Classifications

• • 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

• 1,3,4-OXADIAZOLE PYRIMIDINES AS FUNGICIDES TECHNICAL FIELD The present invention relates to 1,3,4-oxadiazol-2-ylpyrimidine compounds, processes and intermediates for their preparation as well as the uses thereof for controlling harmful microorganisms, in particular phytopathogenic fungi, in crop protection.
• BACKGROUND 1,2,4-oxadiazoles derivatives are well known to be useful as crop protection agents to combat or prevent microorganisms’ infestations.
• WO-2019/122323, WO-2018/118781 and WO-2018/080859 disclose 1,2,4-oxadiazol-3-ylpyrimidines and 1,2,4-oxadiazol-3-ylpyridines derivatives that may be used for the control of microbial pests, particularly fungal pests, on plants.
• Fungicidally active 1,2,4- oxadiazoles are further known from US 2018/317490.
• Some fungicidally active 1,3,4-oxadiazoles are disclosed in WO2020127974 and WO-00/15637.
• 1,3,4-oxadiazoles derivatives are far less common and seldomly used for the control of microbial pests.
• WO-2018/165520, WO-2017/065473 and WO-2017/023133 disclose 1,3,4-oxadiazol-2-ylpyrimidines and 1,3,4-oxadiazol-2-ylpyridines derivatives that may be used as metalloenzyme (histone deacetylase) inhibitors for the treatment of human diseases.
• Numerous fungicidal agents have been developed until now. However, the need remains for the development of new fungicidal compounds as such, so as to provide compounds being effective against a broad spectrum of fungi, having lower toxicity, higher selectivity, being used at lower dosage rate to reduce or avoid unfavorable environmental or toxicological effects whilst still allowing effective pest control.
• the present invention provides new fungicidal compounds which have advantages over known compounds and compositions in at least some of these aspects.
• SUMMARY The present invention relates to compounds of formula (I) as defined herein: wherein R 1 , R 2 , R 3 and X are as recited herein as well as their salts, N-oxides and solvates.
• the present invention also relates to a composition comprising at least one compound of formula (I) as defined herein and at least one agriculturally suitable auxiliary.
• the present invention also relates to the use of a compound of formula (I) as defined herein or a composition as defined herein for controlling harmful microorganism, in particular phytopathogenic fungi, in crop protection.
• the present invention also relates to a method for controlling harmful microorganisms, in particular phytopathogenic fungi, in crop protection, which comprises the step of applying at least one compound of formula (I) as defined herein or a composition as defined herein to the harmful microorganisms and/or their habitat.
• the present invention also relates to processes and intermediates for preparing compounds of formula (I).
• halogen refers to fluorine, chlorine, bromine or iodine atom.
• oxo refers to an oxygen atom which is bound to a carbon atom or sulfur atom via a double bound.
• C 1 -C 8 -alkyl refers to a saturated, branched or straight hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms.
• C 1 -C 8 -alkyl examples include but are not limited to methyl, ethyl, propyl (n-propyl), 1-methylethyl (iso-propyl), butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2- dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2- methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbuty
• said hydrocarbon chain has 1, 2, 3 or 4 carbon atoms (“C 1 -C 4 -alkyl”), e.g. methyl, ethyl, propyl, iso- propyl, butyl, sec-butyl, iso-butyl or tert-butyl.
• C 2 -C 8 -alkenyl refers to an unsaturated, branched or straight hydrocarbon chain having 2, 3, 4, 5, 6, 7 or 8 carbon atoms and comprising at least one double bond.
• C 2 -C 8 - alkenyl examples include but are not limited to ethenyl (or "vinyl"), prop-2-en-1-yl (or “allyl”), prop-1-en-1-yl, but- 3-enyl, but-2-enyl, but-1-enyl, pent-4-enyl, pent-3-enyl, pent-2-enyl, pent-1-enyl, hex-5-enyl, hex-4-enyl,
• C 2 -C 8 -alkynyl refers to a branched or straight hydrocarbon chain having 2, 3, 4, 5, 6, 7 or 8 carbon atoms and comprising at least one triple bond.
• Examples of C 2 -C 8 -alkynyl include but are not limited to ethynyl, prop-1-ynyl, prop-2-ynyl (or “propargyl"), but-1-ynyl, but-2-ynyl, but-3- ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-
• C 1 -C 8 -halogenoalkyl refers to a C 1 -C 8 -alkyl group as defined above in which one or more hydrogen atoms are replaced with halogen atoms that may be the same or different. Typically, C 1 -C 8 -halogenoalkyl comprises up to 9 halogen atoms that can be the same or different. “C 1 -C 8 - halogenoalkyl having 1 to 5 halogen atoms” as used herein refers to a C 1 -C 8 -alkyl group as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 2 -C 8 -halogenoalkenyl refers to a C 2 -C 8 -alkenyl group as defined above in which one or more hydrogen atoms are replaced with one or more halogen atoms that may be the same or different.
• C 2 -C 8 -halogenoalkenyl comprises up to 9 halogen atoms that can be the same or different.
• C 2 -C 8 -halogenoalkynyl refers to a C 2 -C 8 -alkynyl group as defined above in which one or more hydrogen atoms are replaced with one or more halogen atoms that may be the same or
• C 2 -C 8 -halogenoalkynyl comprises up to 9 halogen atoms that can be the same or different.
• C 1 -C 4 -hydroxyalkyl refers to a C 1 -C 4 -alkyl group as defined above in which at least one hydrogen atom is replaced with a hydroxyl group.
• C 1 -C 4 -hydroxyalkyl examples include but are not limited to hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl and 1,3-dihydroxypropan-2-yl.
• C 1 -C 8 -cyanoalkyl refers to a C 1 -C 8 -alkyl group as defined above in which at least one hydrogen atom is replaced with a cyano group.
• C 1 -C 8 -alkoxy refers to a group of formula (C 1 -C 8 -alkyl)-O-, in which the term “C 1 -C 8 -alkyl” is as defined herein.
• C 1 -C 8 -alkoxy examples include but are not limited to methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, n-hexyloxy, 1-methylpentoxy, 2-methylpentoxy, 3- methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2- trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2
• C 1 -C 8 -halogenoalkoxy refers to a C 1 -C 8 -alkoxy group as defined above in which one or more hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkoxy having 1 to 5 halogen atoms refers to a C 1 -C 8 -alkoxy group as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkoxy examples include but are not limited to chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2- chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and 1,1,1-trifluoroprop-2-oxy.
• C 1 -C 8 -alkylsulfanyl refers to a saturated, linear or branched group of formula (C 1 -C 8 -alkyl)-S-, in which the term “C 1 -C 8 -alkyl” is as defined herein.
• C 1 -C 8 -alkylsulfanyl examples include but are not limited to methylsulfanyl, ethylsulfanyl, propylsulfanyl, isopropylsulfanyl, butylsulfanyl, sec-butylsulfanyl, isobutylsulfanyl, tert-butylsulfanyl, pentylsulfanyl, isopentylsulfanyl, hexylsulfanyl group.
• C 1 -C 8 -halogenoalkylsulfanyl having 1 to 5 halogen atoms refers to a C 1 -C 8 - alkylsulfanyl as defined above in which 1 to 5 hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 - alkylsulfinyl include but are not limited to saturated, straight-chain or branched alkylsulfinyl radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms, for example (but not limited to) methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1-methylpropyl- sulfinyl, 2-methylpropylsulfinyl, 1,1-dimethylethylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl, 2- methylbutylsulfinyl, 3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, 1,1- dimethylprop
• C 1 -C 8 -halogenoalkylsulfinyl having 1 to 5 halogen atoms refers to a C 1 -C 8 - alkylsulfinyl as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 - alkylsulfonyl examples include but are not limited to methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methyl- ethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1,1- dimethylethylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3- methylbutylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, hexylsulfonyl, 1-methylpentylsulfonyl,
• C 1 -C 8 -halogenoalkylsulfonyl having 1 to 5 halogen atoms refers to a C 1 -C 8 - alkylsulfonyl as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkylsulfonylamino having 1 to 5 halogen atoms refers to a C 1 - C 8 -alkylsulfonylamino as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -alkylsulfamoyl refers to a sulfamoyl radical having one C 1 -C 8 -alkyl group as defined herein.
• di-(C 1 -C 8 -alkyl)sulfamoyl refers to a sulfamoyl radical having two independently selected C 1 -C 8 -alkyl groups as defined herein.
• C 1 -C 8 -alkylcarbamoyl refers to a carbamoyl radical having one C 1 -C 8 -alkyl group as defined herein.
• di-(C 1 -C 8 -alkyl)carbamoyl refers to a carbamoyl radical having two independently selected C 1 -C 8 -alkyl groups as defined herein.
• C 1 -C 8 -halogenoalkylcarbonyl having 1 to 5 halogen atoms refers to a C 1 -C 8 - alkylcarbonyl as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkylcarbonyloxy having 1 to 5 halogen atoms refers to a C 1 - C 8 -alkylcarbonyloxy as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkylcarbonylamino having 1 to 5 halogen atoms refers to a C 1 - C 8 -alkylcarbonylamino as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkoxycarbonylamino having 1 to 5 halogen atoms refers to a C 1 -C 8 -alkoxycarbonylamino as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -halogenoalkoxycarbonyl having 1 to 5 halogen atoms refers to a C 1 -C 8 - alkoxycarbonyl as defined above in which one to five hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 1 -C 8 -alkylamino refers to an amino radical having one C 1 -C 8 -alkyl group as defined herein.
• C 1 -C 8 -alkylamino examples include but are not limited to N-methylamino, N- ethylamino, N-isopropylamino, N-n-propylamino, N-isopropylamino and N-tert-butylamino.
• di-(C 1 -C 8 -alkyl)amino refers to an amino radical having two independently selected C 1 -C 8 -alkyl groups as defined herein.
• di-(C 1 -C 8 -alkyl)amino examples include but are not limited to N,N-dimethylamino, N,N-diethylamino, N,N-diisopropylamino, N-ethyl-N-methylamino, N- methyl-N-n-propylamino, N-isopropyl-N-n-propylamino and N-tert-butyl-N-methylamino.
• N-(C 1 -C 8 -alkyl)-N-(C 3 -C 7 -cycloalkyl)amino refers to a N,N-disubstituted amino radical having one C 1 -C 8 -alkyl group as defined herein and one C 3 -C 7 -cycloalkyl group as defined herein.
• non-aromatic C 3 -C 12 -carbocycle or “C 3 -C 12 -carbocycle” as used herein refers to a non- aromatic, saturated or partially unsaturated, hydrocarbon ring system in which all of the ring members, which vary from 3 to 12, are carbon atoms.
• the ring system may be monocyclic or polycyclic (fused, spiro or bridged).
• Non-aromatic C 3 -C 12 -carbocycles include but are not limited to C 3 -C 12 -cycloalkyl (mono or bicyclic), C 3 -C 12 -cycloalkenyl (mono or bicyclic), bicyclic system comprising an aryl (e.g. phenyl) fused to a monocyclic C 3 -C 7 -cycloalkyl (e.g. tetrahydronaphthalenyl, indanyl), bicyclic system comprising an aryl (e.g.
• phenyl fused to a monocyclic C 3 -C 8 -cycloalkenyl (e.g. indenyl, dihydronaphthalenyl) and tricyclic system comprising a cyclopropyl connected through one carbon atom to a bicyclic system comprising an aryl (e.g. phenyl) fused to a monocyclic C 3 -C 7 -cycloalkyl or to a monocyclic C 3 -C 8 -cycloalkenyl.
• the non-aromatic C 3 -C 12 -carbocycle can be attached to the parent molecular moiety through any carbon atom.
• C 3 -C 12 -cycloalkyl refers to a saturated, monovalent, mono- or bicyclic hydrocarbon ring which contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms.
• C 3 -C 7 -cycloalkyl designates monocyclic C 3 -C 7 -cycloalkyls which include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
• C 3 -C 5 -cycloalkyl designates monocyclic C 3 -C 5 -cycloalkyls
• bicyclic C 6 -C 12 -cycloalkyls include but are not limited to bicyclo[3.1.1]heptane, bicyclo[2.2.1 ]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, bicyclo[4.2.0]octyl, octahydropentalenyl and bicyclo[4.2.1 ]nonane.
• C 3 -C 7 -halogenocycloalkyl having 1 to 5 halogen atoms refers to a C 3 -C 7 - cycloalkyl group as defined above in which 1 to 5 hydrogen atoms are replaced with halogen atoms that may be the same or different.
• C 3 -C 7 -cycloalkylsulfanyl refers to a group of formula (C 3 -C 7 -cycloalkyl)-S-, in which the term "C 3 -C 7 -cycloalkyl” is as defined herein.
• C 3 -C 7 -cycloalkylcarbamoyl refers to a carbamoyl radical having one C 3 -C 7 - cycloalkyl group as defined herein.
• N-(C 1 -C 8 -alkyl)-N-(C 3 -C 7 -cycloalkyl)carbamoyl refers to a N,N-disubstituted carbamoyl radical having one C 1 -C 8 -alkyl group as defined herein and one C 3 -C 7 -cycloalkyl group as defined herein.
• C 3 -C 7 -cycloalkylamino refers to a (C 3 -C 7 -cycloalkyl)-NH-group, in which the term “C 3 -C 7 -cycloalkyl” is as defined herein.
• C 3 -C 7 -cycloalkylsulfamoyl refers to a sulfamoyl radical having one C 3 -C 7 - cycloalkyl group as defined herein.
• aromatic C 6 -C 14 -carbocycle or “aryl” as used herein refers to an aromatic hydrocarbon ring system in which all of the ring members, which vary from 6 to 14, preferably from 6 to 10, are carbon atoms.
• the ring system may be monocyclic or fused polycyclic (e.g. bicyclic or tricyclic).
• aryl examples include but are not limited to phenyl, azulenyl, naphthyl and fluorenyl.
• the aryl can be attached to the parent molecular moiety through any carbon atom. It is further understood that when said aryl group is substituted with one or more substituents, said substituent(s) may be at any positions on said aryl ring(s). Particularly, in the case of aryl being a phenyl group, said substituent(s) may occupy one or both ortho positions, one or both meta positions, or the para position, or any combination of these positions.
• non-aromatic 3- to 10-membered heterocycle refers to a non- aromatic, saturated or partially unsaturated non-aromatic ring system comprising 1 to 4, or 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. If the ring system contains more than one oxygen atoms, they are not directly adjacent.
• Non aromatic heterocycles include but are not limited to 3- to 7-membered monocyclic non-aromatic heterocycles and 6- to 10- membered polycyclic (e.g. bicyclic or tricyclic) non-aromatic heterocycles.
• non-aromatic 3- to 10- membered heterocycle can be connected to the parent molecular moiety through any carbon atom or nitrogen atom contained within the heterocycle.
