EP0937051A1 - Fungicidal cyclic amides - Google Patents

Fungicidal cyclic amides

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Publication number
EP0937051A1
EP0937051A1 EP97945385A EP97945385A EP0937051A1 EP 0937051 A1 EP0937051 A1 EP 0937051A1 EP 97945385 A EP97945385 A EP 97945385A EP 97945385 A EP97945385 A EP 97945385A EP 0937051 A1 EP0937051 A1 EP 0937051A1
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EP
European Patent Office
Prior art keywords
pho
alkyl
phenyl
dif
haloalkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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EP97945385A
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German (de)
French (fr)
Inventor
Michael Paul Walker
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EIDP Inc
Original Assignee
EI Du Pont de Nemours and Co
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Publication of EP0937051A1 publication Critical patent/EP0937051A1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/66—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms

Definitions

  • This invention relates to certain fungicidal cyclic amides their N-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides.
  • This invention is directed to compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as fungicides:
  • E is 1,2-phenylene optionally substituted with R 3 or both R 3 and R 4 ;
  • A is O, S, N, NR5 or CR 6 ;
  • G is C or N; provided that when G is C, then A is O, S or NR 5 and the floating double bond is attached to G; and when G is N, then A is N or CR 6 and the floating double bond is attached to A; W is O, S, NH, N(C r C 6 alkyl) or NO(C r C 6 alkyl);
  • X is OR 1 , StO ⁇ R 1 or halogen;
  • R 1 is C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl,
  • R 2 is H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl,
  • R 3 and R 4 are each independently halogen, cyano, nitro, hydroxy, C j -C 6 alkyl,
  • C r C 6 haloalkyl C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C r C 6 alkoxy, C r C 6 haloalkoxy, C 2 -C 6 alkenyloxy,
  • R 5 is H, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl,
  • Y is -O-, -S(O) n -, -NR 7 -, -CH 2 O-, -CH 2 NR 7 -, -CH 2 S(O) n - or a direct bond; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to E and the moiety on the right side of the linkage is bonded to Z;
  • Z is phenyl, pyrimidinyl or triazinyl, each substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 6 is H, halogen, C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkeny
  • R 7 is H, C1-C3 alkyl or C 3 -C 6 cycloalkyl; or R 7 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C ⁇ -C alkyl,
  • R 8 is H, 1-2 halogen, Cj-Cg alkyl, Cj-C 6 haloalkyl, C]-C 6 alkoxy,
  • C j -Cg haloalkoxy C -C6 alkenyl, C 2 -Cg haloalkenyl, C 2 -C 6 alkynyl, C j -Cg alkylthio, Ci- haloalkylthio, C ⁇ -C 6 alkylsulfinyl, C j -Cg alkylsulfonyl, C 3 -Cg cycloalkyl, C 3 -Cg alkenyloxy, CO 2 (C r C 6 alkyl), NH(C r C 6 alkyl), N(C r C 6 alkyl) 2 , cyano, nitro,
  • R 9 is phenyl, phenylmethyl, phenoxy, benzoyl, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with one or more R 1 and with one R 1 ; each R 10 is independently halogen, C ⁇ -C alkyl, C ⁇ -C haloalkyl, C 2 -C 4 alkenyl,
  • each R 1 1 is independently halogen, cyano, nitro, C j -C 4 alkyl, C ⁇ -C 4 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C r C 4 alkoxy, Cj-C 4 alkylthio, C ] -C 4 alkylsulfinyl or C ⁇ -C alkylsulfonyl;
  • R 12 is halogen, C j -C alkyl, C ⁇ -C haloalkyl, C -C 6 alkenyl, C 2 -C 6 haloalkenyl,
  • R 14 , R 15 , and R 16 are each independently C r C 6 alkyl, C 2 -C 6 alkenyl, C ⁇ -C 4 alkoxy or phenyl; each R 17 is independently H, C1-C6 alkyl, Cj-Cg haloalkyl, C 2 -C 6 alkenyl,
  • R 18 is C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl,
  • R 18 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C j -C alkyl, C1-C4 haloalkyl, C ⁇ -C alkoxy, C1-C4 haloalkoxy, nitro or cyano; and m and n are each independently 0, 1 or 2; provided that i) when E is 1 ,2-phenylene, A is N, G is N, W is O, X is OMe, R 2 is CH 3 and Z substituted with R 9 is 6-[3,5-bis(trifluoromethyl)phenyl]-4-pyrimidinyl,
  • 6-(2,4-dichlorophenyl)-4-pyrimidinyl 4-[3,5-bis(trifiuoromethyl)phenyl]-2-pyrimidinyl, 2-[3,5-bis(trifluoromethyl)phenyl]-4-pyrimidinyl, 3-[2-(methoxycarbonyl)-6-nitrophenoxy]phenyl, 3-(2,6-dicyanophenoxy)phenyl,
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, propyl, 1 -methylethyl or the different butyl, pentyl or hexyl isomers.
  • alkenyl includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.
  • Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkylene denotes a straight-chain alkanediyl.
  • alkylene examples include CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 , CH 2 CH 2 CH 2 CH 2 CH 2 .
  • Alkoxy includes, for example, methoxy, ethoxy, propoxy, 1-methylethoxy and the different butoxy, pentoxy and hexyloxy isomers.
  • Alkoxy alkyl denotes alkoxy substitution on alkyl.
  • alkoxyalkyl examples include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • Alkoxyalkoxy denotes alkoxy substitution on alkoxy.
  • alkynyloxy includes straight-chain or branched alkynyloxy moieties. Examples of “alkynyloxy” include HC ⁇ CCH 2 O, CH 3 C ⁇ CCH 2 O and CH 3 C ⁇ CCH 2 CH 2 O.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
  • Alkylthioalkyl denotes alkylthio substitution on alkyl.
  • alkylthioalkyl examples include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 .
  • Alkylthioalkylthio denotes alkylthio substitution on alkylthio.
  • alkylthioalkoxy denotes alkylthio substitution on alkoxy.
  • Alkylsulfinyl includes both enantiomers of an alkylsulfinyl group.
  • alkylsulfinyl examples include CH 3 S(O), CH 3 CH 2 S(O), CH 3 CH 2 CH 2 S(O), (CH 3 ) 2 CHS(O) and the different butylsulfinyl, pentylsulfinyl and hexylsulfmyl isomers.
  • alkylsulfonyl examples include CH 3 S(O) 2 , CH 3 CH 2 S(O) 2 , CH 3 CH 2 CH 2 S(O) 2 , (CH 3 ) 2 CHS(O) and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.
  • Alkenylthio is defined analogously to the above examples.
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • Trialkylsilylalkoxyalkoxy denotes trialkylsilylalkoxy substitution on alkoxy.
  • Examples of “trialkylsilylalkoxyalkoxy” includes, for example, (CH 3 ) 3 SiCH 2 CH 2 OCH 2 O.
  • Phenylene denotes -(C 6 H 4 )-.
  • nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides.
  • halogen either alone or in compound words such as “haloalkyl”, includes fluorine, chlorine, bromine or iodine.
  • 1-2 halogen indicates that one or two of the available positions for that substituent may be halogen which are independently selected.
  • alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
  • haloalkyl include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 .
  • haloalkenyl “haloalkynyl", “haloalkoxy”, and the like, are defined analogously to the term “haloalkyl”.
  • haloalkynyl examples include HC ⁇ CCHCl, CF 3 C ⁇ C, CC1 3 C ⁇ C and FCH 2 C ⁇ CCH 2 .
  • haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio examples include CC1 3 S, CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S.
  • haloalkylsulfinyl examples include CF 3 S(O), CCl 3 S(O), CF 3 CH 2 S(O) and CF 3 CF 2 S(O).
  • haloalkylsulfonyl examples include CF 3 S(O) 2 , CCl 3 S(O) 2 , CF 3 CH 2 S(O) 2 and CF 3 CF 2 S(O) 2 .
  • C j -C j The total number of carbon atoms in a substituent group is indicated by the "C j -C j " prefix where i and j are numbers from 1 to 10.
  • C j -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl.
  • alkoxycarbonyl when a compound of Formula I is comprised of one or more aromatic or heterocyclic rings, all substituents are attached to these rings through any available carbon by replacement of a hydrogen on said carbon.
  • Stereoisomers of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s).
  • the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the present invention comprises compounds selected from Formula I, N-oxides and agriculturally suitable salts thereof.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
  • the salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • the salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine, ammonia or triethylamine) or inorganic bases (e.g., hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic group such as a phenol.
  • Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1.
  • R 9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with two or more R 1 * and with one R 12 ; and R 12 is halogen, C r C 4 alkyl, C r C 4 haloalkyl, C r C 4 alkoxy, C r C 4 haloalkoxy, C j -C 4 alkylthio, C j -C 4 haloalkylthio, C ⁇ -C 4 alkylsulfinyl, C!-C 4 haloalkylsulfinyl, Cj-C alkylsulfonyl, C ⁇ -C 4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or
  • R2 is CH 3 ;
  • R 3 and R 4 are each independently halogen or C1-C3 alkyl; and Y is O, CH 2 O or CH 2 S(O) n .
  • Preferred 3. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: A is N or CR 6 ; G is N; R 9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl; or pyrimidinyloxy each substituted on the aromatic ring with two or more R 1 !
  • R 12 is halogen, Cj-C 4 alkyl, Cj-C 4 haloalkyl, C ⁇ -C 4 alkoxy, C ⁇ -C haloalkoxy, C j -C 4 alkylthio, C i -C 4 haloalkylthio, C j -C 4 alkylsulfinyl, C r C 4 haloalkylsulfinyl, C ⁇ -C 4 alkylsulfonyl, C ⁇ -C 4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or N(R 17 ) 2 ; or R 12 is phenyl optionally substituted with halogen, C ⁇ -C 4 alkyl, C ⁇ -C 4 haloalkyl, Cj-C alkoxy, C ⁇ -C haloalkoxy, nitro or cyano.
  • A is N; W is O; X is OR 1 ; R 1 is CH 3 ; R 2 is CH 3 ;
  • R 3 and R 4 are each independently halogen or C ⁇ -C 3 alkyl; and Y is O, CH 2 O or CH 2 S(O) n .
  • R 1 J and R 12 are halogen.
  • the 2,3-dihalo, 2,4-dihalo, 2,5-dihalo, 2,6-dihalo, 3,4-dihalo and 3,5-dihalo compounds e.g. 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 2,6-difluoro, 2-chloro-6-fluoro and 2,6-dichloro
  • 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 2,6-difluoro, 2-chloro-6-fluoro and 2,6-dichloro are of particular note.
  • R 1 * groups where there are two R 1 * groups, the 2,3,4- trihalo, 2,3,5-trihalo, 2,3,6-trihalo, 2,4,5-trihalo, 2,4,6-trihalo and 3,4,5-trihalo compounds (e.g. 2,4,6-trifluoro, 2,3,4-trifluoro, 2,3,5-trifluoro, 2,3,6-trifluoro, 2,3,6- trifluoro, 2,6-dichloro-4-fluoro and 2,4,6-trichloro) are of particular note.
  • R 1 ! groups where there are three R 1 ! groups, the 2,3,4,5-tetrahalo and 2,3,5,6-tetrahalo compounds (e.g. 2,3,5,6- tetrafluoro and 2,3,5,6-tetrachloro) are of particular note.
  • R 1 ! groups compounds where there are at least two R 1 ! groups. This includes compounds where at least two of the total R 1 ] and R 12 groups are other than halogen (e.g. 2,6-diR 11 -4-R 12 and 2,4-diR 11 -6-R 12 compounds where each R 1 1 is other than halogen or where one R 1 1 and R 12 are other than halogen).
  • Compounds where there are at least two R 11 groups also include compounds having two halogen substituents (e.g. 2,6-dihalo-4-R 12 and 2,4-dihalo-6-R 12 ) where R 12 is other than halogen.
  • R 11 and R 12 groups are 2,6-; 2,5-; 2,4-; and 2,3- positioning.
  • R 1 1 and R 12 groups are 2,3,4-; 2,3,5-; 2,3,6-; 2,4,5-; and 2,4,6- positioning.
  • R 11 and R 12 groups is 2,3,5,6 positioning.
  • This invention also relates to fungicidal compositions comprising fungicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent.
  • the preferred compositions of the present invention are those which comprise the above preferred compounds.
  • This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of the compounds of the invention (e.g., as a composition described herein).
