WO2014075874A1 - Microbiocidal pyrazole derivatives - Google Patents

Microbiocidal pyrazole derivatives Download PDF

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WO2014075874A1
WO2014075874A1 PCT/EP2013/071985 EP2013071985W WO2014075874A1 WO 2014075874 A1 WO2014075874 A1 WO 2014075874A1 EP 2013071985 W EP2013071985 W EP 2013071985W WO 2014075874 A1 WO2014075874 A1 WO 2014075874A1
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alkyl
formula
optionally substituted
halogen
independently
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PCT/EP2013/071985
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French (fr)
Inventor
Sarah Sulzer-Mosse
Fredrik Cederbaum
Werner Zambach
Martin Pouliot
Clemens Lamberth
Laura Quaranta
Farhan BOU HAMDAN
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Syngenta Participations Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • 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
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/20—Spiro-condensed systems

Definitions

  • the present invention relates to microbiocidal pyrazole derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity.
  • the invention also relates to preparation of these pyrazole derivatives, to pyrazole derivatives used as intermediates in the preparation of these pyrazole derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the pyrazole derivatives, to preparation of these compositions and to use of the pyrazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.
  • the present invention provides compounds of formula I:
  • G 1 and G 2 are independently O or S;
  • T is CR 12 or N
  • Y 1 and Y 2 are independently CR 13 or N;
  • n 1 or 2;
  • p is 1 or 2, providing that when n is 2, p is 1 ;
  • R 1 and R 2 each independently are C C 4 alkyl, C 3 -C 5 cycloalkyl or C 1 -C 4 haloalkyl;
  • R 3 , R 4 , R 5 , R 6 , R 7 and R 8 each independently are hydrogen, hydroxy, halogen, cyano, C-p C 4 alkyl, C ⁇ alkoxy, C 3 -C 5 cycloalkyl or C-rC 4 haloalkyl;
  • R 9 and R 10 each independently are hydrogen, C-
  • X is O or N-R 15
  • R 11 is hydrogen, C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 5 cycloalkylC.r C 4 alkyl, aryl, CrC 4 alkylsulfonyl, arylsulfonyl, heteroaryl, arylalkyl and heteroarylalkyl wherein alkyl, cycloalkyi, alkenyl are optionally substituted by halogen, and wherein aryl, heteroaryl, arylalkyl and heteroarylalkyl are optionally substituted by one or more R 14 ;
  • R 12 is hydrogen, halogen or hydroxyl
  • R 13 is hydrogen, halogen, cyano, CrC 4 alkyl or CrC 4 alkyoxy;
  • each R 14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, Ci-C 8 alkyl, C 2 - C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-Ci-C 4 alkyl, C 3 -C 8 cycloalkyl-Cr C 4 alkoxy, C 3 -C 8 cycloalkyl-Ci-C 4 alkylthio, CrC 8 alkoxy, C 3 -C 8 cycloalkoxy, CrC 8 alkenyloxy, C 2 -C 8 alkynyloxy, Ci-C 8 alkylthio, Ci-C 8 alkylsulfonyl, CrC 8 alkylsulfinyl, C 3 -C 8 cycloalkylthio, C 3 - Cscycloalkylsulfonyl, C 3 -
  • each R 15 independently is hydrogen, C -C 4 alkyl I C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl, C
  • alkylsulfonyl wherein alkyl, cycloalkyi and alkylsulfonyl are optionally substituted by halogen;
  • each R 1S independently is halogen, cyano, C-i-C 4 alkyl, C C 4 haloalkyl, CrC 4 alkoxy or d-
  • substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents, e.g. one to five substituents, e.g. one to three substituents. Normally not more than three such optional substituents are present at the same time.
  • substituents are indicated as being substituted, e.g. alkyl, unless stated otherwise this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.
  • halogen refers to fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
  • Alkyl substituents may be straight-chained or branched. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso- propyl, iso-butyl, sec-butyl, tert-butyl, iso-amyl or pivaloyl.
  • Alkenyl substituents can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl and allyl.
  • the alkenyl groups are preferably C 2 -C 6 , more preferably C 2 -C 4 and most preferably C2-C3 alkenyl groups.
  • Alkynyl substituents can be in the form of straight or branched chains. Examples are ethynyl and propargyl.
  • the alkynyl groups are preferably C 2 -C 6 , more preferably C 2 -C 4 and most preferably C 2 -C 3 alkynyl groups.
  • Haloalkyl groups may contain one or more identical or different halogen atoms and, for example, may stand for CH 2 CI, CHCI 2 , CCI 3 , CH 2 F, CHF 2 , CF 3 , CF 3 CH 2 , CH 3 CF 2 , CF 3 CF 2 or CCI 3 CCI 2 .
  • Haloalkenyl groups are alkenyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 2,2-difluorovinyl or 1 ,2- d i ch I o ro-2-f I u oro-vi ny I .
  • Haloalkynyl groups are alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 1-chloro-prop-2-ynyl.
  • Alkoxy means a radical -OR, where R is alkyl, e.g. as defined above.
  • Alkoxy groups include, but are not limited to, methoxy, ethoxy, 1 -methylethoxy, propoxy, butoxy, 1 - methylpropoxy and 2-methylpropoxy.
  • Cyano means a -CN group.
  • Amino means an NH 2 group.
  • Hydroxyl or hydroxy stands for a -OH group.
  • Aryl means a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
  • Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member.
  • Monocyclic and bicyclic aromatic ring systems are preferred, monocyclic ring systems are more preferred.
  • monocyclic heteoraryl may be a 5- to 7-membered aromatic ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and sulfur.
  • Bicyclic heteroaryl may be a 9- to 1 1-membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur.
  • Examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl,
  • Heteroaryl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms.
  • a link to a heteroaryl group can be via a carbon atom or via a nitrogen atom.
  • Isocyclic ring system includes aryl and in addition their saturated or partially unsaturated analogues.
  • Heterocyclyl and heterocyclic ring system are used interchangeably and is defined to include heteroaryl and in addition their saturated or partially unsaturated analogues.
  • the different rings of bi- or tricyclic heterocyclic ring systems may be linked via one atom belonging to two different rings (spiro), via two adjacent ring atoms belonging to two different rings (annelated) or via two different, not adjacent ring atoms belonging to two different rings (bridged).
  • asymmetric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric forms, i.e. enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond.
  • Formula I is intended to include all those possible isomeric forms and mixtures thereof.
  • the present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I.
  • formula I is intended to include all possible tautomers.
  • the present invention includes all possible tautomeric forms for a compound of formula I.
  • the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
  • N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991. The following list provides definitions, including preferred definitions, for substituents
  • G 1 and G 2 are independently O or S.
  • G 1 is preferably O.
  • G 2 is preferably S.
  • T is CR 12 or N, preferably CH or N, more preferably CH.
  • Y 1 and Y 2 are independently CR 13 or N.
  • Y 1 is preferably CH or N, more preferably N.
  • Y 2 is preferably CH or N; more preferably CH.
  • n is 1 or 2, preferably 2.
  • p is 1 or 2, providing that when n is 2, p is 1 , preferably p is 1 .
  • p is 1 and n is 2,
  • R 1 and R 2 each independently are Ci-C 4 alkyl, C 3 -C 5 cycloalkyl or Ci-C 4 haloalkyl.
  • R 1 and R 2 are each independently methyl or halomethyl, more preferably methyl, difluoromethyl or trifluoromethyl.
  • R 1 is difluoromethyl or trifluoromethyl.
  • R 2 is methyl or difluoromethyl. In one group of compounds R 1 is trifluoromethyl and R 2 is methyl. In another group of compounds R 1 and R 2 are both difluoromethyl.
  • R 3 , R 4 , R 5 , R 6 , R 7 and R 8 each independently are hydrogen, hydroxy, halogen, cyano, Ci-C 4 alkyl, Ci-C 4 alkoxy, C 3 -C 5 cycloalkyl or Ci-C 4 haloalkyl, and preferably are hydrogen, halogen, Ci-C 4 alkyl, Ci-C 4 alkoxy, or CrC 4 haloalkyl, more preferably hydrogen, halogen, or C-
  • R 9 and R 10 each independently are hydrogen, Ci-C 4 alkyl, C C 4 haloalkyl, C 3 - C 5 cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R 14 ; or R 9 and R 10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by one or more R 14 ;
  • R 11 is hydrogen, Ci-C 4 alkyl, C 3 -C 5 cycloalkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 - C 5 cycloalkylCi-C 4 alkyl, aryl, Ci-C 4 alkylsulfonyl, arylsulfonyl, heteroaryl, arylalkyl and heteroarylalkyl wherein alkyl, cycloalkyl, alkenyl are optionally substituted by halogen, and wherein aryl, heteroaryl, arylalkyl and heteroarylalkyl are optionally substituted by one or more R 14 ;
  • R 11 is hydrogen, C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, C 3 -C 5 cycloalkylCi-C alkyl, allyl, propargyl, C-rC 4 alkylsulfonyl, or benzyl wherein alkyl, allyl, cycloalkyl and alkenyl are optionally substituted by halogen; more preferably R 11 is hydrogen, C 1 -C 4 alkyl, allyl, propargyl, wherein alkyl is optionally substituted by chloro or fluoro.
  • X is O or N-R 15 , preferably X is O, NH, NMe, and more preferably O.
  • R 12 is hydrogen, halogen or hydroxyl; preferably R 12 is hydrogen or halogen, more preferably hydrogen,
  • R 13 is hydrogen, halogen, cyano, C C 4 alkyl or C-
  • Each R 14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, Cr
  • R 14 independently is halogen, cyano, hydroxyl, mercapto, C.
  • R 14 independently is halogen, cyano, Ci-C 4 alkyl, methoxy, NH(CrC 4 alkyl), N(Ci-C 4 alkyl) 2 , Ci-C 4 alkylcarbonyl wherein alkyl is optionally substituted by halogen.
  • Each R 15 independently is hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 3 -C 6 cycloalkyl, d- C 4 alkylsulfonyl, wherein alkyl, cycloalkyl and alkylsulfonyl are optionally substituted by halogen; preferably each R 15 independently is hydrogen, C 1 -C 4 alkyl, C C 2 haloalkyl, C C 2 alkylsulfonyl, wherein alkyl and alkylsulfonyl are optionally substituted by halogen; more preferably each R 15 independently is hydrogen, C C 4 alkyl.
  • Each R 16 independently is halogen, cyano, C -C 4 alkyl, Ci-C 4 haloalkyl, C C 4 alkoxy or Cr haloalkoxy; preferably each R 16 independently is halogen, C 1 -C 4 alkyl, Crdhaloalkyl, C alkoxy or CrCynaloalkoxy; more preferably each R 16 independently is halogen, C C 4 alkyl, C 2 haloalkyl.
  • the compound of formula (I) is a compound wherein:
  • G 2 is S
  • T CH or N
  • Y 1 and Y 2 are independently CH or N;
  • n 1 or 2;
  • p is 1 or 2, providing that when n is 2, p is 1 ;
  • R 1 and R 2 each independently are methyl or halomethyl
  • R 3 , R 4 , R 5 , R 6 , R 7 and R 8 each independently are hydrogen, halogen, Ci-C 4 alkyl, C-p C 4 alkoxy, or C-i-C 4 haloalkyl;
  • R 9 and R 10 each independently are hydrogen, C.
  • X is O, NH or NMe;
  • R 11 hydrogen, C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, C 3 -C 5 cycloalkylC 1 -C 4 alkyl, allyl, propargyl, C C 4 alkylsulfonyl, or benzyl wherein alkyl, allyl, cycloalkyi and alkenyl are optionally substituted by halogen;
  • each R 14 independently is halogen, cyano, hydroxyl, Ci-C 4 alkyl, ethynyl, C 3 -C 5 cycloalkyl, d- C 4 alkoxy, C 3 -C alkenyloxy and C 3 -C alkynyloxy, NH(Ci-C alkyl), N(CrC alkyl) 2 , Cr
  • alkylcarbonyl wherein alkyl, cycloalkyi and alkoxy, are optionally substituted by halogen, or a salt or a N-oxide thereof.
  • the compound of formula (I) is a compound wherein
  • G 2 is S
  • T CH or N
  • Y 1 and Y 2 are independently CH or N;
  • n 1 or 2;
  • p is 1 or 2, providing that when n is 2, p is 1 ;
  • R 1 and R 2 each independently are methyl, difluoromethyl or trifluoromethyl
  • R 3 , R 4 , R 5 , R 6 , R 7 and R 8 each independently are hydrogen
  • X is O
  • R 11 is hydrogen, Ci-C 4 alkyl, allyl, propargyl, wherein alkyl is optionally substituted by chloro or fluoro.
  • each R 14 independently is halogen, cyano, C-i-C 4 alkyl, methoxy, NH(C C 4 alkyl), N(d- C 4 alkyl) 2 , CrC 4 alkylcarbonyl wherein alkyl is optionally substituted by halogen; and a salt or a N-oxide thereof.
  • the compound of formula (I) is a compound wherein, G 1 , is O, G 2 is S, Y 1 is N, and Y 2 is CH.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 and Y 2 have the definitions as described for formula I.
  • R 1 , R 2 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 and Y 2 have the definitions as described for formula I.
  • R 1 , R 2 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 and Y 2 have the definitions as described for formula I.
  • the invention also relates to compounds of formula l-a, formula l-b and formula l-c as shown above.
  • the invention also relates to compounds of formula l-d:
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 1 , G 2 , X, Y 1 and Y 2 have the definitions a: described for formula I.
  • Preferred definitions of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , X, Y 1 and Y 2 are as defined for formula I.
  • the invention also relates to compounds of formula l-e:
  • R 1 , R 2 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 1 and X have the definitions as described for formula I.
  • Preferred definition, s of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 1 and X are as defined for formula I.
  • the invention also relates to compounds of formula l-f:
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 , Y 2 ,n and p have the definition as described for formula I.
  • Preferred definitions of R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 , Y 2 ,n and p are as defined for formula I.
  • the invention also relates to compounds of formula l-g:
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 , Y 2 ,n and p have the definitions as described for formula I.
  • Preferred definitions of R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 T, X, Y 1 , Y 2 ,n and p are as defined for formula I.
  • the invention includes compounds of formula II:
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 2 , T, X, Y 1 , Y 2 ,n and p are as defined for a compound of formula I and E is hydrogen or a protecting group, such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C 4 alkylcarbonyl, benzyl or Ci-C 4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl.
  • These compounds, including salts and N- oxides thereof, are useful as intermediates in the synthesis of compounds of formula I.
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 2 , T, X, Y 1 , Y 2 ,n and p are as defined for formula I.
  • the invention also includes compounds of formula III
  • R 9 , R 10 , G 2 , Y 1 , Y 2 are as defined for a compound of formula I.
  • R 9 , R 10 , G 2 , Y 1 , Y 2 are as defined for formula I.
  • R 9 , R 10 , G 2 , Y 1 , Y 2 are as defined for formula I.
  • the invention also includes compounds of formula IV
  • R 9 , R 10 , R 11 , G 2 , X, Y 1 , Y 2 are as defined for a compound of formula I.
  • R 9 , R 10 , R 11 , G 2 , X, Y 1 , Y 2 are as defined for formula I.
  • R 9 , R 10 , R 11 , G 2 , X, Y 1 , Y 2 are as defined for formula I.
  • the invention also includes compounds of formula V
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 2 , X, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or
  • alkoxycarbonyl e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , X, Y 1 , Y 2 , n and p are as defined for formula I.
  • the invention also includes compounds of formula VI
  • R 3 , R 4 , R 5 , R s , R 7 , R 8 , R 9 , R 10 , G 2 , Y 1 , Y 2 , n and p are as defined for a compound of formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or
  • alkoxycarbonyl e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl.
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , G 2 , Y 1 , Y 2 , n and p are as defined for formula I.
  • the compounds of formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 1 , G 2 , T, X, Y 1 , Y 2 , n and p are as defined for formula I, can be obtained by transformation of a compound of formula Ila, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , G 2 , X, T, Y 1 , Y 2 , n and p are as defined for formula I, with a compound of formula VII, wherein R 1 , R 2 and G 1 is as defined for formula I and Hal is halogen, preferably chloro, and a base, such as pyridine, trieth lamine, ethyl diisopropylamine. This is shown in Scheme 1.
