WO2012066122A1 - 2 - (pyridin- 2 -yl) -quinazoline derivatives and their use as microbicides - Google Patents

2 - (pyridin- 2 -yl) -quinazoline derivatives and their use as microbicides Download PDF

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WO2012066122A1
WO2012066122A1 PCT/EP2011/070459 EP2011070459W WO2012066122A1 WO 2012066122 A1 WO2012066122 A1 WO 2012066122A1 EP 2011070459 W EP2011070459 W EP 2011070459W WO 2012066122 A1 WO2012066122 A1 WO 2012066122A1
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crc
alkoxy
alkyl
alkylthio
alkynyl
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PCT/EP2011/070459
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French (fr)
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Martin Pouliot
Laura Quaranta
Clemens Lamberth
Stephan Trah
Pranab Kanjilal
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Syngenta Participations Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to novel microbiocidally active, in particular fungicidally active, 2-(pyridin-2-yl)-quinazolines. It further relates to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
  • Fungicides are compounds, of natural or synthetic origin, which act to protect plants against damage caused by fungi.
  • Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides.
  • Using fungicides allows a grower to increase the yield of the crop and consequently, increase the value of the crop. Numerous fungicidal agents have been developed. However, the treatment of fungal infestations continues to be a major problem. Furthermore, fungicide resistance has become a serious problem, rendering these agents ineffective for some agricultural uses. As such, a need exists for the development of new fungicidal compounds.
  • Fungicidally active 2-(pyridin-2-yl)-pyrimidines are described in WO2006/010570 and WO2007/116079.
  • the disclosed compounds are characterised by an aryl substituent in pyridine position 6.
  • Fungicidally active 2-(pyridin-2-yl)-pyrimidines are described in WO 2007/116079.
  • the disclosed compounds are characterised by a condensed aliphatic carbocycle or heterocycle.
  • the present invention accordingly relates to compounds of formula (I)
  • C 6 haloalkylsulfonyl CrC 6 alkylsulfinyl, CrC 6 alkylsulfonyl, Ci-C 6 alkylsulfonyl-Ci-C 6 alkyl, C C 6 alkylsulfoximino-CrC 4 alkyl, CrC 6 alkylamino, diCrC 6 alkylamino, C 3 -C 6 cycloalkylamino, C C 6 alkyl-C 3 -C 6 cycloalkylamino, CrC 6 alkylcarbonyl, CrC 6 alkoxycarbonyl, C
  • R 2 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • R 3 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • C 6 haloalkyl C C 4 alkoxy, Ci-C 4 alkoxy-CrC 4 alkyl, C C 4 haloalkoxy, SH, C C 4 alkylthio, C C 4 alkylcarbonythio C C 4 alkylcarbonyloxy;
  • R 4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 - C 6 haloalkynyl, C 3 -C 6 halocycl
  • Each R 5 is independently halogen, cyano, nitro, amino, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 haloalkoxy, CrC 6 alkylthio K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof; with the proviso that when RL is H , then R 4 is not halogen, hydroxyl, 1-naphtyl substituted at the 2-position of the 1-naphtyl, unsubstituted phenyl or unsubstituted 2-pyridy, or
  • R when R is methyl, R 2 and R 3 are H and R 4 is unsubstituted phenyl, then the quinazoline ring is not substituted at the position 6 by a chlorine atom; or
  • R 4 when is methyl then R 4 is not halogen or hydroxyl; or
  • R 4 when R is arylalkyl then R 4 is not hydroxyl.
  • the present invention relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or formula (I) is
  • C 6 haloalkylsulfonyl CrC 6 alkylsulfinyl, CrC 6 alkylsulfonyl, Ci-C 6 alkylsulfonyl-Ci-C 6 alkyl, C C 6 alkylsulfoximino-CrC 4 alkyl, CrC 6 alkylamino, diCrC 6 alkylamino, C3-C 6 cycloalkylamino, C C 6 alkyl-C3-C 6 cycloalkylamino, CrC 6 alkylcarbonyl, CrC 6 alkoxycarbonyl, C
  • R 2 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • R 3 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • Cehaloalkyl C C 4 alkoxy, C C 4 alkoxy-C C 4 alkyl, C C 4 haloalkoxy, SH, C C 4 alkylthio, C C 4 alkylcarbonythio C C 4 alkylcarbonyloxy;
  • R 4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 - C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 alkoxy-Cr C 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkylthio, Ci-C 6 alkylthio-Ci
  • C 6 alkoxycarbonyloxy Ci-C 6 alkylaminocarbonyloxy, diCi-C 6 alkylaminocarbonyloxy, C C 6 alkylcarbonyloxy, Ci-C 6 alkylcarbonylamino, Ci-C 6 alkylcarbonyl-Ci-C 6 alkylamino, C C 6 alkoxyimino, Ci-C 6 alkoxyimino-Ci-C 6 alkyl, triCi.
  • Each R 5 is independently halogen, cyano, nitro, amino, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 haloalkoxy, CrC 6 alkylthio K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof; with the proviso that
  • R 4 when R is methyl then R 4 is not halogen or hydroxyl; or
  • R 4 when R is arylalkyl then R 4 is not hydroxyl.
  • a preferred enmbodiment relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein represents cyano, CHO, NH 2 , CrC 8 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, CrC 6 alkoxy, C
  • R 2 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • R 3 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • C 6 haloalkyl C C 4 alkoxy, Ci-C 4 alkoxy-CrC 4 alkyl, C C 4 haloalkoxy, SH, C C 4 alkylthio, C C 4 alkylcarbonythio C C 4 alkylcarbonyloxy;
  • R 4 represents aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC 6 alkyl, C 2 -C 6 alkenyl, C 2 - C 6 alkynyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 - C 6 halocycloalkyl, CrC
  • Each R 5 is independently halogen, cyano, nitro, amino, hydroxy, d-C 6 alkyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 haloalkoxy, CrC 6 alkylthio
  • K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof.
  • substituents are unsubstituted or substituted. When the substituents are substituted then they are preferably substituted by the substituents given below, wherein the meaning of the substituents for the substituents R 2 , R3, R 4 or R 5 given directly with the meaning of the substituents R ⁇ R 2 , R3, R 4 or R 5 are preferred.
  • the invention covers all agronomically acceptable salts, isomers, structural isomers, stereoisomers, diastereoisomers, enantiomers, tautomers and N-oxides of those
  • Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid.
  • organic carboxylic acids include haloacids such as trifluoroacetic acid.
  • N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Florida, 1991.
  • alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, / ' so-propyl, n-butyl, sec-butyl, / ' so-butyl or te/f-butyl.
  • Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned.
  • the alkenyl and alkynyl groups can be mono- or di-unsaturated.
  • the cycloalkyl groups are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine more preferably chlorine or fluorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy.
  • Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms and comprise at least one halogen atom up to perhalogenated alkyle group.
  • Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2- trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 , 1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl,
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert- butoxy; preferably methoxy and ethoxy.
  • Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2-tetrafluoroethoxy, 2- fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Thioalkyl is, for example, methylthio, ethylthio, propylthio, tert-butylthio, hexylthio.
  • Alkylamino is, for example, methylamino, ethylamino, propylamino, tert-butylamino, hexylamino as well as, for example dimethylamino, diethylamino, dipropylamino, ditert-butylamino, dihexylamino or trimethylamino, triethylamino, tripropylamino, tri tert-butylamino, trihexylamino or 2- to 3-fold substituted amines with different alkyl groups.
  • the aryl groups are groups derived from monoyclic and polycyclic aromatic hydrocarbons by removal of a hydrogen atom from a ring carbon atom.
  • the aryl and heteroaryl groups are, for example, acridinyl, anthracenyl, benzimidazolyl, benzisoxazolyl, benzo[c]thiopheny, benzofuranyl, benzothiazolyl,
  • aryl and heteroaryl groups may also be annealed to alicyclic systems or hetreoalicyclic systems.
  • Alicyclic systems or hetreoalicyclic systems are carbocyclic ring structure which may be saturated or unsaturated (which means having at least one endocyclic double bond or at least one triple bond) wherein in the case of the hetreoalicyclic systems optionally one or more of the carbon atoms are replaced by a heteroatom, but both, the alicyclic systems and the hetreoalicyclic systems may not be a benzenoid or other aromatic system.
  • Examples of such polycyclic ring systems wherein the the aryl and heteroaryl groups are annealed to alicyclic systems or hetreoalicyclic systems are, for example 1 ,2,3,4-tetrahydro-naphthalenyl, 1 ,3-dihydro-2H-1 ,4- benzodiazepinyl, 3,4-dihydro-2H-1 ,5-benzodioxepinyl, 2,3-dihydrobenzofuranyl, 1 ,3- benzodioxolyl or 2,3-dihydro-1 ,4-benzodioxinyl.
  • the alicyclic systems or hetreoalicyclic systems are preferably attached to the rest of the molecule through the aromatic part of the subtituent.
  • Suitable substituents for the aryl or heteroaryl moieties are selected from halogen, cyano, nitro, CHO, C C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C C 6 haloalkyl, C 2 - C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, d-C 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, Ci-C 6 alkoxy-Ci-C 6 alkoxy , Ci-C 6 alkoxy-Ci-C 6 alkylthio, Ci-C 6 alkylthio-Ci-C 6 alkoxy, d- C 6 haloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, Ci-C 4 alkyls
  • the preferred substituents of the substituted alkyl groups, the substituted alkenyl groups, the substituted alkynyl groups, the substituted alkoxy group and the substituted alkylthio group in the compound of formula (I) are selected from the following substituents F, CI, Br, I, -OH, - CN, nitro, -d. 4 alkoxy, -Ci -4 alkylthio, -NR 17 R 18 where R 17 and R 18 are independently H, -Ci.
  • alkynyl wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl groups are either substituted or unsubstituted, preferably these substituents of the substituted groups bear only one further substituent, more preferably are hese substituents of the substituted groups not further substituted.
  • the more preferred substituents of the substituted Ci to C 4 alkyl groups are selected from the following substituents -OH, CN, F, CI, d. 4 alkoxy, d. 4 alkylamino.
  • the alkyl groups are branched or linear.
  • the most preferred alkyl groups are methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl (2-methylpropyl), pentyl, 1-methylpentyl, 1-ethylpentyl, iso-pentyl (3- methylbutyl), hexyl, heptyl, octyl, or nonyl.
  • the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than two further substituents, more preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than one further substituent, most preferred the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) are not further substituted.
  • the preferred alkyl groups and the preferred alkoxy groups are methyl, ethyl, propyl, methoxy and ethoxy groups. Methyl, ethyl and methoxy groups are very particularly preferred.
  • the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein represents cyano, CHO, NH 2 , CrC 8 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 - C 6 cycloalkyl- C 2 -C 6 alkynyl, CrC 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 - C 6 halocycloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 haloalkoxy, CrC 6 alkylthio, C C 6 haloalkylthio, CrC 6 alkylamino, diCrC 6 alkylamino, C 3 -C 6
  • more preferred represents hydrogen, halogen, cyano, hydroxy, CHO, CrC 8 alkyl, C 2 - C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, C 3 -C 6 halocycloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, CrC 6 alkylthio, Ci-C 6 alkylamino, diCi-C 6 alkylamino, C 3 - C 6 cycloalkylamino, CrC 6 alkoxyimino, Ci-C 6 alkoxyimino-Ci-C 6 alkyl;
  • R 2 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • R 3 represents hydrogen, halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • C 6 haloalkyl C C 4 alkoxy, Ci-C 4 alkoxy-CrC 4 alkyl, C C 4 haloalkoxy, SH, C C 4 alkylthio;
  • R 4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or trisubstituted by halogen, cyano, nitro, CHO, CrC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkyl, Ci-C 6 alkoxy-Ci-C 6 alkoxy , Ci-C 6 alkoxy-Ci-C 6 alkylthio, Ci-C 6 alkylthio-Ci-C 6 alkoxy, CrC 6 haloalkoxy, CrC 6 alkylthio, CrC
  • R 4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or
  • Each R 5 is independently halogen, cyano, hydroxy, CrC 6 alkyl, C 3 -C 6 cycloalkyl, C
  • K is an integer selected from 0, 1 ;
  • the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic
  • R ⁇ is C C 6 alkyl, C 3 -C 6 cycloalkyl, C C 6 alkoxy,
  • R 2 is H, C C 6 alkyl, C C 6 alkoxy, CI, F
  • R 3 is H, C C 6 alkyl, C C 6 alkoxy, C C 6 alkylthio
  • R 4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkoxy , C C 6 alkoxy-CrC 6 alkylthio, Ci-C 6 alkylthio-Ci-C 6 alkoxy, CrC 6 alkylthio, CrC 6 haloalkoxy, C C 6 alkylcarbonyl, CrC 6 alkoxycarbonyl, CrC 6 alkylaminocarbonyl, di C
  • R 5 is C C 6 alkyl, C C 6 alkoxy, C C 6 alkylthio, CI, F;
  • K is an integer selected from 0 or 1 , preferably K is 0.
  • the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein
  • F is C C 3 alkyl, C C 3 alkoxy,
  • R 2 is H, C C 3 alkyl, C C 3 alkoxy, F
  • R 3 is H, C C 3 alkyl
  • R 4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of CI, F, C C 3 alkyl, C C 3 haloalkyl, C C 3 alkoxy, Ci-C 6 alkoxy-Ci-C 6 alkoxy , C C 6 alkoxy-CrC 6 alkylthio, d-Cealkylthio-CrCealkoxy, C C 3 alkylthio, C C 3 haloalkoxy, C C 3 alkylcarbonyl, C C 3 alkoxycarbonyl, Ci-C 3 alkylaminocarbonyl, di C
  • R 5 is C C 3 alkyl, C C 3 alkylthio, C C 3 alkoxy, CI, F
  • K is an integer selected from 0 or 1 , preferably K is 0.
  • inventions F1 to F21 are the embodiments F1 to F21 , which are defined as compounds of formula I which are represented by one formula selected from the group consisting of the formulae E1 to E21 as described below, wherein in formulae E1 to E21 the meanings of the substituents R 2 , R 3 and R 4 have the preferred meanings as mentioned above.
  • the embodiment F2.C3 means the following structure
  • R 4 has the preferred meanings as mentioned above or in Table a lines A001 to A226 Or as a further example the embodiment F2.C3 means the following structure
  • R 4 has meanings in Table on lines A001 to A226
  • the compounds of formula II wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula IV, wherein R ⁇ R 2 , R 3 and R 5 are as defined under formula I, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide and optionally an alkylated aniline derivative, or by successive reaction with phosphorus oxychloride and sodium iodide.
  • a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide and optionally an alkylated aniline derivative
  • the compounds of formula IV, wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I can be obtained by transformation of a compound of formula V, wherein R ⁇ R 2 , R 3 are as defined under formula I, with a compound of formula VI, wherein R 5 are as defined under formula I, and a base such as sodium methoxide, sodium ethoxide or potassium te/f-butoxide.
  • the mono- and disubstituted anthranilic acid of formula VI, wherein R 5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula V, wherein R 2 and R 3 are as defined under formula I can be obtained by transformation of a compound of formula VII, wherein R ⁇ R 2 and R 3 are as defined under formula I, with either a cyanide, such as sodium cyanide, potassium cyanide and an activating agent such as methyl iodide, dimethyl sulfate or dimethylcarbamoyl chloride, or a cyanide such as tnmethylsilylcyanide and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
  • a cyanide such as sodium cyanide, potassium cyanide and an activating agent such as methyl iodide, dimethyl sulfate or dimethylcarbamoyl chloride
  • a cyanide such as tnmethylsilylcyanide
  • a base such as triethylamine, ethyldiisopropylamine or pyridine.
  • the compounds of formula VII, wherein R ⁇ R 2 and R 3 are as defined under formula I can be obtained by transformation of a compound of formula VIII, wherein R ⁇ R 2 and R 3 are as defined under formula I, with an oxidatizing agent, such as mefa-chloroperbenzoic acid, hydrogen peroxide or oxone.
  • an oxidatizing agent such as mefa-chloroperbenzoic acid, hydrogen peroxide or oxone.
  • the mono-, di- and trisubstituted pyridines of formula VIII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the compounds of formula IV wherein R 2 , R 3 , and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula X, wherein R ⁇ R 2 , R 3 and R 5 are as defined under formula I, with a base such as sodium hydroxide, sodium methoxide or sodium ethoxide.
  • the compounds of formula X wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XI, wherein R ⁇ R 2 , and R 3 are as defined under formula I, with a compound of formula XII, wherein R 5 are as defined under formula I, a coupling agent such as ⁇ /, ⁇ /'-dicyclohexylcarbodiimide, bis(2-oxo-3- oxazolidinyl)phosphinic chloride, 2-(1 /-/-benzotriazole-1-yl)-1 ,1 ,3,3-tetramethyluronium hexafluorophosphate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride or cyanuric chloride, and, optionally, a base such as triethylamine, ethyldiisopropylamine or N- methylmorpholine
  • the compounds of formula XI, wherein R 2 , and R 3 are as defined under formula I can be obtained by transformation of a compound of formula XIV, wherein R ⁇ R 2 , and R 3 are as defined under formula I, and an oxidizing agent such as potassium permanganate, sodium dichromate or nitric acid.
  • an oxidizing agent such as potassium permanganate, sodium dichromate or nitric acid.
  • the compounds of formula IV wherein R ⁇ R 2 , R3, and R 5 are as defined under formula I
  • R ⁇ R 2 , R3, and R 5 are as defined under formula I
  • R 8 is a C1-C6 alkyl
  • a compound of formula XII wherein R 5 are as defined under formula I
  • a base such as sodium hydroxide, sodium ethoxide or potassium te/f-butoxide.
  • the compounds of formula XIII, wherein R 2 , and R 3 are as defined under formula I and R 8 is a CrC 6 alkyl can be obtained by transformation of a compound of formula (XI), wherein R ⁇ R 2 , and R 3 are as defined under formula I, with a compound of formula XV, wherein R 8 is a CrC 6 alkyl, and an acid such as sulphuric acid, hydrogen chloride or para-toluenesulfonic acid.
  • the compounds of formula IV wherein R ⁇ R 2 , R3, and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XVI, wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I, with a nitrogen source such as formamide, ammonium acetate, ammonium hydroxide or ammonia.
  • a nitrogen source such as formamide, ammonium acetate, ammonium hydroxide or ammonia.
  • the compounds of formula XVI wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XVII, wherein R ⁇ R 2 , and R 3 are as defined under formula I, with a compound of formula XVIII, wherein R 5 are as defined under formula I, and a base such as pyridine, triethylamine or sodium carbonate.
  • the compounds of formula XVII, wherein R 2 , and R 3 are as defined under formula I can be obtained by transformation of a of formula XI, wherein R ⁇ R 2 , and R 3 are as defined under formula I, with a halogenating agent such as sulfonyl chloride, phosphorus oxychloride, oxalyl chloride or cyanuric chloride, and, optionally, a base such as pyridine, triethylamine or sodium carbonate.
  • a halogenating agent such as sulfonyl chloride, phosphorus oxychloride, oxalyl chloride or cyanuric chloride
  • a base such as pyridine, triethylamine or sodium carbonate.
  • the compounds of formula XVI can be obtained in two steps by transformation of a compound of formula XIX, wherein R ⁇ R 2 , R3, and R 5 are as defined under formula I, with a halogenating or acylating agent such as sulfonyl chloride, cyanuric chloride or acetic anhydride, and, optionally, a base such as pyridine, triethylamine or sodium carbonate.
  • a halogenating or acylating agent such as sulfonyl chloride, cyanuric chloride or acetic anhydride
  • a base such as pyridine, triethylamine or sodium carbonate.
  • the compounds of formula XVI, wherein R 2 , R3, and R 5 are as defined under formula I can be obtained by transformation of a compound of formula XX, wherein R ⁇ R 2 and R 3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXI, wherein R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, triethylamine or potassium carbonate, under an atmosphere of carbon monoxide.
  • the compounds of formula XX wherein R ⁇ R 2 and R 3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula VII, wherein R ⁇ R 2 and R 3 are as defined under formula I, with a halide, such as phosphorus oxyhalide, methylsulfonyl chloride or trichloroacetyl chloride, and, optionally, a base such as pyridine or triethylamine.
  • a halide such as phosphorus oxyhalide, methylsulfonyl chloride or trichloroacetyl chloride
  • a base such as pyridine or triethylamine.
  • the compounds of formula XX wherein R 2 and R 3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo
  • a compound of formula (Ilia) wherein is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 ,MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepal
  • the compounds of formula XVI wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XVII , wherein R ⁇ R 2 and R 3 are as defined under formula I, with a compound of formula XXI, wherein R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, triethylamine or potassium carbonate, under an atmosphere of carbon monoxide.
  • a catalyst such as palladium on charcoal, tetrakistriphen
  • the compounds of formula XVI can be obtained by transformation of a compound of formula XXIII, wherein R ⁇ R 2 , R 3 , and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, monoxide.
  • a catalyst such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium a
  • the compounds of formula XXIII, wherein R ⁇ R 2 , R3, and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XVII, wherein R ⁇ R 2 , and R 3 are as defined under formula I, with a compound of formula XXI, wherein R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo,, and a base such as pyridine, triethylamine or sodium carbonate.
  • the compounds of formula IV wherein R 2 , R 3 , and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XXV, wherein R 2 , R 3 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 ,MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(
  • the compounds of formula XXV wherein R 2 , R 3 , and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are a subclass of the compounds of formula IV, wherein R 2 , R 3 , and R 5 are as defined under formula I and substitution is limited to a halogen, and can thus be obtained according to the procedure describing the synthesis of compounds of formula IV.
  • the compounds of formula IV wherein R ⁇ R 2 , R 3 and R 5 are as defined under formula I, can be obtained by transformation of a compound of formula XXVII, wherein R 5 are as defined under formula I, R 8 is a hydrogen or CrC 6 alkyl and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXVI, wherein R ⁇ R 2 and R 3 are as defined under formula I, a catalyst, such as copper(l) chloride, copper(l) bromide or copper(l) iodide, a ligand such as dimethylethylenediamine, proline or BINOL, and a base such as potassium phosphate, sodium carbonate or cesium carbonate.
  • a catalyst such as copper(l) chloride, copper(l) bromide or copper(l) iodide
  • a ligand such as dimethylethylenediamine, proline or BINOL
  • a base such as potassium phosphate,
  • the compounds of formula XXVI, wherein R 2 , and R 3 are as defined under formula I can be obtained by transformation of a compound of formula V, wherein R ⁇ R 2 and R 3 are as defined under formula I, with a base, such as sodium methoxide, and an ammonium salt, such as ammonium chloride.
  • a base such as sodium methoxide
  • an ammonium salt such as ammonium chloride.
  • the compounds of formula 1.1 can be obtained by transformation of a compound of formula XXIX, wherein R 2 , R3, R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 ,MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1]
  • the compounds of formula XXIX wherein R 2 , R 3 , R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XXX, wherein R 2 , R 3 and R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R 4 is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistri
  • the compounds of formula XXX wherein R 2 , R 3 , and R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XXXII, wherein R 2 , R 3 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide.
  • a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide
  • the compounds of formula XXIX wherein R 2 , R3, R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula M, wherein R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula Ml, wherein R 2 and R 3 are as defined under formula I, Hal is a halogen, preferably chloro, bromo or iodo, and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -
  • metallo-substituted pyridines of formula Ml wherein R 2 and R 3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula Mil, wherein R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R 4 is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis
  • the compounds of formula Mil wherein R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula Mill, wherein R 5 are as defined under formula I, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide, and, optionally, a base such as pyridine, triethylamine or diethylaniline.
  • a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide
  • a base such as pyridine, triethylamine or diethylaniline.
  • the compounds of formula Mill wherein R 5 are as defined under formula I, can be obtained by transformation of a compound of formula VI, wherein R 5 are as defined under formula I, with urea, sodium cyanate or potassium cyanate
  • the compounds of formula Mil wherein R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MIV, wherein R 5 are as defined under formula I, with a halogenating agent such as phosgene, diphosgene, triphosgene or carbonyl dibromide. Phosgene or
  • the compounds of formula XXIX wherein R 2 , R3, R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula XXII, wherein R 2 and R 3 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R 4 and R 5 are as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetraki
  • the compounds of formula 1.1 can be obtained by transformation of a compound of formula M, wherein R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula MVI , wherein R ⁇ R 2 and R 3 are as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-
  • the compounds of formula 1.1 can be obtained by transformation of a compound of formula XX, wherein Ri, R 2 and R 3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R 4 and R 5 are as defined under formula I and R 6 .
  • lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride,
  • the compounds of formula 1.1 can be obtained by transformation of a compound of formula MVII, wherein Ri , R 2 , R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (1Mb), wherein R 3 is as defined under formula I and R 6 .
  • R 3 is as defined under formula I and R 6 .
  • lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 wherein either R 7 is independently from each other hydrogen, d-C 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride
  • the compounds of formula MVII, wherein R ⁇ R 2 , R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MVIII, wherein R ⁇ R 2 and R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R 4 is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepal
  • the compounds of formula MVII wherein R 2 , R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo
  • a compound of formula MIX wherein R 2 , R 4 and R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo
  • a compound of formula (Ilia) wherein is as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphos
  • the compounds of formula MIX wherein R 2 , R 4 and R 5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MX, wherein R 2 is as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R 4 and R 5 are as defined under formula I and R 6 is lnCI 2 , lnCI(R 4 ), ln(R 4 ) 2 , MgCI, MgBr, Sn(R 7 ) 3 , ZnCI, ZnBr or B(OR 7 ) 2 , wherein either R 7 is independently from each other hydrogen, CrC 6 alkyl or wherein two R 7 together can form a C 3 -C 8 cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dich
  • the compounds of formula 1.1 can be obtained by transformation of a compound of formula MXI I, wherein R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXVI, wherein R ⁇ R 2 , and R 3 are as defined under formula I, a catalyst, such as copper(l) chloride, copper(l) bromide or copper(l) iodide, a ligand such as dimethylethylenediamine, proline or BINOL, and a base such as potassium phosphate, sodium carbonate or cesium carbonate.
  • a catalyst such as copper(l) chloride, copper(l) bromide or copper(l) iodide
  • a ligand such as dimethylethylenediamine, proline or BINOL
  • a base such as potassium phosphate, sodium carbonate or cesium carbonate.
  • the o/f 70-halogenobenzophenone of formula MXII wherein R 4 and R 5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
  • the reactions to give compounds of formula I are advantageously carried out in aprotic inert organic solvents or in a mixture of aprotic inert organic solvents and water.
  • Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N- dimethylformamide, diethylformamide or N-methylpyrrolidinone.
  • the reaction temperatures are advantageously between -20°C and +120°C.
  • the reactions are slightly exothermic and, as a rule, they can be carried out at ambient temperature.
  • the mixture may be heated briefly to the boiling point of the reaction mixture.
  • the reaction times can also be shortened by adding a few drops of base as reaction catalyst.
  • Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1 ,4-diazabicyclo[2.2.2]octane, 1 ,5-diazabicyclo[4.3.0]non-5-ene or 1 ,5-diazabicyclo[5.4.0]undec-7-ene.
  • inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates, e.g. sodium carbonate and potassium carbonate, hydrogen carbonates, e.g. potassium hydrogen carbonate and sodium hydrogen carbonate, or phosphates, e.g. potassium phosphate, sodium phosphate, may also be used as bases.
