WO2019207058A1 - Microbiocidal oxadiazole derivatives - Google Patents

Microbiocidal oxadiazole derivatives Download PDF

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Publication number
WO2019207058A1
WO2019207058A1 PCT/EP2019/060642 EP2019060642W WO2019207058A1 WO 2019207058 A1 WO2019207058 A1 WO 2019207058A1 EP 2019060642 W EP2019060642 W EP 2019060642W WO 2019207058 A1 WO2019207058 A1 WO 2019207058A1
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alkyl
methyl
hydrogen
formula
ccn
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PCT/EP2019/060642
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French (fr)
Inventor
Thomas James HOFFMAN
Thomas Pitterna
Daniel Stierli
Ramya Rajan
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Syngenta Participations Ag
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Priority to CN201980028118.6A priority Critical patent/CN112041317A/en
Priority to BR112020021629-1A priority patent/BR112020021629A2/en
Publication of WO2019207058A1 publication Critical patent/WO2019207058A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to microbiocidal oxadiazole derivatives, e.g., as active ingredients, which have microbiocidal activity, in particular, fungicidal activity.
  • the invention also relates to agrochemical compositions which comprise at least one of the oxadiazole derivatives, to processes of preparation of these compounds and to uses of the oxadiazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or nonliving materials by phytopathogenic microorganisms, preferably fungi.
  • EP 0 276 432 and WO 2015/185485 describe the use of substituted oxadiazoles for combating phytopathogenic fungi.
  • A-1 , A-2, A-3, or A-4 are optionally substituted by 1 or 2 independently selected halogen groups;
  • R 1 and R 2 are independently selected from hydrogen, methyl and cyano; or R 1 and R 2 , together with the carbon atom to which they are bonded, form a cyclopropyl ring;
  • R 3 represents hydrogen, hydroxy, Ci- 4 alkyl, Ci- 4 haloalkyl, Ci- 4 alkoxy, hydroxyC 2-4 alkyl, C-i- 2 alkoxyC 2-4 alkyl, Ci-2haloalkoxy, Ci- 2 haloalkoxyC 2-4 alkyl, C3- 4 alkenyl, C3- 4 alkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, Ci- 4 alkylcarbonyloxy, N-Ci-2alkylamino, N,N-diCi-2alkylamino, C3-6cycloalkyl or C3- 6cycloalkylCi-2alkyl;
  • Z is selected from Z 1 or Z 2 ; wherein Z 1 is R 4 , wherein R 4 represents hydrogen, cyano, Ci-ealkyl, C-i ehaloalkyl, cyanoC-i ealkyl, hydroxyCi- 4 alkyl, Ci- 4 alkoxyCi- 4 alkyl, Ci- 4 haloalkoxyCi- 4 alkyl, Ci- 2 alkoxyCi- 2 alkoxyCi- 4 alkyl, C3- 5alkenyloxyCi- 4 alkyl, C3-5alkynyloxyCi- 4 alkyl, aminoCi-6alkyl, N-Ci- 4 alkylaminoCi- 4 alkyl, N,N-diCi- 4 alkylanninoCi- 4 alkyl, Ci- 4 alkylcarbonylCi- 4 alkyl, Ci- 4 alkoxycarbonylCi- 4 alkyl, Ci- 4 alkylcarbonyloxyCi-
  • R 4 represents heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 4- to 6-membered nonaromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from cyano, halogen, hydroxy, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy and cyclopropyl, and
  • this cycle may optionally contain 1 group selected from C(O) or S(0)2;
  • Z 2 represents -NR 5 R 6 , wherein R 5 represents hydrogen, cyano, Ci- 4 alkyl, cyanoCi- 4 alkyl, C-i- 4 alkoxy, C3-salkenyl, C3-salkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, Ci- 4 haloalkyl, C3- 4 haloalkenyl, hydroxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkyl, Ci- 2 haloalkoxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkoxyC 2-4 alkyl, N-C-i- 3alkylamino, N,N-diCi-3alkylamino, aminoC 2-4 alkyl, N-Ci- 4 alkylaminoC 2-4 alkyl, N,N-diCi- 4 alkylaminoC 2 - 4 alkyl, Ci-3alkylcarbonyl
  • R 5 represents C3-6cycloalkyl, C3-6cycloalkylCi- 2 alkyl, phenyl, phenylCi-2alkyl, heteroaryl or heteroarylCi-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1 , 2, 3, or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylC-i- 2alkyl wherein the heterocyclyl moiety is a 4- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms or groups individually selected from N, NR 7 , O and S; wherein the cycloalkyl, phenyl, heteroaryl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropy
  • R 5 comprises a cycloalkyl or heterocyclyl
  • these cycles may optionally contain 1 group selected from C(O) or S(0)2;
  • R 6 represents hydrogen, cyano, halogen, hydroxy, amino, methyl, ethyl, propyl, prop-2-enyl, prop-2-ynyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, difluoromethoxy, prop-2-enyloxy, prop-2-ynyloxy, N-methylamino, N,N-dimethylamino, methylcarbonyl, methoxycarbonyl, formylamino, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl or methoxycarbonylamino; and R 7 represents hydrogen, methyl, methoxy, formyl or acyl; or a salt or an N-oxide thereof.
  • 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.
  • an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I).
  • Such an agricultural composition may further comprise at least one additional active ingredient and/or an agrochemically- acceptable diluent or carrier.
  • a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein a fungicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
  • a compound of formula (I) as a fungicide.
  • the use may exclude methods for the treatment of the human or animal body by surgery or therapy.
  • halogen refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
  • cyano means a -CN group.
  • hydroxyl or“hydroxy” means an -OH group.
  • amino means an -NH2 group.
  • acyl means a -C(0)CH3 group.
  • formyl means a -C(0)H group.
  • Ci-6alkyl refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond.
  • Ci- 4 alkyl, C-i salkyl and Ci-2alkyl are to be construed accordingly.
  • Examples of C-i ealkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, and 1-dimethylethyl (tert-butyl).
  • A“Ci-2alkylene” group refers to the corresponding definition of Ci-2alkyl, except that such radical is attached to the rest of the molecule by two single bonds. Examples of Ci-2alkylene, are -CH2- and -CH2CH2-.
  • Ci- 4 alkoxy refers to a radical of the formula R a O- where R a is a C-i- 4 alkyl radical as generally defined above.
  • the terms C-i salkoxy and Ci-2alkoxy are to be construed accordingly.
  • Examples of Ci- 4 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, and tert-butoxy.
  • Ci- 4 haloalkyl refers to a Ci ⁇ alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms.
  • Ci- 4 haloalkyl examples include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, and 3,3,3-trifluoropropyl.
  • cyanoCi- 4 alkyl refers to a Ci- 4 alkyl radical as generally defined above substituted by one or more cyano groups.
  • aminoCi- 4 alkyl refers to a Ci- 4 alkyl radical as generally defined above substituted by one or more amino groups.
  • C3-5alkenyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (Z)-configu ration, having from three to five carbon atoms, which is attached to the rest of the molecule by a single bond.
  • C3- 4 alkenyl is to be construed accordingly.
  • Examples of C3- Csalkenyl include, but are not limited to, prop-1 -enyl, allyl (prop-2-enyl), and but-1-enyl.
  • C3- 4 alkenyloxy refers to a radical of the formula R a O-, where R a is a C3- 4 alkenyl radical as generally defined above.
  • C3-5alkynyl refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from three to five carbon atoms, and which is attached to the rest of the molecule by a single bond.
  • C3- 4 alkynyl is to be construed accordingly. Examples of C3-salkynyl include, but are not limited to, prop- 1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.
  • C3- 4 alkynyloxy refers to a radical of the formula R a O-, where R a is a C3- 4 alkynyl radical as generally defined above.
  • Ci- 4 alkoxyCi- 4 alkyl refers to radical of the formula Rb-0-R a - where Rb is a Ci- 4 alkyl radical as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • Ci- 4 haloalkoxy refers to a Ci- 4 alkoxy group as defined above substituted by one or more of the same or different halogen atoms. Ci shaloalkoxy is to be construed accordingly. Examples of Ci- 4 haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
  • hydroxyC 2-4 alkyl refers to a C 2-4 alkyl radical as generally defined above substituted by one or more hydroxy groups.
  • Ci- 4 alkylcarbonyl refers to a radical of the formula R a C(0)-, where R a is a Ci- 4 alkyl radical as generally defined above.
  • Ci- 2 alkoxyCi- 2 alkoxyCi- 4 alkyl refers to a radical of the formula RcORbOR a -, where R a is a Ci- 4 alkylene radical and Rb is a Ci-2alkylene radical as generally defined above, and R c is a Ci-2alkyl radical as generally defined above.
  • Ci- 4 alkoxycarbonyl refers to a radical of the formula R a OC(0)-, where R a is a Ci- 4 alkyl radical as generally defined above.
  • N-Ci- 4 alkylamino refers to a radical of the formula R a NH- where R a is a Ci- 4 alkyl radical as generally defined above. N-Ci-3alkylamino is to be construed accordingly.
  • the term“N,N-diCi- 4 alkylamino” refers to a radical of the formula R a (Rb)N- where R a and Rb are Ci- 4 alkyl radicals as generally defined above.
  • Ci- 4 alkylcarbonylCi- 4 alkyl refers to a radical of the formula RbC(0)R a - where Rb is a Ci- 4 alkyl as generally defined above and R a is a Ci- 4 alkylene radical as generally defined above.
  • Ci- 4 alkoxycarbonylCi- 4 alkyl refers to a radical of the formula RbOC(0)R a - where Rb is a Ci- 4 alkyl as generally defined above and R a is a Ci- 4 alkylene radical as generally defined above.
  • Ci- 4 alkylcarbonyloxy refers to a radical of the formula R a C(0)0- where R a is a Ci- 4 alkyl as generally defined above.
  • Ci- 4 alkylsulfanyl refers to a radical of the formula R a S-, where R a is a Ci- 4 alkyl radical as generally defined above.
  • Examples of Ci- 4 alkylsulfanyl include, but are not limited to methylsulfanyl.
  • C- 4 alkylsulfonyl refers to a radical of the formula R a S(0) 2 -, where R a is a Ci- 4 alkyl radical as generally defined above.
  • Examples of C-i salkylsulfonyl include, but are not limited to methylsulfonyl.
  • Ci- 4 alkylsulfonylCi- 4 alkyl refers to a radical of the formula RbS(0) 2 R a -, where Rb is a Ci- 4 alkyl radical as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • Ci- 4 alkylsulfonylamino refers to a radical of the formula R a S(0) 2 NH-, where R a is a Ci- 4 alkyl radical as generally defined above.
  • Ci- 4 alkylsulfonylaminoCi- 4 alkyl refers to a radical of the formula RbS(0) 2 NHR a -, where Rb is a Ci- 4 alkyl radical as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • N,N-diCi- 4 alkylamino refers to a radical of the formula (R a )(Rb)N-, wherein R a and Rb are each Ci- 4 alkyl radicals as generally defined above.
  • N,N-diCi- 4 alkylaminoCi- 4 alkyl refers to a radical of the formula (Rc)(Rb)NR a -, wherein Rb and R c are each independently Ci- 4 alkyl radicals as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • N-Ci- 4 alkylaminocarbonylCi- 4 alkyl refers to a radical of the formula (Rb)NHC(0)R a -, wherein Rb is a Ci- 4 alkyl radical as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • N,N-diCi- 4 alkylaminocarbonylCi- 4 alkyl refers to a radical of the formula (Rc)(Rb)NHC(0)R a -, wherein Rb and R c are each independently Ci- 4 alkyl radicals as generally defined above, and R a is a Ci- 4 alkylene radical as generally defined above.
  • C3-6cycloalkyl refers to a stable, monocyclic ring radical which is saturated or partially unsaturated and contains 3 to 6 carbon atoms.
  • C3-scycloalkyl and C3- 4 cycloalkyl are to be construed accordingly.
  • Examples of Cs ecycloalkyl include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclopenten-1-yl, cyclopenten-3-yl, and cyclohexen-3-yl.
  • C3-6cycloalkylCi- 2 alkyl refers to a C3-6cycloalkyl ring as defined above attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
  • Examples of C3- 6cycloalkylCi-2alkyl include, but are not limited to cyclopropyl-methyl and cyclobutyl-ethyl.
  • phenylCi-2alkyl refers to a phenyl ring attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
  • phenylCi-2alkyl include, but are not limited to, benzyl.
  • heteroaryl generally refers to a 5- or 6-membered monocyclic aromatic ring radical which comprises 1 , 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur.
  • the heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom.
  • heteroaryl include but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazinyl, pyridazinyl, pyrimidyl and pyridyl.
  • heteroarylCi-2alkyl refers to a heteroaryl ring as defined above which is attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
  • heterocyclyl or “heterocyclic” generally refers to a stable, saturated or partially saturated, 4- to 6-membered, non-aromatic monocyclic ring, which comprises 1 or 2 heteroatoms individually selected from nitrogen, oxygen and sulfur.
  • the heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom.
  • heterocyclyl examples include, but are not limited to, azetidinyl, oxetanyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, tetrahydropyranyl, dioxolanyl, and morpholinyl.
  • heterocyclylCi-2alkyl refers to a heterocyclic ring as defined above which is attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
  • the presence of one or more possible asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also, atropisomers may occur as a result of restricted rotation about a single bond.
  • the compound of 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).
  • the compound of formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present.
  • 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 an N-oxide, in covalently hydrated form, or in salt form, e.g., an agronomically usable or agrochemically acceptable 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.
  • A is A-1 , A-2, A-3, or A-4,
  • A-1 , A-2, A-3, or A-4 are optionally substituted by 1 or 2 independently selected halogen groups.
  • the halogen is chloro or fluoro, and most preferably, fluoro.
  • A is A-1.
  • A is A-2.
  • A is A-3.
  • A is A-4.
  • A is A-1 optionally substituted by 1 or 2 fluorine groups, or A is unsubstitued A-4. More preferably, A is unsubstitued A-1 (1 ,4-phenylene) or unsubstitued A-4 (2,5-thienylene).
  • R 1 and R 2 are independently selected from hydrogen, methyl and cyano; or R 1 and R 2 , together with the carbon atom to which they are bonded, form a cyclopropyl ring.
  • R 1 and R 2 are independently selected from hydrogen and methyl, and more preferably R 1 and R 2 are hydrogen.
  • R 3 represents hydrogen, hydroxy, Ci- 4 alkyl, Ci- 4 haloalkyl, Ci- 4 alkoxy, hydroxyC 2-4 alkyl, C-i- 2 alkoxyC 2-4 alkyl, Ci-2haloalkoxy, Ci- 2 haloalkoxyC 2-4 alkyl, C3- 4 alkenyl, C3- 4 alkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, Ci- 4 alkylcarbonyloxy, N-Ci-2alkylamino, N,N-diCi-2alkylamino, Cs ecycloalkyl or C3- 6cycloalkylCi-2alkyl.
  • R 3 is hydrogen, Ci- 4 alkyl, Ci- 4 haloalkyl, Ci- 4 alkoxy, Ci-2haloalkoxy or cyclopropyl, more preferably R 3 is hydrogen, Ci- 4 alkyl, Ci-2fluoroalkyl, Ci- 4 alkoxy, Ci-2fluoroalkoxy or cyclopropyl, and most preferably, R 3 is hydrogen, methyl, ethyl, methoxy, 2,2-difluoroethoxy or cyclopropyl.
  • Z is Z 1 , wherein Z 1 is R4, or Z is Z 2 , wherein Z 2 is -NR 5 R 6 .
  • Z is Z 1 .
  • Z is Z 2 .
  • R 4 represents hydrogen, Ci-ealkyl, Ci-ehaloalkyl, cyanoCi-ealkyl, hydroxyCi- 4 alkyl, Ci- 4 alkoxyCi- 4 alkyl, Ci- 4 haloalkoxyCi- 4 alkyl, Ci- 2 alkoxyCi- 2 alkoxyCi- 4 alkyl, C3-5alkenyloxyCi- 4 alkyl, C3-5alkynyloxyCi-
  • this cycle may optionally contain 1 group selected from C(O) or S(0)2.
  • R 4 is hydrogen, cyano, Ci- 4 alkyl, Ci- 4 haloalkyl, cyanoCi- 4 alkyl, hydroxyCi- 4 alkyl, C-i- 2 alkoxyCi- 4 alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-5alkenyloxyCi- 2 alkyl, C3- 5alkynyloxyCi- 2 alkyl, aminoCi- 4 alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, C-i- 2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyCi-2alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-d
  • R 4 is hydrogen, Ci- 4 alkyl, Ci- 4 haloalkyl, cyanoCi- 4 alkyl, hydroxyCi- 4 alkyl or Ci- 2 alkoxyCi- 4 alkyl, and even more preferably, R 4 is hydrogen, Ci- 4 alkyl or C-i- 2 alkoxyCi- 4 alkyl. Most preferably, R 4 is hydrogen, methyl, ethyl, iso-propyl, n-propyl or Ci-2alkoxyCi- salkyl (including -CH2OCH3, -CH(OCH 3 )CH 3 and -C(CH 3 )20CH 3 ).
  • R 4 is heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 5- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the cycloalkyl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
  • Z 2 represents -NR 5 R 6 , wherein:
  • R 5 represents hydrogen, cyano, Ci- 4 alkyl, cyanoCi- 4 alkyl, Ci- 4 alkoxy, C3-salkenyl, C3-salkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, cyanoCi-3alkyl, Ci- 4 haloalkyl, C3- 4 haloalkenyl, hydroxyC 2-4 alkyl, C1- 2 alkoxyC 2-4 alkyl, Ci- 2 haloalkoxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkoxyC 2-4 alkyl, N-Ci-3alkylamino, N,N-diCi- 3alkylamino, aminoC 2-4 alkyl, N-Ci- 4 alkylaminoC 2 ⁇ alkyl, N,N-diCi- 4 alkylaminoC 2-4 alkyl, C1- 3alkylcarbonylCi-3al
  • R 6 represents hydrogen, cyano, halogen, hydroxy, amino, methyl, ethyl, propyl, prop-2-enyl, prop-2-ynyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, difluoromethoxy, prop-2-enyloxy, prop-2-ynyloxy, N-methylamino, N,N-dimethylamino, methylcarbonyl, methoxycarbonyl, formylamino, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl or methoxycarbonylamino.
  • R 5 is hydrogen, cyano, Ci- 4 alkyl, cyanoCi- 4 alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, cyanoCi-2alkyl, Ci- 4 haloalkyl, C3- 4 haloalkenyl, hydroxyC 2-4 alkyl, C-i- 2 alkoxyC 2-4 alkyl, Ci- 2 haloalkoxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkoxyC 2-4 alkyl, N-Ci-2alkylamino, N,N-diCi- 2alkylamino, aminoC 2-4 alkyl, N-Ci-2alkylaminoC2 ⁇ alkyl, N,N-diCi- 2 alkylaminoC 2-4 alkyl, C-i- 2alkylcarbonylCi
  • R 5 is hydrogen, Ci- 4 alkyl, cyanoCi- 4 alkyl, C-i- 4 haloalkyl, hydroxyC 2-4 alkyl, C3- 4 cycloalkyl or C3- 4 cycloalkylCi- 2 alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
  • R 5 is hydrogen, Ci- 4 alkyl, Ci- 4 fluoroalkyl or C3- 4 cycloalkyl.
  • R 5 is methyl, ethyl, n-propyl, iso-propyl, 2,2,2-trifluoroethyl or cyclopropyl.
  • R 6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl, and most preferably R 6 is hydrogen.
  • R 7 represents hydrogen, methyl, methoxy, formyl or acyl.
  • the compound according to formula (I) is selected from a compound 1.1 to 1.15 listed in Table T1 (below).
  • A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups
  • R 1 and R 2 are independently selected from hydrogen and methyl
  • R 3 is hydrogen, Ci- 4 alkyl, Ci-2fluoroalkyl, Ci-2alkoxy, Ci-2fluoroalkoxy or cyclopropyl; and Z is Z1 , and R 4 is hydrogen, cyano, Ci- 4 alkyl, Ci- 4 haloalkyl, cyanoCi- 4 alkyl, hydroxyCi- 4 alkyl, C-i- 2alkoxyCi- 4 alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-salkenyloxyCi- 2 alkyl, C3-5alkynyloxyCi- 2 alkyl, aminoCi- 4 alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, Ci-2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alky
  • A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups
  • R 1 and R 2 are hydrogen
  • R 3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl
  • Z is Z 1
  • R 4 is hydrogen, Ci- 4 alkyl, Ci- 4 haloalkyl, cyanoCi- 4 alkyl, hydroxyCi- 4 alkyl, Ci-2alkoxyCi- 4 alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-salkenyloxyCi- 2 alkyl, C3- 5alkynyloxyCi- 2 alkyl, aminoCi- 4 alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, C-i- 2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyCi-2alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-diC
  • A is unsubstituted A-1 or unsubstituted A-4;
  • R 1 and R 2 are hydrogen
  • R 3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
  • R 4 is is hydrogen, methyl, ethyl, iso-propyl, n-propyl or Ci- 2 alkoxyCi-3alkyl.
  • A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups
  • R 1 and R 2 are independently selected from hydrogen and methyl
  • R 3 is hydrogen, Ci- 4 alkyl, Ci-2fluoroalkyl, Ci-2alkoxy, Ci-2fluoroalkoxy or cyclopropyl; and Z is Z 2 , wherein Z 2 represents -NR 5 R 6 , wherein R 5 is hydrogen, cyano, Ci- 4 alkyl, cyanoCi- 4 alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, cyanoCi-2alkyl, Ci- 4 haloalkyl, C3- 4 haloalkenyl, hydroxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkyl, Ci- 2 haloalkoxyC 2-4 alkyl, Ci-2alkoxyC2- 4 alkoxyC 2-4 alkyl, N-Ci-2alkylamino, N,N-diCi-2alkylamino, aminoC
  • A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups
  • R 1 and R 2 are hydrogen
  • R 3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
  • Z is Z 2 , wherein Z 2 represents -NR 5 R 6 , wherein R 5 is hydrogen, cyano, Ci- 4 alkyl, cyanoCi- 4 alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3- 4 alkenyloxy, C3- 4 alkynyloxy, cyanoCi-2alkyl, Ci- 4 haloalkyl, C3- 4 haloalkenyl, hydroxyC 2-4 alkyl, Ci- 2 alkoxyC 2-4 alkyl, Ci- 2 haloalkoxyC 2-4 alkyl, Ci-2alkoxyC2- 4alkoxyC 2-4 alkyl, N-Ci-2alkylamino, N,N-diCi-2alkylamino, aminoC 2-4 alkyl, N-Ci-2alkylaminoC2- 4alkyl, N,N-diCi- 2 alkylaminoC 2-4 alkyl
  • R 6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl.
  • A is unsubstituted A-1 or unsubstituted A-4;
  • R 1 and R 2 are hydrogen
  • R 3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
  • Z is Z 2 , wherein Z 2 represents -NR 5 R 6 , wherein R 5 is hydrogen, Ci- 4 alkyl, cyanoCi- 4 alkyl, C-i- 4haloalkyl, hydroxyC 2-4 alkyl, or C3- 4 cycloalkyl or C3- 4 cycloalkylCi- 2 alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
  • R 6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl.
  • A is unsubstituted A-1 or unsubstituted A-4;
  • R 1 and R 2 are hydrogen
  • R 3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
  • Z is Z 2 , wherein Z 2 represents -NR 5 R 6 , wherein R 5 is hydrogen, Ci- 4 alkyl, cyanoCi- 4 alkyl, C-i- 4haloalkyl, hydroxyC 2-4 alkyl, C3- 4 cycloalkyl or C3- 4 cycloalkylCi- 2 alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl; and
  • R 6 is hydrogen
  • Compounds of formula (I) feature a thiocarbonyl moiety (eg, thioamide or thiourea) and in vivo are believed to act as a procide to compounds of formula (II) featuring a carbonyl moiety (eg, amide or urea) under suitable conditions, (eg, metabolic processes or biosynthetic transformations).
  • a thiocarbonyl moiety eg, thioamide or thiourea
  • a carbonyl moiety eg, amide or urea
  • the compounds of the present invention may be enantiomers of the compound of formula (I) as represented by a Formula (la) or a Formula (lb), wherein R 1 and R 2 are different substituents.
  • the compounds of formula (I) according to the invention may be present in a reversible equilibrium with the corresponding covalently hydrated forms (eg, the compounds of formula (l-l) and formula (l-ll) as shown below, which may exist in tautomeric form as the compounds of formula (l-lb) and formula (l-l lb)) at the CF3-oxadiazole motif.
  • This dynamic equilibrium may be important for the biological activity of the compounds of formula (I).
  • A including A-1 , A-2, A-3, or A-4
  • R 1 , R 2 , R 3 , Z including Z 1 , Z 2
  • R 4 , R 5 , R 6 , and R 7 with reference to the compounds of formula (I) of the present invention apply generally to the compounds of Formula (l-l) and Formula (l-ll), as well as to the specific disclosures of combinations of A (including A-1 , A-2, A-3, or A-4), R 1 , R 2 , R 3 , Z , R 4 , R 5 , R 6 , and R 7 as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or the compounds 1.1 to 1.15, according to the invention listed in Table T1 (below).
  • Compounds of formula (I), can be prepared from compounds of formula (II), via reactions with a suitable sulfur source [eg, elemental sulfur (Ss), Lawesson’s reagent, or P2S5], in an acceptable solvent (eg, toluene, CH2CI2, CHCI3, tetrahydrofuran, f-butylmethyl ether), at temperatures between 0°C to 100°C.
  • a suitable sulfur source eg, elemental sulfur (Ss), Lawesson’s reagent, or P2S5
  • an acceptable solvent eg, toluene, CH2CI2, CHCI3, tetrahydrofuran, f-butylmethyl ether
  • compounds of formula (I), wherein Z represents -NR 5 R 6 can be prepared from compounds of formula (III) via reactions with a suitable sulfur carbonyl reagent (eg, 1 ,3-dimethyl-l- nitrosothiourea, thiophosgene, thiourea, CS2, or thiocarbonyl-1 , 1 -diimidazole) in the presence of nucleophiles of formula (IV), in a suitable solvent (eg, ethyl acetate, acetone, CH2CI2, CHCI3, acetonitrile, or toluene), optionally with a water co-solvent, in the presence of a suitable base (eg, triethylamine, NaHCCh, Ca 2 CC>3) with heating at temperatures between 0°C and 65°C.