  • T, X, Y 1 , Y 2 , n and p are as defined for formula I, can be obtained by transformation of a compound of formula Ila, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , X, G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I, with a compound of formula VIII , wherein R 1 , R 2 and G 1 is as defined for formula I, an activating reagent such BOP, PyBOP, EDCI, CDI or HATU, and a base, such as pyridine, triethylamine, ethyl diisopropylamine. This is shown in Scheme 2.
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl
  • a compound of formula IX wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C 4 alkylcarbonyl, benzyl or C C 4
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula X wherein R 11 and X are as defined for formula I. This is shown in Scheme 3.
  • alkylcarbonyl benzyl or alkoxycarbonyl, e.g. Ci-C alkylcarbonyl, benzyl or C C
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as
  • alkylcarbonyl benzyl or alkoxycarbonyl, e.g. C C 4 alkylcarbonyl, benzyl or C C 4
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R 9 and R 10 are as defined for formula I, and a base such as potassium bicarbonate. This is shown in Scheme 4.
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl
  • R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as
  • alkylcarbonyl benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or CrC 4
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R 9 and R 10 are as defined for formula I , and an oxidant such as
  • the compounds of formula IX wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C C 4
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl
  • a compound of formula XIV wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , G 2 , T, Y 1 , Y 2 and p are as defined for formula I and E is hydrogen, a protecting group such as
  • alkylcarbonyl benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C C 4
  • alkoxycarbonyl in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R 9 and R 10 are as defined for formula I , and hydroxylamine and a chlorinatin agent such as sodium hypochlorite.
  • R 9 and R 10 are as defined for formula I
  • hydroxylamine and a chlorinatin agent such as sodium hypochlorite
  • C-rC 4 alkylcarbonyl, benzyl or C-rC 4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula XIV, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g.
  • -C 4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula XIV, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , G 2 , T, Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C 4 alkylcarbonyl, benzyl or Ci-C 4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with hydroxalamine. This is shown in Scheme 8.
  • Ci-C alkylcarbonyl, benzyl or Ci-C alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula VI, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , G 2 , Y 1 , Y 2 , n and p are as defined for formula I, with h drogen and a catalyst. This is shown in Scheme 9.
  • C 1 -C4 alkylcarbonyl, benzyl or C -C 4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula XV, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , n and p are as defined for formula I and R 17 is B(OH) 2 or B(OR 18 ) 2 with the two R 18 each independently being C 1 -C4 alkyl or together form a four to six-membered ring with a compound of formula I I I, wherein R 9 , R 10 , G 2 , Y 1 and Y 2 are as defined for formula I and halogen is chloro, bromo or iodo, and with a transition metal, such as tetrakis(triphenylphosphine)palladium, and a ligand.
  • a transition metal such as te
  • the compounds of formula I II wherein R 9 , R 10 , G 2 , Y and Y 2 are as defined for formula I and halogen is chloro, bromo or iodo, can be obtained by transformation of a compound of formula XVI , wherein G 2 , Y 1 , Y 2 are as defined for formula I, with a compound of formula XII , wherein R 9 and R 10 are as defined for formula I, and with hydroxylamine and a chlorinatin reagent such as sodium hypochlorite. This is shown in Scheme 1 1.
  • the compounds of formula IXa wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , G 2 , Y 1 , Y 2 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g.
  • C C4 alkylcarbonyl, benzyl or C-1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula XVI I, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g.
  • C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl can be obtained by transformation of a compound of formula XV, wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , n and p are as defined for formula I and R 17 is B(OH) 2 or B(OR 18 ) 2 with the two R 18 each independently being C1-C4 alkyl or together form a four to six-membered ring with a compound of formula IV, wherein R 9 , R 10 , R 11 , G 2 , X, Y 1 and Y 2 are as defined for formula I and halogen is chloro, bromo or iodo, and with a transition metal, such as tetrakis(triphenylphosphine)palladium, and a li and. This is shown in Scheme 13.
  • novel compounds of formula I have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
  • the compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man.
  • the novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants.
  • the compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
  • compositions comprising a compound of formula I before planting: seed, for example, can be dressed before being sown.
  • the active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation.
  • the composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
  • the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.
  • the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
  • the compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Alternaria spp.), Basidiomycetes (e.g. Corticium spp., Ceratobasidium spp., Waitea spp., Thanatephorus spp., Rhizoctonia spp., Hemileia spp., Puccinia spp., Phakopsora spp., Ustilago spp., Tilletia spp.), Ascomycetes (e.g.
  • Venturia spp. Blumeria spp., Erysiphe spp., Podosphaera spp., Uncinula spp., Monilinia spp., Sclerotinia spp., Colletotrichum spp., Glomerella spp., Fusarium spp., Gibberella spp., Monographella spp., Phaeosphaeria spp., Mycosphaerella spp., Cercospora spp., Pyrenophora spp., Rhynchosporium spp., Magnaporthe spp., Gaeumannomyces spp., Oculimacula spp., Ramularia spp., Botryotinia spp.) and Oomycetes (e.g.
  • Phytophthora spp. Pythium spp., Plasmopara spp., Peronospora spp., Pseudoperonospora spp. Bremia spp).
  • Outstanding activity is observed against downy mildew (e.g. Plasmopara viticola) and late blight (e.g. Phytophthora infestans).
  • the novel compounds of formula I are effective against phytopathogenic gram negative and gram positive bacteria (e.g.
  • Xanthomonas spp Pseudomonas spp, Erwinia amylovora, Ralstonia spp.
  • viruses e.g. tobacco mosaic virus
  • target crops and/or useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor)
  • the useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties.
  • suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties.
  • useful plants and/or “target crops” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • imazamox by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and
  • useful plants and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • useful plants and/or target crops is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191.
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • locus of a plant as used herein is intended to embrace the place on which the plants are growing, where the plant propagation materials of the plants are sown or where the plant propagation materials of the plants will be placed into the soil.
  • An example for such a locus is a field, on which crop plants are growing.
  • plant propagation material is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material” is understood to denote seeds.
  • the compounds of formula I may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.
  • Such carriers are for example described in WO 97/33890.
  • the compounds of formula I are normally 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.
  • further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • the compounds of formula I may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula I or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
  • the invention provides a composition, preferably a fungicidal composition, comprising at least one compound formula I, an agriculturally acceptable carrier and optionally an adjuvant.
  • An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art.
  • said composition 5 may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula I.
  • the compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate.
  • additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate.
  • Suitable additional active ingredients include the following: Azoxystrobin (131860-33-8), Dimoxystrobin (149961-52-4), Enestrobin (238410-1 1-2), Fluoxastrobin (193740-76-0), Kresoxim-methyl (143390-89-0), Metominostrobin (133408-50-1 ), Orysastrobin (248593-16- 0), Picoxystrobin (117428-22-5), Pyraclostrobin (175013-18-0), trifloxystrobin (141517-21-7),
  • Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides, as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by phytopathogenic microorganisms, preferably fungal organisms.
  • useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by phytopathogenic microorganisms, preferably fungal organisms.
  • a further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by
  • phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms which comprises the application of a compound of formula I or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
  • Controlling or preventing means reducing infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
  • a preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying 5 the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation e.g. a composition containing the compound of formula I, and, if desired, 10 a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active
  • the agrochemical formulations and/or compositions will usually contain from 0.1 to 15 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. 20
  • convenient dosages are from 10mg to 1 g of active substance per kg of seeds.
  • Chloroacetylchloride (78.7mg) was added at 0-5°C to a solution of diisopropylethylamine (131 mg) and N-methoxy-7,7-dimethyl-2-[2-(4-piperidyl)thiazol-4-yl]-4-oxa-3-azaspiro[4.5]dec- 2-en-10-imine (250mg) in dichloromethane (3ml). After stirring for 90min at 0-5°C, the reaction mixture was quenched with water, diluted with dichloromethane (15ml) and washed 10 with hydrochloric acid (15ml, 1 M) and sodium bicarbonate (10% in water, 15ml).
  • O-methylhydroxylamine hydrochloride (2.06 g) was added to a solution of 7,7-dimethyl-2-[2- (4-piperidyl)thiazol-4-yl]-4-oxa-3-azaspiro[4.5]dec-2-en-10-one (2.37g) in ethanol (31 ml_). The reaction mixture was stirred for 16h at 60°C, then cooled to 25°C, concentrated and diluted with ethylacetate and sodium hydrogen carbonate solution (10% in water).
  • Triethylamine (9.72g) was added at 0-5°C to a solution of 2-(4-piperidyl)thiazole-4- carbaldehyde dihydrochloride (8.0) in dichloromethane (100ml_).
  • Acetylchloride (2.80g) was added at 0-5°C, the reaction mixture was warmed up and stirred for 16h at 25°C.
  • the reaction mixture was poured onto sodium bicarbonate solution (300ml_; 20% in water) and extracted with dichloromethane. The combined organic phases were washed with brine dried over magnesiumsulfate, filtered and concentrated. The residue was purified by
  • Acetonitrile 43mL was added to a suspension of [2-methoxyimino-5,5-dimethyl- cyclohexyl]methyl-trimethyl-ammonium iodide (3.63g) in sodium hydroxide (16.6mL, 2M in water). After stirring for 15h at 80°C the reaction mixture was cooled and most of the acetonitrile was removed. The residue was diluted with dichloromethane. The organic phase was separated and the water phase was extracted with dichloromethane.
  • This product was used in the next steps without further purification. Depending on workup this product can contain variable amounts of dichloromethane and acetonitrile.
  • Aluminiumoxide (12.2g; alox basic 50-200uM) was added to a solution of (5,5-dimethyl-2- oxo-cyclohexyl)methyl-trimethyl-ammonium iodide (14g) in dichloromethane (140mL). After stirring for 4h at 25°C the reaction mixture was filtered and the solid was washed with 20ml of dichloromethane. This solution contains 4,4-dimethyl-2-methylene-cyclohexanone (5.9 g) and was used in the next step without further purification.
  • ⁇ refers to a carbon-oxygen single bond
  • j refers to a carbon-carbon single bond
  • k refers to a carbon-nitrogen double bond as shown below on the general formula (I):
  • R 9 , R 10 , R 11 are as defined in Table 1.
  • LC/MS Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the methods are:
  • Ionization method Electrospray; Polarity: positive and negative ions; Capillary: 3.00 kV; Cone: 30V; Extractor: 2.00 V; Source Temperature: 150°C; Desolvation Temperature: 350°C; Cone Gas Flow: 0 L/Hr; Desolvation Gas Flow: 650 L/Hr; Mass range: 100 to 900 Da
  • Solvent degasser binary pump, heated column compartment and diode-array detector.
  • Ionization method Electrospray; Polarity: positive and negative ions; Capillary: 3.00 kV; Cone: 30 V; Extractor: 2.00 V; Source Temperature: 150°C; Desolvation Temperature: 350C; Cone Gas Flow: 50 L/Hr; Desolvation Gas Flow: 400 L/Hr; Mass range: 100 to 900 Da
  • Solvent degasser binary pump, heated column compartment and diode-array detector.
  • Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks are inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks are
  • Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and the leaf disks are inoculated with a spore suspension of the fungus. The inoculated leaf disks are incubated at 16°C and 75% rh in darkness in a climate cabinet. 20 hours after inoculation the leaf disks are sprayed with the formulated test compound diluted in water and the leaf disks are incubated at 16°C and 75% rh under 5 a light regime of 12 h light / 12 h darkness in a climate cabinet. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (4 - 6 days after inoculation).
  • 2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound 20 diluted in water.
  • the test plants are inoculated by spraying them with a sporangia suspension 2 days after application.
  • the inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5 - 7 days after application).
  • Bintje are inoculated by spraying them with a sporangia suspension one day before application.
  • the inoculated plants are sprayed in a spray chamber with the formulated test compound diluted in water.
  • the inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (3 - 4 days after application).
  • 2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water.
  • the test plants are inoculated by spraying them with a sporangia suspension 6 days after application.
  • the inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (9 - 1 1 days after application).
  • Plasmopara viticola I grape / leaf disc preventative (grape downy mildew)
  • Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks are inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks are incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease 15 damage appears in untreated check leaf disks (6 - 8 days after application).
  • test plants plants are inoculated by spraying a sporangia suspension on their lower leaf surface one day after application.
  • the inoculated test plants are incubated at 22° C
  • Plasmopara viticola I grape / curative (grape downy mildew)
  • 5-week-old grape seedlings cv. Gutedel are inoculated by spraying a sporangia suspension on their 40 lower leaf surface one day before application.
  • the inoculated grape plants are sprayed in a spray chamber with the formulated test compound diluted in water.
  • the inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (4 - 6 days after application).
  • test plants 5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test 10 compound diluted in water.
  • the test plants are inoculated by spraying a sporangia suspension on their lower leaf surface 6 days after application.
  • the inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (11 - 13 days after application).
  • Mycelia fragments and oospores of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal mycelia/spore mixture is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically

Abstract

The present invention relates to compounds of formula (I) wherein substituents are as defined in the claims. The invention also relates to methods of using the compounds of formula I to control or prevent infestation of plants, propagation material thereof, harvested crops or non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man.