  • a fungicidally effective amount of the compounds of the invention e.g., as a composition described herein.
  • the preferred methods of use are those involving the above preferred compounds.
  • the compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-22.
  • One skilled in the art will recognize that compounds of Formula la and lb are encompassed by Formula I and, therefore, can be prepared by these procedures.
  • the definitions of E, A, G, W, X, R, R ⁇ R 20 , Y, Z, m and n in the compounds of Formulae 1-36 below are as defined above (including the Summary of the Invention) or below.
  • Compounds of Formulae la-Ih are various subsets of the compounds of Formula I, and all substituents for Formulae la-Ih are as defined above for Formula I.
  • a compound of Formula I wherein R 2 is H may exist as tautomer la or lb, or both la and lb.
  • the present invention comprises all tautomeric forms of compounds of Formula I.
  • Procedures 1) to 5 describe syntheses involving construction of the amide ring after the formation of the aryl moiety (E-Y-Z).
  • Procedure 5) describes syntheses of the aryl moiety (E-Y-Z) with the amide ring already in place.
  • the compounds of Formula Ic are prepared by treating compounds of Formula 1 with an appropriate alkyl transfer reagent in an inert solvent with or without additional acidic or basic reagents or other reagents (Scheme 1).
  • Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxy ethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; and halocarbons such as dichloromethane or chloroform.
  • Use of trimethylsilyldiazomethane requires a protic cosolvent such as methanol.
  • compounds of Formula Ic can also be prepared by contacting compounds of Formula 1 with alkyl trichloroacetimidates of Formula 3 and a Lewis acid catalyst.
  • Suitable Lewis acids include trimethylsilyl triflate and tetrafluoroboric acid.
  • the alkyl trichloroacetimidates can be prepared from the appropriate alcohol and trichloroacetonitrile as described in the literature (J. Danklmaier and H. Honig, Synth. Commun., (1990), 20, 203).
  • Compounds of Formula Ic can also be prepared from compounds of Formula 1 by treatment with a trialkyloxonium tetrafluoroborate (i.e., Meerwein's salt) of Formula 4 (Method 3).
  • a trialkyloxonium tetrafluoroborate i.e., Meerwein's salt
  • the use of trialkyloxonium salts as powerful alkylating agents is well known in the art (see U. Sch ⁇ llkopf, U. Groth, C. Deng, Angew. Chem., Int. Ed. Engl,
  • alkylating agents which can convert carbonyl compounds of Formula 1 to compounds of Formula Ic are dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane and propargyl bromide (Method 4). These alkylations can be conducted with or without additional base.
  • Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, or tertiary amines such as triethylamine, pyridine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine.
  • alkali metal alkoxides such as potassium tert-butoxide
  • inorganic bases such as sodium hydride and potassium carbonate
  • tertiary amines such as triethylamine, pyridine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine.
  • X 1 - OH can be prepared by condensation of malonates or malonate derivatives of Formula 5 with an ambident nucleophile of Formula 6 (Scheme 2).
  • Formula 6 are N-substituted hydroxylamines (HO- ⁇ HR 2 ) and substituted hydrazines
  • the malonate esters of Formula 5 can be prepared by methods described hereinafter.
  • Esters of Formula 5 a can be prepared from copper (I)-catalyzed reaction of malonate esters of Formula 7 with substituted aryl halides of Formula 8 according to methods adapted from A. Osuka, T. Kobayashi and H. Suzuki, Synthesis, (1983), 67 and M. S. Malamas, T. C. Hohman, and J. Millen, J. Med. Chem., 1994, 37, 2043-2058, and illustrated in Scheme 3.
  • Malonate esters of Formula 5 a can also be prepared from diester carboxylic acids of Formula 5b after modification of the carboxylic acid functional group to the appropriate Y and Z group.
  • a copper (I)-catalyzed coupling of malonates of Formula 7 with orthobromocarboxylic acids of Formula 8a can be used to prepare compounds of Formula 5b as shown in Scheme 3.
  • Methods to prepare compounds of Formula 8a are common in the art (see P. Beak, V. Snieckus, Ace. Chem. Res., (1982), 15, 306 and Org. React., (1979), 26, 1 and references therein).
  • R C r C 4 alkyl
  • R C j -C 4 alkyl
  • the malonate esters of Formula 5 a can be prepared by treating aryl acetic acid esters of Formula 9 with a dialkyl carbonate or alkyl chloro formate in the presence of a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 4).
  • a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 4).
  • a suitable base such as, but not limited to, sodium metal or sodium hydride
  • R C r C 4 alkyl
  • Esters of Formula 9 can be prepared from acid-catalyzed alcoholysis of aryl acetonitriles of Formula 10 or esterification of aryl acetic acids of Formula 11 as illustrated in Scheme 5 (see Org. Synth., Coll. Vol. I, (1941), 270).
  • esters of formula 9 can be prepared by palladium (O)-catalyzed cross coupling reaction of aryl iodides of Formula 8 with a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 5).
  • a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 5).
  • Scheme 5 for example, see T. Sakamoto, A. Yasuhara, Y. Kondo, H. Yamanaka, Synlett, (1992), 502, and J. F. Fauvarque, A. Jutard, J. Organometal. Chem., (1977), 132, C17.
  • Aryl acetic acid esters of Formula 9 can also be prepared by copper (I)-catalyzed condensation of aryl halides of Formula 12 with compounds of Formula 13 as described in EP-A-307,103 and illustrated below in Scheme 6.
  • R -C 4 alkyl
  • esters of Formula 9 can also be prepared by forming the Y bridge using conventional nucleophilic substitution chemistry (Scheme 7). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 15 or 16 with a nucleophilic ester of Formula 14 affords compounds of Formula 9.
  • a base for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 14.
  • R C j -C alkyl
  • Rl9 OH, SFL CH 2 OH, CH 2 SH, NHR 7
  • Y O, S, CH 2 0, CH 2 S, NR 7
  • Compounds of Formula Ic can also be prepared by reaction of Formula 17 compounds with alkali metal alkoxides (R ⁇ O'M " ) or an alkali metal thioalkoxides (R ⁇ S'M " * " ), (Scheme 8).
  • the leaving group Lg 1 in the amides of Formula 17 are any group known in the art to undergo a displacement reaction of this type. Examples of suitable leaving groups include chlorine, bromine, and sulfonyl and sulfonate groups. Examples of suitable inert solvents are dimethylformamide or dimethyl sulfoxide, dimethoxy ethane methanol.
  • V C j -C 6 alkyl, C j -C 6 haloalkyl or 4-CH 3 -C 6 H 4
  • Compounds of Formula 17a can be prepared from compounds of Formula lb (compounds of Formula 1 wherein X 1 is OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives (Scheme 9).
  • halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives (Scheme 9).
  • Compounds of Formula 17a when Lg 2 is chlorine or bromine are also compounds of Formula Id (compounds of Formula I where X is halogen).
  • compounds of Formula lb can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methanesulfonyl chloride, j9-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding ⁇ -alkylsulfonate of Formula 17a.
  • the reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine).
  • Lg 2 Cl, Br or -OS0 2
  • sulfonyl compounds of Formula 17b can be prepared by oxidation of the corresponding thio compound of Formula 18 using well-known methods for the oxidation of sulfur (see Schrenk, K. In The Chemistry ofSulphones and Sulphoxides; Patai, S. et al., Eds.; Wiley: New York, 1988).
  • Suitable oxidizing reagents include meta-chloroperoxybenzoic acid, hydrogen peroxide and Oxone® (KHSO 5 ).
  • V C ⁇ -C 6 alkyl, -Cg haloalkyl or 4-CH 3 -C 6 H 4
  • the compound of Formula 19 is treated with, for example, excess thionyl chloride, the product formed first is the ring-closed compound of Formula 20.
  • This compound can be isolated or converted in situ to the compound of Formula 17c; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
  • the hydrazides of Formula 19 can be prepared as illustrated in Scheme 12. Condensation of the isocyanate of Formula 21 with the hydrazine of Formula H 2 NNR R 20 in an inert solvent such as tetrahydrofuran affords the hydrazide.
  • Ketene dithioacetals of Formula 22a can be prepared by condensing arylacetic acid esters of Formula 9 with carbon disulfide in the presence of a suitable base, followed by reaction with two equivalents of an Rl -halide, such as iodomethane or propargyl bromide (Scheme 14).
  • Rl is not C 2 -C alkylcarbonyl or C 2 -C 4 alkoxycarbonyl
  • the compounds of Formula 24 can be alkyl chloroformates or dialkyl carbonates. Some of these carbonylating reactions may require the addition of a base to effect reaction.
  • Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, tertiary amines such as triethylamine and triethylenediamine, pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7- ene (DBU).
  • Suitable solvents include polar aprotic solvents such as acetonitrile, dimethylformamide, or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; or halocarbons such as dichloromethane or chloroform.
  • the reaction temperature can vary between 0°C and 150°C and the reaction time can be from 1 to 72 hours depending on the choice of base, solvent, temperature, and substrates.
  • Tl and T 2 are independently Cl, OCCl 3 , 0(C ⁇ -C 4 alkyl), 1-imidazolyl,
  • N-Amino-ureas of Formula 23 can be prepared as illustrated in Scheme 16.
  • Treatment of an arylamine of Formula 25 with phosgene, thiophosgene, NN'-carbonyldiimidazole, or NN'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 26.
  • a base can be added for reactions with phosgene or thiophosgene.
  • Subsequent treatment of the iso(thio)cyanate with an R 2 -substituted hydrazine produces the N-amino-urea of Formula 23.
  • Ureas of Formula 27 are reacted with activated 2-halocarboxylic acid derivatives 28 such as 2-halocarboxylic acid chlorides, 2-halocarboxylic acid esters or 2-haloacyl imidazoles.
  • the initial acylation on the arylamino nitrogen is followed by an intramolecular displacement of the 2-halo group to effect cyclization.
  • Base may be added to accelerate the acylation and/or the subsequent cyclization. Suitable bases include triethylamine and sodium hydride.
  • Formula Id compounds can be prepared by reaction of Formula 26 isocyanates with Formula 29 esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula Id compounds.
  • the ureas of Formula 27 can be prepared by either of the methods illustrated in Scheme 18.
  • the arylamine of Formula 25 can be contacted with an isocyanate or isothiocyanate of Formula R 2 N-C-W as described above.
  • an isocyanate or isothiocyanate of Formula 26 can be condensed with an amine of Formula R 2 -NH 2 to form the urea.
  • the arylamine and iso(thio)cyanates of Formulae 25 and 26, respectively, are commercially available or prepared by well-known methods.
  • isothiocyanates can be prepared by methods described in J. Heterocycl. Chem., (1990), 27, 407. Isocyanates can be prepared as described in March, j.
  • thionating reagents such as P 2 S5 or Lawesson's reagent (2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulfide
  • Compounds of Formula I can be prepared by contacting halides of Formula 30 with various nucleophiles (Scheme 20).
  • the appropriate alcohol or thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide or thioalkoxide which acts as the nucleophile.
  • the halides of Formula 30 can be prepared from the alcohols of Formula 31 with halogenating reagents such as thionyl chloride.
  • the compounds of the present invention are prepared by combinations of reactions as illustrated in the Schemes 1 -20 in which Z is a moiety as described in the summary.
  • Preparation of the compounds containing the radical Z as described in the summary, substituted with R 9 can be accomplished by one skilled in the art by the appropriate combination of reagents and reaction sequences for a particular Z-R 9 .
  • Such reaction sequences can be developed based on known reactions available in the chemical art. For a general reference, see March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985) and references therein. See the following paragraphs for some examples of how R 9 is defined in individual schemes, and the preparation of representative Z-R 9 examples.
  • compounds of Formula Ih can be prepared by reacting electrophiles such as those depicted by Formula 34 with nucleophiles such as those generated by reaction of compounds of Formula 35 with the appropriate base as shown in Scheme 22.
  • compounds of Formula Ih can be prepared by reacting compounds of Formula 34 bearing leaving groups such as bromide or iodide with for example aryl boronic acids of Formula 36 in the presence of a palladium catalyst.
  • Step B Preparation of 5-chloro-2.4-dihydro-4-(2-methoxyphenyl)-2-methyl-3H- 2,4-triazol-3-one
  • 29.85 g of triphosgene was added to a stirred solution of 21 g of the title compound of Step A in 800 mL of dichloromethane under nitrogen.
  • the reaction was heated to reflux and allowed to reflux overnight, cooled, and then concentrated under reduced pressure.