  • a suitable sulfur carbonyl reagent eg, 1 ,3-dimethyl-l- nitrosothiourea, thiophosgene
  • Compounds of formula (V), wherein Z a is hydrogen, -C(0)R 4 , -C(S)R 4 , -C(0)NR 5 R 6 , -C(S)NR 5 R 6 can be prepared from compounds of formula (VI), wherein X is a OH, OS0 2 Me, Cl, Br, or I, preferably Br or I, via reactions with compounds of formula (VII), optionally in the presence of a base (eg, triethylamine, A/,A/-diisopropylethylamine, K2CO3, NaHC03, or Na 2 C03), in a suitable solvent (eg, dimethylacetamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, or acetonitrile) at temperatures between 25°C and 1 10°C.
  • a base eg, triethylamine, A/,A/-diisopropylethylamine, K2
  • a better reaction performance may be gained by the use of a catalyst (eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4-dimethylaminopyridine) and optionally with microwaves irradiation.
  • a catalyst eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4-dimethylaminopyridine
  • microwaves irradiation e.g., BU4NHSO4, B NBr, BU4NI, Nal, or 4-dimethylaminopyridine
  • a catalyst eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4-dimethylaminopyridine
  • compounds of formula (I) can be obtained via coupling transformations with compounds of formula (VIII) and compounds of formula (III) in a suitable solvent (eg, dimethylformamide, dichloromethane or tetrahydrofuran), at temperatures of between 0°C and 100°C, and optionally in the presence of a base such as triethylamine.
  • a suitable solvent eg, dimethylformamide, dichloromethane or tetrahydrofuran
  • compounds of formula (I) can be prepared from compounds of formula (IX) via reactions with trifluoroacetic acid, trifluoroacetic ester (eg, trifluoroacetic methyl ester or trifluoroacetic ethyl ester), trifluoroacetic anhydride, or trifluoroacetyl halide (including trifluoroacetyl fluoride, trifluoroacetyl chloride, and trifluoroacetyl bromide), optionally in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, (eg, toluene, ethyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, or ethanol), at temperatures between 0°C and 75°C.
  • a base eg, pyridine or 4-dimethylaminopyridine
  • suitable solvent eg, toluene, ethyl
  • Compounds of formula (IX) can be prepared from compounds of formula (X) via reactions with a hydroxylamine hydrochloride salt or a hydroxylamine solution in water, in the presence of a base, such as triethylamine or potassium carbonate, in a suitable solvent, such as methanol or ethanol, at temperatures between 0°C and 80°C. In some cases, a better reaction performance may be gained from the use of a catalyst (eg, 8-hydroxyquinoline). For related examples, see Kitamura, S. et al Chem. Pharm. Bull. (2001 ), 49, 268, WO 2017/055473 and WO 2013/066838. This reaction is shown in Scheme 6.
  • Y is NH2
  • a nitrite source eg, NaNCh or iso-amylnitrite
  • a suitable acid eg, hydrochloric acid or HBF4
  • a copper source eg, CuCN
  • an acceptable solvent such as aqueous acetonitrile
  • compounds of formula (XI), wherein Y is NH2, F, Cl, Br, I, or CN can be prepared from compounds of formula (XIII), wherein Z represents NR 5 R 6 , via reactions with a suitable sulfur carbonyl reagent (eg, 1 ,3-dimethyl-1-nitrosothiourea, thiophosgene, thiourea, CS2, or thiocarbonyl-1 , 1- diimidazole) in the presence of nucleophiles of formula (IV), in a suitable solvent (eg, ethyl acetate, acetone, CH2CI2, CHCI3, acetonitrile, or toluene), optionally with a water co-solvent and optionally in the presence of a base (eg, triethylamine, NaHCCh, Ca 2 CC>3), with heating at temperatures between 0°C and 65°C.
  • a suitable sulfur carbonyl reagent eg, 1 ,3-dimethyl
  • Compounds of formula (XIV), wherein Y is CN, Cl, Br, or I, and Z a is hydrogen, C(0)R 4 , C(S)R 4 , C(0)NR 5 R 6 , or C(S)NR 5 R 6 , can be prepared from compounds of formula (XV), wherein X is a OH, OS0 2 Me, Cl, Br, or I, preferably Br or I, via reactions with suitable compounds of formula (VII), optionally in the presence of a base (eg, triethylamine, A/,A/-diisopropylethylamine, K2CO3, NaHC03, or Na 2 C03), in a suitable solvent (eg, dimethylacetamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, or acetonitrile) at temperatures between 25°C and 1 10°C.
  • a base eg, triethylamine, A/,A/-di
  • a better reaction performance may be gained via catalyst use (eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4- dimethylaminopyridine), optionally with microwaves irradiation.
  • catalyst use eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4- dimethylaminopyridine
  • microwaves irradiation e.g., WO 1995/9518122 and Jpn. Kokai Tokkyo Koho, (1993), 05286936; Miyawaki, K. et al Heterocycles (2001 ), 54, 887; WO 2003/028729; WO 2013/066839; and WO 2017/055473. This reaction is shown in Scheme 10.
  • the compounds of formula (XI), wherein Y is formyl, CN, Cl, Br, or I, can be obtained via coupling transformations with compounds of formula (VIII) and compounds of formula (XIII), in a suitable solvent (eg, dimethylformamide, dichloromethane or tetrahydrofuran), at temperatures of between 0°C and 100°C, and optionally in the presence of a base, such as triethylamine.
  • a suitable solvent eg, dimethylformamide, dichloromethane or tetrahydrofuran
  • Compounds of formula (VI), wherein X is Cl or Br can be prepared from compounds of formula (XVI), via reactions with a suitable halogen source (eg, N-bromosuccinimide (NBS) or N- chlorosuccinimide (NCS)) and a radical initiator (eg, (PhC0 2 ) 2 or azobisisobutyronitrile (AIBN)) in a suitable solvent, such as tetrachloromethane, at temperatures between 55°C and 100°C, optionally in the presence of ultraviolet light.
  • a suitable halogen source eg, N-bromosuccinimide (NBS) or N- chlorosuccinimide (NCS)
  • a radical initiator eg, (PhC0 2 ) 2 or azobisisobutyronitrile (AIBN)
  • a suitable solvent such as tetrachloromethane
  • compounds of formula (VI), wherein X is OH, OS0 2 Me, Cl, Br, or I, preferably OH can be prepared from compounds of formula (XVII) via reactions with trifluoroacetic acid, trifluoroacetic ester (including trifluoroacetic methyl ester, trifluoroacetic ethyl ester), trifluoroacetic anhydride, or trifluoroacetyl halide (including trifluoroacetyl fluoride, trifluoroacetyl chloride, and trifluoroacetyl bromide), optionally in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, (eg, toluene, ethyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, or ethanol), at temperatures between 0°C and 75°C.
  • a base eg, pyridine or 4-dimethyla
  • Compounds of formula (XVII), wherein X is OH, OS0 2 Me, Cl, Br, or I, preferably OH, can be prepared from compounds of formula (XVIII) via reactions with a hydroxylamine hydrochloride salt or a hydroxylamine solution in water, optionally in the presence of a base, such as triethylamine or potassium carbonate, in a suitable solvent, such as methanol or ethanol, at temperatures between 0°C and 80°C. In some cases, a better reaction performance may be gained from the use of a catalyst (eg, 8- hydroxyquinoline). For related examples, see Kitamura, S. et al Chem. Pharm. Bull. (2001 ), 49, 268, WO 2017/055473 and WO 2013/066838. This reaction is shown in Scheme 14.
  • compounds of formula (XVIII), wherein X is OH, OS0 2 Me, Cl, Br, or I can be prepared from compounds of formula (XIX), wherein Y is NH2, via radical-nucleophilic aromatic substitution reactions with a suitable nitrite source (eg, NaNC or iso-amylnitrite), an acid (eg, hydrochloric acid or HBF4), and a copper source (eg, CuCN) in an acceptable solvent system, such as acetonitrile and water, at temperatures between 0°C to 100°C.
  • a suitable nitrite source eg, NaNC or iso-amylnitrite
  • an acid eg, hydrochloric acid or HBF4
  • a copper source eg, CuCN
  • compounds of formula (XXI), wherein X is Cl, Br, I, or OSCteMe and Y is formyl, NH2, Cl, Br, I, CN, or 5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl are either commercially available or can be prepared from compounds of formula (XX), via reactions with a suitable acid source (eg, hydrochloric acid, hydrobromic acid, or hydroiodic acid) or a suitable halogen source (eg, tetrabromomethane, tetrachloromethane, or iodine) in the presence of triphenylphosphine, or with methanesulfonyl chloride (CISC Me), in a suitable solvent (eg, dichloromethane), optionally in the presence of a base (eg, triethylamine), at temperatures between 0°C and 100°C.
  • a suitable acid source eg, hydrochloric acid, hydrobromic acid
  • the compounds of formula (I) of the present invention 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 the 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 can 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.
  • the present invention further relates to a method for controlling or preventing infestation of plants or plant propagation material and/or harvested food crops susceptible to microbial attack by treating plants or plant propagation material and/or harvested food crops wherein an effective amount a compound of formula (I) is applied to the plants, to parts thereof or the locus thereof.
  • fungicide as used herein means a compound that controls, modifies, or prevents the growth of fungi.
  • fungicidally effective amount where used means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all dev/ation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
  • 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 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 compounds of formula (I) 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 of formula (I) 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 fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses.
  • These fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses are for example:
  • Absidia corymbifera Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terms, Aureobasidium spp. including A. pullulans, Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. comprising B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C.
  • Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp, Phomopsis viticola, Phytophthora spp.
  • P. infestans Plasmopara spp. including P. halstedii, P. viticola, Pleospora spp., Podosphaera spp. including P. leucotricha, Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P.
  • the compounds of formula (I) may be used for example on turf, ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers, as well as for tree injection, pest management and the like.
  • target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St.
  • perennial and annual crops such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries
  • cereals for example barley, maize (corn), millet, oats
  • Augustine grass and Zoysia grass herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
  • herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme
  • legumes for example beans, lentils, peas and soya beans
  • useful plants is to be understood as also including useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol- pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol- pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • imazamox by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
  • useful plants is to be understood as also including 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.
  • YieldGard® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CrylllB(bl ) toxin); YieldGard Plus® (maize variety that expresses a CrylA(b) and a Cryll IB(b1 ) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CrylF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c) toxin); Bollgard I® (cotton variety that expresses a CrylA(c) toxin); Bollgard II® (cotton variety
  • crops is to be understood as including also crop 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.
  • Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp.
  • insecticidal proteins from Bacillus cereus or Bacillus popilliae such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticid
  • Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins
  • toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
  • agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors
  • steroid metabolism enzymes such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecd
  • d-endotoxins for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins.
  • Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701 ).
  • Truncated toxins for example a truncated CrylAb, are known.
  • modified toxins one or more amino acids of the naturally occurring toxin are replaced.
  • amino acid replacements preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
  • Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO93/07278, W095/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
  • Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
  • the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
  • Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
  • Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a
  • transgenic crops are:
  • Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ( Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylAb toxin. Bt1 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
  • MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
  • MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/ES/96/02.
  • NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810.
  • NK603 * MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • the compounds of formula (I) may be used in controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi (such as Phakopsora pachyrhizi) on soy bean plants.
  • transgenic soybean plants expressing toxins for example insecticidal proteins such as delta-endotoxins, e.g. CrylAc (Cry1 Ac Bt protein).
  • toxins for example insecticidal proteins such as delta-endotoxins, e.g. CrylAc (Cry1 Ac Bt protein).
  • this may include transgenic soybean plants comprising event MON87701 (see U.S. Patent No. 8,049,071 and related applications and patents, as well as WO 2014/170327 A1 (eg, see paragraph [008] reference to Intacta RR2 PROTM soybean)), event MON87751 (US. Patent Application Publication No. 2014/0373191 ) or event DAS- 81419 (U.S. Patent No. 8632978 and related applications and patents).
  • event MON87701 see U.S. Patent No. 8,049,071 and related applications and patents, as well as WO 2014/170327 A1 (eg, see paragraph [008] reference to In
  • transgenic soybean plants may comprise event SYHT0H2 - HPPD tolerance (U.S. Patent Application Publication No. 2014/0201860 and related applications and patents), event MON89788 - glyphosate tolerance (U.S. Pat. No. 7,632,985 and related applications and patents), event MON87708
  • event DAS-40278-9 - tolerance to 2,4- dichlorophenoxyacetic acid and aryloxyphenoxypropionate see WO 201 1/022469, WO 201 1/022470, WO 201 1/022471 , and related applications and patents
  • event 127 - ALS tolerance WO 2010/080829 and related applications and patents
  • event GTS 40-3-2 - glyphosate tolerance event DAS-68416-4- 2,4-dichlorophenoxyacetic acid and glufosinate tolerance
  • event FG72 - glyphosate and isoxaflutole tolerance event BPS-CV127-9 - ALS tolerance and GU262 - glufosinate tolerance or event SYHT04R
  • the compounds of formula (I) may be used in controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi (such as Phakopsora pachyrhizi) on soy bean plants.
  • phytopathogenic diseases especially phytopathogenic fungi (such as Phakopsora pachyrhizi) on soy bean plants.
  • phytopathogenic fungi such as Phakopsora pachyrhizi
  • R-gene stacks conferring a degree of immunity or resistance to specific Phakopsora pachyrhizi, have been been introgressed in the plant genome, see for example:“Fighting Asian Soybean Rust”, Langenbach C, et al, Front Plant Science 7(797) 2016).
  • An elite plant is any plant from an elite line, such that an elite plant is a representative plant from an elite variety.
  • elite soybean varieties that are commercially available to farmers or soybean breeders include: AG00802, A0868, AG0902, A1923, AG2403, A2824, A3704, A4324, A5404, AG5903, AG6202 AG0934; AG1435; AG2031 ; AG2035; AG2433; AG2733; AG2933; AG3334; AG3832; AG4135; AG4632; AG4934; AG5831 ; AG6534; and AG7231 (Asgrow Seeds, Des Moines, Iowa, USA); BPR0144RR, BPR 4077NRR and BPR 4390NRR (Bio Plant Research, Camp Point, III., USA); DKB17-51 and DKB37-51 (DeKalb Genetics, DeKalb, III., USA); DP 4546 RR, and DP 7870 RR (Delta & Pine Land Company, Lubbock,
  • the compounds of formula (I) are used to control Phakopsora pachyrhizi, (including fungicidally-resistant strains thereof, as outlined below) on Elite soybean plant varieties where R-gene stacks, conferring a degree of immunity or resistance to specific Phakopsora pachyrhizi, have been been introgressed in the plant genome.
  • Numerous benefits may be expected to ensue from said use, e.g. improved biological activity, an advantageous or broader spectrum of activity (inc.
  • Phakopsora pachyrhizi sensitive and resistant strains of Phakopsora pachyrhizi
  • an increased safety profile improved crop tolerance, synergistic interactions or potentiating properties, improved onset of action or a longer lasting residual activity, a reduction in the number of applications and/or a reduction in the application rate of the compounds and compositions required for effective control of the phytopathogen ( Phakopsora pachyrhizi), thereby enabling beneficial resistance-management practices, reduced environmental impact and reduced operator exposure.
  • Fungicidal-resistant strains of Phakopsora pachyrhizi have been reported in the scientific literature, with strains resistant to one or more fungicides from at least each of the following fungicidal mode of action classes being observed: sterol demethylation-inhibitors (DMI), quinone-outside-inhibitors (Qol) and succinate dehydrogenase inhibitors (SDHI).
  • DMI sterol demethylation-inhibitors
  • Qol quinone-outside-inhibitors
  • SDHI succinate dehydrogenase inhibitors
  • the compounds of formula (I) may be used to control Phakopsora pachyrhizi which are resistant to one or more fungicides from any of the following fungicidal MoA classes: sterol demethylation-inhibitors (DMI), quinone-outside-inhibitors (Qol) and succinate dehydrogenase inhibitors (SDHI).
  • DMI sterol demethylation-inhibitors
  • Qol quinone-outside-inhibitors
  • SDHI succinate dehydrogenase inhibitors
  • locus means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • 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.
  • vegetative material such as cuttings or tubers, for example potatoes.
  • seeds in the strict sense
  • roots in the strict sense
  • fruits in the tubers
  • bulbs rhizomes
  • parts of plants there can 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 can be protected before transplantation by a total or partial treatment by immersion.
  • 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.
  • Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
  • Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers.
  • the particles contain the active ingredient retained in a solid matrix.
  • Typical solid matrices include fuller’s earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
  • Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
  • Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which treatment is required.
  • Typical carriers for granular formulations include sand, fuller’s earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound.
  • Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils
  • Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.
  • Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates.
  • Encapsulated droplets are typically 1 to 50 microns in diameter.
  • the enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound.
  • Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores.
  • Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring.
  • Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.
  • compositions for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents.
  • Pressurised sprayers wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.
  • Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1 ,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide,
  • Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller’s earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin.
  • a broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application.
  • These agents when used, normally comprise from 0.1 % to 15% by weight of the formulation. They can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes.
  • Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub.
  • alcohol-alkylene oxide addition products such as tridecyl alcohol-C.sub. 16 ethoxylate
  • soaps such as sodium stearate
  • alkylnaphthalenesulfonate salts such as sodium dibutylnaphthalenesulfonate
  • dialkyl esters of sulfosuccinate salts such as sodium di(2-ethylhexyl) sulfosuccinate
  • sorbitol esters such as sorbitol oleate
  • quaternary amines such as lauryl trimethylammonium chloride
  • polyethylene glycol esters of fatty acids such as polyethylene glycol stearate
  • salts of mono and dialkyl phosphate esters such as mono and dialkyl phosphate esters.
  • adjuvants commonly utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti-foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.
  • biocidally active ingredients or compositions may be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention. When applied simultaneously, these further active ingredients may be formulated together with the compositions of the invention or mixed in, for example, the spray tank. These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.
  • Pesticidal agents are referred to herein using their common name are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.
  • compositions of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer).
  • SAR inducers are known and described in, for example, United States Patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.
  • the compounds of formula (I) are normally used in the form of agrochemical 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 defined herein, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
  • the invention therefore 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 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 active ingredient may, in some cases, result in unexpected synergistic activities.
  • Suitable additional active ingredients include the following: acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fung
  • Suitable additional active ingredients also include the following: 3-difluoromethyl-
  • the compounds of the invention may also be used in combination with anthelmintic agents.
  • anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP- 444964 and EP-594291 .
  • Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO- 9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
  • the compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE-19520936.
  • the compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO 96/15121 and also with anthelmintic active cyclic depsipeptides such as those described in WO 96/1 1945, WO 93/19053, WO 93/25543, EP 0 626 375, EP 0 382 173, WO 94/19334, EP 0 382 173, and EP 0 503 538.
  • the compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
  • ectoparasiticides for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
  • the compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers WO 95/19363 or WO 04/72086, particularly the compounds disclosed therein.
  • Organophosphates acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, me
  • Carbamates alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801 , isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
  • Pyrethroids acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E)-(1 R)-cis-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, a- cypermethrin, beta-cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvaler
  • Arthropod growth regulators a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
  • antiparasitics acequinocyl, amitraz, AKD-1022, ANS-1 18, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydra
  • Biological agents Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
  • Bactericides chlortetracycline, oxytetracycline, streptomycin.
  • TX means one compound selected from the group consisting of the compounds as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
  • an acaricide selected from the group of substances consisting of 1 ,1-bis(4-chlorophenyl)-2- ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenyl benzenesulfonate (lUPAC/Chemical Abstracts name) (1059) + TX, 2-fluoro-A/-methyl-A/-1-naphthylacetamide (IUPAC name) (1295) + TX, 4- chlorophenyl phenyl sulfone (IUPAC name) (981 ) + TX, abamectin (1 ) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha- cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet
  • an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, an anthelmintic selected from the group of substances consisting of abamectin (1 ) + TX, crufomate (101 1 ) + TX, dorame
  • an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX, a bactericide selected from the group of substances consisting of 1 -hydroxy- 1 /-/-pyridine-2- thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1 105) + TX, dodicin (1 1 12) + TX
  • a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter ( alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51
  • a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX,
  • a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] and
  • an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541 ) + TX, (E,Z)-tetradeca-4, 10-dien-1-yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec- 1 1-enal (IUPAC name) (436) + TX, (Z)-hexadec-l 1-en-1-yl acetate (IUPAC name) (437) + TX, (Z)- hexadec-13-en-1 1 -
  • an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591 ) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1 137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
  • an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (lUPAC/Chemical Abstracts name) (1058) + TX, 1 , 1-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), + TX, 1 ,2-dichloropropane (lUPAC/Chemical Abstracts name) (1062) + TX, 1 ,2- dichloropropane with 1 ,3-dichloropropene (IUPAC name) (1063) + TX, 1-bromo-2-chloroethane (lUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate (IUPAC name) (1451 ) + TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate (IUPAC name) (1066)
  • a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + T
  • a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, 1 ,2-dibromo-3-chloropropane (lUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2- dichloropropane (IUPAC/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3- dichloropropene (IUPAC name) (1063) + TX, 1 ,3-dichloropropene (233) + TX, 3,4- dichlorotetrahydrothiophene 1 , 1-dioxide (lUPAC/Chemical Abstracts name) (1065) + TX, 3-(4- chlorophenyl)-5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1 ,3,5-thiadiazinan-3- ylacetic acid (IUPAC name) (1286) + TX,
  • a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
  • a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
  • a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891 ) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91 ) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, couma
  • a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
  • an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171 ) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
  • a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
  • a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
  • the active ingredient mixture of the compounds of formula (I) selected from one compound as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below) is preferably in a mixing ratio of from 100:1 to 1 :6000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20:1 to 1 :20, even more especially from 10:1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2: 1 to 1 :2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1 : 1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3:1 , or 3:2, or 2: 1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1
  • the mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
  • the mixtures comprising a compound as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below), and one or more active ingredients as described above can be applied, for example, in a single“ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a“tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
  • compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
  • auxiliaries such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides
  • compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
  • auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries).
  • Another aspect of the invention is related to the use of a compound of formula (I) or of a preferred individual compound as defined herein, 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 or insecticidal mixture comprising at least one compound of formula (I) or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides 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 insects or 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 insects or by phytopathogenic microorganisms, preferably fungal organisms.
  • a further aspect of the 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 insects or 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.
  • 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 insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms
  • a compound of formula (I) or of a preferred individual compound as above-defined as active ingredient to the plants, to parts
  • 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, or insects 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 or insect.
  • the compounds of formula (I) can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula (I) may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation e.g. a composition containing the compound of formula (I), and, if desired, 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).
  • 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.
  • convenient dosages are from 10mg to 1g of active substance per kg of seeds.
  • rates of 0.001 to 50 g of a compound of formula (I) per kg of seed preferably from 0.01 to 10g per kg of seed are generally sufficient.
  • composition comprising a compound of formula (I) according to the present invention is applied either preventative, meaning prior to disease development or curative, meaning after disease development.
  • compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK
  • compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects).
  • appropriate formulation inerts diiluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects.
  • conventional slow release formulations may be employed where long lasting efficacy is intended.
  • formulations to be applied in spraying forms such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g.
  • a seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • suitable seed dressing formulation form e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • seed dressing formulations are known in the art.
  • Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
  • the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) optionally together with other active agents, particularly microbiocides or conservatives or the like.
  • Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent.
  • Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
  • Table 1.1 This table discloses 67 specific compounds of the formula (T-1 ):
  • A is:
  • R 1 , R 2 , and R 3 are hydrogen and R 4 is as defined below in Table 1.
  • Tables 1.2 to 1.19 make available 67 individual compounds of the formula (T-1 A) in which A, R 1 , R 2 , and R 3 are as specifically defined in Tables 1.2 to 1.19, which refer to Table 1 wherein R 4 is specifically defined.
  • Table 1.2 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 , R 2 , and R 2 are hydrogen and R 4 is as defined above in Table 1.
  • Table 1.3 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methyl, and R 4 is as defined above in Table 1.
  • Table 1.4 This table discloses 67 specific compounds of formula (T-1 ) wherein A is: R 1 and R 2 are hydrogen, R 3 is methyl, and R 4 is as defined above in Table 1.
  • Table 1.5 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethyl, and R 4 is as defined above in Table 1.
  • Table 1.6 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethyl, and R 4 is as defined above in Table 1.
  • Table 1.7 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is cyclopropyl, and R 4 is as defined above in Table 1.
  • Table 1.8 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is cyclopropyl, and R 4 is as defined above in Table 1.
  • Table 1.9 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is 2,2-difluoroethoxy and R 4 is as defined above in Table 1.
  • Table 1.10 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is 2,2-difluoroethoxy, and R 4 is as defined above in Table 1.
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and R 4 is as defined above in Table 1.
  • Table 1.12 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and R 4 is as defined above in Table 1.
  • Table 1.13 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and R 4 is as defined above in Table 1.
  • Table 1.14 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 hydrogen, R 2 is methyl, and R 3 is methoxy, and R is as defined above in Table 1.
  • Table 1.15 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy and R 4 is as defined above in Table 1.
  • Table 1.17 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and R 4 is as defined above in Table 1.
  • Table 1.18 This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethoxy and R 4 is as defined above in Table 1.
  • R 1 and R 2 are hydrogen, R 3 is ethoxy, and R 4 is as defined above in Table 1.
  • R 1 , R 2 and R 3 are hydrogen and -NR 5 (R 6 ) is as defined below in Table 2.
  • Tables 2.2 to 2.19 make available 55 individual compounds of the formula (T-2) in which A, R 1 , R 2 , and R 3 are as specifically defined in Tables 2.2 to 2.19, which refer to Table 2, wherein NR 5 (R 6 ) is specifically defined.
  • Table 2.2 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 , R 2 and R 3 are hydrogen and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.3 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.4 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.5 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.6 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.7 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is cyclopropyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • R 1 and R 2 are hydrogen, R 3 is cyclopropyl, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.9 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is 2,2-difluoroethoxy and NR 5 (R 6 ) is as defined above in Table 2.