Description

Microbiocidal Pyrazole Derivatives
The present invention relates to microbiocidal pyrazole derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to preparation of these pyrazole derivatives, to pyrazole derivatives used as intermediates in the preparation of these pyrazole derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the pyrazole derivatives, to preparation of these compositions and to use of the pyrazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.
Certain compounds for use as fungicides are described in WO 2007/014290, WO 2008/013622, WO 2008/013925, WO 2008/091580, WO 2008/091594 and WO
2009/055514.
The present invention provides compounds of formula I:
Figure imgf000002_0001
wherein,
G1 and G2 are independently O or S;
T is CR12 or N;
Y1 and Y2 are independently CR13 or N;
n is 1 or 2;
p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are C C4alkyl, C3-C5cycloalkyl or C1-C4haloalkyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen, hydroxy, halogen, cyano, C-p C4alkyl, C ^alkoxy, C3-C5cycloalkyl or C-rC4haloalkyl;
R9 and R10 each independently are hydrogen, C-|-C4alkyl, Cr^haloalkyl, C3-C5cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10- membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by one or more R14;
X is O or N-R15 R11 is hydrogen, C1-C4alkyl, C3-C5cycloalkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C5cycloalkylC.r C4alkyl, aryl, CrC4alkylsulfonyl, arylsulfonyl, heteroaryl, arylalkyl and heteroarylalkyl wherein alkyl, cycloalkyi, alkenyl are optionally substituted by halogen, and wherein aryl, heteroaryl, arylalkyl and heteroarylalkyl are optionally substituted by one or more R14;
R12 is hydrogen, halogen or hydroxyl;
R13 is hydrogen, halogen, cyano, CrC4alkyl or CrC4 alkyoxy;
each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, Ci-C8alkyl, C2- C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-Ci-C4alkyl, C3-C8cycloalkyl-Cr C4alkoxy, C3-C8cycloalkyl-Ci-C4alkylthio, CrC8alkoxy, C3-C8cycloalkoxy, CrC8alkenyloxy, C2-C8alkynyloxy, Ci-C8alkylthio, Ci-C8alkylsulfonyl, CrC8alkylsulfinyl, C3-C8cycloalkylthio, C3- Cscycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-Ci-C4alkyl, aryl-C-rC4alkoxy, aryl-C C4alkylthio, heterocyclyl, heterocycyl-C C4alkyl, heterocycyl-CrC4alkoxy, heterocycyl-C C4alkylthio, NH(C"rC8alkyl), N(C1-C8alkyl)2, C C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyi, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R16; or R14 is C=NOR11;
each R15 independently is hydrogen, C -C4alkylI C1-C4haloalkyl, C3-C6cycloalkyl, C
C4alkylsulfonyl, wherein alkyl, cycloalkyi and alkylsulfonyl are optionally substituted by halogen; and
each R1S independently is halogen, cyano, C-i-C4alkyl, C C4haloalkyl, CrC4alkoxy or d-
C4haloalkoxy; or
a salt or a N-oxide thereof.
Where substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents, e.g. one to five substituents, e.g. one to three substituents. Normally not more than three such optional substituents are present at the same time. Where a group is indicated as being substituted, e.g. alkyl, unless stated otherwise this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.
The term "halogen" refers to fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
Alkyl substituents may be straight-chained or branched. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso- propyl, iso-butyl, sec-butyl, tert-butyl, iso-amyl or pivaloyl.
Alkenyl substituents can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl and allyl. The alkenyl groups are preferably C2-C6, more preferably C2-C4 and most preferably C2-C3 alkenyl groups.
Alkynyl substituents can be in the form of straight or branched chains. Examples are ethynyl and propargyl. The alkynyl groups are preferably C2-C6, more preferably C2-C4 and most preferably C2-C3 alkynyl groups.
Haloalkyl groups may contain one or more identical or different halogen atoms and, for example, may stand for CH2CI, CHCI2, CCI3, CH2F, CHF2, CF3, CF3CH2, CH3CF2, CF3CF2 or CCI3CCI2.
Haloalkenyl groups are alkenyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 2,2-difluorovinyl or 1 ,2- d i ch I o ro-2-f I u oro-vi ny I .
Haloalkynyl groups are alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 1-chloro-prop-2-ynyl.
Alkoxy means a radical -OR, where R is alkyl, e.g. as defined above. Alkoxy groups include, but are not limited to, methoxy, ethoxy, 1 -methylethoxy, propoxy, butoxy, 1 - methylpropoxy and 2-methylpropoxy.
Cyano means a -CN group.
Amino means an NH2 group.
Hydroxyl or hydroxy stands for a -OH group.
Aryl means a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member. Monocyclic and bicyclic aromatic ring systems are preferred, monocyclic ring systems are more preferred. For example, monocyclic heteoraryl may be a 5- to 7-membered aromatic ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and sulfur. Bicyclic heteroaryl may be a 9- to 1 1-membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur. Examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl,
benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, imiazothiazoyl, quinolinyl, quinoxalinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl, preferably pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thienyl thiazolyl or thiadiazolyl. Heteroaryl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms. A link to a heteroaryl group can be via a carbon atom or via a nitrogen atom.
Isocyclic ring system includes aryl and in addition their saturated or partially unsaturated analogues.
Heterocyclyl and heterocyclic ring system are used interchangeably and is defined to include heteroaryl and in addition their saturated or partially unsaturated analogues. The different rings of bi- or tricyclic heterocyclic ring systems may be linked via one atom belonging to two different rings (spiro), via two adjacent ring atoms belonging to two different rings (annelated) or via two different, not adjacent ring atoms belonging to two different rings (bridged).
The presence of one or more possible asymmetric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric forms, i.e. enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula I is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I. Likewise, formula I is intended to include all possible tautomers. The present invention includes all possible tautomeric forms for a compound of formula I.
In each case, the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991. The following list provides definitions, including preferred definitions, for substituents
G1, G2, T, Y1, Y2, n, p, R1, R2, R3, R4, R5, Rs, R7, R8, R9, R10, R11, R12, R13, R14, R15 and R16 with reference to compounds of formula I and other compounds of the invention carrying the same substituents. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
G1 and G2 are independently O or S.
G1 is preferably O.
G2 is preferably S.
T is CR12 or N, preferably CH or N, more preferably CH.
Y1 and Y2 are independently CR13 or N.
Y1 is preferably CH or N, more preferably N.
Y2 is preferably CH or N; more preferably CH.
n is 1 or 2, preferably 2. p is 1 or 2, providing that when n is 2, p is 1 , preferably p is 1 .
Preferably, p is 1 and n is 2,
R1 and R2 each independently are Ci-C4alkyl, C3-C5cycloalkyl or Ci-C4haloalkyl.
Preferably R1 and R2 are each independently methyl or halomethyl, more preferably methyl, difluoromethyl or trifluoromethyl.
Preferably R1 is difluoromethyl or trifluoromethyl. Preferably R2 is methyl or difluoromethyl. In one group of compounds R1 is trifluoromethyl and R2 is methyl. In another group of compounds R1 and R2 are both difluoromethyl.
R3, R4, R5, R6, R7 and R8 each independently are hydrogen, hydroxy, halogen, cyano, Ci-C4alkyl, Ci-C4alkoxy, C3-C5cycloalkyl or Ci-C4haloalkyl, and preferably are hydrogen, halogen, Ci-C4alkyl, Ci-C4alkoxy, or CrC4haloalkyl, more preferably hydrogen, halogen, or C-|-C4alkyl; even more preferably hydrogen.
R9 and R10 each independently are hydrogen, Ci-C4alkyl, C C4haloalkyl, C3- C5cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by one or more R14;
Preferably, R9 and R10 each independently are hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5cycloalkyl, d- C4alkoxy, Ci-C8alkylthio or C=NOR11.
More preferably, R9 and R10 each independently are hydrogen, Ci-C4alkyl, aryl, or heteroaryl wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, d-dalkyl, C3-C5cycloalkyl, d-C4alkoxy, d-C8alkylthio or C=NOR11.
Even more preferably, R9 and R10 each independently are hydrogen, d-dalkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R 0 together with the carbon atoms to which they are attached form a 5 or 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0) said isocyclic ring being optionally substituted by d-dalkyl, C3-C5cycloalkyl, d-dalkoxy, d-C8alkylthio or C=NOR11 . Even more preferably, R9 and R10 each independently are hydrogen, C1-C4alkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R 0 together with the carbon atoms to which they are attached form a 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0), said isocyclic ring being optionally substituted by d-C4alkyl, C3-C5cycloalkyl, CrC4alkoxy, CrC8alkylthio, or C=NOR11.
R11 is hydrogen, Ci-C4alkyl, C3-C5cycloalkyl, C2-C8alkenyl, C2-C8alkynyl, C3- C5cycloalkylCi-C4alkyl, aryl, Ci-C4alkylsulfonyl, arylsulfonyl, heteroaryl, arylalkyl and heteroarylalkyl wherein alkyl, cycloalkyl, alkenyl are optionally substituted by halogen, and wherein aryl, heteroaryl, arylalkyl and heteroarylalkyl are optionally substituted by one or more R14;
Preferably R11 is hydrogen, C1-C4alkyl, C3-C5cycloalkyl, C3-C5cycloalkylCi-C alkyl, allyl, propargyl, C-rC4alkylsulfonyl, or benzyl wherein alkyl, allyl, cycloalkyl and alkenyl are optionally substituted by halogen; more preferably R11 is hydrogen, C1-C4alkyl, allyl, propargyl, wherein alkyl is optionally substituted by chloro or fluoro.
X is O or N-R15, preferably X is O, NH, NMe, and more preferably O.
R12 is hydrogen, halogen or hydroxyl; preferably R12 is hydrogen or halogen, more preferably hydrogen,
R13 is hydrogen, halogen, cyano, C C4alkyl or C-|-C4 alkyoxy; preferably hydrogen or halogen, more preferably hydrogen,
Each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, Cr
C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-Ci-C4alkyl, C3- C8cycloalkyl-Ci-C alkoxy, C3-C8cycloalkyl-Ci-C4alkylthio, CrC8alkoxy, C3-C8cycloalkoxy, C C8alkenyloxy, C2-C8alkynyloxy, CrC8alkylthio, Ci-C8alkylsulfonyl, Ci-C8alkylsulfinyl, C3- C8cycloalkylthio, C3-C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-CrC alkyl, aryl-CrC alkoxy, aryl-C-i-C alkylthio, heterocyclyl, heterocycyl-Ci-C4alkyl, heterocycyl-Ci-C4alkoxy, heterocycyl-CrC alkylthio, NH(Ci-C8alkyl), N(Ci-C8alkyl)2, Ci-C alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2- C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R 6; or R14 is C=NOR11;
Preferably R14 independently is halogen, cyano, hydroxyl, mercapto, C.|-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, C3-C5cycloalkyl, Ci-C4alkoxy, C-i-C alkenyloxy, C2-C4alkynyloxy, C C alkylsulfonyl, aryl, aryloxy, arylsulfonyl, aryl-Ci-C alkyl, aryl-Ci-C alkoxy, heterocyclyl, NH(C-|-C alkyl), N(Ci-C alkyl)2, Ci-C alkylcarbonyl wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R16; or R14 is
C=NOR11 More preferably R14 independently is halogen, cyano, hydroxyl, C1-C4alkyl, ethynyl, C3- C5cycloalkyl, d-C4alkoxy, C3-C4alkenyloxy, C3-C4alkynyloxy, NH(Ci-C alkyl), N(CrC alkyl)2, CrC4alkylcarbonyl wherein alkyl, cycloalkyl and alkoxy, are optionally substituted by halogen, or R14 is C=NOR11
Even more preferably R14 independently is halogen, cyano, Ci-C4alkyl, methoxy, NH(CrC4alkyl), N(Ci-C4alkyl)2, Ci-C4alkylcarbonyl wherein alkyl is optionally substituted by halogen, or R14 is C=NOH or CNOMe
Even more preferably R14 independently is halogen, cyano, Ci-C4alkyl, methoxy, NH(CrC4alkyl), N(Ci-C4alkyl)2, Ci-C4alkylcarbonyl wherein alkyl is optionally substituted by halogen.
Each R15 independently is hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C3-C6cycloalkyl, d- C4alkylsulfonyl, wherein alkyl, cycloalkyl and alkylsulfonyl are optionally substituted by halogen; preferably each R15 independently is hydrogen, C1-C4alkyl, C C2haloalkyl, C C2alkylsulfonyl, wherein alkyl and alkylsulfonyl are optionally substituted by halogen; more preferably each R15 independently is hydrogen, C C4alkyl.
Each R16 independently is halogen, cyano, C -C4alkyl, Ci-C4haloalkyl, C C4alkoxy or Cr haloalkoxy; preferably each R16 independently is halogen, C1-C4alkyl, Crdhaloalkyl, C alkoxy or CrCynaloalkoxy; more preferably each R16 independently is halogen, C C4alkyl, C C2haloalkyl.
Preferably, the compound of formula (I) is a compound wherein:
G1 is O
G2 is S;
T is CH or N;
Y1 and Y2 are independently CH or N;
n is 1 or 2;
p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are methyl or halomethyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen, halogen, Ci-C4alkyl, C-p C4alkoxy, or C-i-C4haloalkyl;
R9 and R10 each independently are hydrogen, C.|-C4alkyl, aryl, or heteroaryl wherein aryl and heteroaryl are optionally substituted by one or more R14, or
R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10- membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, Ci-C4alkyl, C3-C5cycloalkyl, Ci-C4alkoxy, Ci-C8alkylthio or C=NOR11; X is O, NH or NMe; R11 hydrogen, C1-C4alkyl, C3-C5cycloalkyl, C3-C5cycloalkylC1-C4alkyl, allyl, propargyl, C C4alkylsulfonyl, or benzyl wherein alkyl, allyl, cycloalkyi and alkenyl are optionally substituted by halogen;
each R14 independently is halogen, cyano, hydroxyl, Ci-C4alkyl, ethynyl, C3-C5cycloalkyl, d- C4alkoxy, C3-C alkenyloxy and C3-C alkynyloxy, NH(Ci-C alkyl), N(CrC alkyl)2, Cr
C4alkylcarbonyl wherein alkyl, cycloalkyi and alkoxy, are optionally substituted by halogen, or a salt or a N-oxide thereof.
Preferably, the compound of formula (I) is a compound wherein
G1 is O
G2 is S;
T is CH or N;
Y1 and Y2 are independently CH or N;
n is 1 or 2;
p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are methyl, difluoromethyl or trifluoromethyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen,
R9 and R10 each independently are hydrogen, C dalkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0), said isocyclic ring being optionally substituted by CrC4alkyl, C3- Cscycloalkyl, C C4alkoxy, C C8alkylthio, C=NOMe or C=NOH;
X is O;
R11 is hydrogen, Ci-C4alkyl, allyl, propargyl, wherein alkyl is optionally substituted by chloro or fluoro.;
each R14 independently is halogen, cyano, C-i-C4alkyl, methoxy, NH(C C4alkyl), N(d- C4alkyl)2, CrC4alkylcarbonyl wherein alkyl is optionally substituted by halogen; and a salt or a N-oxide thereof. Preferably, the compound of formula (I) is a compound wherein, G1, is O, G2 is S, Y1 is N, and Y2 is CH.
For the avoidance of doubt, when n is 1 and p is 1 compounds of formula I have the formula according to formula l-a:
Figure imgf000010_0001
in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1 and Y2 have the definitions as described for formula I.
When n is 2 and p is 1 , compounds of formula I have the formula according to formula l-b
Figure imgf000010_0002
in which R1, R2 R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1 and Y2 have the definitions as described for formula I.
When n is 1 and p is 2, compounds of formula I have the formula according to formula l-c:
Figure imgf000010_0003