  • the resulting residue was dissolved in ethyl acetate, washed with distilled water, and then with saturated aqueous sodium chloride solution.
  • the organic layer was dried (MgSO 4 ), filtered, and concentrated under reduced pressure.
  • Step E Preparation of 4-[2-r(6-chloro-4-pyrimidinyl oxy]phenvn-2,4-dihydro-5- methoxy-2-methyl-3H-l,2,4-triazol-3-one 15 g of the intermediate from Step D above were added to a stirred suspension of potassium carbonate (10.3g) in 150 mL of acetonitrile at room temperature. The suspension stirred at room temperature for 1 h. Then 11.1 g of 4,6-dichloropyrimidine were added at room temperature and the reaction was allowed to stir at room temperature for 16 h. The solvent was then removed under reduced pressure and the crude residue was taken up in 150 mL of water.
  • Step F Preparation of 2,4-dihvdro-5-methoxy-2-methyl-4-r2-[r6-(2.4,6- trifluorophenoxyV4-pyrimidinyl1oxy]phenyl1-3H-L2.4-triazol-3-one 0.34 g 2,4,6-trifluorophenol were added to a stirred suspension of potassium carbonate (0.13 g) in 25 mL acetonitrile at room temperature. The resulting suspension was stirred at room temperature for 1 h. Then 0.5 g of the intermediate from Step E were added and the reaction was heated at reflux overnight. The reaction was cooled to room temperature and the solvent was removed under reduced pressure.
  • Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant.
  • the formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
  • Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels.
  • Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble.
  • Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated”). Encapsulation can control or delay release of the active ingredient.
  • Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.
  • the formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
  • High Strength Compositions 90-99 0-10 0-2 Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses.
  • All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.
  • Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, NN-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers.
  • Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate.
  • Liquid diluents include, for example, water, N,N-dimethylforrnamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.
  • Solutions can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry 's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S.
  • Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566. For further information regarding the art of formulation, see U.S. 3,235,361,
  • Compound 8 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
  • Compound 8 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium magnesium bentonite 59.0%.
  • Compound 3 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.
  • the compounds of this invention are useful as plant disease control agents.
  • the present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound.
  • the compounds and compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops.
  • pathogens include Plasmopara viticola, Phytophthora infestans, Peronospora tabacina, Pseudoperonospora cubensis, Pythium aphanidermatum, Alternaria brassicae, Septoria nodorum, Septoria tritici, Cercosporidium personatum, Cercospora arachidicola, Pseudocercosporella herpotrichoides, Cercospora beticola, Botrytis cinerea, Monilinia fructicola, Pyricularia oryzae, Podosphaera leucotricha, Venturia inaequalis, Erysiphe graminis, Uncinula necatur, Puccinia recondita, Puccinia graminis, Hemileia vastatrix, Puccinia striiformis, Puccinia arachidis, Rhizoctonia solani, Sphaerotheca fuligine
  • Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection.
  • agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorfenapyr, chlorpyrifos.
  • fungicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management.
  • Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group azoxystrobin, benomyl, carbendazim, carpropamid, copper salts, cymoxanil, cyproconazole, cyprodinil, dimethomorph, epoxiconazole, famoxadone, fenpropidin, fenpropimorph, flusilazole, flutolanil, fosetyl-aluminum, kasugamycin, kresoxim-methyl, mancozeb, metalaxyl and oxadixyl, pencycuron, probenazole, propiconazole, pyro
  • Specifically preferred mixtures are selected from the group: compound 8 and azoxystrobin, compound 8 and benomyl, compound 8 and carbendazim, compound 8 and carpropamid, compound 8 and copper salts, compound 8 and cymoxanil, compound 8 and cyproconazole, compound 8 and cyprodinil, compound 8 and epoxiconazole, compound 8 and famoxadone, compound 8 and fenpropidin, compound 8 and fenpropimorph, compound 8 and flusilazole, compound 8 and flutolanil, compound 8 and fosetyl-aluminum, compound 8 and kasugamycin, compound 8 and kresoxim-methyl, compound 8 and mancozeb, compound 8 and metalaxyl, compound 8 and oxadixyl, compound 8 and pencycuron, compound 8 and probenazole, compound 8 and propiconazole, compound 8 and pyro
  • Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing.
  • the compounds can also be applied to the seed to protect the seed and seedling.
  • Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 10 g per kilogram of seed.
  • BIOLOGICAL EXAMPLES OF THE INVENTION Test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests. Spraying these
  • TEST A The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20°C for 7 days, after which disease ratings were made.
  • TEST B The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.
  • Puccinia recondita the causal agent of wheat leaf rust
  • TEST C The test suspension was sprayed to the point of run-off on rice seedlings. The following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 h, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made. TEST D
  • test suspension was sprayed to the point of run-off on tomato seedlings.
  • seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.
  • TEST E The test suspension was sprayed to the point of run-off on grape seedlings.
  • the seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20°C for 24 h, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 h, after which disease ratings were made.
  • Plasmopara viticola the causal agent of grape downy mildew
  • TEST F The test suspension was sprayed to the point of run-off on cucumber seedlings. The following day the seedlings were inoculated with a spore suspension o ⁇ Botrytis cinerea (the causal agent of gray mold on many crops) and incubated in a saturated atmosphere at 20°C for 48 h, and moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.
  • a spore suspension o ⁇ Botrytis cinerea the causal agent of gray mold on many crops
  • Results for Tests A-F are given in Table A.
  • a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls).
  • a dash (-) indicates no test results.
  • ND indicates disease control not determined due to phytotoxicity.

Abstract

Compounds of formula (I), and their N-oxides and agriculturally suitable salts, are disclosed which are useful as fungicides wherein E is 1,2-phenylene optionally substituted with R3 or both R?3 and R4¿; A is O, S, N, NR?5 or CR6¿; G is C or N; provided that when G is C, then A is O, S or NR5 and the floating double bond is attached to G; and when G is N, then A is N or CR6 and the floating double bond is attached to A; W is O, S, NH, N(C¿1?-C6 alkyl) or NO(C1-C6 alkyl); X is OR?1¿, S(O)¿mR?1 or halogen; Y is -O-, -S(O)¿n?-, -NR?7¿-, -CH¿2?O-, -CH2NR?7¿-, -CH¿2?S(O)n- or a direct bond; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to E and the moiety on the right side of the linkage is bonded to Z; Z is phenyl, pyrimidinyl or triazinyl, each substituted with R?9¿ and optionally substituted with one or more R10; R2 is H, C¿1?-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4? alkylcarbonyl, C2-C4 alkoxycarbonyl, hydroxy, C1-C2 alkoxy or acetyloxy. Also disclosed are compositions containing the compounds of formula (I) and a method for controlling plant diseases caused by fungal plant pathogens which involves applying an effective amount of a compound of formula (I).

Description

TITLE FUNGICIDAL CYCLIC AMIDES
BACKGROUND OF THE INVENTION
This invention relates to certain fungicidal cyclic amides their N-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides.
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action.
International Publications WO 95/14009 and WO 97/00612 disclose cyclic amides of Formula i as fungicides and/or insecticides:
i Compounds of the present invention are unexpectedly more effective as fungicides than those named in International Publications WO 95/14009 and WO 97/00612.
SUMMARY OF THE INVENTION This invention is directed to compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as fungicides:
I wherein E is 1,2-phenylene optionally substituted with R3 or both R3 and R4; A is O, S, N, NR5 or CR6;
G is C or N; provided that when G is C, then A is O, S or NR5 and the floating double bond is attached to G; and when G is N, then A is N or CR6 and the floating double bond is attached to A; W is O, S, NH, N(CrC6 alkyl) or NO(CrC6 alkyl);
X is OR1, StO^R1 or halogen; R1 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C alkylcarbonyl or C -C4 alkoxycarbonyl; R2 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C -C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl,
C2-C4 alkoxycarbonyl, hydroxy, Cι-C2 alkoxy or acetyloxy; R3 and R4 are each independently halogen, cyano, nitro, hydroxy, Cj-C6 alkyl,
CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, CrC6 alkoxy, CrC6 haloalkoxy, C2-C6 alkenyloxy,
C2-C6 alkynyloxy, CrC6 alkylthio, CrC6 alkylsulfinyl, CrC6 alkylsulfonyl, formyl, C2-C6 alkylcarbonyl, C2-Cs alkoxycarbonyl,
NH2C(O), (CrC4 alkyl)NHC(O), (CrC4 alkyl)2NC(O), (R13)3Si,
(R13)3Ge, (R13)3Si-C≡C, phenyl, phenylethynyl, benzoyl or phenylsulfonyl, each phenyl, phenylethynyl, benzoyl and phenylsulfonyl substituted with R8 and optionally substituted with one or more R10; or when R3 and R4 are attached to adjacent atoms, R3 and R4 can be taken together as C3-C5 alkylene, C3-C5 haloalkylene, C3-C5 alkenylene or
C3-C5 haloalkenylene, each optionally substituted with 1-2 C]-C3 alkyl; R5 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl or C2-C alkoxycarbonyl; Y is -O-, -S(O)n-, -NR7-, -CH2O-, -CH2NR7-, -CH2S(O)n- or a direct bond; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to E and the moiety on the right side of the linkage is bonded to Z; Z is phenyl, pyrimidinyl or triazinyl, each substituted with R9 and optionally substituted with one or more R10; R6 is H, halogen, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C£ alkynyl, C2-C6 haloalkynyl or C3-C6 cycloalkyl;
R7 is H, C1-C3 alkyl or C3-C6 cycloalkyl; or R7 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, Cι-C alkyl,
CpC4 haloalkyl, Ct-C4 alkoxy, Cι-C4 haloalkoxy, nitro or cyano; R8 is H, 1-2 halogen, Cj-Cg alkyl, Cj-C6 haloalkyl, C]-C6 alkoxy,
Cj-Cg haloalkoxy, C -C6 alkenyl, C2-Cg haloalkenyl, C2-C6 alkynyl, Cj-Cg alkylthio, Ci- haloalkylthio, Cι-C6 alkylsulfinyl, Cj-Cg alkylsulfonyl, C3-Cg cycloalkyl, C3-Cg alkenyloxy, CO2(CrC6 alkyl), NH(CrC6 alkyl), N(CrC6 alkyl)2, cyano, nitro,
SiR14R15R16 or GeR14R15R16; R9 is phenyl, phenylmethyl, phenoxy, benzoyl, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with one or more R1 and with one R1 ; each R10 is independently halogen, Cι-C alkyl, Cι-C haloalkyl, C2-C4 alkenyl,
C2-C4 alkynyl, Cj-C4 alkoxy, nitro or cyano; each R1 1 is independently halogen, cyano, nitro, Cj-C4 alkyl, Cι-C4 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, CrC4 alkoxy, Cj-C4 alkylthio, C]-C4 alkylsulfinyl or Cι-C alkylsulfonyl; R12 is halogen, Cj-C alkyl, Cι-C haloalkyl, C -C6 alkenyl, C2-C6 haloalkenyl,
C2-Cg alkynyl, C2-C£ haloalkynyl, C -C6 alkoxyalkyl, C2-C6 alkylthioalkyl, C3-Cg alkoxyalkynyl, C7-Cι0 tetrahydropyranyloxyalkynyl, benzyloxymethyl, Cι-C4 alkoxy, Cj-C haloalkoxy, C3-Cg alkenyloxy, C3-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-Cg haloalkynyloxy, C2-C6 alkoxyalkoxy, C5-C9 trialkylsilylalkoxyalkoxy, C2-C6 alkylthioalkoxy,
