts to the flooded rice field.
  • the compounds I can, however, also be applied to the seeds (coating), either by impregnating the grains or tubers with a liquid formulation of the active ingredient, or by coating them with a solid formulation.
  • Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a. /ha, especially from 20 g to 600 g a.i./ha.
  • the agrochemical compositions generally comprise 0.1 to 99 % by weight, preferably 0.1 to
  • compositions may also comprise further auxiliaries, such as stabilisers, antifoams, viscosity regulators, binders or tackifiers, as well as fertilisers or other active ingredients for obtaining special effects.
  • auxiliaries such as stabilisers, antifoams, viscosity regulators, binders or tackifiers, as well as fertilisers or other active ingredients for obtaining special effects.
  • the compounds of formula I can be mixed with other fungicides, producing in some cases unexpected synergistic effects.
  • Especially preferred mixing partners are azoles, as azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazoie, metconazole, myclobutanil, pefurazoate, penconazole, pyrifenox, prochloraz, propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole; pyrimidinyl carbinoles, as ancymidol, fenarimol, nuarimol;
  • 2-amino-pyrimidines as bupirimate, dimethirimol, ethirimoi; morpholines, as dodemorph, fenpropidin, fenpropimo h, spiroxamin, tridemorph; idinginopyrimidines, as cyprodinil, mepanipyrim, pyrimethanil; pyrroles, as fenpiclonil, fludioxonil; phenyiamides, as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace, oxadixyl; benzimidazoles, as benomyl, carbendazim, debacarb, fuberidazole, thiabendazole; dicarboximides, as chlozolinate, dichlozoline, iprodione, myclozoline, procymidone, vinclozolin; carboxamides, as carboxin
  • N-halomethylthiodicarboximides as captafol, captan, dichlofluanid, fluoromide, folpet, tolyfluanid; copper compounds, as bordeaux-mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, mancopper, oxine-copper; nitrophenol-derivatives, as dinocap, nitrothal-isopropyl; organo-P-derivatives, as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos, toiclofos-methyl; other compounds, as acibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran, diethofencarb, dimethomorph, dithianon,
  • the resulting yellow solution is then concentrated under reduced pressure, dissolved in a mixture of 10 ml tetrahydrofuran and 10 ml acetonitrile, cooled down to 0°C, and successively treated with triethylamine (1.8 ml), trimethylsilyldiazomethane (commercial 2N solution in hexane) (6.05 ml, 13.05 mmol). After 12 hours of stirring at 0°C, the solvents are evaporated under reduced pressure, and the intermediate diazoketone G is rearanged in a mixture of 13 ml of benzylalcohol and 13 ml of trimethylpyridine at 180°C for 8 min.
  • reaction mixture is then extracted with ethyl acetate, the organic layer dried over magnesium sulfate, the solvent removed under reduced pressure, and the crude material chromatographed on silica-gel to afford 0.254g of 2.08g of the title compound as oils.
  • R R 2 and A have the meanings of the corresponding compounds of Table 1.A.
  • R,, R 2 , R 3 and A have the meanings of the corresponding compounds of Table 2.A.
  • R 1 t R 2 , R 3 and A have the meanings of the corresponding compounds of Table 2.A.
  • R 1 t R 2 , R 3 and Z have the meanings of the corresponding compounds of Table 3.A.
  • R 1 R 2 , R 3 and Z have the meanings of the corresponding compounds of Table 4.A.
  • Example B.1 Immunization of Cucumis sativus L against Colletotrichum la ⁇ enarium a) After a cultivation period of 2 weeks, cucumber plants are sprayed with a spray mixture prepared from a wettable powder formulation of the test compound (concentration:
  • the plants are infected with a spore suspension (1.0 x 10 5 spores/ml) of the fungus and incubated for 30 hours at high humidity and a temperature of
  • Evaluation of protective action is made 7 to 8 days after infection and is based on fungus infestation.
  • cucumber plants are treated by soil application with a spray mixture prepared from a wettable powder formulation of the test compound (concentration: 20 ppm, based on the volume of the soil). After 72 hours, the plants are infected with a spore suspension (1.5 x 10 5 spores/ml) of the fungus and incubated for
  • Evaluation of protective action is made 7 to 8 days after infection and is based on fungus infestation.
  • the formulated active ingredient is mixed in various concentrations (100, 10, 1 , 0.1 ppm) with autoclaved and cooled nutrient medium containing 10 000 spores per ml and is poured into microtitre plates. Incubation is then carried out at 22°C in the dark. After 2 to 3 days, fungus growth is measured by spectrophotometry.
  • Example B.2 Action against Phvtophthora infestans on tomato plants a) After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture prepared from a wettable powder formulation of the test compound (0.02 % active ingredient). After 72 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 5 days at 90-100 % relative humidity and 20°C.
  • Example B.3 Action against Pyricularia orvzae on rice plants
  • 2-week-old rice plants are watered with a spray mixture prepared from a wettable powder formulation of the test compound (0.006 % active ingredient, based on the volume of the soil).
  • the pots are then filled with water until the lowermost parts of the stems of the rice plants are standing in water.
  • the treated rice plants are infected with a conidia suspension of the fungus.
  • Fungus infestation is evaluated after incubation of the infected plants for 5 days at 95-100 % relative humidity and approximately 24°C. In comparison with untreated control plants (100 % infestation), fungus infestation on rice plants treated with a spray mixture comprising a compound of the Tables as active ingredient is only approximately 50 %.
  • Example B.4 Action against Cercospora nicotina on tobacco plants a) Foliar application
  • Tobacco plants (8 weeks old) are sprayed with a formulated solution of the test compound (concentration: 0.02 % active ingredient). Four days after treatment, the plants are inoculated with a sporangia suspension of Cercospora nicotina (150 000 spores/ml), kept for 5 days in the dark at 25°C and high humidity and then incubated further under a normal day/night sequence.
  • Example B.5 Action against Ervsiphe graminis on wheat

Abstract

Compounds of formula (I) and process for protecting and immunizing plants against attack by phytopathogenic microorganisms by applying compounds of formula (I) wherein a) X is CR4 and Y is N; or b) X is N and Y is CR5; or c) X and Y are N; and wherein Z is a C1-group to which 1-3 halogen atoms or 1-3 unsubstituted or substituted hetero atoms selected from the group O, S and N are bonded; Z is CN, CO-A, CS-A or CH(OR10)2; A is hydrogen, halogen, OR6, SR7, N(R8)R9, ON(R11)R12 or N(R13)OR14; and wherein R1-R14 have the meanings given in the description.

Description

Thiazole-, isothiazole- and thiadiazole-derivatives having microbicidal and plant immunizing activities.
The invention relates to a method for protecting and immunizing plants against attack by phytopathogenic microorganisms by applying to the plants, to parts of the plants and/or to the locus of the plants a compound of formula I
Figure imgf000003_0001
wherein a) X is CR4 and Y is N; or b) X is N and Y is CR5; or c) X and Y are N; and wherein
Z is a d-group to which 1-3 halogen atoms or 1 -3 unsubstituted or substituted hetero atoms selected from the group O, S and N are bonded;
Ri and R2 are independently H, OH, SH, CN, COOH, N02, NH2, halogen, C C6alkyl, haloC C6alkyl, alkoxyCι-C6alkyl, aminoCrC6alkyl, alkoxaminoCrCβalkyl, Cι-C6alkoxy, halo- Cι-C6alkoxy, CrC6alkanoyloxy, aroyloxy, Cι-C6alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, C C6alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, Cι-C6alkylaminocarbonyl, Cι-C6dialkylaminocarbonyl, Cι.C6alkylthio, haloCrC6alkylthio, CrC6alkylsulfinyl, haloCrC6alkylsulfinyl, Cι-C6alkylsulfonyl, haloCrC6alkylsulfonyl, arylsulfinyl, arylsulfonyl, C2-C6alkenyl, haloC2-C6alkenyl, C2-C6alkinyl, carboxyCι-C6alkyl, alkoxycarbonylCι-C6alkyl, haloalkoxycarbonylC Cβalkyl, C3-C6cycloalkyl, alkanoylC C6alkyl, alkylcarbonyloxyC Cβalkyl, phenylcarbonyloxyCι-C6alkyl, Cι-C6alkylamino, d- C6dialkylamino, C2-C6alkenylamino, Ci-Cβalkanoylamino, CrC6alkoxycarbonylamino, benzylamino, benzoylamino, benzyloxyarbonylamino, phenyl, phenoxy, benzyl or phenethyi, wherein all the aromatic groups are unsubstituted or substituted from 1 to 5 substituents independently selected from halogen, hydroxy, C C4alkyl, halo-Cι-C2alkyl, CrC2alkoxy, halo-C C2alkoxy and nitro; or optionally substituted heterocyclyl; or tr CrCβalky silyl or tri(Cι-C6alkyl)silyloxy; with the proviso that R and R2 are not simultaneously a group selected from OH, SH, NO2, NH2, C C6alkylamino, Cι-C6dialkylamino and C2-C6alkenylamino; or R, and R2 together are =O or =S; or
Ri and R2 together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 8 membered isocyclic or heterocyclic ring; or
R2 and Z together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 7 membered lactone, lactame, thiolactone or thiolactame, which ring may have 1 to 2 additional hetero atoms selected from the group O, S and N; R3, R4 and R5 are independently H, OH, SH, CN, NO2, NH2, halogen, C C6alkyl, haloCrC6alkyl, hydroxyCrC6alkyl, alkoxyCrC6alkyl, aminoCrC6alkyl, alkoxaminod-C6alkyl, Cι-C6alkoxy, d-C6alkylthio, haloCι-C6alkylthio, d-C6alkylsulfinyl, haloCι-C6alkylsulfinyl, d-Cealkylsulfonyl, halod-C6alkylsulfonyl, halo-d-C6alkoxy, C2-C6alkenyl, haloC2-C6alkenyl, C2-C6alkinyl, carboxyd-C6alkyl, d-C6aikanoyl, d-C6alkoxycarbonyl, alkoxycarbonylCι-C6alkyl, haloalkoxycarbonylCι-C6alkyl, C3-C6cycloalkyl, alkanoyld-C6alkyl, alkylcarbonyloxyd-C6alkyl, phenylcarbonyloxyd-C6alkyl, d-Cealkylamino, Cι-C6dialkylamino, C2-C6alkenylamino, d-C6alkanoylamino, d-C6alkoxycarbonylamino, benzylamino, benzoylamino, phenyl, phenoxy, benzyl or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, hydroxy, d-C alkyl, halo-d-C2alkyl, d-C2alkoxy, halo-C C2alkoxy and nitro; or optionally substituted heterocyclyl.
The invention relates also to new compounds of formula I, to the preparation of those compounds, to new intermediates and to agrochemical compositions comprising at least one of those compounds as active ingredient.