  • R 1 and R 2 are hydrogen, R 3 is 2,2-difluoroethoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.1 1 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.12 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.17 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is methoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • Table 2.18 This table discloses 55 specific compounds of formula (T-2) wherein A is:
  • R 1 and R 2 are hydrogen, R 3 is ethoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • R 1 and R 2 are hydrogen, R 3 is ethoxy, and NR 5 (R 6 ) is as defined above in Table 2.
  • the compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.
  • Compounds of formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
  • LC/MS Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method A is as follows:
  • Type of column Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
  • Active ingredient [compound of formula (I)] 25 % 50 % 75 %
  • Kaolin 62 % 27 % The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • Active ingredient [compound of formula (I)] 25 % 50 % 75 %
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Active ingredient [compound of formula (I)] 5 % 6 % 4 %
  • Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
  • Kaolin 82 % The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
  • polyethylene glycol (mol. wt. 200) 3 %
  • Kaolin 89 % The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
  • nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
  • Silicone oil (in the form of a 75 % emulsion in water) 1 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment
  • Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension Formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • AIBN azobisisobutyronitrile
  • DIPEA N,N-di-isopropylethylamine
  • NBS N-bromosuccinimide
  • LC/MS Liquid Chromatography Mass Spectrometry (description of the apparatus and the methods used for LC/MS analysis are given above)
  • Example 1 This example illustrates the preparation of 1-cyclopropyl-3-methyl-1-[[5-[5-(trifluoromethyl)- 1 ,2,4-oxadiazol-3-yl]-2-thienyl]methyl]thiourea (Compound 1.1 1 of Table T1 )
  • Step 1 Preparation of N'-hvdroxy-5-methyl-thiophene-2-carboxamidine
  • Step 3a Preparation of 3-[5-(bromonnethvD-2-thienvn-5-(thfluoronnethvD-1.2.4-oxadiazole
  • Step 4 Preparation of N-[[5-[5-(trifluoromethvn-1 ,2.4-oxadiazol-3-yll-2- thienyllmethyncvclopropanamine
  • Step 5 Preparation of 1-cvclopropyl-3-methyl-1-[[5-[5-(trifluoromethv0-1 ,2.4-oxadiazol-3-yll-2- thienyllmethyllurea
  • N-methoxy-1-[5-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-2- thienyl]methanamine (0.15 g, 0.52 mmol) in dichloromethane (1.6 ml_) was added triethylamine (0.15 ml_, 1.43 mmol).
  • the resultant mixture was cooled to 5°C and then N-methylcarbamoyl chloride (0.06 g, 0.67 mmol) was introduced.
  • the reaction mixture was allowed to reach 25°C and stirred for 1 hour.
  • the resultant residue was added to water and extracted with ethyl acetate.
  • Step 6 Preparation of 1-cvclopropyl-3-methyl-1-[[5-[5-(trifluoromethvn-1 ,2.4-oxadiazol-3-yll-2- thienyllmethynthiourea
  • Example 2 This example illustrates the preparation of 3-cyclopropyl-1-methoxy-1-[[4-[5- (trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]thiourea (Compound 1.7 of Table T1 )
  • Step 3a Preparation of 3-[4-(bromonnethyl)phenyll-5-(thfluoronnethvD-1.2.4-oxadiazole
  • Step 3b Preparation of 3-[4-(bromonnethyl henyll-5-(thfluoronnethvD-1.2.4-oxadiazole from 3-[4-
  • Step 4 Preparation of N-methoxy-1-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yllphenyllmethanamine
  • Step 5 Preparation of 3-cvclopropyl-1-methoxv-1-l l-1 ,2,4-oxadiazol-3- yllphenyllmethyllthiourea
  • Step 1 Preparation of 2.3-difluoro-N'-hvdroxy-4-methyl-benzamidine
  • Step 2 Preparation of 3-(2.3-difluoro-4-nnethyl-phenvD-5-(trifluoronnethvD-1.2.4-oxadiazole
  • Step 3 Preparation of 3-[4-(bromonnethvD-2.3-difluoro-phenvn-5-(thfluoronnethvD-1 ,2,4-oxadiazole
  • the mixture was cooled to 25°C, diluted with dichloromethane, water, and the layers were separated.
  • the succinimide by-product was filtered off and volatiles were removed under vacuum.
  • the resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 100:0 to 4: 1 ) to afford 4.8 g of the title compound as a white solid.
  • Step 4 Preparation of 1-[2.3-difluoro-4-[5-(trifluoromethvn-1.2.4-oxadiazol-3-yllphenyll-N-methoxy- methanamine
  • Step 5 Preparation of N-[[2.3-difluoro-4-[5-(trifluoromethvn-1.2.4-oxadiazol-3-yllphenyllmethyll-N- methoxy-propanamide
  • enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, (e.g., by using chiral starting materials).
  • Table T 1 Melting point imp) data and/or retention times (Rt) for compounds according to formula (I):
  • Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse.
  • the cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar.
  • the leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation.
  • Compounds to be tested are prepared as DMSO solutions (max. 10 mg/mL) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying.
  • the inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system.
  • a single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.
  • Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth.
  • DMSO solutions of the test compound (max. 10 mg/mL) are diluted with 0.025% Tween20 by a factor of 50 and 10 pL of this solution is pipetted into a microtiter plate (96-well format).
  • the nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound.
  • the test plates are incubated in the dark at 24°C and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.
  • Example 1 Fungicidal activity against Puccinia recondita f. so. tritici / wheat / leaf disc preventative (Brown rust)
  • Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf segments were incubated at 19 ° C and 75% relative humidity (rh) under a light regime of 12 hours light / 12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 to 9 days after application).
  • the following compounds at 200 ppm in the applied formulation 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.
  • Example 2 Fungicidal activity against Puccinia recondita f. so. tritici / wheat / leaf disc curative (Brown rust)
  • Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. Plates were stored in darkness at 19°C and 75% relative humidity. The formulated test compound diluted in water was applied 1 day after inoculation. The leaf segments were incubated at 19°C and 75% relative humidity under a light regime of 12 hours light / 12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 to 8 days after application).
  • the following compounds at 200 ppm in the applied formulation 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.
  • Example 3 Fungicidal activity against Phakopsora pachyrhizi / soybean / leaf disc preventative (Asian soybean rust)
  • Soybean leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • leaf discs are inoculated by spraying a spore suspension on the lower leaf surface.
  • 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 (12 to 14 days after application).
  • the following compounds at 200 ppm in the applied formulation 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.
  • Example 4 Fungicidal activity against Glomerella lagenarium (Colletotrichum lagenarium) liquid culture / cucumber / preventative (Anthracnose)
  • Conidia of the fungus from cryogenic storage 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 spores is added. The test plates are incubated at 24 ° C and the inhibition of growth is measured photometrically 3 to 4 days after application.
  • the following compounds at 20 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control under the same conditions, which show extensive disease development.

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Abstract

Compounds of formula (I) wherein the substituents are as defined in claim 1, useful as pesticides, especially as fungicides.

Description

Microbiocidal Oxadiazole Derivatives
The present invention relates to microbiocidal oxadiazole derivatives, e.g., as active ingredients, which have microbiocidal activity, in particular, fungicidal activity. The invention also relates to agrochemical compositions which comprise at least one of the oxadiazole derivatives, to processes of preparation of these compounds and to uses of the oxadiazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or nonliving materials by phytopathogenic microorganisms, preferably fungi. EP 0 276 432 and WO 2015/185485 describe the use of substituted oxadiazoles for combating phytopathogenic fungi.
According to the present invention, there is provided a compound of formula (I):
Figure imgf000002_0001
wherein A-1 , A-2, A-3, or A-4 are optionally substituted by 1 or 2 independently selected halogen groups;
R1 and R2 are independently selected from hydrogen, methyl and cyano; or R1 and R2, together with the carbon atom to which they are bonded, form a cyclopropyl ring;
R3 represents hydrogen, hydroxy, Ci-4alkyl, Ci-4haloalkyl, Ci-4alkoxy, hydroxyC2-4alkyl, C-i- 2alkoxyC2-4alkyl, Ci-2haloalkoxy, Ci-2haloalkoxyC2-4alkyl, C3-4alkenyl, C3-4alkynyl, C3-4alkenyloxy, C3- 4alkynyloxy, Ci-4alkylcarbonyloxy, N-Ci-2alkylamino, N,N-diCi-2alkylamino, C3-6cycloalkyl or C3- 6cycloalkylCi-2alkyl;
Z is selected from Z1 or Z2; wherein Z1 is R4, wherein R4 represents hydrogen, cyano, Ci-ealkyl, C-i ehaloalkyl, cyanoC-i ealkyl, hydroxyCi-4alkyl, Ci-4alkoxyCi-4alkyl, Ci-4haloalkoxyCi-4alkyl, Ci-2alkoxyCi-2alkoxyCi-4alkyl, C3- 5alkenyloxyCi-4alkyl, C3-5alkynyloxyCi-4alkyl, aminoCi-6alkyl, N-Ci-4alkylaminoCi-4alkyl, N,N-diCi- 4alkylanninoCi-4alkyl, Ci-4alkylcarbonylCi-4alkyl, Ci-4alkoxycarbonylCi-4alkyl, Ci-4alkylcarbonyloxyCi- 4alkyl, N-Ci-4alkylaminocarbonylCi-4alkyl, N,N-diCi-4alkylaminocarbonylCi-4alkyl, Ci-4alkylsulfanylCi- 4alkyl, Ci-4alkylsulfonylCi-4alkyl, Ci-4alkylsulfonylaminoCi-4alkyl, Ci-4alkylcarbonylaminoCi-4alkyl or C-i- 4alkoxycarbonylanninoCi-4alkyl; or
R4 represents heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 4- to 6-membered nonaromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from cyano, halogen, hydroxy, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy and cyclopropyl, and
wherein when R4 comprises a heterocyclyl, this cycle may optionally contain 1 group selected from C(O) or S(0)2;
Z2 represents -NR5R6, wherein R5 represents hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, C-i- 4alkoxy, C3-salkenyl, C3-salkynyl, C3-4alkenyloxy, C3-4alkynyloxy, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, Ci-2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2-4alkoxyC2-4alkyl, N-C-i- 3alkylamino, N,N-diCi-3alkylamino, aminoC2-4alkyl, N-Ci-4alkylaminoC2-4alkyl, N,N-diCi-4alkylaminoC2- 4alkyl, Ci-3alkylcarbonylCi-3alkyl, Ci-4alkoxycarbonylCi-3alkyl, Ci-3alkylcarbonyloxyC2-4alkyl, N-C1- 3alkylaminocarbonylCi-3alkyl, N,N-diCi-3alkylaminocarbonylCi-3alkyl, Ci-3alkylsulfonyl, C1- 3alkylsulfonylC2-3alkyl or Ci-3alkylsulfonylaminoC2-3alkyl; or
R5 represents C3-6cycloalkyl, C3-6cycloalkylCi-2alkyl, phenyl, phenylCi-2alkyl, heteroaryl or heteroarylCi-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1 , 2, 3, or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylC-i- 2alkyl wherein the heterocyclyl moiety is a 4- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms or groups individually selected from N, NR7, O and S; wherein the cycloalkyl, phenyl, heteroaryl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl and cyclopropylmethyl, and
wherein when R5 comprises a cycloalkyl or heterocyclyl, these cycles may optionally contain 1 group selected from C(O) or S(0)2;
R6 represents hydrogen, cyano, halogen, hydroxy, amino, methyl, ethyl, propyl, prop-2-enyl, prop-2-ynyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, difluoromethoxy, prop-2-enyloxy, prop-2-ynyloxy, N-methylamino, N,N-dimethylamino, methylcarbonyl, methoxycarbonyl, formylamino, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl or methoxycarbonylamino; and R7 represents hydrogen, methyl, methoxy, formyl or acyl; or a salt or an N-oxide thereof.
Surprisingly, it has 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.
According to a second aspect of the invention, there is provided an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I). Such an agricultural composition may further comprise at least one additional active ingredient and/or an agrochemically- acceptable diluent or carrier.
According to a third aspect of the invention, there is provided a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
According to a fourth aspect of the invention, there is provided the use of a compound of formula (I) as a fungicide. According to this particular aspect of the invention, the use may exclude methods for the treatment of the human or animal body by surgery or therapy.
As used herein, the term "halogen" or“halo” refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
As used herein, cyano means a -CN group.
As used herein, the term“hydroxyl” or“hydroxy” means an -OH group.
As used herein, amino means an -NH2 group.
As used herein, acyl means a -C(0)CH3 group.
As used herein, formyl means a -C(0)H group.
As used herein, the term "Ci-6alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond. Ci-4alkyl, C-i salkyl and Ci-2alkyl are to be construed accordingly. Examples of C-i ealkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, and 1-dimethylethyl (tert-butyl). A“Ci-2alkylene” group refers to the corresponding definition of Ci-2alkyl, except that such radical is attached to the rest of the molecule by two single bonds. Examples of Ci-2alkylene, are -CH2- and -CH2CH2-.
As used herein, the term "Ci-4alkoxy" refers to a radical of the formula RaO- where Ra is a C-i- 4alkyl radical as generally defined above. The terms C-i salkoxy and Ci-2alkoxy are to be construed accordingly. Examples of Ci-4alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, and tert-butoxy. As used herein, the term "Ci-4haloalkyl" refers to a Ci^alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. Examples of Ci-4haloalkyl include, but are not limited to fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, and 3,3,3-trifluoropropyl.
As used herein, the term "cyanoCi-4alkyl" refers to a Ci-4alkyl radical as generally defined above substituted by one or more cyano groups.
As used herein, the term "aminoCi-4alkyl" refers to a Ci-4alkyl radical as generally defined above substituted by one or more amino groups.
As used herein, the term "C3-5alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (Z)-configu ration, having from three to five carbon atoms, which is attached to the rest of the molecule by a single bond. C3-4alkenyl is to be construed accordingly. Examples of C3- Csalkenyl include, but are not limited to, prop-1 -enyl, allyl (prop-2-enyl), and but-1-enyl.
As used herein, the term "C3-4alkenyloxy" refers to a radical of the formula RaO-, where Ra is a C3-4alkenyl radical as generally defined above.
As used herein, the term "C3-5alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from three to five carbon atoms, and which is attached to the rest of the molecule by a single bond. The term "C3-4alkynyl" is to be construed accordingly. Examples of C3-salkynyl include, but are not limited to, prop- 1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.
As used herein, the term "C3-4alkynyloxy" refers to a radical of the formula RaO-, where Ra is a C3-4alkynyl radical as generally defined above.
As used herein, the term "Ci-4alkoxyCi-4alkyl" refers to radical of the formula Rb-0-Ra- where Rb is a Ci-4alkyl radical as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term "Ci-4haloalkoxy" refers to a Ci-4alkoxy group as defined above substituted by one or more of the same or different halogen atoms. Ci shaloalkoxy is to be construed accordingly. Examples of Ci-4haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.
As used herein, the term“hydroxyC2-4alkyl” refers to a C2-4alkyl radical as generally defined above substituted by one or more hydroxy groups.
As used herein, the term "Ci-4alkylcarbonyl" refers to a radical of the formula RaC(0)-, where Ra is a Ci-4alkyl radical as generally defined above.
As used herein, the term “Ci-2alkoxyCi-2alkoxyCi-4alkyl” refers to a radical of the formula RcORbORa-, where Ra is a Ci-4alkylene radical and Rb is a Ci-2alkylene radical as generally defined above, and Rc is a Ci-2alkyl radical as generally defined above.
As used herein, the term“Ci-4alkoxycarbonyl” refers to a radical of the formula RaOC(0)-, where Ra is a Ci-4alkyl radical as generally defined above.
As used herein, the term“N-Ci-4alkylamino” refers to a radical of the formula RaNH- where Ra is a Ci-4alkyl radical as generally defined above. N-Ci-3alkylamino is to be construed accordingly. As used herein, the term“N,N-diCi-4alkylamino” refers to a radical of the formula Ra(Rb)N- where Ra and Rb are Ci-4alkyl radicals as generally defined above.
As used herein, the term“Ci-4alkylcarbonylCi-4alkyl” refers to a radical of the formula RbC(0)Ra- where Rb is a Ci-4alkyl as generally defined above and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term “Ci-4alkoxycarbonylCi-4alkyl” refers to a radical of the formula RbOC(0)Ra- where Rb is a Ci-4alkyl as generally defined above and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term“Ci-4alkylcarbonyloxy” refers to a radical of the formula RaC(0)0- where Ra is a Ci-4alkyl as generally defined above.
As used herein, the term“Ci-4alkylsulfanyl” refers to a radical of the formula RaS-, where Ra is a Ci-4alkyl radical as generally defined above. Examples of Ci-4alkylsulfanyl include, but are not limited to methylsulfanyl.
As used herein, the term“Ci-4alkylsulfonyl” refers to a radical of the formula RaS(0)2-, where Ra is a Ci-4alkyl radical as generally defined above. Examples of C-i salkylsulfonyl include, but are not limited to methylsulfonyl.
As used herein, the term“Ci-4alkylsulfonylCi-4alkyl” refers to a radical of the formula RbS(0)2Ra-, where Rb is a Ci-4alkyl radical as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term“Ci-4alkylsulfonylamino” refers to a radical of the formula RaS(0)2NH-, where Ra is a Ci-4alkyl radical as generally defined above.
As used herein, the term “Ci-4alkylsulfonylaminoCi-4alkyl” refers to a radical of the formula RbS(0)2NHRa-, where Rb is a Ci-4alkyl radical as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term“N,N-diCi-4alkylamino” refers to a radical of the formula (Ra)(Rb)N-, wherein Ra and Rb are each Ci-4alkyl radicals as generally defined above.
As used herein, the term “N,N-diCi-4alkylaminoCi-4alkyl” refers to a radical of the formula (Rc)(Rb)NRa-, wherein Rb and Rc are each independently Ci-4alkyl radicals as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term“N-Ci-4alkylaminocarbonylCi-4alkyl” refers to a radical of the formula (Rb)NHC(0)Ra-, wherein Rb is a Ci-4alkyl radical as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term“N,N-diCi-4alkylaminocarbonylCi-4alkyl” refers to a radical of the formula (Rc)(Rb)NHC(0)Ra-, wherein Rb and Rc are each independently Ci-4alkyl radicals as generally defined above, and Ra is a Ci-4alkylene radical as generally defined above.
As used herein, the term "C3-6cycloalkyl" refers to a stable, monocyclic ring radical which is saturated or partially unsaturated and contains 3 to 6 carbon atoms. C3-scycloalkyl and C3-4cycloalkyl are to be construed accordingly. Examples of Cs ecycloalkyl include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclopenten-1-yl, cyclopenten-3-yl, and cyclohexen-3-yl. As used herein, the term "C3-6cycloalkylCi-2alkyl" refers to a C3-6cycloalkyl ring as defined above attached to the rest of the molecule by a Ci-2alkylene radical as defined above. Examples of C3- 6cycloalkylCi-2alkyl include, but are not limited to cyclopropyl-methyl and cyclobutyl-ethyl.
As used herein, the term "phenylCi-2alkyl" refers to a phenyl ring attached to the rest of the molecule by a Ci-2alkylene radical as defined above. Examples of phenylCi-2alkyl include, but are not limited to, benzyl.
As used herein, the term "heteroaryl" generally refers to a 5- or 6-membered monocyclic aromatic ring radical which comprises 1 , 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heteroaryl include but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazinyl, pyridazinyl, pyrimidyl and pyridyl.
As used herein, the term "heteroarylCi-2alkyl" refers to a heteroaryl ring as defined above which is attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
As used herein, the term "heterocyclyl" or "heterocyclic" generally refers to a stable, saturated or partially saturated, 4- to 6-membered, non-aromatic monocyclic ring, which comprises 1 or 2 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, tetrahydropyranyl, dioxolanyl, and morpholinyl.
As used herein, the term "heterocyclylCi-2alkyl" refers to a heterocyclic ring as defined above which is attached to the rest of the molecule by a Ci-2alkylene radical as defined above.
The presence of one or more possible asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also, atropisomers may occur as a result of restricted rotation about a single bond. The compound of 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, the compound of formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present. 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 an N-oxide, in covalently hydrated form, or in salt form, e.g., an agronomically usable or agrochemically acceptable 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 A (including A-1 , A-2, A-3, or A-4), R1 , R2, R3, Z (including Z1 , Z2), R4, R5, R6, and R7 with reference to the compounds of formula (I) of the present invention. 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.
A is A-1 , A-2, A-3, or A-4,
Figure imgf000008_0001
wherein A-1 , A-2, A-3, or A-4 are optionally substituted by 1 or 2 independently selected halogen groups. Preferably, the halogen is chloro or fluoro, and most preferably, fluoro.
In some embodiments of the invention, A is A-1.
In some embodiments of the invention, A is A-2.
In some embodiments of the invention, A is A-3.
In some embodiments of the invention, A is A-4.
Preferably, A is A-1 optionally substituted by 1 or 2 fluorine groups, or A is unsubstitued A-4. More preferably, A is unsubstitued A-1 (1 ,4-phenylene) or unsubstitued A-4 (2,5-thienylene).
R1 and R2 are independently selected from hydrogen, methyl and cyano; or R1 and R2, together with the carbon atom to which they are bonded, form a cyclopropyl ring. Preferably, R1 and R2 are independently selected from hydrogen and methyl, and more preferably R1 and R2 are hydrogen.
R3 represents hydrogen, hydroxy, Ci-4alkyl, Ci-4haloalkyl, Ci-4alkoxy, hydroxyC2-4alkyl, C-i- 2alkoxyC2-4alkyl, Ci-2haloalkoxy, Ci-2haloalkoxyC2-4alkyl, C3-4alkenyl, C3-4alkynyl, C3-4alkenyloxy, C3- 4alkynyloxy, Ci-4alkylcarbonyloxy, N-Ci-2alkylamino, N,N-diCi-2alkylamino, Cs ecycloalkyl or C3- 6cycloalkylCi-2alkyl. Preferably, R3 is hydrogen, Ci-4alkyl, Ci-4haloalkyl, Ci-4alkoxy, Ci-2haloalkoxy or cyclopropyl, more preferably R3 is hydrogen, Ci-4alkyl, Ci-2fluoroalkyl, Ci-4alkoxy, Ci-2fluoroalkoxy or cyclopropyl, and most preferably, R3 is hydrogen, methyl, ethyl, methoxy, 2,2-difluoroethoxy or cyclopropyl.
Z is Z1, wherein Z1 is R4, or Z is Z2, wherein Z2 is -NR5R6.
In some embodiments of the invention, Z is Z1.
In some embodiments of the invention, Z is Z2.
R4 represents hydrogen, Ci-ealkyl, Ci-ehaloalkyl, cyanoCi-ealkyl, hydroxyCi-4alkyl, Ci-4alkoxyCi- 4alkyl, Ci-4haloalkoxyCi-4alkyl, Ci-2alkoxyCi-2alkoxyCi-4alkyl, C3-5alkenyloxyCi-4alkyl, C3-5alkynyloxyCi-
4alkyl, aminoCi ealkyl, N-Ci-4alkylaminoCi-4alkyl, N,N-diCi-4alkylaminoCi-4alkyl, Ci-4alkylcarbonylCi- 4alkyl, Ci-4alkoxycarbonylCi-4alkyl, Ci-4alkylcarbonyloxyCi-4alkyl, N-Ci-4alkylaminocarbonylCi-4alkyl, N,N-diCi-4alkylaminocarbonylCi-4alkyl, Ci-4alkylsulfanylCi-4alkyl, Ci-4alkylsulfonylCi-4alkyl, C-i- 4alkylsulfonylaminoCi-4alkyl, Ci-4alkylcarbonylaminoCi-4alkyl or Ci-4alkoxycarbonylaminoCi-4alkyl; R4 represents heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 4- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from cyano, halogen, hydroxy, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy and cyclopropyl, and
wherein when R4 comprises a heterocyclyl, this cycle may optionally contain 1 group selected from C(O) or S(0)2.
Preferably, R4 is hydrogen, cyano, Ci-4alkyl, Ci-4haloalkyl, cyanoCi-4alkyl, hydroxyCi-4alkyl, C-i- 2alkoxyCi-4alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-5alkenyloxyCi-2alkyl, C3- 5alkynyloxyCi-2alkyl, aminoCi-4alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, C-i- 2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyCi-2alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi-2alkyl, Ci-2alkylsulfanylCi-2alkyl, C-i- 2alkylsulfonylCi-2alkyl, Ci-2alkylsulfonylaminoCi-2alkyl, Ci-2alkylcarbonylaminoCi-2alkyl or C-i- 2alkoxycarbonylaminoCi-2alkyl. More preferably, R4 is hydrogen, Ci-4alkyl, Ci-4haloalkyl, cyanoCi-4alkyl, hydroxyCi-4alkyl or Ci-2alkoxyCi-4alkyl, and even more preferably, R4 is hydrogen, Ci-4alkyl or C-i- 2alkoxyCi-4alkyl. Most preferably, R4 is hydrogen, methyl, ethyl, iso-propyl, n-propyl or Ci-2alkoxyCi- salkyl (including -CH2OCH3, -CH(OCH3)CH3 and -C(CH3)20CH3).
Preferably, R4 is heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 5- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the cycloalkyl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
Z2 represents -NR5R6, wherein:
R5 represents hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, Ci-4alkoxy, C3-salkenyl, C3-salkynyl, C3- 4alkenyloxy, C3-4alkynyloxy, cyanoCi-3alkyl, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, C1- 2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2-4alkoxyC2-4alkyl, N-Ci-3alkylamino, N,N-diCi- 3alkylamino, aminoC2-4alkyl, N-Ci-4alkylaminoC2^alkyl, N,N-diCi-4alkylaminoC2-4alkyl, C1- 3alkylcarbonylCi-3alkyl, Ci-4alkoxycarbonylCi-3alkyl, Ci-3alkylcarbonyloxyC2-4alkyl, N-C1- 3alkylaminocarbonylCi-3alkyl, N,N-diCi-3alkylaminocarbonylCi-3alkyl, Ci-3alkylsulfonyl, C-i- 3alkylsulfonylC2-3alkyl or Ci-3alkylsulfonylaminoC2-3alkyl; or R5 represents C3-6cycloalkyl, C3- 6cycloalkylCi-2alkyl, phenyl, phenylCi-2alkyl, heteroaryl or heteroarylCi-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1 , 2, 3, or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylCi-2alkyl wherein the heterocyclyl moiety is a 4- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms or groups individually selected from N, NR7, O and S; wherein the cycloalkyl, phenyl, heteroaryl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl and cyclopropylmethyl, and wherein when R5 is cycloalkyl or heterocyclyl, these cycles may optionally contain 1 group selected from C(O) or S(0)2; and
R6 represents hydrogen, cyano, halogen, hydroxy, amino, methyl, ethyl, propyl, prop-2-enyl, prop-2-ynyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, difluoromethoxy, prop-2-enyloxy, prop-2-ynyloxy, N-methylamino, N,N-dimethylamino, methylcarbonyl, methoxycarbonyl, formylamino, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl or methoxycarbonylamino.