in which R1, R2 R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1 and Y2 have the definitions as described for formula I.
The invention also relates to compounds of formula l-a, formula l-b and formula l-c as shown above.
The invention also relates to compounds of formula l-d:
Figure imgf000010_0004
in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R 1, G2, X, Y1 and Y2 have the definitions a: described for formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, X, Y1 and Y2 are as defined for formula I.
The invention also relates to compounds of formula l-e:
Figure imgf000011_0001
in which R1, R2 R3, R4, R5, R6, R7, R8, R9, R10, R 1 and X have the definitions as described for formula I. Preferred definition, s of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R1 and X are as defined for formula I.
The invention also relates to compounds of formula l-f:
Figure imgf000011_0002
wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1, Y2,n and p have the definition as described for formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1, Y2,n and p are as defined for formula I.
The invention also relates to compounds of formula l-g:
Figure imgf000011_0003
in which R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1, Y2,n and p have the definitions as described for formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2 T, X, Y1, Y2,n and p are as defined for formula I. The invention includes compounds of formula II:
Figure imgf000012_0001
wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, T, X, Y1, Y2,n and p are as defined for a compound of formula I and E is hydrogen or a protecting group, such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C4 alkylcarbonyl, benzyl or Ci-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl. These compounds, including salts and N- oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, T, X, Y1, Y2,n and p are as defined for formula I.
The invention also includes compounds of formula III
Figure imgf000012_0002
wherein halogen is bromo, chloro, fluroro or iodo and R9, R10, G2, Y1, Y2 are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R9, R10, G2, Y1, Y2 are as defined for formula I.
The invention also includes compounds of formula IV
Figure imgf000012_0003
wherein halogen is bromo, chloro, fluroro or iodo and R9, R10, R11, G2, X, Y1, Y2 are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R9, R10, R11, G2, X, Y1, Y2 are as defined for formula I.
The invention also includes compounds of formula V
Figure imgf000013_0001
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, X, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or
alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, X, Y1, Y2, n and p are as defined for formula I. The invention also includes compounds of formula VI
Figure imgf000013_0002
Wherein R3, R4, R5, Rs, R7, R8, R9, R10, G2, Y1, Y2, n and p are as defined for a compound of formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or
alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1, Y2, n and p are as defined for formula I.
The compounds of formula I, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2, T, X, Y1, Y2, n and p are as defined for formula I, can be obtained by transformation of a compound of formula Ila, wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, X, T, Y1, Y2, n and p are as defined for formula I, with a compound of formula VII, wherein R1, R2 and G1 is as defined for formula I and Hal is halogen, preferably chloro, and a base, such as pyridine, trieth lamine, ethyl diisopropylamine. This is shown in Scheme 1.
Figure imgf000013_0003
Scheme 1
The compounds of formula I, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G1, G2,
T, X, Y1, Y2, n and p are as defined for formula I, can be obtained by transformation of a compound of formula Ila, wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, X, G2, T, Y1, Y2, n and p are as defined for formula I, with a compound of formula VIII , wherein R1, R2 and G1 is as defined for formula I, an activating reagent such BOP, PyBOP, EDCI, CDI or HATU, and a base, such as pyridine, triethylamine, ethyl diisopropylamine. This is shown in Scheme 2.
Figure imgf000014_0001
Scheme 2
The compounds of formula I I, wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, T, X, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C C4 alkylcarbonyl, benzyl or CrC4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula IX, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C4 alkylcarbonyl, benzyl or C C4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula X wherein R11 and X are as defined for formula I. This is shown in Scheme 3.
Figure imgf000014_0002
Scheme 3
The compounds of formula IX, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as
alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C alkylcarbonyl, benzyl or C C
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XI, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as
alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C C4 alkylcarbonyl, benzyl or C C4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R9 and R10 are as defined for formula I, and a base such as potassium bicarbonate. This is shown in Scheme 4.
Figure imgf000014_0003
Scheme 4 Alternatively, the compounds of formula IX, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C C4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XIII, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as
alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or CrC4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R9 and R10 are as defined for formula I , and an oxidant such as
Figure imgf000015_0001
Scheme 5
Alternatively, the compounds of formula IX, wherein R3, R4, R5, R6, R7, R8, R9, R10, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C C4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XIV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2 and p are as defined for formula I and E is hydrogen, a protecting group such as
alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C C4
alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XII, wherein R9 and R10 are as defined for formula I , and hydroxylamine and a chlorinatin agent such as sodium hypochlorite. This is shown in Scheme 6.
Figure imgf000015_0002
Scheme 6
The compounds of formula XI, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C-rC4 alkylcarbonyl, benzyl or C-rC4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XIV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with hydroxalamine and chlorinating agent such as sodium hypochlorite. This is shown in Scheme 7.
Figure imgf000016_0001
The compounds of formula XIII , wherein R3, R4, R5, R6, R7, R8, G2, T, Y1 , Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C-|-C4 alkylcarbonyl, benzyl or C-|-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XIV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C4 alkylcarbonyl, benzyl or Ci-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with hydroxalamine. This is shown in Scheme 8.
Figure imgf000016_0002
The compounds of formula IXa, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1 , Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. Ci-C alkylcarbonyl, benzyl or Ci-C alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula VI, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1, Y2, n and p are as defined for formula I, with h drogen and a catalyst. This is shown in Scheme 9.
Figure imgf000016_0003
Scheme 9
The compounds of formula VI , wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1 , Y2, n and are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C -C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XV, wherein R3, R4, R5, R6, R7, R8, n and p are as defined for formula I and R17 is B(OH)2 or B(OR18)2 with the two R18 each independently being C1-C4 alkyl or together form a four to six-membered ring with a compound of formula I I I, wherein R9, R10, G2, Y1 and Y2 are as defined for formula I and halogen is chloro, bromo or iodo, and with a transition metal, such as tetrakis(triphenylphosphine)palladium, and a ligand. This is shown in Scheme 10.
Figure imgf000017_0001
Scheme 10
The compounds of formula I II, wherein R9, R10, G2, Y and Y2 are as defined for formula I and halogen is chloro, bromo or iodo, can be obtained by transformation of a compound of formula XVI , wherein G2, Y1 , Y2 are as defined for formula I, with a compound of formula XII , wherein R9 and R10 are as defined for formula I, and with hydroxylamine and a chlorinatin reagent such as sodium hypochlorite. This is shown in Scheme 1 1.
Figure imgf000017_0002
Scheme 1 1
Alternatively, the compounds of formula IXa, wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C C4 alkylcarbonyl, benzyl or C-1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XVI I, wherein R3, R4, R5, R6, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, with a compounds of formula XVII I, wherein R9, R10 are as defined for formula I and Hal is halogen, preferably chloro or bromo or iodo, and with a base. This is shown in Scheme 12.
Figure imgf000017_0003
Scheme 12
The compounds of formula V, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R 1, G2, X, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XV, wherein R3, R4, R5, R6, R7, R8, n and p are as defined for formula I and R17 is B(OH)2 or B(OR18)2 with the two R18 each independently being C1-C4 alkyl or together form a four to six-membered ring with a compound of formula IV, wherein R9, R10, R11, G2, X, Y1 and Y2 are as defined for formula I and halogen is chloro, bromo or iodo, and with a transition metal, such as tetrakis(triphenylphosphine)palladium, and a li and. This is shown in Scheme 13.
Figure imgf000018_0001
Scheme 13
The compounds of formula IV, wherein R9, R10, R11, G2, X, Y1 and Y2 are as defined for formula I and halogen is chloro, bromo or iodo,, can be obtained by transformation of a compound of formula III, wherein R9, R10, G2, Y1 and Y2 are as defined for formula I and halogen is chloro, bromo or iodo, with a compound of formula X, wherein R11 and X are as defined for formula I. This is shown in Scheme 14.
Figure imgf000018_0002
Scheme 14
Surprisingly, it has now been found that the novel compounds of formula I have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
The compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms. It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula I before planting: seed, for example, can be dressed before being sown. The active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
Furthermore the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.
In addition, the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Alternaria spp.), Basidiomycetes (e.g. Corticium spp., Ceratobasidium spp., Waitea spp., Thanatephorus spp., Rhizoctonia spp., Hemileia spp., Puccinia spp., Phakopsora spp., Ustilago spp., Tilletia spp.), Ascomycetes (e.g. Venturia spp., Blumeria spp., Erysiphe spp., Podosphaera spp., Uncinula spp., Monilinia spp., Sclerotinia spp., Colletotrichum spp., Glomerella spp., Fusarium spp., Gibberella spp., Monographella spp., Phaeosphaeria spp., Mycosphaerella spp., Cercospora spp., Pyrenophora spp., Rhynchosporium spp., Magnaporthe spp., Gaeumannomyces spp., Oculimacula spp., Ramularia spp., Botryotinia spp.) and Oomycetes (e.g. Phytophthora spp., Pythium spp., Plasmopara spp., Peronospora spp., Pseudoperonospora spp. Bremia spp). Outstanding activity is observed against downy mildew (e.g. Plasmopara viticola) and late blight (e.g. Phytophthora infestans). Furthermore, the novel compounds of formula I are effective against phytopathogenic gram negative and gram positive bacteria (e.g.
Xanthomonas spp, Pseudomonas spp, Erwinia amylovora, Ralstonia spp.) and viruses (e.g. tobacco mosaic virus).
Within the scope of present invention, target crops and/or useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as turf and ornamentals.
The useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties. By way of example, suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties.
The term "useful plants" and/or "target crops" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and
LibertyLink®.
The term "useful plants" and/or "target crops" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
The term "useful plants" and/or "target crops" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
The term "locus" of a plant as used herein is intended to embrace the place on which the plants are growing, where the plant propagation materials of the plants are sown or where the plant propagation materials of the plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.
The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
The compounds of formula I may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
Suitable carriers and adjuvants, e.g. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
The compounds of formula I are normally 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 e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
The compounds of formula I may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula I or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants. The invention provides a composition, preferably a fungicidal composition, comprising at least one compound formula I, an agriculturally acceptable carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably said composition 5 may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula I.
The compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional
10 active ingredient may, in some cases, result in unexpected synergistic activities. Examples of suitable additional active ingredients include the following: Azoxystrobin (131860-33-8), Dimoxystrobin (149961-52-4), Enestrobin (238410-1 1-2), Fluoxastrobin (193740-76-0), Kresoxim-methyl (143390-89-0), Metominostrobin (133408-50-1 ), Orysastrobin (248593-16- 0), Picoxystrobin (117428-22-5), Pyraclostrobin (175013-18-0), trifloxystrobin (141517-21-7),
15 Azaconazole (60207-31-0), Bromuconazole (1 16255-48-2), Cyproconazole (94361-06-5), Difenoconazole (1 19446-68-3), Diniconazole (83657-24-3), Diniconazole-M (83657-18-5), Epoxiconazole (13385-98-8), Fenbuconazole (114369-43-6), Fluquinconazole (136426-54- 5), Flusilazole (85509-19-9), Flutriafol (76674-21 -0), Hexaconazole (79983-71 -4), Imazalil (58594-72-2), Imibenconazole (86598-92-7), Ipconazole (125225-28-7), Metconazole
20 (1251 16-23-6), Myclobutanil (88671-89-0), Oxpoconazole (174212-12-5), Pefurazoate
(5801 1 -68-0), Penconazole (66246-88-6), Prochloraz (67747-09-5), Propiconazole (60207- 90-1 ), Prothioconazole (178928-70-6), Simeconazole (149508-90-7), Tebuconazole
(107534-96-3), Tetraconazole (1 12281-77-3), Triadimefon (43121-43-3), Triadimenol (55219-65-3), Triflumizole (99387-89-0), Triticonazole (131983-72-7), Diclobutrazol (76738-
25 62-0), Etaconazole (60207-93-4), Fluconazole (86386-73-4), Fluconazole-cis (1 12839-32-4), Thiabendazole (148-79-8), Quinconazole (103970-75-8), Fenpiclonil (74738-17-3),
Fludioxonil (131341-86-1 ), Cyprodinil (121552-61 -2), Mepanipyrim (1 10235-47-7),
Pyrimethanil (531 12-28-0), Aldimorph (91315-15-0), Dodemorph (1593-77-7),
Fenpropimorph (67564-91-4), Tridemorph (81412-43-3), Fenpropidin (67306-00-7),