Thiazole and thiadiazole derivatives having plant-fungicidal activities are known from EP-A-395,174, US 5,135,927, WO 96/17840, and WO 96/29871. EP-A-757,987 and WO 97/20465 discloses thiazole and thiadiazole derivatives exhibiting plant immunizing activities. These compounds have no or very weak direct activity against fungi and bacteria, but protect the plants from phytopathogenic microorganisms by activation and stimulation of the plant's own defence system (immunisation). That mode of action has also become known by the name "Systemic Activated Resistance" ("SAR"). Such compounds and methods are ecologically advantageous and are complementary to current methods in crop protection. It is therefore desirable to provide more compounds and methods for protecting plants by immunizing them against attack by phytopathogenic microorganisms.
Surprisingly it has now been found that compounds of formula I can be used for protecting and immunizing plants against attack by microorganisms, such as phytopathogenic fungi, bacteria and viruses and for improving the qualities of the plants.
The formula I embraces all stereoisomeric forms and mixtures thereof, such as enantiomeric and diastereomeric pure forms and mixtures thereof. The compounds of formula I and, where appropriate, their tautomers can be in the form of salts. Compounds of formula I that have at least one basic centre can form acid addition salts. Furthermore, compounds of formula I having at least one acid group can form salts with bases. Preference is given to agrochemically advantageous salts.
Z is a d-group which means that no additional carbon atoms are directly attached to this group. Examples for the group Z are trihalomethyl, dihalomethyl or halomethyl as chloromethyl; formyl or an acetal or thioacetal thereof; a carboxyiic acid or derivatives thereof, as nitrile, esters, anhydrides, thioesters, amides, amidines, imidic-.hydrazonic- and hydroxamic-acids or derivatives thereof; or heterocyclyl, as 2-imidazolyl, 2-pyrimidinyl and 2- thiazolyl.
Compounds of formula I wherein Ri and R2 are simultaneously a group selected from OH, SH, N02, NH2, d-C6alkylamino, d-C6dialkylamino and C2-C6alkenylamino are not stable in general and are thus not part of this invention.
Unless defined otherwise, the general terms used hereinbefore and hereinafter have the meanings given below:
Hydrocarbon radicals may be saturated or unsaturated, open-chained or cyclic, or mixed open-chained and cyclic, for example cyclopropylmethyl or benzyl.
Alkyl groups are straight-chained or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, sec-amyl, tert-amyl, 1-hexyl or 3-hexyl.
Unsaturated hydrocarbon radicals are alkenyl, alkynyl or alkenynyl groups having not more than three multiple bonds, for example butadienyl, hexatrienyl or 2-penten-4-ynyl. Alkenyl is straight-chained or branched alkenyl, for example allyl, methallyl, 1 -methylvinyl or but-2-en-1-yl. Preference is given to alkenyl radicals having a chain length of 2 to 4 carbon atoms.
Alkynyl may be straight-chained or branched, for example propargyl, but-1-yn-1-yl or but-1 - yn-3-yl. Propargyl is preferred.
Cyclic unsaturated hydrocarbon radicals may be aromatic, for example phenyl and naphthyl, or non-aromatic, for example cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctadienyl, or partially aromatic, for example tetrahydronaphthyl and indanyl. Halogen, or halo, is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
Haloalkyi may contain identical or different halogen atoms, for example fluoromethyl, difiuoromethyl, difluorochloromethyl, trifluoromethyl, chloromethyi, dichloromethyl, trichloro- methyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl, 3,3,3-trifluoro- propyl.
Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec- butoxy and tert-butoxy, preferably methoxy and ethoxy.
Haloalkoxy is, for example, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy and 2,2-difluoroethoxy. Cycloalkyl is cyclopropyl, cyciobutyl, cyclopentyl or cyclohexyl. Alkanoyi is either straight-chained or branched. Examples are formyl, acetyl, propionyl, butyryl, pivaloyl and octanoyl.
A heterocyclyl radical is to be understood as being a 3 to 7-membered, aromatic or non- aromatic ring having hetero atoms N, O and/or S. Furthermore, an unsubstituted or substituted benzo group may be fused onto such a heterocyclyl radical bonded to the rest of the molecule. Examples of heterocyclyl groups are pyridyl, pyrimidinyl, imidazolyl, thiazolyl, 1 ,3,4-thiadiazolyl, triazolyl, thienyl, furanyl, pyrrolyl, morpholinyl, oxazolyl and the corresponding partially or completely hydrogenated rings. Examples of heterocyclyl groups to which a benzo group is fused are quinolyl, isoquinolyl, benzoxazolyl, quinoxalinyl, benzothiazolyl, benzimidazolyl, indolyl and indolinyl. Aryl is phenyl, naphthyl, phenanthryl or fluorenyl, in particular phenyl.
The hydrocarbyl groups, as alkyl, alkenyl, alkynyl, and the haloalkyi, haloalkenyl, haloalkoxy and alkanoyi groups mentioned hereinabove and hereinbelow can be substituted by aryl, hetaryl, aryloxy, hetaryloxy, arylsulfenyl, arylsulfinyl, arylsulfonyl, heterarylsulfenyl, hetarylsulfinyl or heterarylsulfonyl, each of which is unsubstituted or additionally substituted. All the aryl, hetaryl and heterocyclyl groups mentioned hereinabove and hereinbelow can be mono- or polysubstituted, for example by halogen, Cι-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, d-dalkoxy, d-C4alkylthio, Cι-C4haloalkyl, C2-C haloalkenyl, C2-C4-haloalkynyl, d-C4haloalkoxy, halogen, cyano, cyano-d-C2alkyl, cyano-d-C2alkoxy, OH, NO2, SCN, thiocyanomethyl, Si(CH3)3, NH2, NH(d-C alkyl), N(d-C alkyl)2, d-C alkoxymethyl, Cι-C4haloalkylcarbonyl, C C4haloalkyloxycarbonyl, d-C alkylcarbonyl, d-C4- alkoxycarbonyl, aminocarbonyl, Cι-C alkylaminocarbonyl, bis(Cι-C4alkylamino)carbonyl, arylaminocarbonyi, arylaminothiocarbonyl, Cι-C alkoximinomethyl, -CSNH2, -SH, Ci- dalkylthiomethyl, C2-C4alkenyloxy, C2-C alkynyloxy, C2-C4haloalkenyloxy, d- C4alkylsulfinylmethyl, Cι-C4alkylsuifonylmethyl, phenylsulfinylmethyl, phenylsulfonylmethyl, trifluoromethylsulfonyl, C3-C6cycloalkyl, d-C haloalkylcarbonyloxy, d-C4alkyicarbonyloxy, d-C alkoxycarbonyloxy, haloalkoxycarbonyloxy, aminocarbonyloxy, Cι-C alkylaminocarbonyloxy, bis(CrC4alkylamino)carbonyloxy, arylaminocarbonyloxy, arylaminothiocarbonyloxy.
Amongst the compounds and methods of their use the following groups are preferred:
(1 ) Compounds of formula
Figure imgf000007_0001
The compounds of the formula
Figure imgf000007_0002
wherein a) Ri is OCO-CH3 and T is Br,
Figure imgf000008_0001
are known from WO 96/17840 as fungicides, but no indication is given therein to plant immunizing properties of these compounds ; these compounds are thus part of the invention only as far as the method for immunizing plants is concerned.
(2) Compounds of formula
Figure imgf000008_0002
(3) Compounds of formula
Figure imgf000008_0003
(4) Compounds of formula I, wherein
Z is CN, CO-A, CS-A or CH(OR10)2.;
A is hydrogen, halogen, OR6, SR7, N(R8)R9, ON(R, ,)R12 or N(R13)OR14;
R6 to R are independently hydrogen, an unsubstituted or substituted, open-chained, saturated or unsaturated hydrocarbon radical containing up to 8 carbon atoms, an unsubstituted or substituted, cyclic, saturated or unsaturated hydrocarbon radical containing up to 10 carbon atoms, unsubstituted or substituted benzyl or phenethyi, an unsubstituted or substituted acyl group containing up to 8 carbon atoms, an unsubstituted or substituted benzoyl group, or an unsubstituted or substituted heterocyclyl radical; or R8 and R9, or Rn and R1 , together with the nitrogen atom to which they are bonded, form a
5- or 6-membered, unsubstituted or substituted heterocycle having 1 to 3 hetero atoms selected from O, S and or N;
R10 are identical or different and are d-C6alkyl that is unsubstituted or substituted by phenyl, d-C2alkoxy, phenoxy or by benzyloxy; or two substituents ORι0, together with the carbon atom to which they are bonded, form a cyclic acetal group that is unsubstituted or substituted by d-C3alkyl, phenyl, benzyl, hydroxy or by C C3hydroxyalkyl.
(5) Compounds of formula I, wherein Z is CO-A or CS-A;
A is OR6, SR7, N(R8)R9, ON(R„)R12 or N(R13)OR,4;
R6 to R,4 are independently H, Cι-C6alkyl, haloCι-C6alkyl, C C4alkoxycarbonyl, d-C4alkanoyld-C alkyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, phenyl, benzyl, phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 5 substituents independently selected from halogen, d-C4alkyl, halo-d-C2alkyl, d-C2alkoxy, halo- Cι-C2alkoxy and d-C2alkylenedioxy.
(6) Compounds of formula I, wherein
R3 is H, OH, d-C6alkyl, C3-C6cycloalkyl, halod-C6alkyl, d-C6alkoxy or halod-C6alkoxy.
(7) Compounds of formula I, wherein
R, is H, OH, NH2, halogen, COOH, d-C4alkyl, halod-C4alkyi, d-C4alkoxy, d-C alkanoyloxy, aroylyloxy, d-C alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, d-C4alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, Cι-C alkylaminocarbonyl, C,-C dialkylaminocarbonyl, alkanoyld-C alkyl, alkylcarbonyloxyCrC4alkyl, C2-C alkenyl, haloC2-C4alkenyl, Cι-C4alkylamino, Cι-C4dialkylamino, Cι-C4alkanoylamino, d-C4alkoxycarbonylamino, benzylamino, benzoyiamino, phenyl, phenoxy, benzyl or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, hydroxy, d-C4alkyl, halo-Cι-C2alkyl, d-C2alkoxy, halo-Cι-C2alkoxy and nitro; R2 is H, OH, d-C4alkyl, d-C4alkoxy or phenyl; or RT and R2 together are a group selected from
Figure imgf000010_0001
R2+Z together are a group selected from
Figure imgf000010_0002
wherein R17, Ri8 and R19 are independently H or d-C4alkyl;
R3 is H, halogen, CrCealkyl, haloCrC6alkyl, C3-C6-cycloalkyl, C C4 alkoxycarbonyl, phenyl which is unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C4alkyl, halo-d-C2alkyl, CrC2alkoxy, halo-CrC2alkoxy, amino, d-dalkylamino, d-C4dialkylamino, benzylamino, d-C alkanoylamino, benzoylamino, d-dalkoxycarbonylamino, formyl, or a 4-7-membered cyclic or d-C alkyl open-chained acetal or thioacetal thereof;
R4 is H, OH, halogen, amino, d-C6alkyl, Cι-C alkylamino, d-C4alkenylylamino, d-C4dialkylamino, benzylamino, d-C4alkanoylamino, benzoylamino, d-C4alkoxycarbonylamino.