• non-aromatic 3- to 7-membered monocyclic heterocycle refers to a 3-, 4-, 5-, 6- or 7-membered monocyclic ring system containing 1, 2 or 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur where the ring system is saturated or unsaturated but not aromatic.
• the heterocycle may comprise one to three nitrogen atoms, or one or two oxygen atoms, or one or two sulfur atoms, or one to three nitrogen atoms and one oxygen atom, or one to three nitrogen atoms and a sulfur atom or one sulfur atom and one oxygen atom.
• saturated non-aromatic heterocycles include but are not limited to 3-membered ring such as oxiranyl, aziridinyl, 4- membered ring such as azetidinyl, oxetanyl, thietanyl, 5-membered ring such as tetrahydrofuranyl, 1,3- dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, 6-membered ring such as piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazinanyl, hexahydrotriazin
• unsaturated non-aromatic hererocyles include but are not limited to 5-membered ring such as dihydrofuranyl, 1,3-dioxolyl, dihydrothienyl, pyrrolinyl, dihydroimidazolyl, dihydropyrazolyl, isoxazolinyl, dihydrooxazolyl, dihydrothiazolyl or 6-membered ring such as pyranyl, thiopyranyl, thiazinyl and thiadiazinyl.
• 5-membered ring such as dihydrofuranyl, 1,3-dioxolyl, dihydrothienyl, pyrrolinyl, dihydroimidazolyl, dihydropyrazolyl, isoxazolinyl, dihydrooxazolyl, dihydrothiazolyl or 6-membered ring such as pyranyl, thiopyranyl, thiazinyl and thiadiaziny
• Non-aromatic bicyclic heterocycles may consist of a monocyclic heteroaryl as defined herein fused to a monocyclic C 3 -C 7 -cycloalkyl, a monocyclic C 3 -C 8 -cycloalkenyl or a monocyclic non-aromatic heterocycle or may consist of a monocyclic non-aromatic heterocycle fused either to an aryl (e.g. phenyl), a monocyclic C 3 -C 7 -cycloalkyl, a monocyclic C 3 -C 8 -cycloalkenyl or a monocyclic non-aromatic heterocycle.
• aryl e.g. phenyl
• nitrogen atom may be at the bridgehead (e.g. 4,5,6,7- tetrahydropyrazolo[1,5-a]pyridinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridinyl, 5,6,7,8- tetrahydroimidazo[1,2-a]pyridinyl).
• Non-aromatic tricyclic heterocycles may consist of a monocyclic cycloalkyl connected through one common atom to a non-aromatic bicyclic heterocycle.
• aromatic 5- to 14-membered heterocycle or “heteroaryl” as used herein refers to an aromatic ring system comprising 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. If the ring system contains more than one oxygen atom, they are not directly adjacent.
• Aromatic heterocycles include aromatic 5- or 6-membered monocyclic heterocycles and 6- to 14- membered polycyclic (e.g. bicyclic or tricyclic) aromatic heterocycles.
• the 5- to 14-membered aromatic heterocycle can be connected to the parent molecular moiety through any carbon atom or nitrogen atom contained within the heterocycle.
• aromatic 5- or 6-membered monocyclic heterocycle or “monocyclic heteroaryl” as used herein refers to a 5- or 6-membered monocyclic ring system containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur.
• Examples of 5-membered monocyclic heteroaryl include but are not limited to furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, oxatriazolyl, isothiazolyl, thiazolyl, thiadiazolyl and thiatriazolyl.
• Examples of 6-membered monocyclic heteroaryl include but are not limited to pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl.
• 6- to 14-membered polycyclic aromatic heterocycle or “polycyclic heteroaryl” as used herein refers to a 6-, 7-, 8-, 9-, 10-, 11-,12-, 13- or 14-membered polycyclic (e.g. bicyclic or tricyclic) ring system containing 1, 2 or 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur.
• Aromatic bicyclic heterocycles may consist of a monocyclic heteroaryl as defined herein fused to an aryl (e.g. phenyl) or to a monocyclic heteroaryl.
• C 3 -C 7 -cycloalkyloxy designates a group of formula –O-R wherein R is a C 3 - C 7 -cycloalkyl as defined herein.
• the terms “-C 1 -C 8 -alkyl-aryl”, “-C 1 -C 8 -alkyl-heterocyclyl”, “-C 1 -C 8 -alkyl-heteroaryl” and “-C 1 -C 8 -alkyl- C 3 -C 7 -cycloalkyl” as used herein designate a group of formula “-C 1 -C 8 -alkyl-R”, wherein R is respectively an aryl, heterocyclyl, heteroaryl or a C 3 -C 7 -cycloalkyl as defined herein, “C 1 -C 8 -alkyl” is a saturated, branched or straight hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms and where
• substituents refers to a number of substituents that ranges from one to the maximum number of substituents possible based on the number of available bonding sites, provided that the conditions of stability and chemical feasibility are met.
• leaving group as used herein is to be understood as meaning a group which is displaced from a compound in a substitution or an elimination reaction, for example a halogen atom, a trifluoromethanesulfonate (“triflate”) group, alkoxy, methanesulfonate, p-toluenesulfonate, etc.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one or more R 1b substituents;
• R 3 is aryl or heteroaryl, wherein said aryl and heteroaryl may be substituted with one or more R 3b substituents ;
• R 1b is selected from the group consisting of halogen nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, pentafluoro- ⁇ 6 -sulfanyl, formyl, carbamoyl, carbamate, C 1 -C 8 -alkyl, C 3 -C 7 -cycloalkyl, C 1 -C 8 - halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 7 -halogenocycloalkyl having 1 to 5 halogen atoms,
• halogen atoms C 3 -C 7 -cycloalkylcarbonyl, C 1 -C 8 -alkylcarbamoyl, C 3 -C 7 -cycloalkylcarbamoyl, N-(C 1 -C 8 - alkyl)-N-(C 3 -C 7 -cycloalkyl)carbamoyl, di-(C 1 -C 8 -alkyl)carbamoyl, C 1 -C 8 -alkoxycarbonyl, C 1 -C 8 - halogenoalkoxycarbonyl having 1 to 5 halogen atoms, C 3 -C 7 -cycloalkoxycarbonyl, C 1 -C 8 - alkylcarbonyloxy, C 1 -C 8 -halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, C 3 -C 7 -cycloalkoxycarbonyl, C 1 -C 8 -
• the compounds of formula (I) can be used for controlling harmful microorganisms, in particular phytopathogenic fungi, in crop protection.
• the phytopathogenic fungi are selected from the group consisting of the Puccinia species, for example Puccinia recondita, Puccinia graminis or Puccinia striiformis; the Uromyces species, for example Uromyces appendiculatus; and the rust disease pathogens, in particular selected from the group consisting of the Gymnosporangium species, for example Gymnosporangium sabinae; Hemileia species, for example Hemileia vastatrix, and Phakopsora species, for example Phakopsora pachyrhizi or Phakopsora meibomiae.
• the Puccinia species for example Puccinia recondita, Puccinia graminis or Puccinia striiformis
• the Uromyces species for example Uromyces appendiculatus
• the rust disease pathogens in particular selected from the group consisting of the Gymnosporangium species, for
• the rust disease pathogens in particular Phakopsora pachyrhizi and Phakopsora meibomiae.
• the compounds of formula (I) can suitably be in their free form, salt form, N-oxide form or solvate form (e.g. hydrate).
• the compound of formula (I) may be present in the form of different stereoisomers. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. Accordingly, the invention encompasses both pure stereoisomers and any mixture of these isomers.
• a compound can be present in two or more tautomer forms in equilibrium, reference to the compound by means of one tautomeric description is to be considered to include all tautomer forms.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclobutyl ring, which is substituted with one R 1b substituent or substituted with two different R 1b substituents (for the purpose of differentiation marked here as R 1b and R 1b' )
• the compound of the formula (I) may be present in the form of the stereoisomer (I’) and/or in the form of the stereoisomer (I''):
• Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound.
• the invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions.
• the compound of formula (I) may be present in the form of the free compound and/or a salt thereof, such as an agrochemically active salt.
• Agrochemically active salts include acid addition salts of inorganic and organic acids well as salts of customary bases.
• inorganic acids are hydrohalic acids, such as hydrogen fluoride, hydrogen chloride, hydrogen bromide and hydrogen iodide, sulfuric acid, phosphoric acid and nitric acid, and acidic salts, such as sodium bisulfate and potassium bisulfate.
• Useful organic acids include, for example, formic acid, carbonic acid and alkanoic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid and propionic acid, and also glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, saturated or mono- or diunsaturated fatty acids having 6 to 20 carbon atoms, alkylsulfuric monoesters, alkylsulfonic acids (sulfonic acids having straight-chain or branched alkyl radicals having 1 to 20 carbon atoms), arylsulfonic acids or aryldisulfonic acids (aromatic radicals, such as phenyl and naphthyl, which bear one or two sulfonic acid groups), alkylphosphonic acids (phosphonic acids having straight-chain or branched alkyl radicals having 1 to 20 carbon atoms), arylphosphonic
• the compounds of the invention may exist in multiple crystalline and/or amorphous forms. Crystalline forms include unsolvated crystalline forms, solvates and hydrates. Solvates of the compounds of the invention or their salts are stoichiometric compositions of the compounds with solvents.
• Compounds of formula (I) are herein referred to as “active ingredient(s)”. In the above formula (I), X is preferably hydrogen.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 - C 5 -cycloalkyl (cyclopropyl, cyclobutyl or cyclopentyl) ring, wherein said C 3 -C 5 -cycloalkyl is substituted with one or more, preferably one to three, R 1b substituents.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents.
• the C 3 -C 5 -cycloalkyl, preferably cyclobutyl or cyclopropyl, is substituted with one to three, R 1b substituents selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 -
• alkylcarbonyloxy and C 1 -C 4 -halogenoalkylcarbonyloxy more preferably selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• the C 3 -C 5 -cycloalkyl preferably cyclobutyl or cyclopropyl
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one or two R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• R 3 is aryl or heteroaryl, wherein R 3 may be substituted with one or more, preferably one to three, R 3b substituents.
• R 3b substituents are preferably selected from the group consisting of halogen, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms and C 1 -C 4 - alkoxycarbonyl.
• R 3 is aryl, wherein R 3 may be substituted with one or more R 3b substituents.
• R 3 is heteroaryl, wherein R 3 may be substituted with one or more R 3b substituents.
• the heteroaryl is preferably selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl.
• R 3 is more preferably aryl selected from phenyl and naphthyl; or a heteroaryl selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl; wherein said aryl and heteroaryl may be substituted with one to three R 3b substituents, preferably independently selected from the group consisting of fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-
• R 3 is phenyl, wherein the phenyl may be substituted with one to three R 3b substituents.
• the R 3b substituents are independently selected from the group consisting of fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
• R 3 is more preferably phenyl, which is unsubstituted or substituted with one or two substituents independently selected from fluorine, chlorine, bromine, methyl and methoxy.
• R 3 is selected from phenyl and pyridine, wherein the phenyl and the pyridine may be substituted with one to three R 3b substituents, which are preferably independently selected from the group consisting of fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
• R 3 is more preferably phenyl, which is unsubstituted or substituted with one to three R 3b substituents independently selected from fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, iso-propyl, n- propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl, preferably unsubstituted or substituted with one or two substituents independently selected from fluorine, chlorine, bromine, methyl and methoxy.
• R 3 is phenyl, which is substituted with one or two fluorine atoms.
• compounds of the present invention are compounds of the formula (I) or salts, N-oxides or solvates thereof: wherein X is hydrogen or fluorine, R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one to three R 1b substituents, wherein the R 1b substituents are each independently selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 -alkylcarbonyloxy and C 1 -C 4 - halogenoalkyl
• R 3 is phenyl, naphthyl or a heteroaryl selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl; wherein said phenyl, naphthyl or heteroaryl may be substituted with one to three R 3b substituents independently selected from halogen, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1
• X is hydrogen.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents.
• the R 1b substituents are selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 - halogenoalkoxy, C 1 -C 4 -alkylcarbonyloxy and C 1 -C 4 -halogenoalkylcarbonyloxy, more preferably selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl ring, which is substituted with one or two R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• R 3 is phenyl or a 5- or 6-membered heteroaryl selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl.
• the phenyl, naphthyl or heteroaryl may be substituted with one to three R 3b substituents independently selected from the group consisting of chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
• the phenyl, naphthyl or heteroaryl is substituted with one or two fluorine atoms.
• X is hydrogen
• R 3 is phenyl or a 5- or 6-membered heteroaryl selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one or two R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• compounds of the present invention are compounds of the formula (I) or salts, N-oxides or solvates thereof: wherein X is hydrogen or fluorine, R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one or more R 1b substituents; R 3 is aryl, preferably naphthyl or phenyl, more preferably phenyl, wherein said aryl may be substituted with one or more R 3b substituents ; R 1b is selected from the group consisting of halogen nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, pentafluoro- ⁇ 6 -sulfanyl, formyl, carbamoyl, carbamate, C 1 -C 8 -alkyl, C 3 -C 7
• X is hydrogen.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one to three R 1b substituents, wherein the R 1b substituents are selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 - alkylcarbonyloxy and C 1 -C 4 -halogenoalkylcarbonyloxy and/or two geminal R 1b substituents form together a -O-(CH 2 ) 2 -O- or -O-(CH 2 ) 3 -O- group
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 - halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 -alkylcarbonyloxy and C 1 -C 4 - halogenoalkylcarbonyloxy, more preferably selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• R 3 is naphthyl or phenyl, preferably phenyl; wherein said naphthyl and phenyl may be substituted with one to three R 3b substituents independently selected from halogen, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms and C 1 - C 4 -alkoxycarbonyl.
• R 3 is phenyl, which may be substituted with one to three R 3b substituents independently selected from the group consisting of chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
• X is hydrogen
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy
• R 3 is phenyl, which may be substituted with one to three R 3b substituents independently selected from the group consisting of chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and
• R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one or more R 1b substituents;
• R 3 is heteroaryl, preferably a 5- or 6-membered heteroaryl, wherein said heteroaryl may be substituted with one or more R 3b substituents;
• R 1b is selected from the group consisting of halogen nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, pentafluoro- ⁇ 6 -sulfanyl, formyl, carbamoyl, carbamate, C 1 -C 8 -alkyl, C 3 -C 7 -cycloalkyl, C 1 -C 8 - halogenoalkyl having 1 to 5 halogen atoms, C 3 -C 7 -halogenocycloalkyl
• X is hydrogen.
• R 1 and R 2 form, together with the carbon atom to which they are linked, a C 3 -C 5 -cycloalkyl wherein said C 3 -C 5 -cycloalkyl is substituted with one to three R 1b substituents, wherein the R 1b substituents are selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 - alkylcarbonyloxy and C 1 -C 4 -halogenoalkylcarbonyloxy and/or two geminal R 1b substituents form together a -O-(CH 2 ) 2 -O- or -O-(CH 2 ) 3 -O- group
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 - halogenoalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy, C 1 -C 4 -alkylcarbonyloxy and C 1 -C 4 - halogenoalkylcarbonyloxy, more preferably one or two R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy.