Preferably, R5 is hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3-4alkenyloxy, C3-4alkynyloxy, cyanoCi-2alkyl, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, C-i- 2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2-4alkoxyC2-4alkyl, N-Ci-2alkylamino, N,N-diCi- 2alkylamino, aminoC2-4alkyl, N-Ci-2alkylaminoC2^alkyl, N,N-diCi-2alkylaminoC2-4alkyl, C-i- 2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyC2-4alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi-2alkyl, Ci-2alkylsulfonyl, C-i- 2alkylsulfonylC2-3alkyl or Ci-2alkylsulfonylaminoC2-3alkyl, or R5 is C3-4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl. More preferably, R5 is hydrogen, Ci-4alkyl, cyanoCi-4alkyl, C-i- 4haloalkyl, hydroxyC2-4alkyl, C3-4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl. Even more preferably, R5 is hydrogen, Ci-4alkyl, Ci-4fluoroalkyl or C3-4cycloalkyl. Most preferably, R5 is methyl, ethyl, n-propyl, iso-propyl, 2,2,2-trifluoroethyl or cyclopropyl.
Preferably R6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl, and most preferably R6 is hydrogen.
R7 represents hydrogen, methyl, methoxy, formyl or acyl.
Preferably, the compound according to formula (I) is selected from a compound 1.1 to 1.15 listed in Table T1 (below).
Preferably, in a compound according to formula (I) of the invention:
A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups;
R1 and R2 are independently selected from hydrogen and methyl;
R3 is hydrogen, Ci-4alkyl, Ci-2fluoroalkyl, Ci-2alkoxy, Ci-2fluoroalkoxy or cyclopropyl; and Z is Z1 , and R4 is hydrogen, cyano, Ci-4alkyl, Ci-4haloalkyl, cyanoCi-4alkyl, hydroxyCi-4alkyl, C-i- 2alkoxyCi-4alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-salkenyloxyCi-2alkyl, C3-5alkynyloxyCi-2alkyl, aminoCi-4alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, Ci-2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyCi-2alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi-2alkyl, Ci-2alkylsulfanylCi-2alkyl, Ci-2alkylsulfonylCi-2alkyl, Ci-2alkylsulfonylaminoCi-2alkyl, Ci-2alkylcarbonylaminoCi-2alkyl, C-i- 2alkoxycarbonylaminoCi-2alkyl, or heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 5- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
More preferably,
A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups;
R1 and R2 are hydrogen;
R3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl; and
Z is Z1 , and R4 is hydrogen, Ci-4alkyl, Ci-4haloalkyl, cyanoCi-4alkyl, hydroxyCi-4alkyl, Ci-2alkoxyCi- 4alkyl, Ci-2haloalkoxyCi-2alkyl, Ci-2alkoxyCi-2alkoxyCi-2alkyl, C3-salkenyloxyCi-2alkyl, C3- 5alkynyloxyCi-2alkyl, aminoCi-4alkyl, N-Ci-2alkylaminoCi-2alkyl, N,N-diCi-2alkylaminoCi-2alkyl, C-i- 2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, Ci-2alkylcarbonyloxyCi-2alkyl, N-C-i- 2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi-2alkyl, Ci-2alkylsulfanylCi-2alkyl, Ci-2alkylsulfonylCi-2alkyl, Ci-2alkylsulfonylaminoCi-2alkyl, Ci-2alkylcarbonylaminoCi-2alkyl, C-i- 2alkoxycarbonylaminoCi-2alkyl, or heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 5- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
Even more preferably,
A is unsubstituted A-1 or unsubstituted A-4;
R1 and R2 are hydrogen;
R3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
R4 is is hydrogen, methyl, ethyl, iso-propyl, n-propyl or Ci-2alkoxyCi-3alkyl.
Preferably, in a compound according to formula (I) of the invention:
A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups;
R1 and R2 are independently selected from hydrogen and methyl;
R3 is hydrogen, Ci-4alkyl, Ci-2fluoroalkyl, Ci-2alkoxy, Ci-2fluoroalkoxy or cyclopropyl; and Z is Z2, wherein Z2 represents -NR5R6, wherein R5 is hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3-4alkenyloxy, C3-4alkynyloxy, cyanoCi-2alkyl, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, Ci-2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2- 4alkoxyC2-4alkyl, N-Ci-2alkylamino, N,N-diCi-2alkylamino, aminoC2-4alkyl, N-Ci-2alkylaminoC2- 4alkyl, N,N-diCi-2alkylaminoC2-4alkyl, Ci-2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, C-i- 2alkylcarbonyloxyC2-4alkyl, N-Ci-2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi- 2alkyl, Ci-2alkylsulfonyl, Ci-2alkylsulfonylC2-3alkyl, Ci-2alkylsulfonylaminoC2-3alkyl, or R5 is C3- 4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl; and R6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl.
More preferably,
A is A-1 or A-4 optionally substituted by 1 or 2 fluoro groups;
R1 and R2 are hydrogen;
R3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
Z is Z2, wherein Z2 represents -NR5R6, wherein R5 is hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, Ci-2alkoxy, C3-salkenyl, C3-salkynyl, C3-4alkenyloxy, C3-4alkynyloxy, cyanoCi-2alkyl, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, Ci-2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2- 4alkoxyC2-4alkyl, N-Ci-2alkylamino, N,N-diCi-2alkylamino, aminoC2-4alkyl, N-Ci-2alkylaminoC2- 4alkyl, N,N-diCi-2alkylaminoC2-4alkyl, Ci-2alkylcarbonylCi-2alkyl, Ci-2alkoxycarbonylCi-2alkyl, C-i- 2alkylcarbonyloxyC2-4alkyl, N-Ci-2alkylaminocarbonylCi-2alkyl, N,N-diCi-2alkylaminocarbonylCi- 2alkyl, Ci-2alkylsulfonyl, Ci-2alkylsulfonylC2-3alkyl, Ci-2alkylsulfonylaminoC2-3alkyl, or R5 is C3- 4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl; and
R6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl.
Even more preferably,
A is unsubstituted A-1 or unsubstituted A-4;
R1 and R2 are hydrogen;
R3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
Z is Z2, wherein Z2 represents -NR5R6, wherein R5 is hydrogen, Ci-4alkyl, cyanoCi-4alkyl, C-i- 4haloalkyl, hydroxyC2-4alkyl, or C3-4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
R6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl.
Still more preferably,
A is unsubstituted A-1 or unsubstituted A-4;
R1 and R2 are hydrogen;
R3 is hydrogen, methyl, ethyl, methoxy, 2, 2-difluoroethoxy or cyclopropyl;
Z is Z2, wherein Z2 represents -NR5R6, wherein R5 is hydrogen, Ci-4alkyl, cyanoCi-4alkyl, C-i- 4haloalkyl, hydroxyC2-4alkyl, C3-4cycloalkyl or C3-4cycloalkylCi-2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl; and
R6 is hydrogen.
Compounds of formula (I) feature a thiocarbonyl moiety (eg, thioamide or thiourea) and in vivo are believed to act as a procide to compounds of formula (II) featuring a carbonyl moiety (eg, amide or urea) under suitable conditions, (eg, metabolic processes or biosynthetic transformations).
Figure imgf000013_0001
The compounds of the present invention may be enantiomers of the compound of formula (I) as represented by a Formula (la) or a Formula (lb), wherein R1 and R2 are different substituents.
Figure imgf000013_0002
It is understood that when in aqueous media, the compounds of formula (I) according to the invention may be present in a reversible equilibrium with the corresponding covalently hydrated forms (eg, the compounds of formula (l-l) and formula (l-ll) as shown below, which may exist in tautomeric form as the compounds of formula (l-lb) and formula (l-l lb)) at the CF3-oxadiazole motif. This dynamic equilibrium may be important for the biological activity of the compounds of formula (I).
The designations of A (including A-1 , A-2, A-3, or A-4), R1 , R2, R3, Z (including Z1 , Z2), R4, R5, R6, and R7 with reference to the compounds of formula (I) of the present invention apply generally to the compounds of Formula (l-l) and Formula (l-ll), as well as to the specific disclosures of combinations of A (including A-1 , A-2, A-3, or A-4), R1 , R2, R3, Z , R4, R5, R6, and R7 as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or the compounds 1.1 to 1.15, according to the invention listed in Table T1 (below).
Figure imgf000014_0001
(l-lb) (l-llb)
Compounds of the present invention can be made as shown in the following schemes 1 to 16, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).
Compounds of formula (I), can be prepared from compounds of formula (II), via reactions with a suitable sulfur source [eg, elemental sulfur (Ss), Lawesson’s reagent, or P2S5], in an acceptable solvent (eg, toluene, CH2CI2, CHCI3, tetrahydrofuran, f-butylmethyl ether), at temperatures between 0°C to 100°C. For related examples, see Hermant, F. et al Organometallics, (2014), 33, 5643; Heyde, C. et al E. J. Org. Chem. (2000), 19, 3273. This reaction is shown in Scheme 1.
Figure imgf000014_0002
Scheme 1 Alternatively, compounds of formula (I), wherein Z represents -NR5R6, can be prepared from compounds of formula (III) via reactions with a suitable sulfur carbonyl reagent (eg, 1 ,3-dimethyl-l- nitrosothiourea, thiophosgene, thiourea, CS2, or thiocarbonyl-1 , 1 -diimidazole) in the presence of nucleophiles of formula (IV), in a suitable solvent (eg, ethyl acetate, acetone, CH2CI2, CHCI3, acetonitrile, or toluene), optionally with a water co-solvent, in the presence of a suitable base (eg, triethylamine, NaHCCh, Ca2CC>3) with heating at temperatures between 0°C and 65°C. For related examples, see WO 201 1/083999, Scheffer, U. et aU. Am. Chem. Soc. (2005), 727, 221 1 . Black, Shannon L. et aU. Med. Chem. (2003), 46, 5505. This reaction is shown in Scheme 2.
Figure imgf000015_0001
(IV) (IN) (I)
Scheme 2
Compounds of formula (V), wherein Za is hydrogen, -C(0)R4, -C(S)R4, -C(0)NR5R6, -C(S)NR5R6, can be prepared from compounds of formula (VI), wherein X is a OH, OS02Me, Cl, Br, or I, preferably Br or I, via reactions with compounds of formula (VII), optionally in the presence of a base (eg, triethylamine, A/,A/-diisopropylethylamine, K2CO3, NaHC03, or Na2C03), in a suitable solvent (eg, dimethylacetamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, or acetonitrile) at temperatures between 25°C and 1 10°C. In some cases, a better reaction performance may be gained by the use of a catalyst (eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4-dimethylaminopyridine) and optionally with microwaves irradiation. For related examples, see: WO 1995/9518122 and Jpn. Kokai Tokkyo Koho, (1993), 05286936; Miyawaki, K. et al Heterocycles (2001 ), 54, 887; WO 2003/028729; WO 2013/066839; and WO 2017/055473. This reaction is shown in Scheme 3.
Figure imgf000015_0002
Scheme 3
Alternatively, compounds of formula (I), can be obtained via coupling transformations with compounds of formula (VIII) and compounds of formula (III) in a suitable solvent (eg, dimethylformamide, dichloromethane or tetrahydrofuran), at temperatures of between 0°C and 100°C, and optionally in the presence of a base such as triethylamine. For examples, see WO 2004/046162. Compounds of formula (VIII) are commercially available. This reaction is shown in Scheme 4.
Figure imgf000016_0001
Scheme 4
Additionally, compounds of formula (I) can be prepared from compounds of formula (IX) via reactions with trifluoroacetic acid, trifluoroacetic ester (eg, trifluoroacetic methyl ester or trifluoroacetic ethyl ester), trifluoroacetic anhydride, or trifluoroacetyl halide (including trifluoroacetyl fluoride, trifluoroacetyl chloride, and trifluoroacetyl bromide), optionally in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, (eg, toluene, ethyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, or ethanol), at temperatures between 0°C and 75°C. For related examples, see WO 2003/028729, WO 2017/055473, and WO 2010/045251. This reaction is shown in Scheme 5.
Figure imgf000016_0002
(IX) (I)
Scheme 5
Compounds of formula (IX) can be prepared from compounds of formula (X) via reactions with a hydroxylamine hydrochloride salt or a hydroxylamine solution in water, in the presence of a base, such as triethylamine or potassium carbonate, in a suitable solvent, such as methanol or ethanol, at temperatures between 0°C and 80°C. In some cases, a better reaction performance may be gained from the use of a catalyst (eg, 8-hydroxyquinoline). For related examples, see Kitamura, S. et al Chem. Pharm. Bull. (2001 ), 49, 268, WO 2017/055473 and WO 2013/066838. This reaction is shown in Scheme 6.
Figure imgf000016_0003
(X) (IX)
Scheme 6 Compounds of formula (X) can be prepared from compounds of formula (XI), wherein Y is formyl, Cl, Br, or I, via metal-promoted reactions with a cyanide reagent, such as acetone cyanohydrin, dimethylmalononitrile, K4[Fe(CN)6], Zn(CN)2, NaCN, or CuCN, in a suitable solvent (eg, dimethylformamide or N-methylpyrrolidone) at elevated temperatures between 80°C and 120°C, and optionally in the presence of a metal catalyst (eg, Pd or Ni), an organomagnesium, or organolithium reagent. For related examples, see Reeves, J. T. et al J. Am. Chem. Soc. (2015), 137, 9481 ; Ushijima, S., Togo, H. Synlett, (2010), 1067; US 2007/0155739, WO 2017/055473, and WO 2009/022746. This reaction is shown in Scheme 7. Alternatively, compounds of formula (X) can be prepared from compounds of formula (XI), wherein
Y is NH2, via radical-nucleophilic aromatic substitution reactions using a nitrite source (eg, NaNCh or iso-amylnitrite), a suitable acid (eg, hydrochloric acid or HBF4), and a copper source (eg, CuCN) in an acceptable solvent, such as aqueous acetonitrile, at temperatures between 0°C to 100°C. For related examples, see Wen, Q. et a! Tet. Lett. (2014), 55, 1271. This reaction is shown in Scheme 7.
Figure imgf000017_0001
(XI) (X)
Scheme 7
Compounds of formula (XI), wherein Y is CN, NH2, Cl, Br, or I, can be prepared from compounds of formula (XII), via reactions with a suitable sulfur source [eg, elemental sulfur (Ss), Lawesson’s reagent, or P2S5], in an acceptable solvent (eg, CH2CI2, tetrahydrofuran, f-butylmethyl ether), at temperatures between 0°C to 100°C. For related examples, see Hermant, F. et al Organometallics, (2014), 33, 5643; Heyde, C. et al E. J. Org. Chem. (2000), 19, 3273.-This reaction is shown in Scheme 8.
Figure imgf000017_0002
(XII) (XI)
Scheme 8
Alternatively, compounds of formula (XI), wherein Y is NH2, F, Cl, Br, I, or CN, can be prepared from compounds of formula (XIII), wherein Z represents NR5R6, via reactions with a suitable sulfur carbonyl reagent (eg, 1 ,3-dimethyl-1-nitrosothiourea, thiophosgene, thiourea, CS2, or thiocarbonyl-1 , 1- diimidazole) in the presence of nucleophiles of formula (IV), in a suitable solvent (eg, ethyl acetate, acetone, CH2CI2, CHCI3, acetonitrile, or toluene), optionally with a water co-solvent and optionally in the presence of a base (eg, triethylamine, NaHCCh, Ca2CC>3), with heating at temperatures between 0°C and 65°C. For related examples, see WO 201 1/083999, Scheffer, U. et al J. Am. Chem. Soc. (2005), 127, 221 1 . Black, Shannon L. et al J. Med. Chem. (2003), 46, 5505. This reaction is shown in Scheme 9.
Figure imgf000018_0001
(IV) (xiii) (XI)
Scheme 9
Compounds of formula (XIV), wherein Y is CN, Cl, Br, or I, and Za is hydrogen, C(0)R4, C(S)R4, C(0)NR5R6, or C(S)NR5R6, can be prepared from compounds of formula (XV), wherein X is a OH, OS02Me, Cl, Br, or I, preferably Br or I, via reactions with suitable compounds of formula (VII), optionally in the presence of a base (eg, triethylamine, A/,A/-diisopropylethylamine, K2CO3, NaHC03, or Na2C03), in a suitable solvent (eg, dimethylacetamide, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, or acetonitrile) at temperatures between 25°C and 1 10°C. In some cases, a better reaction performance may be gained via catalyst use (eg, BU4NHSO4, B NBr, BU4NI, Nal, or 4- dimethylaminopyridine), optionally with microwaves irradiation. For related examples, see: WO 1995/9518122 and Jpn. Kokai Tokkyo Koho, (1993), 05286936; Miyawaki, K. et al Heterocycles (2001 ), 54, 887; WO 2003/028729; WO 2013/066839; and WO 2017/055473. This reaction is shown in Scheme 10.
Figure imgf000018_0002
(VII) (XV) (XIV)
Scheme 10
The compounds of formula (XI), wherein Y is formyl, CN, Cl, Br, or I, can be obtained via coupling transformations with compounds of formula (VIII) and compounds of formula (XIII), in a suitable solvent (eg, dimethylformamide, dichloromethane or tetrahydrofuran), at temperatures of between 0°C and 100°C, and optionally in the presence of a base, such as triethylamine. For examples, see WO 2004/046162. Compounds of formula (VIII) are commercially available. This reaction is shown in Scheme 1 1.
Figure imgf000019_0001
(VIII) (XIII) (XI)
Scheme 11
Compounds of formula (VI), wherein X is Cl or Br, can be prepared from compounds of formula (XVI), via reactions with a suitable halogen source (eg, N-bromosuccinimide (NBS) or N- chlorosuccinimide (NCS)) and a radical initiator (eg, (PhC02)2 or azobisisobutyronitrile (AIBN)) in a suitable solvent, such as tetrachloromethane, at temperatures between 55°C and 100°C, optionally in the presence of ultraviolet light. For related examples, see WO 2017/055473; Liu, S. et al Synthesis (2001), 14, 2078; and Kompella, A. et al Org. Proc. Res. Dev. (2012), 76, 1794, and WO 2017/055473. This reaction is shown in Scheme 12.
Figure imgf000019_0002
Scheme 12
Alternatively, compounds of formula (VI), wherein X is OH, OS02Me, Cl, Br, or I, preferably OH, can be prepared from compounds of formula (XVII) via reactions with trifluoroacetic acid, trifluoroacetic ester (including trifluoroacetic methyl ester, trifluoroacetic ethyl ester), trifluoroacetic anhydride, or trifluoroacetyl halide (including trifluoroacetyl fluoride, trifluoroacetyl chloride, and trifluoroacetyl bromide), optionally in the presence of a base (eg, pyridine or 4-dimethylaminopyridine) in a suitable solvent, (eg, toluene, ethyl acetate, tetrahydrofuran, 2-methyl tetrahydrofuran, or ethanol), at temperatures between 0°C and 75°C. For related examples, see WO 2003/028729, WO 2017/055473, and WO 2010/045251. This reaction is shown in Scheme 13.
Figure imgf000019_0003
Scheme 13
Compounds of formula (XVII), wherein X is OH, OS02Me, Cl, Br, or I, preferably OH, can be prepared from compounds of formula (XVIII) via reactions with a hydroxylamine hydrochloride salt or a hydroxylamine solution in water, optionally in the presence of a base, such as triethylamine or potassium carbonate, in a suitable solvent, such as methanol or ethanol, at temperatures between 0°C and 80°C. In some cases, a better reaction performance may be gained from the use of a catalyst (eg, 8- hydroxyquinoline). For related examples, see Kitamura, S. et al Chem. Pharm. Bull. (2001 ), 49, 268, WO 2017/055473 and WO 2013/066838. This reaction is shown in Scheme 14.
Figure imgf000020_0001
(xviii) (xvii)
Scheme 14
Compounds of formula (XVIII), wherein X is OH, OS02Me, Cl, Br, or I, are commercially available or can be prepared from compounds of formula (XIX), wherein Y is formyl, Cl, Br, or I, via metal- promoted reactions with a cyanide reagent, such as acetone cyanohydrin, dimethylmalononitrile, K4[Fe(CN)6], Zn(CN)2, NaCN, or CuCN, in a suitable solvent (eg, dimethylformamide or N- methylpyrrolidone) at elevated temperatures between 80°C and 120°C, and optionally in the presence of a metal catalyst (eg, Pd or Ni), an organomagnesium, or organolithium reagent. For related examples, see Reeves, J. T. et al J. Am. Chem. Soc. (2015), 137, 9481 ; Ushijima, S., Togo, H. Synlett, (2010), 1067; US 2007/0155739; WO 2017/055473; and WO 2009/022746. This reaction is shown in Scheme 15.
Alternatively, compounds of formula (XVIII), wherein X is OH, OS02Me, Cl, Br, or I, can be prepared from compounds of formula (XIX), wherein Y is NH2, via radical-nucleophilic aromatic substitution reactions with a suitable nitrite source (eg, NaNC or iso-amylnitrite), an acid (eg, hydrochloric acid or HBF4), and a copper source (eg, CuCN) in an acceptable solvent system, such as acetonitrile and water, at temperatures between 0°C to 100°C. For related examples, see Wen, Q. et al Tet. Lett. (2014), 55, 1271. This reaction is shown in Scheme 15.
Figure imgf000020_0002
(XIX) (XVIII)
Scheme 15
Alternatively, compounds of formula (XXI), wherein X is Cl, Br, I, or OSCteMe and Y is formyl, NH2, Cl, Br, I, CN, or 5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl, are either commercially available or can be prepared from compounds of formula (XX), via reactions with a suitable acid source (eg, hydrochloric acid, hydrobromic acid, or hydroiodic acid) or a suitable halogen source (eg, tetrabromomethane, tetrachloromethane, or iodine) in the presence of triphenylphosphine, or with methanesulfonyl chloride (CISC Me), in a suitable solvent (eg, dichloromethane), optionally in the presence of a base (eg, triethylamine), at temperatures between 0°C and 100°C. For related examples, see Liu, H. et al Bioorg. Med. Chem. (2008), 16, 10013, WO 2014/020350 and Kompella, A. et al Bioorg. Med. Chem. Lett. (2001), 1, 3161 . Compounds of formula (XX) either commercially available or can be prepared using known methods. This reaction is shown in Scheme 16.
Figure imgf000021_0001
(XX) (X IX)
Scheme 16
As already indicated, surprisingly, it has now been found that the compounds of formula (I) of the present invention 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 the 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 can 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.
The present invention further relates to a method for controlling or preventing infestation of plants or plant propagation material and/or harvested food crops susceptible to microbial attack by treating plants or plant propagation material and/or harvested food crops wherein an effective amount a compound of formula (I) is applied to the plants, to parts thereof or the locus thereof.
It is also possible to use compounds of formula (I) as a fungicide. The term“fungicide” as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term“fungicidally effective amount” where used means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all dev/ation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
It may also be 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 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 compounds of formula (I) 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 of formula (I) 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 fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses. These fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses are for example:
Absidia corymbifera, Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terms, Aureobasidium spp. including A. pullulans, Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. inclusing B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C. arachidicola, Cercosporidium personatum, Cladosporium spp, Claviceps purpurea, Coccidioides immitis, Cochliobolus spp, Colletotrichum spp. including C. musae, Cryptococcus neoformans, Diaporthe spp, Didymella spp, Drechslera spp, Elsinoe spp,Epidermophyton spp, Erwinia amylovora, Erysiphe spp. including E. cichoracearum, Eutypa lata, Fusarium spp. including F. culmorum, F. graminearum, F. langsethiae, F. moniliforme, F. oxysporum, F. proliferatum, F. subglutinans, F. solani, Gaeumannomyces graminis, Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulate, Guignardia bidwellii, Gym nosporangium juniperi- virginianae, Helminthosporium spp, Hemileia spp, Histoplasma spp. including H. capsulatum, Laetisaria fuciformis, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum spp, Monilinia spp, Mucor spp, Mycosphaerella spp. including M. graminicola, M. pomi, Oncobasidium theobromaeon, Ophiostoma piceae, Paracoccidioides spp, Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp, Phomopsis viticola, Phytophthora spp. including P. infestans, Plasmopara spp. including P. halstedii, P. viticola, Pleospora spp., Podosphaera spp. including P. leucotricha, Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P. triticina, Pyrenopeziza spp, Pyrenophora spp, Pyricularia spp. including P. oryzae, Pythium spp. including P. ultimum, Ramularia spp, Rhizoctonia spp, Rhizomucor pusillus, Rhizopus arrhizus, Rhynchosporium spp, Scedosporium spp. including S. apiospermum and S. prolificans, Schizothyrium pomi, Sclerotinia spp, Sclerotium spp, Septoria spp, including S. nodorum, S. tritici, Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix spp, Stagonospora nodorum, Stemphylium spp,. Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia spp, Trichoderma spp. including T. harzianum, T. pseudokoningii, T. viride, Trichophyton spp, Typhula spp, Uncinula necator, Urocystis spp, Ustilago spp, Venturia spp. including V. inaequalis, Verticillium spp, and Xanthomonas spp.
The compounds of formula (I) may be used for example on turf, ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers, as well as for tree injection, pest management and the like.
Within the scope of present invention, target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St. Augustine grass and Zoysia grass; herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
The term "useful plants" is to be understood as also including useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol- pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
The term "useful plants" is to be understood as also including 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.
Examples of such plants are: YieldGard® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CrylllB(bl ) toxin); YieldGard Plus® (maize variety that expresses a CrylA(b) and a Cryll IB(b1 ) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CrylF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c) toxin); Bollgard I® (cotton variety that expresses a CrylA(c) toxin); Bollgard II® (cotton variety that expresses a CrylA(c) and a CryllA(b) toxin); VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potato variety that expresses a CrylllA toxin); NatureGard® Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt1 1 corn borer (CB) trait), Agrisure® RW (corn rootworm trait) and Protecta®.