CrC4 alkylthio, CrC4 haloalkylthio, CrC4 alkylsulfinyl, CrC4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4. haloalkylsulfonyl, C3-C6 alkenylthio, C3-C6 haloalkenylthio, C2-C6 alkylthioalkylthio, nitro, cyano, thiocyanato, hydroxy, N(R17)2, SF5, Si(R1 )3, Ge(R1 )3, (Rl )3Si-C≡C-, OSi(Rl3)3, OGe(R1 )3, C(-O)R17, C(=S)Rl7, C(=O)OR17, C(=S)OR17,
C(-O)SRl7, C(=S)SR17, C(=O)N(Rl7)2, C(=S)N(Rl7)2, 0C(O)R17, OC(=S)Rl7, SC(=O)R17, SC(-S)Rl7, N(R17)C(=O)Rl7, N(Rl7)C(=S)R17, OC(=O)OR18, OC(=O)SR18, OC(=O)N(R17)2, SC(-O)OR18, SC(=O)SRl8, S(O)2OR17, S(O)2N(Rl7)2, 0S(0)2R18 or N^OS^R18; or Rl2 is phenyl, phenoxy, benzyl, benzyloxy, phenylsulfonyl, phenylethynyl or pyridinylethynyl, each optionally substituted on the aromatic ring with halogen, CrC alkyl, C1-C haloalkyl, CrC4 alkoxy, CrC4 haloalkoxy, nitro or cyano; each R13 is independently CrC4 alkyl, Cι-C4 haloalkyl, C2-C alkenyl, C 1 -C4 alkoxy or phenyl;
R14, R15, and R16 are each independently CrC6 alkyl, C2-C6 alkenyl, Cι-C4 alkoxy or phenyl; each R17 is independently H, C1-C6 alkyl, Cj-Cg haloalkyl, C2-C6 alkenyl,
C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, phenyl or benzyl, each phenyl and benzyl optionally substituted on the phenyl ring with halogen, Cι-C4 alkyl, Cι-C4 haloalkyl, C1-C4 alkoxy, ι-C4 haloalkoxy, nitro or cyano;
R18 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C2-Cg alkynyl, C2-C6 haloalkynyl or C3-C6 cycloalkyl; or R18 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, Cj-C alkyl, C1-C4 haloalkyl, Cι-C alkoxy, C1-C4 haloalkoxy, nitro or cyano; and m and n are each independently 0, 1 or 2; provided that i) when E is 1 ,2-phenylene, A is N, G is N, W is O, X is OMe, R2 is CH3 and Z substituted with R9 is 6-[3,5-bis(trifluoromethyl)phenyl]-4-pyrimidinyl,
6-(2,4-dichlorophenyl)-4-pyrimidinyl, 4-[3,5-bis(trifiuoromethyl)phenyl]-2-pyrimidinyl, 2-[3,5-bis(trifluoromethyl)phenyl]-4-pyrimidinyl, 3-[2-(methoxycarbonyl)-6-nitrophenoxy]phenyl, 3-(2,6-dicyanophenoxy)phenyl,
3-(6-chloro-5-nitro-4-pyrimidinyloxy)phenyl, 3 - [4-nitro-2-(trifluoromethyl)phenoxy]phenyl, 3 -(2,6-dimethylphenoxy)phenyl, 3 -(2-cyano-3 -fluorophenoxy)phenyl, 3-(2-cyano-6-fluorophenoxy)phenyl, 3-(2,6-dinitrophenoxy)phenyl,
3-(2,5-difluorophenoxy)phenyl, 3-(2,5-dimethylphenoxy)phenyl, 3-(2,5-dichlorophenoxy)phenyl, 3-(3,5-dichlorophenoxy)phenyl, 3-(2,3-difluorophenoxy)phenyl, 3-(2,4-difluorophenoxy)phenyl, 3 ' , 5 '-bis(trifluoromethy 1) [1,1 '-bipheny 1] -3 -yl or 3',5'-dichloro-[l,l'-biphenyl]-3-yl, then Y is other than -O-; and ii) when E is 1,2-phenylene, A is N, G is N, W is O, X is OMe, R2 is CH3 and Z substituted with R9 is
3-(3,5-dichlorophenyl)-5-methyl-l,2,4-triazin-6-yl, then Y is other than -CH2S-; and iii) when A is N, G is N, W is O, X is OMe and EYZ is [2-[[6-[3,5- bis(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-6-methylphenyl] or [2-[3-(2,6-difluorophenoxy)phenoxy]-6-methylphenyl], then R2 is other than CH3. DETAILS OF THE INVENTION In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, propyl, 1 -methylethyl or the different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkylene" denotes a straight-chain alkanediyl. Examples of "alkylene" include CH2CH2CH2, CH2CH2CH2CH2, CH2CH2CH2CH2CH2. "Alkenylene" denotes a straight-chain alkenediyl containing one olefmic bond. Examples of "alkenylene" include CH2CH=CH, CH2CH2CH=CH, CH2CH=CHCH2 and CH2CH=CHCH2CH2. "Alkoxy" includes, for example, methoxy, ethoxy, propoxy, 1-methylethoxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxy alkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. "Alkoxyalkoxy" denotes alkoxy substitution on alkoxy. "Alkenyloxy" includes straight-chain or branched alkenyloxy moieties. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O,
(CH3)CH=CHCH2O, (CH3)CH=C(CH3)CH2O and CH2=CHCH2CH2O. "Alkynyloxy" includes straight-chain or branched alkynyloxy moieties. Examples of "alkynyloxy" include HC≡CCH2O, CH3C≡CCH2O and CH3C≡CCH2CH2O. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2. "Alkylthioalkylthio" denotes alkylthio substitution on alkylthio. Analogously, "alkylthioalkoxy" denotes alkylthio substitution on alkoxy. "Alkylsulfinyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfinyl" include CH3S(O), CH3CH2S(O), CH3CH2CH2S(O), (CH3)2CHS(O) and the different butylsulfinyl, pentylsulfinyl and hexylsulfmyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2, CH3CH2S(O)2, CH3CH2CH2S(O)2, (CH3)2CHS(O) and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkenylthio" is defined analogously to the above examples. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "Trialkylsilylalkoxyalkoxy" denotes trialkylsilylalkoxy substitution on alkoxy. Examples of "trialkylsilylalkoxyalkoxy" includes, for example, (CH3)3SiCH2CH2OCH2O. "Phenylene" denotes -(C6H4)-.
One skilled in the art will appreciate that not all nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. The term "1-2 halogen" indicates that one or two of the available positions for that substituent may be halogen which are independently selected. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, C1CH2, CF3CH2 and CF3CC12. The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (C1)2C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HC≡CCHCl, CF3C≡C, CC13C≡C and FCH2C≡CCH2. Examples of "haloalkoxy" include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O. Examples of "haloalkylthio" include CC13S, CF3S, CC13CH2S and C1CH2CH2CH2S. Examples of "haloalkylsulfinyl" include CF3S(O), CCl3S(O), CF3CH2S(O) and CF3CF2S(O). Examples of "haloalkylsulfonyl" include CF3S(O)2, CCl3S(O)2, CF3CH2S(O)2 and CF3CF2S(O)2.
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are numbers from 1 to 10. For example, Cj-C3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl. Examples of "alkylcarbonyl" include CH3C(=O), CH3CH2CH2C(=O) and (CH3)2CHC(=O). Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OC(=O), (CH3)2CHOC(=O) and the different butoxy- or pentoxycarbonyl isomers. In the above recitations, when a compound of Formula I is comprised of one or more aromatic or heterocyclic rings, all substituents are attached to these rings through any available carbon by replacement of a hydrogen on said carbon.
When a group contains a substituent which can be hydrogen, for example R5 or R6, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). (See, e.g., U.S. Provisional Patent Application Serial No. [Docket No. BA-9183-P1] filed September 4, 1997, which is hereby incorporated by reference in its entirety.) Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula I, N-oxides and agriculturally suitable salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
The salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. The salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine, ammonia or triethylamine) or inorganic bases (e.g., hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic group such as a phenol.
Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: A is O, S or ΝR5; G is C;
R9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with two or more R1 * and with one R12; and R12 is halogen, CrC4 alkyl, CrC4 haloalkyl, CrC4 alkoxy, CrC4 haloalkoxy, Cj-C4 alkylthio, Cj-C4 haloalkylthio, Cι-C4 alkylsulfinyl, C!-C4 haloalkylsulfinyl, Cj-C alkylsulfonyl, Cι-C4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or Ν(R17)2; or R12 is phenyl optionally substituted with halogen, Cι-C4 alkyl, Cι-C4 haloalkyl, Cj-C4 alkoxy, Cι-C haloalkoxy, nitro or cyano.
Preferred 2. Compounds of Preferred 1 wherein: A is O; W is O; X is OR1; R1 is CH3;
R2 is CH3;
R3 and R4 are each independently halogen or C1-C3 alkyl; and Y is O, CH2O or CH2S(O)n. Preferred 3. Compounds of Formula I above, and agriculturally suitable salts thereof, wherein: A is N or CR6; G is N; R9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl; or pyrimidinyloxy each substituted on the aromatic ring with two or more R1 ! and with one R12; and R12 is halogen, Cj-C4 alkyl, Cj-C4 haloalkyl, Cι-C4 alkoxy, Cι-C haloalkoxy, C j -C4 alkylthio, C i -C4 haloalkylthio, C j -C4 alkylsulfinyl, CrC4 haloalkylsulfinyl, Cι-C4 alkylsulfonyl, Cι-C4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or N(R17)2; or R12 is phenyl optionally substituted with halogen, Cι-C4 alkyl, Cι-C4 haloalkyl, Cj-C alkoxy, Cι-C haloalkoxy, nitro or cyano. Preferred 4. Compounds of Preferred 3 wherein:
A is N; W is O; X is OR1; R1 is CH3; R2 is CH3;
R3 and R4 are each independently halogen or Cι-C3 alkyl; and Y is O, CH2O or CH2S(O)n. Of note are compounds where R1 J and R12 are halogen. Where there is one R1 * group, the 2,3-dihalo, 2,4-dihalo, 2,5-dihalo, 2,6-dihalo, 3,4-dihalo and 3,5-dihalo compounds (e.g. 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 2,6-difluoro, 2-chloro-6-fluoro and 2,6-dichloro) are of particular note. Where there are two R1 * groups, the 2,3,4- trihalo, 2,3,5-trihalo, 2,3,6-trihalo, 2,4,5-trihalo, 2,4,6-trihalo and 3,4,5-trihalo compounds (e.g. 2,4,6-trifluoro, 2,3,4-trifluoro, 2,3,5-trifluoro, 2,3,6-trifluoro, 2,3,6- trifluoro, 2,6-dichloro-4-fluoro and 2,4,6-trichloro) are of particular note. Where there are three R1 ! groups, the 2,3,4,5-tetrahalo and 2,3,5,6-tetrahalo compounds (e.g. 2,3,5,6- tetrafluoro and 2,3,5,6-tetrachloro) are of particular note.
Also of note are compounds where there are at least two R1 ! groups. This includes compounds where at least two of the total R1 ] and R12 groups are other than halogen (e.g. 2,6-diR11-4-R12 and 2,4-diR11-6-R12 compounds where each R1 1 is other than halogen or where one R1 1 and R12 are other than halogen). Compounds where there are at least two R11 groups also include compounds having two halogen substituents (e.g. 2,6-dihalo-4-R12 and 2,4-dihalo-6-R12) where R12 is other than halogen. Of particular note when there are a total of two R11 and R12 groups are 2,6-; 2,5-; 2,4-; and 2,3- positioning. Of particular note when there are a total of three R1 1 and R12 groups are 2,3,4-; 2,3,5-; 2,3,6-; 2,4,5-; and 2,4,6- positioning. Of particular note when there are a total of four R11 and R12 groups is 2,3,5,6 positioning. This invention also relates to fungicidal compositions comprising fungicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds.
This invention also relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of the compounds of the invention (e.g., as a composition described herein). The preferred methods of use are those involving the above preferred compounds.
SYNTHESIS DETAILS The compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-22. One skilled in the art will recognize that compounds of Formula la and lb are encompassed by Formula I and, therefore, can be prepared by these procedures. The definitions of E, A, G, W, X, R, R^R20, Y, Z, m and n in the compounds of Formulae 1-36 below are as defined above (including the Summary of the Invention) or below. Compounds of Formulae la-Ih are various subsets of the compounds of Formula I, and all substituents for Formulae la-Ih are as defined above for Formula I.
One skilled in the art will recognize that some compounds of Formula I can exist in one or more tautomeric forms. For example, a compound of Formula I wherein R2 is H may exist as tautomer la or lb, or both la and lb. The present invention comprises all tautomeric forms of compounds of Formula I.
la lb
The compounds of Formula I can be prepared as described below in Procedures 1) to 5). Procedures 1) to 4) describe syntheses involving construction of the amide ring after the formation of the aryl moiety (E-Y-Z). Procedure 5) describes syntheses of the aryl moiety (E-Y-Z) with the amide ring already in place. 1) Alkylation Procedures
The compounds of Formula Ic are prepared by treating compounds of Formula 1 with an appropriate alkyl transfer reagent in an inert solvent with or without additional acidic or basic reagents or other reagents (Scheme 1). Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, dimethylformamide or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxy ethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; and halocarbons such as dichloromethane or chloroform.