• R 3 is a heteroaryl selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl, wherein said heteroaryl may be substituted with one to three R 3b substituents, preferably independently selected from the group consisting of halogen, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 - cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1
• R 3 is a 5- or 6-membered heteroaryl, preferably selected from the group consisting of furyl (furanyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl, wherein said heteroaryl may be substituted with one to three R 3b substituents, preferably independently selected from the group consisting of halogen, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogeno
• X is hydrogen
• R 1 and R 2 form, together with the carbon atom to which they are linked, a cyclopropyl or cyclobutyl ring, which is substituted with one to three R 1b substituents selected from the group consisting of fluorine, hydroxy, methyl, ethyl, trifluoromethyl, methoxy and acetyloxy
• R 3 is pyridinyl, which may be substituted with one to three R 3b substituents independently selected from the group consisting of chlorine, bromine, nitro, cyano, methyl, ethyl, iso-propyl, n-propyl, n-butyl, iso-butyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbony
• compounds of the formula (I) selected from the group consisting of N-[3,3-difluoro-1-(2-fluorophenyl)cyclobutyl]-5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin-2- amine, 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[3-fluoro-1-(2-fluorophenyl)cyclobutyl]pyrimidin-2- amine (cis stereoisomer), 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(2-fluorophenyl)-3-methyl-cyclobutyl]pyrimidin-2- amine (cis stereoisomer), 3-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl]amino]
• the compounds of formula (I) are useful for controlling harmful microorganisms, in particular phytopathogenic fungi, in crop protection (use as fungicide).
• the present invention relates to the use of the compounds of formula (I) for controlling harmful microorganisms, preferably phytopathogenic fungi, in crop protection.
• the present invention also relates to any compounds of formula (I) disclosed in Table 1.
• Intermediates for the preparation of the active ingredients The present invention also relates to intermediates for the preparation of compounds of formula (I). Unless indicated otherwise, the radicals and indices X, R 1 , R 2 and R 3 have the meanings given above for the compounds of formula (I).
• the present invention relates to compounds of formula (II) as well as their acceptable salts, N-oxides or solvates: wherein X, R 1 , R 2 and R 3 have the meanings given above for the compounds of formula (I).
• Processes for the preparation of compounds of formula (I) and intermediates The present invention relates to processes for the preparation of compounds of formula (I) and their intermediates. Unless indicated otherwise, the radicals and indices X, R 1 , R 2 and R 3 have the meanings given above for the compounds of formula (I). These definitions apply not only to the end products of formula (I) but also to all intermediates.
• Compounds of formula (I) can be prepared, according to process P1, by reacting intermediates of formula (II) with a dehydrating agent, such as methyl N-(triethylammoniumsulfonyl)carbamate (Burgess reagent), in a suitable solvent such as tetrahydrofurane, as previously described in WO2017065473.
• a dehydrating agent such as methyl N-(triethylammoniumsulfonyl)carbamate (Burgess reagent)
• a suitable solvent such as tetrahydrofurane
• Process P1 Intermediates of formula (II) can be commercially available or can be prepared according to process P2, by reacting carbohydrazides of formula (III) with compounds of the formula (IVa) or (IVb) (which are either commercially available or may be prepared starting from readily available compounds according to known procedures) in a suitable solvent such as tetrahydrofurane optionally in presence of a base such as triethylamine, preferably at room temperature, as previously described in WO2017065473.
• a suitable solvent such as tetrahydrofurane
• a base such as triethylamine
• Process P2 Carbohydrazides of formula (III) can be commercially available or can be prepared, according to process P3, by reacting a compound of formula (V), wherein LG1 is a leaving group, as for example ethoxy, with hydrazine hydrate in a suitable solvent such as ethanol, as previously described in WO2017065473.
• Process P3 Compounds of formula (V) can be commercially available or may be prepared starting from readily available compounds according to known procedures.
• compounds of formula (V), can be prepared, according to process P4, by reacting a compound of formula (VI), wherein LG1 is an alkoxy like for example ethoxy and wherein LG2 is a leaving group like for example chlorine by nucleophilic substitution with a compound of formula (VII) (as described for example in European Journal of Medicinal Chemistry, 135, 531-543; 2017 or Bioorganic & Medicinal Chemistry, 25(17), 4553-4559; 2017) optionally in presence of a base (like for example N,N- diisopropylethylamine) or an acid (like for example p-toluenesulfonic acid) in a solvent such as for example dichloromethane or 1,4-dioxane.
• a base like for example N,N- diisopropylethylamine
• an acid like for example p-toluenesulfonic acid
• Process P4 Compounds of formula (VI) can be commercially available or may be prepared starting from readily available compounds according to known procedures. Compounds of formula (VII) can be commercially available or may be prepared starting from readily available compounds according to known procedures. Alternatively, carbohydrazides of formula (III) can be prepared, according to process P5, by reacting a compound of formula (VIII) with an acid such as trifluoroacetic acid in a suitable solvent such as dichloromethane, preferably at room temperature, as previously described in Bioorganic & Medicinal Chemistry, 20(1), 487-497; 2012.
• Process P5 Compounds of formula (VIII) can be commercially available or may be prepared, according to process P6, by reacting an acid of formula (IX) with tert-butyl carbazate in presence of a coupling agent like for example (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluoro- phosphate (HATU) or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC ⁇ HCl), in a suitable solvent such as dichloromethane, optionally in presence of a base such as N,N- diisopropylethylamine, as previously described in Tetrahedron, 58(27), 5513-5523; 2002.
• a coupling agent like for example (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridin
• Process P6 Compounds of formula (IX) can be commercially available or may be prepared starting from readily available compounds according to known procedures.
• intermediates of formula (II) can be prepared according to process P7, by reacting a compound of formula (V), wherein LG1 is a leaving group as for example chlorine with 2,2- difluoroacetohydrazide or 2,2,2-trifluoroacetohydrazide in a suitable solvent such as tetrahydrofuran, acetonitrile or dichloromethane, optionally in presence of a base such as triethylamine, preferably at – 60 °C, 0 °C or at room temperature, as previously described in Russian Journal of Organic Chemistry, 43(11), 1686-1695; 2007 or Yingyong Huaxue, 13(5), 5-9; 1996.
• a base such as triethylamine
• 2,2-Difluoroacetohydrazide and 2,2,2-trifluoroacetohydrazide are commercially available or may be prepared, according to known processes, as previously described in Synlett, (12), 1939-1941; 2005, Journal of Organic Chemistry, 78(16), 8054-8064; 2013, Chemistry of Heterocyclic Compounds (New York, NY, United States), 52(2), 133-139; 2016 or WO 2018233633.
• compounds of formula (I) can be prepared, according to process P8, from a compound of formula (X), wherein LG3 is a leaving group by nucleophilic substitution with a compound of formula (VII) (as described for example in European Journal of Medicinal Chemistry, 135, 531-543; 2017 or WO2017065473) optionally in presence of a base (like for example triethylamine) or an acid (like for example p-toluenesulfonic acid) in a solvent such as for example dichloromethane or 1,4-dioxane. It may be necessary to activate the leaving group for example by oxidation with 3-chloroperbenzoic acid when LG3 is SMe.
• a base like for example triethylamine
• an acid like for example p-toluenesulfonic acid
• solvent such as for example dichloromethane or 1,4-dioxane. It may be necessary to activate the leaving group for example by oxidation with 3-chloro
• Process P8 Compounds of formula (X) can be commercially available or may be prepared starting from readily available compounds analogously to process P1 and P2 or P3 and P4 or P7.
• compounds of formula (I) can be prepared, according to process P9, by reacting a compound of formula (XI) with C 1 -C 3 -haloalkylacetic anhydride (which is either commercially available or may be prepared starting from readily available compounds according to known procedures) in a suitable solvent such as dichloromethane, preferably at 0 °C, as previously described in WO2018165520.
• Process P9 Compounds of formula (XI) can be prepared, according to process P10, by reacting a compound of formula (XII) with an azide source such as sodium azide in a suitable solvent such as N,N- dimethylformamide, optionally in presence of a salt such as ammonium chloride and/or lithium chloride preferably at 95 °C, as previously described in WO2018165520.
• an azide source such as sodium azide
• a suitable solvent such as N,N- dimethylformamide
• a salt such as ammonium chloride and/or lithium chloride preferably at 95 °C, as previously described in WO2018165520.
• Process P10 Compounds of formula (XII) can be prepared, according to process P11, by reacting a compound of formula (XIII) wherein LG4 is a leaving group by nucleophilic substitution such as chlorine with a compound of formula (VII) (as previously described in WO2018165520) optionally in presence of a base (like for example triethylamine) or an acid (like for example p-toluenesulfonic acid) in a solvent such as for example ethanol, dichloromethane or 1,4-dioxane.
• a base like for example triethylamine
• an acid like for example p-toluenesulfonic acid
• solvent such as for example ethanol, dichloromethane or 1,4-dioxane.
• Process P11 Compounds of formula (XIII) can be commercially available or may be prepared starting from readily available compounds according to known procedures.
• processes P1 to P11 can be performed if appropriate in the presence of a solvent and if appropriate in the presence of a base.
• Suitable solvents for carrying out processes P1 to P11 according to the invention are customary inert organic solvents. Preference is given to using optionally halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin ; chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane ; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran
• Suitable bases for carrying out processes P1 to P11 according to the invention are inorganic and organic bases which are customary for such reactions.
• alkaline earth metal alkali metal hydride, alkali metal hydroxides or alkali metal alkoxides, such as sodium hydroxide, sodium hydride, calcium hydroxide, potassium hydroxide, potassium tert-butoxide or other ammonium hydroxide
• alkali metal carbonates such as sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, cesium carbonate
• alkali metal or alkaline earth metal acetates such as sodium acetate, potassium acetate, calcium acetate and also tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, N-methylpiperidine, N,N-dimethyl- aminopyridine, 1,4-diazabicyclo
• the reaction temperature can independently be varied within a relatively wide range.
• processes according to the invention are carried out at temperatures between -20°C and 160°C.
• a way to control the temperature for the processes is to use microwave technology.
• Processes P1 to P11 according to the invention are generally independently carried out under atmospheric pressure. However, it is also possible to operate under elevated or reduced pressure. Work-up is carried out by customary methods. Generally, the reaction mixture is treated with water and the organic phase is separated off and, after drying, concentrated under reduced pressure. If appropriate, the remaining residue can be freed by customary methods, such as chromatography or recrystallization, from any impurities that can still be present.
• compositions and formulations The present invention further relates to compositions, in particular compositions for controlling unwanted microorganisms.
• the composition may be applied to the microorganisms and/or in their habitat.
• the composition comprises at least one compound of the invention and at least one agriculturally suitable auxiliary, e.g. carrier(s) and/or surfactant(s).
• a carrier is a solid or liquid, natural or synthetic, organic or inorganic substance that is generally inert.
• the carrier generally improves the application of the compounds, for instance, to plants, plants parts or seeds.
• suitable solid carriers include, but are not limited to, ammonium salts, in particular ammonium sulfates, ammonium phosphates and ammonium nitrates, natural rock flours, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, silica gel and synthetic rock flours, such as finely divided silica, alumina and silicates.
• typically useful solid carriers for preparing granules include, but are not limited to crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, synthetic granules of inorganic and organic flours and granules of organic material such as paper, sawdust, coconut shells, maize cobs and tobacco stalks.
• suitable liquid carriers include, but are not limited to, water, organic solvents and combinations thereof.
• suitable solvents include polar and nonpolar organic chemical liquids, for example from the classes of aromatic and nonaromatic hydrocarbons (such as cyclohexane, paraffins, alkylbenzenes, xylene, toluene, tetrahydronaphthalene, alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride), alcohols and polyols (which may optionally also
• esters including fats and oils
• (poly)ethers unsubstituted and substituted amines, amides (such as dimethylformamide or fatty acid amides) and esters thereof, lactams (such as N-alkylpyrrolidones, in particular N-methylpyrrolidone) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide), oils of vegetable or animal origin.
• the carrier may also be a liquefied gaseous extender, i.e. liquid which is gaseous at standard temperature and under standard pressure, for example aerosol propellants such as halohydrocarbons, butane, propane, nitrogen and carbon dioxide.
• aerosol propellants such as halohydrocarbons, butane, propane, nitrogen and carbon dioxide.
• Preferred solid carriers are selected from clays, talc and silica.
• Preferred liquid carriers are selected from water, fatty acid amides and esters thereof, aromatic and nonaromatic hydrocarbons, lactams and carbonic acid esters.
• the amount of carrier typically ranges from 1 to 99.99%, preferably from 5 to 99.9%, more preferably from 10 to 99.5%, and most preferably from 20 to 99% by weight of the composition.
• Liquid carriers are typically present in a range of from 20 to 90%, for example 30 to 80% by weight of the composition. Solid carriers are typically present in a range of from 0 to 50%, preferably 5 to 45%, for example 10 to 30% by weight of the composition. If the composition comprises two or more carriers, the outlined ranges refer to the total amount of carriers.
• the surfactant can be an ionic (cationic or anionic), amphoteric or non-ionic surfactant, such as ionic or non-ionic emulsifier(s), foam former(s), dispersant(s), wetting agent(s), penetration enhancer(s) and any mixtures thereof.
• surfactants include, but are not limited to, salts of polyacrylic acid, salts of lignosulfonic acid (such as sodium lignosulfonate), salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene oxide and/or propylene oxide with fatty alcohols, fatty acids or fatty amines (for example, polyoxyethylene fatty acid esters such as castor oil ethoxylate, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers), substituted phenols (preferably alkylphenols or arylphenols) and ethoxylates thereof (such as tristyrylphenol ethoxylate), salts of sulfosuccinic esters, taurine derivatives (preferably alkyl taurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty esters of polyols (such a fatty acid esters of g,
• Preferred surfactants are selected from polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty acid esters, alkylbenzene sulfonates, such as calcium dodecylbenzenesulfonate, castor oil ethoxylate, sodium lignosulfonate and arylphenol ethoxylates, such as tristyrylphenol ethoxylate.
• the amount of surfactants typically ranges from 5 to 40%, for example 10 to 20%, by weight of the composition.
• auxiliaries include water repellents, siccatives, binders (adhesive, tackifier, fixing agent, such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, natural phospholipids such as cephalins and lecithins and synthetic phospholipids, polyvinylpyrrolidone and tylose), thickeners and secondary thickeners (such as cellulose ethers, acrylic acid derivatives, xanthan gum, modified clays, e.g. the products available under the name Bentone, and finely divided silica), stabilizers (e.g.
• auxiliaries mineral and vegetable oils, perfumes, waxes, nutrients (including trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, sequestering agents and complex formers.