  • the bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
  • the compounds of formula I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
  • the invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as active ingredient to the plants, to parts thereof or the locus thereof.
  • the compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants.
  • the compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
  • compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
  • the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene
  • the compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium,
  • Xanthomonas spp Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus.
  • the compounds of formula I are also effective against Asian soybean rust (Phakopsora pachyrhizi).
  • useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco
  • useful plants is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • imazamox by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
  • Useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • YieldGard® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CrylllB(bl) toxin); YieldGard Plus® (maize variety that expresses a CrylA(b) and a Cryll I B(b1 ) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CrylF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c) toxin); Bollgard I® (cotton variety that expresses a CrylA(c) toxin); Bollgard II® (cotton variety that
  • useful plants is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191.
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • Crops or the term “useful plants” is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
  • Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ⁇ -endotoxins, e.g. CrylAb, CrylAc, Cryl F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp.
  • insecticidal proteins from Bacillus cereus or Bacillus popilliae such as ⁇ -endotoxins, e.g. CrylAb, CrylAc, Cryl F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins
  • Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect- specific neurotoxins
  • toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
  • agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors;
  • ribosome-inactivating proteins such as ricin, maize-RIP, abrin, luffin, saporin or bryodin
  • steroid metabolism enzymes such as 3-hydroxysteroidoxidase, ecdysteroid-UDP- glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
  • RIP ribosome-inactivating proteins
  • ⁇ -endotoxins for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins.
  • Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701).
  • Truncated toxins for example a truncated CrylAb, are known.
  • modified toxins one or more amino acids of the naturally occurring toxin are replaced.
  • preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810).
  • Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
  • Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
  • the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
  • insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
  • Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available.
  • YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a CrylAc toxin); Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin
  • transgenic crops are:
  • Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylAb toxin. Bt1 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
  • MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150
  • MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
  • NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810.
  • NK603 x MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
  • locus of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil.
  • An example for such a locus is a field, on which crop plants are growing.
  • plant propagation material is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants.
  • Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion.
  • plant propagation material is understood to denote seeds.
  • the compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation. Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
  • compositions are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.
  • the methods of application such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.
  • the compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
  • the compounds of formula I or compositions comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds.
  • further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • a preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant or, if desired as well, a further, other biocidally active ingredient, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active
  • the present invention relates additionally to mixtures comprising at least a compound of formula I and at least a further, other biocidally active ingredient and optionally further ingredients.
  • the further, other biocidally active ingredient are known for example from "The Pesticide Manual” [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council] or its electronic version "e-Pesticide Manual V4.2" or from the website http://www.alanwood.net/pesticides/ or preferably one of the further pesticides listed below.
  • TX means one compound selected from the group consisting of the compounds of formula (I) or a cspecific compound of formulae E1.001.C1 to
  • TX means at least one compound selected from the compounds E1.001.C1 to
  • TX means a specific compound selected from Table 22 (163 specific compounds); an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
  • an acaricide selected from the group of substances consisting of 1 , 1-bis(4-chlorophenyl)-2- ethoxyethanol (lUPAC name) (910) + TX, 2,4-dichlorophenyl benzenesulfonate
  • TX isopropyl 0-(methoxyaminothiophosphoryl)salicylate (lUPAC name) (473) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephosfolan (1261) + TX, mesulfen (alternative name) [CCN] + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methidathion (529) + TX, methiocarb (530) + TX, methomyl
  • development code (development code) (1382) + TX, RA-17 (development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX,
  • spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI-121 (development code) (1404) + TX, sulfiram (alternative name) [CCN] + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphur (754) + TX, SZI-121 (development code) (757) + TX, tau-fluvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, terbam (alternative name) + TX,
  • tetrachlorvinphos (777) + TX, tetradifon (786) + TX, tetranactin (alternative name) (653) + TX, tetrasul (1425) + TX, thiafenox (alternative name) + TX, thiocarboxime (1431) + TX, thiofanox (800) + TX, thiometon (801) + TX, thioquinox (1436) + TX, thuringiensin (alternative name) [CCN] + TX, triamiphos (1441) + TX, triarathene (1443) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trifenofos (1455) + TX, trinactin (alternative name) (653) + TX, vamidothion (847) + TX, vaniliprol
  • an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (lUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (lUPAC name) (347) and triphenyltin hydroxide (lUPAC name) (347) + TX,
  • an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX, an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122)
  • a bactericide selected from the group of substances consisting of 1-hydroxy-1 /-/-pyridine-2- thione (lUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (lUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (lUPAC name) (170) + TX, copper hydroxide (lUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1 105) + TX, dodicin (1 112) + TX, fenaminosulf (1 144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (48
  • a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis
  • a soil sterilant selected from the group of substances consisting of iodomethane (lUPAC name) (542) and methyl bromide (537) + TX,
  • a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX,
  • an insect pheromone selected from the group of substances consisting of (£)-dec-5-en-1-yl acetate with (£)-dec-5-en-1-ol (lUPAC name) (222) + TX, (£)-tridec-4-en-1-yl acetate (lUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (lUPAC name) (541) + TX, (E,Z)- tetradeca-4,10-dien-1-yl acetate (lUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (lUPAC name) (285) + TX, (Z)-hexadec-1 1-enal (lUPAC name) (436) + TX, (Z)-hexadec- 1 1-en-1-yl acetate (lUPAC name) (437) + TX, (Z)-hexadec-13
  • an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (lUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (lUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (lUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1 137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
  • an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (lUPAC/Chemical Abstracts name) (1058) + TX, 1 , 1-dichloro-2,2-bis(4-ethylphenyl)ethane (lUPAC name) (1056), + TX, 1 ,2-dichloropropane (lUPAC/Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (lUPAC name) (1063) + TX, 1-bromo- 2-chloroethane (lUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-1-(3,4- dichlorophenyl)ethyl acetate (lUPAC name) (1451) + TX, 2,2-dichlorovinyl 2- ethylsulphinylethyl methyl phosphate (lUPAC name) (10
  • hexafluorosilicate (alternative name) [CCN] + TX, barium polysulfide (lUPAC/Chemical Abstracts name) (892) + TX, barthrin [CCN] + TX, Bayer 22/190 (development code) (893) + TX, Bayer 22408 (development code) (894) + TX, bendiocarb (58) + TX, benfuracarb (60) + TX, bensultap (66) + TX, beta-cyfluthrin (194) + TX, beta-cypermethrin (203) + TX, bifenthrin (76) + TX, bioallethrin (78) + TX, bioallethrin S-cyclopentenyl isomer (alternative name) (79) + TX, bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX
  • chlordecone (963) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorethoxyfos (129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131) + TX, chlorfluazuron (132) + TX, chlormephos (136) + TX, chloroform [CCN] + TX, chloropicrin (141) + TX, chlorphoxim (989) + TX, chlorprazophos (990) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, chromafenozide (150) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, cis-resmethrin (alternative name) + TX, c
  • methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofluthrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + T
  • development code (development code) (1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX, ryania (alternative name) (1387) + TX, ryanodine (traditional name) (1387) + TX, sabadilla (alternative name) (725) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, SI-0205 (compound code) + TX, SI-0404 (compound code) + TX, SI-0405 (compound code) + TX, silafluofen (728) + TX, SN 72129
  • a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (lUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (lUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913)
  • a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, 1 ,2-dibromo-3-chloropropane (lUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2-dichloropropane (I U PA C/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (lUPAC name) (1063) + TX, 1 ,3-dichloropropene (233) + TX, 3,4- dichlorotetrahydrothiophene 1 , 1 -dioxide (lUPAC/Chemical Abstracts name) (1065) + TX, 3- (4-chlorophenyl)-5-methylrhodanine (lUPAC name) (980) + TX, 5-methyl-6-thioxo- 1 ,3,5- thiadiazinan-3-ylacetic acid (lU
  • a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
  • a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
  • a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (lUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (lUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol
  • a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (lUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (lUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
  • an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (lUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
  • a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
  • a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
  • azaconazole 60207-31-0] + TX, bitertanol [70585-36-3] + TX, bromuconazole [116255-48-2] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [1 19446-68-3] + TX, diniconazole
  • aldimorph (CAS 91315-15-0); arsenates (CAS 1327-53-3); benalaxyl -M (CAS 98243-83-5); benthiavalicarb (CAS 413615-35-7); cadmium chloride (CAS 10108-64-2); cedar leaf oil (CAS 8007-20-3); chlorine (CAS 7782-50-5); cinnamaldehyde (CAS: 104-55-2); copper ammoniumcarbonate (CAS 33113-08-5); copper oleate (CAS 1120-44-1); iodocarb (3-lodo- 2-propynyl butyl carbamate) (CAS 55406-53-6); hymexazole (CAS 10004-44-1); manganous dimethyldithiocarbamate (CAS 15339-36-3); mercury (CAS 7487-94-7; 21908-53-2; 7546-30- 7); metrafenone (CAS 220899-03-6); neem oil (hydrophobic extract) (CAS 800
  • Compound B-1.1 (“enestrobin”) is described in EP-0-936-213; compound B-3.1 (“flumorph”) in US-6,020,332, CN-1-167-568, CN-1-155-977 and in EP-0-860-438; compound B-5.1 (“mandipropamid”) in WO 01/87822; compound B-5.2 in WO 98/46607; compound B-5.3 (“fluopicolide”) in WO 99/42447; compound B-5.4 (“cyflufenamid”) in WO 96/19442;
  • compound B-5.8 (3-difluoromethyl-1-methyl-1 H-pyrazole-4- carboxylic acid (2-bicyclopropyl-2-yl-phenyl)-amide) is described in WO 03/74491 ;
  • compound B-5.9 (3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (9-isopropyp-1 , 2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide) is described in WO 04/35589 and in WO 06/37632;
  • compound B-5.10 (1 ,3-dimethyl-5-fluoro-1 H-pyrazole-4-carboxylic acid [2- (1 ,3-dimethylbutyl)phenyl]-amide) is described in WO 03/10149;
  • compound B-5.1 1 (3- difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (3',4'-dichloro-5
  • Sedaxane ( ⁇ /-[2-[1 , 1 '- bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1 /-/-pyrazole-4-carboxamide) is described in WO 2003/074491 and is registered under the CAS-Reg.
  • the compound of formula (VI) is described in WO 2008/014870; the compound of formula (Via) is described in WO 2010/063700; a compound of formula (Vlb) (Fluxapyroxad) is described in WO2006087343 and WO2009007344 and is registered under the CAS-RegNr.: 907204-31-3, a compound of formula (Vic) which is 3-(difluoromethyl)-N-methoxy-1-methyl- N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]-1 H-pyrazole-4-carboxamide is described in WO2010063700; (S)-[3-(4-Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y I]- pyridin-3-yl-methanol, 3-(4-Chloro-2-fluoro-phenyl)-5 -
  • component (B) in combination with component TX surprisingly and substantially may enhance the effectiveness of the latter against fungi, and vice versa. Additionally, the method of the invention is effective against a wider spectrum of such fungi that can be combated with the active ingredients of this method, when used solely.
  • the weight ratio of component TX to component (B) is from 2000 : 1 to 1 : 1000.
  • a non-limiting example for such weight ratios is compound of formula I : compound of formula B-2 is 10: 1.
  • the weight ratio of component TX to component (B) is preferably from 100 : 1 to 1 : 100; more preferably from 20 : 1 to 1 : 50.
  • the active ingredient mixture of component TX to component (B) comprises compounds of formula I and a further, other biocidally active ingredients or compositions or if desired, a solid or liquid adjuvant preferably in a mixing ratio of from 1000: 1 to 1 : 1000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20: 1 to 1 :20, even more especially from 10:1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2:1 to 1 :2, and a ratio of from 4: 1 to 2: 1 being likewise preferred, above all in a ratio of 1 :1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3: 1 , or 3:2, or 2: 1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2, or 1
  • Those mixing ratios are understood to include, on the one hand, ratios by weight and also, on other hand, molar ratios. It has been found, surprisingly, that certain weight ratios of component TX to component (B) are able to give rise to synergistic activity. Therefore, a further aspect of the invention are compositions, wherein component TX and component (B) are present in the composition in amounts producing a synergistic effect. This synergistic activity is apparent from the fact that the fungicidal activity of the composition comprising component TX and component (B) is greater than the sum of the fungicidal activities of component TX and of component (B). This synergistic activity extends the range of action of component TX and component (B) in two ways.
  • synergism corresponds to a positive value for the difference of (O-E). In the case of purely complementary addition of activities (expected activity), said difference (O-E) is zero. A negative value of said difference (O-E) signals a loss of activity compared to the expected activity.
  • compositions according to the invention can also have further surprising advantageous properties.
  • advantageous properties are: more advantageuos degradability; improved toxicological and/or ecotoxicological behaviour; or improved characteristics of the useful plants including: emergence, crop yields, more developed root system, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, improved plant vigor, and early germination.
  • compositions according to the invention have a systemic action and can be used as foliar, soil and seed treatment fungicides.
  • compositions according to the invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of plants which grow later are also protected from attack by phytopathogenic microorganisms.
  • compositions according to the invention can be applied to the phytopathogenic microorganisms, the useful plants, the locus thereof, the propagation material thereof, storage goods or technical materials threatened by microorganism attack.
  • compositions according to the invention may be applied before or after infection of the useful plants, the propagation material thereof, storage goods or technical materials by the microorganisms.
  • a further aspect of the present invention is a method of controlling diseases on useful plants or on propagation material thereof caused by phytopathogens, which comprises applying to the useful plants, the locus thereof or propagation material thereof a composition according to the invention.
  • Preferred is a method, which comprises applying to the useful plants or to the locus thereof a composition according to the invention, more preferably to the useful plants.
  • a method which comprises applying to the propagation material of the useful plants a composition according to the invention.
  • the components (B) are known. Where the components (B) are included in "The Pesticide Manual” [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular component (B); for example, the compound "abamectin” is described under entry number (1). Most of the components (B) are referred to hereinabove by a so-called “common name”, the relevant "ISO common name” or another "common name” being used in individual cases.
  • the designation is not a "common name”
  • the nature of the designation used instead is given in round brackets for the particular component (B); in that case, the lUPAC name, the lUPAC/Chemical Abstracts name, a "chemical name”, a “traditional name”, a “compound name” or a “develoment code” is used or, if neither one of those designations nor a "common name” is used, an "alternative name" is employed.
  • aldimorph (CAS 91315-15-0); arsenates (CAS 1327-53-3); benalaxyl -M (CAS 98243-83-5); benthiavalicarb (CAS 413615-35-7); cadmium chloride (CAS 10108-64-2); cedar leaf oil (CAS 8007-20-3); chlorine (CAS 7782-50-5); cinnamaldehyde (CAS: 104-55-2); copper ammoniumcarbonate (CAS 33113-08-5); copper oleate (CAS 1120-44-1); iodocarb (3-lodo- 2-propynyl butyl carbamate) (CAS 55406-53-6); hymexazole (CAS 10004-44-1); manganous dimethyldithiocarbamate (CAS 15339-36-3); mercury (CAS 7487-94-7; 21908-53-2; 7546-30- 7); metrafenone (CAS 220899-03-6); neem oil (hydrophobic extract) (CAS 800
  • Compound B-1.1 (“enestrobin”) is described in EP-0-936-213; compound B-3.1 (“flumorph”) in US-6,020,332, CN-1-167-568, CN-1-155-977 and in EP-0-860-438; compound B-5.1 (“mandipropamid”) in WO 01/87822; compound B-5.2 in WO 98/46607; compound B-5.3 (“fluopicolide”) in WO 99/42447; compound B-5.4 (“cyflufenamid”) in WO 96/19442;
  • compound B-5.8 (3-difluoromethyl-1-methyl-1 H-pyrazole-4- carboxylic acid (2-bicyclopropyl-2-yl-phenyl)-amide) is described in WO 03/74491 ;
  • compound B-5.9 (3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (9-isopropyp-1 , 2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide) is described in WO 04/35589 and in WO 06/37632;
  • compound B-5.10 (1 ,3-dimethyl-5-fluoro-1 H-pyrazole-4-carboxylic acid [2- (1 ,3-dimethylbutyl)phenyl]-amide) is described in WO 03/10149;
  • compound B-5.1 1 (3- difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (3',4'-dichloro-5
  • Sedaxane ( ⁇ /-[2-[1 , 1 '- bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1 /-/-pyrazole-4-carboxamide) is described in WO 2003/074491 and is registered under the CAS-Reg. 874967-67-6;
  • the compound of formula (VI) is described in WO 2008/014870; and the compounds of formula (VII) is described in WO 2007/048556.
  • Fomesafen is registered under the CAS-Reg. No. 72178-02-0.
  • composition stands for the various mixtures or combinations of components TX and (B), for example in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.
  • the order of applying the components TX and (B) is not essential for working the present invention.
  • compositions according to the invention may also comprise more than one of the active components (B), if, for example, a broadening of the spectrum of disease control is desired. For instance, it may be advantageous in the agricultural practice to combine two or three components (B) with component TX.
  • An example is a composition comprising a compound of formula (I), azoxystrobin and cyproconazole.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i. /ha, most preferably from 20g to 600g a.i./ha.
  • convenient rates of application are from 10mg to 1 g of active substance per kg of seeds.
  • the rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
  • the compounds of formula (I), or a pharmaceutical salt thereof, described above may also have an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal.
  • Animal can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human.
  • Treatment means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection.
  • prevention means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
  • a compound of formula (I) in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal.
  • a compound of formula (I) as a pharmaceutical agent.
  • a compound of formula (I) as an antimicrobial agent in the treatment of an animal.
  • a pharmaceutical composition comprising as an active ingredient a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal.
  • This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs.
  • this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion.
  • this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection.
  • this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
  • the compounds of formula (I) may be effective against various microbial species able to cause a microbial infection in an animal.
  • microbial species are those causing Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terms, A. nidulans and A. niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C.
  • Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terms, A. nidulans and A. niger
  • Blastomycosis such as Blastomyces dermatitidis
  • Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C.
  • Fusarium Spp such as Fusarium oxysporum and Fusarium solani
  • Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolificans.
  • Microsporum Spp Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and
  • Histoplasma Spp Histoplasma Spp.
  • Example P1 Preparation of 2-(6-Methyl-pyridin-2-yl)-4-phenyl-quinazoline) a) To a mixture of anthranilamide (5.00 g, 36.7 mmol) and triethylamine (10.2 ml 73.4 mmol,) in DCE (75 ml) was successively added bis(2-oxo-3-oxazolidinyl)phosphinic chloride (1 1.22 g, 44.07 mmol) and 6-methylpicolinic acid (5.666 g, 41.32 mmol). The mixture was stirred under reflux for 1 h and then cooled to RT.
  • Example P2 Preparation of 2-(6-Ethyl-pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline a) To a mixture of anthranilamide (5.00 g 36.7 mmol) and triethylamine (10.2 ml 73.4 mmol) in DCE (75 ml) was added bis(2-oxo-3-oxazolidinyl)phosphinic chloride (11.22 g 44.07 mmol) and 6-bromopicolinic acid (8.35 g, 41.3 mmol). The mixture was heated under reflux for 1 h and then cooled to RT.
  • the resulting cloudy solution was canulated to a solution of 2-(6-bromo-pyridin-2-yl)-4-(methoxy-phenyl)-quinazoline (0.100 g, 0.255 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (0.029 g, 0.025 mmol) in THF (0.5 ml) under inert atmosphere and the resulting mixture was heated under reflux overnight. The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na 2 S0 4 and concentrated under reduced pressure.
  • Example P3 Preparation of 2-(4-Methoxy-6-methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)- quinazoline a) To a solution of 4-chloro-2-picoline (2.00 g, 15.7 mmol) in CH 2 CI 2 (18.4 ml) was added portionwise mefa-chloroperbenzoic acid (5.024 g, 20.38 mmol) over a period of 1 h. The suspension was stirred overnight at RT and the concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/MeOH; 100/0 to 90/10) to afford 4-chloro-2-methyl-pyridine 1 -oxide as a yellow oil.
  • the tetrakis(triphenylphosphine)palladium(0) (0.093 g, 0.080 mmol) was added and the mixture was heated under MW irradiation at 1 10 °C for 25 min.
  • the reaction mixture was cooled, diluted with water and extracted with ethyl acetate.
  • the combined organic layers were dried over Na 2 S0 4 and concentrated under reduced pressure.
  • the residue was purified by flash column chromatography (CH 2 CI 2 /AcOEt; 100/0 to 80/20) to afford 2-(4-chloro-6-methyl- pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline as a yellow powder.
  • Example P4 Preparation of A/,A/-Diethyl-4-[2-(6-methyl-2-pyridyl)quinazolin-4-yl]aniline a) To a vial containing 2-(6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one (0.200g, 0.843 mmol) was added phosphorus oxychloride (0.309 ml, 3.37 mmol) and diethylaniline (0.337 ml, 2.1 1 mmol). The mixture was heated under MW irradiation at 120 °C for 1 h.
  • the resulting cloudy solution was canulated to a solution of 2-(4-chloro-6-methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)- quinazoline (0.140 g, 0.387 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (0.045 g, 0.040 mmol) in THF (0.5ml) under inert atmosphere and the resulting mixture was heated under reflux overnight. The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na 2 S0 4 and concentrated under reduced pressure.
  • Example P6 Preparation of 6-methoxy-2-(6-methyl-2-pyridyl)-4-phenyl-quinazoline a) Preparation of 2-methyl-pyridin-1 -oxide: To a solution of 2-picoline (2g, 22mmol) in ethyl acetate (20ml) in a 50 ml round bottom flask was added 3-chloroperbenzoic acid (50%, 7.39g, 43mmol) in small portions over a period of 10 min. at 0°C. After complete addition, the reaction mixture was stirred at room temperature till TLC indicated completion of the reaction. Reaction mass was concentrated under reduced pressure and subjected to column chromatography using 5% methanol in dichloromethane as eluent to afford the desired product as viscous liquid.
  • reaction mixture was then stirred at 60°C till the completion of the reaction (TLC).
  • TLC cold (room temperature) reaction mixture was filtered through a celite bed and the clear filtrate was evaporated to dryness and was directly subjected to flash column chromatography.
  • the desired 8-methoxy-2-(6-methyl-pyridin-2-yl) -4-phenyl-quinazoline was obtained as solid, M .P.100 -102°C
  • Example P10 Preparation of 2-(5-Fluoro-6-methyl-pyridin-2-yl)-4-phenyl-quinazoline a) Preparation of 2-(6-chloro-5-fluoro-pyridin-2-yl)-benzo[d][1 ,3]oxazin-4-one: To a solution of 6-chloro-5-fluoro-pyridine-2-carboxylic acid (2.20g, 12.50 mmol) in dichloroethane (60 ml) and Et 3 N (4.4 ml, 31.30 mmol), at room temperature, anthranilic acid amide (1.88g, 13.8 mmol) was added followed by bis(2-oxo-3-oxazolidinyl)phosphonic chloride (3.51 g, 13.8 mmol).
  • the suspension was stirred at 80°C during 1.5 hour, under nitrogen atmosphere. After evaporation of the volatiles under reduced pressure, water was added and the mixture was filtered. The filtered solid (6-chloro-5-fluoro-pyridine-2-carboxylic acid (2-carbamoyl- phenyl)-amide) was washed with water and diethylether, dried overnight under vacuum and used for the next step without purification.
  • 6-chloro-5-fluoro-pyridine-2-carboxylic acid (2-carbamoyl-phenyl)-amide (2.70 g, 9.19 mmol) was stirred in tetrahydrofurane (50 ml) and 1 M aq NaOH (37 ml) was added at room temperature. The suspension was stirred at reflux during 6 hours then cooled to room temperature. After avaporation of the volatiles under reduced pressure to one third of the volume the mixture was filtered.
  • the line A001 signifies a phenyl group
  • A010 signifies a para-tolyl group
  • Table 1.1 This table discloses the 226 specific compounds E1.001.C1 to E1. 226. C1 of formula
  • R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines A 001 to A 226 of Table A and Ri ,R 2 and R 3 have the specific meaning as given in the embodiment C1.
  • the specific compound E1.023.C1 is the compound of the formula E1 , in which R 4 has the specific meaning given in the line A 023 of the Table A:
  • Table 1.2 This table discloses the 226 specific compounds E1.001.C2 to E1. 226.C2 as in Table 1.1 but R ⁇ R 2 and R3 have the specific meaning as given in the embodiment C2.
  • Table 1.3 This table discloses the 226 specific compounds E1.001.C3 to E1. 226.C3 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C3.
  • Table 1.4 This table discloses the 226 specific compounds E1.001.C4 to E1. 226.C4 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C4.
  • Table 1.5 This table discloses the 226 specific compounds E1.001.C5 to E1. 226.
  • Table 1.6 This table discloses the 226 specific compounds E1.001.C6 to E1. 226.C6 as in Table 1.1 but R 2 and R 3 have the specific meaning as given in the embodiment C6.
  • Table 1.7 This table discloses the 226 specific compounds E1.001.C7 to E1. 226.C7 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C7.
  • Table 1.9 This table discloses the 226 specific compounds E1.001.C9 to E1. 226.C9 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C9.
  • Table 1.10 This table discloses the 226 specific compounds E1.001.C10 to E1. 226. C10 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C10.
  • Table 1.11 This table discloses the 226 specific compounds E1.001.C1 1 to E1. 226. C11 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C11.
  • Table 1.12 This table discloses the 226 specific compounds E1.001.C12 to E1. 226. C12 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C12.
  • Table 1.13 This table discloses the 226 specific compounds E1.001.C13 to E1. 226.
  • Table 1.14 This table discloses the 226 specific compounds E1.001.C14 to E1. 226. C14 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C14.
  • Table 1.15 This table discloses the 226 specific compounds E1.001.C15 to E1. 226. C15 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C15.
  • Table 1.16 This table discloses the 226 specific compounds E1.001.C16 to E1. 226. C16 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C16.
  • Table 1.17 This table discloses the 226 specific compounds E1.001.C17 to E1. 226.C17 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C17.
  • Table 1.18 This table discloses the 226 specific compounds E1.001.C18 to E1. 226. C18 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C18.
  • Table 1.19 This table discloses the 226 specific compounds E1.001.C19 to E1. 226. C19 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C19.
  • Table 1.20 This table discloses the 226 specific compounds E1.001.C20 to E1. 226.
  • Table 1.21 This table discloses the 226 specific compounds E1.001.C21 to E1. 226.C21 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C21.
  • Table 1.22 This table discloses the 226 specific compounds E1.001.C22 to E1. 226. C22 as in Table 1.1 but R 2 and R 3 have the specific meaning as given in the embodiment C22.
  • Table 1.23 This table discloses the 226 specific compounds E1.001.C23 to E1. 226. C23 as in Table 1.1 but R 2 and R 3 have the specific meaning as given in the embodiment C23.
  • Table 1.24 This table discloses the 226 specific compounds E1.001.C24 to E1. 226.C24 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C24.
  • Table 1.25 This table discloses the 226 specific compounds E1.001.C25 to E1. 226. C25 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C25.
  • Table 1.26 This table discloses the 226 specific compounds E1.001.C26 to E1. 226. C26 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C26.
  • Table 1.27 This table discloses the 226 specific compounds E1.001.C27 to E1. 226.
  • Table 1.28 This table discloses the 226 specific compounds E1.001.C28 to E1. 226. C28 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C28.