Scheme 1
Methods 1-4
1 Ic
X^ OH or SH X ^ OR SR1
Method 1 : U-CH=N2 (U = H or (CH3)3Si)
2
NH Method 2: JL ; Lewis acid cι3<r ^OR1
3
Method 3: (R1)30+ BF4-
4
Method 4: (R1)2S04; R1OS02V; or R^hal; optional base
(hal = F, Cl, Br, or I)
(V = CrC6 alkyl, Cj-C6 haloalkyl, or 4-CH3-C6H4) For example, compounds of Formula Ic can be prepared by the action of diazoalkane reagents of Formula 2 such as diazomethane (U = H) or trimethylsilyldiazomethane (U = (CH3)3Si) on compounds of Formula 1 (Method 1). Use of trimethylsilyldiazomethane requires a protic cosolvent such as methanol. For examples of these procedures, see Chem. Pharm. Bull, (1984), 32, 3759. As indicated in Method 2, compounds of Formula Ic can also be prepared by contacting compounds of Formula 1 with alkyl trichloroacetimidates of Formula 3 and a Lewis acid catalyst. Suitable Lewis acids include trimethylsilyl triflate and tetrafluoroboric acid. The alkyl trichloroacetimidates can be prepared from the appropriate alcohol and trichloroacetonitrile as described in the literature (J. Danklmaier and H. Honig, Synth. Commun., (1990), 20, 203).
Compounds of Formula Ic can also be prepared from compounds of Formula 1 by treatment with a trialkyloxonium tetrafluoroborate (i.e., Meerwein's salt) of Formula 4 (Method 3). The use of trialkyloxonium salts as powerful alkylating agents is well known in the art (see U. Schδllkopf, U. Groth, C. Deng, Angew. Chem., Int. Ed. Engl,
(1981), 20, 798).
Other alkylating agents which can convert carbonyl compounds of Formula 1 to compounds of Formula Ic are dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane and propargyl bromide (Method 4). These alkylations can be conducted with or without additional base. Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, or tertiary amines such as triethylamine, pyridine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and triethylenediamine. See R. E. Benson,
T. L. Cairns, J Am. Chem. Soc, (1948), 70, 2115 for alkylation examples using agents of this type.
Compounds of Formula la (compounds of Formula 1 wherein G = C, W = O and
X1 - OH) can be prepared by condensation of malonates or malonate derivatives of Formula 5 with an ambident nucleophile of Formula 6 (Scheme 2). The nucleophiles of
Formula 6 are N-substituted hydroxylamines (HO-ΝHR2) and substituted hydrazines
(HΝ(R5)-ΝHR2). Examples of such nucleophiles are N-methylhydroxylamine and methylhydrazine. The malonate esters of Formula 5 can be prepared by methods described hereinafter. The esters of Formula 5 can also be activated by first hydrolyzing the ester to form the corresponding carboxylic acid, and then converting the acid into the acid chloride (T = Cl) using thionyl chloride or oxalyl chloride, or into the acyl imidazole (T = 1 -imidazolyl) by treating with 1,1 -carbonyldiimidazole.
Scheme 2
5 la T = 0(C!-C4 alkyl), Cl, 1 -imidazolyl
Esters of Formula 5 a can be prepared from copper (I)-catalyzed reaction of malonate esters of Formula 7 with substituted aryl halides of Formula 8 according to methods adapted from A. Osuka, T. Kobayashi and H. Suzuki, Synthesis, (1983), 67 and M. S. Malamas, T. C. Hohman, and J. Millen, J. Med. Chem., 1994, 37, 2043-2058, and illustrated in Scheme 3.
Malonate esters of Formula 5 a can also be prepared from diester carboxylic acids of Formula 5b after modification of the carboxylic acid functional group to the appropriate Y and Z group. A copper (I)-catalyzed coupling of malonates of Formula 7 with orthobromocarboxylic acids of Formula 8a (see A. Bruggink, A. McKillop, Tetrahedron, (1975), 31, 2607) can be used to prepare compounds of Formula 5b as shown in Scheme 3. Methods to prepare compounds of Formula 8a are common in the art (see P. Beak, V. Snieckus, Ace. Chem. Res., (1982), 15, 306 and Org. React., (1979), 26, 1 and references therein).
Scheme 3
5a R = CrC4 alkyl
C02H
E/C°2H CuBr
I NaH I I
Br 1 1
OR OR
RO^^ ^CC^R
8a 7 5b
R = Cj -C4 alkyl
Additionally, the malonate esters of Formula 5 a can be prepared by treating aryl acetic acid esters of Formula 9 with a dialkyl carbonate or alkyl chloro formate in the presence of a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 4). For example, see J. Am. Chem. Soc, (1928), 50, 2758. Scheme 4
9 5a
R = CrC4 alkyl
Esters of Formula 9 can be prepared from acid-catalyzed alcoholysis of aryl acetonitriles of Formula 10 or esterification of aryl acetic acids of Formula 11 as illustrated in Scheme 5 (see Org. Synth., Coll. Vol. I, (1941), 270).
Additionally, esters of formula 9 can be prepared by palladium (O)-catalyzed cross coupling reaction of aryl iodides of Formula 8 with a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 5). For example, see T. Sakamoto, A. Yasuhara, Y. Kondo, H. Yamanaka, Synlett, (1992), 502, and J. F. Fauvarque, A. Jutard, J. Organometal. Chem., (1977), 132, C17.
Scheme 5
E/Y^Z ROH E^Y\ ROH E^Z
1 ^ 1 Λ acid 1 -
H2<^ ^O add H2C^O
^CN
1 |
OR OH
10 9 1 1
1 i BrZnCH2C02R or
(1) R3SnC≡COR
Pd° cat.
(2) H+
E^Z
| 1 I
8
R = CrC4 a tlkyl Aryl acetic acid esters of Formula 9 can also be prepared by copper (I)-catalyzed condensation of aryl halides of Formula 12 with compounds of Formula 13 as described in EP-A-307,103 and illustrated below in Scheme 6.
Scheme 6
12 9
R = -C4 alkyl
Y = = 0, S, NR7
Some esters of Formula 9 can also be prepared by forming the Y bridge using conventional nucleophilic substitution chemistry (Scheme 7). Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 15 or 16 with a nucleophilic ester of Formula 14 affords compounds of Formula 9. A base, for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 14.
Scheme 7
Lg — Z or
14 9
R = Cj-C alkyl
Rl9 = OH, SFL CH2OH, CH2SH, NHR7
Y = O, S, CH20, CH2S, NR7
Lg = Br, Cl, I, OSθ2(4-Me-Ph) 2) Displacement and Conjugate Addition/Elimination Procedures
Compounds of Formula Ic can also be prepared by reaction of Formula 17 compounds with alkali metal alkoxides (RΪO'M ") or an alkali metal thioalkoxides (R^S'M"*"), (Scheme 8). The leaving group Lg1 in the amides of Formula 17 are any group known in the art to undergo a displacement reaction of this type. Examples of suitable leaving groups include chlorine, bromine, and sulfonyl and sulfonate groups. Examples of suitable inert solvents are dimethylformamide or dimethyl sulfoxide, dimethoxy ethane methanol.
Scheme 8
V = Cj-C6 alkyl, Cj-C6 haloalkyl or 4-CH3-C6H4
M = K or Na
Compounds of Formula 17a can be prepared from compounds of Formula lb (compounds of Formula 1 wherein X1 is OH) by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding β-halo-substituted derivatives (Scheme 9). Compounds of Formula 17a when Lg2 is chlorine or bromine are also compounds of Formula Id (compounds of Formula I where X is halogen). Alternatively, compounds of Formula lb can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methanesulfonyl chloride, j9-toluenesulfonyl chloride, and trifluoromethanesulfonyl anhydride, to form the corresponding β-alkylsulfonate of Formula 17a. The reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine). Scheme 9
lb 17a
Lg2 = Cl, Br or -OS02V V = Cj-C6 alkyl, Cj-C6 haloalkyl or 4-CH3-C6H4 hal = Br, Cl or F
As illustrated in Scheme 10, sulfonyl compounds of Formula 17b can be prepared by oxidation of the corresponding thio compound of Formula 18 using well-known methods for the oxidation of sulfur (see Schrenk, K. In The Chemistry ofSulphones and Sulphoxides; Patai, S. et al., Eds.; Wiley: New York, 1988). Suitable oxidizing reagents include meta-chloroperoxybenzoic acid, hydrogen peroxide and Oxone® (KHSO5).
Scheme 10
18 17b
V = Cι-C6 alkyl, -Cg haloalkyl or 4-CH3-C6H4
Alternatively, halo-compounds of Formula 17c (compounds of Formula 17a wherein A = N, G = N, and W - O) can be prepared from hydrazides of Formula 19 as illustrated in Scheme 11. When R20 = C(=S)S(CrC4 alkyl), the compound of Formula 19 is treated with, for example, excess thionyl chloride, the product formed first is the ring-closed compound of Formula 20. This compound can be isolated or converted in situ to the compound of Formula 17c; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
Alternatively, when R20 = H or Me the hydrazide of Formula 19 is cyclized with phosgene to form the cyclic urea of Formula 17c wherein hal = Cl. This procedure is described in detail in J Org. Chem., (1989), 54, 1048. Scheme 11
17c hal = Cl, Br, I
The hydrazides of Formula 19 can be prepared as illustrated in Scheme 12. Condensation of the isocyanate of Formula 21 with the hydrazine of Formula H2NNR R20 in an inert solvent such as tetrahydrofuran affords the hydrazide.
Scheme 12
R20 = C(=S)S(C1-C4 alkyl), H or Me 3) Conjugate Addition/Cyclization Procedures
In addition to the methods disclosed above, compounds of Formula I wherein X = SRl and G = C (Formula le) can be prepared by treating a ketenedithioacetal of Formula 22 with an ambident nucleophile of Formula 6 (Scheme 13). The nucleophiles of Formula 6 are described above. Scheme 13
22 R = Cj-C4 alkyl le
Ketene dithioacetals of Formula 22a can be prepared by condensing arylacetic acid esters of Formula 9 with carbon disulfide in the presence of a suitable base, followed by reaction with two equivalents of an Rl -halide, such as iodomethane or propargyl bromide (Scheme 14).
Scheme 14
E^Z 1) CS2, base E-^Z
I
2) 2 equiv. R -hal
I
OR SR1 OR hal = Cl, Br or I R = Cι-C4 alkyl 22a
Rl is not C2-C alkylcarbonyl or C2-C4 alkoxycarbonyl
Compounds of Formula lc (compounds of Formula 1 wherein A = N, G = N) can be prepared by condensation of N-amino-ureas of Formula 23 with a carbonylating agent of Formula 24 (Scheme 15). The carbonylating agents of Formula 24 are carbonyl or thiocarbonyl transfer reagents such as phosgene, thiophosgene, diphosgene (ClC(=O)OCCl3), triphosgene (Cl3COC(=O)OCCl3), NN'-carbonyldiimidazole, NN'-thiocarbonyldiimidazole, and l,l'-carbonyldi(l,2,4-triazole). Alternatively, the compounds of Formula 24 can be alkyl chloroformates or dialkyl carbonates. Some of these carbonylating reactions may require the addition of a base to effect reaction. Appropriate bases include alkali metal alkoxides such as potassium tert-butoxide, inorganic bases such as sodium hydride and potassium carbonate, tertiary amines such as triethylamine and triethylenediamine, pyridine, or 1 ,8-diazabicyclo[5.4.0]undec-7- ene (DBU). Suitable solvents include polar aprotic solvents such as acetonitrile, dimethylformamide, or dimethyl sulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; or halocarbons such as dichloromethane or chloroform. The reaction temperature can vary between 0°C and 150°C and the reaction time can be from 1 to 72 hours depending on the choice of base, solvent, temperature, and substrates.
Scheme 15
23 lc
Tl and T2 are independently Cl, OCCl3, 0(Cι-C4 alkyl), 1-imidazolyl,
1,2,4-triazolyl Xl = OH or SH X = O or S
N-Amino-ureas of Formula 23 can be prepared as illustrated in Scheme 16. Treatment of an arylamine of Formula 25 with phosgene, thiophosgene, NN'-carbonyldiimidazole, or NN'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 26. A base can be added for reactions with phosgene or thiophosgene. Subsequent treatment of the iso(thio)cyanate with an R2-substituted hydrazine produces the N-amino-urea of Formula 23.