• the choice of the auxiliaries depends on the intended mode of application of the compound of the invention and/or on the physical properties of the compound(s).
• the auxiliaries may be chosen to impart particular properties (technical, physical and/or biological properties) to the compositions or use forms prepared therefrom. The choice of auxiliaries may allow customizing the compositions to specific needs.
• composition of the invention may be provided to the end user as ready-for-use formulation, i.e. the compositions may be directly applied to the plants or seeds by a suitable device, such as a spraying or dusting device.
• a suitable device such as a spraying or dusting device.
• the compositions may be provided to the end user in the form of concentrates which have to be diluted, preferably with water, prior to use.
• the composition of the invention can be prepared in conventional manners, for example by mixing the compound of the invention with one or more suitable auxiliaries, such as disclosed herein above.
• the composition comprises a fungicidally effective amount of the compound(s) of the invention.
• the term "effective amount” denotes an amount, which is sufficient for controlling harmful fungi on cultivated plants or in the protection of materials and which does not result in a substantial damage to the treated plants. Such an amount can vary in a broad range and is dependent on various factors, such as the fungal species to be controlled, the treated cultivated plant or material, the climatic conditions and the specific
• the composition according to the invention contains from 0.01 to 99% by weight, preferably from 0.05 to 98% by weight, more preferred from 0.1 to 95% by weight, even more preferably from 0.5 to 90% by weight, most preferably from 1 to 80% by weight of the compound of the invention. It is possible that a composition comprises two or more compounds of the invention. In such case the outlined ranges refer to the total amount of compounds of the present invention.
• the composition of the invention may be in any customary composition type, such as solutions (e.g. aqueous solutions), emulsions, water- and oil-based suspensions, powders (e.g. wettable powders, soluble powders), dusts, pastes, granules (e.g.
• soluble granules, granules for broadcasting suspoemulsion concentrates, natural or synthetic products impregnated with the compound of the invention, fertilizers and also microencapsulations in polymeric substances.
• the compound of the invention may be present in a suspended, emulsified or dissolved form.
• suitable composition types are solutions, water-soluble concentrates (e.g. SL, LS), dispersible concentrates (DC), suspensions and suspension concentrates (e.g. SC, OD, OF, FS), emulsifiable concentrates (e.g. EC), emulsions (e.g. EW, EO, ES, ME, SE), capsules (e.g.
• compositions types are defined by the Food and Agriculture Organization of the United Nations (FAO). An overview is given in the "Catalogue of pesticide formulation types and international coding system", Technical Monograph No.2, 6th Ed. May 2008, CropLife International.
• the composition of the invention is in form of one of the following types: EC, SC, FS, SE, OD and WG, more preferred EC, SC, OD and WG. Further details about examples of composition types and their preparation are given below. If two or more compounds of the invention are present, the outlined amount of compound of the invention refers to the total amount of compounds of the present invention. This applies mutatis mutandis for any further component of the composition, if two or more representatives of such component, e.g. wetting agent, binder, are present. i) Water-soluble concentrates (SL, LS) 10-60 % by weight of at least one compound of the invention and 5-15 % by weight surfactant (e.g.
• polyoxyethylene fatty alcohol ether are dissolved in such amount of water and/or water-soluble solvent (e.g. alcohols such as propylene glycol or carbonates such as propylene carbonate) to result in a total amount of 100 % by weight.
• water-soluble solvent e.g. alcohols such as propylene glycol or carbonates such as propylene carbonate
• Dispersible concentrates 5-25 % by weight of at least one compound of the invention and 1-10 % by weight surfactant and/or binder (e.g. polyvinylpyrrolidone) are dissolved in such amount of organic solvent (e.g. cyclohexanone) to result in a total amount of 100 % by weight. Dilution with water gives a dispersion.
• Emulsifiable concentrates EC 15-70 % by weight of at least one compound of the invention and 5-10 % by weight surfactant (e.g.
• Emulsions EW, EO, ES 5-40 % by weight of at least one compound of the invention and 1-10 % by weight surfactant (e.g. a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate) are dissolved in 20-40 % by weight water- insoluble organic solvent (e.g. aromatic hydrocarbon).
• water-insoluble organic solvent e.g. aromatic hydrocarbon or fatty acid amide
• SC, FS Water-based
• surfactant e.g. sodium lignosulfonate and polyoxyethylene fatty alcohol ether
• thickener e.g. xanthan gum
• the water is added in such amount to result in a total amount of 100 % by weight. Dilution with water gives a stable suspension of the active substance.
• binder e.g. polyvinylalcohol
• 20-60 % by weight of at least one compound of the invention are comminuted with addition of 2-10 % by weight surfactant (e.g. sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1-2 % by weight thickener (e.g.
• modified clay in particular Bentone, or silica
• organic carrier to give a fine active substance oil suspension.
• the organic carrier is added in such amount to result in a total amount of 100 % by weight. Dilution with water gives a stable dispersion of the active substance.
• Water-dispersible granules and water-soluble granules (WG, SG) 50-80 % by weight of at least one compound of the invention are ground finely with addition of surfactant (e.g. sodium lignosulfonate and polyoxyethylene fatty alcohol ether) and converted to water-dispersible or water-soluble granules by means of technical appliances (e. g. extrusion, spray tower, fluidized bed).
• the surfactant is used in such amount to result in a total amount of 100 % by weight. Dilution with water gives a stable dispersion or solution of the active substance.
• Water-dispersible powders and water-soluble powders (WP, SP, WS) 50-80 % by weight of at least one compound of the invention are ground in a rotor-stator mill with addition of 1-8 % by weight surfactant (e.g. sodium lignosulfonate, polyoxyethylene fatty alcohol ether) and such amount of solid carrier, e.g. silica gel, to result in a total amount of 100 % by weight. Dilution with water gives a stable dispersion or solution of the active substance.
• surfactant e.g. sodium lignosulfonate, polyoxyethylene fatty alcohol ether
• solid carrier e.g. silica gel
• Gel (GW, GF) In an agitated ball mill, 5-25 % by weight of at least one compound of the invention are comminuted with addition of 3-10 % by weight surfactant (e.g. sodium lignosulfonate), 1-5 % by weight binder (e.g. carboxymethylcellulose) and such amount of water to result in a total amount of 100 % by weight. This results in a fine suspension of the active substance. Dilution with water gives a stable suspension of the active substance.
• surfactant e.g. sodium lignosulfonate
• binder e.g. carboxymethylcellulose
• Microcapsules An oil phase comprising 5-50 % by weight of at least one compound of the invention, 0-40 % by weight water-insoluble organic solvent (e.g. aromatic hydrocarbon), 2-15 % by weight acrylic monomers (e.g.
• methylmethacrylate, methacrylic acid and a di- or triacrylate are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol). Radical polymerization initiated by a radical initiator results in the formation of poly(meth)acrylate microcapsules.
• a protective colloid e.g. polyvinyl alcohol
• an oil phase comprising 5-50 % by weight of at least one compound of the invention, 0-40 % by weight water-insoluble organic solvent (e.g. aromatic hydrocarbon), and an isocyanate monomer (e.g. diphenylmethene-4,4'-diisocyanatae) are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol).
• a polyamine e.g.
• hexamethylenediamine results in the formation of polyurea microcapsules.
• the monomers amount to 1-10 % by weight of the total CS composition.
• Dustable powders (DP, DS) 1-10 % by weight of at least one compound of the invention are ground finely and mixed intimately with such amount of solid carrier, e.g. finely divided kaolin, to result in a total amount of 100 % by weight.
• Granules (GR, FG) 0.5-30 % by weight of at least one compound of the invention are ground finely and associated with such amount of solid carrier (e.g. silicate) to result in a total amount of 100 % by weight. Granulation is achieved by extrusion, spray-drying or the fluidized bed.
• Ultra-low volume liquids 1-50 % by weight of at least one compound of the invention are dissolved in such amount of organic solvent, e.g. aromatic hydrocarbon, to result in a total amount of 100 % by weight.
• the compositions types i) to xiii) may optionally comprise further auxiliaries, such as 0.1-1 % by weight preservatives, 0.1-1 % by weight antifoams, 0.1-1 % by weight dyes and/or pigments, and 5-10% by weight antifreezes.
• the compound and the composition of the invention can be mixed with other active ingredients like fungicides, bactericides, acaricides, nematicides, insecticides, biological control agents or herbicides. Mixtures with fertilizers, growth regulators, safeners, nitrification inhibitors, semiochemicals and/or other agriculturally beneficial agents are also possible. This may allow to broaden the activity spectrum or to prevent development of resistance. Examples of known fungicides, insecticides, acaricides, nematicides and bactericides are disclosed in the Pesticide Manual, 17th Edition.
• fungicides which could be mixed with the compound and the composition of the invention are: 1) Inhibitors of the ergosterol biosynthesis, for example (1.001) cyproconazole, (1.002) difenoconazole, (1.003) epoxiconazole, (1.004) fenhexamid, (1.005) fenpropidin, (1.006) fenpropimorph, (1.007) fenpyrazamine, (1.008) fluquinconazole, (1.009) flutriafol, (1.010) imazalil, (1.011) imazalil sulfate, (1.012) ipconazole, (1.013) metconazole, (1.014) myclobutanil, (1.015) paclobutrazol, (1.016) prochloraz, (1.017) propiconazole, (1.018) prothioconazole, (1.019) pyrisoxazole, (1.020) spiroxamine, (1.021) tebucon
• Inhibitors of the respiratory chain at complex I or II for example (2.001) benzovindiflupyr, (2.002) bixafen, (2.003) boscalid, (2.004) carboxin, (2.005) fluopyram, (2.006) flutolanil, (2.007) fluxapyroxad,
• Inhibitors of the respiratory chain at complex III for example (3.001) ametoctradin, (3.002) amisulbrom, (3.003) azoxystrobin, (3.004) coumethoxystrobin, (3.005) coumoxystrobin, (3.006) cyazofamid, (3.007) dimoxystrobin, (3.008) enoxastrobin, (3.009) famoxadone, (3.010) fenamidone, (3.011) flufenoxystrobin, (3.012) fluoxastrobin, (3.013) kresoxim-methyl, (3.014) metominostrobin, (3.015) orysastrobin, (3.016) picoxystrobin, (3.017) pyraclostrobin, (3.018) pyrametostrobin, (3.019) pyraoxystrobin, (3.020) trifloxystrobin, (3.021) (2E)-2- ⁇ 2-[( ⁇ [(1E)-1-(3- ⁇ [(E)
• Inhibitors of the mitosis and cell division for example (4.001) carbendazim, (4.002) diethofencarb, (4.003) ethaboxam, (4.004) fluopicolide, (4.005) pencycuron, (4.006) thiabendazole, (4.007) thiophanate- methyl, (4.008) zoxamide, (4.009) pyridachlometyl, (4.010) 3-chloro-5-(4-chlorophenyl)-4-(2,6- difluorophenyl)-6-methylpyridazine, (4.011) 3-chloro-5-(6-chloropyridin-3-yl)-6-methyl-4-(2,4,6- trifluorophenyl)pyridazine, (4.012) 4-(2-bromo-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl- 1H-pyrazol-5-amine, (4.013) 4-
• Compounds capable to induce a host defence for example (6.001) acibenzolar-S-methyl, (6.002) isotianil, (6.003) probenazole, (6.004) tiadinil.
• Inhibitors of the amino acid and/or protein biosynthesis for example (7.001) cyprodinil, (7.002) kasugamycin, (7.003) kasugamycin hydrochloride hydrate, (7.004) oxytetracycline, (7.005) pyrimethanil, (7.006) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline.
• Inhibitors of the ATP production for example (8.001) silthiofam.
• Inhibitors of the cell wall synthesis for example (9.001) benthiavalicarb, (9.002) dimethomorph, (9.003) flumorph, (9.004) iprovalicarb, (9.005) mandipropamid, (9.006) pyrimorph, (9.007) valifenalate, (9.008) (2E)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one, (9.009) (2Z)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one.
• Inhibitors of the lipid and membrane synthesis for example (10.001) propamocarb, (10.002) propamocarb hydrochloride, (10.003) tolclofos-methyl.
• Inhibitors of the melanin biosynthesis for example (11.001) tricyclazole, (11.002) tolprocarb.
• Inhibitors of the nucleic acid synthesis for example (12.001) benalaxyl, (12.002) benalaxyl-M (kiralaxyl), (12.003) metalaxyl, (12.004) metalaxyl-M (mefenoxam).
• Inhibitors of the signal transduction for example (13.001) fludioxonil, (13.002) iprodione, (13.003) procymidone, (13.004) proquinazid, (13.005) quinoxyfen, (13.006) vinclozolin.
• Compounds capable to act as an uncoupler for example (14.001) fluazinam, (14.002) meptyldinocap.
• fungicides selected from the group consisting of (15.001) abscisic acid, (15.002) benthiazole, (15.003) bethoxazin, (15.004) capsimycin, (15.005) carvone, (15.006) chinomethionat, (15.007) cufraneb, (15.008) cyflufenamid, (15.009) cymoxanil, (15.010) cyprosulfamide, (15.011) flutianil, (15.012) fosetyl- aluminium, (15.013) fosetyl-calcium, (15.014) fosetyl-sodium, (15.015) methyl isothiocyanate, (15.016) metrafenone, (15.017) mildiomycin, (15.018) natamycin, (15.019) nickel dimethyldithiocarbamate, (15.020) nitrothal-isopropyl, (15.021) oxamocarb, (15.022) oxathiapiprolin, (15.023)
• biological control is defined as control of harmful organisms such as a phytopathogenic fungi and/or insects and/or acarids and/or nematodes by the use or employment of a biological control agent.
• biological control agent is defined as an organism other than the harmful organisms and / or proteins or secondary metabolites produced by such an organism for the purpose of biological control. Mutants of the second organism shall be included within the definition of the biological control agent.
• mutant refers to a variant of the parental strain as well as methods for obtaining a mutant or variant in which the pesticidal activity is greater than that expressed by the parental strain.
• the ”parent strain“ is defined herein as the original strain before mutagenesis.
• the parental strain may be treated with a chemical such as N-methyl-N'-nitro-N-nitrosoguanidine, ethylmethanesulfone, or by irradiation using gamma, x-ray, or UV-irradiation, or by other means well known to those skilled in the art.
• Known mechanisms of biological control agents comprise enteric bacteria that control root rot by out-competing fungi for space on the surface of the root.
• Bacterial toxins such as antibiotics, have been used to control pathogens.
• the toxin can be isolated and applied directly to the plant or the bacterial species may be administered so it produces the toxin in situ.
• a ”variant is a strain having all the identifying characteristics of the NRRL or ATCC Accession Numbers as indicated in this text and can be identified as having a genome that hybridizes under conditions of high stringency to the genome of the NRRL or ATCC Accession Numbers.
• “Hybridization” refers to a reaction in which one or more polynucleotides react to form a complex that is stabilized via hydrogen bonding between the bases of the nucleotide residues.