  • Table 1.29 This table discloses the 226 specific compounds E1.001.C29 to E1. 226.C29 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C29.
  • Table 1.30 This table discloses the 226 specific compounds E1.001.C30 to E1. 226.C30 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C30.
  • Table 1.31 This table discloses the 226 specific compounds E1.001.C31 to E1. 226.C31 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C31.
  • Table 1.32 This table discloses the 226 specific compounds E1.001.C32 to E1. 226.C32 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C32.
  • Table 1.33 This table discloses the 226 specific compounds E1.001.C33 to E1. 226.C33 as in Table 1.1 but R ⁇ R 2 and R 3 have the specific meaning as given in the embodiment C33.
  • Table 2.1 This table discloses the 226 specific compounds E2.001.C1 to E2.226. C1 of the formula
  • each of the of the variables , R 2 , R3, and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 2.2 to 2.33 each of these tables discloses 226 specific compounds E2.001.CX to E2.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • the compound E2.158.C21 has the following formula:
  • Table 3.1 This table discloses the 226 specific compounds E3.001.C1 to E3.226.C1 of the formula
  • each of these tables discloses 226 specific compounds E3.001.CX to E3.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 4.1 This table discloses the 226 specific compounds E4.001.C1 to E4. 226. C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 4.2 to 4.33 each of these tables discloses 226 specific compounds E4.001.CX to E4.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 5.1 This table discloses the 226 specific compounds E5.001.C1 to E5. 226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 5.2 to 5.33 each of these tables discloses 226 specific compounds E5.001.CX to E5.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 6.1 This table discloses the 226 specific compounds E6.001.C1 to E6.226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 6.2 to 6.33 each of these tables discloses 226 specific compounds E6.001.CX to E6.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 7.1 This table discloses the 226 specific compounds E7.001.C1 to E7.226.C1 of the formula
  • each of the of the variables R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 7.2 to 7.33 each of these tables discloses 226 specific compounds E7.001.CX to E7.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 8.1 This table discloses the 226 specific compounds E8.001.C1 to E8.226.C1 of the formula
  • each of these tables discloses 226 specific compounds E8.001.CX to E8.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 9.1 This table discloses the 226 specific compounds E9.001.C1 to E9.226.C1 of the formula
  • each of the of the variables , R 2 , R3, and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 9.2 to 9.33 each of these tables discloses 226 specific compounds E9.001.CX to E9.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • each of these tables discloses 226 specific compounds E10.001.CX to E10.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 1 1.1 This table discloses the 226 specific compounds E11.001.C1 to E11.226. C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 1 1.2 to 1 1.33 each of these tables discloses 226 specific compounds E11.001.CX to E11.226. CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • each of these tables discloses 226 specific compounds E12.001.CX to E12.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 13.1 This table discloses the 226 specific compounds E13.001.C1 to E13.226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 13.2 to 13.33 each of these tables discloses 226 specific compounds E13.001.CX to E13.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
  • Table 14.1 This table discloses the 226 specific compounds E14.001.C1 to E14.226.C1 of the formula
  • each of these tables discloses 226 specific compounds E14.001.CX to E14.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 15.1 This table discloses the 226 specific compounds E15.001.C1 to E15.226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 15.2 to 15.33 each of these tables discloses 226 specific compounds E15.001.CX to E15.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 16.1 This table discloses the 226 specific compounds E16.001.C1 to E16.001.C1 of the formula
  • each of these tables discloses 226 specific compounds E16.001.CX to E16.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 17.1 This table discloses the 226 specific compounds E17.001.C1 to E17.226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 17.2 to 17.33 each of these tables discloses 226 specific compounds E17.001.CX to E17.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 18.1 This table discloses the 226 specific compounds E18.001.C1 to E18.226.C1 of the formula
  • each of these tables discloses 226 specific compounds E18.001.CX to E18.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 19.1 This table discloses the 226 specific compounds E19.001.C1 to E19.226.C1 of the formula
  • each of the of the variables , R 2 , R 3 , and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 19.2 to 19.33 each of these tables discloses 226 specific compounds E19.001.CX to E19.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 20.1 This table discloses the 226 specific compounds E20.001.C1 to E20.226.C1 of the formula
  • each of these tables discloses 226 specific compounds E20.001.CX to E20.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 21.1 This table discloses the 226 specific compounds E21.001.C1 to E21.226. C1 of the formula
  • each of the of the variables , R 2 , R3, and R 4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
  • Tables 21.2 to 21.33 each of these tables discloses 226 specific compounds E21.001.CX to E21.226. CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
  • Table 22 shows selected m.p. and/or LCMS data and retention times/MW for compounds of Tables 1 to 21.
  • Type of column Waters ACQUITY U 'LC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
  • Instrument Parameter lonisation method: Electrospray ; Polarity: positive (negative) ions Capillary (kV) 3.00, Cone (V) 30.00 , Extractor (V) 2.00, Source Temperature (°C) 100, Desolvation Temperature (°C) 250, Cone Gas Flow (L/Hr) 50, Desolvation Gas Flow (L/Hr) 400
  • HP 1100 HPLC from Agilent solvent degasser, quaternary pump (ZCQ) / binary pump (ZDQ), heated column compartment and diode-array detector.
  • Instrument Parameter lonisation method: Electrospray ; Polarity: positive (negative) ions Capillary (kV) 3.80, Cone (V), Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 350, Cone Gas Flow (L/Hr) OFF, Desolvation Gas Flow (L/Hr) 600
  • Table 22 Melting point data and/or retention times for compounds of Table 1 to 21
  • Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
  • Example F-2 Emulsifiable concentrate
  • Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
  • Examples F-3.1 to F-3.4 Solutions Components F-3.1 F-3.2 F-3.3 F-3.4
  • N-methylpyrrolid-2-one 20% - - epoxidised coconut oil - - 1 % 5% benzin (boiling range: 160-190°) - - 94% -
  • the solutions are suitable for use in the form of microdrops.
  • the novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.
  • Example F7 Flowable concentrate for seed treatment
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a
  • suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • Biological example 1 fungicidal activity against Alternaria solani I tomato / leaf disc (early blight)
  • Tomato leaf disks cv. Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated leaf disks were incubated at 23 °C / 21°C (day/night) and 80% relative humidity (rh) under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5 - 7 days after application).
  • Biological example 2 fungicidal activity against Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) / wheat / leaf disc preventative (Powdery mildew on wheat)
  • Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated by shaking powdery mildew infected plants above the test plates 1 day after application.
  • the inoculated leaf disks were incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
  • DMSO fetal sulfate
  • Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores iss added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Biological example 5 fungicidal activity against Glomerella lagena um (Colletotrichum lagena um) I liquid culture (Anthracnose)
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was measured photometrically 3-4 days after application.
  • nutrient broth PDB potato dextrose broth
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
  • nutrient broth PDB potato dextrose broth
  • Biological example 9 fungicidal activity against Phaeosphaeria nodorum (Septoria nodorum) /wheat / leaf disc preventative (Glume blotch)
  • Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated test leaf disks were incubated at 20°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
  • Tomato leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks were incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
  • Biological example 1 1 fungicidal activity against Plasmopara viticola I grape / leaf disc preventative (late blight)
  • Grape vine leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks were incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
  • Biological example 12 fungicidal activity against Puccinia recondita f. sp. tritici / wheat / leaf disc preventative (Brown rust)
  • Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks were inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
  • Biological example 13 fungicidal activity against Pyrenophora teres I barley / leaf disc preventative (Net blotch)
  • Barley leaf segments cv. Hasso were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf segmens were inoculated with a spore suspension of the fungus 2 days after application.
  • the inoculated leaf segments were incubated at 20°C and 65% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5 - 7 days after application).
  • Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal material was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
  • nutrient broth PDB potato dextrose broth

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Abstract

Compounds of formula I wherein the other substituents R1, R2, R3, R4, R5 and R6 are as defined in claim 1, and their use as microbicides.

Description

2 - (PYRIDIN- 2 -YL) -QUINAZOLINE DERIVATIVES AND THEIR USE AS MICROBICIDES
The present invention relates to novel microbiocidally active, in particular fungicidally active, 2-(pyridin-2-yl)-quinazolines. It further relates to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
Fungicides are compounds, of natural or synthetic origin, which act to protect plants against damage caused by fungi. Current methods of agriculture rely heavily on the use of fungicides. In fact, some crops cannot be grown usefully without the use of fungicides. Using fungicides allows a grower to increase the yield of the crop and consequently, increase the value of the crop. Numerous fungicidal agents have been developed. However, the treatment of fungal infestations continues to be a major problem. Furthermore, fungicide resistance has become a serious problem, rendering these agents ineffective for some agricultural uses. As such, a need exists for the development of new fungicidal compounds.
Fungicidally active 2-(pyridin-2-yl)-pyrimidines are described in WO2006/010570 and WO2007/116079. The disclosed compounds are characterised by an aryl substituent in pyridine position 6.
Fungicidally active 2-(pyridin-2-yl)-pyrimidines are described in WO 2007/116079. The disclosed compounds are characterised by a condensed aliphatic carbocycle or heterocycle.
It has been found that novel 2-(pyridin-2-yl)-pyrimidines with an aromatic ring condensed to the pyrimidine ring and aryl or heteroaryl substituents in the pyrimidine ring have
microbiocidal activity.
The present invention accordingly relates to compounds of formula (I)
Figure imgf000003_0001
wherein
represents hydrogen, halogen, cyano, hydroxy, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, C
C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, CrC6haloalkylsulfinyl, C
C6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, Ci-C6alkylsulfonyl-Ci-C6alkyl, C C6alkylsulfoximino-CrC4alkyl, CrC6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, C C6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, C
C6alkylaminocarbonyl, diCrC6alkylaminocarbonyl, CrC6alkoxyimino, CrCealkoxyimino-Cr C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy; R4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6alkoxy-Cr C6alkoxy, Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, C
C6alkylthio, CrC6haloalkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diC C6alkylamino, C3-C6cycloalkylamino, (CrC6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C C6alkoxycarbonyloxy, CrC6alkylaminocarbonyloxy, diCi-C6alkylaminocarbonyloxy, C C6alkylcarbonyloxy, CrC6alkylcarbonylamino, CrCealkylcarbonyl-CrCealkylamino, C C6alkoxyimino, C Cealkoxyimino-C Cealkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, Ci-C6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, CrC6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof; with the proviso that when RL is H , then R4 is not halogen, hydroxyl, 1-naphtyl substituted at the 2-position of the 1-naphtyl, unsubstituted phenyl or unsubstituted 2-pyridy, or
when R is methyl, R2 and R3 are H and R4 is unsubstituted phenyl, then the quinazoline ring is not substituted at the position 6 by a chlorine atom; or
when is methyl then R4 is not halogen or hydroxyl; or
when R is arylalkyl then R4 is not hydroxyl.
In a further embodiment the present invention relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or formula (I) is
Figure imgf000004_0001
wherein represents hydrogen, halogen, cyano, hydroxy, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, C
C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, CrC6haloalkylsulfinyl, C
C6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, Ci-C6alkylsulfonyl-Ci-C6alkyl, C C6alkylsulfoximino-CrC4alkyl, CrC6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, C C6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, C
C6alkylaminocarbonyl, diCrC6alkylaminocarbonyl, CrC6alkoxyimino, CrCealkoxyimino-Cr C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
Cehaloalkyl, C C4alkoxy, C C4alkoxy-C C4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy;
R4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6alkoxy-Cr C6alkoxy, Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, C C6alkylthio, CrC6haloalkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diC C6alkylamino, C3-C6cycloalkylamino, (CrC6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C
C6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diCi-C6alkylaminocarbonyloxy, C C6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, Ci-C6alkylcarbonyl-Ci-C6alkylamino, C C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, CrC6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof; with the proviso that
when R is methyl then R4 is not halogen or hydroxyl; or
when R is arylalkyl then R4 is not hydroxyl.
In a preferred enmbodiment relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein represents cyano, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, C
C6alkoxy-CrC6alkyl, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C
C6haloalkylsulfinyl, CrC6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, C
C6alkylsulfonyl-CrC6alkyl, Ci-C6alkylsulfoximino-CrC4alkyl, Ci-C6alkylamino, diC
C6alkylamino, C3-C6cycloalkylamino, Ci-C6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C
C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy; R4 represents aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy, C C6alkoxy-CrC6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, C C6haloalkylthio, Ci-C4alkylsulfinyl, CrC4alkylsulfonyl, CrC6alkylamino, diCi-C6alkylamino, C3-C6cycloalkylamino, (Ci-C6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, C
C6alkoxycarbonyl, CrC6alkylaminocarbonyl, diCrC6alkylaminocarbonyl, C
C6alkoxycarbonyloxy, CrC6alkylaminocarbonyloxy, diCrC6alkylaminocarbonyloxy, C
C6alkylcarbonyloxy, CrC6alkylcarbonylamino, CrCealkylcarbonyl-CrCealkylamino, C C6alkoxyimino, C Cealkoxyimino-C Cealkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, d-C6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof.
Unless otherwise stated, the substituents are unsubstituted or substituted. When the substituents are substituted then they are preferably substituted by the substituents given below, wherein the meaning of the substituents for the substituents R2, R3, R4 or R5 given directly with the meaning of the substituents R^ R2, R3, R4 or R5 are preferred.
In a preferred embodiment, the substituents given for are not substituted.
The invention covers all agronomically acceptable salts, isomers, structural isomers, stereoisomers, diastereoisomers, enantiomers, tautomers and N-oxides of those
compounds. The compounds of formula I may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula I may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers. There may be double bonds present in the molecule, such as C=C or C=N bonds, in which case compounds of formula (I) may exist as single isomers or mixtures of isomers. Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. Also atropisomerism may occur as a result of a restricted rotation abaout a single bond or polymorphism may occur as a result e.g. of difference in crystal packing can result from the existence of different conformers of the same molecul.
Suitable salts of the compounds of formula I include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid. Other examples of organic carboxylic acids include haloacids such as trifluoroacetic acid. N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Florida, 1991.
The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, /'so-propyl, n-butyl, sec-butyl, /'so-butyl or te/f-butyl. Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or di-unsaturated. The cycloalkyl groups are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine more preferably chlorine or fluorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy. Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms and comprise at least one halogen atom up to perhalogenated alkyle group. Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2- trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 , 1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl,
difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl. Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert- butoxy; preferably methoxy and ethoxy. Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2-tetrafluoroethoxy, 2- fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Thioalkyl is, for example, methylthio, ethylthio, propylthio, tert-butylthio, hexylthio. Alkylamino is, for example, methylamino, ethylamino, propylamino, tert-butylamino, hexylamino as well as, for example dimethylamino, diethylamino, dipropylamino, ditert-butylamino, dihexylamino or trimethylamino, triethylamino, tripropylamino, tri tert-butylamino, trihexylamino or 2- to 3-fold substituted amines with different alkyl groups. The aryl groups are groups derived from monoyclic and polycyclic aromatic hydrocarbons by removal of a hydrogen atom from a ring carbon atom. The heteroaryl groups are derived from heteroarenes by removal of a hydrogen atom from any ring atom and the heteroarenes are monoyclic and polycyclic aromatic hydrocarbons wherein one or more methine (-CH=) and/or vinylene (-CH=CH-) groups are replaced by trivalent or divalent heteroatoms, respectively, in such a way as to maintain the continuous ττ-electron system characteristic of aromatic systems. The aryl and heteroaryl groups are, for example, acridinyl, anthracenyl, benzimidazolyl, benzisoxazolyl, benzo[c]thiopheny, benzofuranyl, benzothiazolyl,
benzothiophenyl, benzoxazolyl, cinnolinyl, furyl, imidazolyl, indazolyl, indolyl,
isobenzofuranyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthalenyl, naphthyl, oxadiazolyl, oxazolyl, phenyl, preferablythesgroupsareoptionallymono-, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, thiadiazolyl, thiazoyl, thienyl, which can be optionally substituted, preferably these groups are optionally mono-, di- or trisubstituted. Further to this, the aryl and heteroaryl groups may also be annealed to alicyclic systems or hetreoalicyclic systems. Alicyclic systems or hetreoalicyclic systems are carbocyclic ring structure which may be saturated or unsaturated (which means having at least one endocyclic double bond or at least one triple bond) wherein in the case of the hetreoalicyclic systems optionally one or more of the carbon atoms are replaced by a heteroatom, but both, the alicyclic systems and the hetreoalicyclic systems may not be a benzenoid or other aromatic system. Examples of such polycyclic ring systems wherein the the aryl and heteroaryl groups are annealed to alicyclic systems or hetreoalicyclic systems are, for example 1 ,2,3,4-tetrahydro-naphthalenyl, 1 ,3-dihydro-2H-1 ,4- benzodiazepinyl, 3,4-dihydro-2H-1 ,5-benzodioxepinyl, 2,3-dihydrobenzofuranyl, 1 ,3- benzodioxolyl or 2,3-dihydro-1 ,4-benzodioxinyl. The alicyclic systems or hetreoalicyclic systems are preferably attached to the rest of the molecule through the aromatic part of the subtituent.
Suitable substituents for the aryl or heteroaryl moieties are selected from halogen, cyano, nitro, CHO, C C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C C6haloalkyl, C2- C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-C6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, d- C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, Ci-C4alkylsulfinyl, CrC4alkylsulfonyl, d- C4alkylamino, diCrC4alkylamino, C3-C6cycloalkylamino, (Ci-C6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylaminocarbonyl, diC C6alkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, C3- C6dialkylaminocarbonyloxy, CrC6alkylcarbonyloxy, CrC6alkylcarbonylamino, d- C6alkylcarbonyl CrC6alkylamino or Ci-C6alkoxyimino, C Cealkoxyimino-C Cealkyl, triCi. 6alkylsilyl, Ci-C6alkoxy-C2-C6alkynyl, Ci-C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio, C2- C6alkynyl and hydroxy-C2-C6alkynyl and Ci-C6alkylthio-Ci-C6alkyl andhydroxy- CrC6alkyl.
The preferred substituents of the substituted alkyl groups, the substituted alkenyl groups, the substituted alkynyl groups, the substituted alkoxy group and the substituted alkylthio group in the compound of formula (I) are selected from the following substituents F, CI, Br, I, -OH, - CN, nitro, -d.4alkoxy, -Ci-4 alkylthio, -NR17R18 where R17 and R18 are independently H, -Ci. 4alkyl or substituted -Ci-4alkyl or combine with the interjacent nitrogen to form a five- or six- membered ring which may comprise one or two or three heteroatoms (one or two N, O or S atoms in addition to the interjacent nitrogen atom), in which case the heterocyclic ring is unsubstituted or the heterocyclic ring is substituted by one or two Ci-4 alkyl groups, -C(0)H, - C(0)(Ci-4 alkyl), -C(0)(d.4 alkoxy), -C(0)NH2, -C(0)NH(d.4 alkyl), -C(0)N(d.4 alkyl)(d.4 alkyl), -OC(0)NH(d.4 alkyl), -OC(0)N(d.4 alkyl)(d.4 alkyl), -NHC(0)(d.4 alkyl),-
NHC(0)(d.4 alkoxy), -N(d.4 alkyl )C(0)(d.4 alkyl), -N(d.4 alkyl )C(0)(d.4 alkoxy), -OC(O) (d-4 alkyl ), -OC(0)(d.4 alkoxy), -Si(d.4 alkyl)3, -Si(d.4 alkoxy)3, aryl, aryloxy, -(d.8 - perhaloalkyl) , arylCi.4alkynyl, -d.6alkynyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl groups are either substituted or unsubstituted, preferably these substituents of the substituted groups bear only one further substituent, more preferably are hese substituents of the substituted groups not further substituted.
The more preferred substituents of the substituted Ci to C4 alkyl groups are selected from the following substituents -OH, CN, F, CI, d.4alkoxy, d.4alkylamino. The alkyl groups are branched or linear. The most preferred alkyl groups are methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl (2-methylpropyl), pentyl, 1-methylpentyl, 1-ethylpentyl, iso-pentyl (3- methylbutyl), hexyl, heptyl, octyl, or nonyl.
Preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than two further substituents, more preferably the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) bear not more than one further substituent, most preferred the alkyl groups in the compound of formula (I) and/or the alkoxy groups in the compound of formula (I) are not further substituted.
In the preferred compounds of the formula (I) the preferred alkyl groups and the preferred alkoxy groups are methyl, ethyl, propyl, methoxy and ethoxy groups. Methyl, ethyl and methoxy groups are very particularly preferred.
In particularly preferred embodiments of the invention, the preferred groups for to R5 in any combination thereof, are as set out below
Preferably the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein represents cyano, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3- C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio, C C6haloalkylthio, CrC6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, C
C6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, CrC6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl;
more preferred represents hydrogen, halogen, cyano, hydroxy, CHO, CrC8alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6alkylthio, Ci-C6alkylamino, diCi-C6alkylamino, C3- C6cycloalkylamino, CrC6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio; R4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or trisubstituted by halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C
C4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diC C6alkylaminocarbonyl, CrC6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diC
C6alkylaminocarbonyloxy, CrC6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, C
C6alkylcarbonyl-Ci-C6alkylamino or Ci-C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, C C6alkoxy-C2-C6alkynyl, Ci-C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy- C2-C6alkynyl, Ci-C6alkylthio-Ci-C6alkyl or hydroxy- CrC6alkyl;
more preferred R4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or
trisubstituted by halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6alkylthio, Ci-C6alkylamino, diC C6alkylamino, C3-C6cycloalkylamino, CrC6alkylcarbonyl, or CrC6alkoxyimino, C
C6alkoxyimino-CrC6alkyl, CrC6alkoxy-C2-C6alkynyl, CrC6alkoxyimino-C2-C6alkynyl, C C6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, Ci-C6alkylthio-Ci-C6alkyl or hydroxy- C C6alkyl;
Each R5 is independently halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 ;
Even more preferably the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic
microorganisms wherein R† is C C6alkyl, C3-C6cycloalkyl, C C6alkoxy,
R2 is H, C C6alkyl, C C6alkoxy, CI, F
R3 is H, C C6alkyl, C C6alkoxy, C C6alkylthio
R4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkoxy , C C6alkoxy-CrC6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6alkylthio, CrC6haloalkoxy, C C6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylaminocarbonyl, di C
C6dialkylaminocarbonyl, CrC6alkoxycarbonyloxy, CrC6alkylaminocarbonyloxy, diC
C6dialkylaminocarbonyloxy, CrC6alkylcarbonyloxy, CrC6alkylcarbonylamino, C
C6alkylcarbonyl- CrC6alkylamino; or pyridyl, thienyl, dihydro-benzofuran, benzo[1 ,3]dioxole, 3,4-Dihydro-2H-benzo[b][1 ,4]dioxepine which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, d-C6alkyl, CrC6haloalkyl, C C6alkoxy, CrC6alkylthio and CrC6haloalkoxy;
R5 is C C6alkyl, C C6alkoxy, C C6alkylthio, CI, F;
K is an integer selected from 0 or 1 , preferably K is 0.
Most preferably the present invention relates to compounds of formula (I) and/or method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms wherein
F is C C3alkyl, C C3alkoxy,
R2 is H, C C3alkyl, C C3alkoxy, F
R3 is H, C C3alkyl
R4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of CI, F, C C3alkyl, C C3haloalkyl, C C3alkoxy, Ci-C6alkoxy-Ci-C6alkoxy , C C6alkoxy-CrC6alkylthio, d-Cealkylthio-CrCealkoxy, C C3alkylthio, C C3haloalkoxy, C C3alkylcarbonyl, C C3alkoxycarbonyl, Ci-C3alkylaminocarbonyl, di C
C3dialkylaminocarbonyl, C C3alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diC
C6dialkylaminocarbonyloxy, CrC6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, C
C6alkylcarbonyl- Ci-C6alkylamino; or pyridyl, thienyl, dihydro-benzofuran, benzo[1 ,3]dioxole, 3,4-Dihydro-2H-benzo[b][1 ,4]dioxepine which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, CrC6alkyl, CrC6haloalkyl, C C6alkoxy, CrC6alkylthio and CrC6haloalkoxy;
R5 is C C3alkyl, C C3alkylthio, C C3alkoxy, CI, F
K is an integer selected from 0 or 1 , preferably K is 0.
Further preferred embodiments of the present invention are the embodiments F1 to F21 , which are defined as compounds of formula I which are represented by one formula selected from the group consisting of the formulae E1 to E21 as described below, wherein in formulae E1 to E21 the meanings of the substituents R2, R3 and R4 have the preferred meanings as mentioned above.
Further preferred embodiments of the present invention are the embodiments F1.C1 to F21.C33 which are 693 specific embodiments, which are defined as compounds of formula I which are represented by one formula selected from the group consisting of the formulae E1 to E21 as described below, wherein in formulae E1 to E21 the meanings of the substituents Ri , R2, R3 have the meanings given as C1 to C33 and R4 has the preferred meanings as mentioned above or in Table a lines A001 to A226
As an example the embodiment F2.C3 means the following structure
Figure imgf000014_0001
R4 has the preferred meanings as mentioned above or in Table a lines A001 to A226 Or as a further example the embodiment F2.C3 means the following structure
Figure imgf000014_0002
R4 has meanings in Table on lines A001 to A226
Compounds of formula I may be prepared as shown in the following schemes. The compounds of formula 1.1 , wherein R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula II, wherein R^ R2, R3 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula III, wherein R4 is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 ,1- bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000015_0001
The compounds of formula II, wherein R^ R2, R3, and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula IV, wherein R^ R2, R3 and R5 are as defined under formula I, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide and optionally an alkylated aniline derivative, or by successive reaction with phosphorus oxychloride and sodium iodide.
Figure imgf000015_0002
The compounds of formula IV, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula V, wherein R^ R2, R3 are as defined under formula I, with a compound of formula VI, wherein R5 are as defined under formula I, and a base such as sodium methoxide, sodium ethoxide or potassium te/f-butoxide.
Figure imgf000016_0001
The mono- and disubstituted anthranilic acid of formula VI, wherein R5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula V, wherein R2 and R3 are as defined under formula I, can be obtained by transformation of a compound of formula VII, wherein R^ R2 and R3 are as defined under formula I, with either a cyanide, such as sodium cyanide, potassium cyanide and an activating agent such as methyl iodide, dimethyl sulfate or dimethylcarbamoyl chloride, or a cyanide such as tnmethylsilylcyanide and a base, such as triethylamine, ethyldiisopropylamine or pyridine.
Figure imgf000016_0002
The compounds of formula VII, wherein R^ R2 and R3 are as defined under formula I, can be obtained by transformation of a compound of formula VIII, wherein R^ R2 and R3 are as defined under formula I, with an oxidatizing agent, such as mefa-chloroperbenzoic acid, hydrogen peroxide or oxone.
Figure imgf000017_0001
The mono-, di- and trisubstituted pyridines of formula VIII are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
Alternatively, the compounds of formula IV, wherein R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula X, wherein R^ R2, R3 and R5 are as defined under formula I, with a base such as sodium hydroxide, sodium methoxide or sodium ethoxide.
Figure imgf000017_0002
The compounds of formula X, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XI, wherein R^ R2, and R3 are as defined under formula I, with a compound of formula XII, wherein R5 are as defined under formula I, a coupling agent such as Λ/,Λ/'-dicyclohexylcarbodiimide, bis(2-oxo-3- oxazolidinyl)phosphinic chloride, 2-(1 /-/-benzotriazole-1-yl)-1 ,1 ,3,3-tetramethyluronium hexafluorophosphate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride or cyanuric chloride, and, optionally, a base such as triethylamine, ethyldiisopropylamine or N- methylmorpholine.