30 Spiroxamine (118134-30-8), Isopyrazam (881685-58-1 ), Sedaxane (874967-67-6), Bixafen (581809-46-3), Penthiopyrad (183675-82-3), Fluxapyroxad (907204-31 -3), Boscalid (188425- 85-6), Penflufen (494793-67-8), Fluopyram (658066-35-4), Mandipropamid (374726-62-2), Benthiavalicarb (413615-35-7), Dimethomorph (1 10488-70-5), Chlorothalonil (1897-45-6), Fluazinam (79622-59-6), Dithianon (3347-22-6), Metrafenone (220899-03-6), Tricyclazole
35 (41814-78-2), Mefenoxam (70630-17-0), Metalaxyl (57837-19-1 ), Acibenzolar (126448-41 -7) (Acibenzolar-S-methyl (126448-41 -7)), Mancozeb (8018-01 -7), Ametoctradine (865318-97-4) Cyflufenamid (180409-60-3), and Kresoxim-methyl (143390-89-0), Ipconazole (125225-28- 7), Amisulbrom (348635-87-0), Cyflufenamid (180409-60-3), Ethaboxam (16650-77-3), Fluopicolide (2391 10-15-7), Fluthianil (304900-25-2), Isotianil (224049-04-1 ), Proquinazid (189278-12-4), Valiphenal (283159-90-0), 1-methyl-cyclopropene (3100-04-7), Trifloxystrobin (141517-21-7), Sulfur (7704-34-9), Copper ammoniumcarbonate (CAS 331 13-08-5); Copper oleate (CAS 1 120-44-1 ); Folpet (133-07-3), Quinoxyfen (124495-18-7), Captan (133-06-2), Fenhexamid (126833-17-8), Glufosinate and its salts (51276-47-2, 35597-44-5 (S-isomer)), Glyphosate (1071-83-6 ) and its salts (69254-40-6 (Diammonium), 34494-04-7
(Dimethylammonium), 38641-94-0 (Isopropylammonium), 40465-66-5 (Monoammonium), 70901-20-1 (Potassium), 70393-85-0 (Sesquisodium), 81591-81 -3 (Trimesium)), 1-methyl-3- difluoromethyl-1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1-methyl-indan-4- yl)-amide (1072957-71 -1 ), 1-methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (4'- methylsulfanyl-biphenyl-2-yl)-amide, 1-methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide, (5-Chloro-2,4-dimethyl-pyridin-3- yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy-pyridin-3- ylH2,3,4-trimethoxy-6-methyl-phenyl)-methanone, 2-{2-[(E)-3-(2,6-Dichloro-phenyl)-1- methyl-prop-2-en-(E)-ylideneaminooxymethyl]-phenyl}-2-[(Z)-methoxyimino]-N-methyl- acetamide, 3-[5-(4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine.
Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides, as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by phytopathogenic microorganisms, preferably fungal organisms.
A further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by
phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
Controlling or preventing means reducing infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying 5 the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, e.g. a composition containing the compound of formula I, and, if desired, 10 a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active
compounds (surfactants).
The agrochemical formulations and/or compositions will usually contain from 0.1 to 15 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. 20 When used as seed drenching agent, convenient dosages are from 10mg to 1 g of active substance per kg of seeds.
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
25 Preparation Examples:
Preparation of 2-[3,5-bis(difluoromethvnpyrazol-1 -yll-1-[4-r4-[10-methoxyimino-7.7-dimethyl- 4-oxa-3-azaspiror4.5ldec-2-en-2-yllthiazol-2-yll-1-piperidyllethanone
Figure imgf000024_0001
30 2-chloro-1-[4-[4-[10-methoxyimino-7,7-dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]thiazol-2- yl]-1-piperidyl]ethanone (156 mg) was added at 5°C to a mixture of 3,5-bis(difluoromethyl)- 1 H-pyrazole (61 mg) and potassium hydroxide solution (120mg; 20% in water) in dimethyl formamide (2 ml_). The reaction mixture was stirred for 16h at ambient temperature and for 3h at 65°C. Potassium hydroxide (60mg; 20% in water) was added and the reaction mixture
35 was stirred for further 45min at 65°C then diluted with water (1 OOmL) and filtrated. The residue was dried in a vacuum oven and purified over silica to give 2-[3,5- bis(difluoromethyl)pyrazol-1 -yl]-1-[4-[4-[10-methoxyimino-7,7-dimethyl-4-oxa-3- azaspiro[4.5]dec-2-en-2-yl]thiazol-2-yl]-1 -piperidyl]ethanone (106mg) as white foam LC-MS (Method A) UV Detection: 220 nm; Rt = 0.1 .08 MS: (M+1 ) = 585
Figure imgf000025_0001
Chloroacetylchloride (78.7mg) was added at 0-5°C to a solution of diisopropylethylamine (131 mg) and N-methoxy-7,7-dimethyl-2-[2-(4-piperidyl)thiazol-4-yl]-4-oxa-3-azaspiro[4.5]dec- 2-en-10-imine (250mg) in dichloromethane (3ml). After stirring for 90min at 0-5°C, the reaction mixture was quenched with water, diluted with dichloromethane (15ml) and washed 10 with hydrochloric acid (15ml, 1 M) and sodium bicarbonate (10% in water, 15ml). The organic phase was separated, dried over sodium sulfate, filtrated and concentrated. The residue was purified by chromatographie over silica to give 2-chloro-1-[4-[4-[10-methoxyimino-7,7- dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]thiazol-2-yl]-1 -piperidyl]ethanone (280mg) as an oran e oil. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.1 .08 , MS: (M+1 ) = 453.
Figure imgf000025_0002
Sodium hydroxide (2.22ml_; 5M in water) was added to a solution of 1-[4-[4-[(10- methoxyimino-7,7-dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]thiazol-2-yl]-1 - piperidyl]ethanone (464mg) in ethanol (7.4ml). After stirring for 16h at 85°C the reaction mixture was concentrated and ethylacetate (50ml) was added, insoluble was filtered and the
20 filtrate washed with water. The organic phase was separated dried over magnesium sulfate and concentrated to give an orange solid. All solid material were suspended in ethanol and put for 1 min into an ultrasonic bath. Insoluble material was filtered and the filtrate was concentrated to give N-methoxy-7,7-dimethyl-2-[2-(4-piperidyl)thiazol-4-yl]-4-oxa-3- azaspiro[4.5]dec-2-en-10-imine (399mg) as orange solid. LC-MS (Method A) UV Detection:
25 2 = 0.82, MS: (M+1 ) = 377.
Figure imgf000025_0003
Sodium hypochlorite (11.8mL, 12% in water) was added dropwise over 40min to a solution of 2-(1 -acetyl-4-piperidyl)thiazole-4-carbaldehyde oxime (1 g) and N-methoxy-4,4-dimethyl-2- methylene-cyclohexanimine (2.75g; 24% solution in a dichloromethane/acetonitrile; 1/1 ) and triethylamine (40mg). After stirring for 90min at ambient temperature the reaction mixture was diluted with ethylacetate and water. The phases were separate ant the organic phase was washed with water, dried over sodium sulfate, filtrated and concentrated. The residue was purified over silica to give 1-[4-[4-[10-methoxyimino-7,7-dimethyl-4-oxa-3- 5 azaspiro[4.5]dec-2-en-2-yl]thiazol-2-yl]-1 -piperidyl]ethanone as a light yellow foam (616mg). LC-MS (Method A) UV Detection: 220 nm; Rt = 1.03, MS: (M+1 ) = 419.
Alternative preparation of N-methoxy-7.7-dimethyl-2-r2-(4-piperidyl')thiazol-4-yll-4-oxa-3- azaspiro[4.5ldec-2-en-10-imine
Figure imgf000026_0001
O-methylhydroxylamine hydrochloride (2.06 g) was added to a solution of 7,7-dimethyl-2-[2- (4-piperidyl)thiazol-4-yl]-4-oxa-3-azaspiro[4.5]dec-2-en-10-one (2.37g) in ethanol (31 ml_). The reaction mixture was stirred for 16h at 60°C, then cooled to 25°C, concentrated and diluted with ethylacetate and sodium hydrogen carbonate solution (10% in water). Insoluble 15 material was filtered and dried to give N-methoxy-7,7-dimethyl-2-[2-(4-piperidyl)thiazol-4-yl]- 4-oxa-3-azaspiro[4.5]dec-2-en-10-imine (2.22g) as beige powder. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.82, MS: (M+1 ) = 377.
Figure imgf000026_0002
20 A solution of HCI (10.6mL; 4M in dioxane) was added to a solution tert-butyl 4-[4-(7,7- dimethyl-10-oxo-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl)thiazol-2-yl]piperidine-1 -carboxylate (3.13g) in dioxane (28mL). After stirring for 4h at 25°C and 16h at 60°C the reaction mixture was cooled to 20°C and the precipitated solid was filtered. The solid was washed with ethylacetate to give 7,7-dimethyl-2-[2-(4-piperidyl)thiazol-4-yl]-4-oxa-3-azaspiro[4.5]dec-2-en-
25 10-one hydrochloride (2.47g) as white solid. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.71 , MS: (M+1 ) = 348.
Figure imgf000026_0003
Sodium hypochlorite (15.4g 12% in water) was added dropwise within 30min to a solution of 30 tert-butyl 4-[4-[hydroxyiminomethyl]thiazol-2-yl]piperidine-1-carboxylate (3.8g), triethylamine (0.124g) and 4,4-dimethyl-2-methylene-cyclohexanone (1.86g in 50mL dichloromethane) in ethylacetate (60ml_). After stirring for 16h at 25°C the reaction mixture was diluted with ethylacetate and washed with water. The organic phase was separated, dried over sodium sulfate, concentrated and the residue was purified by chromatographie over silica to give tert- butyl 4-[4-(7,7-dimethyl-10-oxo-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl)thiazol-2-yl]piperidine-1- carboxylate (3.13g) as white solid. LC-MS (Metod A) UV Detection: 220 nm; Rt = 1.17, MS: (M+1 ) = 348 (only Mass of deprotected compound was dedected).
Alternative preparation of 1-r4-i4-[10-methoxyimino-7.7-dimethyl-4-oxa-3-azaspiro[4.5ldec-2- n-2-yllthiazol-2-yll-1-piperidyllethanone
Figure imgf000027_0001
To a solution of 1-acetylpiperidine-4-carbothioamide (0.1299 g) and 2-chloro-1-[(10- methoxyimino-7,7-dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]ethanone (0.200 g) in DMF (2 ml_) , was added sodium bromide (0.1076 g). The reaction mixture was stirred at 80°C for 2h, cooled to ambient temperature, dilutes with water and extracted with ethyl acetate. The combined organic phases were washed with water, dried over magnesium sulfate, filtered and concentrated. The residue was purified by chromatographie over silica to give 1-[4-[4- [10-methoxyimino-7,7-dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]thiazol-2-yl]-1- piperidyl]ethanone (0.216g) as a white foam. LC-MS (Method A) UV Detection: 220 nm; Rt = 1.03, MS: (M+) = 419.
Figure imgf000027_0002
A solution of 3-chloro-N-hydroxy-2-oxo-propanimidoyl chloride (2.1g) in ethylacetate (10ml) was added at 25°C within 30min to a well stirred mixture of N-methoxy-4,4-dimethyl-2- methylene-cyclohexanimine (5g; 30% in dichloromethane) and sodiumbicarbonate (4.52g) in ethylacetate (1 OmL). After stirring for 16h at 25°C the reaction mixture was diluted with etylacetate and washed with water. The organic phase was dried over magnesium sulfate, filtered and concentrated and the residue was purified by chromatographie over silica to give 2-chloro-1-[10-methoxyimino-7,7-dimethyl-4-oxa-3-azaspiro[4.5]dec-2-en-2-yl]ethanone (1.21g) as yellow oil. LC-MS (Method A) UV Detection: 220 nm; Rt = 1.13, MS: (M+) = 287.
Preparation of 2-(1 -acetyl-4-piperidvDthiazole-4-carbaldehvde oxime
Figure imgf000028_0001
Hydroxylamine hydrochloride was added to a solution of 2-(1-acetyl-4-piperidyl)thiazole-4- carbaldehyde (3.9g) in ethanol (65ml_). After stirring for 16h at 25°C the reaction mixture was concentrated and water was added and the insoluble material was filtrated and dried to give 2-(1 -acetyl-4-piperidyl)thiazole-4-carbaldehyde oxime (2.53g) as white solid. LC-MS (Method
= 0.54, MS: (M+) = 254.
Figure imgf000028_0002
Triethylamine (9.72g) was added at 0-5°C to a solution of 2-(4-piperidyl)thiazole-4- carbaldehyde dihydrochloride (8.0) in dichloromethane (100ml_). Acetylchloride (2.80g) was added at 0-5°C, the reaction mixture was warmed up and stirred for 16h at 25°C. The reaction mixture was poured onto sodium bicarbonate solution (300ml_; 20% in water) and extracted with dichloromethane. The combined organic phases were washed with brine dried over magnesiumsulfate, filtered and concentrated. The residue was purified by
chromatographie over silica to give 2-(1 -acetyl-4-piperidyl)thiazole-4-carbaldehyde (3.05g) as yellow oil. . LC-MS (Method A) UV Detection: 220 nm; Rt = 0.49, MS: (M+) = 239.
Pre aration of N-methoxy-4,4-dimethyl-2-methylene-cyclohexanimine
Figure imgf000028_0003
Acetonitrile (43mL) was added to a suspension of [2-methoxyimino-5,5-dimethyl- cyclohexyl]methyl-trimethyl-ammonium iodide (3.63g) in sodium hydroxide (16.6mL, 2M in water). After stirring for 15h at 80°C the reaction mixture was cooled and most of the acetonitrile was removed. The residue was diluted with dichloromethane. The organic phase was separated and the water phase was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and carefully concentrated to give N-methoxy-4,4-dimethyl-2-methylene-cyclohexanimine (1.7g) which contains according to 1 HNMR 45% of dichloromethane. 1 H-NMR (CDCI3, 400 MHz): 5.38 (s, 1 H), 4.80 (s, 1 H), 3.90 (s,3H), 2.52 (t, 2H), 2.16 (s, 2H), 1.48 (t, 2H), 0.95 (s, 6H).
This product was used in the next steps without further purification. Depending on workup this product can contain variable amounts of dichloromethane and acetonitrile.
Figure imgf000029_0001
lodomethane (16.6g) was added to a solution of 1-[2-methoxyimino-5,5-dimethyl-cyclohexyl]- Ν,Ν-dimethyl-methanamine (12.35g) in methanol (68ml_). The reaction mixture was stirred for 16h at ambient temperature then concentrated under reduced pressure to give [2- methoxyimino-5,5-dimethyl-cyclohexyl]methyl-trimethyl-ammonium iodide (20.1g) as a yellow solid. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.60, MS: (M+) = 227.
Figure imgf000029_0002
Sodium acetate (6.44g) and O-methylhydroxyl amine hydrochloride (6.56g) were added to a solution of 2-(dimethylaminomethyl)-4,4-dimethyl-cyclohexanone (12g) in ethanol (80mL). After stirring for 3h at ambient temperature the reaction mixture was concentrated and to the residue sodium hydroxide (10% in water) was added. The mixture was extracted with diethyl ether and the combined organic phases were dried over magnesium sulfate, filtered and concentrated to give 1-[2-methoxyimino-5,5-dimethyl-cyclohexyl]-N,N-dimethyl-methanamine (12.6g) as a colorless liquid. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.56+0.61 , MS: ( +1 ) = 213
Preparation of 4.4-dimethyl-2-methylene-cvclohexanone
Figure imgf000029_0003
Aluminiumoxide (12.2g; alox basic 50-200uM) was added to a solution of (5,5-dimethyl-2- oxo-cyclohexyl)methyl-trimethyl-ammonium iodide (14g) in dichloromethane (140mL). After stirring for 4h at 25°C the reaction mixture was filtered and the solid was washed with 20ml of dichloromethane. This solution contains 4,4-dimethyl-2-methylene-cyclohexanone (5.9 g) and was used in the next step without further purification.
The content of 4,4-dimethyl-2-methylene-cyclohexanone in the above solution was assumed to be same as in small scale test reaction with CD2CI2 as solvent. The conversion was followed by 1 H-NMR measurements. After 2h of stirring: 1 H-NMR(CD2CI2, 400 MHz): 5.68 (m,1 H); 5.00 (m,1 H); 2.33 (t, 2H); 2.29 (s, 2H); 1 .64 (t, 2H); 0.97 (s, 6H)
Figure imgf000030_0001
lodomethane (26.5g) was added to a solution of 2-(dimethylaminomethyl)-4,4-dimethyl- cyclohexanone (17g) in methanol (110mL). After stirring for 4h at 25°C the reaction mixture was concentrated to give (5,5-dimethyl-2-oxo-cyclohexyl)methyl-trimethyl-ammonium iodide (29.8g) as light yellow solid. LC-MS (Method A) UV Detection: 220 nm; Rt = 0.30, MS: (M+) = 198.
Figure imgf000030_0002
Dimethyl(methylene)ammonium chloride (16.1 g) was added to a solution of 4,4- dimethylcyclohexanone (20.5 g) in acetonitrile (82mL). After stirring at ambient temperature for 16h the reaction mixture was filtered and the white solid was washed with diethylether to give 2-(dimethylaminomethyl)-4,4-dimethyl-cyclohexanone hydrochloride (28.9g) as a white solid. 1 H-NMR (CDCI3, 400 MHz): 3.58 (m,1 H); 3.31 (m,1 H); 2.80 (d, 3H); 2.70 (d, 3H); 2.75- 2.51 (m, 2H); 2.27 (m, 1 H); 2.03 (m, 1 H); 1.72 (m, 1 H); 1.57 (m, 1 H); 1.37 (t, 1 H); 1.26 (s, 3H); 0.97 (s, 3H).