• the hydrogen bonding may occur by Watson-Crick base pairing, Hoogstein binding, or in any other sequence-specific manner.
• the complex may comprise two strands forming a duplex structure, three or more strands forming a multi- stranded complex, a single self-hybridizing strand, or any combination of these.
• Hybridization reactions can be performed under conditions of different “stringency”. In general, a low stringency hybridization reaction is carried out at about 40 °C in 10 X SSC or a solution of equivalent ionic strength/temperature. A moderate stringency hybridization is typically performed at about 50 °C in 6 X SSC, and a high stringency hybridization reaction is generally performed at about 60 °C in 1 X SSC.
• a variant of the indicated NRRL or ATCC Accession Number may also be defined as a strain having a genomic sequence that is greater than 85%, more preferably greater than 90% or more preferably greater than 95% sequence identity to the genome of the indicated NRRL or ATCC Accession Number.
• a polynucleotide or polynucleotide region (or a polypeptide or polypeptide region) has a certain percentage (for example, 80%, 85%, 90%, or 95%) of “sequence identity” to another sequence means that, when
• NRRL is the abbreviation for the Agricultural Research Service Culture Collection, an international depositary authority for the purposes of deposing microorganism strains under the Budapest treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure, having the address National Center for Agricultural Utilization Research, Agricultural Research service, U.S. Department of Agriculture, 1815 North university Street, Peroira, Illinois 61604 USA.
• ATCC is the abbreviation for the American Type Culture Collection, an international depositary authority for the purposes of deposing microorganism strains under the Budapest treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure, having the address ATCC Patent Depository, 10801 University Boulevard., Manassas, VA 10110 USA.
• biological control agents which may be combined with the compound and the composition of the invention are: (A) Antibacterial agents selected from the group of: (A1) bacteria, such as (A1.1) Bacillus subtilis, in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661, U.S.
• DSM 10271 (available from Novozymes as TAEGRO ® or TAEGRO ® ECO (EPA Registration No.70127-5)); (A1.5) a Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297; (A1.6) Bacillus subtilis strain BU1814, (available as VELONDIS ® PLUS, VELONDIS ® FLEX and VELONDIS ® EXTRA from BASF SE); (A1.7) Bacillus mojavensis strain R3B (Accession No.
• NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC, a subsidiary of Mitsui & Co.;
• Bacillus subtilis CX-9060 from Certis USA LLC, a subsidiary of Mitsui & Co.;
• A1.9 Paenibacillus polymyxa, in particular strain AC-1 (e.g. TOPSEED ® from Green Biotech Company Ltd.);
• A1.10 Pseudomonas proradix (e.g. PRORADIX ® from Sourcon Padena);
• Pantoea agglomerans in particular strain E325 (Accession No. NRRL B-21856) (available as BLOOMTIME BIOLOGICAL TM FD BIOPESTICIDE from Northwest Agri Products); and
• (A2) fungi such as (A2.1) Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 ormixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR ® and BLOSSOM PROTECT ® from bio-ferm, CH); (A2.2) Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem); (A2.3) Saccharomyces cerevisiae, in particular strains CNCM No. I-3936, CNCM No. I-3937, CNCM No. I-3938 or CNCM No.
• B biological fungicides selected from the group of: (B1) bacteria, for example (B1.1) Bacillus subtilis, in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661 and described in U.S. Patent No. 6,060,051); (B1.2) Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No. NRRL B- 30087 and described in U.S. Patent No.
• Bacillus pumilus in particular strain GB34 (available as Yield Shield® from Bayer AG, DE);
• Bacillus amyloliquefaciens in particular strain D747 (available as Double NickelTM from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No.
• Bacillus subtilis Y1336 (available as BIOBAC ® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277); (B1.7) Bacillus subtilis strain MBI 600 (available as SUBTILEX from BASF SE), having Accession Number NRRL B-50595, U.S. Patent No. 5,061,495; (B1.8) Bacillus subtilis strain GB03 (available as Kodiak® from Bayer AG, DE); (B1.9) Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No.
• DSM 10271 (available from Novozymes as TAEGRO ® or TAEGRO ® ECO (EPA Registration No.70127- 5)); (B1.10) Bacillus mycoides, isolate J , having Accession No. B-30890 (available as BMJ TGAI ® or WG and LifeGard TM from Certis USA LLC, a subsidiary of Mitsui & Co.); (B1.11) Bacillus licheniformis, in particular strain SB3086 , having Accession No. ATCC 55406, WO 2003/000051 (available as ECOGUARD ® Biofungicide and GREEN RELEAF TM from Novozymes); (B1.12) a Paenibacillus sp. strain having Accession No.
• Bacillus amyloliquefaciens strain FZB42 Bacillus amyloliquefaciens strain FZB42, Accession No. DSM 23117 (available as RHIZOVITAL ® from ABiTEP, DE); (B1.17) Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO ® (WG) and PRESENCE ® (WP) from FMC Corporation); (B1.18) Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC,
• NOGALL TM from BASF SE
• Bacillus subtilis KTSB strain FOLIACTIVE ® from Donaghys
• Bacillus subtilis IAB/BS03 AVIV TM from STK Bio-Ag Technologies
• Bacillus subtilis strain Y1336 available as BIOBAC ® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos. 4764, 5454, 5096 and 5277
• Bacillus amyloliquefaciens isolate B246 e.g.
• AVOGREEN TM from University of Pretoria
• Bacillus methylotrophicus strain BAC-9912 from Chinese Academy of Sciences’ Institute of Applied Ecology
• B1.31 Pseudomonas proradix e.g. PRORADIX ® from Sourcon Padena
• B1.32 Streptomyces griseoviridis strain K61 also known as Streptomyces galbus strain K61
• DSM 7206 Streptomyces griseoviridis strain K61
• MYCOSTOP ® from Verdera; PREFENCE ® from BioWorks; cf. Crop Protection 2006, 25, 468-475
• B1.33 Pseudomonas fluorescens strain A506 e.g.
• BLIGHTBAN ® A506 by NuFarm and (B2) fungi, for example: (B2.1) Coniothyrium minitans, in particular strain CON/M/91-8 (Accession No. DSM-9660; e.g. Contans ® from Bayer CropScience Biologics GmbH); (B2.2) Metschnikowia fructicola, in particular strain NRRL Y-30752; (B2.3) Microsphaeropsis ochracea; (B2.5) Trichoderma atroviride, in particular strain SC1 (having Accession No. CBS 122089, WO 2009/116106 and U.S. Patent No.
• strain 321U from Adjuvants Plus
• strain ACM941 as disclosed in Xue (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea, Can Jour Plant Sci 83(3): 519-524), or strain IK726 (Jensen DF, et al. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain ‘IK726’; Australas Plant Pathol.
• Trichoderma viride in particular strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137); (B2.37) Trichoderma asperellum, in particular strain SKT-1, having Accession No. FERM P-16510 (e.g. ECO-HOPE® from Kumiai Chemical Industry), strain T34 (e.g. T34 Biocontrol by Biocontrol Technologies S.L., ES) or strain ICC 012 from Isagro; (B2.38) Trichoderma atroviride, strain CNCM I-1237 (e.g.
• Esquive® WP from Agrauxine, FR (B2.39) Trichoderma atroviride, strain no. V08/002387; (B2.40) Trichoderma atroviride, strain NMI no. V08/002388; (B2.41) Trichoderma atroviride, strain NMI no. V08/002389;
• B2.42 Trichoderma atroviride, strain NMI no. V08/002390; (B2.43) Trichoderma atroviride, strain LC52 (e.g. Tenet by Agrimm Technologies Limited); (B2.44) Trichoderma atroviride, strain ATCC 20476 (IMI 206040); (B2.45) Trichoderma atroviride, strain T11 (IMI352941/ CECT20498); (B2.46) Trichoderma harmatum; (B2.47) Trichoderma harzianum; (B2.48) Trichoderma harzianum rifai T39 (e.g.
• NM 99/06216 e.g., BOTRY- ZEN ® by Botry-Zen Ltd, New Zealand and BOTRYSTOP ® from BioWorks, Inc.
• Verticillium albo-atrum (formerly V. dahliae), strain WCS850 having Accession No. WCS850, deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG ® by Tree Care Innovations);
• Verticillium chlamydosporium B2.87) mixtures of Trichoderma asperellum strain ICC 012 (also known as Trichoderma harzianum ICC012), having Accession No.
• IMI 392151 e.g., BIO-TAM TM from Isagro USA, Inc. and BIODERMA ® by Agrobiosol de Mexico, S.A. de
• ATCC 20906 (e.g., ROOTSHIELD ® PLUS WP and TURFSHIELD ® PLUS WP from BioWorks, US); (B2.93) Trichoderma hamatum, having Accession No. ATCC 28012; (B2.94) Ampelomyces quisqualis strain AQ10, having Accession No.
• CNCM I-807 e.g., AQ 10 ® by IntrachemBio Italia
• B2.95 Phlebiopsis gigantea strain VRA 1992 (ROTSTOP ® C from Danstar Ferment);
• B2.96 Penicillium steckii (DSM 27859; WO 2015/067800) from BASF SE;
• B2.97 Chaetomium globosum (available as RIVADIOM ® by Rivale);
• B2.100 Dilophosphora alopecuri (available as TWIST FUNGUS ® );
• B2.101 Fusarium oxysporum, strain Fo47 (available as FUSACLEAN ® by Natural Plant Protection);
• B2.102 Pseudozyma flocculosa, strain PF-A22 UL (available as SPORODEX ® L
• strain ICC 080 IMI CC 392151 CABI
• BIODERMA ® AGROBIOSOL DE MEXICO, S.A. DE C.V.
• B2.104 Trichoderma fertile (e.g. product TrichoPlus from BASF);
• B2.105 Muscodor roseus, in particular strain A3-5 (Accession No. NRRL 30548);
• B2.106 Simplicillium lanosoniveum; biological control agents having an effect for improving plant growth and/or plant health which may be combined in the compound combinations according to the invention including (C1) bacteria selected from the group consisting of Bacillus pumilus, in particular strain QST2808 (having Accession No. NRRL No.
• Bacillus subtilis in particular strain QST713/AQ713 (having NRRL Accession No. B-21661and described in U.S. Patent No. 6,060,051; available as SERENADE ® OPTI or SERENADE ® ASO from Bayer CropScience LP, US); Bacillus subtilis, in particular strain AQ30002 (having Accession Nos. NRRL B-50421 and described in U.S. Patent Application No. 13/330,576); Bacillus subtilis, in particular strain AQ30004 (and NRRL B-50455 and described in U.S.
• Patent Application No.13/330,576) Sinorhizobium meliloti strain NRG-185-1 (NITRAGIN ® GOLD from Bayer CropScience); Bacillus subtilis strain BU1814, (available as TEQUALIS ® from BASF SE); Bacillus subtilis rm303 (RHIZOMAX ® from Biofilm Crop Protection); Bacillus amyloliquefaciens pm414 (LOLI- PEPTA ® from Biofilm Crop Protection); Bacillus mycoides BT155 (NRRL No. B-50921), Bacillus mycoides EE118 (NRRL No. B-50918), Bacillus mycoides EE141 (NRRL No.
• Bacillus mycoides BT46-3 (NRRL No. B-50922), Bacillus cereus family member EE128 (NRRL No. B-50917), Bacillus thuringiensis BT013A (NRRL No. B-50924) also known as Bacillus thuringiensis 4Q7, Bacillus cereus family member EE349 (NRRL No. B-50928), Bacillus amyloliquefaciens SB3281 (ATCC # PTA- 7542; WO 2017/205258), Bacillus amyloliquefaciens TJ1000 (available as QUIKROOTS ® from Novozymes); Bacillus firmus, in particular strain CNMC I-1582 (e.g. VOTIVO ® from BASF SE); Bacillus pumilus, in particular strain GB34 (e.g. YIELD SHIELD ® from Bayer Crop Science, DE); Bacillus
• amyloliquefaciens in particular strain IN937a; Bacillus amyloliquefaciens, in particular strain FZB42 (e.g. RHIZOVITAL ® from ABiTEP, DE); Bacillus amyloliquefaciens BS27 (Accession No. NRRL B-5015); a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO ® (WG), PRESENCE ® (WP) from FMC Corporation); Bacillus cereus, in particular strain BP01 (ATCC 55675; e.g.
• MEPICHLOR ® from Arysta Lifescience, US
• Bacillus subtilis in particular strain MBI 600 (e.g. SUBTILEX ® from BASF SE); Bradyrhizobium japonicum (e.g. OPTIMIZE ® from Novozymes); Mesorhizobium cicer (e.g., NODULATOR from BASF SE); Rhizobium leguminosarium biovar viciae (e.g., NODULATOR from BASF SE); Delftia acidovorans, in particular strain RAY209 (e.g. BIOBOOST ® from Brett Young Seeds); Lactobacillus sp. (e.g.
• LACTOPLANT ® from LactoPAFI Paenibacillus polymyxa, in particular strain AC-1 (e.g. TOPSEED ® from Green Biotech Company Ltd.); Pseudomonas proradix (e.g. PRORADIX ® from Sourcon Padena); Azospirillum brasilense (e.g., VIGOR ® from KALO, Inc.); Azospirillum lipoferum (e.g., VERTEX-IF TM from TerraMax, Inc.); a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE ® from Agrinos); Pseudomonas aeruginosa, in particular strain PN1; Rhizobium leguminosarum, in particular bv.
• INVIGORATE ® available as INVIGORATE ® from Agrinos
• Pseudomonas aeruginosa in particular strain
• strain Z25 (Accession No. CECT 4585); Azorhizobium caulinodans, in particular strain ZB-SK-5; Azotobacter chroococcum, in particular strain H23; Azotobacter vinelandii, in particular strain ATCC 12837; Bacillus siamensis, in particular strain KCTC 13613T; Bacillus tequilensis, in particular strain NII- 0943; Serratia marcescens, in particular strain SRM (Accession No. MTCC 8708); Thiobacillus sp. (e.g.
• C2 fungi selected from the group consisting of Purpureocillium lilacinum (previously known as Paecilomyces lilacinus) strain 251 (AGAL 89/030550; e.g. BioAct from Bayer CropScience Biologics GmbH)Penicillium bilaii, strain ATCC 22348 (e.g. JumpStart ® from Acceleron BioAg), Talaromyces flavus,strain V117b; Trichoderma atroviride strain CNCM I-1237 (e.g. Esquive® WP from Agrauxine, FR), Trichoderma viride, e.g.
• Purpureocillium lilacinum previously known as Paecilomyces lilacinus
• strain ATCC 22348 e.g. JumpStart ® from Acceleron BioAg
• Talaromyces flavus strain V117b
• Trichoderma atroviride strain LC52 also known as Trichoderma atroviride strain LU132; e.g. Sentinel from Agrimm Technologies Limited
• Trichoderma atroviride strain SC1 described in International Application No. PCT/IT2008/000196
• Trichoderma asperellum strain kd e.g. T-Gro from Andermatt Biocontrol
• Trichoderma asperellum strain Eco-T Plantt Health Products, ZA
• Trichoderma harzianum strain T-22 e.g.