Figure imgf000018_0001
The mono- and disubstituted anthranilamides of formula XII, wherein R5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula XI, wherein R2, and R3 are as defined under formula I, can be obtained by transformation of a compound of formula XIV, wherein R^ R2, and R3 are as defined under formula I, and an oxidizing agent such as potassium permanganate, sodium dichromate or nitric acid.
Figure imgf000018_0002
The mono-, di- and trisubstituted 2-methylpyridines of formula XIV, wherein R^ R2, and R3 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
Alternatively, the compounds of formula IV, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XIII, wherein R^ R2, and R3 are as defined under formula I and R8 is a C1-C6 alkyl, with a compound of formula XII, wherein R5 are as defined under formula I, and a base such as sodium hydroxide, sodium ethoxide or potassium te/f-butoxide.
Figure imgf000019_0001
The compounds of formula XIII, wherein R2, and R3 are as defined under formula I and R8 is a CrC6alkyl, can be obtained by transformation of a compound of formula (XI), wherein R^ R2, and R3 are as defined under formula I, with a compound of formula XV, wherein R8 is a CrC6alkyl, and an acid such as sulphuric acid, hydrogen chloride or para-toluenesulfonic acid.
Figure imgf000019_0002
Alternatively, the compounds of formula IV, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XVI, wherein R^ R2, R3, and R5 are as defined under formula I, with a nitrogen source such as formamide, ammonium acetate, ammonium hydroxide or ammonia.
Figure imgf000019_0003
The compounds of formula XVI, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XVII, wherein R^ R2, and R3 are as defined under formula I, with a compound of formula XVIII, wherein R5 are as defined under formula I, and a base such as pyridine, triethylamine or sodium carbonate.
Figure imgf000020_0001
The mono- and disubstituted anthranilic acids of formula XVIII, wherein R5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula XVII, wherein R2, and R3 are as defined under formula I, can be obtained by transformation of a of formula XI, wherein R^ R2, and R3 are as defined under formula I, with a halogenating agent such as sulfonyl chloride, phosphorus oxychloride, oxalyl chloride or cyanuric chloride, and, optionally, a base such as pyridine, triethylamine or sodium carbonate.
Figure imgf000020_0002
Alternatively, the compounds of formula XVI, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained in two steps by transformation of a compound of formula XIX, wherein R^ R2, R3, and R5 are as defined under formula I, with a halogenating or acylating agent such as sulfonyl chloride, cyanuric chloride or acetic anhydride, and, optionally, a base such as pyridine, triethylamine or sodium carbonate.
Figure imgf000020_0003
The compounds of formula XIX, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XVII, wherein R^ R2, and R3 are as defined under formula I, with a compound of formula XVIII, wherein R5 are as defined
.
Figure imgf000021_0001
Alternatively, the compounds of formula XVI, wherein R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XX, wherein R^ R2 and R3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXI, wherein R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, triethylamine or potassium carbonate, under an atmosphere of carbon monoxide. For examples of similar reactions see S. Cacchi, G. Fabrizi and F. Marinelli in Synlett 1996, 997.
Figure imgf000021_0002
The mono- and disubstituted 2-halogenoanilines of formula XXI, wherein R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. The compounds of formula XX, wherein R^ R2 and R3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula VII, wherein R^ R2 and R3 are as defined under formula I, with a halide, such as phosphorus oxyhalide, methylsulfonyl chloride or trichloroacetyl chloride, and, optionally, a base such as pyridine or triethylamine.
Figure imgf000022_0001
Alternatively, the compounds of formula XX, wherein R2 and R3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XXII, wherein R2 and R3 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2,MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1- bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000022_0002
(XXII) (Ilia) (XX)
Alternatively, the compounds of formula XVI, wherein R^ R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XVII , wherein R^ R2 and R3 are as defined under formula I, with a compound of formula XXI, wherein R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, triethylamine or potassium carbonate, under an atmosphere of carbon monoxide.
Figure imgf000023_0001
Alternatively, the compounds of formula XVI, wherein R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XXIII, wherein R^ R2, R3, and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo,, with a catalyst, such as palladium on charcoal, tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride, and a base such as pyridine, monoxide.
Figure imgf000023_0002
The compounds of formula XXIII, wherein R^ R2, R3, and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XVII, wherein R^ R2, and R3 are as defined under formula I, with a compound of formula XXI, wherein R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo,, and a base such as pyridine, triethylamine or sodium carbonate.
Figure imgf000023_0003
Alternatively, the compounds of formula IV, wherein R2, R3, and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XXV, wherein R2, R3 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2,MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or
Figure imgf000024_0001
The compounds of formula XXV, wherein R2, R3, and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are a subclass of the compounds of formula IV, wherein R2, R3, and R5 are as defined under formula I and substitution is limited to a halogen, and can thus be obtained according to the procedure describing the synthesis of compounds of formula IV.
Alternatively, the compounds of formula IV, wherein R^ R2, R3 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XXVII, wherein R5 are as defined under formula I, R8 is a hydrogen or CrC6alkyl and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXVI, wherein R^ R2 and R3 are as defined under formula I, a catalyst, such as copper(l) chloride, copper(l) bromide or copper(l) iodide, a ligand such as dimethylethylenediamine, proline or BINOL, and a base such as potassium phosphate, sodium carbonate or cesium carbonate. For examples of similar reactions see 1) H. Fu et al. in Chem. Comm. 2008, 6333; 2) H. Fu et al. in Angew. Chem. Int. Ed. 2009, 48, 348; 3) H. Liu et al. in Green Chem. 2009, 11, 1881.
Figure imgf000025_0001
The compounds of formula XXVI, wherein R2, and R3 are as defined under formula I, can be obtained by transformation of a compound of formula V, wherein R^ R2 and R3 are as defined under formula I, with a base, such as sodium methoxide, and an ammonium salt, such as ammonium chloride.
Figure imgf000025_0002
Alternatively, the compounds of formula 1.1 , wherein R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XXIX, wherein R2, R3, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2,MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000025_0003
The compounds of formula XXIX, wherein R2, R3, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XXX, wherein R2, R3 and R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R4 is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000026_0001
The compounds of formula XXX, wherein R2, R3, and R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula XXXII, wherein R2, R3 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide.
Figure imgf000026_0002
Alternatively, the compounds of formula XXIX, wherein R2, R3, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula M, wherein R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula Ml, wherein R2 and R3 are as defined under formula I, Hal is a halogen, preferably chloro, bromo or iodo, and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000027_0001
The metallo-substituted pyridines of formula Ml, wherein R2 and R3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. The compounds of formula M, wherein R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula Mil, wherein R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R4 is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000028_0001
The compounds of formula Mil, wherein R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula Mill, wherein R5 are as defined under formula I, with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide, and, optionally, a base such as pyridine, triethylamine or diethylaniline.
Figure imgf000028_0002
The compounds of formula Mill, wherein R5 are as defined under formula I, can be obtained by transformation of a compound of formula VI, wherein R5 are as defined under formula I, with urea, sodium cyanate or potassium cyanate
Figure imgf000028_0003
(VI) O (Mill)
Alternatively, the compounds of formula Mil, wherein R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MIV, wherein R5 are as defined under formula I, with a halogenating agent such as phosgene, diphosgene, triphosgene or carbonyl dibromide. Phosgene or
Figure imgf000029_0001
The mono- and disubstituted anthranilonitriles of formula MIV, wherein R5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
Alternatively, the compounds of formula XXIX, wherein R2, R3, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo.can be obtained by transformation of a compound of formula XXII, wherein R2 and R3 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R4 and R5 are as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 ,1- bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000029_0002
The 2-metallo-substituted quinazolines of formula MV, wherein R4 and R5 are as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
The compounds of formula XXII, wherein R2 and R3 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, are a subclass of the compounds of formula XX, wherein R2 and R3 are as defined under formula I and substitution is limited to a halogen, and can thus be obtained according to the procedure describing the synthesis of compounds of formula XX. Alternatively, the compounds of formula 1.1 , wherein R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula M, wherein R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula MVI , wherein R^ R2 and R3 are as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000030_0001
The metallo-substituted pyridines of formula MVI, wherein R^ R2 and R3 are as defined under formula I, may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
Alternatively, the compounds of formula 1.1 , wherein R^ R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula XX, wherein Ri, R2 and R3 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R4 and R5 are as defined under formula I and R6.is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000031_0001
Alternatively, the compounds of formula 1.1 , wherein R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula MVII, wherein Ri , R2, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula (1Mb), wherein R3 is as defined under formula I and R6.is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, d-C6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 ,1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000031_0002
The compounds of formula MVII, wherein R^ R2, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MVIII, wherein R^ R2 and R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula III, wherein R4 is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll)
Figure imgf000032_0001
Alternatively, the compounds of formula MVII, wherein R2, R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MIX, wherein R2, R4 and R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula (Ilia), wherein is as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1- bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000032_0002
The compounds of formula MIX, wherein R2, R4 and R5 are as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, can be obtained by transformation of a compound of formula MX, wherein R2 is as defined under formula I and Hal are halogens, preferably chloro, bromo or iodo, with a compound of formula MV, wherein R4 and R5 are as defined under formula I and R6 is lnCI2, lnCI(R4), ln(R4)2, MgCI, MgBr, Sn(R7)3, ZnCI, ZnBr or B(OR7)2, wherein either R7 is independently from each other hydrogen, CrC6alkyl or wherein two R7 together can form a C3-C8cycloalkyl, and a catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1 , 1-bis(diphenylphosphino) ferrocene]dichloropalladium(ll), palladium acetate or bis(diphenylphosphine)palladium(ll) chloride.
Figure imgf000033_0001
The monosubstituted 2,4,6-trihalogenopyridines of formula MX, wherein R2 is as defined under formula I, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar.
Alternatively, the compounds of formula 1.1 , wherein R2, R3, R4 and R5 are as defined under formula I, can be obtained by transformation of a compound of formula MXI I, wherein R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, with a compound of formula XXVI, wherein R^ R2, and R3 are as defined under formula I, a catalyst, such as copper(l) chloride, copper(l) bromide or copper(l) iodide, a ligand such as dimethylethylenediamine, proline or BINOL, and a base such as potassium phosphate, sodium carbonate or cesium carbonate.
Figure imgf000033_0002
The o/f 70-halogenobenzophenone of formula MXII, wherein R4 and R5 are as defined under formula I and Hal is a halogen, preferably chloro, bromo or iodo, are known compounds or may be obtained readily from known compounds using processes that are routine in the art and with which the skilled man will be familiar. The reactions to give compounds of formula I are advantageously carried out in aprotic inert organic solvents or in a mixture of aprotic inert organic solvents and water. Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N- dimethylformamide, diethylformamide or N-methylpyrrolidinone. The reaction temperatures are advantageously between -20°C and +120°C. In general, the reactions are slightly exothermic and, as a rule, they can be carried out at ambient temperature. To shorten the reaction time, or else to start the reaction, the mixture may be heated briefly to the boiling point of the reaction mixture. The reaction times can also be shortened by adding a few drops of base as reaction catalyst. Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1 ,4-diazabicyclo[2.2.2]octane, 1 ,5-diazabicyclo[4.3.0]non-5-ene or 1 ,5-diazabicyclo[5.4.0]undec-7-ene. However, inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates, e.g. sodium carbonate and potassium carbonate, hydrogen carbonates, e.g. potassium hydrogen carbonate and sodium hydrogen carbonate, or phosphates, e.g. potassium phosphate, sodium phosphate, may also be used as bases. The bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.
The compounds of formula I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.
It has now been found that the compounds of formula I according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisams, such as fungi, bacteria or viruses.
The invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as active ingredient to the plants, to parts thereof or the locus thereof. The compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants. The compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
Furthermore, the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene
management.
The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium,
Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara). Furthermore, the novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against
Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). The compounds of formula I are also effective against Asian soybean rust (Phakopsora pachyrhizi). Within the scope of the invention, useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.
The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®. The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus. Examples of such plants are: YieldGard® (maize variety that expresses a CrylA(b) toxin); YieldGard Rootworm® (maize variety that expresses a CrylllB(bl) toxin); YieldGard Plus® (maize variety that expresses a CrylA(b) and a Cryll I B(b1 ) toxin); Starlink® (maize variety that expresses a Cry9(c) toxin); Herculex I® (maize variety that expresses a CrylF(a2) toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c) toxin); Bollgard I® (cotton variety that expresses a CrylA(c) toxin); Bollgard II® (cotton variety that expresses a CrylA(c) and a CryllA(b) toxin); VIPCOT® (cotton variety that expresses a VIP toxin); NewLeaf® (potato variety that expresses a CrylllA toxin); NatureGard® Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt1 1 corn borer (CB) trait), Agrisure® RW (corn rootworm trait) and Protecta®.
The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
The term "crops" or the term "useful plants" is to be understood as including also crop plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.
Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, e.g. CrylAb, CrylAc, Cryl F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1 , Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect- specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors;
ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP- glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood by δ-endotoxins, for example CrylAb, CrylAc, Cry1 F, Cry1 Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1 , Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated CrylAb, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3A toxin (see WO 03/018810). Examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available.
Examples of such plants are: YieldGard® (maize variety that expresses a CrylAb toxin); YieldGard Rootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus® (maize variety that expresses a CrylAb and a Cry3Bb1 toxin); Starlink® (maize variety that expresses a Cry9C toxin); Herculex I® (maize variety that expresses a Cry1 Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylAc toxin); Bollgard I® (cotton variety that expresses a CrylAc toxin); Bollgard II® (cotton variety that expresses a CrylAc and a Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and a CrylAb toxin); NewLeaf® (potato variety that expresses a Cry3A toxin); Nature- Gard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.
Further examples of such transgenic crops are:
1. Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated CrylAb toxin. Bt1 1 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a CrylAb toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1 150
Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1 F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 x MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a CrylAb toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer.
The term "locus" of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.
The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants.
Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
The compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation. Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
To this end compounds of formula I and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other
formulations for obtaining special effects.
Suitable carriers and adjuvants (auxiliaries) can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
The compounds of formula I or compositions, comprising a compound of formula I as acitve ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
A preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as acitve ingredient and an inert carrier, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant or, if desired as well, a further, other biocidally active ingredient, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active
compounds (surfactants).
The present invention relates additionally to mixtures comprising at least a compound of formula I and at least a further, other biocidally active ingredient and optionally further ingredients. The further, other biocidally active ingredient are known for example from "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council] or its electronic version "e-Pesticide Manual V4.2" or from the website http://www.alanwood.net/pesticides/ or preferably one of the further pesticides listed below.
The following mixtures of the compounds of TX with a further active ingredient (B) are preferred (the abbreviation "TX" means one compound selected from the group consisting of the compounds of formula (I) or a cspecific compound of formulae E1.001.C1 to
E21.226.C33 described in Tables 1.1 to 21.33 of the present invention, thus the abbreviation "TX" means at least one compound selected from the compounds E1.001.C1 to
E21.226.C33, or the abbreviation "TX" means a specific compound selected from Table 22 (163 specific compounds); an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX,
an acaricide selected from the group of substances consisting of 1 , 1-bis(4-chlorophenyl)-2- ethoxyethanol (lUPAC name) (910) + TX, 2,4-dichlorophenyl benzenesulfonate
(lUPAC/Chemical Abstracts name) (1059) + TX, 2-fluoro-A/-methyl-A/-1-naphthylacetamide (IUPAC name) (1295) + TX, 4-chlorophenyl phenyl sulfone (lUPAC name) (981) + TX, abamectin (1) + TX, acequinocyl (3) + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, alpha-cypermethrin (202) + TX, amidithion (870) + TX, amidoflumet [CCN] + TX, amidothioate (872) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, aramite (881) + TX, arsenous oxide (882) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azobenzene (lUPAC name) (888) + TX, azocyclotin (46) + TX, azothoate (889) + TX, benomyl (62) + TX, benoxafos (alternative name) [CCN] + TX, benzoximate (71) + TX, benzyl benzoate (lUPAC name) [CCN] + TX, bifenazate (74) + TX, bifenthrin (76) + TX, binapacryl (907) + TX, brofenvalerate (alternative name) + TX, bromocyclen (918) + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bromopropylate (94) + TX, buprofezin (99) + TX,
butocarboxim (103) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, calcium polysulfide (lUPAC name) (11 1) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (115) + TX, carbofuran (118) + TX, carbophenothion (947) + TX, CGA 50'439 (development code) (125) + TX, chinomethionat (126) + TX, chlorbenside (959) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorfenapyr (130) + TX, chlorfenethol (968) + TX, chlorfenson (970) + TX,
chlorfensulphide (971) + TX, chlorfenvinphos (131) + TX, chlorobenzilate (975) + TX, chloromebuform (977) + TX, chloromethiuron (978) + TX, chloropropylate (983) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, cinerin l (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, clofentezine (158) + TX, closantel (alternative name) [CCN] + TX, coumaphos (174) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, cufraneb (1013) + TX, cyanthoate (1020) + TX, cyflumetofen (CAS Reg. No.: 400882-07-7) + TX, cyhalothrin (196) + TX, cyhexatin (199) + TX, cypermethrin (201) + TX, DCPM (1032) + TX, DDT (219) + TX, demephion (1037) + TX, demephion-O (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diazinon (227) + TX, dichlofluanid (230) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicofol (242) + TX, dicrotophos (243) + TX, dienochlor (1071) + TX, dimefox (1081) + TX, dimethoate (262) + TX, dinactin (alternative name) (653) + TX, dinex (1089) + TX, dinex-diclexine (1089) + TX, dinobuton (269) + TX, dinocap (270) + TX, dinocap-4 [CCN] + TX, dinocap-6 [CCN] + TX, dinocton (1090) + TX, dinopenton (1092) + TX, dinosulfon (1097) + TX,
dinoterbon (1098) + TX, dioxathion (1102) + TX, diphenyl sulfone (lUPAC name) (1103) + TX, disulfiram (alternative name) [CCN] + TX, disulfoton (278) + TX, DNOC (282) + TX, dofenapyn (1 113) + TX, doramectin (alternative name) [CCN] + TX, endosulfan (294) + TX, endothion (1 121) + TX, EPN (297) + TX, eprinomectin (alternative name) [CCN] + TX, ethion (309) + TX, ethoate-methyl (1134) + TX, etoxazole (320) + TX, etrimfos (1 142) + TX, fenazaflor (1147) + TX, fenazaquin (328) + TX, fenbutatin oxide (330) + TX, fenothiocarb (337) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fen- pyroximate (345) + TX, fenson (1 157) + TX, fentrifanil (1161) + TX, fenvalerate (349) + TX, fipronil (354) + TX, fluacrypyrim (360) + TX, fluazuron (1166) + TX, flubenzimine (1 167) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenoxuron (370) + TX, flumethrin (372) + TX, fluorbenside (1174) + TX, fluvalinate (1 184) + TX, FMC 1 137 (development code) (1 185) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1192) + TX, formparanate (1 193) + TX, gamma-HCH (430) + TX, glyodin (1205) + TX, halfenprox (424) + TX, heptenophos (432) + TX, hexadecyl cyclopropanecarboxylate (lUPAC/Chemical Abstracts name) (1216) + TX, hexythiazox (441) + TX, iodomethane (lUPAC name) (542) + TX, isocarbophos
(alternative name) (473) + TX, isopropyl 0-(methoxyaminothiophosphoryl)salicylate (lUPAC name) (473) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, lindane (430) + TX, lufenuron (490) + TX, malathion (492) + TX, malonoben (1254) + TX, mecarbam (502) + TX, mephosfolan (1261) + TX, mesulfen (alternative name) [CCN] + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methidathion (529) + TX, methiocarb (530) + TX, methomyl (531) + TX, methyl bromide (537) + TX, metolcarb (550) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naled (567) + TX, NC-184 (compound code) + TX, NC-512 (compound code) + TX, nifluridide (1309) + TX, nikkomycins (alternative name) [CCN] + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, parathion (615) + TX, permethrin (626) + TX, petroleum oils
(alternative name) (628) + TX, phenkapton (1330) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosphamidon (639) + TX, phoxim (642) + TX, pirimiphos-methyl (652) + TX,
polychloroterpenes (traditional name) (1347) + TX, polynactins (alternative name) (653) + TX, proclonol (1350) + TX, profenofos (662) + TX, promacyl (1354) + TX, propargite (671) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothoate (1362) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, quinalphos (711) + TX, quintiofos (1381) + TX, R-1492
(development code) (1382) + TX, RA-17 (development code) (1383) + TX, rotenone (722) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, sophamide (1402) + TX,
spirodiclofen (738) + TX, spiromesifen (739) + TX, SSI-121 (development code) (1404) + TX, sulfiram (alternative name) [CCN] + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphur (754) + TX, SZI-121 (development code) (757) + TX, tau-fluvalinate (398) + TX, tebufenpyrad (763) + TX, TEPP (1417) + TX, terbam (alternative name) + TX,
tetrachlorvinphos (777) + TX, tetradifon (786) + TX, tetranactin (alternative name) (653) + TX, tetrasul (1425) + TX, thiafenox (alternative name) + TX, thiocarboxime (1431) + TX, thiofanox (800) + TX, thiometon (801) + TX, thioquinox (1436) + TX, thuringiensin (alternative name) [CCN] + TX, triamiphos (1441) + TX, triarathene (1443) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trifenofos (1455) + TX, trinactin (alternative name) (653) + TX, vamidothion (847) + TX, vaniliprole [CCN] and YI-5302 (compound code) + TX,
an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (lUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (lUPAC name) (347) and triphenyltin hydroxide (lUPAC name) (347) + TX,
an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX, an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1 122) + TX, fenthion (346) + TX, pyridin-4-amine (lUPAC name) (23) and strychnine (745) + TX,
a bactericide selected from the group of substances consisting of 1-hydroxy-1 /-/-pyridine-2- thione (lUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (lUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (lUPAC name) (170) + TX, copper hydroxide (lUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1 105) + TX, dodicin (1 112) + TX, fenaminosulf (1 144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (lUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX,
a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis
(alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa calif ornica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide
(scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) and Verticillium lecanii (alternative name) (848) + TX,