(8) Amongst group (7) those, wherein
R3 is H, OH, halogen, CrC6alkyl, halod-C6alkyl, C3-C6-cycloalkyl, CrC6alkoxy, alkoxycarbonylCrC6alkyl, phenyl, benzyl, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C4alkyl, halo- d-C2alkyl, d-C2alkoxy and halo-d-C2alkoxy; or formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof;
R4 is H, OH, halogen, amino, CrC6alkyl, d-C4alkyiamino, d-dalkenylylamino,
CrC4dialkylamino, benzylamino, CrC4alkanoylamino, benzoylamino, or d -dalkoxycarbonylamino. (9) Amongst group (6) those, wherein Z is CO-A or CS-A;
A is hydrogen, halogen, OR6, SR7, N(R8)R9, ON(Rn)R12 or N(R13)ORi4; R6 to R9 and Rn to R are independently hydrogen, an unsubstituted or substituted, open- chained, saturated or unsaturated hydrocarbon radical containing up to 8 carbon atoms, an unsubstituted or substituted, cyclic, saturated or unsaturated hydrocarbon radical containing up to 10 carbon atoms, unsubstituted or substituted benzyl or phenethyi, an unsubstituted or substituted acyl group containing up to 8 carbon atoms, an unsubstituted or substituted benzoyl group, or an unsubstituted or substituted heterocyclyl radical; or R8 and R9, or Rn and R12, together with the nitrogen atom to which they are bonded, form a 5- or 6-membered, unsubstituted or substituted heterocycle having 1 to 3 hetero atoms selected from O, S and/or N;
R10 are identical or different and are d-Cβalkyl that is unsubstituted or substituted by phenyl, d-C2alkoxy, phenoxy or by benzyloxy; or two substituents ORι0, together with the carbon atom to which they are bonded, form a cyclic acetal group that is unsubstituted or substituted by CrC3alkyl, phenyl, benzyl, hydroxy or by d-C3hydroxyalkyl.
(10) Amongst group (9) those, wherein A is OR6, SR7, or N(R8)R9;
R6, R7, R8 R9 are independently H, d-C6alkyl, haloC C6alkyl, C C alkoxycarbonyl, alkoxycarbonyld-C6alkyl, d-dalkanoyld-dalkyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C alkyl, halo-d-C2alkyl, d-C2alkoxy, halo-d-C2alkoxy.
(11 ) Amongst group (9) those, wherein Z is CO-A;
A is OR6 or N(R8)R9;
Rt is H, OH, halogen, d-C4alkyl, halod-dalkyl, d-dalkoxy, halo-C C4alkoxy, amino, d-dalkylamino, C C4dialkylamino, benzylamino; phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 2 substituents independently selected from halogen, halo-CrC2alkyl, C C2alkoxy, halo-d-C2alkoxy; R2 is H, OH, halogen, d-dalkyl, halod-C6alkyl, or phenyl,
R3 is H, OH, d-C6alkyl, C3-C6cycloalkyl, halod-C6alkyl, C C6alkoxy or haloC C6alkoxy,
R is H or Cl,
R6, R8 and R9 are independently H, d-C6alkyl, haloCrC6alkyl, d-C6alkoxy, haloCrC6alkoxy, d-C alkoxycarbonyl, d-C alkanoylCrC alkyl, C -C6cycloalkyl,
C3-C6cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-dalkyl, halo-d-C2alkyl, d-C2alkoxy, halo-d-C2alkoxy.
(12) Amongst group (11 ) those, wherein R, is H, OH, halogen, d-C4alkyl;
R2 is H.
R3 is H, cyclopropyl or CF3,
R4 is Cl.
(13) Amongst group (9) those, wherein
R3 is H, halogen, d-C alkyl, haloC C4alkyl, C3-C6-cycloalkyl, C C alkoxycarbonyl, formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof.
(14) Compounds of formula
Figure imgf000012_0001
Z is CO-A;
A is hydrogen, OR6, SR7, N(R8)R9;
Ri is H, OH, halogen or d-dalkyl,
R2 is H;
R3 is H, OH, CrC6alkyl, C3-C6cycloalkyl, haloCrC6alkyl, CrC6alkoxy, halod-C6alkoxy, formyl, or a 4-7-membered cyclic or d-dalkyl open-chained acetal or thioacetal thereof;
R4 is Cl;
R6, R7, R8 and R9 are independently H, CrC6alkyl, halod-C6alkyl, CrC6alkoxy, haloCrC6alkoxy, Cι-C alkoxycarbonyl, CrC alkanoylCrC alkyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-dalkyl, halo-CrC2alkyl, d-C2alkoxy, halo-d-C2alkoxy.
(15) Amongst group (14) those, wherein
A is OR6 or SR7;
R, and R2 are H;
R3 is CrC6alkyl, C3-C6cycioalkyl, CF3 or formyl;
R4 is Cl;
R6 and R7 are independently H, d-C6alkyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted with 1 to 2 substituents independently selected from halogen, d-dalkyl, halo-d-C2alkyl, d-C2alkoxy and halo-d-C2alkoxy.
Also preferred are the compounds of the tables.
The compounds of formula I may be prepared as outlined in the following reaction schemes.
Abbreviations: position to which the rest of the molecule is attached
Figure imgf000013_0001
Hal: halogen
L: leaving group, preferably chlorine, bromine, mesylate or tosylate.
R: a group which is inert under the reaction conditions
Scheme 1
Het-COOR Het-CH, Het-H
Figure imgf000014_0001
carbonylation
Het-CH2-Hal Het-CH2-COOR .;eductlon Het-CH(OH)-COOR e.g. CO/cat: cobalt-carbonyl e.g. Hj/cat
Of particular importance is the reaction step
Figure imgf000014_0002
1.1 1.1
wherein X, Y and R3 are as defined for formula I, which comprises reaction of a compound of formula 11.1 with carbon monoxide under pressure of 2-20 bars, preferably 5-10 bars, in presence of a catalyst, for example cobalt carbonyl and optionally a phase transfer catalyst.
Scheme 2
Figure imgf000014_0003
Scheme 3
Het
Figure imgf000015_0001
Scheme 4
Figure imgf000015_0002
Scheme 5
Figure imgf000015_0003
Figure imgf000015_0004
Th e functional groups of the compounds of formula I can be converted by known methods. For example, carboxylic acid derivatives can be converted as follows:
Scheme 6
Figure imgf000016_0001
thionating agent reduction -H20 e.g. H^cat e.g. Lawesson reagent e.g. SOCL
Figure imgf000016_0002
acetalisation with alcohol or glycol
Figure imgf000016_0003
Of importance are the syntheses of schemes 7 and 8
Scheme 7
Figure imgf000017_0001
Figure imgf000017_0002
Figure imgf000017_0003
Figure imgf000017_0005
Figure imgf000017_0004
Scheme 8
Figure imgf000018_0001
acetalisation reduction e.g. :LiAIH4
Figure imgf000018_0003
Figure imgf000018_0002
Figure imgf000018_0004
hydrolysis
Figure imgf000018_0005
Figure imgf000018_0006
E: optionally substituted C2-C5methylene
Of particular importance is the reaction step
Figure imgf000018_0007
II.A.1 I.A.1
which comprises reaction of a compound of formula II.A.1 with carbon monoxide under pressure of 2-20 bars, preferably 5-10 bars, in presence of a catalyst, for example cobalt carbonyl and optionally a phase transfer catalyst. Particulartly preferred is this reaction with compounds wherein R3 is d-C6alkyl, CF3 or an acetal group, and R4 is Cl.
Suitable bases, leaving groups, solvents and catalysts are known to the skilled person.
The thiazoles, isothiazoles and thiadiazoles can be synthesized by known methods or in analogy thereto according to the following references:
1.1 1.3-Thiazoles
Ahluwalia V. K. et a/, Heterocycles, 32, (1991), 907. Fukatsu H. et a/, Heterocycles, 29, (1989) 1517. Byers J. R.et a/, Org. Synthesis II, (1943) 31.
1.2 1 ,2-lsothiazoles
R. G. Micetich, Can J. Chem.; (1970), 48, 2006. Adams A., Slack, J. Chem. Soc. (1959) 3061. Buttimore D. et a/, J. Chem. Soc. (1963) 2032. Wooldrige K.R.H. Adv. Het. Chem. (1972), 14, 1.
1.3 1.2.3-Thiadiazoles
Hurd C. D., Mori E. J., J. Am. Chem. Soc, (1995), 5359. Ramsky S. I. et a/., Acta Pharm. Suecica 10, (1973), 285. Scheitauer S., Mayer R. Chem. Ber. 100, (1967), 1413. R. Raap, Can. J. Chem. (1968), 46. 2255.
The compounds of the invention can be used in the agricultural sector and related fields preventively and/or curatively. Besides their microbicidal properties, the compounds exhibit plant immunizing properties, i.e. plants can be protected by activation and stimulation of the plant's own defense system (immunization) which is known as "Systemic Activated Resistance" ("SAR").
Accordingly, with the compounds and methods of the invention, it is possible to control plant diseases on the one hand by strengthening the plant by activating its own defence system and on the other hand by additionally controlling the pathogens directly. The compounds offer a long lasting protection against a variety of pathogenes in different crops. The compounds I can also be used as dressings in the treatment of seed (fruit, tubers, grains) and plant cuttings to provide protection against fungus infections as well as against phytopathogenic fungi which occur in the soil.
The compounds I are effective, for example, against phytopathogenic fungi belonging to the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Moreover, they are effective against the classes of the Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and Oomycetes (e.g. Phyto- phthora, Pythium, Plasmopara).
Target crops to be protected within the scope of the present invention comprise e.g. the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, stone fruit 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 (marrows, cucumber, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocados, cinnamon, camphor); and plants such as tobacco, nuts, coffee, aubergines, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.
The compounds I are generally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession, with further compounds. These further compounds can be, for example, fertilisers or micronutrient donors or other preparations that influence plant growth. 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 other application- promoting adjuvants customarily employed in formulation technology. Suitable solvents, carriers and adjuvants are known to the skilled person. A preferred method of applying a compound of formula I, or an agrochemical composition comprising at least one of those compounds, is application to the leaves (foliar application). The frequency and rate of application depend upon the risk of infestation by the corresponding pathogen. The compounds I can, however, also penetrate the plant through the roots via the soil (systemic action) if the locus of the plant is impregnated with a liquid formulation or if the substances are introduced in solid form into the soil, e.g. in the form of granules (soil application). In paddy rice crops, such granules can be applied in metered amounts to the flooded rice field. In order to treat seed, the compounds I can, however, also be applied to the seeds (coating), either by impregnating the grains or tubers with a liquid formulation of the active ingredient, or by coating them with a solid formulation.
Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a. /ha, especially from 20 g to 600 g a.i./ha.
When the compounds are used as seed dressings, dosages of from 10 mg to 1 g of active ingredient per kg of seed are advantageously employed.
The agrochemical compositions generally comprise 0.1 to 99 % by weight, preferably 0.1 to
95 % by weight, of a compound of formula I, 99.9 to 1 % by weight, preferably 99.8 to 5 % by weight, of a solid or liquid adjuvant and 0 to 25 % by weight, preferably 0.1 to 25 % by weight, of a surfactant.
Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The compositions may also comprise further auxiliaries, such as stabilisers, antifoams, viscosity regulators, binders or tackifiers, as well as fertilisers or other active ingredients for obtaining special effects.
The compounds of formula I can be mixed with other fungicides, producing in some cases unexpected synergistic effects.
Especially preferred mixing partners are azoles, as azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazoie, metconazole, myclobutanil, pefurazoate, penconazole, pyrifenox, prochloraz, propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole; pyrimidinyl carbinoles, as ancymidol, fenarimol, nuarimol;
2-amino-pyrimidines, as bupirimate, dimethirimol, ethirimoi; morpholines, as dodemorph, fenpropidin, fenpropimo h, spiroxamin, tridemorph; aniiinopyrimidines, as cyprodinil, mepanipyrim, pyrimethanil; pyrroles, as fenpiclonil, fludioxonil; phenyiamides, as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace, oxadixyl; benzimidazoles, as benomyl, carbendazim, debacarb, fuberidazole, thiabendazole; dicarboximides, as chlozolinate, dichlozoline, iprodione, myclozoline, procymidone, vinclozolin; carboxamides, as carboxin, fenfuram, flutoianil, mepronil, oxycarboxin, thifluzamide; guanidines, as guazatine, dodine, iminoctadine; strobilurines, as azoxystrobin, kresoxim-methyl, SSF-126 (metominostrobin or fenominostrobin; SSF-129 (α-methoximino-N-methyl-2-[(2,5-dimethylphenoxy)methyl]- benzeneacetamide), trifloxystrobin (2-[α-{[(α-methyl-3-trifluormethyl-benzyl)imino]-oxy}-o- tolyl] -glyoxylsaure-methylester-O-methyloxim); dithiocarbamates, as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram;
N-halomethylthiodicarboximides, as captafol, captan, dichlofluanid, fluoromide, folpet, tolyfluanid; copper compounds, as bordeaux-mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, mancopper, oxine-copper; nitrophenol-derivatives, as dinocap, nitrothal-isopropyl; organo-P-derivatives, as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos, toiclofos-methyl; other compounds, as acibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran, diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone, fentin, ferimzone.fluazinam, flusulfamide, fenhexamid, fosetyl-aluminium, hymexazol, kasugamycin, methasulfocarb, pencycuron, phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforine, validamycin. Examples
A. Preparation Examples
Abbreviations: Me = methyl; Et = ethyl; Pr = n-propyl; i-Pr = isopropyl; Bu = n-butyl; i-Bu isobutyl; sec-Bu = sec-butyl; t-butyl = tert-butyl, Ph = phenyl; Ac = acetyl, THF = tetrahydrofuran; TPP = triphenylphosphine; Val = valine; m.p. = melting point
1. Compound No.1.1 (E)
Figure imgf000023_0001
A mixture of thiazole A (synthesized according to EP 0279239) (25.5 g, 0.1 1 Mol) and thionyl chloride (26.2 g, 0.22 Mol) in 25ml of toluene, is held at reflux for 1.5 hours. After, evaporation of the toluene under reduced pressure, 24 g of the acid chloride B (b.p 90-92°, 45mbar) is distilled through a Vigreux column.
To the acid chloride B (97.5 g, 0.39 Mol) in 11 dry tetrahydrofuran at -70°C under nitrogen atmosphere, NaAIH2(OCH2CH2OCH3)2 (commercial solution 3.5M in toluene, 0.429Mol), diluted in 300ml of toluene, is added dropwise. After 45min of stirring at -70°C, the cooling bath is removed and the reaction is quenched with 370 ml of 3.5N HCI is added. The organic phase extracted with ethyl acetate, dried over sodium sulfate, concentrated under reduced pressure and flash-chromatographed to afford 67.5g of the alcohol C as an oil. A mixture of alcohol C (60 g, 0.276 Mol) and thionyl chloride (98.5 g, 0828 Mol) in 400 ml of dichloromethane containing 0.1 ml of dimethyl formamide is stirred at reflux for 8 hours: Another portion of thionyl chloride (16.4 g, 0.138 Mol) is then added and the reaction heated for additional 16 hours. After the reaction is cooled down to room temperature, the solvent is removed under reduced pressure (60°C, 200 mbar) and the resulting crude yellow oil is distilled through a 5 cm Vigreux column (92-95°C, 20 mbar) to give 53.5 g of compound D as an colorless oil.
A mixture of compound D (125 g, 1.059 Mol), benzyltriethylammonium chloride (4.8 g, 0.042 Mol), cobalt carbonyl (7.2 g, 0.042 Mol), sodium carbonate (101 g, 2.4 Mol), 1.5 I of water and 1.361 of dichloromethane is stirred under carbon monoxide pressure (10 bars) for 24 hours at room temperature. The biphasic mixture is then filtered over celite, extracted two times with dichloromethane. The water phase is acidified with105 ml of concentrated HCI and extracted with ethyl acetate. The organic layer is then washed with brine, dried over sodium sulfate, treated with active charcoal at 60°C, filtered over celite and concentrated in vacuo to give 1 14 g of the acid E which is used without further purification.
2. Compound No 2.5 (J) (by Arndt-Eistert-reaction)
Figure imgf000024_0001
J
To compound G (2.0 g, 10.44 mmol) dissolved in 20 ml of dichloromethane at 0°C, is added oxalyl chloride (0.9 ml, 10.5 mmol). After the development of carbon dioxide stopped, 0.1 ml of dimethylformamide is added and the yellow suspension is stirred at room temperature for 3 hours. The resulting yellow solution is then concentrated under reduced pressure, dissolved in a mixture of 10 ml tetrahydrofuran and 10 ml acetonitrile, cooled down to 0°C, and successively treated with triethylamine (1.8 ml), trimethylsilyldiazomethane (commercial 2N solution in hexane) (6.05 ml, 13.05 mmol). After 12 hours of stirring at 0°C, the solvents are evaporated under reduced pressure, and the intermediate diazoketone G is rearanged in a mixture of 13 ml of benzylalcohol and 13 ml of trimethylpyridine at 180°C for 8 min. The dark mixture is cooled down to room tempature, diluted with ethyl acetate, washed 3 times with citric acid (10% aqueous solution). The ethyl acetate layer is dried over magnesium sulfate, filtered, evaporated under reduced pressure, and flash-chromatographed to give the compound J as an oil. 3. Compound No.1.2
Figure imgf000025_0001
2-Chloro-4-trifluoromethyl-5-acetic acid (10 g, 40.71 mmol) in 100 ml of methanol is heat- refluxed in presence of concentrated sulfuric acid (4 g, 40.71 mol) for 12hours. After cooling at room temperature, the methanol is distilled off under reduced pressure, the residue is dissolved in ethyl acetate, and successively washed with a saturated solution of sodium bicarbonate (3 times) and brine. After drying over magnesium sulfate, the ethyl acetate layer is filtered, evaporated under reduced pressure and flash-chromatographed on silica- gel to give 10.36g of the the title compound as a pale red oil.
4. Compound No.1.21
Figure imgf000025_0002
The acid chloride of comp. 1.2 (78.5 g, 0.2973 Mol) and L-Valine methyl ester hydrochloride are suspended in 600 ml of toluene, and heated at 110°C for 25 minutes. The resulting clear solution is cooled down to room temperature, extracted successively with water, a saturated solution of sodium bicarbonate, brine. The organic layer is then dried over sodium sulfate and the solvent removed under reduced pressure to give a crude oil which is chromatographed on silica-gel to afford 102g of the title compound (mp:51-53°C).
5. Compound No.1.76
Figure imgf000025_0003
A mixture of compound 1.2 (9 g, 34.7 mmol) and N-Bromosuccinimide (15.49 g, 87 mmol) in 200 ml of carbon tetrachloride, irradiated with a 150W quartz lamp is heated at reflux temperature. After 1.5 hours of stirring, the mixture is cooled down to room temperature and filtered over celite. After removal of the solvent under reduced pressure, the filtrate is suspended in hexane at 60°C and the solid filtered over celite. The hexane evaporated under reduced pressure to give a red oil, which after distillation (150°C, 0.13mbars) gives 10g of the title compound as a pale red oil.
6. Compound No. 1.97
Figure imgf000026_0001
A mixture of compound 1.76 (1 g, 2.9 mmol) and (0.63 g, 5.9 mmol) of benzylamin is stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture is removed under reduced pressure, and chromatographed on silica to give 0.8 g of the title compound as an oil.
7. Compound No.1.82
Figure imgf000026_0002
Compound 1.2 (1 g, 3.8 mmol) is added to a suspension of sodium hydride (55% in mineral oil) (0.17g, 4,2mmol) in tetrahydrofuran at -50°C, and the resulting red solution stirred for 1 hour at -35°C. After this period, methyl iodide (0.7 g, 5 mmol) is rapidly added. After 2 hours of stirring, the reaction is quenched with a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer is dried over magnesium sulfate, evaporated under reduced pressure and chromatographed on silica to give 0.72 g of the title compound as a pale yellow oil. 8. Compound No.1.92
Figure imgf000027_0001
Compound 1.2 (1 g, 3.8 mmol) is added to a suspension of sodium hydride (55% in mineral oil) (0.17 g, 4,2 mmol) in dry tetrahydrofuran at -50°C, and the resulting red solution stirred for 1 hr at -35°C. Methyl chloroformiate ( 6 mmol) is then added, and after 2hours of stirring, the reaction is quenched with a saturated aqueous ammonium chloride solution, and heated up to room temperature. After extraction with ethyl acetate, the organic layer is dried over magnesium sulfate, filtered and evaporated under reduced pressure. The reaction mixture is purified on silica to afford 0.79g of the title compound as a white solid.