The term "crops" is to be understood as including also crop 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.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as d-endotoxins, e.g. CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
Further, in the context of the present invention there are to be understood by d-endotoxins, for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701 ). Truncated toxins, for example a truncated CrylAb, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO93/07278, W095/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651. The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a CrylAc toxin); Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a CrylAb toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt1 1 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1. Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ( Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylAb toxin. Bt1 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer ( Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylAb toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1 160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1 F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 * MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
The compounds of formula (I) may be used in controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi (such as Phakopsora pachyrhizi) on soy bean plants.
In particular, transgenic soybean plants expressing toxins, for example insecticidal proteins such as delta-endotoxins, e.g. CrylAc (Cry1 Ac Bt protein). Accordingly, this may include transgenic soybean plants comprising event MON87701 (see U.S. Patent No. 8,049,071 and related applications and patents, as well as WO 2014/170327 A1 (eg, see paragraph [008] reference to Intacta RR2 PRO™ soybean)), event MON87751 (US. Patent Application Publication No. 2014/0373191 ) or event DAS- 81419 (U.S. Patent No. 8632978 and related applications and patents).
Other transgenic soybean plants may comprise event SYHT0H2 - HPPD tolerance (U.S. Patent Application Publication No. 2014/0201860 and related applications and patents), event MON89788 - glyphosate tolerance (U.S. Pat. No. 7,632,985 and related applications and patents), event MON87708
- dicamba tolerance (U.S. Patent Application Publication No. US 201 1/0067134 and related applications and patents), event DP-356043-5 - glyphosate and ALS tolerance (U.S. Patent Application Publication No. US 2010/0184079 and related applications and patents), event A2704-12 - glufosinate tolerance (U.S. Patent Application Publication No. US 2008/0320616 and related applications and patents), event DP-305423-1 - ALS tolerance (U.S. Patent Application Publication No. US 2008/0312082 and related applications and patents), event A5547-127 - glufosinate tolerance (U.S. Patent Application Publication No. US 2008/0196127 and related applications and patents), event DAS-40278-9 - tolerance to 2,4- dichlorophenoxyacetic acid and aryloxyphenoxypropionate (see WO 201 1/022469, WO 201 1/022470, WO 201 1/022471 , and related applications and patents), event 127 - ALS tolerance (WO 2010/080829 and related applications and patents), event GTS 40-3-2 - glyphosate tolerance, event DAS-68416-4- 2,4-dichlorophenoxyacetic acid and glufosinate tolerance, event FG72 - glyphosate and isoxaflutole tolerance, event BPS-CV127-9 - ALS tolerance and GU262 - glufosinate tolerance or event SYHT04R
- HPPD tolerance. The compounds of formula (I) may be used in controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi (such as Phakopsora pachyrhizi) on soy bean plants. In particular, there are known in the scientific literature certain Elite soybean plant varieties where R-gene stacks, conferring a degree of immunity or resistance to specific Phakopsora pachyrhizi, have been been introgressed in the plant genome, see for example:“Fighting Asian Soybean Rust”, Langenbach C, et al, Front Plant Science 7(797) 2016).
An elite plant is any plant from an elite line, such that an elite plant is a representative plant from an elite variety. Non-limiting examples of elite soybean varieties that are commercially available to farmers or soybean breeders include: AG00802, A0868, AG0902, A1923, AG2403, A2824, A3704, A4324, A5404, AG5903, AG6202 AG0934; AG1435; AG2031 ; AG2035; AG2433; AG2733; AG2933; AG3334; AG3832; AG4135; AG4632; AG4934; AG5831 ; AG6534; and AG7231 (Asgrow Seeds, Des Moines, Iowa, USA); BPR0144RR, BPR 4077NRR and BPR 4390NRR (Bio Plant Research, Camp Point, III., USA); DKB17-51 and DKB37-51 (DeKalb Genetics, DeKalb, III., USA); DP 4546 RR, and DP 7870 RR (Delta & Pine Land Company, Lubbock, Tex., USA); JG 03R501 , JG 32R606C ADD and JG 55R503C (JGL Inc., Greencastle, Ind., USA); NKS 13-K2 (NK Division of Syngenta Seeds, Golden Valley, Minnesota, USA); 90M01 , 91 M30, 92M33, 93M1 1 , 94M30, 95M30, 97B52, P008T22R2; P16T17R2; P22T69R; P25T51 R; P34T07R2; P35T58R; P39T67R; P47T36R; P46T21 R; and P56T03R2 (Pioneer Hi-Bred International, Johnston, Iowa, USA); SG4771 NRR and SG5161 NRR/STS (Soygenetics, LLC, Lafayette, Ind., USA); S00-K5, S1 1-L2, S28-Y2, S43-B1 , S53-A1 , S76-L9, S78-G6, S0009-M2; S007-Y4; S04-D3; S14-A6; S20-T6; S21-M7; S26-P3; S28-N6; S30-V6; S35-C3; S36-Y6; S39-C4; S47-K5; S48-D9; S52-Y2; S58-Z4; S67-R6; S73-S8; and S78-G6 (Syngenta Seeds, Henderson, Ky., USA); Richer (Northstar Seed Ltd. Alberta, CA); 14RD62 (Stine Seed Co. la., USA); or Armor 4744 (Armor Seed, LLC, Ar., USA).
Thus, in a further preferred embodiment, the compounds of formula (I) are used to control Phakopsora pachyrhizi, (including fungicidally-resistant strains thereof, as outlined below) on Elite soybean plant varieties where R-gene stacks, conferring a degree of immunity or resistance to specific Phakopsora pachyrhizi, have been been introgressed in the plant genome. Numerous benefits may be expected to ensue from said use, e.g. improved biological activity, an advantageous or broader spectrum of activity (inc. sensitive and resistant strains of Phakopsora pachyrhizi), an increased safety profile, improved crop tolerance, synergistic interactions or potentiating properties, improved onset of action or a longer lasting residual activity, a reduction in the number of applications and/or a reduction in the application rate of the compounds and compositions required for effective control of the phytopathogen ( Phakopsora pachyrhizi), thereby enabling beneficial resistance-management practices, reduced environmental impact and reduced operator exposure.
Fungicidal-resistant strains of Phakopsora pachyrhizi have been reported in the scientific literature, with strains resistant to one or more fungicides from at least each of the following fungicidal mode of action classes being observed: sterol demethylation-inhibitors (DMI), quinone-outside-inhibitors (Qol) and succinate dehydrogenase inhibitors (SDHI). See for example:“Sensitivity of Phakopsora pachyrhizi towards quinone-outside-inhibitors and demethylation-inhibitors, and corresponding resistance mechanisms.” Schmitz HK et al, Pest Manag Sci (2014) 70: 378-388;“First detection of a SDH variant with reduced SDHI sensitivity in Phakopsora pachyrhizi’ Simoes K et al, J Plant Dis Prot (2018) 125: 21-2;“Competitive fitness of Phakopsora pachyrhizi isolates with mutations in the CYP51 and CYTB genes.” Klosowski AC et al, Phytopathology (2016) 106: 1278-1284;“Detection of the F129L mutation in the cytochrome b gene in Phakopsora pachyrhizi.” Klosowski AC et al, Pest Manag Sci (2016) 72: 121 1-1215.
Thus, in a preferred embodiment, the compounds of formula (I) may be used to control Phakopsora pachyrhizi which are resistant to one or more fungicides from any of the following fungicidal MoA classes: sterol demethylation-inhibitors (DMI), quinone-outside-inhibitors (Qol) and succinate dehydrogenase inhibitors (SDHI).
The term“locus” as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
The term“plants” refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
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 can 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 can 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.
Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller’s earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.
Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which treatment is required. Typical carriers for granular formulations include sand, fuller’s earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound. Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins.
Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.
Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically 1 to 50 microns in diameter. The enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound. Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores. Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.
Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurised sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.
Suitable agricultural adjuvants and carriers that are useful in formulating the compositions of the invention in the formulation types described above are well known to those skilled in the art. Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1 ,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide, 1 ,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1 , 1 , 1-trichloroethane, 2-heptanone, alpha pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, m ethoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerine and N-methyl-2-pyrrolidinone. Water is generally the carrier of choice for the dilution of concentrates.
Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller’s earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin.
A broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. These agents, when used, normally comprise from 0.1 % to 15% by weight of the formulation. They can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub. 18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono and dialkyl phosphate esters.
Other adjuvants commonly utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti-foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.
In addition, further, other biocidally active ingredients or compositions may be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention. When applied simultaneously, these further active ingredients may be formulated together with the compositions of the invention or mixed in, for example, the spray tank. These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.
Pesticidal agents are referred to herein using their common name are known, for example, from "The Pesticide Manual", 15th Ed., British Crop Protection Council 2009.
In addition, the compositions of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer). SAR inducers are known and described in, for example, United States Patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.
The compounds of formula (I) are normally used in the form of agrochemical 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 defined herein, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
The invention therefore 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 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 active ingredient may, in some cases, result in unexpected synergistic activities.
Examples of suitable additional active ingredients include the following: acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorous fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
Examples of suitable additional active ingredients also include the following: 3-difluoromethyl-
1 -methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano- naphthalen-5-yl)-amide, 3-difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid methoxy-[1-methyl-2- (2,4,6-trichlorophenyl)-ethyl]-amide, 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-Ch loro-2, 4- dimethyl-pyridin-3-yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy- pyridin-3-yl)-(2,3,4-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, (E)-N-methyl-2- [2- (2, 5- dimethylphenoxymethyl) phenyl]-2-methoxy-iminoacetamide, 4-bromo-2-cyano-N, N-dimethyl-6- trifluoromethylbenzimidazole-1-sulphonamide, a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-y- butyrolactone, 4-chloro-2-cyano-N,N - dimethyl-5-p-tolylimidazole-1 -sulfonamide, N-allyl-4, 5,-dimethyl-
2-trimethylsilylthiophene-3-carboxamide, N- (l-cyano-1 , 2-d i m ethyl p ropy I )-2- (2, 4-dichlorophenoxy) propionamide, N- (2-methoxy-5-pyridyl)-cyclopropane carboxamide, (.+-.)-cis-1-(4-chlorophenyl)-2-(1 H- 1 ,2,4-triazol-1-yl)-cycloheptanol, 2-(1-ferf-butyl)-1-(2-chlorophenyl)-3-(1 ,2,4-triazol-1-yl)-propan-2-ol, 2',6'-dibromo-2-methyl-4-trifluoromethoxy-4'-trifluoromethyl-1 ,3-thiazole- 5-carboxanilide, 1-imidazolyl- 1-(4'-chlorophenoxy)-3,3-dimethylbutan-2-one, methyl (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4- yloxy]phenyl]3-methoxyacrylate, methyl (E)-2-[2-[6-(2-thioamidophenoxy)pyrimidin-4-yloxy]phenyl]-3- methoxyacrylate, methyl (E)-2-[2-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2,6-difluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2- [3-(pyrimidin-2-yloxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(5-methylpyrimidin-2- yloxy)-phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(phenyl-sulphonyloxy)phenoxy]phenyl-3- methoxyacrylate, methyl (E)-2-[2-[3-(4-nitrophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2- [2-phenoxyphenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dimethyl-benzoyl)pyrrol-1-yl]-3- methoxyacrylate, methyl (E)-2-[2-(3-methoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2[2-(2- phenylethen-1-yl)-phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dichlorophenoxy)pyridin-3-yl]-3- methoxyacrylate, methyl (E)-2-(2-(3-(1 , 1 ,2,2-tetrafluoroethoxy)phenoxy)phenyl)-3-methoxyacrylate, methyl (E)-2-(2-[3-(alpha-hydroxybenzyl)phenoxy]phenyl)-3-methoxyacrylate, methyl (E)-2-(2-(4- phenoxypyridin-2-yloxy)phenyl)-3-methoxyacrylate, methyl (E)-2-[2-(3-n-propyloxy-phenoxy)phenyl]3- methoxyacrylate, methyl (E)-2-[2-(3-isopropyloxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2- [3-(2-fluorophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3-ethoxyphenoxy)phenyl]-3- methoxyacrylate, methyl (E)-2-[2-(4-ferf-butyl-pyridin-2-yloxy)phenyl]-3-methoxyacrylate, methyl (E)-2- [2-[3-(3-cyanophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[(3-methyl-pyridin-2- yloxymethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-methyl-phenoxy)pyrimidin-4- yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(5-bromo-pyridin-2-yloxymethyl)phenyl]-3- methoxyacrylate, methyl (E)-2-[2-(3-(3-iodopyridin-2-yloxy)phenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-chloropyridin-3-yloxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E),(E)-2-[2- (5,6-dimethylpyrazin-2-ylmethyloximinomethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-{2-[6-(6- methylpyridin-2-yloxy)pyrimidin-4-yloxy]phenyl}-3-methoxy-acrylate, methyl (E),(E)-2-{ 2-(3- methoxyphenyl)methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-(6-(2- azidophenoxy)-pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[6-phenylpyrimidin-4- yl)-methyloximinomethyl]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[(4-chlorophenyl)- methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-[6-(2-n-propylphenoxy)-1 ,3,5-triazin- 4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[(3-nitrophenyl)methyloximinomethyl]phenyl}-3- methoxyacrylate, 3-chloro-7-(2-aza-2,7,7-trimethyl-oct-3-en-5-ine), 2,6-dichloro-N-(4- trifluoromethylbenzyl)-benzamide, 3-iodo-2-propinyl alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3- bromo-2,3-diiodo-2-propenyl ethylcarbamate, 2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2-propinyl n-butylcarbamate, 3-iodo-2-propinyl n-hexylcarbamate, 3-iodo-2-propinyl cyclohexyl-carbamate, 3-iodo-2-propinyl phenylcarbamate; phenol derivatives, such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol, 5-hydroxy- 2(5H)-furanone; 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylenedithiazolinone, 4,5-dichloro-(3H)-1 ,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1 ,3,5-thiadiazine-2-thione, N-(2-p- chlorobenzoylethyl)-hexaminium chloride, acibenzolar, acypetacs, alanycarb, albendazole, aldimorph, allicin, allyl alcohol, ametoctradin, amisulbrom, amobam, ampropylfos, anilazine, asomate, aureofungin, azaconazole, azafendin, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiazole, benzalkonium chloride, benzamacril, benzamorf, benzohydroxamic acid, benzovindiflupyr, berberine, bethoxazin, biloxazol, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, boscalid, bromothalonil, bromuconazole, bupirimate, buthiobate, butylamine calcium polysulfide, captafol, captan, carbamorph, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chitosan, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlorozolinate, chlozolinate, climbazole, clotrimazole, clozylacon, copper containing compounds such as copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinolate, copper silicate, copper sulphate, copper tallate, copper zinc chromate and Bordeaux mixture, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, debacarb, decafentin, dehydroacetic acid, di-2-pyridyl disulphide 1 , 1 '-dioxide, dichlofluanid, diclomezine, dichlone, dicloran, dichlorophen, dichlozoline, diclobutrazol, diclocymet, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetachlone, dimetconazole, dimethomorph, dimethirimol, diniconazole, diniconazole-M, dinobuton, dinocap, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, dithioether, dodecyl dimethyl ammonium chloride, dodemorph, dodicin, dodine, doguadine, drazoxolon, edifenphos, enestroburin, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethilicin, ethyl (Z)-N-benzyl-N ([methyl (methyl-thioethylideneamino- oxycarbonyl) amino] thio)4J-alaninate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpicoxamid, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, flupicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutanil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexylthiofos, hydrargaphen, hydroxyisoxazole, hymexazole, imazalil, imazalil sulphate, imibenconazole, iminoctadine, iminoctadine triacetate, inezin, iodocarb, ipconazole, ipfentrifluconazole, iprobenfos, iprodione, iprovalicarb, isopropanylbutyl carbamate, isoprothiolane, isopyrazam, isotianil, isovaledione, izopamfos, kasugamycin, kresoxim-methyl, LY186054, LY21 1795, LY248908, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mefenoxam, mefentrifluconazole, mepanipyrim, mepronil, mercuric chloride, mercurous chloride, meptyldinocap, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl iodide, methyl isothiocyanate, metiram, metiram-zinc, metominostrobin, metrafenone, metsulfovax, milneb, moroxydine, myclobutanil, myclozolin, nabam, natamycin, neoasozin, nickel dimethyldithiocarbamate, nitrostyrene, nitrothal-iso-propyl, nuarimol, octhilinone, ofurace, organomercury compounds, orysastrobin, osthol, oxadixyl, oxasulfuron, oxathiapiprolin, oxine-copper, oxolinic acid, oxpoconazole, oxycarboxin, parinol, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenamacril, phenazin oxide, phosdiphen, phosetyl-AI, phosphorus acids, phthalide, picoxystrobin, piperalin, polycarbamate, polyoxin D, polyoxrim, polyram, probenazole, prochloraz, procymidone, propamidine, propamocarb, propiconazole, propineb, propionic acid, proquinazid, prothiocarb, prothioconazole, pydiflumetofen, pyracarbolid, pyraclostrobin, pyrametrostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinacetol, quinazamid, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenzazole, santonin, sedaxane, silthiofam, simeconazole, sipconazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, sultropen, tebuconazole, tebfloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, 2-(thiocyanomethylthio) benzothiazole, thiophanate-methyl, thioquinox, thiram, tiadinil, timibenconazole, tioxymid, tolclofos- methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumazole, triforine, triflumizole, triticonazole, uniconazole, urbacide, validamycin, valifenalate, vapam, vinclozolin, zarilamid, zineb, ziram, and zoxamide.
The compounds of the invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP- 444964 and EP-594291 . Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO- 9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
The compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE-19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO 96/15121 and also with anthelmintic active cyclic depsipeptides such as those described in WO 96/1 1945, WO 93/19053, WO 93/25543, EP 0 626 375, EP 0 382 173, WO 94/19334, EP 0 382 173, and EP 0 503 538.
The compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
The compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers WO 95/19363 or WO 04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that the compounds of the invention may be used in combination with include but are not restricted to the following:
Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, methacriphos, methamidophos, methidathion, methyl-parathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate, phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, pirimiphos-methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon, vamidothion.
Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801 , isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717. Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E)-(1 R)-cis-2,2-dimethyl- 3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, a- cypermethrin, beta-cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t-fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.
Arthropod growth regulators: a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-1 18, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196, neem guard, nidinorterfuran, nitenpyram, SD-35651 , WL-108477, pirydaryl, propargite, protrifen bute, pymethrozine, pyridaben, pyrimidifen, NC-1 1 1 1 , R-195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601 , silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.
Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
Bactericides: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel, triclabendazole.