a soil sterilant selected from the group of substances consisting of iodomethane (lUPAC name) (542) and methyl bromide (537) + TX,
a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX,
diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] and uredepa (alternative name) [CCN] + TX,
an insect pheromone selected from the group of substances consisting of (£)-dec-5-en-1-yl acetate with (£)-dec-5-en-1-ol (lUPAC name) (222) + TX, (£)-tridec-4-en-1-yl acetate (lUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (lUPAC name) (541) + TX, (E,Z)- tetradeca-4,10-dien-1-yl acetate (lUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (lUPAC name) (285) + TX, (Z)-hexadec-1 1-enal (lUPAC name) (436) + TX, (Z)-hexadec- 1 1-en-1-yl acetate (lUPAC name) (437) + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate
(lUPAC name) (438) + TX, (Z)-icos-13-en-10-one (lUPAC name) (448) + TX, (Z)-tetradec- 7-en-1-al (lUPAC name) (782) + TX, (Z)-tetradec-9-en-1-ol (lUPAC name) (783) + TX, (Z)- tetradec-9-en-1-yl acetate (lUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (lUPAC name) (283) + TX, (9Z, 11 E)-tetradeca-9, 11-dien-1-yl acetate (lUPAC name) (780) + TX, (9Z, 12E)-tetradeca-9,12-dien-1-yl acetate (lUPAC name) (781) + TX, 14- methyloctadec-1-ene (lUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5- one (lUPAC name) (544) + TX, alpha-multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-1-yl acetate (lUPAC name) (286) + TX, dodec-9-en-1-yl acetate (lUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1-yl acetate (lUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (lUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, gossyplure (alternative name) (420) + TX, grandlure (421) + TX, grandlure I (alternative name) (421) + TX, grandlure II (alternative name) (421) + TX, grandlure III (alternative name) (421) + TX, grandlure IV (alternative name) (421) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2,13-dien-1-yl acetate (lUPAC name) (588) + TX, octadeca-3,13-dien-1-yl acetate (lUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetradec-1 1-en-1-yl acetate (lUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure Bi (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) and trunc-call (alternative name) [CCN] + TX,
an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (lUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (lUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (lUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1 137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,
an insecticide selected from the group of substances consisting of 1-dichloro-1-nitroethane (lUPAC/Chemical Abstracts name) (1058) + TX, 1 , 1-dichloro-2,2-bis(4-ethylphenyl)ethane (lUPAC name) (1056), + TX, 1 ,2-dichloropropane (lUPAC/Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (lUPAC name) (1063) + TX, 1-bromo- 2-chloroethane (lUPAC/Chemical Abstracts name) (916) + TX, 2,2,2-trichloro-1-(3,4- dichlorophenyl)ethyl acetate (lUPAC name) (1451) + TX, 2,2-dichlorovinyl 2- ethylsulphinylethyl methyl phosphate (lUPAC name) (1066) + TX, 2-(1 ,3-dithiolan-2-yl)phenyl dimethylcarbamate (lUPAC/ Chemical Abstracts name) (1 109) + TX, 2-(2- butoxyethoxy)ethyl thiocyanate (lUPAC/Chemical Abstracts name) (935) + TX, 2-(4,5- dimethyl-1 ,3-dioxolan-2-yl)phenyl methylcarbamate (I U PA C/ Chemical Abstracts name) (1084) + TX, 2-(4-chloro-3,5-xylyloxy)ethanol (lUPAC name) (986) + TX, 2-chlorovinyl diethyl phosphate (lUPAC name) (984) + TX, 2-imidazolidone (lUPAC name) (1225) + TX, 2-isovalerylindan-1 ,3-dione (lUPAC name) (1246) + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate (lUPAC name) (1284) + TX, 2-thiocyanatoethyl laurate (lUPAC name) (1433) + TX, 3-bromo-1-chloroprop-1-ene (lUPAC name) (917) + TX, 3-methyl-1- phenylpyrazol-5-yl dimethylcarbamate (lUPAC name) (1283) + TX, 4-methyl(prop-2- ynyl)amino-3,5-xylyl methylcarbamate (lUPAC name) (1285) + TX, 5,5-dimethyl-3- oxocyclohex-1-enyl dimethylcarbamate (lUPAC name) (1085) + TX, abamectin (1) + TX, acephate (2) + TX, acetamiprid (4) + TX, acethion (alternative name) [CCN] + TX, acetoprole [CCN] + TX, acrinathrin (9) + TX, acrylonitrile (lUPAC name) (861) + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, aldrin (864) + TX, allethrin (17) + TX, allosamidin (alternative name) [CCN] + TX, allyxycarb (866) + TX, alpha-cypermethrin (202) + TX, alpha-ecdysone (alternative name) [CCN] + TX, aluminium phosphide (640) + TX, amidithion (870) + TX, amidothioate (872) + TX, aminocarb (873) + TX, amiton (875) + TX, amiton hydrogen oxalate (875) + TX, amitraz (24) + TX, anabasine (877) + TX, athidathion (883) + TX, AVI 382 (compound code) + TX, AZ 60541 (compound code) + TX, azadirachtin (alternative name) (41) + TX, azamethiphos (42) + TX, azinphos-ethyl (44) + TX, azinphos-methyl (45) + TX, azothoate (889) + TX, Bacillus thuringiensis delta endotoxins (alternative name) (52) + TX, barium
hexafluorosilicate (alternative name) [CCN] + TX, barium polysulfide (lUPAC/Chemical Abstracts name) (892) + TX, barthrin [CCN] + TX, Bayer 22/190 (development code) (893) + TX, Bayer 22408 (development code) (894) + TX, bendiocarb (58) + TX, benfuracarb (60) + TX, bensultap (66) + TX, beta-cyfluthrin (194) + TX, beta-cypermethrin (203) + TX, bifenthrin (76) + TX, bioallethrin (78) + TX, bioallethrin S-cyclopentenyl isomer (alternative name) (79) + TX, bioethanomethrin [CCN] + TX, biopermethrin (908) + TX, bioresmethrin (80) + TX, bis(2-chloroethyl) ether (I UPAC name) (909) + TX, bistrifluron (83) + TX, borax (86) + TX, brofenvalerate (alternative name) + TX, bromfenvinfos (914) + TX, bromocyclen (918) + TX, bromo-DDT (alternative name) [CCN] + TX, bromophos (920) + TX, bromophos-ethyl (921) + TX, bufencarb (924) + TX, buprofezin (99) + TX, butacarb (926) + TX, butathiofos (927) + TX, butocarboxim (103) + TX, butonate (932) + TX, butoxycarboxim (104) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, calcium arsenate [CCN] + TX, calcium cyanide (444) + TX, calcium polysulfide (lUPAC name) (11 1) + TX, camphechlor (941) + TX, carbanolate (943) + TX, carbaryl (1 15) + TX, carbofuran (118) + TX, carbon disulfide (lUPAC/Chemical Abstracts name) (945) + TX, carbon tetrachloride (lUPAC name) (946) + TX, carbophenothion (947) + TX, carbosulfan (1 19) + TX, cartap (123) + TX, cartap hydrochloride (123) + TX, cevadine (alternative name) (725) + TX, chlorbicyclen (960) + TX, chlordane (128) + TX,
chlordecone (963) + TX, chlordimeform (964) + TX, chlordimeform hydrochloride (964) + TX, chlorethoxyfos (129) + TX, chlorfenapyr (130) + TX, chlorfenvinphos (131) + TX, chlorfluazuron (132) + TX, chlormephos (136) + TX, chloroform [CCN] + TX, chloropicrin (141) + TX, chlorphoxim (989) + TX, chlorprazophos (990) + TX, chlorpyrifos (145) + TX, chlorpyrifos-methyl (146) + TX, chlorthiophos (994) + TX, chromafenozide (150) + TX, cinerin I (696) + TX, cinerin II (696) + TX, cinerins (696) + TX, cis-resmethrin (alternative name) + TX, cismethrin (80) + TX, clocythrin (alternative name) + TX, cloethocarb (999) + TX, closantel (alternative name) [CCN] + TX, clothianidin (165) + TX, copper acetoarsenite [CCN] + TX, copper arsenate [CCN] + TX, copper oleate [CCN] + TX, coumaphos (174) + TX, coumithoate (1006) + TX, crotamiton (alternative name) [CCN] + TX, crotoxyphos (1010) + TX, crufomate (101 1) + TX, cryolite (alternative name) (177) + TX, CS 708 (development code) (1012) + TX, cyanofenphos (1019) + TX, cyanophos (184) + TX, cyanthoate (1020) + TX, cyclethrin [CCN] + TX, cycloprothrin (188) + TX, cyfluthrin (193) + TX, cyhalothrin (196) + TX, cypermethrin (201) + TX, cyphenothrin (206) + TX, cyromazine (209) + TX, cythioate (alternative name) [CCN] + TX, d-limonene (alternative name) [CCN] + TX, d-tetramethrin (alternative name) (788) + TX, DAEP (1031) + TX, dazomet (216) + TX, DDT (219) + TX, decarbofuran (1034) + TX, deltamethrin (223) + TX, demephion (1037) + TX, demephion-0 (1037) + TX, demephion-S (1037) + TX, demeton (1038) + TX, demeton-methyl (224) + TX, demeton-0 (1038) + TX, demeton-O-methyl (224) + TX, demeton-S (1038) + TX, demeton-S-methyl (224) + TX, demeton-S-methylsulphon (1039) + TX, diafenthiuron (226) + TX, dialifos (1042) + TX, diamidafos (1044) + TX, diazinon (227) + TX, dicapthon (1050) + TX, dichlofenthion (1051) + TX, dichlorvos (236) + TX, dicliphos (alternative name) + TX, dicresyl
(alternative name) [CCN] + TX, dicrotophos (243) + TX, dicyclanil (244) + TX, dieldrin -SO-
CI 070) + TX, diethyl 5-methylpyrazol-3-yl phosphate (lUPAC name) (1076) + TX, diflubenzuron (250) + TX, dilor (alternative name) [CCN] + TX, dimefluthrin [CCN] + TX, dimefox (1081) + TX, dimetan (1085) + TX, dimethoate (262) + TX, dimethrin (1083) + TX, dimethylvinphos (265) + TX, dimetilan (1086) + TX, dinex (1089) + TX, dinex- diclexine (1089) + TX, dinoprop (1093) + TX, dinosam (1094) + TX, dinoseb (1095) + TX, dinotefuran (271) + TX, diofenolan (1099) + TX, dioxabenzofos (1 100) + TX, dioxacarb (1 101) + TX, dioxathion (1 102) + TX, disulfoton (278) + TX, dithicrofos (1108) + TX, DNOC (282) + TX, doramectin (alternative name) [CCN] + TX, DSP (11 15) + TX, ecdysterone (alternative name) [CCN] + TX, El 1642 (development code) (11 18) + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, EMPC (1120) + TX, empenthrin (292) + TX, endosulfan (294) + TX, endothion (1 121) + TX, endrin (1 122) + TX, EPBP (1 123) + TX, EPN (297) + TX, epofenonane (1124) + TX, eprinomectin (alternative name) [CCN] + TX, esfenvalerate (302) + TX, etaphos (alternative name) [CCN] + TX, ethiofencarb (308) + TX, ethion (309) + TX, ethiprole (310) + TX, ethoate-methyl (1134) + TX, ethoprophos (312) + TX, ethyl formate (I UPAC name) [CCN] + TX, ethyl-DDD (alternative name) (1056) + TX, ethylene dibromide (316) + TX, ethylene dichloride (chemical name) (1136) + TX, ethylene oxide [CCN] + TX, etofenprox (319) + TX, etrimfos (1 142) + TX, EXD (1 143) + TX, famphur (323) + TX, fenamiphos (326) + TX, fenazaflor (1 147) + TX, fenchlorphos (1148) + TX, fenethacarb (1149) + TX, fenfluthrin (1 150) + TX, fenitrothion (335) + TX, fenobucarb (336) + TX, fenoxacrim (1153) + TX, fenoxycarb (340) + TX, fenpirithrin (1155) + TX, fenpropathrin (342) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fenthion (346) + TX, fenthion-ethyl [CCN] + TX, fenvalerate (349) + TX, fipronil (354) + TX, flonicamid (358) + TX, flubendiamide (CAS. Reg. No.: 272451-65-7) + TX, flucofuron (1 168) + TX, flucycloxuron (366) + TX, flucythrinate (367) + TX, fluenetil (1169) + TX, flufenerim [CCN] + TX, flufenoxuron (370) + TX, flufenprox (1171) + TX, flumethrin (372) + TX, fluvalinate (1184) + TX, FMC 1 137 (development code) (1 185) + TX, fonofos (1 191) + TX, formetanate (405) + TX, formetanate hydrochloride (405) + TX, formothion (1 192) + TX, formparanate (1 193) + TX, fosmethilan (1194) + TX, fospirate (1195) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furathiocarb (412) + TX, furethrin (1200) + TX, gamma- cyhalothrin (197) + TX, gamma-HCH (430) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, GY-81 (development code) (423) + TX, halfenprox (424) + TX, halofenozide (425) + TX, HCH (430) + TX, HEOD (1070) + TX, heptachlor (1211) + TX, heptenophos (432) + TX, heterophos [CCN] + TX, hexaflumuron (439) + TX, HHDN (864) + TX, hydramethylnon (443) + TX, hydrogen cyanide (444) + TX, hydroprene (445) + TX, hyquincarb (1223) + TX, imidacloprid (458) + TX, imiprothrin (460) + TX, indoxacarb (465) + TX, iodomethane (lUPAC name) (542) + TX, IPSP (1229) + TX, isazofos (1231) + TX, isobenzan (1232) + TX, isocarbophos (alternative name) (473) + TX, isodrin (1235) + TX, isofenphos (1236) + TX, isolane (1237) + TX, isoprocarb (472) + TX, isopropyl O- (methoxyaminothiophosphoryl)salicylate (lUPAC name) (473) + TX, isoprothiolane (474) + TX, isothioate (1244) + TX, isoxathion (480) + TX, ivermectin (alternative name) [CCN] + TX, jasmolin I (696) + TX, jasmolin II (696) + TX, jodfenphos (1248) + TX, juvenile hormone I (alternative name) [CCN] + TX, juvenile hormone II (alternative name) [CCN] + TX, juvenile hormone III (alternative name) [CCN] + TX, kelevan (1249) + TX, kinoprene (484) + TX, lambda-cyhalothrin (198) + TX, lead arsenate [CCN] + TX, lepimectin (CCN) + TX, leptophos (1250) + TX, lindane (430) + TX, lirimfos (1251) + TX, lufenuron (490) + TX, lythidathion (1253) + TX, m-cumenyl methylcarbamate (lUPAC name) (1014) + TX, magnesium phosphide (lUPAC name) (640) + TX, malathion (492) + TX, malonoben (1254) + TX, mazidox (1255) + TX, mecarbam (502) + TX, mecarphon (1258) + TX, menazon (1260) + TX, mephosfolan (1261) + TX, mercurous chloride (513) + TX, mesulfenfos (1263) + TX, metaflumizone (CCN) + TX, metam (519) + TX, metam- potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methacrifos (1266) + TX, methamidophos (527) + TX, methanesulphonyl fluoride (lUPAC/Chemical Abstracts name) (1268) + TX, methidathion (529) + TX, methiocarb (530) + TX, methocrotophos (1273) + TX, methomyl (531) + TX, methoprene (532) + TX, methoquin-butyl (1276) + TX, methothrin (alternative name) (533) + TX, methoxychlor (534) + TX,
methoxyfenozide (535) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, methylchloroform (alternative name) [CCN] + TX, methylene chloride [CCN] + TX, metofluthrin [CCN] + TX, metolcarb (550) + TX, metoxadiazone (1288) + TX, mevinphos (556) + TX, mexacarbate (1290) + TX, milbemectin (557) + TX, milbemycin oxime (alternative name) [CCN] + TX, mipafox (1293) + TX, mirex (1294) + TX, monocrotophos (561) + TX, morphothion (1300) + TX, moxidectin (alternative name) [CCN] + TX, naftalofos (alternative name) [CCN] + TX, naled (567) + TX, naphthalene
(lUPAC/Chemical Abstracts name) (1303) + TX, NC-170 (development code) (1306) + TX, NC-184 (compound code) + TX, nicotine (578) + TX, nicotine sulfate (578) + TX, nifluridide (1309) + TX, nitenpyram (579) + TX, nithiazine (131 1) + TX, nitrilacarb (1313) + TX, nitrilacarb 1 : 1 zinc chloride complex (1313) + TX, NNI-0101 (compound code) + TX, NNI-0250 (compound code) + TX, nornicotine (traditional name) (1319) + TX, novaluron (585) + TX, noviflumuron (586) + TX, 0-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate (lUPAC name) (1057) + TX, 0,0-diethyl 0-4-methyl-2-oxo-2H- chromen-7-yl phosphorothioate (lUPAC name) (1074) + TX, Ο,Ο-diethyl 0-6-methyl-2- propylpyrimidin-4-yl phosphorothioate (lUPAC name) (1075) + TX, 0,0, 0',Ο'-tetrapropyl dithiopyrophosphate (lUPAC name) (1424) + TX, oleic acid (lUPAC name) (593) + TX, omethoate (594) + TX, oxamyl (602) + TX, oxydemeton-methyl (609) + TX, oxydeprofos (1324) + TX, oxydisulfoton (1325) + TX, pp'-DDT (219) + TX, para-dichlorobenzene
[CCN] + TX, parathion (615) + TX, parathion-methyl (616) + TX, penfluron (alternative name) [CCN] + TX, pentachlorophenol (623) + TX, pentachlorophenyl laurate (lUPAC name) (623) + TX, permethrin (626) + TX, petroleum oils (alternative name) (628) + TX, PH 60-38 (development code) (1328) + TX, phenkapton (1330) + TX, phenothrin (630) + TX, phenthoate (631) + TX, phorate (636) + TX, phosalone (637) + TX, phosfolan (1338) + TX, phosmet (638) + TX, phosnichlor (1339) + TX, phosphamidon (639) + TX, phosphine (lUPAC name) (640) + TX, phoxim (642) + TX, phoxim-methyl (1340) + TX, pirimetaphos (1344) + TX, pirimicarb (651) + TX, pirimiphos-ethyl (1345) + TX, pirimiphos-methyl (652) + TX, polychlorodicyclopentadiene isomers (lUPAC name) (1346) + TX, polychloroterpenes (traditional name) (1347) + TX, potassium arsenite [CCN] + TX, potassium thiocyanate [CCN] + TX, prallethrin (655) + TX, precocene I (alternative name) [CCN] + TX, precocene II (alternative name) [CCN] + TX, precocene III (alternative name) [CCN] + TX, primidophos (1349) + TX, profenofos (662) + TX, profluthrin [CCN] + TX, promacyl (1354) + TX, promecarb (1355) + TX, propaphos (1356) + TX, propetamphos (673) + TX, propoxur (678) + TX, prothidathion (1360) + TX, prothiofos (686) + TX, prothoate (1362) + TX, protrifenbute [CCN] + TX, pymetrozine (688) + TX, pyraclofos (689) + TX, pyrazophos (693) + TX, pyresmethrin (1367) + TX, pyrethrin I (696) + TX, pyrethrin II (696) + TX, pyrethrins (696) + TX, pyridaben (699) + TX, pyridalyl (700) + TX, pyridaphenthion (701) + TX, pyrimidifen (706) + TX, pyrimitate (1370) + TX, pyriproxyfen (708) + TX, quassia (alternative name) [CCN] + TX, quinalphos (71 1) + TX, quinalphos- methyl (1376) + TX, quinothion (1380) + TX, quintiofos (1381) + TX, R-1492
(development code) (1382) + TX, rafoxanide (alternative name) [CCN] + TX, resmethrin (719) + TX, rotenone (722) + TX, RU 15525 (development code) (723) + TX, RU 25475 (development code) (1386) + TX, ryania (alternative name) (1387) + TX, ryanodine (traditional name) (1387) + TX, sabadilla (alternative name) (725) + TX, schradan (1389) + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, SI-0009 (compound code) + TX, SI-0205 (compound code) + TX, SI-0404 (compound code) + TX, SI-0405 (compound code) + TX, silafluofen (728) + TX, SN 72129 (development code) (1397) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoride (lUPAC/Chemical Abstracts name) (1399) + TX, sodium hexafluorosilicate (1400) + TX, sodium pentachlorophenoxide (623) + TX, sodium selenate (lUPAC name) (1401) + TX, sodium thiocyanate [CCN] + TX, sophamide (1402) + TX, spinosad (737) + TX, spiromesifen (739) + TX, spirotetrmat (CCN) + TX, sulcofuron (746) + TX, sulcofuron- sodium (746) + TX, sulfluramid (750) + TX, sulfotep (753) + TX, sulphuryl fluoride (756) + TX, sulprofos (1408) + TX, tar oils (alternative name) (758) + TX, tau-fluvalinate (398) + TX, tazimcarb (1412) + TX, TDE (1414) + TX, tebufenozide (762) + TX, tebufenpyrad (763) + TX, tebupirimfos (764) + TX, teflubenzuron (768) + TX, tefluthrin (769) + TX, temephos (770) + TX, TEPP (1417) + TX, terallethrin (1418) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachloroethane [CCN] + TX, tetrachlorvinphos (777) + TX, tetramethrin (787) + TX, theta-cypermethrin (204) + TX, thiacloprid (791) + TX, thiafenox (alternative name) + TX, thiamethoxam (792) + TX, thicrofos (1428) + TX, thiocarboxime (1431) + TX, thiocyclam (798) + TX, thiocyclam hydrogen oxalate (798) + TX, thiodicarb (799) + TX, thiofanox (800) + TX, thiometon (801) + TX, thionazin (1434) + TX, thiosultap (803) + TX, thiosultap-sodium (803) + TX, thuringiensin (alternative name) [CCN] + TX, tolfenpyrad (809) + TX, tralomethrin (812) + TX, transfluthrin (813) + TX, transpermethrin (1440) + TX, triamiphos (1441) + TX, triazamate (818) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, trichlorfon (824) + TX, trichlormetaphos-3 (alternative name) [CCN] + TX, trichloronat (1452) + TX, trifenofos (1455) + TX, triflumuron (835) + TX, trimethacarb (840) + TX, triprene (1459) + TX, vamidothion (847) + TX, vaniliprole [CCN] + TX, veratridine (alternative name) (725) + TX, veratrine (alternative name) (725) + TX, XMC (853) + TX, xylylcarb (854) + TX, YI-5302 (compound code) + TX, zeta-cypermethrin (205) + TX, zetamethrin (alternative name) + TX, zinc phosphide (640) + TX, zolaprofos (1469) and ZXI 8901 (development code) (858) + TX, cyantraniliprole [736994-63-19] + TX, chlorantraniliprole [500008-45-7] + TX, cyenopyrafen [560121-52-0] + TX, cyflumetofen [400882-07-7] + TX, pyrifluquinazon
[337458-27-2] + TX, spinetoram [187166-40-1 + 187166-15-0] + TX, spirotetramat [203313- 25-1] + TX, sulfoxaflor [946578-00-3] + TX, flufiprole [704886-18-0] + TX, meperfluthrin
[915288-13-0] + TX, tetramethylfluthrin [84937-88-2] + TX,
a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (lUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (lUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (lUPAC name) (347) and triphenyltin hydroxide (lUPAC name) (347) + TX, pyriprole [394730-71-3] + TX,
a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, 1 ,2-dibromo-3-chloropropane (lUPAC/Chemical Abstracts name) (1045) + TX, 1 ,2-dichloropropane (I U PA C/ Chemical Abstracts name) (1062) + TX, 1 ,2-dichloropropane with 1 ,3-dichloropropene (lUPAC name) (1063) + TX, 1 ,3-dichloropropene (233) + TX, 3,4- dichlorotetrahydrothiophene 1 , 1 -dioxide (lUPAC/Chemical Abstracts name) (1065) + TX, 3- (4-chlorophenyl)-5-methylrhodanine (lUPAC name) (980) + TX, 5-methyl-6-thioxo- 1 ,3,5- thiadiazinan-3-ylacetic acid (lUPAC name) (1286) + TX, 6-isopentenylaminopurine
(alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (1 18) + TX, carbon disulfide (945) + TX, carbosulfan (1 19) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion (1 158) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (lUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231) + TX, ivermectin (alternative name) [CCN] + TX, kinetin (alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam- potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (lUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) and zeatin (alternative name) (210) + TX, fluensulfone
[318290-98-1] + TX,
a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,
a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX,
a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1 ,3-dione (lUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (lUPAC name) (748) + TX, alpha-chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (91) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol
(alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301) + TX, flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1 183) + TX, flupropadine hydrochloride (1 183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (lUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (lUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (lUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoro- acetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX,
a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (lUPAC name) (934) + TX, 5-(1 ,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (lUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,
an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (lUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX,
a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX,
a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) and thiophanate-methyl (802) + TX,
and biologically active compounds selected from the group consisting of azaconazole (60207-31-0] + TX, bitertanol [70585-36-3] + TX, bromuconazole [116255-48-2] + TX, cyproconazole [94361-06-5] + TX, difenoconazole [1 19446-68-3] + TX, diniconazole
[83657-24-3] + TX, epoxiconazole [106325-08-0] + TX, fenbuconazole [114369-43-6] + TX, fluquinconazole [136426-54-5] + TX, flusilazole [85509-19-9] + TX, flutriafol [76674- 21-0] + TX, hexaconazole [79983-71-4] + TX, imazalil [35554-44-0] + TX, imibenconazole [86598-92-7] + TX, ipconazole [125225-28-7] + TX, metconazole [125116-23-6] + TX, myclobutanil [88671-89-0] + TX, pefurazoate [101903-30-4] + TX, penconazole [66246-88- 6] + TX, prothioconazole [178928-70-6] + TX, pyrifenox [88283-41-4] + TX, prochloraz [67747-09-5] + TX, propiconazole [60207-90-1] + TX, simeconazole [149508-90-7] + TX, tebuconazole [107534-96-3] + TX, tetraconazole [1 12281-77-3] + TX, triadimefon [43121- 43-3] + TX, triadimenol [55219-65-3] + TX, triflumizole [99387-89-0] + TX, triticonazole [131983-72-7] + TX, ancymidol [12771-68-5] + TX, fenarimol [60168-88-9] + TX, nuarimol [63284-71-9] + TX, bupirimate [41483-43-6] + TX, dimethirimol [5221-53-4] + TX, ethirimol [23947-60-6] + TX, dodemorph [1593-77-7] + TX, fenpropidine [67306-00-7] + TX, fenpropimorph [67564-91-4] + TX, spiroxamine [118134-30-8] + TX, tridemorph
[81412-43-3] + TX, cyprodinil [121552-61-2] + TX, mepanipyrim [110235-47-7] + TX, pyrimethanil [53112-28-0] + TX, fenpiclonil [74738-17-3] + TX, fludioxonil [131341-86-1] + TX, benalaxyl [71626-11-4] + TX, furalaxyl [57646-30-7] + TX, metalaxyl [57837-19-1] + TX, R-metalaxyl [70630-17-0] + TX, ofurace [58810-48-3] + TX, oxadixyl [77732-09-3] + TX, benomyl [17804-35-2] + TX, carbendazim [10605-21-7] + TX, debacarb [62732-91-6] + TX, fuberidazole [3878-19-1] + TX, thiabendazole [148-79-8] + TX, chlozolinate [84332- 86-5] + TX, dichlozoline [24201-58-9] + TX, iprodione [36734-19-7] + TX, myclozoline [54864-61-8] + TX, procymidone [32809-16-8] + TX, vinclozoline [50471-44-8] + TX, boscalid [188425-85-6] + TX, carboxin [5234-68-4] + TX, fenfuram [24691-80-3] + TX, flutolanil [66332-96-5] + TX, mepronil [55814-41-0] + TX, oxycarboxin [5259-88-1] + TX, penthiopyrad [183675-82-3] + TX, thifluzamide [130000-40-7] + TX, guazatine [108173-90- 6] + TX, dodine [2439-10-3] [112-65-2] (free base) + TX, iminoctadine [13516-27-3] + TX, azoxystrobin [131860-33-8] + TX, dimoxystrobin [149961-52-4] + TX, enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1 , 93} + TX, fluoxastrobin [361377-29-9] + TX, kresoxim-methyl [143390-89-0] + TX, metominostrobin [133408-50-1] + TX, trifloxystrobin [141517-21-7] + TX, orysastrobin [248593-16-0] + TX, picoxystrobin [1 17428-22-5] + TX, pyraclostrobin [175013-18-0] + TX, ferbam [14484-64-1] + TX, mancozeb [8018-01-7] + TX, maneb [12427-38-2] + TX, metiram [9006-42-2] + TX, propineb [12071-83-9] + TX, thiram [137-26-8] + TX, zineb [12122-67-7] + TX, zi ram [137-30-4] + TX, captafol [2425- 06-1] + TX, captan [133-06-2] + TX, dichlofluanid [1085-98-9] + TX, fluoroimide [41205- 21-4] + TX, folpet [133-07-3 ] + TX, tolylfluanid [731-27-1] + TX, bordeaux mixture [801 1- 63-0] + TX, copperhydroxid [20427-59-2] + TX, copperoxychlorid [1332-40-7] + TX, coppersulfat [7758-98-7] + TX, copperoxid [1317-39-1] + TX, mancopper [53988-93-5] + TX, oxine-copper [10380-28-6] + TX, dinocap [131-72-6] + TX, nitrothal-isopropyl [10552- 74-6] + TX, edifenphos [17109-49-8] + TX, iprobenphos [26087-47-8] + TX,
isoprothiolane [50512-35-1] + TX, phosdiphen [36519-00-3] + TX, pyrazophos [ 3457-18- 6] + TX, tolclofos-methyl [57018-04-9] + TX, acibenzolar-S-methyl [135158-54-2] + TX, anilazine [101-05-3] + TX, benthiavalicarb [413615-35-7] + TX, blasticidin-S [2079-00-7] + TX, chinomethionat [2439-01-2] + TX, chloroneb [2675-77-6] + TX, chlorothalonil [1897- 45-6] + TX, cyflufenamid [180409-60-3] + TX, cymoxanil [57966-95-7] + TX, dichlone [117-80-6] + TX, diclocymet [139920-32-4] + TX, diclomezine [62865-36-5] + TX, dicloran [99-30-9] + TX, diethofencarb [87130-20-9] + TX, dimethomorph [110488-70-5] + TX, SYP-LI90 (Flumorph) [211867-47-9] + TX, dithianon [3347-22-6] + TX, ethaboxam
[162650-77-3] + TX, etridiazole [2593-15-9] + TX, famoxadone [131807-57-3] + TX, fenamidone [161326-34-7] + TX, fenoxanil [115852-48-7] + TX, fentin [668-34-8] + TX, fenmzone [89269-64-7] + ΎΧ, fluazinam [79622-59-6] + TX, fluopicolide [239110-15-7] + TX, flusulfamide [106917-52-6] + TX, fenhexamid [126833-17-8] + TX, fosetyl-aluminium [39148-24-8] + TX, hymexazol [10004-44-1] + TX, iprovalicarb [140923-17-7] + TX, IKF-916 (Cyazofamid) [120116-88-3] + TX, kasugamycin [6980-18-3] + TX, methasulfo- carb [66952-49-6] + TX, metrafenone [220899-03-6] + TX, pencycuron [66063-05-6] + TX, phthalide [27355-22-2] + TX, polyoxins [1 11 13-80-7] + TX, probenazole [27605-76-1] + TX, propamocarb [25606-41-1] + TX, proquinazid [189278-12-4] + TX, pyroquilon
[57369-32-1] + TX, quinoxyfen [124495-18-7] + TX, quintozene [82-68-8] + TX, sulphur [7704-34-9] + TX, tiadinil [223580-51-6] + TX, triazoxide [72459-58-6] + TX, tricyclazole [41814-78-2] + TX, triforine [26644-46-2] + TX, validamycin [37248-47-8] + TX, zoxamide (RH7281) [156052-68-5] + TX, mandipropamid [374726-62-2] + TX, isopyrazam [881685- 58-1] + TX, sedaxane [874967-67-6] + TX, 3-difluoromethyl-1-methyl-1 H-pyrazole-4- carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide (dislosed in WO 2007/048556) + TX, 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid [2-(2,4-dichlorophenyl)-2-methoxy-1-methyl-ethyl]-amide (disclosed in WO
2008/148570) + TX, 1-[4-[4-[(5S)5-(2,6-difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3- thiazol-2-yl]piperidin-1-yl]-2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone + TX, 1- [4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2-yl]piperidin-1-yl]-2-[5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone [1003318-67-9], both disclosed in WO 2010/123791 , WO 2008/013925, WO 2008/013622 and WO 201 1/051243 page 20) +TX, S)-[3-(4-Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl-methanol + TX, 3-(4-Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y l]-pyridin-3-yl- methanol + TX and 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro- biphenyl-2-yl)-amide (dislosed in WO 2006/087343) + TX, 3-(difluoromethyl)-N-methoxy-1- methyl-N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]-1 H-Pyrazole-4-carboxamide + TX,
The following components (B) are registered under a CAS-Reg. No.