9. Compound No. 1.99
Figure imgf000027_0002
To a suspension of sodium hydride (55% in mineral oil)(0.61 g, 25.4 mmol) at -50°C, is added compound 1.2 (3 g, 11.55 mmol). After 2.5 hours of stirring at -30°C, the red mixture is cooled down to -78°C, treated with methyliodide (4.92 g, 34,65 mmol), and slowly heated up to -20C over a period of 1.5hrs. After hydrolysis with a saturated aqueous ammonium chloride solution, the reaction mixture is extracted with ethyl acetate, dried over magnesium sulfate, and after evaporation of the solvent under reduced pressure, the resulting crude material is purified by flash-chromatography to give 2.06g of the title compound as an oil. 10. Compound No.1.100
Figure imgf000028_0001
To a tetrahydrofuran solution kept at -78°C of lithium diisopropylamide, prepared at 0°C from diisopropylamine (0.83 ml, 5.9 mmol) and n-butyl lithium (3.33 ml, 5.3 mmol), 2-chloro- 4-trifluoromethyl-thiazole is slowly added (1 g, 5.33 mmol). After 2 hours of stirring, the green solution is transferred, via a canula to a flask containing a solution of ethylglyoxylate (50% toluene commercial solution) (15ml, 10.6mmol) in tetrahydrofuran kept at -78°C. After 5 minutes, the mixture is treated with a saturated aqueous ammonium chloride solution, extracted with ethyl acetate and concentrated in vacuo. The resulting crude residue is then purified by chromatography on silica-gel to give 0.28 g of the title compound as an oil.
11. Compound No.1.106
Figure imgf000028_0002
2-chloro-4-trifluoromethyl-thiazole (0.5 g, 2,66 mmol) dissolved in tetrahydrofurane is treated at -78°C with lithium hexamethyldisilyamide (commercial solution, 1 M in tetrahydrofuran, 2,67ml), stirred for 1.5 hours, followed by the addition of ethylpyruvate (0.305 ml, 2.9 mmol). After the reaction is completed, it is quenched with a saturated aqueous ammonium chloride solution, extracted with ethyl acetate. The organic layer is dried over magnesium sulfate, concentrated under reduced pressure and chromatographed on silica-gel to afford 0.730 g of the title compound as a yellow oil. 12. Compound No. 1.113
Figure imgf000029_0001
2-Chloro-4-trifluoromethyl-thiazole (2 g, 10.66 mmol) dissolved in tetrahydrofuran is treated at -78°C with lithium hexamethyldisilyamide (commercial solution, 1 M in tetrahydrofuran, 2,67 ml), stirred for 1.5 hours, followed by the addition of ethylbromopyruvate (1.79 ml, 12.79 mmol). After the reaction is completed, it is quenched with a saturated aqueous ammonium chloride solution and heated up to room temperature. The reaction mixture is then extracted with ethyl acetate, the organic layer dried over magnesium sulfate, the solvent removed under reduced pressure, and the crude material chromatographed on silica-gel to afford 0.254g of 2.08g of the title compound as oils.
13. Compounds Nos. 2.18 (Q). 2.19 (R). 2.25 (S) (Scheme 13)
(a) A mixture of compound K (179 g, 0.871 Mol) NBS (159.8 g, 0.871 Mol) and Azoisobutyronitrile (AIBN) (14.6 g, 87 mmol) in 600 ml of CCI4 is heated at reflux for 16 hrs. After cooling, the crude mixture is filtered, concentrated under reduced pressure and flash- chromatographed to afford 190 g of compound L contaminated with the starting material K.
(b) To a solution of compound L (189.4 g, 0.666 Mol) in 1.5 I of acetonitrile, is added 0.3 I of 4A molecular sieves followed by N-methylmorpholine-N-oxide (139.2 g, 0.99 Mol). After 2.5 hrs. of stirring at room temperature, the mixture is filtered on silicagel, concentrated in vacuo and purified by flash-chromatography to give 92 g of aldehyde M.
(c) A solution of aldehyde L (91.25 g, 0.415 Mol), ethylene glycol (29 ml, 0.5 Mol) and p-toluenesulfonic acid (9.12 g, 41 mmol) is heated for 16 hrs. at reflux in 300 ml of benzene while water is destilled off. After cooling, the crude mixture is extracted with water and ether, the organic phase is then dried over MgSO , concentrated under reduced pressure and purified by flash-chromatography to give 65 g of the dioxolane N. Scheme 13
Figure imgf000030_0001
Figure imgf000030_0002
Figure imgf000030_0003
(d) To a suspension of LiAIH (1.78 g, 45.4 mmol) in 220 ml of dry THF at 0°C, is added dropwise compound N (10 g, 37.9 mmol) dissolved in 100 ml of THF. After 5 min of stirring the reaction is completed. The mixture is successively treated with 1.78 ml of water, 1.78 ml of NaOH (15% aqueous solution) and 5.34 ml of water. The suspension is then filtered over celite, extracted 3 times with ethylacetate and water. The combined organic phases are concentrated under reduced pressure and chromatographed on silica to afford 31 g of the alcohol O. (e) To a solution of compound O ( 9.85 g, 44.46 mmol) in 180 ml of CCI4 is added triphenlyphosphine (11.8 g, 44.46 mmol). The mixture is stirred at 85°C for 24 hrs. After cooling, the crude solution is concentrated under reduced pressure and purified by chromatography on silica to afford 6.4 g of compound P.
(f) A mixture of compound P (7.43 g, 30.9 mmol), benzyltriethylammonium chloride (283 mg, 1.24 mmol), cobalt carbonyl (423 mg, 1.24 mmol), sodium carbonate (5.83 g, 69.4 mmol), 68 ml of water and 62 ml of dichloromethane is stirred under carbon monoxide pressure (10 bars) for 24 hours at room temperature. The biphasic mixture is then filtered over celite, extracted two times with dichloromethane. The water phase is acidified to pH 2 with concentrated HCI and extracted with ethyl acetate. The organic layer is then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give 3.2 g of the acid Q which is used without further purification.
(g) A solution of the acid Q in THF is carefully treated at room temperature with an ether solution diazomethane. The reaction is monitored by tic. After completion of the reaction, the crude mixture is concentrated under reduced pressure and chromatographed to 2 g of the methylester R.
(h) Compound R (1.61 g, 6.47 mmol) is stirred for 40 min in 19 ml of THF, 19 ml of water and 9 ml of trifluoroacetic acid. After evaporation of the solvent, the crude mixture is diluted with ether and washed with NaHCO3 (sat. aqueous solution). The ether phase is concentrated under reduced pressure to afford the aldehyde S which is an oil. The aldehyde group may be converted by known methods into many different other groups.
Table 1.A
Table 1
Figure imgf000032_0001
No. Phys. data m.p °C
1.1. H H OH 122-123°C
1.2. H H OMe oil
1.3. H H oil
O-^— C02Et
1.4. H H Of-Bu oil
1.5. H H OCH2CH=CH2 oil
Figure imgf000032_0002
1.7. H H OCH2Ph oil
1.8. H H /=\ oil
OCH w // -OMe
1.9. H H solid
Figure imgf000032_0003
Figure imgf000032_0004
No. R2 Phys. data m.p °C
Figure imgf000033_0001
1.20. H H OCH2COMe oil
Figure imgf000033_0002
1.22. H H NMe2
1.23. H H NHMe
1.24. H H NHEt
1.25. H H NHn-Bu
1.26. H H NHt-Bu
Figure imgf000033_0003
No. Ri Phys. data m.p°C
Figure imgf000034_0001
1.33. H H r solid
NHCH_
Figure imgf000034_0002
1.35. H H solid
Figure imgf000034_0003
1.36. H H 115-6
NHCH ■,-<D
Figure imgf000034_0004
No. Phys. data m.p°C
Figure imgf000035_0001
1.45. H H solid
Figure imgf000035_0002
1.46. H H NHCH2Ph 110-1
Figure imgf000035_0003
1.48. H H MeO 115
NHCH.
< >
Figure imgf000035_0004
No. Ri Phys. data m.p °C
Figure imgf000036_0001
1.57. H H ONHCOOCH2Ph oil
1.58. H H ONHCH(CH3)2 oil
1.59. H H ONHC(CH3)3 oil
1.60. H H ON=C(CH3)OEt oil
1.61. H H ONHCOOC(CH3)3 oil
1.62. H H ONHCOOEt oil
1.63. H H ONHSO2Ph 114-20
1.64. H H NHOC(Ph)3 177
1.65. H H NHOCH2Ph 78-85
1.66. H H NHOMe 117-8
1.67. H H NHOCH2CH=CH2 73-4 ~N R~! R~ 2 A Phys. data m.p °C
1.68. H H NHOC(CH3)3 solid
1.69. H H NHOPh
1.70. H H F solid
NHOCH2— > F
1.71. H H SMe oil
1.72. H H SEt
1.73. H H SPh
1.74. H H SCH2Ph
1.75. Br H OH oil
1.76. Br H OMe oil
1.77. F H OH
1.78. F H OMe oil
1.79. Cl H OMe
1.80. Cl H OH
1.81. Me H OH oil
1.82. Me H OMe oil
1.83. Et H OMe oil
1.84. Et H OH oil
1.85. Pr H OH
1.86. Pr H OMe
1.87. nBu H OH
1.88. nBu H OMe
1.89. CH2CH-=CH2 H OH oil
1.90. CH2Ph H OH 127-8°C
1.91. CH2Ph H OMe oil
1.92. COOMe H OMe oil
1.93. CH2COOH H OH 130-1 oC
1.94. NH2 H OH 166-7°C
1.95. NH2.HCI H OMe 176-7°C
1.96. NEt2 H OMe 56-8°C No. Ri R2 A Phys. data m.p °C _
1.97. NHCH2Ph H OMe
1.98. Me Me OH 137-8°C
1.99. Me Me OMe oil
1.100. OH H OEt oil
1.101. OH H OH
1.102. OAc H OEt oil
Figure imgf000038_0001
i .iua. H OEt oil
/= *
0CO- J
1.104. OMe H OEt oil
1.105. OSi-t-BuMe2 H OEt oil
1.106. OH Me OEt oil
1.107. OH CF3 OMe oil
1.108. OH Ph OEt 77-9°C
1.109. OH CH2Br OEt oil
Figure imgf000038_0002
1.111. H OMe 151 -2°C
Figure imgf000038_0003
1.112. RI+R2 =O H OEt oil
1.113. R1+R2 H OEt oil
Figure imgf000038_0004
Table 1.B
Compounds of the formula
Figure imgf000039_0001
wherein the R1 t R2 and A have the meanings of the corresponding compounds of Table 1.A.
Table 1 ,C
Compounds of the formula
Figure imgf000039_0002
wherein R R2 and A have the meanings of the corresponding compounds of Table 1.A.