• Trianum-P from Andermatt Biocontrol or Koppert Myrothecium verrucaria strain AARC-0255 (e.g. DiTeraTM from Valent Biosciences); Penicillium bilaii strain ATCC ATCC20851; Pythium oligandrum strain M1 (ATCC 38472; e.g. Polyversum from Bioprepraty, CZ); Trichoderma virens strain GL-21 (e.g. SoilGard® from Certis, USA); Verticillium albo-atrum (formerly V. dahliae) strain WCS850 (CBS 276.92; e.g. Dutch Trig from Tree Care Innovations); Trichoderma atroviride, in particular strain no.
• AARC-0255 e.g. DiTeraTM from Valent Biosciences
• Penicillium bilaii strain ATCC ATCC20851 e.g. Polyversum from Bioprepraty, CZ
• amylopogon e.g. comprised in Myco-Sol from Helena Chemical Company
• Rhizopogon fulvigleba e.g. comprised in Myco-Sol from Helena Chemical Company
• Trichoderma virens strain GI-3 insecticidally active biological control agents selected from (D1) bacteria selected from the group consisting of Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372; e.g. XENTARI ® from Valent BioSciences); Bacillus mycoides, isolate J. (e.g.
• Bacillus sphaericus in particular Serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. VECTOLEX ® from Valent BioSciences, US); Bacillus thuringiensis subsp. kurstaki strain BMP 123 from Becker Microbial Products, IL; Bacillus thuringiensis subsp. aizawai, in particular serotype H-7 (e.g. FLORBAC ® WG from Valent BioSciences, US); Bacillus thuringiensis subsp. kurstaki strain HD-1 (e.g.
• MBI-206 TGAI and ZELTO ® from Marrone Bio Innovations Chromobacterium subtsugae, in particular strain PRAA4-1T (MBI-203; e.g. GRANDEVO ® from Marrone Bio Innovations); Paenibacillus popilliae (formerly Bacillus popilliae; e.g. MILKY SPORE POWDER TM and MILKY SPORE GRANULAR TM from St. Gabriel Laboratories); Bacillus thuringiensis subsp. israelensis (serotype H-14) strain AM65-52 (Accession No. ATCC 1276) (e.g.
• VECTOBAC ® by Valent BioSciences, US Bacillus thuringiensis var. kurstaki strain EVB-113-19 (e.g., BIOPROTEC ® from AEF Global); Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428; e.g. NOVODOR ® FC from BioFa DE); Bacillus thuringiensis var. japonensis strain Buibui; Bacillus thuringiensis subsp. kurstaki strain ABTS 351; Bacillus thuringiensis subsp. kurstaki strain PB 54; Bacillus thuringiensis subsp.
• israeltaki strain SA 11 Bacillus thuringiensis subsp. kurstaki strain SA 12; Bacillus thuringiensis subsp. kurstaki strain EG 2348; Bacillus thuringiensis var. Colmeri (e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory); Bacillus thuringiensis subsp. aizawai strain GC-91; Serratia entomophila (e.g. INVADE ® by Wrightson Seeds); Serratia marcescens, in particular strain SRM (Accession No.
• MTCC 8708 Wolbachia pipientis ZAP strain
• Wolbachia pipientis ZAP strain e.g., ZAP MALES ® from MosquitoMate
• Beauveria bassiana strain ATCC 74040 e.g. NATURALIS ® from Intrachem Bio Italia
• Beauveria bassiana strain GHA (Accession No. ATCC74250; e.g.
• Beauveria bassiana strain ATP02 (Accession No. DSM 24665).
• Isaria fumosorosea (previously known as Paecilomyces fumosoroseus) strain apopka 97 is particularly preferred;
• bacteria and fungi which can be added as 'inoculant' to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health.
• Examples are: Agrobacterium spp., Azorhizobium caulinodans, Azospirillum spp., Azotobacter spp., Bradyrhizobium spp., Burkholderia spp., in particular Burkholderia cepacia (formerly known as Pseudomonas cepacia), Gigaspora spp., or Gigaspora monosporum, Glomus spp., Laccaria spp., Lactobacillus buchneri, Paraglomus spp., Pisolithus tinctorus, Pseudomonas spp., Rhizobium spp., in particular Rhizobium trifolii, Rhizopogon spp., Scleroderma spp., Suillus spp., and Streptomyces spp.; and (G) plant extracts and products formed by microorganisms including proteins and secondary metabolites which can be used as
• insects as well as the term “insecticidal” refers to the ability of a substance to increase mortality or inhibit growth rate of insects.
• insects comprises all organisms in the class “Insecta”.
• Nematicide and “nematicidal” refers to the ability of a substance to increase mortality or inhibit the growth rate of nematodes.
• nematode comprises eggs, larvae, juvenile and mature forms of said organism.
• Acaricide and “acaricidal” refers to the ability of a substance to increase mortality or inhibit growth rate of ectoparasites belonging to the class Arachnida, sub-class Acari.
• insecticides, acaricides and nematicides, respectively, which could be mixed with the compound and the composition of the invention are: (1) Acetylcholinesterase (AChE) inhibitors, such as, for example, carbamates, for example alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trim
• GABA-gated chloride channel blockers such as, for example, cyclodiene-organochlorines, for example chlordane and endosulfan or phenylpyrazoles (fiproles), for example ethiprole and fipronil.
• Sodium channel modulators such as, for example, pyrethroids, e.g.
• Nicotinic acetylcholine receptor (nAChR) competitive modulators such as, for example, neonicotinoids, e.g. acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam or nicotine or sulfoxaflor or flupyradifurone.
• Nicotinic acetylcholine receptor (nAChR) allosteric modulators such as, for example, spinosyns, e.g. spinetoram and spinosad.
• Glutamate-gated chloride channel (GluCl) allosteric modulators such as, for example, avermectins/milbemycins, for example abamectin, emamectin benzoate, lepimectin and milbemectin.
• Juvenile hormone mimics such as, for example, juvenile hormone analogues, e.g. hydroprene, kinoprene and methoprene or fenoxycarb or pyriproxyfen.
• Miscellaneous non-specific (multi-site) inhibitors such as, for example, alkyl halides, e.g.
• methyl bromide and other alkyl halides or chloropicrine or sulphuryl fluoride or borax or tartar emetic or methyl isocyanate generators, e.g. diazomet and metam.
• Modulators of Chordotonal Organs such as, for example pymetrozine or flonicamid.
• Mite growth inhibitors such as, for example clofentezine, hexythiazox and diflovidazin or etoxazole.
• Microbial disruptors of the insect gut membrane such as, for example Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, Bacillus thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis, and B.t. plant proteins: Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/35Ab1.
• Inhibitors of mitochondrial ATP synthase such as, ATP disruptors such as, for example, diafenthiuron or organotin compounds, for example azocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon.
• Uncouplers of oxidative phosphorylation via disruption of the proton gradient such as, for example, chlorfenapyr, DNOC and sulfluramid.
• Nicotinic acetylcholine receptor channel blockers such as, for example, bensultap, cartap hydrochloride, thiocylam, and thiosultap-sodium.
• Inhibitors of chitin biosynthesis type 0, such as, for example, bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron.
• Inhibitors of chitin biosynthesis type 1, for example buprofezin.
• Moulting disruptor in particular for Diptera, i.e. dipterans
• cyromazine azine.
• Ecdysone receptor agonists such as, for example, chromafenozide, halofenozide, methoxyfenozide and tebufenozide.
• Octopamine receptor agonists such as, for example, amitraz.
• Mitochondrial complex III electron transport inhibitors such as, for example, hydramethylnone or acequinocyl or fluacrypyrim.
• Mitochondrial complex I electron transport inhibitors such as, for example from the group of the METI acaricides, e.g.
• Voltage-dependent sodium channel blockers such as, for example indoxacarb or metaflumizone.
• Inhibitors of acetyl CoA carboxylase such as, for example, tetronic and tetramic acid derivatives, e.g. spirodiclofen, spiromesifen and spirotetramat.
• Mitochondrial complex IV electron transport inhibitors such as, for example, phosphines, e.g.
• cyanides e.g. calcium cyanide, potassium cyanide and sodium cyanide.
• Mitochondrial complex II electron transport inhibitors such as, for example, beta-ketonitrile derivatives, e.g. cyenopyrafen and cyflumetofen and carboxanilides, such as, for example, pyflubumide.
• Ryanodine receptor modulators such as, for example, diamides, e.g.
• chlorantraniliprole, cyantraniliprole and flubendiamide further active compounds such as, for example, Afidopyropen, Afoxolaner, Azadirachtin, Benclothiaz, Benzoximate, Bifenazate, Broflanilide, Bromopropylate, Chinomethionat, Chloroprallethrin, Cryolite, Cyclaniliprole, Cycloxaprid, Cyhalodiamide, Dicloromezotiaz, Dicofol, epsilon-Metofluthrin, epsilon- Momfluthrin, Flometoquin, Fluazaindolizine, Fluensulfone, Flufenerim, Flufenoxystrobin, Flufiprole, Fluhexafon, Fluopyram, Fluralaner, Fluxametamide, Fufenozide, Guadipyr, Heptafluthrin, Imid
• herbicides which could be mixed with the compound and the composition of the invention are: Acetochlor, acifluorfen, acifluorfen-sodium, aclonifen, alachlor, allidochlor, alloxydim, alloxydim- sodium, ametryn, amicarbazone, amidochlor, amidosulfuron, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H- indol-6-yl)pyridine-2-carboxylic acid, aminocyclopyrachlor, aminocyclopyrachlor-potassium, aminocyclopyrachlor-methyl, aminopyralid, amitrole, ammoniumsulfamate, anilofos, asulam, atrazine, azafenidin, azimsulfuron, beflubutamid, benazolin, benazolin-ethyl, benfluralin, benfuresate, bensulfuron, bens
• plant growth regulators are: Acibenzolar, acibenzolar-S-methyl, 5-aminolevulinic acid, ancymidol, 6-benzylaminopurine, Brassinolid, catechine, chlormequat chloride, cloprop, cyclanilide, 3-(cycloprop-1-enyl) propionic acid, daminozide, dazomet, n-decanol, dikegulac, dikegulac-sodium, endothal, endothal-dipotassium, -disodium, and - mono(N,N-dimethylalkylammonium), ethephon, flumetralin, flurenol, flurenol-butyl, flurprimidol, forchlorfenuron, gibberellic acid, inabenfide, in
• Examples of safeners which could be mixed with the compound and the composition of the invention are, for example, benoxacor, cloquintocet (-mexyl), cyometrinil, cyprosulfamide, dichlormid, fenchlorazole (- ethyl), fenclorim, flurazole, fluxofenim, furilazole, isoxadifen (-ethyl), mefenpyr (-diethyl), naphthalic anhydride, oxabetrinil, 2-methoxy-N-( ⁇ 4-[(methylcarbamoyl)amino]phenyl ⁇ - sulphonyl)benzamide (CAS 129531-12-0), 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (CAS 71526- 07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine (CAS
• nitrification inhibitors which can be mixed with the compound and the composition of the invention are selected from the group consisting of 2-(3,4-dimethyl-1 H-pyrazol-1 -yl)succinic acid, 2- (4,5-dimethyl-1 H-pyrazol-1 -yl)succinic acid, 3,4-dimethyl pyrazolium glycolate, 3,4-dimethyl pyrazolium citrate, 3,4-dimethyl pyrazolium lactate, 3,4-dimethyl pyrazolium mandelate, 1 ,2,4-triazole, 4-Chloro-3-methylpyrazole, N-((3(5)-methyl-1H-pyrazole-1-yl)methyl)acetamide, N-((3(5)-methyl-1 H- pyrazole-1-yl)methyl)formamide, N-((3(5),4-dimethylpyrazole-1-yl)methyl)formamide, N-((4-chloro- 3(5)-methyl-pyrazole-1-yl
• benzoquinone sorgoleone 4-amino-1,2,4-triazole hydrochloride, 1-amido-2-thiourea, 2-amino-4-chloro- 6-methylpyrimidine, 2-mercapto-benzothiazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiodiazole (terrazole, etridiazole), 2-sulfanilamidothiazole, 3-methylpyrazol, 1,2,4-triazol thiourea, cyan amide, melamine, zeolite powder, catechol, benzoquinone, sodium tetraborate, allylthiourea, chlorate salts, and zinc sulfate.
• the compound and the composition of the invention may be combined with one or more agriculturally beneficial agents.
• agriculturally beneficial agents include biostimulants, plant growth regulators, plant signal molecules, growth enhancers, microbial stimulating molecules, biomolecules, soil amendments, nutrients, plant nutrient enhancers, etc., such as lipo-chitooligosaccharides (LCO), chitooligosaccharides (CO), chitinous compounds, flavonoids, jasmonic acid or derivatives thereof (e.g., jasmonates), cytokinins, auxins, gibberellins, absiscic acid, ethylene, brassinosteroids, salicylates, macro- and micro-nutrients, linoleic acid or derivatives thereof, linolenic acid or derivatives thereof, karrikins, and beneficial microorganisms (e.g., Rhizobium spp., Bradyrhizobium spp., Sinorhizobium spp., Azorh
• the compound and the composition of the invention have potent microbicidal activity and/or plant defense modulating potential. They can be used for controlling unwanted microorganisms, such as unwanted fungi and bacteria, on plants. They can be particularly useful in crop protection (they control microorganisms that cause plants diseases) or for protecting materials (e.g. industrial materials, timber, storage goods) as described in more details herein below. More specifically, the compound and the composition of the invention can be used to protect seeds, germinating seeds, emerged seedlings, plants, plant parts, fruits, harvest goods and/or the soil in which the plants grow from unwanted microorganisms. Control or controlling as used herein encompasses protective, curative and eradicative treatment of unwanted microorganisms.
• Unwanted microorganisms may be pathogenic bacteria, pathogenic virus, pathogenic oomycetes or pathogenic fungi, more specifically phytopathogenic bacteria, phytopathogenic virus, phytopathogenic oomycetes or phytopathogenic fungi. As detailed herein below, these phytopathogenic microorganims are the causal agents of a broad spectrum of plants diseases.
• the compound and the composition of the invention can be used as fungicides.
• fungicide refers to a compound or composition that can be used in crop protection for the control of unwanted fungi, such as Plasmodiophoromycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes and/or for the control of Oomycetes.
• the compound and the composition of the invention may also be used as antibacterial agent.
• they may be used in crop protection, for example for the control of unwanted bacteria, such as Pseudomonadaceae, Rhizobiaceae, Xanthomonadaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.
• unwanted bacteria such as Pseudomonadaceae, Rhizobiaceae, Xanthomonadaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.
• the compound and the composition of the invention may also be used as antiviral agent in crop protection.