This solid was then suspended in diethylether (130ml) and triethylamine (65. Og) was added. After stirring for 3h at ambient temperature the reaction mixture was filtered and the filtrate was concentrated to give 2-(dimethylaminomethyl)-4,4-dimethyl-cyclohexanone (20.8g) as a colorless liquid which was used without further purification in next steps.
P rep a rati o n of l-^-^-rS-iN-methoxy-C-phenyl-carbonimidoyll^.S-dihvdroisoxazol-S- yllthiazol-2-yll-1-piperidyll-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yllethanone
Figure imgf000030_0003
To a cooled suspension (0°C) of N-methoxy-1-phenyl-1 -[3-[2-(4-piperidyl)thiazol-4-yl]-4,5- dihydroisoxazol-5-yl]methanimine trifluoroacetic acid salt (0.1 11 g) in dichloromethane (1.15 mL) was added triethylamine (0.058 g) and the mixture was stirred for 5 min. Then a solution of 2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl chloride (0.053 g) in dichloromethane (3mL) was added slowly and the mixture was stirred at 0°C for 30 min, after which LCMS showed complete consumption of the starting material. The reaction mixture was diluted with water and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with 1 M HCI, sat. aq. sodiumbicarbonate, brine, dried over
sodiumsulfate, filtered and concentrated under reduced pressure to give 1 10 mg of brown oil. The residue was purified by flash chromatography to give 1 -[4-[4-[5-[N-methoxy-C-phenyl- carbonimidoyl]-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-1 -piperidyl]-2-[5-methyl-3- (trifluoromethyl)pyrazol-1-yl]ethanone (51 mg) as a white foamy solid. LC-MS (Method B) UV Detection: 220 nm; Rt = 1.76, 1 .81 , MS: (M+1 ) = 561.
Figure imgf000031_0001
To a dry flask containing tert-butyl 4-[4-[5-[N-methoxy-C-phenyl-carbonimidoyl]-4,5- dihydroisoxazol-3-yl]thiazol-2-yl]piperidine-1-carboxylate (0.10 g) under an atmosphere of argon was added trifluoroacetic acid (1.0 ml_) and the mixture was stirred at rt for 1 h. LCMS indicated complete consumption of the starting material. Removal of trifluoroacetic acid under vacuo afforded N-methoxy-1-phenyl-1 -[3-[2-(4-piperidyl)thiazol-4-yl]-4,5- dihydroisoxazol-5-yl]methanimine trifluoroacetic acid salt (0.12 g) as a colorless oil which was directly used in the next step without further purification. LC-MS (Method B) UV
Detection: 220 nm; Rt = 0.88, 0.91 , MS: (M+1 ) = 371.
Figure imgf000031_0002
To a solution of tert-butyl 4-[4-[hydroxyiminomethyl]thiazol-2-yl]piperidine-1 -carboxylate (0.440 g), bisacetoxy iodobenzene (0.660 g) and trifluoroacetic acid (0.0531 g) in methanol (29.0 mL) under an argon atmosphere was added N-methoxy-1-phenyl-prop-2-en-1-imine (0.58 g) was added and the white suspension was stirred at room temperature overnight. The colorless solution was concentrated and purified by flash chromatography to give tert- butyl 4-[4-[5-[N-methoxy-C-phenyl-carbonimidoyl]-4,5-dihydroisoxazol-3-yl]thiazol-2- yl]piperidine-1-carboxylate (680 mg) as a white foam. LC-MS (Method B) UV Detection: 220 nm; Rt = 1.96, 2.01 , MS: (M+Na) = 493. Preparation of N-methoxy-1 -phenyl-prop-2-en-1-imine
Figure imgf000032_0001
To a suspension of [3-methoxyimino-3-phenyl-propyl]-trimethyl-ammonium iodide (0.720 g) in acetonitrile (7.2 mL) was added an aqueous solution of sodium hydroxide (2.0 mol/L; 3.4 mL) and the mixture was stirred at room temperature for 3h. The reaction mixture was diluted with dichloromethane and water and the phases were separated. The aqueous phase was extracted with dichloromethane and the combined organic phases were washed with water, dried over sodiumsulfate, filtered and concentrated to give N-methoxy-1-phenyl-prop-2-en-1- imine (445 mg) as a pale yellow oil. LC-MS (Method B) UV Detection: 220 nm; Rt = 1 .48, 1.56, MS: (M+1 ) = 162.
Figure imgf000032_0002
To a solution of 3-methoxyimino-N,N-dimethyl-3-phenyl-propan-1-amine (0.350 g) in methanol (3.0 mL) was added methyl iodide (0.484 g) and the mixture was stirred at room temperature for 3 h. Removal of the solvent under reduced pressure afforded [3- methoxyimino-3-phenyl-propyl]-trimethyl-ammonium iodide (0.570 g) as a pale yellow solid. LC-MS (Method B) UV Detection: 220 nm; Rt = 0.48, 0.57, MS: (M+) = 221.
Figure imgf000032_0003
To a solution of 3-(dimethylamino)-1-phenyl-propan-1-one (2.00 g) in ethanol (12 mL, 1.0 mol/L) were added sodium acetate (1.12 g) and O-methylhyroxylamine hydrochloride (1.15 g) and the reaction mixture was stirred at room temperature for 4 h. The solvent was removed under reduced pressure and the residue was basified with an aqueous solution of sodium hydroxide (10% w/w) until pH 13-14. The aqueous phase was extracted with diethylether and the combined organic phases were dried over sodiumsulfate, filtered and concentrated. The residue was purified by flash chromatography to give 3-methoxyimino- N,N-dimethyl-3-phenyl-propan-1 -amine (3.04 mmol, 660 mg) as a mixture of (E) and (Z) isomers. LC-MS (Method B) UV Detection: 220 nm; Rt = 0.43, 0.52, MS: (M - N(CH3)2) = 162. Table 1 below illustrates examples of individual compounds of formula I according to the invention. Table 1 : individual compounds of formula I according to the invention
In Table 1 below, Ί" refers to a carbon-oxygen single bond, "j" refers to a carbon-carbon single bond and "k" refers to a carbon-nitrogen double bond as shown below on the general formula (I):
Figure imgf000033_0001
Entry. R» R R
No.
001 H H H
002 Me H H
003 iPr H H
004 nPr H H
005 cyclopropyl H H
006 H H
JO
007 H H
¾? F
008 H H
F
009 H H
J?
CI
010 H H
V- Me
Figure imgf000034_0001
Figure imgf000035_0001
Figure imgf000036_0001
Figure imgf000037_0001
Figure imgf000038_0001
Figure imgf000039_0001
Figure imgf000040_0001
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
Figure imgf000105_0001
Figure imgf000106_0001
Figure imgf000107_0001
Figure imgf000108_0001
Figure imgf000109_0001
Figure imgf000110_0001
Figure imgf000111_0001
Figure imgf000112_0001
Figure imgf000113_0001
Figure imgf000114_0001
Figure imgf000115_0001
H3C
Figure imgf000116_0001
N-OH
Figure imgf000116_0002
N-0
CH3
Figure imgf000116_0003
HO-N
Figure imgf000116_0004
O-N
H3C
Figure imgf000116_0005
Op F
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
where a) 889 compounds of formula (la. a):
Figure imgf000127_0002
wherein R , R , R are as defined in Table 1. b) 889 compounds of formula (la.b):
Figure imgf000128_0001
wherein R , R , R are as defined in Table 1. c) 889 compounds of formula (la.c):
Figure imgf000128_0002
wherein R9, R10, R11 are as defined in Table 1. d) 889 compounds of formula (la.d):
Figure imgf000128_0003
Wherein R9, R10, R11 are as defined in Table 1. e) 889 compounds of formula (la.e):
Figure imgf000129_0001
wherein R , R , R are as defined in Table 1. f) 889 compounds of formula (la.f):
Figure imgf000129_0002
wherein R , R , R are as defined in Table 1. g) 889 compounds of formula (la.g):
Figure imgf000129_0003
wherein R9, R10, R11 are as defined in Table 1. h) 889 compounds of formula (la.h):
Figure imgf000130_0001
wherein R9, R10, R11 are as defined in Table 1. i) 889 compounds of formula (la.i):
Figure imgf000130_0002
wherein R9, R10, R11 are as defined in Table 1. j) 889 compounds of formula (la.j):
Figure imgf000130_0003
wherein R9, R10, R11 are as defined in Table 1. k) 889 compounds of formula (la.k):
Figure imgf000131_0001
wherein R9, R10, R11 are as defined in Table 1. I) 889 compounds of formula (la. I):
Figure imgf000131_0002
wherein R9, R10, R11 are as defined in Table 1. m) 889 compounds of formula (la.m):
Figure imgf000131_0003
Wherein R9, R10, R11 are as defined n) 889 compounds of formula (la.n)
Figure imgf000132_0001
wherein R9, R 0, R are as defined in Table 1. o) 889 compounds of formula (la.o):
Figure imgf000132_0002
wherein R9, R10, R11 are as defined in Table 1. p) 889 compounds of formula (la.p):
Figure imgf000132_0003
wherein R9, R10, R11 are as defined in Table 1. q) 889 compounds of formula (la.q):
Figure imgf000133_0001
wherein R9, R10, R11 are as defined in Table 1. r) 889 compounds of formula (la.r):
Figure imgf000133_0002
wherein R9, R10, R11 are as defined in Table 1. s) 889 compounds of formula (lb. a):
Figure imgf000133_0003
wherein R9, R10, R11 are as defined in Table 1. t) 889 compounds of formula (Ib.b):
Figure imgf000134_0001
wherein R , R , R are as defined in Table 1. u) 889 compounds of formula (Ib.c):
Figure imgf000134_0002
wherein R9, R 0, R11 are as defined in Table 1.. v) 889 compounds of formula (Ib.d):
Figure imgf000134_0003
Wherein R9, R10, R11 are as defined in Table 1. w) 889 compounds of formula (Ib.e):
Figure imgf000135_0001
wherein R , R , R are as defined in Table 1. x) 889 compounds of formula (Ib.f):
Figure imgf000135_0002
wherein R9, R10, R11 are as defined in Table 1. y) 889 compounds of formula (Ib.g):
Figure imgf000135_0003
wherein R9, R10, R11 are as defined in Table 1. z) 889 compounds of formula (Ib.h):
Figure imgf000136_0001
aa) 889 compounds of formula (Ib.i):
Figure imgf000136_0002
wherein R9, R10, R11 are as defined in Table 1. ab) 889 compounds of formula (Ib.j):
Figure imgf000136_0003
wherein R9, R10, R11 are as defined in ac) 889 compounds of formula (Ib.k):
Figure imgf000137_0001
wherein R9, R10, R11 are as defined in Table 1. ad) 889 compounds of formula (lb. I):
Figure imgf000137_0002
wherein R9, R10, R11 are as defined in Table 1.. ae) 889 compounds of formula (Ib.m):
Figure imgf000137_0003
Wherein R9, R10, R11 are as defined in Table 1. af) 889 compounds of formula (Ib.n):
Figure imgf000138_0001
wherein R9, R10, R11 are as defined in Table 1. ag) 889 compounds of formula (Ib.o):
Figure imgf000138_0002
wherein R9, R10, R11 are as defined in Table 1. ah) 889 compounds of formula (Ib.p):
Figure imgf000138_0003
wherein R9, R10, R11 are as defined in Table 1. ai) 889 compounds of formula (Ib.q):
Figure imgf000139_0001
wherein R9, R10, R11 are as defined in Table 1. aj) 889 compounds of formula (Ib.r):
Figure imgf000139_0002
wherein R9, R10, R11 are as defined in Table 1. ak) 889 compounds of formula (lea):
Figure imgf000139_0003
wherein R9, R10, R11 are as defined in Table 1. al) 889 compounds of formula (Ic.b):
Figure imgf000140_0001
wherein R9, R10, R11 are as defined in Table 1. am) 889 compounds of formula (Ice):
Figure imgf000140_0002
wherein R9, R10, R11 are as defined in Table 1.. an) 889 compounds of formula (led):
Figure imgf000140_0003
Wherein R9, R10, R11 are as defined in Table 1. ao) 889 compounds of formula (Ice):
Figure imgf000141_0001
wherein R9, R10, R11 are as defined in Table 1. ap) 889 compounds of formula (Ic.f):
Figure imgf000141_0002
ar) 889 compounds of formula (Ic.h):
Figure imgf000142_0001
wherein R9, R10, R11 are as defined in Table 1. as) 889 compounds of formula (Ic.i):
Figure imgf000142_0002
wherein R9, R10, R11 are as defined in Table 1. at) 889 compounds of formula (lc.j):
Figure imgf000142_0003
wherein R9, R10, R11 are as defined in Table 1. au) 889 compounds of formula (Ic.k):
Figure imgf000143_0001
wherein R9, R10, R11 are as defined in Table 1. av) 889 compounds of formula (Id):
Figure imgf000143_0002
wherein R9, R10, R11 are as defined in Table 1.. aw) 889 compounds of formula (Ic.m):
Figure imgf000143_0003
Wherein R9, R10, R11 are as defined in Table 1. ax) 889 compounds of formula (Ic.n):
Figure imgf000144_0001
wherein R9, R10, R11 are as defined in Table 1. ay) 889 compounds of formula (Ic.o):
Figure imgf000144_0002
wherein R9, R10, R11 are as defined in Table 1. az) 889 compounds of formula (Ic.p):
Figure imgf000144_0003
wherein R9, R10, R11 are as defined in Table 1. ba) 889 compounds of formula (Icq):
Figure imgf000145_0001
wherein R , R , R are as defined in Table 1. bb) 889 compounds of formula (Ic.r):
Figure imgf000145_0002
wherein R9, R10, R11 are as defined in Table 1. be) 889 compounds of formula (l.d.a):
Figure imgf000145_0003
wherein R9, R10, R11 are as defined in bd) 889 compounds of formula (Id.b):
Figure imgf000146_0001
wherein R9, R10, R11 are as defined in Table 1. be) 889 compounds of formula (Id.c):
Figure imgf000146_0002
wherein R9, R10, R11 are as defined in Table 1.. bf) 889 compounds of formula (Id.d):
Wherein R9, R10, R11 are as defined in Table 1. bg) 889 compounds of formula (Id.e):
Figure imgf000147_0001
wherein R9, R10, R11 are as defined in Table 1. bh) 889 compounds of formula (Id.f):
Figure imgf000147_0002
wherein R9, R10, R11 are as defined in Table 1. bi) 889 compounds of formula (Id.g):
Figure imgf000147_0003
wherein R9, R10, R11 are as defined in Table 1. bj) 889 compounds of formula (Id.h):
Figure imgf000148_0001
wherein R9, R10, R11 are as defined in Table 1. bk) 889 compounds of formula (Id.i):
Figure imgf000148_0002
wherein R9, R10, R11 are as defined in Table 1. bl) 889 compounds of formula (I.e. a):
Figure imgf000148_0003
wherein R9, R10, R11 are as defined in Table 1. bm) 889 compounds of formula (I.e.b):
Figure imgf000149_0001
wherein R9, R10, R11 are as defined in Table 1. bn) 889 compounds of formula (le.c):
Figure imgf000149_0002
wherein R9, R10, R11 are as defined in Table 1.. bo) 889 compounds of formula (le.d):
Figure imgf000149_0003
Wherein R9, R10, R11 are as defined in Table 1. bp) 889 compounds of formula (le.e):
Figure imgf000150_0001
wherein R9, R10, R11 are as defined in Table 1. bq) 889 compounds of formula (le.f):
Figure imgf000150_0002
wherein R9, R10, R11 are as defined in Table 1. br) 889 compounds of formula (le.g):
Figure imgf000150_0003
wherein R9, R10, R11 are as defined in Table 1. bs) 889 compounds of formula (le.h):
Figure imgf000151_0001
wherein R9, R10, R11 are as defined in Table 1. bt) 889 compounds of formula (le.i):
Figure imgf000151_0002
wherein R9, R10, R11 are as defined in Table 1.
Throughout this description, temperatures are given in degrees Celsius and "m.p." means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the methods are:
Method A
SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Instrument Parameter:
Ionization method: Electrospray; Polarity: positive and negative ions; Capillary: 3.00 kV; Cone: 30V; Extractor: 2.00 V; Source Temperature: 150°C; Desolvation Temperature: 350°C; Cone Gas Flow: 0 L/Hr; Desolvation Gas Flow: 650 L/Hr; Mass range: 100 to 900 Da
Acquity UPLC from Waters:
Binary pump, heated column compartment and diode-array detector.
Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3 , 1.8 μΐη, 30 x 2.1 mm,
Temp: 60 °C
DAD Wavelength range (nm): 210 to 500
Solvent Gradient:
A = H20 + 5% MeOH + 0.05 % HCOOH; B= Acetonitril + 0.05 % HCOOH
Time A% B% Flow (ml/min)
0.00 90 10 0.85
1.20 0 100.0 0.85
1.50 0 100.0 0.85
Method B: ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer) Instrument Parameter:
Ionization method: Electrospray; Polarity: positive and negative ions; Capillary: 3.00 kV; Cone: 30 V; Extractor: 2.00 V; Source Temperature: 150°C; Desolvation Temperature: 350C; Cone Gas Flow: 50 L/Hr; Desolvation Gas Flow: 400 L/Hr; Mass range: 100 to 900 Da
Acquity UPLC from Waters:
Binary pump, heated column compartment and diode-array detector.
Solvent degasser, binary pump, heated column compartment and diode-array detector.
Column: Waters UPLC HSS T3 , 1.8 μΐτι, 30 x 2.1 mm,
Temp: 60 °C
DAD Wavelength range (nm): 210 to 500
Solvent Gradient:
A = H20 + 5% MeOH + 0.05 % HCOOH; B= Acetonitril + 0.05 % HCOOH
Time A% B% Flow (ml/min)
0.00 90 10 0.85
2.70 0 100.0 0.85
3.00 0 100.0 0.85
Table 2: Melting point and LC/MS data for compounds compounds according to the invention ı52
Figure imgf000153_0001
Figure imgf000154_0001
Figure imgf000155_0001
Figure imgf000156_0001
Figure imgf000157_0001