Phys. data of compound(s) of Table 1.C:
No. R, R2 A Phys. data m.p. °C
1.C.1 H H OH oil
Table 2.A
Figure imgf000040_0001
No Ri R3 Phys. data m.p.°C
2.1. H H H OCH2Ph oil
2.2. H H H OH
2.3. H H Me OCH2Ph oil
2.4. H H Me OH
2.5. H H Et OCH2Ph oil
2.6. H H Et OMe oil
2.7. H H Et OH 191 -3
2.8. H H n-Pr OMe oil
2.9. H H 2-Pr OMe oil
2.10. H H 2-Pr OH
2.11. H H cyclo-Pr OMe oil
2.12. H H t-Bu OMe oil
2.13. H H t-Bu OH
2.14. H H Ph OMe oil
2.15. H Ή CH2Ph OMe oil
2.16. H H 2-thiophenyl OMe oil
2.17. H H COOMe OMe oil
2.18. H H o— . OH oil
•O
2.19. H H OMe oil
A3
Figure imgf000041_0001
m.p.°C
Figure imgf000041_0002
2.21. H H s— v OH
2.22. H H s— OH
A s —
2.23. H H s^ OH
AJ
Figure imgf000041_0003
2.25. H H CCHHOO OOMMee oil
2.26. H H CCHH22OOHH OOMMee solid
2.27. H H CCHH22CCII OOMMee oil
2.28. H H CH2Br OMe
2.29. H H CH2F OMe
2.30. H H CH2NHCOO- OMe t-Bu
2.31. H H CH2NEt2 OMe
2.32. H H CH2NH2 OMe
2.33. H H CH2NHOH OMe
2.34. H H CH=CH2 OMe
2.35. H H CH=CHCOOMe OMe
2.36. H H CH=CHMe OMe
2.37. H H CH=CBr2 OMe
2.38. H H CHOHMe OMe
2.39. H H CHOHEt OMe
2.40. H H CHOHCIMe OMe
2.41. H H CHOHFMe OMe
2.42. H H CHOHBrMe OMe
Figure imgf000042_0001
m.p.°C _
2.43. H CH=CF2 OMe
2.44. H H COEt OMe
2.45. H H CHOHMe OMe
2.46. H H CHCIMe OMe
2.47. H H CHFMe OMe
2.48. H H CHBrMe OMe
2.49. H H 4-CI-Ph OMe
2.50. H H 3-MeO-Ph OMe
2.51. H H 2,4-Me2-Ph OMe
2.52. H H — _ OMe
2.53. Br H COHMe2 OCH2Ph
2.54. Br H COHEt2 OH
2.55. F H Et OCH2Ph
2.56. Cl H Et OH
2.57. Cl H n-Pr OCH2Ph
2.58. Me H 2-Pr OMe
2.59. Et H cyclo-Pr OH
2.60. Et H t-Bu OMe
2.61. Pr H t-Bu OMe
2.62. Pr H Ph OH
2.63. nBu H CH2Ph OMe
2.64. nBu H 2-thiophen OMe
2.65. CH2CH=CH2 H COOMe OH
2.66. CH2Ph H OMe
-0
2.67. CH2Ph H OMe
-0
2.68. COOMe H OMe o ' No Phys.data m.p.°C
2.69. CH2COOH H OMe
■o
2.70. NH2 H OMe
Figure imgf000043_0001
2.73. NHCH2Ph H CHO OCH2Ph 2.74. Me H CH2OH OH 2.75. Me H CH2CI OCH2Ph 2.76. OH H CH2Br OMe 2.77. OH H CH2F OH 2.78. OAc H CHCI2 OMe
Figure imgf000043_0002
2.80. OMe H Me OH 2.81. OSi-t-BuMe2 H Me OMe 2.82. OH H Et OMe 2.83. OH H Et OH 2.84. OH H Et OMe 2.85. OH H n-Pr OMe 2.86. VF' CF3 2-Pr OMe
Figure imgf000043_0003
2.88. R1+R2 =O CH2Br cyclo-Pr OMe
Figure imgf000044_0001
m.p.°C
Figure imgf000044_0002
2.90. H H cyclo-Pr OCH2Ph oil
Table 2.B
Compounds of the formula
Figure imgf000044_0003
wherein R,, R2, R3 and A have the meanings of the corresponding compounds of Table 2.A.
Table 2.C
Compounds of the formula
Figure imgf000044_0004
wherein R1 t R2, R3 and A have the meanings of the corresponding compounds of Table 2.A.
Phys. data of compounds of Table 2.C:
Figure imgf000044_0005
m.p.°C
2.C.3 H H Me OCH2Ph oil
2.C.5 H H Et OCHsPh oil
2.C.7 H H Et OH oil
2.C.20 H H OH solid
Figure imgf000044_0006
2.C.90 H H cyclo-Pr OCH2Ph oil Table 3.A
Figure imgf000045_0001
No. Ri R2+ Z R3 Phys. data m.p.°C
Figure imgf000045_0002
Figure imgf000045_0003
3.3. H CF3 solid
3.4. H CF3 solid
Figure imgf000045_0004
Figure imgf000045_0005
No. Ri R2+Z Phys. data m.p.°C
Figure imgf000046_0001
No. Ri R2+ Z Phys. data m.p.°C
Figure imgf000047_0001
3.19. H cyclo-Pr
Figure imgf000047_0002
Figure imgf000047_0003
Table 3.B
Compounds of the formula
Figure imgf000048_0001
wherein R1 t R2, R3 and Z have the meanings of the corresponding compounds of Table 3.A.
Table 3.C
Compounds of the formula
Figure imgf000048_0002
wherein Ri, R2, R3 and Z have the meanings of the corresponding compounds of Table 3. A.
Table 4.A
Figure imgf000049_0001
No. Ri R2 R3 R4 Z Phys.data m.p.°C
4.1. H H CF3 Ph COOMe oil
4.2. H H Me CF3 COOH
4.3. H H CF3 H COOH
4.4. H H CF3 H COOMe oil
4.5. H H Me H COOEt solid
4.6. R!+R2 =O Me H COOEt solid
4.7. Rι+R ; =O Me NHCOOEt COOEt solid
4.8. Rι+R2 =O Me NHn-Bu COOEt solid
4.9. R1+R2 =O Me NHt-Bu COOEt solid
4.10. H H Me NHMe COOEt solid
4.11. H H Me NHCH2CH=CH2 COOH solid
4.12. H H Et NH-t-Bu COOEt solid
4.13. H H Ph p-PhSO2NH2 COOEt solid
4.14. H H p-CIPh NHPh COOEt solid
4.15. H H OH OH COOH solid
4.16. R!+R2 =O Me NH-COOEt COSMe
4.17. R1+R2 =O Me NH-n-Bu COSMe
4.18. R1+R2 =O Me NH-t-Bu COSMe
4.19. H H CF3 CF3 COSMe
4.20. H H CF3 OMe COOMe
4.21. H H CF3 OEt COOMe
4.22. H H CF3 O-n-Pr COOMe
4.23. H H CF3 SMe COOMe
4.24. H H CF3 SEt COOMe No. Ri R2 R3 R4 Z Phys.data m.p.°C
4.25. H H CF3 SPh COOMe
4.26. H H CF3 NMe2 COOMe
4.27. H H CF3 NEt2 COOMe
4.28. H H CF3 NH2 COOMe
4.29. H H CF3 SH COOMe
4.30. H H CF3 NH2 CSOMe
4.31. H H Me Cl solid
Figure imgf000050_0001
4.32. H H CF3 Ph CSOMe
4.33. H H Me CF3 CSOH
4.34. H H CF3 H CSOH
4.35. H H CF3 H CSOMe
4.36. H H Me H CSOEt
4.37. R!+R2 =S Me H COOEt
4.38. R1+R2 =S Me NHCOOEt COOEt
4.39. R1+R2 =S Me NH-n-Bu CSOEt
4.40. R1+R2 =S Me NH-t-Bu CSOEt
4.41. H H Me NHMe CSOEt
4.42. H H Me NHCH2CH=CH2 CSOH
4.43. H H Et NHt-Bu CSOEt
4.44. H H Ph p-PhSO2NH2 CSOEt
4.45. H H p-CIPh NHPh CSOEt
4.46. H H OH OH CSOH
4.47. R!+R2 =O Me NH-COOEt CSSMe
4.48. R1+R2 =O Me NHn-Bu CSSMe
4.49. Rι+R2 =S Me NHt-Bu CSSMe
4.50. H H Et CF3 COSMe
4.51. H H Et OMe COOMe
4.52. H H n-Pr OEt COOMe
4.53. H H i-Pr n-Pr COOMe
4.54. H H OH SMe COOMe No. Ri R2 R3 FU Z Phys.data m.p.°C
4.55. H H OH SEt COOMe
4.56. H H CF3 SPh CONHMe
4.57. H H CF3 NMe2 CONHMe
4.58. H H CF3 NEt2 CONHMe
4.59. H H CF3 NH2 CSNHMe
4.60. H H CF3 SH CSNHMe
4.61. H H CF3 CSNHMe
Table 4.B
Compounds of the formula
Figure imgf000051_0001
wherein Ri, R2, R3, R and Z have the meanings of the corresponding compounds of Table 4.A.
Table 4.C
Compounds of the formula
Figure imgf000051_0002
wherein R1 ( R2, R3 and Z have the meanings of the corresponding compounds of Table 4.A.
Formulation Examples for similar purposes of pesticidal use are descibed for example in WO 97/33890. Biological Examples
Example B.1 : Immunization of Cucumis sativus L against Colletotrichum laαenarium a) After a cultivation period of 2 weeks, cucumber plants are sprayed with a spray mixture prepared from a wettable powder formulation of the test compound (concentration:
200 ppm). After 72 hours, the plants are infected with a spore suspension (1.0 x 105 spores/ml) of the fungus and incubated for 30 hours at high humidity and a temperature of
23°C. Incubation is then continued at normal humidity and 22°C to 23°C.
Evaluation of protective action is made 7 to 8 days after infection and is based on fungus infestation. b) After a cultivation period of 2 weeks, cucumber plants are treated by soil application with a spray mixture prepared from a wettable powder formulation of the test compound (concentration: 20 ppm, based on the volume of the soil). After 72 hours, the plants are infected with a spore suspension (1.5 x 105 spores/ml) of the fungus and incubated for
30 hours at high humidity and a temperature of 23°C. Incubation is then continued at normal humidity and 22°C.
Evaluation of protective action is made 7 to 8 days after infection and is based on fungus infestation.
Compounds of the Tables exhibit good activity in tests (a) and (b) and reduce fungus infestation to 0 to 20 %. On the other hand, Colletotrichum infestation is 90 % on untreated and infected control plants.
c) Comparison test: Direct action against Colletotrichum laαenarium
The formulated active ingredient is mixed in various concentrations (100, 10, 1 , 0.1 ppm) with autoclaved and cooled nutrient medium containing 10 000 spores per ml and is poured into microtitre plates. Incubation is then carried out at 22°C in the dark. After 2 to 3 days, fungus growth is measured by spectrophotometry.
With compounds of the Tables, no inhibition of fungus growth is observed; on the other hand, when the fungicide "Benomyl" (commercial product) is used as comparison substance at 0.2 ppm, 50 % inhibition (EC50) of fungus growth occurs. is.