• the compound and the composition of the invention may have effects on diseases from plant viruses, such as the tobacco mosaic virus (TMV), tobacco rattle virus, tobacco stunt virus (TStuV), tobacco leaf curl virus (VLCV), tobacco nervilia mosaic virus (TVBMV), tobacco necrotic dwarf virus (TNDV), tobacco streak virus (TSV), potato virus X (PVX), potato viruses Y, S, M, and A, potato acuba mosaic virus (PAMV), potato mop-top virus (PMTV), potato leaf-roll virus (PLRV), alfalfa mosaic virus (AMV), cucumber mosaic virus (CMV), cucumber green mottlemosaic virus (CGMMV), cucumber yellows virus (CuYV), watermelon mosaic virus (WMV), tomato spotted wilt virus (TSWV), tomato ringspot virus (TomRSV), sugarcane mosaic virus (SCMV), rice drawf virus, rice stripe virus, rice black- streaked drawf virus, strawberry mottle virus (SMoV), strawberry vein banding virus (SVBV), strawberry mild yellow edge virus (
• the present invention also relates to a method for controlling unwanted microorganisms, such as unwanted fungi, oomycetes and bacteria, on plants comprising the step of applying at least one compound of the invention or at least one composition of the invention to the microorganisms and/or their habitat (to the plants, plant parts, seeds, fruits or to the soil in which the plants grow).
• unwanted microorganisms such as unwanted fungi, oomycetes and bacteria
• Suitable substrates that may be used for cultivating plants include inorganic based substrates, such as mineral wool, in particular stone wool, perlite, sand or gravel; organic substrates, such as peat, pine bark or sawdust; and petroleum based substrates such as polymeric foams or plastic beads.
• Effective and plant-compatible amount means an amount that is sufficient to control or destroy the fungi present or liable to appear on the cropland and that does not entail any appreciable symptom of phytotoxicity for said crops. Such an amount can vary within a wide range depending on the fungus to be controlled, the type of crop, the crop growth stage, the climatic conditions and the respective compound
• Plants and plant parts The compound and the composition of the invention may be applied to any plants or plant parts.
• Plants mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants).
• Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the genetically modified plants (GMO or transgenic plants) and the plant cultivars which are protectable and non-protectable by plant breeders’ rights.
• Plant cultivars are understood to mean plants which have new properties ("traits”) and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques.
• Plant parts can be cultivars, varieties, bio- or genotypes.
• Plant parts are understood to mean all parts and organs of plants above and below the ground, such as shoots, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.
• the plant parts also include harvested material and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, slips and seeds.
• Plants which may be treated in accordance with the methods of the invention include the following: cotton, flax, grapevine, fruit, vegetables, such as Rosaceae sp.
• pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds and peaches, and soft fruits such as strawberries
• Ribesioidae sp. Juglandaceae sp.
• Betulaceae sp. Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (for example banana trees and plantations), Rubiaceae sp.
• Theaceae sp. for example coffee
• Theaceae sp. Sterculiceae sp.
• Rutaceae sp. for example lemons, oranges and grapefruit
• Solanaceae sp. for example tomatoes
• Liliaceae sp. for example lettuce
• Umbelliferae sp. for example lettuce
• Umbelliferae sp. for example lettuce
• Umbelliferae sp. for example lettuce
• Cicurbitaceae sp. for example cucumber
• Alliaceae sp. for example leek, onion
• Papilionaceae sp. for example peas
• major crop plants such as Gramineae sp.
• Asteraceae sp. for example sunflower
• Brassicaceae sp. for example white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, and oilseed rape, mustard, horseradish and cress
• Fabacae sp. for example bean, peanuts
• Papilionaceae sp. for example soya bean
• Solanaceae sp. for example potatoes), Chenopodiaceae sp.
• Plants and plant cultivars which may be treated by the above disclosed methods include plants and plant cultivars which are resistant against one or more biotic stresses, i.e. said plants show a better defense
• Plants and plant cultivars which may be treated by the above disclosed methods include those plants which are resistant to one or more abiotic stresses.
• Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.
• Plants and plant cultivars which may be treated by the above disclosed methods include those plants characterized by enhanced yield characteristics.
• Increased yield in said plants may be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation.
• Yield may furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance.
• Further yield traits include seed composition, such as carbohydrate content and composition for example cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
• Plants and plant cultivars which may be treated by the above disclosed methods include plants and plant cultivars which are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses.
• Transgenic plants, seed treatment and integration events The compound according to the invention can be advantageously used to treat transgenic plants, plant cultivars or plant parts that received genetic material which imparts advantageous and/or useful properties (traits) to these plants, plant cultivars or plant parts.
• a transgenic event is created by the insertion of a specific recombinant DNA molecule into a specific position (locus) within the chromosome of the plant genome.
• the insertion creates a novel DNA sequence referred to as an “event” and is characterized by the inserted recombinant DNA molecule and some amount of genomic DNA immediately adjacent to/flanking both ends of the inserted DNA.
• Such trait(s) or transgenic event(s) include, but are not limited to, pest resistance, water use efficiency, yield performance, drought tolerance, seed quality, improved nutritional quality, hybrid seed production, and herbicide tolerance, in which the trait is measured with respect to a plant lacking
• Such advantageous and/or useful properties are better plant growth, vigor, stress tolerance, standability, lodging resistance, nutrient uptake, plant nutrition, and/or yield, in particular improved growth, increased tolerance to high or low temperatures, increased tolerance to drought or to levels of water or soil salinity, enhanced flowering performance, easier harvesting, accelerated ripening, higher yields, higher quality and/or a higher nutritional value of the harvested products, better storage life and/or processability of the harvested products, and increased resistance against animal and microbial pests, such as against insects, arachnids, nematodes, mites, slugs and snails.
• Bt Cry or VIP proteins which include the CrylA, CryIAb, CryIAc, CryIIA, CryIIIA, CryIIIB2, Cry9c Cry2Ab, Cry3Bb and CryIF proteins or toxic fragments thereof and also hybrids or combinations thereof, especially the CrylF protein or hybrids derived from a CrylF protein (e.g. hybrid CrylA-CrylF proteins or toxic fragments thereof), the CrylA-type proteins or toxic fragments thereof, preferably the CrylAc protein or hybrids derived from the CrylAc protein (e.g.
• hybrid CrylAb-CrylAc proteins or the CrylAb or Bt2 protein or toxic fragments thereof, the Cry2Ae, Cry2Af or Cry2Ag proteins or toxic fragments thereof, the CrylA.105 protein or a toxic fragment thereof, the VIP3Aa19 protein, the VIP3Aa20 protein, the VIP3A proteins produced in the COT202 or COT203 cotton events, the VIP3Aa protein or a toxic fragment thereof as described in Estruch et al.
• DNA sequences encoding proteins which confer properties of tolerance to certain herbicides on the transformed plant cells and plants mention will be particularly be made to the bar or PAT gene or the Streptomyces coelicolor gene described in WO2009/152359 which confers tolerance to glufosinate herbicides, a gene encoding a suitable EPSPS (5-Enolpyruvylshikimat-3-phosphat-synthase) which confers tolerance to herbicides having EPSPS as a target, especially herbicides such as glyphosate and its salts, a gene encoding
• EPSPS 5-Enolpyruvylshikimat-3-phosphat-synthase
• herbicide tolerance traits include at least one ALS (acetolactate synthase) inhibitor (e.g. WO2007/024782), a mutated Arabidopsis ALS/AHAS gene (e.g. U.S. Patent 6,855,533), genes encoding 2,4-D- monooxygenases conferring tolerance to 2,4-D (2,4- dichlorophenoxyacetic acid) and genes encoding Dicamba monooxygenases conferring tolerance to dicamba (3,6-dichloro-2- methoxybenzoic acid).
• ALS acetolactate synthase
• a mutated Arabidopsis ALS/AHAS gene e.g. U.S. Patent 6,855,533
• Yet another example of such properties is resistance to one or more phytopathogenic fungi, for example Asian Soybean Rust.
• DNA sequences encoding proteins which confer properties of resistance to such diseases mention will particularly be made of the genetic material from glycine tomentella, for example from any one of publically available accession lines PI441001 , PI483224, PI583970, PI446958, PI499939, PI505220, PI499933, PI441008, PI505256 or PI446961 as described in WO2019/103918.
• transgenic events in transgenic plants or plant cultivars which can be treated with preference in accordance with the invention include Event 531/ PV-GHBK04 (cotton, insect control, described in WO2002/040677), Event 1143-14A (cotton, insect control, not deposited, described in WO2006/128569); Event 1143-51B (cotton, insect control, not deposited, described in WO2006/128570); Event 1445 (cotton, herbicide tolerance, not deposited, described in US-A 2002- 120964 or WO2002/034946); Event 17053 (rice, herbicide tolerance, deposited as PTA-9843, described in WO2010/117737); Event 17314 (rice, herbicide tolerance, deposited as PTA-9844, described in WO2010/1177
• Event BLRl oilseed rape, restoration of male sterility, deposited as NCIMB 41193, described in WO2005/074671
• Event CE43-67B cotton, insect control, deposited as DSM ACC2724, described in US-A 2009-217423 or WO2006/128573
• Event CE44-69D cotton, insect control, not deposited, described in US-A 2010- 0024077
• Event CE44-69D cotton, insect
• Event CE46-02A cotton, insect control, not deposited, described in WO2006/128572
• Event COT102 cotton, insect control, not deposited, described in US-A 2006-130175 or WO2004/039986
• Event COT202 cotton, insect control, not deposited, described in US-A 2007-067868 or WO2005/054479
• Event COT203 cotton, insect control, not deposited, described in WO2005/054480
• Event DAS21606-3 / 1606 soybean, herbicide tolerance, deposited as PTA-11028, described in WO2012/033794
• Event DAS40278 corn, herbicide tolerance, deposited as ATCC PTA-10244, described in WO2011/022469
• Event DAS-44406-6 / pDAB8264.44.06.l (soybean, herbicide tolerance, deposited as PTA-11336, described in WO2012/
• Event LLRice62 rice, herbicide tolerance, deposited as ATCC 203352, described in WO2000/026345
• Event LLRICE601 rice, herbicide tolerance, deposited as ATCC PTA-2600, described in US-A 2008-2289060 or WO2000/026356
• Event LY038 corn, quality trait, deposited as ATCC PTA-5623, described in US-A 2007-028322 or WO2005/061720
• Event MIR162 corn, insect control, deposited as PTA-8166, described in US-A 2009-300784 or WO2007/142840
• Event MIR604 (corn, insect control, not deposited, described in US-A 2008-167456 or WO2005/103301)
• Event MON15985 cotton, insect control, deposited as ATCC PTA-2516, described in US-A 2004- 250317 or WO2002/100163
• Event MON810 corn, insect control, not deposited, described in US- A 2002-102582
• Event MON863 corn
• genes/events which impart the desired traits in question may also be present in combinations with one another in the transgenic plants.
• pathogens of fungal diseases which may be treated in accordance with the invention include: diseases caused by powdery mildew pathogens, for example Blumeria species, for example Blumeria graminis; Podosphaera species, for example Podosphaera leucotricha; Sphaerotheca species, for example Sphaerotheca fuliginea; Uncinula species, for example Uncinula necator; diseases caused by rust disease pathogens, for example Gymnosporangium species, for example Gymnosporangium sabinae; Hemileia species, for example Hemileia vastatrix; Phakopsora species, for example Phakopsora pachyrhizi or Phakopsora meibomiae; Puccinia species, for example Puccinia recondita, Puccinia graminis oder Puccinia striiformis; Uromyces species, for example Uromyces append
• Phytophthora species for example Phytophthora infestans
• Plasmopara species for example Plasmopara viticola
• Pseudoperonospora species for example Pseudoperonospora humuli or Pseudoperonospora cubensis
• Pythium species for example Pythium ultimum
• Sclerotinia species for example Sclerotinia sclerotiorum; Verticilium species, for example Verticilium alboatrum; seed- and soil-borne rot and wilt diseases, and also diseases of seedlings, caused, for example, by Alternaria species, for example Alternaria brassicicola; Aphanomyces species, for example Aphanomyces euteiches; Ascochyta species, for example Ascochyta lentis; Aspergillus species, for example Aspergillus flavus; Cladosporium species, for example Cladosporium herbarum; Cochliobolus species, for example Cochliobolus sativus (conidial form: Drechslera, Bipolaris Syn: Helminthosporium); Colletotrichum species, for example Colletotrichum coccodes; Fusarium species, for example Fusarium culmorum; Gibberella species, for example Gibberella zeae; Mac
• Pseudomonas species for example Pseudomonas syringae pv. lachrymans
• Erwinia species for example Erwinia amylovora
• Liberibacter species for example Liberibacter asiaticus
• Xyella species for example Xylella fastidiosa
• Ralstonia species for example Ralstonia solanacearum
• Dickeya species for example Dickeya solani
• Clavibacter species for example Clavibacter michiganensis
• Streptomyces species for example Streptomyces scabies.
• phytophthora rot (Phytophthora megasperma), brown stem rot (Phialophora gregata), pythium rot (Pythium aphanidermatum, Pythium irregulare, Pythium debaryanum, Pythium myriotylum, Pythium ultimum), rhizoctonia root rot, stem decay, and damping-off (Rhizoctonia solani), sclerotinia stem decay (Sclerotinia sclerotiorum), sclerotinia southern blight (Sclerotinia rolfsii), thielaviopsis root rot (Thielaviopsis basicola).
• Mycotoxins include particularly, but not exclusively, the following: deoxynivalenol (DON), nivalenol, 15-Ac-DON, 3-Ac-DON, T2- and HT2- toxin, fumonisins, zearalenon, moniliformin, fusarin, diaceotoxyscirpenol (DAS), beauvericin, enniatin, fusaroproliferin, fusarenol, ochratoxins, patulin, ergot alkaloids and aflatoxins which can be produced, for example, by the following fungi: Fusarium spec., such as F.
• verticillioides and also by Aspergillus spec., such as A. flavus, A. parasiticus, A. nomius, A. ochraceus, A. clavatus, A. terreus, A. versicolor, Penicillium spec., such as P. verrucosum, P. viridicatum, P. citrinum, P. expansum, P. claviforme, P. roqueforti, Claviceps spec., such as C. purpurea, C. fusiformis, C. paspali, C. africana, Stachybotrys spec. and others.
• Aspergillus spec. such as A. flavus, A. parasiticus, A. nomius, A. ochraceus, A. clavatus, A. terreus, A. versicolor, Penicillium spec., such as P. verrucosum, P. viridicatum, P. citr
• the compound and the composition of the invention may also be used in the protection of materials, especially for the protection of industrial materials against attack and destruction by phytopathogenic fungi.
• the compound and the composition of the invention may be used as antifouling compositions, alone or in combinations with other active ingredients.
• Industrial materials in the present context are understood to mean inanimate materials which have been prepared for use in industry.