Scheme 16
CWC12 or
23
Compounds of Formula Id (compounds of Formula 1 wherein A = CR6, G = N, and χ = O) can be prepared by either method illustrated in Scheme 17. Ureas of Formula 27 are reacted with activated 2-halocarboxylic acid derivatives 28 such as 2-halocarboxylic acid chlorides, 2-halocarboxylic acid esters or 2-haloacyl imidazoles. The initial acylation on the arylamino nitrogen is followed by an intramolecular displacement of the 2-halo group to effect cyclization. Base may be added to accelerate the acylation and/or the subsequent cyclization. Suitable bases include triethylamine and sodium hydride. Alternatively, Formula Id compounds can be prepared by reaction of Formula 26 isocyanates with Formula 29 esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula Id compounds.
Scheme 17
R2NHCHR6C(0)0RJI
Id 29
^\, optional base
N <
W R = C]-C4 alkyl
26
The ureas of Formula 27 can be prepared by either of the methods illustrated in Scheme 18. The arylamine of Formula 25 can be contacted with an isocyanate or isothiocyanate of Formula R2N-C-W as described above. Alternatively, an isocyanate or isothiocyanate of Formula 26 can be condensed with an amine of Formula R2-NH2 to form the urea. The arylamine and iso(thio)cyanates of Formulae 25 and 26, respectively, are commercially available or prepared by well-known methods. For example, isothiocyanates can be prepared by methods described in J. Heterocycl. Chem., (1990), 27, 407. Isocyanates can be prepared as described in March, j. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 944, 1166 and also in Synthetic Communications, (1993), 25(3), 335 and references therein. For methods describing the preparation of arylamines of Formula 25 that are not commercially available, see M. S. Gibson In The Chemistry of the Amino Group; Patai, S., Ed.; Interscience Publishers, 1968; p 37 and Tetrahedron Lett. (1982), 23(7), 699 and references therein. Scheme 18
4) Thionation Procedures
Compounds of Formula lg, compounds of Formula I wherein W = S, can be prepared by treating compounds of Formula If (I wherein W = O) with thionating reagents such as P2S5 or Lawesson's reagent (2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulfide) as illustrated in Scheme 19 (see Bull. Soc. Chim. Belg., (1978), 87, 229; and Tetrahedron Lett., (1983), 24, 3815).
Scheme 19
If ^
5) Aryl Moiety (E-Y-Z) Synthesis Procedures
Compounds of Formula I (wherein Y is CH2O, CH2S, or CH2NR7) can be prepared by contacting halides of Formula 30 with various nucleophiles (Scheme 20). The appropriate alcohol or thiol is treated with a base, for example sodium hydride, to form the corresponding alkoxide or thioalkoxide which acts as the nucleophile. The halides of Formula 30 can be prepared from the alcohols of Formula 31 with halogenating reagents such as thionyl chloride. Scheme 20
30 Y= CH20, CH2S or CH NR7 I
Halogenation
31
The compounds of the present invention are prepared by combinations of reactions as illustrated in the Schemes 1 -20 in which Z is a moiety as described in the summary. Preparation of the compounds containing the radical Z as described in the summary, substituted with R9 (defined as any group attached to Z as depicted in each of the individual schemes) can be accomplished by one skilled in the art by the appropriate combination of reagents and reaction sequences for a particular Z-R9. Such reaction sequences can be developed based on known reactions available in the chemical art. For a general reference, see March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985) and references therein. See the following paragraphs for some examples of how R9 is defined in individual schemes, and the preparation of representative Z-R9 examples.
As shown in Scheme 21, compounds of Formula I can be prepared by reacting electrophiles of Formula 33 with anions of Formula 32 (generated by reacting compounds of Formula 32 with the appropriate base). Scheme 21
Also, compounds of Formula Ih can be prepared by reacting electrophiles such as those depicted by Formula 34 with nucleophiles such as those generated by reaction of compounds of Formula 35 with the appropriate base as shown in Scheme 22. Alternatively, compounds of Formula Ih can be prepared by reacting compounds of Formula 34 bearing leaving groups such as bromide or iodide with for example aryl boronic acids of Formula 36 in the presence of a palladium catalyst.
Scheme 22
R9-B(OH)2 36
34 Ih
Pd Catalyst Lg4 = Br, I
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula I. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula I.
One skilled in the art will also recognize that compounds of Formula I and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. *H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, m = multiplet and br s = broad singlet. J values indicate coupling constants and are reported in Hz.
EXAMPLE 1
Step A: Preparation of N-(2-methoxyphenyl>2,2-dimethylhvdrazinecarboxamide
To a stirred solution of 15.0 g of 2-methoxyphenyl isocyanate in 100 mL of toluene at 5 °C under nitrogen was slowly added 7.65 mL of 1,1-dimethylhydrazine in 10 mL toluene. The cooling bath was then removed and the reaction was allowed to stir for an additional 10 min, and was then concentrated under reduced pressure. The resulting material was dissolved in diethyl ether and concentrated again. A solid was obtained which was triturated with hexanes to afford 21 g of the title compound of Step A as a white solid. lH ΝMR (CDC13) δ 8.6 (br s,lH), 8.24 (m,lH), 6.95 (m,2H), 6.85 (m,lH), 5.35 (br s,lH), 3.89 (s,3H), 2.60 (s,6H).
Step B: Preparation of 5-chloro-2.4-dihydro-4-(2-methoxyphenyl)-2-methyl-3H- 2,4-triazol-3-one To a stirred solution of 21 g of the title compound of Step A in 800 mL of dichloromethane under nitrogen was added 29.85 g of triphosgene. The reaction was heated to reflux and allowed to reflux overnight, cooled, and then concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with distilled water, and then with saturated aqueous sodium chloride solution. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The solid was recrystallized from dichloromethane and the resulting solid was triturated with diethyl ether to afford 10 g of the title compound of Step B as a white solid melting at 152-154 °C. IH ΝMR (CDC13) δ 7.45 (t,lH),7.25 (d,lH), 7.05 (m,2H), 3.84 (s,3H), 3.53 (s,3H). Step C: Preparation of 5-chloro-2,4-dihvdro-4-(2-hvdroxyphenyl)-2-methyl-
3H-1.2.4-triazol-3-one The title compound of Step B (7.7 g) was dissolved in 65 mL of dichloromethane under nitrogen, cooled to -78 °C, and 34 mL of a 1.0 M boron tribromide solution in dichloromethane was then added over 0.5 h with stirring. After the addition, the cooling bath (dry ice/acetone) was kept in place for an additional 0.5 h and then the reaction was allowed to warm to room temperature. Ice was added to the reaction mixture which was then diluted with diethyl ether and the product was extracted using IN aqueous sodium hydroxide solution. The aqueous layer was acidified with 6N aqueous hydrochloric acid solution and extracted with dichloromethane and then with ethyl acetate. The organic layers were combined, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting residue was triturated with diethyl ether to afford 5.54 g of the title compound of Step C as a white solid. lΗ NMR (CDC13) δ 8.18 (s,lΗ), 7.11 (t,2H), 6.91 (t,lH), 6.76 (d,lH), 3.56 (s,3H). Step D: Preparation of 2,4-dihydro-4-(2-hvdroxyphenyl)-5-methoxy-2 -methyl-
3H-1.2.4-triazol-3-one To a stirred solution of 5.54 g of the title compound of Step C in 50 mL of methanol and 25 mL of 1,2 -dimethoxy ethane under nitrogen was added 18.6 mL of 30% sodium methoxide solution in methanol. The reaction was heated at reflux for 5.5 h and then cooled to room temperature. The mixture was diluted with diethyl ether and the product was extracted using IN aqueous sodium hydroxide solution. The aqueous layer was acidified with 6N aqueous hydrochloric acid solution and extracted with dichloromethane. The organic layer was dried (MgSO ), filtered, and then concentrated under reduced pressure. The resulting residue was triturated with diethyl ether to afford 3.85 g of the title compound of Step D as a white solid (85% pure). lΗ NMR (CDC13) δ 8.40 (br s,lΗ), 7.20 (m,2H), 7.03 (d,lH), 6.94 (t,lH), 4.00 (s,3H), 3.48 (s,3H).
Step E: Preparation of 4-[2-r(6-chloro-4-pyrimidinyl oxy]phenvn-2,4-dihydro-5- methoxy-2-methyl-3H-l,2,4-triazol-3-one 15 g of the intermediate from Step D above were added to a stirred suspension of potassium carbonate (10.3g) in 150 mL of acetonitrile at room temperature. The suspension stirred at room temperature for 1 h. Then 11.1 g of 4,6-dichloropyrimidine were added at room temperature and the reaction was allowed to stir at room temperature for 16 h. The solvent was then removed under reduced pressure and the crude residue was taken up in 150 mL of water. The resulting solids were then filtered, triturated twice with water and suction-dried overnight to yield 19.1g of the desired intermediate. NMR(CDC13; 300MHz): δ 3.36 (s,3H), 3.80 (s,3H), 6.93 (d,lH,J=0.9Hz), 7.13 (d,lH,J=8.2Hz), 7.29 (m,lH), 7.45 (m,lH), 8.58 (d,lH, J=7Hz). Step F: Preparation of 2,4-dihvdro-5-methoxy-2-methyl-4-r2-[r6-(2.4,6- trifluorophenoxyV4-pyrimidinyl1oxy]phenyl1-3H-L2.4-triazol-3-one 0.34 g 2,4,6-trifluorophenol were added to a stirred suspension of potassium carbonate (0.13 g) in 25 mL acetonitrile at room temperature. The resulting suspension was stirred at room temperature for 1 h. Then 0.5 g of the intermediate from Step E were added and the reaction was heated at reflux overnight. The reaction was cooled to room temperature and the solvent was removed under reduced pressure. The crude residue was then purified via column chromatography (1 :l/hexanes:ethyl acetate as eluent) to yield 0.34 g of the desired product. NMR(CDC13; 300MHz): δ 3.37 (s,3H), 3.77 (s,3H), 6.57 (d,lH, J=0.8Hz), 6.77-6.84 (m,2H), 7.35-7.55 (m,4H), 8.36 (d,lH,J=0.8Hz).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 18 can be prepared. The following abbreviations are used in the Tables which follow: Me = methyl, F = fluorine, Cl = chlorine, Br = bromine, I = iodine, NO2 = nitro, CN = cyano, Ph = phenyl and PhO = phenoxy.
Structure for Tables 1-4 Table 1
R3 = H
R9
2,3-diF-PhO 2,4-diF-PhO 2,5-diF-PhO 2,6-diF-PhO 2,3-diCl-PhO
2,5-diCl-PhO 2,6-diCl-PhO 2,3-diMe-PhO 2,4-diMe-PhO 2,5-diMe-PhO
2,6-diMe-PhO 2,3-diBr-PhO 2,4-diBr-PhO 2,5-diBr-PhO 2,6-diBr-PhO
2,3-diN02-PhO 2,4-diN02-Ph0 2,5-diN02-PhO 2,6-diN02-PhO 3,5-diF-PhO
3,5-diCl-PhO 3,5-diBr-PhO 3,5-diN02-Ph0 3,5-diMe-PhO Table 2
R3 = CH3
2,3-diF-PhO 2,4-diF-PhO 2,5-diF-PhO 2,6-diF-PhO 2,3-diCl-PhO
2,4-diCl-PhO 2,5-diCl-PhO 2,6-diCl-PhO 2,3-diMe-PhO 2,4-diMe-PhO
2,5-diMe-PhO 2,6-diMe-PhO 2,3-diBr-PhO 2,4-diBr-PhO 2,5-diBr-PhO
2,6-diBr-PhO 2,3-diN02-PhO 2,4-diN02-PhO 2,5-diN02-PhO 2,6-diN02-PhO
3,5-diF-PhO 3,5-diCl-PhO 3,5-diBr-PhO 3,5-diN02-PhO 3,5-diMe-PhO
Table 3
R3 = H
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Table 4
R3 = CH3
E?.
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-Ph0 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-Ph0
2,6-diF-4-Br-Ph0 2,6-diF-4-Cl-Ph0 2,6-diF-4-I-Ph0 2,6-diCl-4-Br-Ph0
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-Ph0 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-Ph0 2,6-diBr-4-CN-PhO 2,6-diBr-4-HC =C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Structure for Tables 5-8
Table 5
R3 = H
R
2,6-diF-PhO 2,3-diCl-PhO 2,4-diCl-PhO 2,6-diCl-PhO 2,3-diMe-PhO
2,4-diMe-PhO 2,3-diBr-PhO 2,4-diBr-PhO 2,5-diBr-PhO 2,6-diBr-PhO
2,3-diN02-PhO 2,4-diN02-PhO 2,5-diN02-PhO 3,5-diF-PhO 3,5-diCl-PhO
3,5-diBr-PhO 3,5-diN02-PhO 3,5-diMe-PhO
Table 6
R3 = CH?