- 51 -
Example B.2: Action against Phvtophthora infestans on tomato plants a) After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture prepared from a wettable powder formulation of the test compound (0.02 % active ingredient). After 72 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 5 days at 90-100 % relative humidity and 20°C.
Compounds of the Tables exhibit good activity in the tests and reduce fungus infestation to 0 to 20 %. On the other hand, Phytophthora infestation is 60 % on untreated and infected control plants.
Example B.3: Action against Pyricularia orvzae on rice plants
2-week-old rice plants are watered with a spray mixture prepared from a wettable powder formulation of the test compound (0.006 % active ingredient, based on the volume of the soil). The pots are then filled with water until the lowermost parts of the stems of the rice plants are standing in water. After 96 hours, the treated rice plants are infected with a conidia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 5 days at 95-100 % relative humidity and approximately 24°C. In comparison with untreated control plants (100 % infestation), fungus infestation on rice plants treated with a spray mixture comprising a compound of the Tables as active ingredient is only approximately 50 %.
Example B.4: Action against Cercospora nicotina on tobacco plants a) Foliar application
Tobacco plants (8 weeks old) are sprayed with a formulated solution of the test compound (concentration: 0.02 % active ingredient). Four days after treatment, the plants are inoculated with a sporangia suspension of Cercospora nicotina (150 000 spores/ml), kept for 5 days in the dark at 25°C and high humidity and then incubated further under a normal day/night sequence.
Evaluation of the symptoms in the tests is based on the leaf surface infested with fungus. Infestation is approximately 60 % on the control plants; on plants treated with compounds of the Tables, infestation is 0 to 30 %. Example B.5: Action against Ervsiphe graminis on wheat
Protective action: 18-day-old wheat plants are sprayed with a formulated solution of the test compound (0.02 % active ingredient). Immediately after the treatment the plants are incubated under cylinders. 24 hours later, the plants are covered. After a further 3 days, the treated plants are cut off above the primary leaf. The primary leaves are arranged horizontally and are inoculated in a dusting bell with Erysiphe graminis spores (spore density: 0.2 mg/m2). The test is carried out in a climatic chamber with 12 hours of light (18 KLux), at 20°C and 12 hours of darkness, at 18°C. infestation is evaluated 9 and 13 days after inoculation.
Compounds of the Tables exhibit good activity in the tests and reduce fungus infestation to 0 to 20 %. On the other hand, Erysiphe infestation is 70 % on untreated and infected control plants.

Claims

Claims
1. A process for protecting and immunizing plants against attack by phytopathogenic microorganisms which comprises applying a compound of formula I as active ingredient to the plants, to parts of the plants and/or to the locus of the plants
Figure imgf000055_0001
wherein a) X is CR4 and Y is N; or b) X is N and Y is CR5; or c) X and Y are N; and wherein
Z is a Ci-group to which 1-3 halogen atoms or 1-3 unsubstituted or substituted hetero atoms selected from the group O, S and N are bonded;
Ri and R2 are independently H, OH, SH, CN, COOH, NO2, NH2, halogen, d-C6alkyl, haloC C6alkyl, alkoxyCι-C6alkyl, aminoCι-C6alkyl, alkoxaminoCι-C6alkyl, d-Cealkoxy, halo- Cι-C6alkoxy, Cι-C6alkanoyloxy, aroyloxy, d-Cβalkoxycarbonyl, aryloxycarbonyl, benzyloxy- carbonyl, CrC6alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, Cι-C6alkylamino- carbonyl, Cι-C6dialkylaminocarbonyl, C .C6alkylthio, haloC C6alkylthio, Cι-C6alkylsulfinyl, haloCrC6alkylsulfinyl, Cι-C6alkylsulfonyl, haloCι-C6alkylsulfonyl, arylsulfinyl, arylsulfonyl, C2-C6alkenyl, haloC2-C6alkenyl, C2-C6alkinyl, carboxyCrC6alkyl, alkoxycarbonylCrC6alkyl, haloalkoxycarbonylCι-C6alkyl, C3-C6cycloalkyl, alkanoylCι-C6alkyl, alkylcarbonyloxy- Cι-C6alkyl, phenylcarbonyloxyCrC6alkyl, Cι-C6alkylamino, Cι-C6dialkylamino, C2-C6alkenylamino, d-Cβalkanoylamino, CrCβalkoxycarbonyiamino, benzylamino, benzoylamino, benzyloxyarbonylamino, phenyl, phenoxy, benzyl or phenethyi, wherein all the aromatic groups are unsubstituted or substituted from 1 to 5 substituents independently selected from halogen, hydroxy, C C alkyl, halo-CrC2alkyl, C C2alkoxy, halo-Cι-C2alkoxy and nitro; or optionally substituted heterocyclyl; or tri(Cι-C6alkyl)silyl or tri(Cι-C6alkyl)silyloxy; with the proviso that Ri and R2 are not simultaneously a group selected from OH, SH, NO2, NH2, CrC6alkylamino, Cι-C6dialkylamino and C2-C6alkenylamino; or Ri and R2 together are =O or =S; or
Ri and R2 together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 8 membered isocyclic or heterocyclic ring; or
R2 and Z together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 7 membered lactone, lactame, thiolactone or thiolactame, which ring may have 1 to 2 additional hetero atoms selected from the group O, S and N; R3, R4 and R5 are independently H, OH, SH, CN, NO2, NH2, halogen, Cι-C6alkyl, halo- Cι-C6alkyl, hydroxyCι-C6alkyl, alkoxyCrC6alkyl, aminod-Cβalkyl, alkoxaminod-C6alkyl, Cι-C6alkoxy, d-C6alkylthio, halod-C6alkylthio, d-C6alkylsulfinyl, halod-C6alkylsulfinyl, Cι-C6alkylsulfonyl, halod-C6alkylsulfonyl, halo-Cι-C6alkoxy, C2-C6alkenyl, haioC2-C6alkenyl, C2-C6alkinyl, carboxyCrC6alkyl, d-C6alkanoyl, d-C6alkoxycarbonyl, alkoxycarbonyl- Cι-C6alkyl, haloalkoxycarbonyld-C6alkyl, C3-C6cycloalkyl, alkanoylCι-C6alkyl, alkylcarbonyloxyCι-C6alkyi, phenylcarbonyloxyCι-C6alkyl, Cι-C6alkylamino, Cι-C6dialkylamino, C2-C6alkenyiamino, C -C6alkanoylamino, Cι-C6alkoxycarbonylamino, benzylamino, benzoylamino, phenyl, phenoxy, benzyl or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, hydroxy, Cι-C alkyl, halo-Cι-C2alkyi, d-C2alkoxy, halo-Cι-C2alkoxy and nitro; or optionally substituted heterocyclyl.
2. A compound of formula I
Figure imgf000056_0001
wherein a) X is CR4 and Y is N; or b) X is N and Y is CR5; or c) X and Y are N; and wherein
Z is a d-group to which 1-3 halogen atoms or 1-3 unsubstituted or substituted hetero atoms selected from the group O, S and N are bonded;
R, and R2 are independently H, OH, SH, CN, COOH, NO2) NH2, halogen, d-C6alkyl, haloCι-C6alkyl, alkoxyd-C6alkyl, aminod-C6alkyl, alkoxaminod-C6alkyl, d-C6alkoxy, halo- Cι-C6alkoxy, Cι-C6alkanoyloxy, aroyloxy, d-C6alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, d-C6alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, Cι-C6alkylaminocarbonyI, Cι-C6dialkylaminocarbonyl, d.C6alkylthio, haloCι-C6alkylthio, Cι-C6alkylsulfinyl, haloCrC6alkylsulfinyl, Cι-C6alkylsulfonyl, halod-C6alkylsulfonyl, arylsulfinyl, arylsulfonyl, C2-C6alkenyl, haloC2-C6alkenyl, C2-C6alkinyl, carboxyd-C6alkyl, alkoxycarbonylCι-C6alkyl, haloalkoxycarbonylCι-C6alkyl, C3-C6cycloalkyl, alkanoylCι-C6aikyl, alkylcarbonyloxyCι-C6alkyl, phenylcarbonyloxyCι-C6alkyl, d-C6alkylamino, Cι-C6dialkylamino, C2-C6alkenylamino, CrC6alkanoylamino, Cι-C6alkoxycarbonylamino, benzylamino, benzoylamino, benzyloxyarbonylamino, phenyl, phenoxy, benzyl or phenethyi, wherein all the aromatic groups are unsubstituted or substituted from 1 to 5 substituents independently selected from halogen, hydroxy, d-C alkyl, halo-Cι-C2alkyl, Cι-C2alkoxy, halo-Cι-C2alkoxy and nitro; or optionally substituted heterocyclyl; or tri(Cι-C6alkyl)silyl or tri(Cι-C6alkyl)silyloxy; with the proviso that Ri and R2 are not simultaneously a group selected from OH, SH, NO2, NH2, Cι-C6alkylamino, d-C6dialkylamino and C2-C6alkenylamino; or Ri and R2 together are =O or =S; or
Ri and R2 together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 8 membered isocyclic or heterocyclic ring; or
R2 and Z together with the carbon atom to which they are bonded are an unsubstituted or substituted 3 to 7 membered lactone, lactame, thiolactone or thiolactame, which ring may have 1 to 2 additional hetero atoms selected from the group O, S and N; R3, R4 and R5 are independently H, OH, SH, CN, NO2, NH2, halogen, C -C6alkyl, haloCι-C6alkyl, hydroxyd-C6alkyl, alkoxyCι-C6alkyl, aminoCι-C6alkyl, alkoxaminod-C6alkyi, C -C6alkoxy, C C6alkylthio, haloCι-C6alkylthio, d-C6alkylsulfinyl, halod-C6alkylsulfinyl, Cι-C6alkylsulfonyl, halod-C6alkylsulfonyl, halo-CrC6alkoxy, C2-C6alkenyl, haloC2-C6alkenyl, C2-C6alkinyl, carboxyd-C6alkyl, d-C6alkanoyl, d-C6alkoxycarbonyl, alkoxycarbonylCι-C6alkyl, haloalkoxycarbonyld-C6alkyl, C3-C6cycloalkyl, alkanoyld-C6alkyl, alkylcarbonyloxyCι-C6alkyl, phenylcarbonyloxyd-C6alkyl, Cι-C6alkylamino, Cι-C6dialkylamino, C2-C6alkenylamino, d-C6alkanoylamino, d-C6alkoxycarbonylamino, benzylamino, benzoylamino, phenyl, phenoxy, benzyl or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, hydroxy, d-C alkyl, halo-d-C2alkyl, Ci-Cjalkoxy, halo-d-C2alkoxy and nitro; or optionally substituted heterocyclyl; with the exception of the compounds of the formula
5in a) Ri is OCO-CH3 and T is Br,
Figure imgf000058_0002
c) R, is OH and T is H.