The following mixtures of the compounds of formula (I) with active ingredients are preferred. The abbreviation “TX” means one compound selected from the group consisting of the compounds as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
an acaricide selected from the group of substances consisting of 1 ,1-bis(4-chlorophenyl)-2- ethoxyethanol (IUPAC name) (910) + TX, 2,4-dichlorophenyl benzenesulfonate (lUPAC/Chemical Abstracts name) (1059) + TX, 2-fluoro-A/-methyl-A/-1-naphthylacetamide (IUPAC name) (1295) + TX, 4- chlorophenyl phenyl sulfone (IUPAC name) (981 ) + TX, abamectin (1 ) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha- cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet [CCN] + TX, amidothioate (872) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, aramite (881 ) + TX, arsenous oxide (882) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azobenzene (IUPAC name) (888) + TX, azocyclotin (46) + TX, azothoate (889) + TX, benomyl (62) + TX, benoxafos (alternative name) [CCN] + TX, benzoximate (71 ) + TX, benzyl benzoate (IUPAC name) [CCN] + TX, bifenazate (74) + TX, bifenthrin (76) + TX, binapacryl (907) + TX, brofenvalerate (alternative name) + TX, bromocyclen (918) + TX, bromophos (920) + TX, bromophos-ethyl (921 ) + TX, bromopropylate (94) + TX, buprofezin (99) + TX, butocarboxim (103) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, calcium polysulfide (IUPAC name) (1 1 1 ) + TX, camphechlor (941 ) + TX, carbanolate (943) + TX, carbaryl (1 15) + TX, carbofuran (1 18) + TX, carbophenothion (947) + TX, CGA 50’439 (development code) (125) + TX, chinomethionat (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, chlorfenethol (968) + TX, chlorfenson (970) + TX, chlorfensulfide (971 ) + TX, chlorfenvinphos (131 ) + TX, chlorobenzilate (975) + TX, chloromebuform (977) + TX, chloromethiuron (978) + TX, chloropropylate (983) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, clofentezine (158) + TX, closantel (alternative name) [CCN] + TX, coumaphos (174) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, cufraneb (1013) + TX, cyanthoate (1020) + TX, cyflumetofen (CAS Reg. No.: 400882-07-7) + TX, cyhalothrin (196) + TX, cyhexatin (199) + TX, cypermethrin (201 ) + TX, DCPM (1032) + TX, DDT (219) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton- O (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulfon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diazinon (227) + TX, dichlofluanid (230) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicofol (242) + TX, dicrotophos (243) + TX, dienochlor (1071 ) + TX, dimefox (1081 ) + TX, dimethoate (262) + TX, dinactin (alternative name) (653) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinobuton (269) + TX, dinocap (270) + TX, dinocap-4 [CCN] + TX, dinocap-6 [CCN] + TX, dinocton (1090) + TX, dino- penton (1092) + TX, dinosulfon (1097) + TX, dinoterbon (1098) + TX, dioxathion (1 102) + TX, diphenyl sulfone (IUPAC name) (1 103) + TX, disulfiram (alternative name) [CCN] + TX, disulfoton (278) + TX, DNOC (282) + TX, dofenapyn (1 1 13) + TX, doramectin (alternative name) [CCN] + TX, endosulfan (294) + TX, endothion (1 121 ) + TX, EPN (297) + TX, eprinomectin (alternative name) [CCN] + TX, ethion (309) + TX, ethoate-methyl (1 134) + TX, etoxazole (320) + TX, etrimfos (1 142) + TX, fenazaflor (1 147) + TX, fenazaquin (328) + TX, fenbutatin oxide (330) + TX, fenothiocarb (337) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fenpyroximate (345) + TX, fenson (1 157) + TX, fentrifanil (1 161 ) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrypyrim (360) + TX, fluazuron (1 166) + TX, flubenzimine (1 167) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1 169) + TX, flufenoxuron (370) + TX, flumethrin (372) + TX, fluorbenside (1 174) + TX, fluvalinate (1 184) + TX, FMC 1 137 (development code) (1 185) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1 192) + TX, formparanate (1 193) + TX, gamma-HCH (430) + TX, glyodin (1205) + TX, halfenprox (424) + TX, heptenophos (432) + TX, hexadecyl cyclopropanecarboxylate (lUPAC/Chemical Abstracts name) (1216) + TX, hexythiazox (441 ) + TX, iodomethane (IUPAC name) (542) + TX, isocarbophos (alternative name) (473) + TX, isopropyl 0-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephosfolan (1261 ) + TX, mesulfen (alternative name) [CCN] + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methidathion (529) + TX, methiocarb (530) + TX, methomyl (531 ) + TX, methyl bromide (537) + TX, metolcarb (550) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, monocrotophos (561 ) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naled (567) + TX, NC-184 (compound code) + TX, NC-512 (compound code) + TX, nifluridide (1309) + TX, nikkomycins (alternative name) [CCN] + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, parathion (615) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, phenkapton (1330) + TX, phenthoate (631 ) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosphamidon (639) + TX, phoxim (642) + TX, pirimiphos-methyl (652) + TX, polychloroterpenes (traditional name) (1347) + TX, polynactins (alternative name) (653) + TX, proclonol (1350) + TX, profenofos (662) + TX, promacyl (1354) + TX, propargite (671 ) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothoate (1362) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridaphenthion (701 ) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, quinalphos (71 1 ) + TX, quintiofos (1381 ) + TX, R-1492 (development code) (1382) + TX, RA-17 (development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX, spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI-121 (development code) (1404) + TX, sulfiram (alternative name) [CCN] + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulfur (754) + TX, SZI-121 (development code) (757) + TX, tau-fluvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, terbam (alternative name) + TX, tetrachlorvinphos (777) + TX, tetradifon (786) + TX, tetranactin (alternative name) (653) + TX, tetrasul (1425) + TX, thiafenox (alternative name) + TX, thiocarboxime (1431 ) + TX, thiofanox (800) + TX, thiometon (801 ) + TX, thioquinox (1436) + TX, thuringiensin (alternative name) [CCN] + TX, triamiphos (1441 ) + TX, triarathene (1443) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trifenofos (1455) + TX, trinactin (alternative name) (653) + TX, vamidothion (847) + TX, vaniliprole [CCN] and YI-5302 (compound code) + TX,
an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, an anthelmintic selected from the group of substances consisting of abamectin (1 ) + TX, crufomate (101 1 ) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291 ) + TX, emamectin benzoate (291 ) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,
an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX, a bactericide selected from the group of substances consisting of 1 -hydroxy- 1 /-/-pyridine-2- thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1 105) + TX, dodicin (1 1 12) + TX, fenaminosulf (1 144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (61 1 ) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter ( alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51 ) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51 ) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51 ) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51 ) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51 ) + TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51 ) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperia carnea (alternative name) (151 ) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191 ) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431 ) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491 ) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741 ) + TX, Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848) + TX, bacillus subtilis var. amyloliquefaciens Strain FZB24 (available from Novozymes Biologicals Inc., 5400 Corporate Circle, Salem, VA 24153, U.S.A. and known under the trade name Taegro®) + TX,
a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN] + TX,
an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541 ) + TX, (E,Z)-tetradeca-4, 10-dien-1-yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec- 1 1-enal (IUPAC name) (436) + TX, (Z)-hexadec-l 1-en-1-yl acetate (IUPAC name) (437) + TX, (Z)- hexadec-13-en-1 1 -yn-1 -yl acetate (IUPAC name) (438) + TX, (Z)-icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782) + TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783) + TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283) + TX, (9Z, 1 1 E)-tetradeca-9, 1 1-dien-1-yl acetate (IUPAC name) (780) + TX, (9Z, 12E)-tetradeca-9, 12-dien-1-yl acetate (IUPAC name) (781 ) + TX, 14-methyloctadec-1-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544) + TX, alpha- multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-1-yl acetate (IUPAC name) (286) + TX, dodec-9-en-1-yl acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1 -yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, gossyplure (alternative name) (420) + TX, grandlure (421 ) + TX, grandlure I (alternative name) (421 ) + TX, grandlure II (alternative name) (421 ) + TX, grandlure III (alternative name) (421 ) + TX, grandlure IV (alternative name) (421 ) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481 ) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2, 13-dien-1-yl acetate (IUPAC name) (588) + TX, octadeca-3, 13-dien- 1-yl acetate (IUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetrad ec- 1 1-en- 1-yl acetate (IUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure Bi (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN] + TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591 ) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1 137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (lUPAC/Chemical Abstracts name) (1058) + TX, 1 , 1-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), + TX, 1 ,2-dichloropropane (lUPAC/Chemical Abstracts name) (1062) + TX, 1 ,2- dichloropropane with 1 ,3-dichloropropene (IUPAC name) (1063) + TX, 1-bromo-2-chloroethane (lUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate (IUPAC name) (1451 ) + TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate (IUPAC name) (1066) + TX, 2-(1 ,3-dithiolan-2-yl)phenyl dimethylcarbamate (IUPAC/ Chemical Abstracts name) (1 109) + TX, 2-(2-butoxyethoxy)ethyl thiocyanate (lUPAC/Chemical Abstracts name) (935) + TX, 2-(4,5- dimethyl-1 ,3-dioxolan-2-yl)phenyl methylcarbamate (IUPAC/ Chemical Abstracts name) (1084) + TX, 2- (4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986) + TX, 2-chlorovinyl diethyl phosphate (IUPAC name) (984) + TX, 2-imidazolidone (IUPAC name) (1225) + TX, 2-isovalerylindan-1 ,3-dione (IUPAC name) (1246) + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate (IUPAC name) (1284) + TX, 2- thiocyanatoethyl laurate (IUPAC name) (1433) + TX, 3-bromo-1-chloroprop-1-ene (IUPAC name) (917) + TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate (IUPAC name) (1283) + TX, 4-methyl(prop-2- ynyl)amino-3,5-xylyl methylcarbamate (IUPAC name) (1285) + TX, 5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate (IUPAC name) (1085) + TX, abamectin (1 ) + TX, acephate (2) + TX, acetamiprid (4) + TX, acethion (alternative name) [CCN] + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, acrylonitrile (IUPAC name) (861 ) + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, aldrin (864) + TX, allethrin (17) + TX, allosamidin (alternative name) [CCN] + TX, allyxycarb (866) + TX, alpha- cypermethrin (202) + TX, alpha-ecdysone (alternative name) [CCN] + TX, aluminium phosphide (640) + TX, amidithion (870) + TX, amidothioate (872) + TX, aminocarb (873) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, anabasine (877) + TX, athidathion (883) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azadirachtin (alternative name) (41 ) + TX, azamethiphos (42) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azothoate (889) + TX, Bacillus thuringiensis delta endotoxins (alternative name) (52) + TX, barium hexafluorosilicate (alternative name) [CCN] + TX, barium polysulfide (lUPAC/Chemical Abstracts name) (892) + TX, barthrin [CCN] + TX, Bayer 22/190 (development code) (893) + TX, Bayer 22408 (development code) (894) + TX, bendiocarb (58) + TX, benfuracarb (60) + TX, bensultap (66) + TX, beta-cyfluthrin (194) + TX, beta-cypermethrin (203) + TX, bifenthrin (76) + TX, bioallethrin (78) + TX, bioallethrin S- cyclopentenyl isomer (alternative name) (79) + TX, bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX, bis(2-chloroethyl) ether (IUPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate (alternative name) + TX, bromfenvinfos (914) + TX, bromocyclen (918) + TX, bromo-DDT (alternative name) [CCN] + TX, bromophos (920) + TX, bromophos-ethyl (921 ) + TX, bufencarb (924) + TX, buprofezin (99) + TX, butacarb (926) + TX, butathiofos (927) + TX, butocarboxim (103) + TX, butonate (932) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, calcium arsenate [CCN] + TX, calcium cyanide (444) + TX, calcium polysulfide (IUPAC name) (1 1 1 ) + TX, camphechlor (941 ) + TX, carbanolate (943) + TX, carbaryl (1 15) + TX, carbofuran (1 18) + TX, carbon disulfide (lUPAC/Chemical Abstracts name) (945) + TX, carbon tetrachloride (IUPAC name) (946) + TX, carbophenothion (947) + TX, carbosulfan (1 19) + TX, cartap (123) + TX, cartap hydrochloride (123) + TX, cevadine (alternative name) (725) + TX, chlorbicyclen (960) + TX, chlordane (128) + TX, chlordecone (963) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorethoxyfos (129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131 ) + TX, chlorfluazuron (132) + TX, chlormephos (136) + TX, chloroform [CCN] + TX, chloropicrin (141 ) + TX, chlorphoxim (989) + TX, chlorprazophos (990) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, chromafenozide (150) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, cis-resmethrin (alternative name) + TX, cismethrin (80) + TX, clocythrin (alternative name) + TX, cloethocarb (999) + TX, closantel (alternative name) [CCN] + TX, clothianidin (165) + TX, copper acetoarsenite [CCN] + TX, copper arsenate [CCN] + TX, copper oleate [CCN] + TX, coumaphos (174) + TX, coumithoate (1006) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, crufomate (101 1 ) + TX, cryolite (alternative name) (177) + TX, CS 708 (development code) (1012) + TX, cyanofenphos (1019) + TX, cyanophos (184) + TX, cyanthoate (1020) + TX, cyclethrin [CCN] + TX, cycloprothrin (188) + TX, cyfluthrin (193) + TX, cyhalothrin (196) + TX, cypermethrin (201 ) + TX, cyphenothrin (206) + TX, cyromazine (209) + TX, cythioate (alternative name) [CCN] + TX, d-limonene (alternative name) [CCN] + TX, cf-tetramethrin (alternative name) (788) + TX, DAEP (1031 ) + TX, dazomet (216) + TX, DDT (219) + TX, decarbofuran (1034) + TX, deltamethrin (223) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diamidafos (1044) + TX, diazinon (227) + TX, dicapthon (1050) + TX, dichlofenthion (1051 ) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicresyl (alternative name) [CCN] + TX, dicrotophos (243) + TX, dicyclanil (244) + TX, dieldrin (1070) + TX, diethyl 5- methylpyrazol-3-yl phosphate (IUPAC name) (1076) + TX, diflubenzuron (250) + TX, dilor (alternative name) [CCN] + TX, dimefluthrin [CCN] + TX, dimefox (1081 ) + TX, dimetan (1085) + TX, dimethoate (262) + TX, dimethrin (1083) + TX, dimethylvinphos (265) + TX, dimetilan (1086) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinoprop (1093) + TX, dinosam (1094) + TX, dinoseb (1095) + TX, dinotefuran (271 ) + TX, diofenolan (1099) + TX, dioxabenzofos (1 100) + TX, dioxacarb (1 101 ) + TX, dioxathion (1 102) + TX, disulfoton (278) + TX, dithicrofos (1 108) + TX, DNOC (282) + TX, doramectin (alternative name) [CCN] + TX, DSP (1 1 15) + TX, ecdysterone (alternative name) [CCN] + TX, El 1642 (development code) (1 1 18) + TX, emamectin (291 ) + TX, emamectin benzoate (291 ) + TX, EMPC (1 120) + TX, empenthrin (292) + TX, endosulfan (294) + TX, endothion (1 121 ) + TX, endrin (1 122) + TX, EPBP (1 123) + TX, EPN (297) + TX, epofenonane (1 124) + TX, eprinomectin (alternative name) [CCN] + TX, esfenvalerate (302) + TX, etaphos (alternative name) [CCN] + TX, ethiofencarb (308) + TX, ethion (309) + TX, ethiprole (310) + TX, ethoate-m ethyl (1 134) + TX, ethoprophos (312) + TX, ethyl formate (IUPAC name) [CCN] + TX, ethyl-DDD (alternative name) (1056) + TX, ethylene dibromide (316) + TX, ethylene dichloride (chemical name) (1 136) + TX, ethylene oxide [CCN] + TX, etofenprox (319) + TX, etrimfos (1 142) + TX, EXD (1 143) + TX, famphur (323) + TX, fenamiphos (326) + TX, fenazaflor (1 147) + TX, fenchlorphos (1 148) + TX, fenethacarb (1 149) + TX, fenfluthrin (1 150) + TX, fenitrothion (335) + TX, fenobucarb (336) + TX, fenoxacrim (1 153) + TX, fenoxycarb (340) + TX, fenpirithrin (1 155) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fensulfothion (1 158) + TX, fenthion (346) + TX, fenthion-ethyl [CCN] + TX, fenvalerate (349) + TX, fipronil (354) + TX, flonicamid (358) + TX, flubendiamide (CAS. Reg. No.: 272451-65-7) + TX, flucofuron (1 168) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1 169) + TX, flufenerim [CCN] + TX, flufenoxuron (370) + TX, flufenprox (1 171 ) + TX, flumethrin (372) + TX, fluvalinate (1 184) + TX, FMC 1 137 (development code) (1 185) + TX, fonofos (1 191 ) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1 192) + TX, formparanate (1 193) + TX, fosmethilan (1 194) + TX, fospirate (1 195) + TX, fosthiazate (408) + TX, fosthietan (1 196) + TX, furathiocarb (412) + TX, furethrin (1200) + TX, gamma-cyhalothrin (197) + TX, gamma-HCH (430) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, GY-81 (development code) (423) + TX, halfenprox (424) + TX, halofenozide (425) + TX, HCH (430) + TX, HEOD (1070) + TX, heptachlor (121 1 ) + TX, heptenophos (432) + TX, heterophos [CCN] + TX, hexaflumuron (439) + TX, HHDN (864) + TX, hydramethylnon (443) + TX, hydrogen cyanide (444) + TX, hydroprene (445) + TX, hyquincarb (1223) + TX, imidacloprid (458) + TX, imiprothrin (460) + TX, indoxacarb (465) + TX, iodomethane (IUPAC name) (542) + TX, IPSP (1229) + TX, isazofos (1231 ) + TX, isobenzan (1232) + TX, isocarbophos (alternative name) (473) + TX, isodrin (1235) + TX, isofenphos (1236) + TX, isolane (1237) + TX, isoprocarb (472) + TX, isopropyl 0-(methoxy- aminothiophosphoryl)salicylate (IUPAC name) (473) + TX, isoprothiolane (474) + TX, isothioate (1244) + TX, isoxathion (480) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, juvenile hormone I (alternative name) [CCN] + TX, juvenile hormone II (alternative name) [CCN] + TX, juvenile hormone III (alternative name) [CCN] + TX, kelevan (1249) + TX, kinoprene (484) + TX, lambda-cyhalothrin (198) + TX, lead arsenate [CCN] + TX, lepimectin (CCN) + TX, leptophos (1250) + TX, lindane (430) + TX, lirimfos (1251 ) + TX, lufenuron (490) + TX, lythidathion (1253) + TX, m-cumenyl methylcarbamate (IUPAC name) (1014) + TX, magnesium phosphide (IUPAC name) (640) + TX, malathion (492) + TX, malonoben (1254) + TX, mazidox (1255) + TX, mecarbam (502) + TX, mecarphon (1258) + TX, menazon (1260) + TX, mephosfolan (1261 ) + TX, mercurous chloride (513) + TX, mesulfenfos (1263) + TX, metaflumizone (CCN) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methanesulfonyl fluoride (lUPAC/Chemical Abstracts name) (1268) + TX, methidathion (529) + TX, methiocarb (530) + TX, methocrotophos (1273) + TX, methomyl (531 ) + TX, methoprene (532) + TX, methoquin-butyl (1276) + TX, methothrin (alternative name) (533) + TX, methoxychlor (534) + TX, methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofluthrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561 ) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + TX, naled (567) + TX, naphthalene (lUPAC/Chemical Abstracts name) (1303) + TX, NC-170 (development code) (1306) + TX, NC-184 (compound code) + TX, nicotine (578) + TX, nicotine sulfate (578) + TX, nifluridide (1309) + TX, nitenpyram (579) + TX, nithiazine (131 1 ) + TX, nitrilacarb (1313) + TX, nitrilacarb 1 :1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, nornicotine (traditional name) (1319) + TX, novaluron (585) + TX, noviflumuron (586) + TX, 0-5-dichloro-4- iodophenyl O-ethyl ethylphosphonothioate (IUPAC name) (1057) + TX, 0,0-diethyl 0-4-methyl-2-oxo- 2/-/-chromen-7-yl phosphorothioate (IUPAC name) (1074) + TX, 0,0-diethyl 0-6-methyl-2- propylpyrimidin-4-yl phosphorothioate (IUPAC name) (1075) + TX, O,O,O',O'-tetrapropyl dithiopyrophosphate (IUPAC name) (1424) + TX, oleic acid (IUPAC name) (593) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydemeton-methyl (609) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, para-dichlorobenzene [CCN] + TX, parathion (615) + TX, parathion-methyl (616) + TX, penfluron (alternative name) [CCN] + TX, pentachlorophenol (623) + TX, pentachlorophenyl laurate (IUPAC name) (623) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, PH 60-38 (development code) (1328) + TX, phenkapton (1330) + TX, phenothrin (630) + TX, phenthoate (631 ) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosnichlor (1339) + TX, phosphamidon (639) + TX, phosphine (IUPAC name) (640) + TX, phoxim (642) + TX, phoxim-methyl (1340) + TX, pirimetaphos (1344) + TX, pirimicarb (651 ) + TX, pirimiphos-ethyl (1345) + TX, pirimiphos-methyl (652) + TX, polychlorodicyclopentadiene isomers (IUPAC name) (1346) + TX, polychloroterpenes (traditional name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, prallethrin (655) + TX, precocene I (alternative name) [CCN] + TX, precocene II (alternative name) [CCN] + TX, precocene III (alternative name) [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [CCN] + TX, promacyl (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothiofos (686) + TX, prothoate (1362) + TX, protrifenbute [CCN] + TX, pymetrozine (688) + TX, pyraclofos (689) + TX, pyrazophos (693) + TX, pyresmethrin (1367) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridaphenthion (701 ) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, pyriproxyfen (708) + TX, quassia (alternative name) [CCN] + TX, quinalphos (71 1 ) + TX, quinalphos-methyl (1376) + TX, quinothion (1380) + TX, quintiofos (1381 ) + TX, R-1492 (development code) (1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX, ryania (alternative name) (1387) + TX, ryanodine (traditional name) (1387) + TX, sabadilla (alternative name) (725) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, SI-0205 (compound code) + TX, SI-0404 (compound code) + TX, SI-0405 (compound code) + TX, silafluofen (728) + TX, SN 72129 (development code) (1397) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoride (lUPAC/Chemical Abstracts name) (1399) + TX, sodium hexafluorosilicate (1400) + TX, sodium pentachlorophenoxide (623) + TX, sodium selenate (IUPAC name) (1401 ) + TX, sodium thiocyanate [CCN] + TX, sophamide (1402) + TX, spinosad (737) + TX, spiromesifen (739) + TX, spirotetrmat (CCN) + TX, sulcofuron (746) + TX, sulcofuron-sodium (746) + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulfuryl fluoride (756) + TX, sulprofos (1408) + TX, tar oils (alternative name) (758) + TX, tau-fluvalinate (398) + TX, tazimcarb (1412) + TX, TDE (1414) + TX, tebufenozide (762) + TX, tebufenpyrad (763) + TX, tebupirimfos (764) + TX, teflubenzuron (768) + TX, tefluthrin (769) + TX, temephos (770) + TX, TEPP (1417) + TX, terallethrin (1418) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachloroethane [CCN] + TX, tetrachlorvinphos (777) + TX, tetramethrin (787) + TX, theta-cypermethrin (204) + TX, thiacloprid (791 ) + TX, thiafenox (alternative name) + TX, thiamethoxam (792) + TX, thicrofos (1428) + TX, thiocarboxime (1431 ) + TX, thiocyclam (798) + TX, thiocyclam hydrogen oxalate (798) + TX, thiodicarb (799) + TX, thiofanox (800) + TX, thiometon (801 ) + TX, thionazin (1434) + TX, thiosultap (803) + TX, thiosultap-sodium (803) + TX, thuringiensin (alternative name) [CCN] + TX, tolfenpyrad (809) + TX, tralomethrin (812) + TX, transfluthrin (813) + TX, transpermethrin (1440) + TX, triamiphos (1441 ) + TX, triazamate (818) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trichlormetaphos-3 (alternative name) [CCN] + TX, trichloronat (1452) + TX, trifenofos (1455) + TX, triflumuron (835) + TX, trimethacarb (840) + TX, triprene (1459) + TX, vamidothion (847) + TX, vaniliprole [CCN] + TX, veratridine (alternative name) (725) + TX, veratrine (alternative name) (725) + TX, XMC (853) + TX, xylylcarb (854) + TX, YI-5302 (compound code) + TX, zeta-cypermethrin (205) + TX, zetamethrin (alternative name) + TX, zinc phosphide (640) + TX, zolaprofos (1469) and ZXI 8901 (development code) (858) + TX, cyantraniliprole [736994-63-19 + TX, chlorantraniliprole [500008-45-7] + TX, cyenopyrafen [560121-52-0] + TX, cyflumetofen [400882-07-7] + TX, pyrifluquinazon [337458-27-2] + TX, spinetoram [187166-40-1 + 187166-15-0] + TX, spirotetramat [203313-25-1] + TX, sulfoxaflor [946578-00-3] + TX, flufiprole [704886-18-0] + TX, meperfluthrin [915288-13-0] + TX, tetramethylfluthrin [84937-88-2] + TX, triflumezopyrim (disclosed in WO 2012/0921 15) + TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprole [394730-71-3] + TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, 1 ,2-dibromo-3-chloropropane (lUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2- dichloropropane (IUPAC/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3- dichloropropene (IUPAC name) (1063) + TX, 1 ,3-dichloropropene (233) + TX, 3,4- dichlorotetrahydrothiophene 1 , 1-dioxide (lUPAC/Chemical Abstracts name) (1065) + TX, 3-(4- chlorophenyl)-5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1 ,3,5-thiadiazinan-3- ylacetic acid (IUPAC name) (1286) + TX, 6-isopentenylaminopurine (alternative name) (210) + TX, abamectin (1 ) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (1 18) + TX, carbon disulfide (945) + TX, carbosulfan (1 19) + TX, chloropicrin (141 ) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051 ) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291 ) + TX, emamectin benzoate (291 ) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion (1 158) + TX, fosthiazate (408) + TX, fosthietan (1 196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231 ) + TX, ivermectin (alternative name) [CCN] + TX, kinetin (alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam- sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (IUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) and zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891 ) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91 ) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301 ) + TX, flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1 183) + TX, flupropadine hydrochloride (1 183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341 ) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371 ) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851 ) and zinc phosphide (640) + TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171 ) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
and biologically active compounds selected from the group consisting of ametoctradin [865318- 97-4] + TX, amisulbrom [348635-87-0] + TX, azaconazole [60207-31-0] + TX, benzovindiflupyr [1072957-71-1] + TX, bitertanol [70585-36-3] + TX, bixafen [581809-46-3] + TX, bromuconazole [1 16255-48-2] + TX, coumoxystrobin [850881-70-8] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [1 19446-68-3] + TX, diniconazole [83657-24-3] + TX, enoxastrobin [238410-1 1-2] + TX, epoxiconazole [106325-08-0] + TX, fenbuconazole [1 14369-43-6] + TX, fenpyrazamine [473798-59-3] + TX, fluquinconazole [136426-54-5] + TX, flusilazole [85509-19-9] + TX, flutriafol [76674-21-0] + TX, fluxapyroxad [907204-31-3] + TX, fluopyram [658066-35-4] + TX, fenaminstrobin [366815-39-6] + TX, isofetamid [875915-78-9] + TX, hexaconazole [79983-71-4] + TX, imazalil [35554-44-0] + TX, imiben- conazole [86598-92-7] + TX, ipconazole [125225-28-7] + TX, ipfentrifluconazole [1417782-08-1 ] + TX, isotianil [224049-04-1] + TX, mandestrobin [173662-97-0] (can be prepared according to the procedures described in WO 2010/093059) + TX, mefentrifluconazole [1417782-03-6] + TX, metconazole [1251 16- 23-6] + TX, myclobutanil [88671-89-0] + TX, paclobutrazol [76738-62-0] + TX, pefurazoate [101903-30- 4] + TX, penflufen [494793-67-8] + TX, penconazole [66246-88-6] + TX, prothioconazole [178928-70-6] + TX, pyrifenox [88283-41-4] + TX, prochloraz [67747-09-5] + TX, propiconazole [60207-90-1] + TX, simeconazole [149508-90-7] + TX, tebuconazole [107534-96-3] + TX, tetraconazole [1 12281-77-3] + TX, triadimefon [43121-43-3] + TX, triadimenol [55219-65-3] + TX, triflumizole [99387-89-0] + TX, triticonazole [131983-72-7] + TX, ancymidol [12771-68-5] + TX, fenarimol [60168-88-9] + TX, nuarimol [63284-71-9] + TX, bupirimate [41483-43-6] + TX, dimethirimol [5221-53-4] + TX, ethirimol [23947-60- 6] + TX, dodemorph [1593-77-7] + TX, fenpropidin [67306-00-7] + TX, fenpropimorph [67564-91-4] + TX, spiroxamine [1 18134-30-8] + TX, tridemorph [81412-43-3] + TX, cyprodinil [121552-61-2] + TX, mepanipyrim [1 10235-47-7] + TX, pyrimethanil [531 12-28-0] + TX, fenpiclonil [74738-17-3] + TX, fludioxonil [131341-86-1] + TX, fluindapyr [1383809-87-7] + TX, benalaxyl [71626-1 1-4] + TX, furalaxyl [57646-30-7] + TX, metalaxyl [57837-19-1] + TX, R-metalaxyl [70630-17-0] + TX, ofurace [58810-48-3] + TX, oxadixyl [77732-09-3] + TX, benomyl [17804-35-2] + TX, carbendazim [10605-21-7] + TX, debacarb [62732-91-6] + TX, fuberidazole [3878-19-1] + TX, thiabendazole [148-79-8] + TX, chlozolinate [84332-86-5] + TX, dichlozoline [24201-58-9] + TX, iprodione [36734-19-7] + TX, myclozoline [54864-61-8] + TX, procymidone [32809-16-8] + TX, vinclozoline [50471-44-8] + TX, boscalid [188425-85-6] + TX, carboxin [5234-68-4] + TX, fenfuram [24691-80-3] + TX, flutolanil [66332- 96-5] + TX, flutianil [958647-10-4] + TX, mepronil [55814-41-0] + TX, oxycarboxin [5259-88-1] + TX, penthiopyrad [183675-82-3] + TX, thifluzamide [130000-40-7] + TX, guazatine [108173-90-6] + TX, dodine [2439-10-3] [1 12-65-2] (free base) + TX, iminoctadine [13516-27-3] + TX, azoxystrobin [131860- 33-8] + TX, dimoxystrobin [149961-52-4] + TX, enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1 , 93} + TX, fluoxastrobin [361377-29-9] + TX, kresoxim-methyl [143390-89-0] + TX, metominostrobin [133408-50-1] + TX, trifloxystrobin [141517-21-7] + TX, orysastrobin [248593-16-0] + TX, picoxystrobin [1 17428-22-5] + TX, pyraclostrobin [175013-18-0] + TX, pyraoxystrobin [862588-1 1-2] + TX, ferbam [14484-64-1] + TX, mancozeb [8018-01-7] + TX, maneb [12427-38-2] + TX, metiram [9006-42-2] + TX, propineb [12071-83-9] + TX, thiram [137-26-8] + TX, zineb [12122-67-7] + TX, ziram [137-30-4] + TX, captafol [2425-06-1] + TX, captan [133-06-2] + TX, dichlofluanid [1085-98-9] + TX, fluoroimide [41205-