2,3-diF-PhO 2,4-diF-PhO 2,5-diF-PhO 2,3-diCl-PhO 2,4-diCl-PhO
2,5-diCl-PhO 2,6-diCl-PhO 2,3-diMe-PhO 2,4-diMe-PhO 2,5-diMe-PhO
2,6-diMe-PhO 2,3-diBr-PhO 2,4-diBr-PhO 2,5-diBr-PhO 2,6-diBr-PhO
2,3-diN02-PhO 2,4-diN02-PhO 2,5-diN02-PhO 2,6-diN02-Ph0 3,5-diF-PhO
3,5-diCl-PhO 3,5-diBr-PhO 3,5-diN02-Ph0 3,5-diMe-PhO Table 7
R3 = H s
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Table 8
R3 = CH3
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO 2,4-diF-6-Me-PhO
2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO 2,4-diF-6-I-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Structure for Tables 9-12 Table 9
R3 = H
2,3,4-triF-Ph 2,3,5-triF-Ph 2,3,6-triF-Ph 2,4,5-triF-Ph
2,4,6-triF-Ph 2,3,4-triCl-Ph 2,3,5-triCl-Ph 2,3,6-triCl-Ph
2,4,5-triCl-Ph 2,4,6-triCl-Ph 2,3,4-triBr-Ph 2,3,5-triBr-Ph
2,3,6-triBr-Ph 2,4,5-triBr-Ph 2,4,6-triBr-Ph 2,3,4-triMe-Ph
2,3,5-triMe-Ph 2,3,6-triMe-Ph 2,4,5-triMe-Ph 2,4,6-triMe-Ph
2,6-diF-4-N02-Ph 2,6-diF-4-CN-Ph 2,6-diF-4-Me-Ph 2,6-diF-4-HC≡C-Ph
2,6-diF-4-Br-Ph 2,6-diF-4-Cl-Ph 2,6-diF-4-I-Ph 2,6-diCl-4-Br-Ph
2,6-diCl-4-CN-Ph 2,6-diCl-4-HC≡C-Ph 2,6-diCl-4-N02-Ph 2,6-diCl-4-I-Ph
2,6-diBr-4-CN-Ph 2,6-diBr-4-HC≡C-Ph 2,6-diBr-4-N02-Ph 2,6-diBr-4-I-Ph
2,6-diBr-4-Me-Ph 2,6-diMe-4-CN-Ph 2,6-diMe-4-HC≡C-Ph 2,6-diMe-4-N02-Ph
2,6-diMe-4-I-Ph 2,6-diMe-4-F-Ph 2,6-diMe-4-Cl-Ph 2,6-diMe-4-Br-Ph
2,4-diF-6-Me-Ph 2-Br-6-F-4-Me-Ph 2-Br-6-CN-4-F-Ph 2-Br-4-F-6-Me-Ph
2,4-diF-6-I-Ph 2,4-diF-6-CN-Ph 2,4-diF-6-N02-Ph 2,4-diF-6-HC≡C-Ph
2,4-diF-6-Br-Ph
Table 10
R3 = CH3 £
2,3,4-triF-Ph 2,3,5-triF-Ph 2,3,6-triF-Ph 2,4,5-triF-Ph
2,4,6-triF-Ph 2,3,4-triCl-Ph 2,3,5-triCl-Ph 2,3,6-triCl-Ph
2,4,5-triCl-Ph 2,4,6-triCl-Ph 2,3,4-triBr-Ph 2,3,5-triBr-Ph
2,3,6-triBr-Ph 2,4,5-triBrPh 2,4,6-triBr-Ph 2,3,4-triMe-Ph
2,3,5-triMe-Ph 2,3,6-triMe-Ph 2,4,5-triMe-Ph 2,4,6-triMe-Ph
2,6-diF-4-N02-Ph 2,6-diF-4-CN-Ph 2,6-diF-4-Me-Ph 2,6-diF-4-HC≡C-Ph
2,6-diF-4-Br-Ph 2,6-diF-4-Cl-Ph 2,6-diF-4-I-Ph 2,6-diCl-4-Br-Ph
2,6-diCl-4-CN-Ph 2,6-diCl-4-HC≡C-Ph 2,6-diCl-4-N02-Ph 2,6-diCl-4-I-Ph
2,6-diBr-4-CN-Ph 2,6-diBr-4-HC≡C-Ph 2,6-diBr-4-N02-Ph 2,6-diBr-4-I-Ph 2,6-diBr-4-Me-Ph 2,6-diMe-4-CN-Ph 2,6-diMe-4-HC≡C-Ph 2,6-diMe-4-N02-Ph
2,6-diMe-4-I-Ph 2,6-diMe-4-F-Ph 2,6-diMe-4-Cl-Ph 2,6-diMe-4-Br-Ph
2,4-diF-6-Me-Ph 2-Br-6-F-4-Me-Ph 2-Br-6-CN-4-F-Ph 2-Br-4-F-6-Me-Ph
2,4-diF-6-I-Ph 2,4-diF-6-CN-Ph 2,4-diF-6-N02-Ph 2,4-diF-6-HC≡C-Ph
2,4-diF-6-Br-Ph
Table 11
R3 = H
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HG≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO -Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Table 12
R3 = CH3
X?
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-Ph0 2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-Ph0
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-Ph0
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
< Structure for Tables 13-18
Table 13
Y = -0-. R3 = H
2,3,4-triF-Ph 2,3,5-triF-Ph 2,3,6-triF-Ph 2,4,5-triF-Ph
2,4,6-triF-Ph 2,3,4-triCl-Ph 2,3,5-triCl-Ph 2,3,6-triCl-Ph
2,4,5-triCl-Ph 2,4,6-triCl-Ph 2,3,4-triBr-Ph 2,3,5-triBr-Ph
2,3,6-triBr-Ph 2,4,5-triBr-Ph 2,4,6-triBr-Ph 2,3,4-triMe-Ph
2,3,5-triMe-Ph 2,3,6-triMe-Ph 2,4,5-triMe-Ph 2,4,6-triMe-Ph
2,6-diF-4-N02-Ph 2,6-diF-4-CN-Ph 2,6-diF-4-Me-Ph 2,6-diF-4-HC≡C-Ph
2,6-diF-4-Br-Ph 2,6-diF-4-Cl-Ph 2,6-diF-4-I-Ph 2,6-diCl-4-Br-Ph
2,6-diCl-4-CN-Ph 2,6-diCl-4-HC≡C-Ph 2,6-diCl-4-N02-Ph 2,6-diCl-4-I-Ph
2,6-diBr-4-CN-Ph 2,6-diBr-4-HC≡C-Ph 2,6-diBr-4-N02-Ph 2,6-diBr-4-I-Ph
2,6-diBr-4-Me-Ph 2,6-diMe-4-CN-Ph 2,6-diMe-4-HC≡C-Ph 2,6-diMe-4-N02-Ph
2,6-diMe-4-I-Ph 2,6-diMe-4-F-Ph 2,6-diMe-4-Cl-Ph 2,6-diMe-4-Br-Ph
2,4-diF-6-Me-Ph 2-Br-6-F-4-Me-Ph 2-Br-6-CN-4-F-Ph 2-Br-4-F-6-Me-Ph
2,4-diF-6-I-Ph 2,4-diF-6-CN-Ph 2,4-diF-6-N02-Ph 2,4-diF-6-HC≡C-Ph
2,4-diF-6-Br-Ph
Table 14
Y = -CH S-. R3 = H
2,3,4-triF-Ph 2,3,5-triF-Ph 2,3,6-triF-Ph 2,4,5-triF-Ph
2,4,6-triF-ph 2,3,4-tricι-Ph 2,3,5-trici-Ph 2,3,6-triCl-Ph
2,4,5-trici-Ph 2,4,6-tricι-Ph 2,3,4-triBr-Ph 2,3,5-triBr-Ph
2,3,6-triBr-Ph 2,4,5-triBr-Ph 2,4,6-triBr-Ph 2,3,4-triMe-Ph
2,3,5-triMe-Ph 2,3,6-triMe-Ph 2,4,5-triMe-Ph 2,4,6-triMe-Ph 2,6-diF-4-N02-Ph 2,6-diF-4-CN-Ph 2,6-diF-4-Me-Ph 2,6-diF-4-HC≡C-Ph
2,6-diF-4-Br-Ph 2,6-diF-4-Cl-Ph 2,6-diF-4-I-Ph 2,6-diCl-4-Br-Ph
2,6-diCl-4-CN-Ph 2,6-diCl-4-HC≡C-Ph 2,6-diCl-4-N02-Ph 2,6-diCl-4-I-Ph
2,6-diBr-4-CN-Ph 2,6-diBr-4-HC≡C-Ph 2,6-diBr-4-N02-Ph 2,6-diBr-4-I-Ph
2,6-diBr-4-Me-Ph 2,6-diMe-4-CN-Ph 2,6-diMe-4-HC≡C-Ph 2,6-diMe-4-N02-Ph
2,6-diMe-4-I-Ph 2,6-diMe-4-F-Ph 2,6-diMe-4-Cl-Ph 2,6-diMe-4-Br-Ph
2,4-diF-6-Me-Ph 2-Br-6-F-4-Me-Ph 2-Br-6-CN-4-F-Ph 2-Br-4-F-6-Me-Ph
2,4-diF-6-I-Ph 2,4-diF-6-CN-Ph 2,4-diF-6-N02-Ph 2,4-diF-6-HC≡C-Ph
2,4-diF-6-Br-Ph
Table 15
Y = -CH2S-. R3 = CH?
R£
2,3,4-triF-Ph 2,3,5-triF-Ph 2,3,6-triF-Ph 2,4,5-triF-Ph
2,4,6-triF-Ph 2,3,4-triCl-Ph 2,3,5-triCl-Ph 2,3,6-triCl-Ph
2,4,5-triCl-Ph 2,4,6-triCl-Ph 2,3,4-triBr-Ph 2,3,5-triBr-Ph
2,3,6-triBr-Ph 2,4,5-triBr-Ph 2,4,6-triBr-Ph 2,3,4-triMe-Ph
2,3,5-triMe-Ph 2,3,6-triMe-Ph 2,4,5-triMe-Ph 2,4,6-triMe-Ph
2,6-diF-4-N02-Ph 2,6-diF-4-CN-Ph 2,6-diF-4-Me-Ph 2,6-diF-4-HC≡C-Ph
2,6-diF-4-Br-Ph 2,6-diF-4-Cl-Ph 2,6-diF-4-I-Ph 2,6-diCl-4-Br-Ph
2,6-diCl-4-CN-Ph 2,6-diCl-4-HC≡C-Ph 2,6-diCl-4-N02-Ph 2,6-diCl-4-I-Ph
2,6-diBr-4-CN-Ph 2,6-diBr-4-HC≡C-Ph 2,6-diBr-4-N02-Ph 2,6-diBr-4-I-Ph
2,6-diBr-4-Me-Ph 2,6-diMe-4-CN-Ph 2,6-diMe-4-HC≡C-Ph 2,6-diMe-4-N02-Ph
2,6-diMe-4-I-Ph 2,6-diMe-4-F-Ph 2,6-diMe-4-Cl-Ph 2,6-diMe-4-Br-Ph
2,4-diF-6-Me-Ph 2-Br-6-F-4-Me-Ph 2-Br-6-CN-4-F-Ph 2-Br-4-F-6-Me-Ph
2,4-diF-6-I-Ph 2,4-diF-6-CN-Ph 2,4-diF-6-N02-Ph 2,4-diF-6-HC≡C-Ph
2,4-diF-6-Br-Ph
Table 16
Y = -0-. R3 = H
R9
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO 2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Table 17
Y = -CH2S-, R3 = H
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HG≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO
2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-PhO
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-PhO
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-PhO
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-PhO
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Table 18
Y = -CH2S-. R3 = CH?