aldimorph (CAS 91315-15-0); arsenates (CAS 1327-53-3); benalaxyl -M (CAS 98243-83-5); benthiavalicarb (CAS 413615-35-7); cadmium chloride (CAS 10108-64-2); cedar leaf oil (CAS 8007-20-3); chlorine (CAS 7782-50-5); cinnamaldehyde (CAS: 104-55-2); copper ammoniumcarbonate (CAS 33113-08-5); copper oleate (CAS 1120-44-1); iodocarb (3-lodo- 2-propynyl butyl carbamate) (CAS 55406-53-6); hymexazole (CAS 10004-44-1); manganous dimethyldithiocarbamate (CAS 15339-36-3); mercury (CAS 7487-94-7; 21908-53-2; 7546-30- 7); metrafenone (CAS 220899-03-6); neem oil (hydrophobic extract) (CAS 8002-65-1);
orysastrobin CAS 248593-16-0); paraformaldehyde (CAS 30525-89-4); penthiopyrad (CAS 183675-82-3); phosphoric acid (CAS 7664-38-2); potassium bicarbonate (CAS 298-14-6); sodium bicarbonate (CAS 144-55-8); sodium diacetate (CAS 127-09-3); sodium propionate (CAS 137-40-6) ;TCMTB (CAS 21564-17-0); and tolyfluanid (CAS 731-27-1). Compound B-1.1 ("enestrobin") is described in EP-0-936-213; compound B-3.1 ("flumorph") in US-6,020,332, CN-1-167-568, CN-1-155-977 and in EP-0-860-438; compound B-5.1 ("mandipropamid") in WO 01/87822; compound B-5.2 in WO 98/46607; compound B-5.3 ("fluopicolide") in WO 99/42447; compound B-5.4 ("cyflufenamid") in WO 96/19442;
compound B-5.5 in WO 99/14187; compound B-5.6 ("pyribencarb") is registered under CAS- Reg. No. 325156-49-8; compound B-5.7 ("amisulbrom" or "ambromdole") is registered under CAS-Reg. No. 348635-87-0; compound B-5.8 (3-difluoromethyl-1-methyl-1 H-pyrazole-4- carboxylic acid (2-bicyclopropyl-2-yl-phenyl)-amide) is described in WO 03/74491 ; compound B-5.9 (3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (9-isopropyp-1 , 2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide) is described in WO 04/35589 and in WO 06/37632; compound B-5.10 (1 ,3-dimethyl-5-fluoro-1 H-pyrazole-4-carboxylic acid [2- (1 ,3-dimethylbutyl)phenyl]-amide) is described in WO 03/10149; compound B-5.1 1 (3- difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (3',4'-dichloro-5-fluoro-1 ,1 '-biphenyl-2- yl)-amide; "bixafen") is registered under CAS-Reg. No.: 581809-46-3 and described in WO 03/70705; compound B-5.12 (N-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-
(trifluoromethyl)benzamid; "fluopyram") is registered under CAS-Reg. No: 658066-35-4 and described in WO 04/16088; compounds B-5.13, B-5.14 and B-5.15 are described in WO 2007/17450; compounds B-5.16, B-5.17 and B-5.18 are described in WO 2006/120219; The compounds of formula IV are for example described in WO 04/067528, WO 2005/085234, WO 2006/1 11341 , WO 03/015519, WO 2007/020050, WO 2006/040113, and WO
2007/093402. The compound of formula V is described in WO 2001/094339. Isopyraxam (3- (difluoromethyl)-1-methyl-/V-[1 ,2,3,4-tetrahydro-9-(1-methylethyl)-1 ,4-methanonaphthalen-5- yl]-1 /-/-pyrazole-4-carboxamide) is described in WO 2004/035589, in WO 2006/037632 and in EP1556385B1 and is registered under the CAS-Reg. 881685-58-1. Sedaxane (Λ/-[2-[1 , 1 '- bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1 /-/-pyrazole-4-carboxamide) is described in WO 2003/074491 and is registered under the CAS-Reg. 874967-67-6; 1-[4-[4- [5-(2,6-Difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2-yl]piperidin-1-yl]-2-[5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone is described in WO2010123791 , WO2008013925 and WO2008013622 and is registered under the CAS-RegNr.: 1003318-67- 9. The compound of formula (VI) is described in WO 2008/014870; the compound of formula (Via) is described in WO 2010/063700; a compound of formula (Vlb) (Fluxapyroxad) is described in WO2006087343 and WO2009007344 and is registered under the CAS-RegNr.: 907204-31-3, a compound of formula (Vic) which is 3-(difluoromethyl)-N-methoxy-1-methyl- N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]-1 H-pyrazole-4-carboxamide is described in WO2010063700; (S)-[3-(4-Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y I]- pyridin-3-yl-methanol, 3-(4-Chloro-2-fluoro-phenyl)-5 -(2,4-difluoro-phenyl)-isoxazol-4-y I]- pyridin-3-yl-methanol are found in WO2010069881 and the compounds of formula (VII) is described in WO 2007/048556. Fomesafen is registered under the CAS-Reg. No. 72178-02- 0.
It has been found that the use of component (B) in combination with component TX surprisingly and substantially may enhance the effectiveness of the latter against fungi, and vice versa. Additionally, the method of the invention is effective against a wider spectrum of such fungi that can be combated with the active ingredients of this method, when used solely.
In general, the weight ratio of component TX to component (B) is from 2000 : 1 to 1 : 1000. A non-limiting example for such weight ratios is compound of formula I : compound of formula B-2 is 10: 1. The weight ratio of component TX to component (B) is preferably from 100 : 1 to 1 : 100; more preferably from 20 : 1 to 1 : 50.
The active ingredient mixture of component TX to component (B) comprises compounds of formula I and a further, other biocidally active ingredients or compositions or if desired, a solid or liquid adjuvant preferably in a mixing ratio of from 1000: 1 to 1 : 1000, especially from 50: 1 to 1 :50, more especially in a ratio of from 20: 1 to 1 :20, even more especially from 10:1 to 1 : 10, very especially from 5: 1 and 1 :5, special preference being given to a ratio of from 2:1 to 1 :2, and a ratio of from 4: 1 to 2: 1 being likewise preferred, above all in a ratio of 1 :1 , or 5:1 , or 5:2, or 5:3, or 5:4, or 4:1 , or 4:2, or 4:3, or 3: 1 , or 3:2, or 2: 1 , or 1 :5, or 2:5, or 3:5, or 4:5, or 1 :4, or 2:4, or 3:4, or 1 :3, or 2:3, or 1 :2, or 1 :600, or 1 :300, or 1 :150, or 1 :35, or 2:35, or 4:35, or 1 :75, or 2:75, or 4:75, or 1 :6000, or 1 :3000, or 1 :1500, or 1 :350, or 2:350, or 4:350, or 1 :750, or 2:750, or 4:750. Those mixing ratios are understood to include, on the one hand, ratios by weight and also, on other hand, molar ratios. It has been found, surprisingly, that certain weight ratios of component TX to component (B) are able to give rise to synergistic activity. Therefore, a further aspect of the invention are compositions, wherein component TX and component (B) are present in the composition in amounts producing a synergistic effect. This synergistic activity is apparent from the fact that the fungicidal activity of the composition comprising component TX and component (B) is greater than the sum of the fungicidal activities of component TX and of component (B). This synergistic activity extends the range of action of component TX and component (B) in two ways. Firstly, the rates of application of component TX and component (B) are lowered whilst the action remains equally good, meaning that the active ingredient mixture still achieves a high degree of phytopathogen control even where the two individual components have become totally ineffective in such a low application rate range. Secondly, there is a substantial broadening of the spectrum of phytopathogens that can be controlled. A synergistic effect exists whenever the action of an active ingredient combination is greater than the sum of the actions of the individual components. The action to be expected E for a given active ingredient combination obeys the so-called COLBY formula and can be calculated as follows (COLBY, S.R. "Calculating synergistic and antagonistic responses of herbicide combination". Weeds, Vol. 15, pages 20-22; 1967):
ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture
X = % action by active ingredient A) using p ppm of active ingredient
Y = % action by active ingredient B) using q ppm of active ingredient.
According to COLBY, the expected (additive) action of active ingredients A)+B) using
X · Y
p+q ppm of active ingredient is E = X + Y - If the action actually observed (O) is greater than the expected action (E), then the action of the combination is super-additive, i.e. there is a synergistic effect. In mathematical terms, synergism corresponds to a positive value for the difference of (O-E). In the case of purely complementary addition of activities (expected activity), said difference (O-E) is zero. A negative value of said difference (O-E) signals a loss of activity compared to the expected activity.
However, besides the actual synergistic action with respect to fungicidal activity, the compositions according to the invention can also have further surprising advantageous properties. Examples of such advantageous properties that may be mentioned are: more advantageuos degradability; improved toxicological and/or ecotoxicological behaviour; or improved characteristics of the useful plants including: emergence, crop yields, more developed root system, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, improved plant vigor, and early germination.
Some compositions according to the invention have a systemic action and can be used as foliar, soil and seed treatment fungicides.
With the compositions according to the invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of plants which grow later are also protected from attack by phytopathogenic microorganisms.
The compositions according to the invention can be applied to the phytopathogenic microorganisms, the useful plants, the locus thereof, the propagation material thereof, storage goods or technical materials threatened by microorganism attack.
The compositions according to the invention may be applied before or after infection of the useful plants, the propagation material thereof, storage goods or technical materials by the microorganisms. A further aspect of the present invention is a method of controlling diseases on useful plants or on propagation material thereof caused by phytopathogens, which comprises applying to the useful plants, the locus thereof or propagation material thereof a composition according to the invention. Preferred is a method, which comprises applying to the useful plants or to the locus thereof a composition according to the invention, more preferably to the useful plants. Further preferred is a method, which comprises applying to the propagation material of the useful plants a composition according to the invention.
The components (B) are known. Where the components (B) are included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council], they are described therein under the entry number given in round brackets hereinabove for the particular component (B); for example, the compound "abamectin" is described under entry number (1). Most of the components (B) are referred to hereinabove by a so-called "common name", the relevant "ISO common name" or another "common name" being used in individual cases. If the designation is not a "common name", the nature of the designation used instead is given in round brackets for the particular component (B); in that case, the lUPAC name, the lUPAC/Chemical Abstracts name, a "chemical name", a "traditional name", a "compound name" or a "develoment code" is used or, if neither one of those designations nor a "common name" is used, an "alternative name" is employed.
The following components B) are registered under a CAS-Reg. No.
aldimorph (CAS 91315-15-0); arsenates (CAS 1327-53-3); benalaxyl -M (CAS 98243-83-5); benthiavalicarb (CAS 413615-35-7); cadmium chloride (CAS 10108-64-2); cedar leaf oil (CAS 8007-20-3); chlorine (CAS 7782-50-5); cinnamaldehyde (CAS: 104-55-2); copper ammoniumcarbonate (CAS 33113-08-5); copper oleate (CAS 1120-44-1); iodocarb (3-lodo- 2-propynyl butyl carbamate) (CAS 55406-53-6); hymexazole (CAS 10004-44-1); manganous dimethyldithiocarbamate (CAS 15339-36-3); mercury (CAS 7487-94-7; 21908-53-2; 7546-30- 7); metrafenone (CAS 220899-03-6); neem oil (hydrophobic extract) (CAS 8001-65-1);
orysastrobin CAS 248593-16-0); paraformaldehyde (CAS 30525-89-4); penthiopyrad (CAS 183675-82-3); phosphoric acid (CAS 7664-38-2); potassium bicarbonate (CAS 298-14-6); sodium bicarbonate (CAS 144-55-8); sodium diacetate (CAS 127-09-3); sodium propionate (CAS 137-40-6) ;TCMTB (CAS 21564-17-0); and tolyfluanid (CAS 731-27-1).
Compound B-1.1 ("enestrobin") is described in EP-0-936-213; compound B-3.1 ("flumorph") in US-6,020,332, CN-1-167-568, CN-1-155-977 and in EP-0-860-438; compound B-5.1 ("mandipropamid") in WO 01/87822; compound B-5.2 in WO 98/46607; compound B-5.3 ("fluopicolide") in WO 99/42447; compound B-5.4 ("cyflufenamid") in WO 96/19442;
compound B-5.5 in WO 99/14187; compound B-5.6 ("pyribencarb") is registered under CAS- Reg. No. 325156-49-8; compound B-5.7 ("amisulbrom" or "ambromdole") is registered under CAS-Reg. No. 348635-87-0; compound B-5.8 (3-difluoromethyl-1-methyl-1 H-pyrazole-4- carboxylic acid (2-bicyclopropyl-2-yl-phenyl)-amide) is described in WO 03/74491 ; compound B-5.9 (3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (9-isopropyp-1 , 2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide) is described in WO 04/35589 and in WO 06/37632; compound B-5.10 (1 ,3-dimethyl-5-fluoro-1 H-pyrazole-4-carboxylic acid [2- (1 ,3-dimethylbutyl)phenyl]-amide) is described in WO 03/10149; compound B-5.1 1 (3- difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (3',4'-dichloro-5-fluoro-1 ,1 '-biphenyl-2- yl)-amide; "bixafen") is registered under CAS-Reg. No.: 581809-46-3 and described in WO 03/70705; compound B-5.12 (N-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2- (trifluoromethyl)benzamid; "fluopyram") is registered under CAS-Reg. No: 658066-35-4 and described in WO 04/16088; compounds B-5.13, B-5.14 and B-5.15 are described in WO 2007/17450; compounds B-5.16, B-5.17 and B-5.18 are described in WO 2006/120219; The compounds of formula IV are for example described in WO 04/067528, WO 2005/085234, WO 2006/1 11341 , WO 03/015519, WO 2007/020050, WO 2006/040113, and WO
2007/093402. The compound of formula V is described in WO 2001/094339. Isopyraxam (3- (difluoromethyl)-1-methyl-/V-[1 ,2,3,4-tetrahydro-9-(1-methylethyl)-1 ,4-methanonaphthalen-5- yl]-1 /-/-pyrazole-4-carboxamide) is described in WO 2004/035589, in WO 2006/037632 and in EP1556385B1 and is registered under the CAS-Reg. 881685-58-1. Sedaxane (Λ/-[2-[1 , 1 '- bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1 /-/-pyrazole-4-carboxamide) is described in WO 2003/074491 and is registered under the CAS-Reg. 874967-67-6; The compound of formula (VI) is described in WO 2008/014870; and the compounds of formula (VII) is described in WO 2007/048556. Fomesafen is registered under the CAS-Reg. No. 72178-02-0. Throughout this document the expression "composition" stands for the various mixtures or combinations of components TX and (B), for example in a single "ready-mix" form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the components TX and (B) is not essential for working the present invention.
The compositions according to the invention may also comprise more than one of the active components (B), if, for example, a broadening of the spectrum of disease control is desired. For instance, it may be advantageous in the agricultural practice to combine two or three components (B) with component TX. An example is a composition comprising a compound of formula (I), azoxystrobin and cyproconazole.
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i. /ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient rates of application are from 10mg to 1 g of active substance per kg of seeds. The rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
The compounds of formula (I), or a pharmaceutical salt thereof, described above may also have an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal. "Animal" can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human. "Treatment" means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection. "Prevention" means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.
According to the present invention there is provided the use of a compound of formula (I) in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal. There is also provided the use of a compound of formula (I) as a pharmaceutical agent. There is also provided the use of a compound of formula (I) as an antimicrobial agent in the treatment of an animal. According to the present invention there is also provided a pharmaceutical composition comprising as an active ingredient a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal. This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs. Alternatively this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion. Alternatively this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection. Alternatively this pharmaceutical composition can be in inhalable form, such as an aerosol spray.
The compounds of formula (I) may be effective against various microbial species able to cause a microbial infection in an animal. Examples of such microbial species are those causing Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terms, A. nidulans and A. niger, those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causing Coccidioidomycosis such as Coccidioides immitis; those causing Cryptococcosis such as Cryptococcus neoformans; those causing Histoplasmosis such as Histoplasma capsulatum and those causing Zygomycosis such as Absidia corymbifera, Rhizomucor pusillus and Rhizopus arrhizus. Further examples are Fusarium Spp such as Fusarium oxysporum and Fusarium solani and Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolificans. Still further examples are Microsporum Spp, Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and
Histoplasma Spp. The following non-limiting examples illustrate the above-described invention in greater detail without limiting it.
Preparatory examples: Example P1 : Preparation of 2-(6-Methyl-pyridin-2-yl)-4-phenyl-quinazoline) a) To a mixture of anthranilamide (5.00 g, 36.7 mmol) and triethylamine (10.2 ml 73.4 mmol,) in DCE (75 ml) was successively added bis(2-oxo-3-oxazolidinyl)phosphinic chloride (1 1.22 g, 44.07 mmol) and 6-methylpicolinic acid (5.666 g, 41.32 mmol). The mixture was stirred under reflux for 1 h and then cooled to RT. The resulting precipitate was filtered and the off white solid was thoroughly washed with NaHC03 and water. The product was dried in vacuo overnight to afford A/-(2-carbamoylphenyl)-6-methyl-pyridine-2-carboxamide as a white solid. The product was used in the next reaction without further purification.
LCMS: 1.41 min; method A; [M+H]+ = 256 b) To a mixture of A/-(2-carbamoylphenyl)-6-methyl-pyridine-2-carboxamide (8.183 g, 32.06 mmol) in EtOH (100 ml) was added 2N NaOH (50 ml, 96 mmol). The reaction mixture heated under reflux for 1 h and then cooled to RT. The solution was acidified with 6M HCI and the resulting precipitate was filtered, washed with water, sat. NaHC03, and again with water to afford 2-(6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one as a white solid. The product was used in the next step without further purification.
LCMS: 1.62 min; method A; [M+H]+ = 238 c) To a vial containing 2-(6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one (1.00 g, 4.22 mmol) was added phosphorus oxychloride (1.5 ml, 17 mmol). The mixture was heated under MW irradiation at 100 °C for 5 min. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in dichloromethane before the residual phosphorus derivatives were quenched by pouring slowly into a sat. aqueous solution of NaHC03 at 0°C. The mixture was then extracted with dichloromethane, and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure to afford 4-chloro-2-(6-methyl-pyridin-2-yl)-quinazoline as a yellow oil which was used in the next step without further purification.
LCMS: 1.54 min; method A; [M+H]+ = 256 d) To a solution of 4-chloro-2-(6-methyl-pyridin-2-yl)-quinazoline (0.050 g, 0.20 mmol) in DME (1.3 ml) was added phenylboronic acid (0.029 g, 0.24 mmol) and an aqueous solution of sodium carbonate 2M (0.294 ml, 0.587 mmol). The reaction mixture was then degassed under vacuum in an ultrasonic bath during 10 min and put under an inert atmosphere. The tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.010 mmol) was then added and the mixture was heated under MW irradiation at 110°C for 25 min. The reaction mixture was cooled, diluted with water and extracted with ethyl acetate. The combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/AcOEt; 95/5) to afford 2-(6-methyl-pyridin-2-yl)-4- phenyl-quinazoline as a white powder,
mp: 173-176 °C. LCMS: 1.51 min; method A; [M+H]+ = 298.
Example P2: Preparation of 2-(6-Ethyl-pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline a) To a mixture of anthranilamide (5.00 g 36.7 mmol) and triethylamine (10.2 ml 73.4 mmol) in DCE (75 ml) was added bis(2-oxo-3-oxazolidinyl)phosphinic chloride (11.22 g 44.07 mmol) and 6-bromopicolinic acid (8.35 g, 41.3 mmol). The mixture was heated under reflux for 1 h and then cooled to RT. The resulting precipitate was filtered and the off white solid was thoroughly washed with NaHC03 and water. The product was dried in vacuo overnight to afford 6-bromo-/V-(2-carbamoylphenyl)pyridine-2-carboxamide as a white solid. The product was used in the next step without further purification.
LCMS: 1.50 min; method A; [M+H]+ = 321 b) To a mixture of 6-bromo-/V-(2-carbamoylphenyl)pyridine-2-carboxamide (9.50 g, 29. 7 mmol) in EtOH (100 ml) was added 2N NaOH (50 ml, 100 mmol). The reaction mixture was heated under reflux for 1 h and then cooled to RT. The solution was acidified with 6M HCI and the resulting precipitate was filtered, washed with water, sat. NaHC03, and again with water to afford 2-(6-bromo-pyridin-2-yl)-3/-/-quinazolin-4-one as a white solid. The product was used in the next step without further purification.
LCMS: 1.66 min; method A; [M+H]+ = 304 c) To a vial containing 2-(6-bromo-pyridin-2-yl)-3/-/-quinazolin-4-one (1.00 g 3.31 mmol) was added phosphorus oxybromide (3.80 g, 13.2 mmol). The mixture was heated under MW irradiation at 120 °C for 20 min. The reaction mixture was dissolved in dichloromethane and quenched by pouring slowly in a sat. solution of NaHC03 at 0°C. The aqueous layer was extracted with dichoromethane and the combined organic layers were washed with brine, dried over Na2S04 and concentrated to afford 4-bromo-2-(6-bromo-pyridin-2-yl)-quinazoline as a yellow solid. The product was used in the next step without further purification.
LCMS: 1.91 min; method A; [M+H]+ = 366 d) To a solution of 4-bromo-2-(6-bromo-pyridin-2-yl)-quinazoline (1.160 g, 3.178 mmol) in DME (20 ml) was added 3-methoxyphenylboronic acid (0.579 g, 3.81 mmol) and an aqueous solution of sodium carbonate 2M (4.76 ml, 9.53 mmol). The reaction mixture was then degassed under vacuum in an ultrasonic bath during 10 min and put under an inert atmosphere. The tetrakis(triphenylphosphine)palladium(0) (0.184 g, 0.159 mmol) was then added and the mixture was heated at 70 °C for 7h. The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was triturated in ether to afford 2-(6-bromo-pyridin-2-yl)-4-(methoxy- phenyl)-quinazoline as a beige powder. The product was used in the next step without further purification.
LCMS: 2.02 min; method A; [M+H]+ = 394 e) To a stirred suspension of anhydrous lnCI3 (0.039 g, 0.18 mmol) in dry THF (0.5 ml) at 0°C was added dropwise a solution of ethylmagnesium bromide (3M, 0.102 ml, 0.306 mmol). The mixture was warmed to RT and stirred for an additional 1 h. The resulting cloudy solution was canulated to a solution of 2-(6-bromo-pyridin-2-yl)-4-(methoxy-phenyl)-quinazoline (0.100 g, 0.255 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (0.029 g, 0.025 mmol) in THF (0.5 ml) under inert atmosphere and the resulting mixture was heated under reflux overnight. The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 95/5 to 80/20) to afford 2-(6-ethyl-pyridin-2-yl)- 4-(3-methoxy-phenyl)-quinazoline as a beige powder,
mp: 124-126 °C. LCMS: 1.69 min; method A; [M+H]+ = 342
Example P3: Preparation of 2-(4-Methoxy-6-methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)- quinazoline a) To a solution of 4-chloro-2-picoline (2.00 g, 15.7 mmol) in CH2CI2 (18.4 ml) was added portionwise mefa-chloroperbenzoic acid (5.024 g, 20.38 mmol) over a period of 1 h. The suspension was stirred overnight at RT and the concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/MeOH; 100/0 to 90/10) to afford 4-chloro-2-methyl-pyridine 1 -oxide as a yellow oil.
LCMS: 0.47 min; method A; [M+H]+ = 144 b) To a solution of 4-chloro-2-methyl-pyridine 1 -oxide (2.250 g, 15.67 mmol) in acetonitrile (50 ml) was added Et3N (6.55 ml, 47.0 mmol,) and TMSCN (1 1.76 ml, 94.03 mmol). The resulting brown solution was heated overnight under reflux and then quenched with 60 mL of sat. aqueous NaHC03. The aqueous phase was extracted with CH2CI2 and the combined organic layers were washed with water and brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 100/0 to 0/100) to afford 4-chloro-6-methyl-pyridine-2-carbonitrile as a light orange powder.
LCMS: 1.35 min; method A; [M+H]+ = 153 c) To a solution of 4-chloro-6-methyl-pyridine-2-carbonitrile (0.460 g, 3.02 mmol) in anhydrous methanol (1 ml) was added sodium methoxide (30% wt, 0.201 ml, 1.055 mmol). The reaction mixture was stirred at RT for 1 h before a solution of anthranilic acid (0.517 g, 3.77 mmol) in dry methanol (6 mL) was added. The resulting yellow solution was stirred at RT for an additional 45 min and then heated under reflux overnight. The reaction mixture was then cooled to 0 °C and kept at this temperature for 1 h. The resulting yellow precipitate was filtered to afford 2-(4-chloro-6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one. The product was used in the next step without further purification.
LCMS: 1.87 min; method A; [M+H]+ = 272 d) To a vial containing 2-(4-chloro-6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one (0.435 g, 1.60 mmol) was added phosphorus oxychloride (0.586 ml, 6.40 mmol). The mixture was heated under MW irradiation at 100 °C for 5 min. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in dichloromethane before the residual phosphorus derivatives were quenched by pouring slowly into a sat. aqueous solution of NaHC03 at 0°C. The mixture was then extracted with dichloromethane, and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure to afford 4-chloro-2-(4-chloro-6-methyl-pyridin-2-yl)-quinazoline. The product was used in the next step without further purification.
LCMS: 1.96 min; method A; [M+H]+ = 290 e) To a solution of 4-chloro-2-(4-chloro-6-methyl-pyridin-2-yl)-quinazolinein DME (10 ml) was added 3-methoxyphenylboronic acid (0.268 g, 1.761 mmol) and an aqueous solution of sodium carbonate 2M (2.4 ml, 4.8 mmol). The reaction mixture was then degassed under vacuum in an ultrasonic bath during 10 min and put under an inert atmosphere. The tetrakis(triphenylphosphine)palladium(0) (0.093 g, 0.080 mmol) was added and the mixture was heated under MW irradiation at 1 10 °C for 25 min. The reaction mixture was cooled, diluted with water and extracted with ethyl acetate. The combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/AcOEt; 100/0 to 80/20) to afford 2-(4-chloro-6-methyl- pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline as a yellow powder.
LCMS: 2.07 min; method A; [M+H]+ = 362 f) To a solution of 2-(4-chloro-6-methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline (0.090 g, 0.25 mmol) in dry methanol (0.3 ml) was added sodium methoxide (30% wt, 0.538 ml, 0.995 mmol). The reaction mixture was heated under reflux for 72 h and then water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/AcOEt; 100/0 to 80/20) to afford 2-(4-methoxy-6- methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline as a white powder.