21-4] + TX, folpet [133-07-3 ] + TX, tolylfluanid [731-27-1] + TX, bordeaux mixture [801 1-63-0] + TX, copperhydroxid [20427-59-2] + TX, copperoxychlorid [1332-40-7] + TX, coppersulfat [7758-98-7] + TX, copperoxid [1317-39-1] + TX, mancopper [53988-93-5] + TX, oxine-copper [10380-28-6] + TX, dinocap [131-72-6] + TX, nitrothal-isopropyl [10552-74-6] + TX, edifenphos [17109-49-8] + TX, iprobenphos [26087-47-8] + TX, isoprothiolane [50512-35-1] + TX, phosdiphen [36519-00-3] + TX, pyrazophos [13457-18-6] + TX, tolclofos-m ethyl [57018-04-9] + TX, acibenzolar-S-methyl [135158-54-2] + TX, anilazine [101-05-3] + TX, benthiavalicarb [413615-35-7] + TX, blasticidin-S [2079-00-7] + TX, chinomethionat [2439-01-2] + TX, chloroneb [2675-77-6] + TX, chlorothalonil [1897-45-6] + TX, cyflufenamid [180409-60-3] + TX, cymoxanil [57966-95-7] + TX, dichlone [1 17-80-6] + TX, diclocymet [139920-32-4] + TX, diclomezine [62865-36-5] + TX, dicloran [99-30-9] + TX, diethofencarb [87130-20- 9] + TX, dimethomorph [1 10488-70-5] + TX, SYP-LI90 (Flumorph) [21 1867-47-9] + TX, dithianon [3347-
22-6] + TX, ethaboxam [162650-77-3] + TX, etridiazole [2593-15-9] + TX, famoxadone [131807-57-3] + TX, fenamidone [161326-34-7] + TX, fenoxanil [1 15852-48-7] + TX, fentin [668-34-8] + TX, ferimzone [89269-64-7] + TX, fluazinam [79622-59-6] + TX, fluopicolide [2391 10-15-7] + TX, flusulfamide [106917- 52-6] + TX, fenhexamid [126833-17-8] + TX, fosetyl-aluminium [39148-24-8] + TX, hymexazol [10004- 44-1] + TX, iprovalicarb [140923-17-7] + TX, IKF-916 (Cyazofamid) [1201 16-88-3] + TX, kasugamycin [6980-18-3] + TX, methasulfocarb [66952-49-6] + TX, metrafenone [220899-03-6] + TX, pencycuron [66063-05-6] + TX, phthalide [27355-22-2] + TX, picarbutrazox [500207-04-5] + TX, polyoxins [1 1 1 13- 80-7] + TX, probenazole [27605-76-1] + TX, propamocarb [25606-41-1] + TX, proquinazid [189278-12- 4] + TX, pydiflumetofen [1228284-64-7] + TX, pyrametostrobin [915410-70-7] + TX, pyroquilon [57369- 32-1] + TX, pyriofenone [688046-61-9] + TX, pyribencarb [799247-52-2] + TX, pyrisoxazole [847749- 37-5] + TX, quinoxyfen [124495-18-7] + TX, quintozene [82-68-8] + TX, sulfur [7704-34-9] + TX, Timorex Gold™ (plant extract containing tea tree oil from the Stockton Group) + TX, tebufloquin [376645-78-2] + TX, tiadinil [223580-51-6] + TX, triazoxide [72459-58-6] + TX, tolprocarb [91 1499-62-2] + TX, triclopyricarb [902760-40-1] + TX, tricyclazole [41814-78-2] + TX, triforine [26644-46-2] + TX, validamycin [37248-47-8] + TX, valifenalate [283159-90-0] + TX, zoxamide (RH7281 ) [156052-68-5] + TX, mandipropamid [374726-62-2] + TX, isopyrazam [881685-58-1] + TX, phenamacril + TX, sedaxane [874967-67-6] + TX, trinexapac-ethyl [95266-40-3] + TX, 3-difluoromethyl-1 -methyl-1 H-pyrazole-4- carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide (dislosed in WO 2007/048556) + TX, 3-difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro- biphenyl-2-yl)-amide (disclosed in WO 2006/087343) + TX, [(3S,4R,4aR,6S,6aS, 12R, 12aS, 12bS)-3- [(cyclopropylcarbonyl)oxy]- 1 ,3,4,4a,5,6,6a, 12, 12a, 12b-decahydro-6, 12-dihydroxy-4,6a,12b-trinnethyl- 1 1-oxo-9-(3-pyridinyl)-2/-/, 1 1 /-/naphtho[2, 1-b]pyrano[3,4-e]pyran-4-yl]methyl-cyclopropanecarboxylate [915972-17-7] + TX and 1 ,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2- trifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1 H-pyrazole-4-carboxannide [926914-55-8] + TX, or a biologically active compound selected from the group consisting of N-[(5-chloro-2-isopropyl- phenyl)methyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-pyrazole-4-carboxamide (can be prepared according to the procedures described in WO 2010/130767) + TX, 2,6-Dimethyl-1 H,5H- [1 ,4]dithiino[2,3-c:5,6-c']dipyrrole-1 ,3,5,7(2H,6H)-tetrone (can be prepared according to the procedures described in WO 201 1/138281 ) + TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1 ,4]dithiino[1 ,2-c]isothiazole-3- carbonitrile + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3- amine (can be prepared according to the procedures described in WO 2012/031061 ) + TX, 3- (difluoromethyl)-N-(7-fluoro-1 , 1 ,3-trimethyl-indan-4-yl)-1-methyl-pyrazole-4-carboxamide (can be prepared according to the procedures described in WO 2012/084812) + TX, CAS 850881-30-0 + TX, 3- (3,4-dichloro-1 ,2-thiazol-5-ylmethoxy)-1 ,2-benzothiazole 1 , 1-dioxide (can be prepared according to the procedures described in WO 2007/129454) + TX, 2-[2-[(2,5-dimethylphenoxy)methyl]phenyl]-2- methoxy-N-methyl-acetamide + TX, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone (can be prepared according to the procedures described in WO 2005/070917) + TX, 2-[2-fluoro-6-[(8- fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol (can be prepared according to the procedures described in WO 201 1/081 174) + TX, 2-[2-[(7,8-difluoro-2-methyl-3-quinolyl)oxy]-6-fluoro- phenyl]propan-2-ol (can be prepared according to the procedures described in WO 201 1/081 174) + TX, oxathiapiprolin + TX [1003318-67-9], tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl- methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, N-[2-(3,4-difluorophenyl)phenyl]-3- (trifluoromethyl)pyrazine-2-carboxamide (can be prepared according to the procedures described in WO 2007/ 072999) + TX, 3-(difluoromethyl)-1-methyl-N-[(3R)-1 , 1 ,3-trimethylindan-4-yl]pyrazole-4- carboxamide (can be prepared according to the procedures described in WO 2014/013842) + TX, 2,2,2- trifluoroethyl N-[2-methyl-1-[[(4-methylbenzoyl)amino]methyl]propyl]carbamate + TX, (2RS)-2-[4-(4- chlorophenoxy)-a,a,a-trifluoro-o-tolyl]-1-(1 H-1 ,2,4-triazol-1-yl)propan-2-ol + TX, (2RS)-2-[4-(4- chlorophenoxy)-a,a,a-trifluoro-o-tolyl]-3-methyl-1-(1 H-1 ,2,4-triazol-1-yl)butan-2-ol + TX, 2- (difluoromethyl)-N-[(3R)-3-ethyl-1 , 1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 2- (difluoromethyl)-N-[3-ethyl-1 , 1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-dimethyl-4- phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl- phenyl]-N-ethyl-N-methyl-formamidine (can be prepared according to the procedures described in WO 2007/031513) + TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]- 4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl] methanesulfonate (can be prepared according to the procedures described in WO 2012/025557) + TX, but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl- methylene]amino]oxymethyl]-2-pyridyl]carbamate (can be prepared according to the procedures described in WO 2010/000841 ) + TX, 2-[[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl]- 4H-1 ,2,4-triazole-3-thione (can be prepared according to the procedures described in WO 2010/146031 ) + TX, methyl N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate + TX, 3- chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine (can be prepared according to the procedures described in WO 2005/121 104) + TX, 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-1-(1 ,2,4- triazol-1-yl)propan-2-ol (can be prepared according to the procedures described in WO 2013/024082) + TX, 3-chloro-4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine (can be prepared according to the procedures described in WO 2012/020774) + TX, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine- 3-carbonitrile (can be prepared according to the procedures described in WO 2012/020774) + TX, (R)- 3-(difluoromethyl)-1-methyl-N-[1 , 1 ,3-trimethylindan-4-yl]pyrazole-4-carboxamide (can be prepared according to the procedures described in WO 201 1/162397 ) + TX, 3-(difluoromethyl)-N-(7-fluoro-1 , 1 ,3- trimethyl-indan-4-yl)-1-methyl-pyrazole-4-carboxamide (can be prepared according to the procedures described in WO 2012/084812) + TX, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl- phenyl]-4-methyl-tetrazol-5-one (can be prepared according to the procedures described in WO 2013/162072) + TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1- yl)phenoxy]methyl]phenyl]tetrazol-5-one (can be prepared according to the procedures described in WO 2014/051 165) + TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyinnino-N, 3-dimethyl- pent-3-enamide + TX, (4-phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate + TX, N-(5- chloro-2-isopropylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methylpyrazole-4-carboxamide [1255734-28-1] (can be prepared according to the procedures described in WO 2010/130767) + TX, 3- (difluoromethyl)-N-[(R)-2,3-dihydro-1 , 1 ,3-trimethyl-1 H-inden-4-yl]-1-methylpyrazole-4-carboxamide [1352994-67-2] + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4- (4,5-dichloro-thiazol-2-yloxy)-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, N'-(2,5- dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4-(4,5-dichloro-thiazol-2-yloxy)- 2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX,
Figure imgf000050_0001
(fenpicoxamid [517875-34-2] (as described in WO
2003/035617)) + TX, (1 S)-2,2-bis(4-fluorophenyl)-1-methylethyl N-{[3-(acetyloxy)-4-methoxy-2- pyridyl]carbonyl}-L-alaninate [1961312-55-9] (as described in WO 2016/122802) + TX, 2- (difluoromethyl)-N-(l ,1 ,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-(3- ethyl-1 , 1-dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-(1 ,1-dimethyl-3- propyl-indan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-(3-isobutyl-1 , 1-dimethyl-indan-4- yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-[(3R)-1 , 1 ,3-trimethylindan-4-yl]pyridine-3- carboxamide + TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1 ,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, and 2-(difluoromethyl)-N-[(3R)-1 , 1-dimethyl-3-propyl-indan-4-yl]pyridine-3-carboxamide + TX, wherein each of these carboxamide compounds can be prepared according to the procedures described in WO 2014/095675 and/or WO 2016/139189.
The references in brackets behind the active ingredients, e.g. [3878-19-1] refer to the Chemical Abstracts Registry number. The above described mixing partners are known. Where the active ingredients are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. TomLin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular compound; for example, the compound "abamectin" is described under entry number (1 ). Where "[CCN]" is added hereinabove to the particular compound, the compound in question is included in the "Compendium of Pesticide Common Names", which is accessible on the internet [A. Wood; Compendium of Pesticide Common Names, Copyright © 1995-2004]; for example, the compound "acetoprole" is described under the internet address http://www.alanwood.net/pesticides/acetoprole.html.
Most of the active ingredients described above are referred to hereinabove by a so-called "common name", the relevant "ISO common name" or another "common name" being used in individual cases. If the designation is not a "common name", the nature of the designation used instead is given in round brackets for the particular compound; in that case, the IUPAC name, the lUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "develoment code" is used or, if neither one of those designations nor a "common name" is used, an "alternative name" is employed.“CAS Reg. No” means the Chemical Abstracts Registry Number.
The active ingredient mixture of the compounds of formula (I) selected from one compound as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below) is preferably in a mixing ratio of from 100:1 to 1 :6000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20:1 to 1 :20, even more especially from 10:1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2: 1 to 1 :2, and a ratio of from 4:1 to 2:1 being likewise preferred, above all in a ratio of 1 : 1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3:1 , or 3:2, or 2: 1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2, or 1 :600, or 1 :300, or 1 :150, or 1 :35, or 2:35, or 4:35, or 1 :75, or 2:75, or 4:75, or 1 :6000, or 1 :3000, or 1 : 1500, or 1 :350, or 2:350, or 4:350, or 1 :750, or 2:750, or 4:750. Those mixing ratios are by weight.
The mixtures as described above can be used in a method for controlling pests, which comprises applying a composition comprising a mixture as described above to the pests or their environment, with the exception of a method for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body.
The mixtures comprising a compound as represented in Tables 1.1 to 1.19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below), and one or more active ingredients as described above can be applied, for example, in a single“ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a“tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying a compound as represented in Tables 1.1 to 1 .19, Tables 2.1 to 2.19, or a compound 1.1 to 1.15 listed in Table T1 (below) and the active ingredient(s) as described above, is not essential for working the present invention.
The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematocides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and/or compressing a solid active ingredient and in the presence of at least one auxiliary for example by intimately mixing and/or grinding the active ingredient with the auxiliary (auxiliaries). These processes for the preparation of the compositions and the use of the compounds (I) for the preparation of these compositions are also a subject of the invention.
Another aspect of the invention is related to the use of a compound of formula (I) or of a preferred individual compound as defined herein, 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 or insecticidal mixture comprising at least one compound of formula (I) or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides 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 insects or by phytopathogenic microorganisms, preferably fungal organisms.
A further aspect of the 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 insects or 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, or insects 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 or insect. However, the compounds of formula (I) can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula (I) may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, e.g. a composition containing the compound of formula (I), and, if desired, 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). 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. When used as seed drenching agent, convenient dosages are from 10mg to 1g of active substance per kg of seeds.
When the combinations of the present invention are used for treating seed, rates of 0.001 to 50 g of a compound of formula (I) per kg of seed, preferably from 0.01 to 10g per kg of seed are generally sufficient.
Suitably, a composition comprising a compound of formula (I) according to the present invention is applied either preventative, meaning prior to disease development or curative, meaning after disease development.
The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects). Also conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly, formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
A seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) optionally together with other active agents, particularly microbiocides or conservatives or the like. Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
Table 1.1 : This table discloses 67 specific compounds of the formula (T-1 ):
Figure imgf000054_0001
wherein A is:
Figure imgf000054_0002
R1 , R2, and R3 are hydrogen and R4 is as defined below in Table 1.
Each of Tables 1.2 to 1.19 (which follow Table 1.1 ) make available 67 individual compounds of the formula (T-1 A) in which A, R1 , R2, and R3 are as specifically defined in Tables 1.2 to 1.19, which refer to Table 1 wherein R4 is specifically defined.
Table 1
Figure imgf000054_0003
Figure imgf000055_0004
Table 1.2: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000055_0001
R1 , R2, and R2 are hydrogen and R4 is as defined above in Table 1.
Table 1.3: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000055_0002
R1 and R2 are hydrogen, R3 is methyl, and R4 is as defined above in Table 1.
Table 1.4: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000055_0003
R1 and R2 are hydrogen, R3 is methyl, and R4 is as defined above in Table 1.
Table 1.5: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0001
R1 and R2 are hydrogen, R3 is ethyl, and R4 is as defined above in Table 1.
Table 1.6: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0002
R1 and R2 are hydrogen, R3 is ethyl, and R4 is as defined above in Table 1.
Table 1.7: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0003
R1 and R2 are hydrogen, R3 is cyclopropyl, and R4 is as defined above in Table 1.
Table 1.8: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0004
R1 and R2 are hydrogen, R3 is cyclopropyl, and R4 is as defined above in Table 1.
Table 1.9: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0005
R1 and R2 are hydrogen, R3 is 2,2-difluoroethoxy and R4 is as defined above in Table 1. Table 1.10: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000056_0006
R1 and R2 are hydrogen, R3 is 2,2-difluoroethoxy, and R4 is as defined above in Table 1.
Table This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0001
R1 and R2 are hydrogen, R3 is methoxy, and R4 is as defined above in Table 1.
Table 1.12: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0002
R1 and R2 are hydrogen, R3 is methoxy, and R4 is as defined above in Table 1.
Table 1.13: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0003
R1 and R2 are hydrogen, R3 is methoxy, and R4 is as defined above in Table 1.
Table 1.14: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0004
R1 hydrogen, R2 is methyl, and R3 is methoxy, and R is as defined above in Table 1.
Table 1.15: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0005
R1 hydrogen, R2 is methyl, and R3 is methoxy, and R4 is as defined above in Table 1. Table 1.16: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000057_0006
R1 and R2 are hydrogen, R3 is methoxy and R4 is as defined above in Table 1.
Table 1.17: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000058_0001
R1 and R2 are hydrogen, R3 is methoxy, and R4 is as defined above in Table 1.
Table 1.18: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000058_0002
R1 and R2 are hydrogen, R3 is ethoxy and R4 is as defined above in Table 1.
Table 1.19: This table discloses 67 specific compounds of formula (T-1 ) wherein A is:
Figure imgf000058_0003
R1 and R2 are hydrogen, R3 is ethoxy, and R4 is as defined above in Table 1.
Table 2.1 : This table discloses 55 specific compounds of the formula (T-2):
Figure imgf000058_0004
wherein A is
Figure imgf000058_0005
R1 , R2 and R3 are hydrogen and -NR5(R6) is as defined below in Table 2.
Each of Tables 2.2 to 2.19 (which follow Table 2.1 ) make available 55 individual compounds of the formula (T-2) in which A, R1 , R2, and R3 are as specifically defined in Tables 2.2 to 2.19, which refer to Table 2, wherein NR5(R6) is specifically defined.
Table 2
Figure imgf000058_0006
Figure imgf000059_0001
Table 2.2: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0001
R1 , R2 and R3 are hydrogen and NR5(R6) is as defined above in Table 2.
Table 2.3: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0002
R1 and R2 are hydrogen, R3 is methyl, and NR5(R6) is as defined above in Table 2. Table 2.4: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0003
R1 and R2 are hydrogen, R3 is methyl, and NR5(R6) is as defined above in Table 2. Table 2.5: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0004
R1 and R2 are hydrogen, R3 is ethyl, and NR5(R6) is as defined above in Table 2. Table 2.6: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0005
R1 and R2 are hydrogen, R3 is ethyl, and NR5(R6) is as defined above in Table 2. Table 2.7: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0006
R1 and R2 are hydrogen, R3 is cyclopropyl, and NR5(R6) is as defined above in Table 2. Table 2.8: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000060_0007
R1 and R2 are hydrogen, R3 is cyclopropyl, and NR5(R6) is as defined above in Table 2. Table 2.9: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0001
R1 and R2 are hydrogen, R3 is 2,2-difluoroethoxy and NR5(R6) is as defined above in Table 2.
Table 2.10: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0002
R1 and R2 are hydrogen, R3 is 2,2-difluoroethoxy, and NR5(R6) is as defined above in Table 2. Table 2.1 1 : This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0003
R1 and R2 are hydrogen, R3 is methoxy, and NR5(R6) is as defined above in Table 2.
Table 2.12: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0004
R1 and R2 are hydrogen, R3 is methoxy, and NR5(R6) is as defined above in Table 2.
Table 2.13: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0005
and R1 and R2 are hydrogen, R3 is methoxy, and NR5(R6) is as defined above in Table 2. Table 2.14: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000061_0006
and R1 hydrogen, R2 is methyl, and R3 is methoxy, and NR5(R6) is as defined above in Table 2. Table 2.15: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000062_0001
and R1 hydrogen, R2 is methyl, and R3 is methoxy, and NR5(R6) is as defined above in Table 2. Table 2.16: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000062_0002
R1 and R2 are hydrogen, R3 is methoxy, and NR5(R6) is as defined above in Table 2. Table 2.17: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000062_0003
R1 and R2 are hydrogen, R3 is methoxy, and NR5(R6) is as defined above in Table 2. Table 2.18: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000062_0004
R1 and R2 are hydrogen, R3 is ethoxy, and NR5(R6) is as defined above in Table 2.
Table 2.19: This table discloses 55 specific compounds of formula (T-2) wherein A is:
Figure imgf000062_0005
R1 and R2 are hydrogen, R3 is ethoxy, and NR5(R6) is as defined above in Table 2.
EXAMPLES
The Examples which follow serve to illustrate the invention.
The compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.
Compounds of formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
Throughout this description, temperatures are given in degrees Celsius (°C) and“mp.” means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method A is as follows:
The description of the LC/MS apparatus and the method A is:
SQ Detector 2 from Waters
Ionisation method: Electrospray
Polarity: positive and negative ions
Capillary (kV) 3.0, Cone (V) 30.00, Extractor (V) 2.00, Source Temperature (°C) 150, Desolvation
Temperature (°C) 350, Cone Gas Flow (L/Hr) 0, Desolvation Gas Flow (L/Hr) 650
Mass range: 100 to 900 Da
DAD Wavelength range (nm): 210 to 500
Method Waters ACQUITY UPLC with the following HPLC gradient conditions:
(Solvent A: Water/Methanol 20: 1 + 0.05% formic acid and Solvent B: Acetonitrile+ 0.05% formic acid)
Time (minutes) A (%) B (%) Flow rate (ml/min)
0 100 0 0.85
1.2 0 100 0.85
1.5 0 100 0.85
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
Formulation Examples
Wettable powders a) b) c)
Active ingredient [compound of formula (I)] 25 % 50 % 75 %
sodium lignosulfonate 5 % 5 %
sodium lauryl sulfate 3 % - 5 %
sodium diisobutylnaphthalenesulfonate 6 % 10 %
phenol polyethylene glycol ether 2 %
(7-8 mol of ethylene oxide)
highly dispersed silicic acid 5 % 10 % 10 %
Kaolin 62 % 27 % The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
Powders for dry seed treatment a) b) c)
Active ingredient [compound of formula (I)] 25 % 50 % 75 %
light mineral oil 5 % 5 % 5 %
highly dispersed silicic acid 5 % 5 %
Kaolin 65 % 40 %
Talcum 20 %
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Emulsifiable concentrate
active ingredient [compound of formula (I)] 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 mol of ethylene oxide)
calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 mol of ethylene oxide) 4 %
Cyclohexanone 30 %
xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Dusts a) b) c)
Active ingredient [compound of formula (I)] 5 % 6 % 4 %
Talcum 95 %
Kaolin 94 %
mineral filler 96 %
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
Extruder granules
Active ingredient [compound of formula (I)] 15 %
sodium lignosulfonate 2 %
Carboxymethylcellulose 1 %
Kaolin 82 % The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
Coated granules
Active ingredient [compound of formula (I)] 8 %
polyethylene glycol (mol. wt. 200) 3 %
Kaolin 89 % The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
Suspension concentrate
Active ingredient [compound of formula (I)] 40 %
propylene glycol 10 %
nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
Sodium lignosulfonate 10 %
Carboxymethylcellulose 1 %
Silicone oil (in the form of a 75 % emulsion in water) 1 %
Water 32 % The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment
Active ingredient [compound of formula (I)] 40 %
propylene glycol 5 %
copolymer butanol PO/EO 2 %
tristyrenephenole with 10-20 moles EO 2 %
1 ,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 %
monoazo-pigment calcium salt 5 %
Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
Water 45.3 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Slow-Release Capsule Suspension 28 parts of a combination of the compound of formula (I) are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1 ). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1 ,6- diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension Formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
List of Abbreviations:
AIBN = azobisisobutyronitrile
brs = broad singlet
DMF = dimethylformannide
DMA = dimethylacetamide
DIPEA = N,N-di-isopropylethylamine
EtOAc = ethyl acetate
HCI = hydrochloric acid
mp = melting point
°C = degrees Celsius
MeOH = methyl alcohol
NaOH = sodium hydroxide
NBS = N-bromosuccinimide
min = minutes
rt = room temperature
h = hour(s)
TFAA = trifluoroacetic acid anhydride
THF = tetrahydrofuran
Rt = retention time (in minutes)
LC/MS = Liquid Chromatography Mass Spectrometry (description of the apparatus and the methods used for LC/MS analysis are given above)
Preparation Examples
Using the synthetic techniques described both above and below, compounds of formula (I) may be prepared accordingly. Example 1 : This example illustrates the preparation of 1-cyclopropyl-3-methyl-1-[[5-[5-(trifluoromethyl)- 1 ,2,4-oxadiazol-3-yl]-2-thienyl]methyl]thiourea (Compound 1.1 1 of Table T1 )
Figure imgf000067_0001
Step 1 : Preparation of N'-hvdroxy-5-methyl-thiophene-2-carboxamidine
Figure imgf000067_0003
To a suspension of 5-methylthiophene-2-carbonitrile (9.0 g, 73 mmol) in ethanol (365 ml_) stirring at room temperature was added triethylamine (20.6 ml_, 146 mmol) followed by the portion wise introduction of hydroxylamine hydrochloride (10.3 g, 146 mmol). The reaction contents were heated at reflux for 3.5 hours, cooled to 25°C, and concentrated under reduced pressure to provide 32.0 g of the title compound as a crude residue which was used in the next transformations without further purification. LC/MS (Method A) retention time = 0.24 minutes, 156 (M+H).
Step 2: Preparation of 3-(5-methyl-2-thienvD-5-(trifluoronnethvD-1.2.4-oxadiazole
Figure imgf000067_0002
To a suspension of crude N'-hydroxy-5-methyl-thiophene-2-carboxamidine (32.0 g) in tetrahydrofuran (1000 ml_) was introduced pyridine (24 ml_, 292 mmol) and the contents were cooled to 10°C. To this suspension, trifluoracetic anhydride (30.9 ml_, 219 ml_) was introduced dropwise. The reaction mixture was allowed to warm to 25°C overnight, and then concentrated at reduced pressure. The resultant residue was dissolved in ethyl acetate, washed with an aqueous 1 M HCI solution, water, and a saturated aqueous Na2CC>3 solution. The organic layer was dried over sodium sulfate, filtered, and the volatiles were removed at reduced pressure. The crude residue was purified by flash chromatography over silica gel using a cyclohexane/EtOAc eluent gradient to afford 13.1 g of the title compound as a clear oil. LC/MS (Method A) retention time = 1 .13 minutes, mass not detected.
Ή NMR (400 MHz, CDCIs) d ppm: 7.68 (d, 1 H), 6.84 (d, 1 H), 2.57 (s, 3H).
19F NMR (400 MHz, CDCIs) d ppm: -65.44 (s).
Step 3a: Preparation of 3-[5-(bromonnethvD-2-thienvn-5-(thfluoronnethvD-1.2.4-oxadiazole
Figure imgf000068_0001
To a solution of 3-(5-methyl-2-thienyl)-5-(trifluoromethyl)-1 ,2,4-oxadiazole (13.1 g, 55.7 mmol) and tetrachloromethane (1 1 1 ml_) under argon atmosphere was added AIBN (0.93 g, 5.6 mmol) then NBS (1 1.02 g, 61.3 mmol). The contents were heated at 70°C for 18 hours. The mixture was cooled to 25°C then diluted with dichloromethane and water. The layers were separated, the organic phase was dried over sodium sulfate, and the volatiles were removed under reduced pressure. The crude residue was purified by flash chromatography over silica gel using a cyclohexane/EtOAc eluent gradient to afford 3.86 g of the title compound as a yellow oil. LC/MS (Method A) retention time = 1 .14 minutes, mass not detected.
Ή NMR (400 MHz, CDCIs) d ppm: 8.1 1 (d, 1 H), 7.55 (d, 1 H), 4.53 (s, 2H).
19F NMR (400 MHz, CDCIs) d ppm: -65.31 (s).
3-[5-(dibromomethyl)-2-thienyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole was isolated as by-product as a yellow amorphous solid (13.0 g)
Figure imgf000068_0002
Ή NMR (400 MHz, CDCIs) d ppm: 7.73 (d, 1 H), 7.32 (d, 1 H), 6.91 (s, 1 H).
Step 4: Preparation of N-[[5-[5-(trifluoromethvn-1 ,2.4-oxadiazol-3-yll-2- thienyllmethyncvclopropanamine
Figure imgf000068_0003
To a solution of 3-[5-(bromomethyl)-2-thienyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole (2 g, 6.39 mmol) in tetrahydrofuran (5 ml_) was introduced cyclopropylamime (2.21 ml_, 31.9 mmol) dropwise and resultant suspension was stirred overnight. The solid contents were filtered off and volatiles were removed under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel using a cyclohexane/EtOAc eluent gradient to afford 1.70 g of the title compound as a yellow oil. LC/MS (Method A) retention time = 0.57 minutes, (M+H) not observed. Ή NMR (400 MHz, CDCIs) d ppm: 7.70 (d, 1 H), 7.02 (d, 1 H), 4.09 (s, 2H), 2.25 (m, 1 H), 1.95 (brs, 1 H), 0.50 (m, 4H).