Figure imgf000158_0001
Figure imgf000159_0001
Figure imgf000160_0001
160
Figure imgf000161_0001
Figure imgf000162_0001
ı63
Figure imgf000164_0001
ı64
Figure imgf000165_0001
ı65
Figure imgf000166_0001
ı66
Figure imgf000167_0001
Figure imgf000168_0001

Figure imgf000169_0001

Figure imgf000170_0001
Figure imgf000171_0001
Figure imgf000172_0001
Figure imgf000173_0001
ı73
Figure imgf000174_0001
Figure imgf000175_0001
Figure imgf000176_0001
Figure imgf000177_0001
ı77
Figure imgf000178_0001
Figure imgf000179_0001

Figure imgf000180_0001
180
Figure imgf000181_0001
Figure imgf000182_0001
The compounds according to the present invention can be prepared according to the 5 above-mentioned reaction schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).
Biological examples
The compounds listed below are those from Table 2.
10
Phytophthora infestans I tomato / leaf disc preventative (tomato late blight)
Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are
15 incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
Compounds 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 20 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 1 1 1 , 1 12 , 113 , 114 , 1 15 , 1 16 , 117 , 1 18 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 127 , 129 , 131 , 132 , 133 , 25 135 , 136 , 137 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
30 Phytophthora infestans I tomato / leaf disc curative (tomato late blight) Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and the leaf disks are inoculated with a spore suspension of the fungus. The inoculated leaf disks are incubated at 16°C and 75% rh in darkness in a climate cabinet. 20 hours after inoculation the leaf disks are sprayed with the formulated test compound diluted in water and the leaf disks are incubated at 16°C and 75% rh under 5 a light regime of 12 h light / 12 h darkness in a climate cabinet. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (4 - 6 days after inoculation).
Compounds 1 , 2 , 5 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ,
10 53 , 54 , 55 , 56 , 57 , 59 , 60 , 61 , 62 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 96 , 97 , 98 , 99 , 100 , 101 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 1 1 1 , 1 12 , 114 , 115 , 1 16 , 1 17 , 118 , 120 , 121 , 122 , 123 , 124 , 125 , 127 , 132 , 133 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 165 at 200 ppm give at least 80% disease
15 control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Phytophthora infestans I potato / preventative (potato late blight)
2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound 20 diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 2 days after application. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5 - 7 days after application).
Compounds 1 , 2 , 7 , 9 , 10 , 13 , 15 , 16 , 19 , 20 , 22 , 23 , 24 , 26 , 31 , 32 , 42 , 45 , 52 , 56 , 59 , 25 69 , 71 , 74 , 78 , 80 , 84 , 91 , 92 , 94 , 96 , 105 , 106 , 107 , 110 , 114 , 1 15 , 1 16 , 117 , 120 , 125 at
200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Phytophthora infestans I potato / curative (potato late blight)
30 2-week old potato plants cv. Bintje are inoculated by spraying them with a sporangia suspension one day before application. The inoculated plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (3 - 4 days after application).
35 Compounds 1 , 2 , 7 , 9 , 10 , 13 , 15 , 16 , 19 , 20 , 22 , 23 , 24 , 26 , 31 , 42 , 45 , 52 , 56 , 59 , 69 , 71 , 74 , 78 , 80 , 84 , 91 , 92 , 94 , 96 , 105 , 106 , 107 , 110 , 114 , 115 , 1 16 , 1 17 , 120 , 125at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Phytophthora infestans I potato / long lasting (potato late blight)
2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 6 days after application. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (9 - 1 1 days after application).
Compounds 1 , 2 , 7 , 9 , 10 , 13 , 15 , 16 , 19 , 20 , 22 , 23 , 24 , 26 , 31 , 32 , 42 , 45 , 52 , 56 , 59 , 5 69 , 71 , 74 , 78 , 80 , 84 , 91 , 92 , 94 , 96 , 105 , 106 , 107 , 110 , 114 , 1 15 , 1 16 , 117 , 120 , 125 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Plasmopara viticola I grape / leaf disc preventative (grape downy mildew)
10 Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease 15 damage appears in untreated check leaf disks (6 - 8 days after application).
Compounds 1 , 2 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 65 , 66 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 78 , 79 , 80 , 81 , 82 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 100 , 101 , 103 , 20 104 , 105 , 106 , 107 , 109 , 110 , 111 , 112 , 1 13 , 1 14 , 115 , 116 , 1 17 , 1 18 , 120 , 121 , 122 , 123 , 124 , 125 , 127 , 129 , 132 , 133 , 134 , 135 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
25
Plasmopara viticola I grape / preventative (grape downy mildew)
5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants plants are inoculated by spraying a sporangia suspension on their lower leaf surface one day after application. The inoculated test plants are incubated at 22° C
30 and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (6 - 8 days after application).
Compounds 1 , 2 , 7 , 9 , 10 , 13 , 15 , 16 , 19 , 20 , 22 , 23 , 24 , 26 , 31 , 32 , 33 , 34 , 37 , 40 , 42 , 44 , 45 , 47 , 50 , 51 , 52 , 56 , 59 , 69 , 71 , 74 , 78 , 80 , 84 , 91 , 92 , 94 , 96 , 105 , 106 , 107 , 1 10 , 114 , 115 , 116 , 1 17 , 120 , 125 , 133 , 151 , 152 at 200 ppm give at least 80% disease control in this
35 test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Plasmopara viticola I grape / curative (grape downy mildew)
5-week-old grape seedlings cv. Gutedel are inoculated by spraying a sporangia suspension on their 40 lower leaf surface one day before application. The inoculated grape plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (4 - 6 days after application). Compounds 1 , 7 , 13 , 15 , 16 , 19 , 20 , 23 , 26 , 31 , 42 , 45 , 52 , 56 , 59 , 74 , 78 , 80 , 91 , 92 , 94 , 96 , 105 , 106 , 107 , 1 10 , 1 14 , 1 15 , 116 , 1 17 at 200 ppm give at least 80% disease control in this 5 test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Plasmopara viticola I grape / long lasting (grape downy mildew)
5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test 10 compound diluted in water. The test plants are inoculated by spraying a sporangia suspension on their lower leaf surface 6 days after application. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (11 - 13 days after application).
Compounds 1 , 7 , 9 , 10 , 13 , 15 , 16 , 19 , 20 , 22 , 23 , 24 , 26 , 31 , 42 , 45 , 52 , 56 , 59 , 69 , 71 , 15 74 , 78 , 80 , 84 , 91 , 92 , 94 , 96 , 106 , 107 , 1 10 , 114 , 115 , 1 16 , 1 17 , 120 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
20 Pythium ultimum I liquid culture (seedling damping off)
Mycelia fragments and oospores of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal mycelia/spore mixture is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically
25 2-3 days after application.
Compounds 1 , 7 , 13 , 15 , 16 , 17 , 19 , 20 , 22 , 23 , 24 , 31 , 33 , 35 , 36 , 37 , 41 , 42 , 43 , 44 , 50 , 51 , 52 , 53 , 54 , 56 , 60 , 61 , 62 , 68 , 69 , 71 , 79 , 80 , 84 , 88 , 91 , 92 , 93 , 94 , 96 , 105 , 107 , 110 , 133 , 162 , 163 , 165 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