LCMS: 1.28 min; method A; [M+H]+ = 358
Example P4: Preparation of A/,A/-Diethyl-4-[2-(6-methyl-2-pyridyl)quinazolin-4-yl]aniline a) To a vial containing 2-(6-methyl-pyridin-2-yl)-3/-/-quinazolin-4-one (0.200g, 0.843 mmol) was added phosphorus oxychloride (0.309 ml, 3.37 mmol) and diethylaniline (0.337 ml, 2.1 1 mmol). The mixture was heated under MW irradiation at 120 °C for 1 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in dichloromethane before the residual phosphorus derivatives were quenched by pouring slowly into a sat. aqueous solution of NaHC03 at 0°C. The mixture was then extracted with dichloromethane, and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 95/5 to 80/20) to afford A/,/V-diethyl-4-[2-(6-methyl-2- pyridyl)quinazolin-4-yl]aniline as a yellow powder,
mp : 114-118°C. LCMS: 1.67 min ; method A; [M+H]+ = 369
Example P5: Preparation of 2-(4,6-Dimethylpyridin-2-yl)-4-(3-methoxy-phenyl)-quinazoline
To a stirred suspension of anhydrous lnCI3 (0.060 g, 0.27 mmol) in dry THF (0.6 ml) at 0°C was added dropwise a solution of methylmagnesium chloride (3M, 0.258 ml, 0.774 mmol). The mixture was warmed to RT and stirred for an additional 1 h. The resulting cloudy solution was canulated to a solution of 2-(4-chloro-6-methyl-pyridin-2-yl)-4-(3-methoxy-phenyl)- quinazoline (0.140 g, 0.387 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (0.045 g, 0.040 mmol) in THF (0.5ml) under inert atmosphere and the resulting mixture was heated under reflux overnight. The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 50/50 to 60/40). The resulting solid was further purified by trituration with diethylether to afford 2-(4,6-dimethyl-pyridin-2-yl)- 4-(3-methoxy-phenyl)-quinazoline as a yellow powder. mp: 121 -124 °C. LCMS: 1 .54 min ; method B; [M+H]+ = 342
Example P6: Preparation of 6-methoxy-2-(6-methyl-2-pyridyl)-4-phenyl-quinazoline a) Preparation of 2-methyl-pyridin-1 -oxide: To a solution of 2-picoline (2g, 22mmol) in ethyl acetate (20ml) in a 50 ml round bottom flask was added 3-chloroperbenzoic acid (50%, 7.39g, 43mmol) in small portions over a period of 10 min. at 0°C. After complete addition, the reaction mixture was stirred at room temperature till TLC indicated completion of the reaction. Reaction mass was concentrated under reduced pressure and subjected to column chromatography using 5% methanol in dichloromethane as eluent to afford the desired product as viscous liquid.
1HNMR (400MHZ, CDCI3): δ 8.23 (d, J = 6 Hz, 1 H), 7.46 (d, J = 9.2 Hz, 1 H), 7.2 - 7.3 (m, 2H), 2.33 (s, 3H). b) Preparation of 2-cyano-6-methylpyridine: To a mixture of 2-methyl-pyridin-1 -oxide (1 g, 9mmol) and Toluene in a microwave vessel was added trimethylsilyl cyanide (1 .36g, 13.76mmol) followed by carbamoyl chloride (1 .48g, 13.76mmol).The reaction mixture was heated in microwave reactor at 70°C for 40 min. Reaction mixture was cooled to room temperature and washed with saturated sodium bicarbonate solution, dried over sodium sulphate, concentrated under reduced pressure followed by purification using flash chromatography. The desired product was obtained as white solid, M. P. 73 - 75°C. 1HNMR (400MHZ, CDCIs): 5 7.65 (dd, J = 7.6, 8.0Hz, 1 H), 7.45 (d, J = 8.0 Hz, 1 H), 7.32 (d, J = 7.8Hz, 1 H), 2.55(s, 3H) c) Preparation of 6-Chloro-2-(6-methyl-pyridin-2-yl)-quinazolin-4-ylamine: A solution of 2- amino-5-chloro benzonitrile (1 .43g, 9.34mmol) in anhydrous THF (15 ml) was slowly added drop wise to a stirred suspension of sodium hydride (60% in oil suspension, 0.448g, 18.69mmol) in anhydrous THF (10 ml) during 15 min under N2 atmosphere at 0°C. After completion of the addition the cold bath was removed and the reaction mixture was slowly warmed to room temperature. A solution of 2-cyano-6-methyl pyridine (1 g, 8.47mmol) in anhydrous THF (10 ml) was added drop wise under stirring to the above mixture and then the whole mixture was refluxed till the completion of the reaction (TLC). The reaction mixture was again cooled to 0°C, the excess sodium hydride was decomposed by slow addition of water (10ml) and 12N hydrochloric acid (1 ml). The organic solvent was evaporated under reduced pressure, to the residual material a mixture of 1 :1 water and ethyl acetate (50 ml) was added. It was then basified to pH 9 using 1 N sodium hydroxide solution, the layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 50 ml). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure. Crystallisation from cold ethyl acetate provided the pure product. M.P. 264 - 266°C.
1HNMR (400MHZ, DMSO-d6): δ 8.42 (s, 1 H), 8.18 (d, J = 8 Hz, 1 H), 8 (br s, 2H), 7.77-7.84 (m, 3H), 7.33 (d, J = 8 Hz, 1 H), 2.5 (s, 1 H). d) Preparation of 6-chloro-2-(6-methyl-pyridin-2-yl)-quinazolin-4-ol: 6-Chloro-2-(6-methyl- pyridin-2-yl)-quinazolin-4-ylamine (1.5g, 5.55mmol) in 1 N hydrochloric acid (30ml) was heated at 150°C under stirring in a pressure vessel for 6h. The fluffy white solid precipitate was then suction filtered, washed with water and dried under reduced pressure to give the desired hydroxyl derivative. M.P. 196 - 198°C.
1HNMR (400MHZ, DMSO-d6): δ 11.8 (s, 1 H), 8.24 (d, J = 7.6 Hz, 1 H), 8.12 (d, J = 2.6 Hz, 1 H), 7.96 (dd J = 7.6, 8.0Hz, 1 H), 7.9 (dd , J= 8.72, 2.53 Hz, 1 H), 7.83 (d, J = 8.4 Hz, 1 H), 7.52 (d, J = 7.6 Hz, 1 H), 2.63 (s, 3H) e) Preparation of 6-Chloro-2-(6-methyl-pyridin-2-yl)-4-phenyl-quinazoline: To 6-chloro-2-(6- methyl-pyridin-2-yl)-quinazolin-4-ol (1g, 3.7mmol), in a 100ml round bottom flask, phosphoryl bromide (10.5g, 36.9mmol) was added portion wise at 0°C and the reaction mixture was warmed to room temperature and finally was boiled at 1 10°C for 3h. After cooling to 0°C the reaction mixture was diluted with ethyl acetate (40 ml) and was neutralised very carefully with 20% sodium hydroxide solution at the same temperature. The aqueous layer was separated and was further extracted with ethyl acetate (3 x 15 ml). The combined organic extracts were dried over sodium sulphate and were concentrated under reduced pressure. The resulting 4- bromo-6-chloro-2-(6-methyl-pyridin-2-yl)-quinazoline was directly used in the next step without any purification.
1HNMR (400MHZ, CDCI3): δ 8.25 (d, J = 7.6 Hz, 1 H), 8.13 (br s, 1 H), 7.97 (dd, J = 8.0, 7.6Hz, 1 H), 7.9 (dd, J = 8.7, 2.55 Hz, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.53 (d, J = 7.6 Hz, 1 H), 2.63 (s, 3H).
To a solution of 4-bromo-6-chloro-2-(6-methylpyridin-2-yl)-quinazoline (0.8 g, 2.4mmol), as obtained above, in dry dimethoxyethane under nitrogen was added [1 , 1- Bis(diphenylphosphino)ferrocene]dichloropalladim(ll)[PdCI2(dppf)2) (0.088g, 0.12mmol), phenylboronic acid(0.349g, 2.87mmol) followed by sodium carbonate (0.759g, 7.2mmol) and the reaction mixture was refluxed till the completion of the reaction (TLC). Reaction mixture was cooled to room temperature, filtered through a celite bed and the clear filtrate was evaporated to dryness. The residual mixture was directly subjected to flash column chromatography. The desired 6-chloro-2-(6-methyl-pyridin-2-yl)-4-phenyl-quinazoline was obtained as a white solid, M.P. 202 -204°C.
1HNMR (400MHZ, CDCI3): δ 8.53 (d, J = 8 Hz, 1 H), 8.30 (d, J = 5.6 Hz, 1 H), 8.13 (d, J = 2.4 Hz , 1 H), 7.83-7.90 (m,3H), 7.78 (dd, J = 7.6 Hz each, 1 H), 7.60-7.65 (m, 3H), 7.30 (d, J = 7.6 Hz, 1 H), 2.78 (s,3H) f) To a solution of 6-Chloro-2-(6-methylpyridin-2-yl)-4-phenyl-quinazoline (0.2g, 0.6mmol) in dry methanol was added a solution of freshly prepared sodium methoxide (0.065g, 1.2 mmol) in dry methanol (3 ml_). The reaction vessel was then stirred at 150 °C in a microwave oven for one hour. After cooling the reaction mixture to room temperature, the solvent was evaporated to dryness. The resulting residue was directly subjected to column
chromatography. The desired 6-methoxy-2-(6-methyl-2-pyridyl)-4-phenyl-quinazoline was obtained as a solid,
mp: 156 -158 °C
1HNMR (400 MHZ, CDCI3): δ 8.50 (d, J = 7.6 Hz, 1 H), 8.26 (d, J = 9.2 Hz, 1 H), 7.92 -7.83 (m, 2H), 7.75 (dd, J = 8.0, 1 H), 7.62 -7.56 (m, 4H), 7.41 (d, J = 2.4 Hz ,1 H), 7.26 (dd, J = 4.8, 2.5 Hz, 1 H), 3.86 (s, 3H), 2.77 (s, 3H).
Example P7: Preparation of 2-(6-methyl-2-pyridyl)-6-methylsulfanyl-4-phenyl-quinazoline
To a solution of 6-Chloro-2-(6-methylpyridin-2-yl)-4-phenyl-quinazoline (0.2g, 0.6mmol) in dry methanol (3 ml_) was added the sodium thiomethoxide (0.084g,1.2 mmol). The reaction vessel was then stirred at 150 °C in a microwave oven for one hour. After cooling the solvent was evaporated to dryness, the resulting residue diluted with ethyl acetate and treated with a sodium hypochlorite solution (70-75%). The water phase was further extracted with ethyl acetate (5ml X 3). The combined organic layers were dried over sodium sulphate, concentrated under reduced pressure and purified by flash column chromatography to afford 2-(6-methyl-2-pyridyl)-6-methylsulfanyl-4-phenyl-quinazoline as a solid mp: 1 18 -120 °C
1H NMR (400 MHZ, CDCI3): δ 8.51 (d, J = 8.0 Hz, 1 H), 8.23 (d, J = 9.2 Hz, 1 H), 7.92-7.86 (m, 3H), 7.79-7.74 (m, 2H), 7.62-7.59 (m, 3H), 7.28 (d, J = 8.0 Hz, 1 H), 2.77 (s, 3H), 2.52 (s, 3H). Example P8: Preparation of 6-methyl-2-(6-methyl-2-pyridyl)-4-phenyl-quinazoline
To a solution of 6-Chloro-2-(6-methylpyridin-2-yl)-4-phenyl-quinazoline (0.3g, 0.9mmol) in dioxane under nitrogen was added palladium tetrakistriphenylphosphene (0.052g, 0.045mmol), trimethyl boroxine (0.226g, 1.8mmol) and anhydrous potassium carbonate (0.375g, 2.7mmol). The reaction mixture was stirred till the completion of the reaction as monitored by TLC. The reaction mixture was cooled to RT and then filtered through a pad of celite. The resulting clear filtrate was concentrated under reduced pressure and directly subjected to flash column chromatography to afford the desired 6-methyl-2-(6-methyl-2- pyridyl)-4-phenyl-quinazoline as solid.
mp: 198 -200 °C
1HNMR (400 MHZ, CDCI3): 5 8.51 (d, J = 7.6 Hz, 1 H), 8.24 (d, 8.4Hz, 1 H), 7.89 -7.87 (m, 3H), 7.76 (dd, J = 8.5Hz, J= 6HZ, 2H), 7.61 - 7.58 (m, 3H), 7.28 (s, 1 H), 2.78 (s, 1 H), 2.53 (s, 1 H). Example P9: Preparation of 8-Methoxy-2-(6-methyl-pyridin-2-yl)-4-phenyl-quinazoline
To a solution of 8-chloro-2-(6-methyl-pyridin-2-yl)-4-phenyl-quinazoline (0.2g, 0.6mmol) in dry methanol under nitrogen was added Bis(dibenzylideneacetone)palladium(0) [Pd2dba] (0.017g, 0.03mmol), 2-Di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl(0.025g, 0.06mmol) [tert-butyl Xphos] followed by a solution of freshly prepared sodium methoxide (0.05g, 0.9mmol) in dry methanol (2 ml_). The reaction mixture was then stirred at 60°C till the completion of the reaction (TLC). The cold (room temperature) reaction mixture was filtered through a celite bed and the clear filtrate was evaporated to dryness and was directly subjected to flash column chromatography. The desired 8-methoxy-2-(6-methyl-pyridin-2-yl) -4-phenyl-quinazoline was obtained as solid, M .P.100 -102°C
1HNMR (400MHZ, CDCI3): δ 8.52 (d, J = 8 Hz, 1 H), 7.87-7.91 (m, 2H), 7.68 -7.78 (m, 2H), 7.56 -7.61 (m, 3H), 7.51 (dd, J = 8.0, 8.4 Hz, 1 H), 7.23-7.28 (m, 2H), 4.12 (s, 3H), 2.76 (s, 3H). Example P10: Preparation of 2-(5-Fluoro-6-methyl-pyridin-2-yl)-4-phenyl-quinazoline a) Preparation of 2-(6-chloro-5-fluoro-pyridin-2-yl)-benzo[d][1 ,3]oxazin-4-one: To a solution of 6-chloro-5-fluoro-pyridine-2-carboxylic acid (2.20g, 12.50 mmol) in dichloroethane (60 ml) and Et3N (4.4 ml, 31.30 mmol), at room temperature, anthranilic acid amide (1.88g, 13.8 mmol) was added followed by bis(2-oxo-3-oxazolidinyl)phosphonic chloride (3.51 g, 13.8 mmol). The suspension was stirred at 80°C during 1.5 hour, under nitrogen atmosphere. After evaporation of the volatiles under reduced pressure, water was added and the mixture was filtered. The filtered solid (6-chloro-5-fluoro-pyridine-2-carboxylic acid (2-carbamoyl- phenyl)-amide) was washed with water and diethylether, dried overnight under vacuum and used for the next step without purification.
6-chloro-5-fluoro-pyridine-2-carboxylic acid (2-carbamoyl-phenyl)-amide (2.70 g, 9.19 mmol) was stirred in tetrahydrofurane (50 ml) and 1 M aq NaOH (37 ml) was added at room temperature. The suspension was stirred at reflux during 6 hours then cooled to room temperature. After avaporation of the volatiles under reduced pressure to one third of the volume the mixture was filtered. The filtered solid (2-(6-chloro-5-fluoro-pyridin-2-yl)- benzo[d][1 ,3]oxazin-4-one) was washed with water and diethylether, dried overnight under vacuum and used for the next step without purification. LCMS: 1.67 min; method A; [M+H]+ = 276.
b) Preparation of 2-(5-Fluoro-6-methyl-pyridin-2-yl)-3H-quinazolin-4-one: To 6-chloro-5- fluoro-pyridin-2-yl)-benzo[d][1 ,3]oxazin-4-one (1.00 g, 3.26 mmol) in dioxane (12 ml), an aqueous solution of sodium carbonate 2M (0.90 g, 6.53 mmol) was added followed by trimethylboroxine (0.68 ml, 4.90 mmol). The tetrakis(triphenylphosphine)palladium(0) (377 mg, 0.33 mmol) was then added and the mixture was heated under MW conditions (140°C, 15 min). The reaction mixture was cooled to RT and water was added. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2CI2/MeOH; 100/0 to 97/3) to afford 2-(5-Fluoro-6-methyl- pyridin-2-yl)-3H-quinazolin-4-one as a white solid. LCMS: 1.69 min; method A; [M+H]+ = 256. c) Preparation of 4-chloro-2-(5-fluoro-6-methyl-pyridin-2-yl)-quinazoline: To 2-(5-Fluoro-6- methyl-pyridin-2-yl)-3H-quinazolin-4-one (0.77 g, 2.26 mmol) in toluene (7 ml) phosphoryl choride (5.2 ml, 56.6 mmol) was added and the mixture stirred at 1 10°C during 2 hours, then cooled to room temperature. The volatiles were evaporated under reduced pressure. Dichloromethane and water were added to the crude residue and the pH adjusted to 9 by addition of 1 M aq. NaOH solution. The aqueous phase was extracted with dichloromethane and the combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 95/5 to 80/20) to afford 4-chloro-2-(5-fluoro-6-methyl- pyridin-2-yl)-quinazoline as a beige powder. LCMS: 1.82 min; method A; [M+H]+ = 274.
d) Preparation of 2-(5-Fluoro-6-methyl-pyridin-2-yl)-4-phenyl-quinazoline: In a sealed tube to a solution of 4-chloro-2-(5-fluoro-6-methyl-pyridin-2-yl)-quinazoline (80.0 mg, 0.29 mmol) in dimethoxyethane (6 ml) a 3M aq Na2C03 solution was added (0.29 ml, 0.88 mmol) followed by phenylboronic acid (71.0 mg, 0.58 mmol). The mixture was degassed with an argon flux. After addition of 1 ,1 '-Bis(diphenylphosphino)ferrocene-palladium(ll)dichloride dichloromethane complex (24 mg, 0.03 mmol) the mixture was stirred overnight at 90°C under an argon atmosphere. After cooling to room temperature, the mixture was diluted with ethyl acetate and water. The separated organic layer was washed with 2M aq NaOH solution, with 10% aq ammonia solution and with brine, then dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 95/5 to 80/20) to afford 2-(5-Fluoro-6-methyl-pyridin-2- yl)-4-phenyl-quinazoline as a white solid. Mp: 173-175°C. LCMS: 1.95 min; method A; [M+H]+ = 316.
Table A below defines chemical designations for the substituents R2, R3, R4 and R5 for the compounds of formula I:
Figure imgf000078_0001
Table A: chemical designations for substituents R1: R?, R¾, R4 and Rs of the compound of formula I:
For example, the line A001 signifies a phenyl group, or A010 signifies a para-tolyl group.
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
The pre Ferred embodiment C1 consist of 1 the combination of = H, R2 = H and R3 = H.
The pre Ferred embodiment C2 consist of 1 he combination of = CH3, R2 = H and R3 = H.
The pre Ferred embodiment C3 consist of 1 the combination of = CI, R2 = H and R3 = H.
The pre Ferred embodiment C4 consist of 1 the combination of = OCH3, R2 = H and R3 = H.
The pre Ferred embodiment C5 consist of 1 the combination of = CH(CH2)2, R2 = H and R3 = H.
The pre Ferred embodiment C6 consist of 1 the combination of = H, R2 = CH3 and R3 = H.
The pre Ferred embodiment C7 consist of 1 the combination of = H, R2 = OCH3 and R3 = H.
The pre Ferred embodiment C8 consist of 1 the combination of = H, R2 = F and R3 = H.
The pre Ferred embodiment C9 consist of 1 the combination of = CH3, R2 = CH3 and R3 = H.
The pre Ferred embodiment C10 consist ol " the combination of = CH3, R2 = OCH3 and R3 = H.
The pre Ferred embodiment C1 1 consist ol F the combination of = CH3, R2 = F and R3 = H.
The pre Ferred embodiment C12 consist ol " the combination of = CH(CH2)2, R2 = CH3 and R3 = H.
The pre Ferred embodiment C13 consist ol " the combination of = CH(CH2)2, R2 = OCH3 and R3 = H
The pre Ferred embodiment C14 consist ol " the combination of = CH(CH2)2, R2 = F and R3 = H.
The pre Ferred embodiment C15 consist ol " the combination of = H , R2 = H and R3 = CH3.
The pre Ferred embodiment C16 consist ol " the combination of = H , R2 = H and R3 = CI.
The pre Ferred embodiment C17 consist ol " the combination of = H , R2 = H and R3 = OCH3.
The pre Ferred embodiment C18 consist ol " the combination of = H , R2 = H and R3 = SCH3.
The pre Ferred embodiment C19 consist ol " the combination of = H, R2 = H and R3 = CH(CH2)2.
The pre Ferred embodiment C20 consist ol " the combination of = CH3, R2 = H and R3 = CH3.
The pre Ferred embodiment C21 consist ol " the combination of = CH3, R2 = H and R3 = CI.
The pre Ferred embodiment C22 consist ol " the combination of = CH3, R2 = H and R3 = OCH3.
The pre Ferred embodiment C23 consist ol " the combination of = CH3, R2 = H and R3 = SCH3.
The pre Ferred embodiment C24 consist ol " the combination of = CH3, R2 = H and R3 = CH(CH2)2.
The pre Ferred embodiment C25 consist ol F the combination of = H, R2 = CH3 and R3 = CH3.
The pre Ferred embodiment C26 consist ol " the combination of = H, R2 = OCH3 and R3 = CH3.
The pre Ferred embodiment C27 consist ol " the combination of = H, R2 = F and R3 = CH3.
The pre Ferred embodiment C28 consist ol " the combination of = H, R2 = CH3 and R3 = OCH3.
The pre Ferred embodiment C29 consist ol " the combination of = H , R2 = OCH3 and R3 = OCH3.
The pre Ferred embodiment C30 consist ol " the combination of = H, R2 = F and R3 = OCH3.
The pre Ferred embodiment C31 consist ol " the combination of = CH3, R2 = CH3 and R3 = CH3.
The pre Ferred embodiment C32 consist ol " the combination of = CH3, R2 = OCH3 and R3 = CH3.
The pre Ferred embodiment C33 consist ol " the combination of = CH3, R2 = F and R3 = CH3. Table 1.1 : This table discloses the 226 specific compounds E1.001.C1 to E1. 226. C1 of formula
Figure imgf000097_0001
in which, for each of these 226 specific compounds, R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines A 001 to A 226 of Table A and Ri ,R2 and R3 have the specific meaning as given in the embodiment C1. For example, the specific compound E1.023.C1 is the compound of the formula E1 , in which R4 has the specific meaning given in the line A 023 of the Table A:
Figure imgf000097_0002
According to the same system, also all of the other 226 specific compounds disclosed in the Table 1 as well as all of the specific compounds disclosed in the Tables 2 to 21 are specified analogously.
Table 1.2: This table discloses the 226 specific compounds E1.001.C2 to E1. 226.C2 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C2. Table 1.3: This table discloses the 226 specific compounds E1.001.C3 to E1. 226.C3 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C3. Table 1.4: This table discloses the 226 specific compounds E1.001.C4 to E1. 226.C4 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C4. Table 1.5: This table discloses the 226 specific compounds E1.001.C5 to E1. 226. C5 as in Table 1.1 but R2 and R3 have the specific meaning as given in the embodiment C5. Table 1.6: This table discloses the 226 specific compounds E1.001.C6 to E1. 226.C6 as in Table 1.1 but R2 and R3 have the specific meaning as given in the embodiment C6. Table 1.7: This table discloses the 226 specific compounds E1.001.C7 to E1. 226.C7 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C7. Table 1.8: This table discloses the 226 specific compounds E1.001.C8 to E1. 226.C8 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C8. Table 1.9: This table discloses the 226 specific compounds E1.001.C9 to E1. 226.C9 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C9.
Table 1.10: This table discloses the 226 specific compounds E1.001.C10 to E1. 226. C10 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C10. Table 1.11 : This table discloses the 226 specific compounds E1.001.C1 1 to E1. 226. C11 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C11. Table 1.12: This table discloses the 226 specific compounds E1.001.C12 to E1. 226. C12 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C12. Table 1.13: This table discloses the 226 specific compounds E1.001.C13 to E1. 226. C13 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C13. Table 1.14: This table discloses the 226 specific compounds E1.001.C14 to E1. 226. C14 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C14. Table 1.15: This table discloses the 226 specific compounds E1.001.C15 to E1. 226. C15 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C15. Table 1.16: This table discloses the 226 specific compounds E1.001.C16 to E1. 226. C16 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C16. Table 1.17: This table discloses the 226 specific compounds E1.001.C17 to E1. 226.C17 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C17. Table 1.18: This table discloses the 226 specific compounds E1.001.C18 to E1. 226. C18 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C18. Table 1.19: This table discloses the 226 specific compounds E1.001.C19 to E1. 226. C19 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C19. Table 1.20: This table discloses the 226 specific compounds E1.001.C20 to E1. 226. C20 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C20. Table 1.21 : This table discloses the 226 specific compounds E1.001.C21 to E1. 226.C21 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C21. Table 1.22: This table discloses the 226 specific compounds E1.001.C22 to E1. 226. C22 as in Table 1.1 but R2 and R3 have the specific meaning as given in the embodiment C22. Table 1.23: This table discloses the 226 specific compounds E1.001.C23 to E1. 226. C23 as in Table 1.1 but R2 and R3 have the specific meaning as given in the embodiment C23. Table 1.24: This table discloses the 226 specific compounds E1.001.C24 to E1. 226.C24 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C24. Table 1.25: This table discloses the 226 specific compounds E1.001.C25 to E1. 226. C25 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C25. Table 1.26: This table discloses the 226 specific compounds E1.001.C26 to E1. 226. C26 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C26. Table 1.27: This table discloses the 226 specific compounds E1.001.C27 to E1. 226. C27 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C27. Table 1.28: This table discloses the 226 specific compounds E1.001.C28 to E1. 226. C28 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C28. Table 1.29: This table discloses the 226 specific compounds E1.001.C29 to E1. 226.C29 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C29. Table 1.30: This table discloses the 226 specific compounds E1.001.C30 to E1. 226.C30 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C30. Table 1.31 : This table discloses the 226 specific compounds E1.001.C31 to E1. 226.C31 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C31.
Table 1.32: This table discloses the 226 specific compounds E1.001.C32 to E1. 226.C32 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C32.
Table 1.33: This table discloses the 226 specific compounds E1.001.C33 to E1. 226.C33 as in Table 1.1 but R^ R2 and R3 have the specific meaning as given in the embodiment C33.