Step 5: Preparation of 1-cvclopropyl-3-methyl-1-[[5-[5-(trifluoromethv0-1 ,2.4-oxadiazol-3-yll-2- thienyllmethyllurea
Figure imgf000069_0001
To a stirring solution of N-methoxy-1-[5-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-2- thienyl]methanamine (0.15 g, 0.52 mmol) in dichloromethane (1.6 ml_) was added triethylamine (0.15 ml_, 1.43 mmol). The resultant mixture was cooled to 5°C and then N-methylcarbamoyl chloride (0.06 g, 0.67 mmol) was introduced. The reaction mixture was allowed to reach 25°C and stirred for 1 hour. The resultant residue was added to water and extracted with ethyl acetate. The organic layer was washed a saturated aqueous NaCI solution and dried over sodium sulfate. Volatiles were removed under reduced pressure and the resultant crude residue was purified by flash chromatography over silica gel using a cyclohexane/EtOAc eluent gradient to afford 0.14 g the title compound as a yellow oil. LC/MS (Method A) retention time = 0.98 minutes, 347 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 7.70 (d, 1 H), 7.05 (d, 1 H), 5.45 (brs, 1 H), 4.70 (s, 2H), 2.90 (s, 3H), 2.45 (m, 1 H), 0.89 (m, 2H), 0.82 (m, 2H).
Step 6: Preparation of 1-cvclopropyl-3-methyl-1-[[5-[5-(trifluoromethvn-1 ,2.4-oxadiazol-3-yll-2- thienyllmethynthiourea
To a suspension of N-[[5-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-2- thienyl]methyl]cyclopropanamine (0.09 g, 0.27 mmol) in toluene (1 ml_) was introduced phosphorus pentasulfide (0.07 g, 0.29 mmol) and the reaction was heated at reflux. After 2 hours, the contents were allowed to reach 25°C then poured into a water and ethyl acetate mixture. The layers were separated, the organic layer was dried over sodium sulfate, concentrated under reduced pressure, and the resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 1 :0 to 1 : 1 ) to provide 0.02 g of the title compound as a yellow gum. LC/MS (Method A) retention time = 1.07 minutes, 363 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 7.70 (d, 1 H), 7.12 (d, 1 H), 6.15 (brs, 1 H), 5.45 (s, 2H), 3.70 (s, 3H), 2.50 (m, 1 H), 1 .05 (m, 2H), 0.95 (m, 2H).
19F NMR (400 MHz, CDCIs) d ppm: -65.38 (s).
Example 2: This example illustrates the preparation of 3-cyclopropyl-1-methoxy-1-[[4-[5- (trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]thiourea (Compound 1.7 of Table T1 )
Figure imgf000070_0001
Step 1 : Preparation of N'-hvdroxy-4-methyl-benzamidine
Figure imgf000070_0002
To a suspension of 4-methylbenzonitrile (35 g, 0.29 mol) in ethanol (220 ml_) and water (440 ml_) was added at room temperature hydroxylamine hydrochloride (41.1 g, 0.58 mol), potassium carbonate (65.4 g, 0.47 mol), and 8-hydroxyquinoline (0.22 g, 1.5 mmol). The reaction mixture was heated at 80°C for 4 hours, then cooled to room temperature, and diluted with 2N HCI until pH 8. The volatiles were removed under reduced pressure and the reaction contents were filtered, washed with water, and dried under vacuum to afford 39.1 g of the title compound. LC/MS (Method A) retention time = 0.23 minutes, 151 .0 (M+H).
Step 2: Preparation of 3-(p-tolvD-5-(trifluoronnethvD-1.2.4-oxadiazole
Figure imgf000070_0003
To a solution of N'-hydroxy-4-methyl-benzamidine (38.7 g, 0.25 mol) in 2-methyltetrahydrofuran (750 ml_) was added trifluoracetic anhydride at 0°C. The reaction mixture was stirred at 15°C for two hours then diluted with water. The organic layer was separated, washed successively with a saturated aqueous sodium bicarbonate solution, a saturated aqueous ammonium chloride solution, and water then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel (heptane/EtOAc eluent gradient 99: 1 to 90: 10) to afford 54.1 g of the title compound as clear oil, which solidified after storage. LC/MS (Method A) retention time = 1.15 minutes, mass not detected.
Ή NMR (400 MHz, CDCIs) d ppm: 8.00 (d, 2H), 7.32 (d, 2H), 2.45 (s, 3H).
19F NMR (400 MHz, CDCIs) d ppm: -65.41 (s).
Step 3a: Preparation of 3-[4-(bromonnethyl)phenyll-5-(thfluoronnethvD-1.2.4-oxadiazole
Figure imgf000071_0001
A mixture of 3-(p-tolyl)-5-(trifluoromethyl)-1 ,2,4-oxadiazole (56.0 g, 0.24 mol) and NBS (45.4 g, 0.25 mol) in tetrachloromethane (480 ml_) under argon was heated to 70°C. AIBN (4.03 g, 24 mmol) was added and the reaction mixture was stirred at 65°C for 18 hours. The mixture was then cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the organic layer was washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohehane/EtOAc eluent gradient 100:0 to 95:5) to afford 44.7 g of the title compound as a white solid mp: 58-63°C.
Ή NMR (400 MHz, CDCIs) d ppm: 8.1 1 (d, 2H), 7.55 (d, 2H), 4.53 (s, 2H).
19F NMR (400 MHz, CDCIs) d ppm: -65.32 (s).
3-[4-(dibromomethyl)phenyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole was isolated as by-product as white solid mp: 61-66°C.
Ή NMR (400 MHz, CDCIs) d ppm: 8.15 (d, 2H), 7.73 (d, 2H), 6.68 (s, 1 H).
19F NMR (400 MHz, CDCIs) d ppm: -65.34 (s).
Step 3b: Preparation of 3-[4-(bromonnethyl henyll-5-(thfluoronnethvD-1.2.4-oxadiazole from 3-[4-
(dibromonnethvDphenvn-5-(thfluoronnethvD-1.2.4-oxadiazole
Figure imgf000071_0002
To a 1 :9 ratio mixture of 3-[4-(bromomethyl)phenyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole and 3- [4-(dibromomethyl)phenyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole (10.2 g) in acetonitrile (95 ml_), water (1.9 ml_) and DIPEA (6.20 ml_, 35.7 mmol) was added diethylphosphite (4.7 ml_, 35.7 mmol) at 5°C. The mixture was stirred at 5-10°C for two hours, aqueous 1 M HCI was added, and volatiles were removed under reduced pressure. The resultant white slurry was extracted with dichloromethane and the total combined organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 99: 1 to 9: 1 ) to afford 7.10 g of the title compound as a white solid mp: 58-63°C.
Ή NMR (400 MHz, CDCIs) d ppm: 8.1 1 (d, 2H), 7.55 (d, 2H), 4.53 (s, 2H). 19F NMR (400 MHz, CDCIs) d ppm: -65.32 (s).
Step 4: Preparation of N-methoxy-1-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yllphenyllmethanamine
Figure imgf000072_0001
To a solution of O-methylhydroxylamine hydrochloride (1 1.2 g, 131.3 mmol) in dichloromethane (91 ml_) was introduced DIPEA (19.1 g, 147.7 mmol) via dropwise addition. After 20 minutes, 3-[4- (bromomethyl)phenyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole (14.0 g, 16.4 mmol) was introduced as a dichloromethane (4 ml_) solution. The reaction mixture was stirred at room temperature for 24 hours, then poured into water and the layers were separated. The organic layer was washed with water, the organic fraction was concentrated under reduced pressure, and the resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 1 :0 to 7:3) to give 4.4 g of the title compound as a yellowish oil.
Ή NMR (400 MHz, CDCIs) d ppm: 8.09 (d, 2H), 7.53 (d, 2H), 5.33 (brs, 1 H), 4.12 (s, 2H), 3.50 (s, 3H).
Step 5: Preparation of 3-cvclopropyl-1-methoxv-1-l
Figure imgf000072_0002
l-1 ,2,4-oxadiazol-3- yllphenyllmethyllthiourea
To a solution of cyclopropylamine (0.10 g, 1.75 mmol), triethylamine (0.49 ml_, 3.5 mmol) and tetrahydrofuran (5.3 ml_) cooled via ice bath was introduced portion wise thiocarbonyl dichloride (0.200 g, 1.75 mmol). After reaching 25°C over 1 hour, to the orange suspension was introduced N-methoxy- 1-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methanamine (0.53 g, 1.93 mmol) dissolved in tetrahydrofuran (1.5 ml_) and the reaction contents were stirred overnight. Then a saturated NaHCCh solution was added to the mixture and the aqueous layer was extracted with dichloromethane. The total combined organic layer was washed with a saturated NaHCCh dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a cyclohexane/ethyl acetate eluent gradient to afford 0.155 g the title compound as a yellow solid mp: 58-63°C. LC/MS (Method A) retention time = 1.1 1 minutes, 373 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 8.12 (d, 2H), 7.55 (d, 2H), 7.05 (brs, 1 H), 5.36 (m, 2H),
3.60 (s, 3H), 3.13 (m, 1 H), 0.85 (m, 2H), 0.62 (m, 2H).
Example 3: Preparation of N-[[2,3-difluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]-N- methoxy-propanethioamide (Compound 1.14 of Table T1 )
Figure imgf000073_0001
Step 1 : Preparation of 2.3-difluoro-N'-hvdroxy-4-methyl-benzamidine
Figure imgf000073_0002
To a suspension of 2,3-difluoro-4-methylbenzonitrile (5.0 g, 32.6 mmol) in ethanol (1 1 1 ml_) at 25°C was added hydroxylamine hydrochloride (4.5 g, 65.3 mmol). The reaction mixture was heated at 80°C for 2 hours. After cooling to room temperature the volatiles were removed under reduced pressure thus affording a white solid that was used in the next step without purification.
Ή NMR (400 MHz, CDCIs) d ppm: 7.30 (m, 1 H), 6.95 (m, 1 H), 5.05 (brs, 2H), 2.30 (s, 3H).
Step 2: Preparation of 3-(2.3-difluoro-4-nnethyl-phenvD-5-(trifluoronnethvD-1.2.4-oxadiazole
Figure imgf000073_0003
To a solution of 2,3-difluoro-N'-hydroxy-4-methyl-benzamidine (2.6 mmol) in tetrahydrofuran (108 ml_) cooled via an ice bath was added TFAA (6.9 ml_, 49 mmol). The reaction mixture was stirred at 25°C overnight and then diluted with water. The organic layer was separated, washed successively with a saturated aqueous sodium bicarbonate solution, a saturated aqueous ammonium chloride solution, water, t dried over sodium sulfate, filtered, and concentrated under reduced pressure. The title compound (6.6 g) was isolated as a light brown solid that was used in the next transformation without further purification. LC/MS (Method A) retention time = 1 .16 minutes, 265 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 7.76 (d, 1 H), 7.12 (d, 1 H), 2.41 (s, 3H).
19F NMR (400 MHz, CDCIs) d ppm: -65.41 (s), -133.3 (s), -140.1 (s).
Step 3: Preparation of 3-[4-(bromonnethvD-2.3-difluoro-phenvn-5-(thfluoronnethvD-1 ,2,4-oxadiazole
Figure imgf000074_0001
A mixture of 3-(2,3-difluoro-4-methyl-phenyl)-5-(trifluoromethyl)-1 ,2,4-oxadiazole (6.0 g, 22.7 mmol) and NBS (4.29 g, 24 mmol) in tetrachloromethane (45 ml_) under argon was heated to 70°C. AIBN (0.38 g, 2.27 mmol) was added and the reaction mixture stirred at 65°C for 18 h. Additional amounts of NBS (4.29 g, 24 mmol) and AIBN (0.19 g, 1.14 mmol) were introduced and the contents were heated overnight at 68°C. The mixture was cooled to 25°C, diluted with dichloromethane, water, and the layers were separated. The succinimide by-product was filtered off and volatiles were removed under vacuum. The resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 100:0 to 4: 1 ) to afford 4.8 g of the title compound as a white solid.
Ή NMR (400 MHz, CDCIs) d ppm: 7.80 (m, 1 H), 7.37 (m, 1 H), 4.55 (s, 2H).
19F NMR (400 MHz, CDCIs) d ppm: -65.1 (s), -131 .2 (s), -139.1 (s).
Step 4: Preparation of 1-[2.3-difluoro-4-[5-(trifluoromethvn-1.2.4-oxadiazol-3-yllphenyll-N-methoxy- methanamine
Figure imgf000074_0002
A solution of O-methylhydroxylamine hydrochloride (3.5 g, 42 mmol) in dichloromethane (8 ml_) was treated dropwise with DIPEA (8.3 ml_, 47 mmol) followed by a solution of 3-[4-(bromomethyl)-2,3- difluoro-phenyl]-5-(trifluoromethyl)-1 ,2,4-oxadiazole (2 g, 5.2 mmol) in dichloromethane (5 ml_). After 18 hours, water was introduced (10 ml_) and the reaction contents were extracted twice with dichloromethane and the combined organic layers were dried over sodium sulfate and filtered. The resultant residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 1 :0 to 1 :1 ) to afford 1.1 g of the title compound as a pale yellow oil. LC/MS (Method A) retention time = 1.03 minutes, 310 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 7.84 (t, 1 H), 7.38 (t, 1 H), 5.87 (brs, 1 H), 4.20 (s, 2H), 3.52 (s, 3H).
19F NMR (400 MHz, CDCIs) d ppm: -65.21 (s), -132.53 (s), -147.50 (s).
Step 5: Preparation of N-[[2.3-difluoro-4-[5-(trifluoromethvn-1.2.4-oxadiazol-3-yllphenyllmethyll-N- methoxy-propanamide
Figure imgf000075_0001
A solution of 1-[2,3-difluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]-N-methoxy- methanamine (0.12 g, 0.39 mmol) in dichloromethane (2 ml_) was added triethylamine (0.1 1 ml_, 0.78 mmol) followed by propanoyl chloride (0.04 ml_, 0.43 mmol). After 2 hours, the reaction contents were concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 1 :0 to 1 :1 ) to afford 0.10 g of the title compound as a colourless oil. LC/MS (Method A) retention time = 1 .09 minutes, 366 (M+H).
1H NMR (400 MHz, CDCIs) d ppm: 7.82 (m, 1 H), 7.46 (m, 1 H), 4.95 (s, 2H), 3.73 (s, 3H), 2.53 (m, 2H), 1.17 (m, 3H). l-N-
Figure imgf000075_0002
To a suspension of N-[[5-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-2- thienyl]methyl]cyclopropanamine (0.07 g, 0.20 mmol) in toluene (0.8 ml_) was introduced phosphorus pentasulfide (0.05 g, 0.21 mmol) and the reaction was heated at reflux. After 4 hours, the contents were allowed to reach 25°C then poured into a water and ethyl acetate mixture. The layers were separated, the organic fraction was dried over sodium sulfate and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel (cyclohexane/EtOAc eluent gradient 1 :0 to 1 : 1 ) to provide 0.03 g of the title compound as a yellow gum. LC/MS (Method A) retention time = 1 .17 minutes, 382 (M+H).
Ή NMR (400 MHz, CDCIs) d ppm: 7.83 (m, 1 H), 7.43 (m, 1 H), 5.38 (s, 2H), 3.83 (s, 3H), 2.90 (m, 2H), 1.30 (m, 3H).
19F NMR (400 MHz, CDCIs) d ppm: -65.3 (s), -131.9 (s), -141.1 (s).
Where necessary, enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, (e.g., by using chiral starting materials). Table T 1 : Melting point imp) data and/or retention times (Rt) for compounds according to formula (I):
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
BIOLOGICAL EXAMPLES
Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse. The cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar. The leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation. Compounds to be tested are prepared as DMSO solutions (max. 10 mg/mL) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying. The inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system. A single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.
General examples of liquid culture tests in well plates:
Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/mL) are diluted with 0.025% Tween20 by a factor of 50 and 10 pL of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24°C and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.
Example 1 : Fungicidal activity against Puccinia recondita f. so. tritici / wheat / leaf disc preventative (Brown rust)
Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19°C and 75% relative humidity (rh) under a light regime of 12 hours light / 12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 to 9 days after application).
The following compounds at 200 ppm in the applied formulation 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.
Compounds (from Table T1 ) 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.1 1 , 1.12, 1.13, 1.14, and 1.15.
Example 2: Fungicidal activity against Puccinia recondita f. so. tritici / wheat / leaf disc curative (Brown rust)
Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. Plates were stored in darkness at 19°C and 75% relative humidity. The formulated test compound diluted in water was applied 1 day after inoculation. The leaf segments were incubated at 19°C and 75% relative humidity under a light regime of 12 hours light / 12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 to 8 days after application).
The following compounds at 200 ppm in the applied formulation 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.
Compounds (from Table T1 ) 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 17, 1.8, 1.9, 1.10, 1.1 1 , 1.12, 1.13, 1.14, and 1.15.
Example 3: Fungicidal activity against Phakopsora pachyrhizi / soybean / leaf disc preventative (Asian soybean rust)
Soybean leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. After an incubation period in a climate cabinet of 24-36 hours in darkness at 20°C and 75% rh leaf disc are kept at 20°C with 12 h light/day and 75% rh. 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 (12 to 14 days after application).
The following compounds at 200 ppm in the applied formulation 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.
Compounds (from Table T1 ) 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.1 1 , 1.12, 1.13, 1.14, and 1.15.
Example 4: Fungicidal activity against Glomerella lagenarium (Colletotrichum lagenarium) liquid culture / cucumber / preventative (Anthracnose)
Conidia of the fungus from cryogenic storage 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 spores is added. The test plates are incubated at 24°C and the inhibition of growth is measured photometrically 3 to 4 days after application.
The following compounds at 20 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control under the same conditions, which show extensive disease development.
Compounds (from Table T1 ) 1.1 , 1.2, 1.3, 1.4, 1.5, 1.6, 17, 1.8, 1.9, 1.10, 1.1 1 , 1.12, 1.13, 1.14, and 1.15.

Claims

CLAIMS:
1. A compound of formula (I):
Figure imgf000081_0001
wherein A-1 , A-2, A-3, or A-4 are optionally substituted by 1 or 2 independently selected halogen groups;
R1 and R2 are independently selected from hydrogen, methyl and cyano; or
R1 and R2, together with the carbon atom to which they are bonded, form a cyclopropyl ring;
R3 represents hydrogen, hydroxy, Ci-4alkyl, Ci-4haloalkyl, Ci-4alkoxy, hydroxyC2-4alkyl, C-i- 2alkoxyC2-4alkyl, Ci-2haloalkoxy, Ci-2haloalkoxyC2-4alkyl, C3-4alkenyl, C3-4alkynyl, C3-4alkenyloxy, C3- 4alkynyloxy, Ci-4alkylcarbonyloxy, N-Ci-2alkylamino, N,N-diCi-2alkylamino, C3-6cycloalkyl or C3- 6cycloalkylCi-2alkyl;
Z is selected from Z1 or Z2; wherein
Z1 is R4, wherein R4 represents hydrogen, cyano, Ci-ealkyl, Ci ehaloalkyl, cyanoCi ealkyl, hydroxyCi-4alkyl, Ci-4alkoxyCi-4alkyl, Ci-4haloalkoxyCi-4alkyl, Ci-2alkoxyCi-2alkoxyCi-4alkyl, C3- 5alkenyloxyCi-4alkyl, C3-salkynyloxyCi-4alkyl, aminoCi ealkyl, N-Ci-4alkylaminoCi-4alkyl, N,N-diCi- 4alkylaminoCi-4alkyl, Ci-4alkylcarbonylCi-4alkyl, Ci-4alkoxycarbonylCi-4alkyl, Ci-4alkylcarbonyloxyCi- 4alkyl, N-Ci-4alkylaminocarbonylCi-4alkyl, N,N-diCi-4alkylaminocarbonylCi-4alkyl, Ci-4alkylsulfanylCi- 4alkyl, Ci-4alkylsulfonylCi-4alkyl, Ci-4alkylsulfonylaminoCi-4alkyl, Ci-4alkylcarbonylaminoCi-4alkyl or C-i- 4alkoxycarbonylaminoCi-4alkyl; or R4 represents heterocyclylCi-2alkyl, wherein the heterocyclyl moiety is a 4- to 6-membered nonaromatic ring which comprises 1 or 2 heteroatoms individually selected from N, O and S, wherein the heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from cyano, halogen, hydroxy, amino, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy and cyclopropyl, and
wherein when R4 comprises a heterocyclyl, this cycle may optionally contain 1 group selected from C(O) or S(0)2;
Z2 represents -NR5R6, wherein R5 represents hydrogen, cyano, Ci-4alkyl, cyanoCi-4alkyl, C-i- 4alkoxy, C3-salkenyl, C3-salkynyl, C3-4alkenyloxy, C3-4alkynyloxy, Ci-4haloalkyl, C3-4haloalkenyl, hydroxyC2-4alkyl, Ci-2alkoxyC2-4alkyl, Ci-2haloalkoxyC2-4alkyl, Ci-2alkoxyC2-4alkoxyC2-4alkyl, N-C-i- 3alkylamino, N,N-diCi-3alkylamino, aminoC2-4alkyl, N-Ci-4alkylaminoC2-4alkyl, N,N-diCi-4alkylaminoC2- 4alkyl, Ci-3alkylcarbonylCi-3alkyl, Ci-4alkoxycarbonylCi-3alkyl, Ci-3alkylcarbonyloxyC2-4alkyl, N-C-i- 3alkylaminocarbonylCi-3alkyl, N,N-diCi-3alkylaminocarbonylCi-3alkyl, C-i salkylsulfonyl, C-i- 3alkylsulfonylC2-3alkyl or Ci-3alkylsulfonylaminoC2-3alkyl; or
R5 represents Cs ecycloalkyl, C3-6cycloalkylCi-2alkyl, phenyl, phenylCi-2alkyl, heteroaryl or heteroarylCi-2alkyl wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1 , 2, 3, or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylC-i- 2alkyl wherein the heterocyclyl moiety is a 4- to 6-membered non-aromatic ring which comprises 1 or 2 heteroatoms or groups individually selected from N, NR7, O and S; wherein the cycloalkyl, phenyl, heteroaryl or heterocyclyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen, methyl, ethyl, propyl, isopropyl, prop-2-enyl, prop-2-ynyl, cyclopropyl and cyclopropylmethyl, and
wherein when R5 comprises a cycloalkyl or heterocyclyl, these cycles may optionally contain 1 group selected from C(O) or S(0)2;
R6 represents hydrogen, cyano, halogen, hydroxy, amino, methyl, ethyl, propyl, prop-2-enyl, prop-2-ynyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, difluoromethoxy, prop-2-enyloxy, prop-2-ynyloxy, N-methylamino, N,N-dimethylamino, methylcarbonyl, methoxycarbonyl, formylamino, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl or methoxycarbonylamino; and
R7 represents hydrogen, methyl, methoxy, formyl or acyl; or a salt or an N-oxide thereof.
2. The compound according to claim 1 , wherein A is A-1 optionally substituted by 1 or 2 fluorine groups, or A is unsubstituted A-4.
3. The compound according to claim 1 or claim 2, wherein R1 and R2 are independently selected from hydrogen and methyl, and preferably R1 and R2 are hydrogen.
4. The compound according to any one of claims 1 to 3, wherein R3 is hydrogen, Ci-4alkyl, C-i- 4haloalkyl, Ci-4alkoxy, Ci-2haloalkoxy or cyclopropyl.
5. The compound according to any one of claims 1 to 4, wherein R3 is hydrogen, methyl, ethyl, methoxy, 2,2-difluoroethoxy or cyclopropyl.
6. The compound according to any one of claims 1 to 5, wherein Z is R4, and wherein R4 is hydrogen, Ci-4alkyl, Ci-4haloalkyl, cyanoCi-4alkyl, hydroxyCi-4alkyl or Ci-2alkoxyCi-4alkyl.
7. The compound according to claim 6, wherein R4 is hydrogen, Ci-4alkyl or Ci-2alkoxyCi-4alkyl.
8. The compound according to any one of claims 1 to 5, wherein Z is -NR5R6, and wherein R5 is hydrogen, Ci-4alkyl, cyanoCi-4alkyl, Ci-4haloalkyl, hydroxyC2-4alkyl, C3-4cycloalkyl or C3-4cycloalkylCi- 2alkyl, wherein the cycloalkyl is optionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen or methyl.
9. The compound according to claim 8, wherein R5 is hydrogen, Ci-4alkyl, Ci-4fluoroalkyl or C3- 4cycloalkyl.
10. The compound according to claim 9, wherein R5 is methyl, ethyl, n-propyl, iso-propyl, 2,2,2- trifluoroethyl or cyclopropyl.
1 1. The compound according to any one of claims 8 to 10, wherein R6 is hydrogen, methyl, ethyl, n-propyl or iso-propyl, and preferably R6 is hydrogen.
12. An agrochemical composition comprising a fungicidally effective amount of a compound according to any one of claims 1 to 1 1.
13. The composition according to claim 12, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.
14. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound according to any of claims 1 to 1 1 , or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
15. Use of a compound according to any one of claims 1 to 1 1 as a fungicide.
PCT/EP2019/060642 2018-04-26 2019-04-25 Microbiocidal oxadiazole derivatives WO2019207058A1 (en)

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WO2017055473A1 (en) * 2015-10-02 2017-04-06 Syngenta Participations Ag Microbiocidal oxadiazole derivatives
WO2017178245A1 (en) * 2016-04-11 2017-10-19 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
WO2018153730A1 (en) * 2017-02-21 2018-08-30 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi

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WO2017055473A1 (en) * 2015-10-02 2017-04-06 Syngenta Participations Ag Microbiocidal oxadiazole derivatives
WO2017178245A1 (en) * 2016-04-11 2017-10-19 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
WO2018153730A1 (en) * 2017-02-21 2018-08-30 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi

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Publication number Priority date Publication date Assignee Title
WO2021090865A1 (en) * 2019-11-07 2021-05-14 日本農薬株式会社 Oxadiazoline compound or salts thereof, agricultural and horticultural bactericide containing said compound, and method for using same

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