• industrial materials which are to be protected from microbial alteration or destruction may be adhesives, glues, paper, wallpaper and board/cardboard, textiles, carpets, leather, wood, fibers and tissues, paints and plastic articles, cooling lubricants and other materials which can be infected with or destroyed by microorganisms.
• Parts of production plants and buildings for example cooling-water circuits, cooling and heating systems and ventilation and air-conditioning units, which may be impaired by the proliferation of microorganisms may also be mentioned within the scope of the materials to be protected.
• Industrial materials within the scope of the present invention preferably include adhesives, sizes, paper and card, leather, wood, paints, cooling lubricants and heat transfer fluids, more preferably wood.
• the compound and the composition of the invention may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
• the compound and the composition of the invention may also be used against fungal diseases liable to grow on or inside timber.
• Timber means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood.
• the compound and the composition of the invention may be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, buildings, moorings and signalling systems, from fouling.
• the compound and the composition of the invention may also be employed for protecting storage goods.
• Storage goods are understood to mean natural substances of vegetable or animal origin or processed products thereof which are of natural origin, and for which long-term protection is desired.
• Storage goods of vegetable origin for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, may be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting.
• Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture.
• Storage goods of animal origin are, for example, hides, leather, furs and hairs.
• the compound and the composition of the invention may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.
• Microorganisms capable of degrading or altering industrial materials include, for example, bacteria, fungi, yeasts, algae and slime organisms.
• the compound and the composition of the invention preferably act against fungi, especially moulds, wood-discoloring and wood-destroying fungi (Ascomycetes, Basidiomycetes, Deuteromycetes and Zygomycetes), and against slime organisms and algae.
• microorganisms of the following genera Alternaria, such as Alternaria tenuis; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium globosum; Coniophora, such as Coniophora puetana; Lentinus, such as Lentinus tigrinus; Penicillium, such as Penicillium glaucum; Polyporus, such as Polyporus versicolor; Aureobasidium, such as Aureobasidium pullulans; Sclerophoma, such as Sclerophoma pityophila; Trichoderma, such as Trichoderma viride; Ophiostoma spp., Ceratocystis spp., Humicola spp., Petriella spp., Trichurus spp., Coriolus spp., Gloeophyllum spp., Pleurotus spp., Poria
• the compound and the composition of the invention may also be used to protect seeds from unwanted microorganisms, such as phytopathogenic microorganisms, for instance phytopathogenic fungi or phytopathogenic oomycetes.
• seed(s) as used herein include dormant seeds, primed seeds, pregerminated seeds and seeds with emerged roots and leaves.
• the present invention also relates to a method for protecting seeds from unwanted microorganisms which comprises the step of treating the seeds with the compound or the composition of the invention.
• the treatment of seeds with the compound or the composition of the invention protects the seeds from phytopathogenic microorganisms, but also protects the germinating seeds, the emerging seedlings and the plants after emergence from the treated seeds. Therefore, the present invention also relates to a method for protecting seeds, germinating seeds and emerging seedlings.
• the seeds treatment may be performed prior to sowing, at the time of sowing or shortly thereafter. When the seeds treatment is performed prior to sowing (e.g.
• the seeds treatment may be performed as follows: the seeds may be placed into a mixer with a desired amount of the compound or the composition of the invention, the seeds and the compound or the composition of the invention are mixed until an homogeneous distribution on seeds is achieved. If appropriate, the seeds may then be dried.
• the invention also relates to seeds coated with the compound or the composition of the invention.
• the seeds are treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment.
• seeds can be treated at any time between harvest and shortly after sowing. It is customary to use seeds which have been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seeds which have been harvested, cleaned and dried down to a moisture content of less than 15% by weight. Alternatively, it is also possible to use seeds which, after drying, for example, have been treated with water and then dried again, or seeds just after priming, or seeds stored in primed conditions or pre-germinated seeds, or seeds sown on nursery trays, tapes or paper.
• the amount of the compound or the composition of the invention applied to the seeds is typically such that the germination of the seed is not impaired, or that the resulting plant is not damaged. This must be ensured particularly in case the compound of the invention would exhibit phytotoxic effects at certain application rates.
• the intrinsic phenotypes of transgenic plants should also be taken into consideration when determining the amount of the compound of the invention to be applied to the seed in order to achieve optimum seed and germinating plant protection with a minimum amount of compound being employed.
• the compound of the invention can be applied as such, directly to the seeds, i.e. without the use of any other components and without having been diluted.
• the composition of the invention can be applied to the seeds.
• the compound and the composition of the invention are suitable for protecting seeds of any plant variety.
• Preferred seeds are that of cereals (such as wheat, barley, rye, millet, triticale, and oats), oilseed rape, maize, cotton, soybean, rice, potatoes, sunflower, beans, coffee, peas, beet (e.g. sugar beet and fodder beet), peanut, vegetables (such as tomato, cucumber, onions and lettuce), lawns and ornamental plants. More preferred are seeds of wheat, soybean, oilseed rape, maize and rice.
• the compound and the composition of the invention may be used for treating transgenic seeds, in particular seeds of plants capable of expressing a polypeptide or protein which acts against pests, herbicidal damage or abiotic stress, thereby increasing the protective effect.
• Seeds of plants capable of expressing a polypeptide or protein which acts against pests, herbicidal damage or abiotic stress may contain at least one heterologous gene which allows the expression of said polypeptide or protein.
• These heterologous genes in transgenic seeds may originate, for example, from microorganisms of the species Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium.
• These heterologous genes preferably originate from Bacillus sp., in which case the gene product is effective against the European corn borer and/or the Western corn rootworm.
• the heterologous genes originate from Bacillus thuringiensis.
• the compound of the invention can be applied as such, or for example in the form of as ready-to-use solutions, emulsions, water- or oil-based suspensions, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural products impregnated with the compound of the invention, synthetic substances impregnated with the compound of the invention, fertilizers or microencapsulations in polymeric substances.
• Application is accomplished in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming or spreading-on.
• the compound of the invention by the ultra-low volume method, via a drip irrigation system or drench application, to apply it in-furrow or to inject it into the soil stem or trunk. It is further possible to apply the compound of the invention by means of a wound seal, paint or other wound dressing.
• the effective and plant-compatible amount of the compound of the invention which is applied to the plants, plant parts, fruits, seeds or soil will depend on various factors, such as the compound/composition employed, the subject of the treatment (plant, plant part, fruit, seed or soil), the type of treatment (dusting, spraying, seed dressing), the purpose of the treatment (curative and protective), the type of microorganisms, the development stage of the microorganisms, the sensitivity of the microorganisms, the crop growth stage and the environmental conditions.
• the application rates can vary within a relatively wide range, depending on the kind of application.
• the application rate may range from 0.1 to 10000 g/ha, preferably from 10 to 1000 g/ha, more preferably from 50 to 300 g/ha (in the case of application by watering or dripping, it is even possible to reduce the application rate, especially when inert substrates such as rockwool or perlite are used).
• the application rate may range from 0.1 to 200 g per 100 kg of seeds, preferably from 1 to 150 g per 100 kg of seeds, more preferably from 2.5 to 25 g per 100 kg of seeds, even more preferably from 2.5 to 12.5 g per 100 kg of seeds.
• the application rate may range from 0.1 to 10000 g/ha, preferably from 1 to 5000 g/ha. These application rates are merely examples and are not intended to limit the scope of the present invention.
• the compound and the composition of the invention can be used in combination with models e.g. embedded in computer programs for site specific crop management, satellite farming, precision farming or precision agriculture.
• models support the site specific management of agricultural sites with data from various sources such as soils, weather, crops (e.g. type, growth stage, plant health), weeds (e.g. type, growth stage), diseases, pests, nutrients, water, moisture, biomass, satellite data, yield etc. with the purpose to optimize profitability, sustainability and protection of the environment.
• such models can be used in combination with models.
• the compound of the invention can be applied to a crop plant according to appropriate dose regime if a model models the development of a fungal disease and calculates that a threshold has been reached for which it is recommendable to apply the compound of the invention to the crop plant.
• Commercially available systems which include agronomic models are e.g. FieldScripts TM from The climate Corporation, Xarvio TM from BASF, AGLogic TM from John Deere, etc.
• the compound of the invention can also be used in combination with smart spraying equipment such as e.g.
• Such an equipment usually includes input sensors (such as e.g. a camera) and a processing unit configured to analyze the input data and configured to provide a decision based on the analysis of the input data to apply the compound of the invention to the crop plants (respectively the weeds) in a specific and precise manner.
• input sensors such as e.g. a camera
• processing unit configured to analyze the input data and configured to provide a decision based on the analysis of the input data to apply the compound of the invention to the crop plants (respectively the weeds) in a specific and precise manner.
• the use of such smart spraying equipment usually also requires positions systems (e.g. GPS receivers) to localize recorded data and to guide or to control farm vehicles; geographic information systems (GIS) to represent the information on intelligible maps, and appropriate farm vehicles to perform the required farm action such as the spraying.
• GPS geographic information systems
• fungal diseases can be detected from imagery acquired by a camera.
• fungal diseases can be identified and/or classified based on that imagery.
• identification and/ classification can make use of image processing algorithms.
• image processing algorithms can utilize machine learning algorithms, such as trained neutral networks, decision trees and utilize artificial intelligence algorithms. In this manner, the compounds described herein can be applied only where needed. Aspects of the present teaching may be further understood in light of the following examples, which should not be construed as limiting the scope of the present teaching in any way.
• LogP value is determined by measurement of LC-UV, in a neutral range, with 0.001 molar ammonium acetate solution in water and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile).
• LogP value is determined by measurement of LC-UV, in an acidic range, with 0.1% phosphoric acid and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile). If more than one LogP value is available within the same method, all the values are given and separated by “+”.
• the peak list of an example has therefore the form: ⁇ 1 (intensity 1 ); ⁇ 2 (intensity 2 );........; ⁇ i (intensity i ); hence; ⁇ n (intensity n )
• Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.
• DMSO dimethyl sulfoxide
• the 1 H-NMR peak lists are similar to classical 1 H-NMR prints and contains therefore usually all peaks, which are listed at classical NMR-interpretation. Additionally they can show like classical 1 H-NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities.
• the peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%). Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via “side-products-fingerprints”.
• An expert who calculates the peaks of the target compounds with known methods (MestreC, ACD- simulation, but also with empirically evaluated expectation values) can isolate the peaks of the target compounds as needed optionally using additional intensity filters. This isolation would be similar to relevant peak picking at classical 1 H-NMR interpretation.
• Step 2 preparation of 2-chloro-5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-pyrimidine
• 2-chloro-N'-(difluoroacetyl)pyrimidine-5-carbohydrazide 184 mmol
• acetonitrile 400 mL
• 50 mL of N,N-dimethylformamide 50 mL
• 87.5 g of p-toluenesulfonyl chloride (459 mmol) followed by 128 mL of triethylamine (918 mmol).
• reaction mixture was stirred at -20 °C for 3 hours.
• the reaction mixture was filtered and concentrated under reduced pressure.
• the residue was purified by column chromatography on silica gel (gradient petroleum ether/ethyl acetate) followed by a trituration with tert-butyl methyl ether at 20 °C for 3 hours to yield 100 g (100% purity, 47% yield) of the title compound as an off-white solid.
• Step 3 preparation of cis-3-( ⁇ 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl ⁇ amino)-3-(2- fluorophenyl)cyclobutanol (compound I.003)
• a solution of 393 mg (1.80 mmol) of cis-3-amino-3-(2-fluorophenyl)cyclobutanol and 400 mg (1.72 mmol) of 2-chloro-5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-pyrimidine in 5 mL of 1,4-dioxane was added 1.20 mL (6.88 mmol) of N,N-diisopropylethylamine under argon.
• the reaction mixture was stirred at 105 °C for 18 hours.
• the resulting mixture was cooled to room temperature, diluted by water
• Preparation example 2 cis-3-( ⁇ 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl ⁇ amino)-3-(2- fluorophenyl)cyclobutyl acetate (compound I.002) To a solution of 100 mg (0.26 mmol) of 1 cis-3-( ⁇ 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin- 2-yl ⁇ amino)-3-(2-fluorophenyl)cyclobutanol (compound I.003) and 69 ⁇ L (0.39 mmol) of N,N- diisopropylethylamine in 1.5 mL of dry tetrahydrofurane was added at 0 °C dropwise 25 mg (0.31 mmol) of acetyl chloride.
• Mass (M+H) 420.
• PHOTOSTABILITY DATA Measurement of the UV stability reported with the half-life time of the photo degradation was performed by irradiating the samples for 24h with the full UV/VIS Spectrum as available on a SUNTEST XLS+ going from 250nm to 800nm, followed by an analysis of the analyte and its possible degradation products via reversed phase liquid chromatography with UV-detection coupled to a single quadrupole mass spectrometer using the following method: The analyte is determined by measurement of LC-UV-MS , with 0.085% (v/v) formic acid in water and 0.1% (v/v) formic acid acetonitrile as eluent (linear gradient from 5% acetonitrile to 95% acetonitrile).
• the analyte is identified and determined via UV and MS-spectrum.
• the half-life time is determined over the course of 5 time points at 0h, 2h, 4h, 6h and 24h in triplicates each time point. All time points are normalized on detector responses received at 0h.
• the half-life time is determined fitting the results to a 1 st order degradation function and is returned with the unit [h].
• Table 3 provides the half-life times of a selected number of compounds from table 1 and some reference compounds known from WO2019/122323.
• the young plants of wheat were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of Acetone/Dimethyl sulfoxide/ Tween ® 80. After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Puccinia recondita spores. The contaminated wheat plants were incubated for 24 hours at 20°C and at 100% relative humidity and then for 9 days at 20°C and at 70-80% relative humidity.
• the young plants of soybean were treated by spraying the active ingredient prepared as described above.
• Control plants were treated only with an aqueous solution of Acetone/Dimethyl sulfoxide/ Tween® 80.
• the plants were contaminated by spraying the leaves with an aqueous suspension of Phakospora pachyrhizi spores.
• the contaminated soybean plants were incubated for 24 hours at 24°C and at 100% relative humidity and then for 10 days at 24°C and at 70-80% relative humidity. The test was evaluated 11 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.
• Solvent 24.5 parts by weight of acetone 24.5 parts by weight of dimethyl sulfoxide
• Emulsifier 1 part by weight of polyoxyethylene sorbitan monooleate To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier, and the concentrate was diluted with water to the desired concentration.
• the plants were placed in an incubation cabinet at approximately 24°C and a relative atmospheric humidity of approximately 80 % and a day / night interval of 12h.
• 8 days after the application the plant were inoculated with an aqueous spore suspension of the causal agent of soybean rust (Phakopsora pachyrhizi) and stay for 24h without light in the incubation cabinet at approximately 24°C and a relative atmospheric humidity of 95 %.
• the plants remained in the incubation cabinet at approximately 24°C and a relative atmospheric humidity of approximately 80 % and a day / night interval of 12h.
• the test was evaluated 7 days after the inoculation.

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• 2021
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