3. A compound according to claim 2 of formula I.A
Figure imgf000058_0003
4. A compound according to claim 2 of formula I.B
Figure imgf000058_0004
5. A compound according to claim 2 of formula I.C
Figure imgf000059_0001
6. A compound according to claim 2 wherein Z is CN, CO-A, CS-A or CH(OR10)2.;
A is hydrogen, halogen, OR6, SR7, N(R8)R9, ON(Rn)Rι2 or N(Rι3)OR14;
R6 to Rι are independently hydrogen, an unsubstituted or substituted, open-chained, saturated or unsaturated hydrocarbon radical containing up to 8 carbon atoms, an unsubstituted or substituted, cyclic, saturated or unsaturated hydrocarbon radical containing up to 10 carbon atoms, unsubstituted or substituted benzyl or phenethyi, an unsubstituted or substituted acyl group containing up to 8 carbon atoms, an unsubstituted or substituted benzoyl group, or an unsubstituted or substituted heterocyclyl radical; or
R8 and R9, or Rn and Rι2, together with the nitrogen atom to which they are bonded, form a
5- or 6-membered, unsubstituted or substituted heterocycle having 1 to 3 hetero atoms selected from O, S and/or N;
Rio are identical or different and are d-C6alkyl that is unsubstituted or substituted by phenyl, Cι-C2alkoxy, phenoxy or by benzyloxy; or two substituents OR10, together with the carbon atom to which they are bonded, form a cyclic acetal group that is unsubstituted or substituted by Cι-C3alkyl, phenyl, benzyl, hydroxy or by d-C3hydroxyalkyl.
7. A compound according to claim 2 wherein
Ri is H, OH, NH2, halogen, COOH, d-C4alkyl, haloCι-C4alkyl, d-C4alkoxy, C.- dalkanoyioxy, aroylyloxy, Cι-C4alkoxycarbonyl, aryloxycarbonyl, benzyloxycarbonyl, Cι-C alkylcarbonyl, arylcarbonyl, benzylcarbonyl, aminocarbonyl, Cι-C4alkylaminocarbonyl, Cι-C4dialkylaminocarbonyl, alkanoyld-dalkyl, alkylcarbonyloxyd-C alkyl, C2-C4alkenyl, haloC2-C alkenyl, Cι-C4alkyiamino, d-C4dialkylamino, d-dalkanoylamino, d- dalkoxycarbonylamino, benzylamino, benzoylamino, phenyl, phenoxy, benzyl or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, hydroxy, d-dalkyl, halo-d-C2alkyl, d-C2alkoxy, halo-d-C2alkoxy and nitro;
R2 is H, OH, C C alkyl, C C4alkoxy or phenyl; or
Ri and R2 together are a group selected from
Figure imgf000060_0001
R2+Z together are a group selected from
Figure imgf000060_0002
wherein Rι7, Rι8 and R19 are independently H or d-C4alkyl;
R3 is H, halogen, CrC6alkyl, haloCrC6alkyl, C3-C6-cycloalkyl, Cι-C4 alkoxycarbonyl, phenyl which is unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-C4alkyl, halo-Cι-C2alkyl, Cι-C2alkoxy, halo-d-C2alkoxy, amino,
Cι-C4alkylamino, Cι-C4dialkylamino, benzylamino, d-dalkanoylamino, benzoylamino,
Cι-C4alkoxycarbonylamino, formyl, or a 4-7-membered cyclic or d-C alkyl open-chained acetal or thioacetal thereof;
R4 is H, OH, halogen, amino, d-C6alkyl, Cι-C4alkylamino, Cι-C4alkenylylamino, d-ddialkylamino, benzylamino, Cι-C4alkanoylamino, benzoylamino,
Cι-C4alkoxycarbonylamino.
8. A compound according to claim 3 of formula I.A
Figure imgf000061_0001
wherein
Z is CO-A;
A is hydrogen, OR6, SR7, N(R8)R9;
Ri is H, OH, halogen or Cι-C4alkyl,
R2 is H;
R3 is H, OH, Cι-C6alkyl, C3-C6cycloalkyl, haloC C6alkyl, Cι-C6alkoxy or haloCrC6alkoxy, formyl, or a 4-7-membered cyclic or Cι-C4alkyl open-chained acetal or thioacetal thereof;
R4 is Cl;
Re, R7, Re and R9 are independently H, d-C6alkyl, halod-C6alkyl, d-C6alkoxy, haloCι-C6alkoxy, CrC4alkoxycarbonyl, Cι-C alkanoylCι-C4alkyl, C3-C6cycloalkyl,
C3-C6cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-dalkyl, halo-d-C2alkyl, d-C2alkoxy, halo-Cι-C2alkoxy.
9. A process for the preparation of a compound of formula 1.1
Figure imgf000061_0002
11.1 1.1
wherein X, Y and R3 are as defined for formula I, which comprises reaction of a compound of formula 11.1 with carbon monoxide under pressure of 2-20 bars in presence of a catalyst.
10. A composition for protecting and immunizing plants against attack by microorganisms, comprising a compound of formula I of claim 1 together with a suitable carrier. AMENDED CLAIMS
[received by the International Bureau on 09 June 1999 (09.06.99); original claims 2 and 10 amended; remaining claims unchanged (4 pages)]
A) with the exception of the compounds of the formula
Figure imgf000062_0001
wherein a) Ri is OCO-CH3 and T is Br,
Figure imgf000062_0002
and
B) with the exception of thiadiazole derivatives having the formula
Figure imgf000062_0003
wherein R' is methyl or phenyl,
H„C
A is CH2, CHCI, CHCH3, C(CH3)2, CH-C6H5, X ] , and
B is CHO, CN, COOH, COOCH3, COOC2H5, COOC3H7(iso), COOC8Hι7(n), COOCH2CH=CH2, CONH2, CONHCH3, CONHC3H7(iso), CON(CH3)2, pyrrolidinoyi, morpholinoyi, 4-methoxicarbonyi-piperazinoyl, 4-oxo-piperidinoyl, CH(SCH3)(SOCH3), CONH-C6H4-OCH3(4) or CON(CH3)C6H5; and
C) with the exception of thiazolyl derivatives having the formula
Figure imgf000063_0001
wherein
R20 is hydrogen, CH3, C2H5,
R21 is hydrogen, CH3, C2H5,
R2 is hydrogen, C C3alkyl, n-C H9, Cl or Br,
R23 is hydrogen, CH3, C2H5, or
R22 and R23 together with the ring to which they are attached form a condensed six- membered carbocyclic aromatic ring which may be monochlorinated, and
G represents CH or N; and
D) with the exception of 7-(1 ,2,3-thiadiazolyl-5-acetamido)-3-(5-methyl-1 ,3,4-thiadiazol-2- ylthiomethyl)-3-cephem-4-carboxylic acid.
3. A compound according to claim 2 of formula I.A
Figure imgf000063_0002
4. A compound according to claim 2 of formula I.B.
Figure imgf000064_0001
Figure imgf000065_0001
wherein
Z is CO-A;
A is hydrogen, OR6, SR7, N(R8)R9;
Ri IS H, OH, halogen or d-C4alkyl,
R2 is H;
R3 is H, OH, Cι-C6alkyl, C3-C6cycloalkyl, haloC C6alkyl, d-C6alkoxy or haloCι-C6alkoxy, formyl, or a 4-7-membered cyclic or Cι-C alkyl open-chained acetal or thioacetal thereof;
R4 is Cl;
R6, R7, R8 and R9 are independently H, d-C6alkyl, halod-C6alkyl, d-C6alkoxy, haloCι-C6alkoxy, CrC4alkoxycarbonyl, Cι-C4alkanoyld-C4alkyl, C3-C6cycloalkyl,
C3-C6cycloalkylmethyl, phenyl, benzyl, or phenethyi, the phenyl rings of which are unsubstituted or substituted from 1 to 3 substituents independently selected from halogen, d-dalkyl, halo-d-C2alkyl, C C2alkoxy, halo-d-C2alkoxy.
9. A process for the preparation of a compound of formula 1.1
Figure imgf000065_0002
11.1 1.1
wherein X, Y and R3 are as defined for formula I, which comprises reaction of a compound of formula 11.1 with carbon monoxide under pressure of 2-20 bars in presence of a catalyst.
10. A composition for protecting and immunizing plants against attack by microorganisms, comprising a compound of formula I of claim 2 together with a suitable carrier. STATEMENT UNDER ARTICLE 19
The amendments effected in claim 2 will restore the novelty by way of disclaimer. They take the following references of the International Search Report into account:
- WO 98 14437 A (NIHON NOHYAKU Co., Ltd.)
Examples 307 to 321, 325, 327 to 331, 335, 336, 347, 383, 384 and 385 (identical to 422); [disclaimer B]
- DE 19 53 861 A (Fujisawa Pharmaceutical Co. Ltd.)
Example 16, which is identical to DE 22 62 262, example 65; [disclaimer D]
- DE 22 62 262 A (Fujisawa Pharmaceutical Co. Ltd.)
Example 65, which is identical to DE 19 53 861 A, example 16; [disclaimer D]
- EP 0 213 079 A (Ciba-Geigy AG)
Compounds Nos. 1.01 to 1.22, 1.50 to 1.54, 3.01 to 3.22, 3.58 and 3.59. [disclaimer C]
PCT/EP1998/008335 1997-12-22 1998-12-18 Thiazole-, isothiazole- and thiadiazole-derivatives having microbicidal and plant immunizing activities WO1999032464A1 (en)

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WO2009030450A2 (en) 2007-09-03 2009-03-12 Syngenta Limited Novel herbicides
US7759373B2 (en) 2001-04-16 2010-07-20 Mitsubishi Tanabe Pharma Corporation Large conductance calcium-activated K channel opener
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WO2001087863A1 (en) * 2000-05-15 2001-11-22 Basf Aktiengesellschaft 3-arylisothiazoles and their use as herbicides
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US7087623B2 (en) 2001-04-17 2006-08-08 Sepracor Inc. Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof
EP2527333A1 (en) 2007-06-28 2012-11-28 Syngenta Limited Pyrandione, thiopyrandione and cyclohexanetrione compounds having herbicidal properties
WO2009030450A2 (en) 2007-09-03 2009-03-12 Syngenta Limited Novel herbicides
US9018411B2 (en) 2009-12-07 2015-04-28 Cardioxyl Pharmaceuticals, Inc. Bis-acylated hydroxylamine derivatives
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CN108752287A (en) * 2018-05-21 2018-11-06 南开大学 The preparation method and purposes of heterocycle tertiary alcohol derivative
CN108912108A (en) * 2018-06-27 2018-11-30 中国科学院上海有机化学研究所 Trifluoromethyl compound and preparation method thereof and its application in pesticide
CN108912108B (en) * 2018-06-27 2021-09-03 中国科学院上海有机化学研究所 Trifluoromethyl compound, preparation method thereof and application thereof in pesticide

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