Claims

What is claimed is:
Figure imgf000186_0001
wherein,
G1 and G2 are independently O or S;
T is CR12 or N;
Y1 and Y2 are independently CR13 or N;
n is 1 or 2;
p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are Ci-C4alkyl, C3-C5cycloalkyl or C1-C4haloalkyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen, hydroxy, halogen, cyano, C-p
C4alkyl, Cr^alkoxy, C3-C5cycloalkyl or Ci-C4haloalkyl;
R9 and R10 each independently are hydrogen, Ci-C alkyl, Ci-C haloalkyl, C3-C5cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10- membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by one or more R14;
X is O or N-R15
R11 is hydrogen, Ci-C alkyl, C3-C5cycloalkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C5cycloalkylCr C4alkyl, aryl, Ci-C4alkylsulfonyl, arylsulfonyl, heteroaryl, arylalkyi and heteroarylalkyi wherein alkyl, cycloalkyl, alkenyl are optionally substituted by halogen, and wherein aryl, heteroaryl, arylalkyi and heteroarylalkyi are optionally substituted by one or more R14;
R12 is hydrogen, halogen or hydroxyl;
R13 is hydrogen, halogen, cyano, Ci-C4alkyl or C1-C4 alkyoxy;
each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, Ci-C8alkyl, C2- C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C-rC4alkyl, C3-C8cycloalkyl-C-r C4alkoxy, C3-C8cycloalkyl-C1-C4alkylthio, C-|-C8alkoxy, C3-C8cycloalkoxy, C-rC8alkenyloxy, C2-C8alkynyloxy, C-|-C8alkylthio, C-|-C8alkylsurionyl, CrCsalkylsulfinyl, C3-C8cycloalkylthio, C3- C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-Ci-C4alkyl, aryl-Ci-C4alkoxy, aryl-C C4alkylthio, heterocyclyl, heterocycyl-C C4alkyl, heterocycyl-C1-C4alkoxy, heterocycyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, C C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R16; or R14 is C=NOR11;
each R15 independently is hydrogen, CrC4alkyl, CrC4haloalkyl, C3-C6cycloalkyl, Ci- C4alkylsulfonyl, wherein alkyl, cycloalkyl and alkylsulfonyl are optionally substituted by halogen; and
each R16 independently is halogen, cyano, Ci-C4alkyl, CrC haloalkyl, Ci-C alkoxy or Ci- C4haloalkoxy; or
a salt or a N-oxide thereof.
2. A compound according to claim 1 , wherein R9 and R10 each independently are hydrogen, C-|-C4alkyl, Ci-C4haloalkyl, C3-C5cycloalkyl, aryl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O, N, S or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, d-C alkyl, C
C4haloalkyl, C3-C5cycloalkyl, C C4alkoxy, C C8alkylthio or C=NOR11.
3. A compound according to claim 1 , wherein R9 and R10 each independently are hydrogen, CrC alkyl, aryl, or heteroaryl wherein aryl and heteroaryl are optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10-membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, Ci-C4alkyl, C3-C5cycloalkyl, C C4alkoxy, CrCsalkylthio or C=NOR11
4. A compound according to claim 1 , wherein R9 and R10 each independently are hydrogen, Ci-C4alkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 5 or 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0) said isocyclic ring being optionally substituted by C C4alkyl, C3-C5cycloalkyl, C dalkoxy, C-rC8alkylthio or C=NOR11
5. A compound according to claim 1 , wherein R9 and R10 each independently are hydrogen, Ci-C4alkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0), said isocyclic ring being optionally substituted by C1-C4alkyl, C3-C5cycloalkyl, C1-C4alkoxy, CrCealkylthio, or
C=NOR11.
6. A compound according to claim 1 , wherein R1 is hydrogen, Ci-C4alkyl, C3-C5cycloalkyl, allyl, propargyl, CrC4alkylsulfonyl, or benzyl wherein alkyl, cydoalkyi are optionally substituted by halogen.
7. A compound according to claim 1 , wherein
G1 is O
G2 is S;
T is CH or N;
Y1 and Y2 are independently CH or N;
n is 1 or 2;
p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are methyl or halomethyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen, halogen, C -C4alkyl, Cr
C4alkoxy, or Cr haloalkyl;
R9 and R10 each independently are hydrogen, Cr^alkyl, aryl, or heteroaryl wherein aryl and heteroaryl are optionally substituted by one or more R14, or
R9 and R10 together with the carbon atoms to which they are attached form a 5- to 10- membered isocyclic or heterocyclic ring optionally comprising one or two ring members selected from O or a carbonyl group, said isocyclic or heterocyclic ring being optionally substituted by halogen, Ci-C4alkyl, C3-C5cycloalkyl, Ci-C4alkoxy, Ci-C8alkylthio or C=NOR11; X is O, NH or NMe;
R11 hydrogen, Ci-C4alkyl, C3-C5cycloalkyl, C3-C5cycloalkylCi-C4alkyl, allyl, propargyl, C C4alkylsulfonyl, or benzyl wherein alkyl, allyl, cydoalkyi and alkenyl are optionally substituted by halogen;
each R14 independently is halogen, cyano, hydroxyl, C C^lkyl, ethynyl, C3-C5cycloalkyl, C-p C4alkoxy, C3-C4alkenyloxy and C3-C4alkynyloxy, NH(C1-C4alkyl), N(C1-C4alkyl)2, C-p
C4alkylcarbonyl wherein alkyl, cydoalkyi and alkoxy, are optionally substituted by halogen, or a salt or a N-oxide thereof.
8. A compound according to claim 1 , wherein
G is O
G2 is S;
T is CH or N;
Y1 and Y2 are independently CH or N;
n is 1 or 2; p is 1 or 2, providing that when n is 2, p is 1 ;
R1 and R2 each independently are methyl, difluoromethyl or trifluoromethyl;
R3, R4, R5, R6, R7 and R8 each independently are hydrogen,
R9 and R10 each independently are hydrogen, Ci-C4alkyl or aryl, wherein aryl is optionally substituted by one or more R14; or R9 and R10 together with the carbon atoms to which they are attached form a 6-membered isocyclic ring, optionally comprising one or two ring members being C(=0), said isocyclic ring being optionally substituted by Ci-C4alkyl, C3- Cscycloalkyl, or Ci-C4alkoxy, CrC8alkylthio, C=NOMe or C=NOH;
X is O;
R11 is hydrogen, Ci-C4alkyl, allyl, propargyl, wherein alkyl is optionally substituted by chloro or fluoro.;
each R14 independently is halogen, cyano, C1-C4alkyl, methoxy, NH(CrC4alkyl), N(C C4alkyl)2, C-|-C4alkylcarbonyl wherein alkyl is optionally substituted by halogen; and a salt or a N-oxide thereof.
9. A compound according to any one of claims 1 to 8, wherein G1, is O, G2 is S, Y1 is N, and Y2 is CH.
10. A compound according to any one of claims 1 to 8, wherein p is 1 and n is 2.
11. A compound of formula II:
Figure imgf000189_0001
wherein R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, T, X, Y1, Y2,n and p are as defined for a compound of formula I in anyone of claims 1 to 10 and E is hydrogen or a protecting group, and salts and N-oxides thereof, or a compound of formula III
Figure imgf000189_0002
wherein halogen is bromo, chloro, fluroro or iodo and R9, R10, G2, Y1, Y2 are as defined for a compound of formula I in anyone of claims 1 to 10, and salts and N-oxides thereof, or a com ound of formula IV
Figure imgf000190_0001
wherein halogen is bromo, chloro, fluroro or iodo and R9, R10, R11, G2, X, Y1, Y2 are as defined for a compound of formula I in anyone of claims 1 to 10, and salts and N-oxides thereof, or
a compound of formula V
Figure imgf000190_0002
wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, G2, X, Y1, Y2, n and p are as defined for formula I in anyone of claims 1 to 10, and E is hydrogen or a protecting group, and salts and N-oxides thereof, or
15 a compounds of formula VI
Figure imgf000190_0003
Wherein R3, R4, R5, R6, R7, R8, R9, R10, G2, Y1, Y2, n and p are as defined for a compound of formula I in anyone of claims 1 to 10 and E is hydrogen, or a protecting group and salts and N-oxides thereof.
20
12. A composition comprising at least one compound as defined in any one of claims 1 to 1 1 and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising one or more additional pesticidally active compounds.
25 13. A method of controlling or preventing an infestation of plants, propagation material thereof, harvested crops or of non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, which comprises the application of a compound as defined in any one of claims 1 to 12, to the plant, to parts of the plants or to the locus thereof, to propagation material thereof or to any part of the non-living materials.
PCT/EP2013/071985 2012-11-13 2013-10-21 Microbiocidal pyrazole derivatives WO2014075874A1 (en)

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9266876B2 (en) 2012-02-02 2016-02-23 Actelion Pharmaceuticals Ltd. 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
WO2016202761A1 (en) 2015-06-17 2016-12-22 Bayer Cropscience Aktiengesellschaft Active compound combinations
WO2017047337A1 (en) * 2015-09-18 2017-03-23 株式会社エス・ディー・エス バイオテック Method for manufacturing 4-(4-formylthiazolyl)piperidine compound
KR20170036104A (en) 2014-08-13 2017-03-31 가부시키가이샤 에스디에스 바이오텍크 Condensed 11-member ring compound and agriculture and horticultural fungicide comprising same
US9951063B2 (en) 2014-03-24 2018-04-24 Idorsia Pharmaceuticals Ltd 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
US10047080B2 (en) 2015-01-15 2018-08-14 Idorsia Pharmaceuticals Ltd. (R)-2-methyl-piperazine derivatives as CXCR3 receptor modulators
US10053457B2 (en) 2015-01-15 2018-08-21 Idorsia Pharmaceuticals Ltd. Hydroxyalkyl-piperazine derivatives as CXCR3 receptor modulators
WO2018193387A1 (en) 2017-04-19 2018-10-25 Pi Industries Ltd. Heterocyclic compounds with microbiocidal properties
WO2019048989A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungicidal heterocyclic compounds
WO2019048988A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungidal heterocyclic compounds
US10259807B2 (en) 2013-07-22 2019-04-16 Idorsia Pharmaceuticals Ltd. 1-(piperazin-1-yl)-2-([1,2,4]triazol-1-yl)-ethanone derivatives
US11274076B2 (en) 2016-02-08 2022-03-15 Gowan Company, L.L.C. Process for preparing 1, 2-benzenedimethanol compound
US11903387B2 (en) 2016-02-08 2024-02-20 Gowan Company, L.L.C. Fungicidal composition

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008013622A2 (en) * 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008091580A2 (en) * 2007-01-25 2008-07-31 E. I. Du Pont De Nemours And Company Fungicidal amides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008013622A2 (en) * 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008013925A2 (en) * 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008091580A2 (en) * 2007-01-25 2008-07-31 E. I. Du Pont De Nemours And Company Fungicidal amides

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9266876B2 (en) 2012-02-02 2016-02-23 Actelion Pharmaceuticals Ltd. 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
US10259807B2 (en) 2013-07-22 2019-04-16 Idorsia Pharmaceuticals Ltd. 1-(piperazin-1-yl)-2-([1,2,4]triazol-1-yl)-ethanone derivatives
US9951063B2 (en) 2014-03-24 2018-04-24 Idorsia Pharmaceuticals Ltd 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
US10104891B2 (en) 2014-08-13 2018-10-23 Sds Biotech K.K. Fused 11-membered compounds and agricultural/horticultural fungicides containing them
KR20170036104A (en) 2014-08-13 2017-03-31 가부시키가이샤 에스디에스 바이오텍크 Condensed 11-member ring compound and agriculture and horticultural fungicide comprising same
US9980487B2 (en) 2014-08-13 2018-05-29 Sds Biotech K.K. Fused 11-membered compounds and agricultural/horticultural fungicides containing them
US10047080B2 (en) 2015-01-15 2018-08-14 Idorsia Pharmaceuticals Ltd. (R)-2-methyl-piperazine derivatives as CXCR3 receptor modulators
US10053457B2 (en) 2015-01-15 2018-08-21 Idorsia Pharmaceuticals Ltd. Hydroxyalkyl-piperazine derivatives as CXCR3 receptor modulators
WO2016202761A1 (en) 2015-06-17 2016-12-22 Bayer Cropscience Aktiengesellschaft Active compound combinations
JPWO2017047337A1 (en) * 2015-09-18 2018-03-22 株式会社エス・ディー・エス バイオテック Process for producing 4- (4-formylthiazolyl) piperidine compound
WO2017047337A1 (en) * 2015-09-18 2017-03-23 株式会社エス・ディー・エス バイオテック Method for manufacturing 4-(4-formylthiazolyl)piperidine compound
US11274076B2 (en) 2016-02-08 2022-03-15 Gowan Company, L.L.C. Process for preparing 1, 2-benzenedimethanol compound
US11903387B2 (en) 2016-02-08 2024-02-20 Gowan Company, L.L.C. Fungicidal composition
WO2018193387A1 (en) 2017-04-19 2018-10-25 Pi Industries Ltd. Heterocyclic compounds with microbiocidal properties
WO2019048989A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungicidal heterocyclic compounds
WO2019048988A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungidal heterocyclic compounds

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