Table 2.1 : This table discloses the 226 specific compounds E2.001.C1 to E2.226. C1 of the formula
Figure imgf000100_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 2.2 to 2.33: each of these tables discloses 226 specific compounds E2.001.CX to E2.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33. As an example the compound E2.158.C21 has the following formula:
Figure imgf000100_0002
Table 3.1 : This table discloses the 226 specific compounds E3.001.C1 to E3.226.C1 of the formula
(E3),
Figure imgf000100_0003
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 3.2 to 3.33: each of these tables discloses 226 specific compounds E3.001.CX to E3.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 4.1 : This table discloses the 226 specific compounds E4.001.C1 to E4. 226. C1 of the formula
Figure imgf000101_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 4.2 to 4.33: each of these tables discloses 226 specific compounds E4.001.CX to E4.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33. Table 5.1 : This table discloses the 226 specific compounds E5.001.C1 to E5. 226.C1 of the formula
Figure imgf000102_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 5.2 to 5.33: each of these tables discloses 226 specific compounds E5.001.CX to E5.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 6.1 : This table discloses the 226 specific compounds E6.001.C1 to E6.226.C1 of the formula
Figure imgf000102_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 6.2 to 6.33: each of these tables discloses 226 specific compounds E6.001.CX to E6.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33. Table 7.1 : This table discloses the 226 specific compounds E7.001.C1 to E7.226.C1 of the formula
Figure imgf000103_0001
in which, for each of these 226 specific compounds, each of the of the variables R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 7.2 to 7.33: each of these tables discloses 226 specific compounds E7.001.CX to E7.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 8.1 : This table discloses the 226 specific compounds E8.001.C1 to E8.226.C1 of the formula
Figure imgf000103_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 8.2 to 8.33: each of these tables discloses 226 specific compounds E8.001.CX to E8.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33. Table 9.1 : This table discloses the 226 specific compounds E9.001.C1 to E9.226.C1 of the formula
Figure imgf000104_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 9.2 to 9.33: each of these tables discloses 226 specific compounds E9.001.CX to E9.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 10.1 : This table discloses the 226 specific compounds E10.001.C1 to E10.226.C1 of the formula
Figure imgf000104_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 10.2 to 10.33: each of these tables discloses 226 specific compounds E10.001.CX to E10.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 1 1.1 : This table discloses the 226 specific compounds E11.001.C1 to E11.226. C1 of the formula
Figure imgf000105_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 1 1.2 to 1 1.33: each of these tables discloses 226 specific compounds E11.001.CX to E11.226. CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 12.1 : This table discloses the 226 specific compounds E12.001.C1 to E12.226.C1 of the formula
Figure imgf000105_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 12.2 to 12.33: each of these tables discloses 226 specific compounds E12.001.CX to E12.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33. Table 13.1 : This table discloses the 226 specific compounds E13.001.C1 to E13.226.C1 of the formula
Figure imgf000106_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 13.2 to 13.33: each of these tables discloses 226 specific compounds E13.001.CX to E13.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33.
Table 14.1 : This table discloses the 226 specific compounds E14.001.C1 to E14.226.C1 of the formula
Figure imgf000106_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 14.2 to 14.33: each of these tables discloses 226 specific compounds E14.001.CX to E14.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33 Table 15.1 : This table discloses the 226 specific compounds E15.001.C1 to E15.226.C1 of the formula
Figure imgf000107_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 15.2 to 15.33: each of these tables discloses 226 specific compounds E15.001.CX to E15.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 16.1 : This table discloses the 226 specific compounds E16.001.C1 to E16.001.C1 of the formula
Figure imgf000107_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 16.2 to 16.33: each of these tables discloses 226 specific compounds E16.001.CX to E16.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33 Table 17.1 : This table discloses the 226 specific compounds E17.001.C1 to E17.226.C1 of the formula
Figure imgf000108_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 17.2 to 17.33: each of these tables discloses 226 specific compounds E17.001.CX to E17.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 18.1 : This table discloses the 226 specific compounds E18.001.C1 to E18.226.C1 of the formula
Figure imgf000108_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 18.2 to 18.33: each of these tables discloses 226 specific compounds E18.001.CX to E18.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 19.1 : This table discloses the 226 specific compounds E19.001.C1 to E19.226.C1 of the formula
Figure imgf000109_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 19.2 to 19.33: each of these tables discloses 226 specific compounds E19.001.CX to E19.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 20.1 : This table discloses the 226 specific compounds E20.001.C1 to E20.226.C1 of the formula
Figure imgf000109_0002
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1. Tables 20.2 to 20.33: each of these tables discloses 226 specific compounds E20.001.CX to E20.226.CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 21.1 : This table discloses the 226 specific compounds E21.001.C1 to E21.226. C1 of the formula
Figure imgf000110_0001
in which, for each of these 226 specific compounds, each of the of the variables , R2, R3, and R4 has the specific meaning given in the corresponding line, appropriately selected from the 226 lines E1.001.C1 to E1.226.C1 of the Table 1.1.
Tables 21.2 to 21.33: each of these tables discloses 226 specific compounds E21.001.CX to E21.226. CX, where CX corresponds to each of the embodiments C2 to C33, in analogy with tables 1.2 to 1.33
Table 22 shows selected m.p. and/or LCMS data and retention times/MW for compounds of Tables 1 to 21.
Throughout this description, temperatures are given in degrees Celsius and "m.p." means melting point.
The analytical methods used are described here below: Method U :
ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer) lonisation method: Electrospray
Polarity: positive ions Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700
Mass range: 100 to 800 Da
DAD Wavelength range (nm): 210 to 400
Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9: 1 ,0.1 % formic acid and Solvent B: Acetonitrile,0.1 % formic acid )
Figure imgf000111_0001
Type of column: Waters ACQUITY U 'LC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60°C.
Method A
ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Instrument Parameter: lonisation method: Electrospray ; Polarity: positive (negative) ions Capillary (kV) 3.00, Cone (V) 30.00 , Extractor (V) 2.00, Source Temperature (°C) 100, Desolvation Temperature (°C) 250, Cone Gas Flow (L/Hr) 50, Desolvation Gas Flow (L/Hr) 400
Mass range: 100 to 900 Da (LC8 apolar: 150 - 1000 Da)
HP 1100 HPLC from Agilent: solvent degasser, quaternary pump (ZCQ) / binary pump (ZDQ), heated column compartment and diode-array detector.
Column: Phenomenex Gemini C18, 3 μηι particle size, 1 10 Angstrom, 30 x 3 mm,
Temp: 60 °C
DAD Wavelength range (nm): 200 to 500
Solvent Gradient:
A = water + 0.05 % HCOOH B= Acetonitril/Methanol (4: 1 , v:v) + 0.04 % HCOOH
Figure imgf000112_0001
Method B ZMD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Instrument Parameter: lonisation method: Electrospray ; Polarity: positive (negative) ions Capillary (kV) 3.80, Cone (V), Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 350, Cone Gas Flow (L/Hr) OFF, Desolvation Gas Flow (L/Hr) 600
Mass range: 100 to 900 Da
HP 1 100 HPLC from Agilent: solvent degasser, binary pump, heated column compartment and diode-array detector.
Column: Phenomenex Gemini C18, 3 μηι particle size, 1 10 Angstrom, 30 x 3 mm,
Temp: 60 °C
DAD Wavelength range (nm): 200 to 500
Solvent Gradient:
A = water + 0.05 % HCOOH
B= Acetonitril/Methanol (4: 1 , v:v) + 0.04 % HCOOH
Figure imgf000112_0002
Table 22: Melting point data and/or retention times for compounds of Table 1 to 21
Figure imgf000113_0001
Figure imgf000114_0001
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
-122-
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
Figure imgf000132_0001
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0001
Figure imgf000136_0001
Figure imgf000137_0001
Figure imgf000138_0001
Figure imgf000139_0001
Formulation examples for compounds of formula I: Example F-2.1 to F-2.2: Emulsifiable concentrates
Figure imgf000140_0001
Emulsions of any desired concentration can be prepared by diluting such concentrates with water.
Example F-2: Emulsifiable concentrate
Figure imgf000140_0002
Emulsions of any desired concentration can be prepared by diluting such concentrates with water. Examples F-3.1 to F-3.4: Solutions Components F-3.1 F-3.2 F-3.3 F-3.4
Compound of Tables 1-22 80% 10% 5% 95% propylene glycol monomethyl ether 20% - - - polyethylene glycol 70%
(relative molecular mass: 400 atomic mass units)
N-methylpyrrolid-2-one - 20% - - epoxidised coconut oil - - 1 % 5% benzin (boiling range: 160-190°) - - 94% -
The solutions are suitable for use in the form of microdrops.
Examples F-4.1 to F-4.4: Granulates
Figure imgf000141_0001
The novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.
Examples F-5.1 and F-5.2: Dusts
Figure imgf000141_0002
Ready for use dusts are obtained by intimately mixing all components
Examples F-6.1 to F-6.3: Wettable powders
Components F-6.1 F-6.2 F-6.3
Compound of Tables 1-22 25% 50% 75%
sodium lignin sulfonate 5% 5% - sodium lauryl sulfate 3% - 5% sodium diisobutylnaphthalene sulfonate 6% 10% - octylphenolpolyethylene glycol ether 2%
(7 to 8 mol ethylenoxy units)
highly dispersed silicic acid 5% 10% 10%
kaolin 62% 27% -
All components are mixed and the mixture is thoroughly ground in a suitable mill to give wettable powders which can be diluted with water to suspensions of any desired
concentration. Example F7: Flowable concentrate for seed treatment
Figure imgf000142_0001
The finely ground active ingredient is intimately mixed with the adjuvants, giving a
suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Biological examples:
Biological example 1 : fungicidal activity against Alternaria solani I tomato / leaf disc (early blight)
Tomato leaf disks cv. Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf disks were incubated at 23 °C / 21°C (day/night) and 80% relative humidity (rh) under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5 - 7 days after application). Compounds (from table 22) 4, 8, 9, 10, 13, 76, 114, 123, 134, 135 and 139 at 200 ppm give at least 70% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 2: fungicidal activity against Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) / wheat / leaf disc preventative (Powdery mildew on wheat)
Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated by shaking powdery mildew infected plants above the test plates 1 day after application. The inoculated leaf disks were incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
Compounds (from table 22) 1 , 3, 4, 5, 7, 9, 10, 15, 16, 17, 24, 25, 27, 32, 34, 35, 38, 40, 41 , 42, 43, 44, 45, 46, 48, 60, 61 , 62, 63, 66, 74, 84, 85, 104, 1 10, 11 1 , 1 13, 1 14, 122, 123, 124, 126, 127, 130, 134, 135, 151 , 154, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 3: fungicidal activity against Botryotinia fuckeliana (Botrytis cinerea) I liquid culture (Gray mould)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
Compounds (from table 22) 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 18, 23, 24, 25, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 54, 55, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 68, 69, 71 , 72, 73, 75, 76, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 96, 101 , 102, 104, 105, 106, 107, 1 12, 1 15, 121 , 124, 125, 126, 127, 128, 129, 130, 134, 135, 136, 137, 138, 139, 140, 141 , 143, 145, 146, 147, 148, 149, 151 , 153, 154, 155, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 4: fungicidal activity against Gaeumannomyces graminis I liquid culture (Take-all of cereals)
Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores iss added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4-5 days after application.
Compounds (from table 22) 1 , 2, 3, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 53, 55, 56, 58, 60, 62, 64, 65, 66, 67, 69, 70, 71 , 72, 73, 74, 75, 78, 79, 83, 85, 87, 90, 92, 93, 94, 98, 99, 101 , 102, 103, 104, 105, 106, 107, 108, 109, 110, 1 11 , 1 12, 1 13, 1 14, 1 15, 116, 117, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 130, 143, 144, 145, 148, 149, 150, 151 , 153, 154, 155, 156, 157, 158, 159, 162 and 163 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 5: fungicidal activity against Glomerella lagena um (Colletotrichum lagena um) I liquid culture (Anthracnose)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was measured photometrically 3-4 days after application.
Compounds (from table 22) 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 31 , 32, 33, 34, 35, 37, 39, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 55, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 69, 70, 71 , 72, 73, 75, 76, 79, 80, 81 , 83, 84, 85, 86, 87, 90, 92, 93, 98, 99, 101 , 102, 104, 105, 106, 107, 109, 1 10, 11 1 , 1 12, 1 13, 1 14, 1 17, 120, 121 , 122, 123, 125, 126, 127, 130, 134, 135, 136, 137, 139, 140, 141 , 145, 146, 148, 149, 151 , 153, 154, 155, 156, 157, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 6: fungicidal activity against Monographella nivalis (Microdochium nivale) / liguid culture (foot rot cereals)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
Compounds (from table 22) 1 , 2, 9, 11 , 13, 14, 15, 16, 17, 19, 20, 23, 24, 25, 34, 35, 37, 40, 41 , 42, 43, 45, 46, 47, 48, 52, 59, 60, 61 , 62, 63, 64, 76, 79, 81 , 82, 84, 85, 86, 87, 90, 95, 96, 101 , 102, 103, 104, 105, 106, 109, 1 10, 11 1 , 1 12, 1 13, 1 14, 115, 1 16, 120, 121 , 122, 123, 125, 127, 128, 130, 134, 137, 139, 140, 143, 145, 146, 147, 149, 151 , 153, 154, 155, 158, 159, 161 and 162 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 7: fungicidal activity against Mvcosphaerella arachidis (Cercospora arachidicola) I liguid culture (early leaf spot)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
Compounds (from table 22) 1 , 3, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 27, 28, 29, 30, 31 , 33, 34, 35, 37, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 55, 56, 58, 59, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 72, 73, 75, 76, 79, 80, 81 , 83, 85, 86, 87, 90, 91 , 93, 96, 98, 99, 101 , 102, 104, 105, 106, 107, 109, 1 10, 1 11 , 1 12, 1 13, 1 14, 1 15, 1 17, 120, 121 , 122, 125, 126, 127, 128, 129, 130, 134, 136, 137, 139, 140, 141 , 142, 143, 144, 145, 146, 147, 148, 149, 151 , 153, 154, 155, 156, 157, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 8: fungicidal activity against Mycosphaerella praminicola (Septoria tritici) I liguid culture (Septoria blotch)
Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 4- 5 days after application.
Compounds (from table 22) 1 , 2, 3, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 27, 28, 29, 31 , 33, 34, 35, 37, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 55, 56, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 69, 70, 71 , 72, 73, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 90, 91 , 92, 93, 94, 96, 98, 101 , 102, 104, 105, 106, 107, 109, 1 10, 1 11 , 1 12, 1 13, 1 14, 1 15, 117, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 130, 134, 135, 148, 149, 151 , 154, 155, 156, 157, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 9: fungicidal activity against Phaeosphaeria nodorum (Septoria nodorum) /wheat / leaf disc preventative (Glume blotch)
Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated test leaf disks were incubated at 20°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
Compounds (from table 22) 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 13, 14, 15, 16, 17, 20, 23, 24, 25, 27, 32, 34, 35, 37, 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 52, 55, 59, 60, 61 , 62, 63, 65, 66, 68, 69, 72, 73, 76, 81 , 83, 84, 85, 86, 88, 89, 90, 91 , 96, 104, 105, 106, 109, 110, 1 1 1 , 1 12, 1 13, 1 14, 1 15, 1 17, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 130, 134, 135, 140, 141 , 148, 149, 151 , 154, 155, 157, 158, 159, 161 and 162 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 10: fungicidal activity against Phytophthora infestans I tomato / leaf disc preventative (late blight)
Tomato leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
Compounds (from table 22) 3, 4, 7, 9 at 200 ppm give at least 70% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 1 1 : fungicidal activity against Plasmopara viticola I grape / leaf disc preventative (late blight)
Grape vine leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
Compounds (from table 22) 1 , 2, 3, 4, 5, 7, 8, 9, 10, 1 1 , 13, 43, 46, 52, 61 , 65, 76, 83, 90, 107, 1 12, 1 13, 1 17, 123, 125, 127, 130, 142, 148, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 12: fungicidal activity against Puccinia recondita f. sp. tritici / wheat / leaf disc preventative (Brown rust)
Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
Compounds (from table 22) 1 , 3, 4, 6, 7, 9, 10, 1 1 , 13, 17, 23, 24, 25, 27, 34, 35, 38, 40, 41 , 42, 43, 45, 46, 59, 60, 61 , 76, 84, 85, 86, 87, 96, 104, 106, 1 12, 1 13, 125, 126, 130, 134, 149, 158 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Biological example 13: fungicidal activity against Pyrenophora teres I barley / leaf disc preventative (Net blotch)
Barley leaf segments cv. Hasso were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segmens were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments were incubated at 20°C and 65% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5 - 7 days after application).
Compounds (from table 22) 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 13, 14, 15, 16, 17, 23, 24, 25, 27, 34, 35, 37, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 50, 52, 55, 60, 61 , 62, 63, 64, 65, 66, 70, 75, 76, 79, 81 , 83, 84, 85, 86, 87, 88, 96, 104, 105, 106, 107, 109, 1 10, 112, 1 13, 1 14, 117, 120, 121 , 123, 124, 125, 126, 127, 130, 134, 135, 140, 148, 149, 151 , 154, 157, 158, 159 and 162 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development. Biological example 14: fungicidal activity against Thanatephorus cucumeris (Rhizoctonia solani) I liquid culture (foot rot, damping-off)
Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal material was added. The test plates were incubated at 24°C and the inhibition of growth was determined photometrically 3-4 days after application.
Compounds (from table 22) 1 , 2, 3, 5, 6, 7, 8, 9, 13, 16, 17, 18, 31 , 37, 42, 43, 46, 47, 49, 52, 55, 58, 59, 64, 66, 73, 76, 79, 84, 86, 87, 90, 102, 104, 105, 106, 110, 125, 134, 139, 145, 146, 148, 149, 151 , 154, 155, 158, 159 and 161 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

Claims

Claims
1. A compound of formul
Figure imgf000150_0001
wherein
represents hydrogen, halogen, cyano, hydroxy, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, C
C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, CrC6haloalkylsulfinyl, C
C6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, Ci-C6alkylsulfonyl-Ci-C6alkyl, C C6alkylsulfoximino-CrC4alkyl, Ci-C6alkylamino, diCi-C6alkylamino, C3-C6cycloalkylamino, C C6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, C
C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, Ci-C6alkoxyimino, Ci-C6alkoxyimino-Cr C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy;
R4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6alkoxy-Cr C6alkoxy, Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, C C6alkylthio, CrC6haloalkylthio, Ci-C4alkylsulfinyl, CrC4alkylsulfonyl, CrC6alkylamino, diC C6alkylamino, C3-C6cycloalkylamino, (Ci-C6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylaminocarbonyl, diCrC6alkylaminocarbonyl, C
C6alkoxycarbonyloxy, CrC6alkylaminocarbonyloxy, diCrC6alkylaminocarbonyloxy, C C6alkylcarbonyloxy, CrC6alkylcarbonylamino, CrCealkylcarbonyl-CrCealkylamino, C C6alkoxyimino, C Cealkoxyimino-C Cealkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, CrC6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof; with the proviso that when RL is H , then R4 is not halogen, hydroxyl, 1-naphtyl substituted at the 2-position of the 1-naphtyl, unsubstituted phenyl or unsubstituted 2-pyridy, or
when R is methyl, R2 and R3 are H and R4 is unsubstituted phenyl, then the quinazoline ring is not substituted at the position 6 by a chlorine atom; or
when R is methyl then R4 is not halogen or hydroxyl; or
when R is arylalkyl then R4 is not hydroxyl.
2. A compound of formula I according to claim 1 , wherein
represents cyano, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, C
C6alkoxy-CrC6alkyl, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C
C6haloalkylsulfinyl, CrC6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, C
C6alkylsulfonyl-CrC6alkyl, Ci-C6alkylsulfoximino-CrC4alkyl, Ci-C6alkylamino, diC
C6alkylamino, C3-C6cycloalkylamino, CrC6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, CrC6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C C6alkoxyimino, C Cealkoxyimino-C Cealkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy;
R4 represents aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy, C
C6alkoxy-CrC6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, C C6haloalkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, (CrC6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, C
C6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C
C6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diCi-C6alkylaminocarbonyloxy, C C6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, Ci-C6alkylcarbonyl-Ci-C6alkylamino, C C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, CrC6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof.
3. A compound of formula I according to claim 2, wherein R4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or trisubstituted by halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C
C4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diCi-C6alkylamino, C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diC C6alkylaminocarbonyl, CrC6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diC
C6alkylaminocarbonyloxy, CrC6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, C
C6alkylcarbonyl-Ci-C6alkylamino or CrC6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, C C6alkoxy-C2-C6alkynyl, Ci-C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy- C2-C6alkynyl, Ci-C6alkylthio-Ci-C6alkyl or hydroxy- d-C6alkyl;
4. A compound of formula I according to claim 2, wherein
represents cyano, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3- C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio, C C6haloalkylthio, Ci-C6alkylamino, diCi-C6alkylamino, C3-C6cycloalkylamino, C
C6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, Ci-C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio;
R4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or trisubstituted by halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C
C4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diC C6alkylaminocarbonyl, CrC6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, did- C6alkylaminocarbonyloxy, CrC6alkylcarbonyloxy, CrC6alkylcarbonylamino, C C6alkylcarbonyl-CrC6alkylamino or Ci-C6alkoxyimino, C Cealkoxyimino-C Cealkyl, C C6alkoxy-C2-C6alkynyl, Ci-C6alkoxyimino-C2-C6alkynyl, Ci-C6alkylthio-C2-C6alkynyl, hydroxy- C2-C6alkynyl, Ci-C6alkylthio-Ci-C6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 ;
5. A compound of formula I according to claim 2, wherein
represents hydrogen, halogen, cyano, hydroxy, CHO, CrC8alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C3-C6halocycloalkyl, CrC6alkoxy, CrC6alkoxy-Cr C6alkyl, CrC6alkylthio, CrC6alkylamino, diCi-C6alkylamino, C3-C6cycloalkylamino, C C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio;
R4 represents aryl or heteroaryl; or aryl or heteroaryl mono-, di- or trisubstituted by halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, Ci-C6alkoxy-Ci-C6alkoxy , Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6alkylthio, Ci-C6alkylamino, diCrC6alkylamino, C3- C6cycloalkylamino, CrC6alkylcarbonyl, or CrC6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, CrC6alkoxy-C2-C6alkynyl, CrC6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, Ci-C6alkylthio-Ci-C6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, C C4alkylthio K is an integer selected from 0, 1 ;
6. A compound of formula I according to claim 2, wherein
Ri is C C6alkyl, C3-C6cycloalkyl, C C6alkoxy,
R2 is H, C C6alkyl, C C6alkoxy, CI, F
R3 is H, C C6alkyl, C C6alkoxy, C C6alkylthio
R4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, d-C6alkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkoxy , C C6alkoxy-CrC6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6alkylthio, CrC6haloalkoxy, C C6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, di C
C6dialkylaminocarbonyl, CrC6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diC
C6dialkylaminocarbonyloxy, CrC6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, C
C6alkylcarbonyl- CrC6alkylamino; or pyridyl, thienyl, dihydro-benzofuran, benzo[1 ,3]dioxole, 3,4-Dihydro-2H-benzo[b][1 ,4]dioxepine which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, CrC6alkyl, CrC6haloalkyl, C C6alkoxy, CrC6alkylthio and CrC6haloalkoxy;
R5 is C C6alkyl, C C6alkoxy, C C6alkylthio, CI, F;
K is an integer selected from 0 or 1 , preferably K is 0.
7. A compound of formula I according to claim 2, wherein
Ri is C C3alkyl, C C3alkoxy,
R2 is H, C C3alkyl, C C3alkoxy, F
R3 is H, C C3alkyl
R4 is phenyl which can be mono-, di- or trisubstituted by substituents selected from the group consisting of CI, F, C C3alkyl, C C3haloalkyl, C C3alkoxy, Ci-C6alkoxy-Ci-C6alkoxy , C C6alkoxy-CrC6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, C C3alkylthio, C C3haloalkoxy, C C3alkylcarbonyl, C C3alkoxycarbonyl, Ci-C3alkylaminocarbonyl, di C
C3dialkylaminocarbonyl, C C3alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diC
C6dialkylaminocarbonyloxy, CrC6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, C
C6alkylcarbonyl- Ci-C6alkylamino; or pyridyl, thienyl, dihydro-benzofuran, benzo[1 ,3]dioxole, 3,4-Dihydro-2H-benzo[b][1 ,4]dioxepine which can be mono-, di- or trisubstituted by substituents selected from the group consisting of halogen, CrC6alkyl, CrC6haloalkyl, C C6alkoxy, CrC6alkylthio and CrC6haloalkoxy;
R5 is C C3alkyl, C C3alkylthio, C C3alkoxy, CI, F
K is an integer selected from 0 or 1 , preferably K is 0.
8. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I according to claim 1 or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
9. A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I according to claim 1 and at least one auxiliary.
10. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I or a composition, comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof, wherein the compound o
Figure imgf000156_0001
wherein
Ri represents hydrogen, halogen, cyano, hydroxy, CHO, NH2, CrC8alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkyl- C2-C6alkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-C6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, C
C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, CrC6haloalkylsulfinyl, C
C6haloalkylsulfonyl, CrC6alkylsulfinyl, CrC6alkylsulfonyl, Ci-C6alkylsulfonyl-Ci-C6alkyl, C C6alkylsulfoximino-CrC4alkyl, CrC6alkylamino, diCrC6alkylamino, C3-C6cycloalkylamino, C C6alkyl-C3-C6cycloalkylamino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, C C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, CrC6alkoxyimino, CrCealkoxyimino-Cr Cealkyl;
R2 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, C C4haloalkoxy, Ci-C4alkoxy-CrC4alkyl, C C4alkylthio;
R3 represents hydrogen, halogen, cyano, hydroxy, CrC6alkyl, C3-C6cycloalkyl, C
C6haloalkyl, C C4alkoxy, Ci-C4alkoxy-CrC4alkyl, C C4haloalkoxy, SH, C C4alkylthio, C C4alkylcarbonythio C C4alkylcarbonyloxy;
R4 represents halogen, OH, aryl or heteroaryl; or aryl or heteroaryl which is substituted, preferably when the aryl or heteroaryl is substituted they are mono-, di- or trisubstituted wherin the subtituents are preferably selected from halogen, cyano, nitro, CHO, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C3-C6halocycloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6alkoxy-Cr C6alkoxy, Ci-C6alkoxy-Ci-C6alkylthio, Ci-C6alkylthio-Ci-C6alkoxy, CrC6haloalkoxy, C C6alkylthio, CrC6haloalkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, CrC6alkylamino, diC C6alkylamino, C3-C6cycloalkylamino, (CrC6alkyl)(C3-C6cycloalkyl)amino, CrC6alkylcarbonyl, CrC6alkoxycarbonyl, Ci-C6alkylaminocarbonyl, diCi-C6alkylaminocarbonyl, C
C6alkoxycarbonyloxy, Ci-C6alkylaminocarbonyloxy, diCi-C6alkylaminocarbonyloxy, C C6alkylcarbonyloxy, Ci-C6alkylcarbonylamino, Ci-C6alkylcarbonyl-Ci-C6alkylamino, C C6alkoxyimino, Ci-C6alkoxyimino-Ci-C6alkyl, triCi.6alkylsilyl, CrC6alkoxy-C2-C6alkynyl, C C6alkoxyimino-C2-C6alkynyl, CrC6alkylthio-C2-C6alkynyl, hydroxy-C2-C6alkynyl, C
C6alkylthio-CrC6alkyl or hydroxy- CrC6alkyl;
Each R5 is independently halogen, cyano, nitro, amino, hydroxy, CrC6alkyl, C3-C6cycloalkyl, CrC6haloalkyl, CrC6alkoxy, Ci-C6alkoxy-Ci-C6alkyl, CrC6haloalkoxy, CrC6alkylthio
K is an integer selected from 0, 1 or 2; or a salt or a N-oxide thereof, with the proviso that when Ri is methyl then R4 is not halogen or hydroxyl; or when Ri is arylalkyi then R4 is not hydroxyl.
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