2,3,4-triF-PhO 2,3,5-triF-PhO 2,3,6-triF-PhO 2,4,5-triF-PhO
2,4,6-triF-PhO 2,3,4-triCl-PhO 2,3,5-triCl-PhO 2,3,6-triCl-PhO
2,4,5-triCl-PhO 2,4,6-triCl-PhO 2,3,4-triBr-PhO 2,3,5-triBr-PhO
2,3,6-triBr-PhO 2,4,5-triBr-PhO 2,4,6-triBr-PhO 2,3,4-triMe-PhO
2,3,5-triMe-PhO 2,3,6-triMe-PhO 2,4,5-triMe-PhO 2,4,6-triMe-PhO
2,6-diF-4-N02-PhO 2,6-diF-4-CN-PhO 2,6-diF-4-Me-PhO 2,6-diF-4-HC≡C-PhO
2,6-diF-4-Br-PhO 2,6-diF-4-Cl-PhO 2,6-diF-4-I-PhO 2,6-diCl-4-Br-PhO
2,6-diCl-4-CN-PhO 2,6-diCl-4-HC≡C-PhO 2,6-diCl-4-N02-PhO 2,6-diCl-4-I-PhO
2,6-diBr-4-CN-PhO 2,6-diBr-4-HC≡C-PhO 2,6-diBr-4-N02-PhO 2,6-diBr-4-I-PhO 2,6-diBr-4-Me-PhO 2,6-diMe-4-CN-PhO 2,6-diMe-4-HC≡C-PhO 2,6-diMe-4-N02-Ph0
2,6-diMe-4-I-PhO 2,6-diMe-4-F-PhO 2,6-diMe-4-Cl-PhO 2,6-diMe-4-Br-Ph0
2,4-diF-6-Me-PhO 2-Br-6-F-4-Me-PhO 2-Br-6-CN-4-F-PhO 2-Br-4-F-6-Me-Ph0
2,4-diF-6-I-PhO 2,4-diF-6-CN-PhO 2,4-diF-6-N02-PhO 2,4-diF-6-HC≡C-Ph0
2,4-diF-6-Br-PhO 2,3,5,6-tetraF-PhO 2,3,4,5-tetraF-PhO 2,3,4,5,6-pentaF-PhO
Formulation/Utility
Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispersible and Water-soluble 5-90 0-94 1-15 Granules, Tablets and Powders.
Suspensions, Emulsions, Solutions 5-50 40-95 0-15 (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.01-99 5-99.99 0-15
High Strength Compositions 90-99 0-10 0-2 Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity. Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, NN-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylforrnamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry 's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566. For further information regarding the art of formulation, see U.S. 3,235,361,
Col. 6, line 16 through Col. 7, line 19 and Examples 10-41 ; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-D.
Example A Wettable Powder
Compound 8 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
Example B Granule
Compound 9 10.0% attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%.
Example C
Extruded Pellet
Compound 8 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium magnesium bentonite 59.0%.
Example D
Emulsifiable Concentrate
Compound 3 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops. These pathogens include Plasmopara viticola, Phytophthora infestans, Peronospora tabacina, Pseudoperonospora cubensis, Pythium aphanidermatum, Alternaria brassicae, Septoria nodorum, Septoria tritici, Cercosporidium personatum, Cercospora arachidicola, Pseudocercosporella herpotrichoides, Cercospora beticola, Botrytis cinerea, Monilinia fructicola, Pyricularia oryzae, Podosphaera leucotricha, Venturia inaequalis, Erysiphe graminis, Uncinula necatur, Puccinia recondita, Puccinia graminis, Hemileia vastatrix, Puccinia striiformis, Puccinia arachidis, Rhizoctonia solani, Sphaerotheca fuliginea, Fusarium oxysporum, Verticillium dahliae, Pythium aphanidermatum, Phytophthora megasperma, Sclerotinia sclerotiorum, Sclerotium rolfsii, Erysiphe polygon!, Pyrenophora teres, Gaeumannomyces graminis, Rynchosporium secalis, Fusarium roseum, Bremia lactucae and other generea and species closely related to these pathogens. Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of such agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorfenapyr, chlorpyrifos. chlorpyrifos-methyl, cyfluthrin, beta-cyfiuthrin, cyhalothrin, lambda-cyhalothrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, esfenvalerate, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methyl 7-chloro- 2,5-dihydro-2-[[N-(methoxycarbonyl)-N-[4-
(trifluoromethoxy)phenyl]amino]carbonyl]indeno[l,2-e][l,3,4]oxadiazine-4a(3H)- carboxylate (DPX-JW062), monocrotophos, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, rotenone, sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiodicarb, tralomethrin, trichlorfon and triflumuron; fungicides such as azoxystrobin, benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, carpropamid, chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole, cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph, diniconazole, diniconazole-M, dodine, edifenphos, epoxiconazole (BAS 480F), famoxadone, fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimorph, fluazinam, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl, mancozeb, maneb, mepronil, metalaxyl, metconazole, S-methyl 7-benzothiazolecarbothioate (CGA 245704), myclobutanil, neo-asozin (ferric methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propiconazole, pyrifenox, pyroquilon, quinoxyfen, spiroxamine (KWG4168), sulfur, tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon, triadimenol, tricyclazole, triticonazole, validamycin and vinclozolin; nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi. In certain instances, combinations with other fungicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management. Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group azoxystrobin, benomyl, carbendazim, carpropamid, copper salts, cymoxanil, cyproconazole, cyprodinil, dimethomorph, epoxiconazole, famoxadone, fenpropidin, fenpropimorph, flusilazole, flutolanil, fosetyl-aluminum, kasugamycin, kresoxim-methyl, mancozeb, metalaxyl and oxadixyl, pencycuron, probenazole, propiconazole, pyroquilon, tricyclazole, validamycin. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-D) are selected from the group: compound 8 and azoxystrobin, compound 8 and benomyl, compound 8 and carbendazim, compound 8 and carpropamid, compound 8 and copper salts, compound 8 and cymoxanil, compound 8 and cyproconazole, compound 8 and cyprodinil, compound 8 and epoxiconazole, compound 8 and famoxadone, compound 8 and fenpropidin, compound 8 and fenpropimorph, compound 8 and flusilazole, compound 8 and flutolanil, compound 8 and fosetyl-aluminum, compound 8 and kasugamycin, compound 8 and kresoxim-methyl, compound 8 and mancozeb, compound 8 and metalaxyl, compound 8 and oxadixyl, compound 8 and pencycuron, compound 8 and probenazole, compound 8 and propiconazole, compound 8 and pyroquilon, compound 8 and tricyclazole, compound 8 and validamycin, compound 9 and azoxystrobin, compound 9 and benomyl, compound 9 and carbendazim, compound 9 and carpropamid, compound 9 and copper salts, compound 9 and cymoxanil, compound 9 and cyproconazole, compound 9 and cyprodinil, compound 9 and epoxiconazole, compound 9 and famoxadone, compound 9 and fenpropidin, compound 9 and fenpropimorph, compound 9 and flusilazole, compound 9 and flutolanil, compound 9 and fosetyl-aluminum, compound 9 and kasugamycin, compound 9 and kresoxim-methyl, compound 9 and mancozeb, compound 9 and metalaxyl, compound 9 and oxadixyl, compound 9 and pencycuron, compound 9 and probenazole, compound 9 and propiconazole, compound 9 and pyroquilon, compound 9 and tricyclazole, compound 9 and validamycin, compound 3 and azoxystrobin, compound 3 and benomyl, compound 3 and carbendazim, compound 3 and carpropamid, compound 3 and copper salts, compound 3 and cymoxanil, compound 3 and cyproconazole, compound 3 and cyprodinil, compound 3 and epoxiconazole, compound 3 and famoxadone, compound 3 and fenpropidin, compound 3 and fenpropimorph, compound 3 and flusilazole, compound 3 and flutolanil, compound 3 and fosetyl-aluminum, compound 3 and kasugamycin, compound 3 and kresoxim-methyl, compound 3 and mancozeb, compound 3 and metalaxyl, compound 3 and oxadixyl, compound 3 and pencycuron, compound 3 and probenazole, compound 3 and propiconazole, compound 3 and pyroquilon, compound 3 and tricyclazole, and compound 3 and validamycin.
Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to the seed to protect the seed and seedling.
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 10 g per kilogram of seed.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-E for compound descriptions. The following abbreviations are used in the Index Tables which follow: F = fluorine, Cl = chlorine, Br = bromine, Me = methyl, Et = ethyl, PhO = phenoxy and MeO = methoxy. The abbreviation "Ex. No." stands for "Example Number" and is followed by a number indicating in which example the compound is prepared. The abbreviation "Cmpd No." stands for Compound Number and the abbreviation "mp" stands for melting point. INDEX TABLE A
Cmpd No. Structure mp °C
*See Index Table E for *H NMR data INDEX TABLE B
Cmpd No.
CEx. No.) E3. R? RlO mp °C
3 Me 2,6-diF-PhO H 164-166
4 Me 2,4-diF-PhO H 148-149
5 Me 2,3-diF-PhO H 133-135
6 Me 2,6-diCl-PhO H 140-143
7 H 2,4-diF-PhO H oil*
8 (Ex. 1) H 2,4,6-triF-PhO H 125-126
9 Me 2,4,6-triF-PhO H 178-180
10 H 2,5-diF-PhO H oil*
1 1 Me 2,5-diF-PhO H 1 13-115
12 Me 2,6-diMe-PhO H 122-123
13 Me 2,4,6-triMe-PhO H 123-124
14 H 2,4,6-triMe-PhO H 154-156
15 H 2,3,4-triF-PhO H 120-122
16 Me 2,3,4-triF-PhO H 98-100
17 H 2,3,5-triF-PhO H 161-163
18 Me 2,3,5-triF-PhO H 164-166
19 Me 2,3,6-triF-PhO H 168-169
20 H 2,4,5-triF-PhO H 122-124
21 Me 2,4,5-triF-PhO H 178-180
22 H 2,6-diCl-4-F-PhO H 212-213
23 H 2,6-diBr-4-F-PhO H 208-210
24 H 2,3,6-triF-PhO H 142-144
25 H 2,3,5,6-tetraF-PhO H 138-140
26 Me 2,3,5,6-tetraF-PhO H 188-191
27 Me 2,4,6-triF-PhO 5-Me 218-220
28 H 2,4,6-triF-PhO 5-Et 128-130
29 Me 2,4,6-triF-PhO 5-Et 153-154 Cmpd No.
(Ex. No.) s s2 __ mp °C
30 H 2,4,6-triF-PhO 2-Me 144-145
31 Me 2,6-diF-4-Br-PhO H 195-198
44 Me 2,4,6-triF-PhO 2-Me 115-118
45 Me 2-Cl-4,6-diF-PhO H 179-181
46 Me 4-I-2,6-diF-PhO H 180-184
47 H 2-Cl-4,6-diF-PhO H 178-179
48 Me 4-Cl-2,6-diF-PhO H 196
49 H 4-Cl-2,6-diF-PhO H 165
50 Me 2-I-4,6-diF-PhO H 132-135
51 Me 2_F-4-Cl-PhO H 156-157
52 Me 2-Cl-5-Me-PhO H 139-141
53 Me 2-F-4-Br-PhO H 150-153
54 Me 2-F-4-Me-PhO H 136-138
55 Me 3,5-diCF3-PhO H 133-135
56 Me 2-F-5-CF3-PhO H 168-171
57 Me 2,4,6-triF-PhO SMe 158-160
58 Me 2,6-diF-PhCH2 H 138-140
59 Me 2-Cl-4-F-PhO H 144-146
60 Me 2,6-diF-4-(CH2=CH)-PhO H 130-132
*See Index Table E for lH NMR data.
INDEX TABLE C
Cmpd No. si R9 RlO mp °C
32 H 3,5-diCl-PhO MeO oil*
33 H 2,4-diF-PhO MeO 50-61
34 H 2,6-diF-PhO MeO 49-57
35 H 2,6-diCl-PhO H 49-56 36 H 2,4-diF-PhO H 52-57
37 H 2,6-diF-PhO H 163-167
38 CH3 2,4-diF-PhO H 56-61
39 CH3 2,6-diF-PhO H 52-59
40 H 3,5-diCl-Ph H 214-217
41 CH3 3,5-diCl-Ph H 187-199
42 CH3 3,5-diCF3-Ph H 56-66
43 CH3 3-F-4-CH3-Ph H 188-194
*See Index Table E for ]H NMR data.
INDEX TABLE D
Cmpd No. R3 Y £ mp °C
2 H 0 2,4-diF-Ph oil*
61 CH3 O 3,4-diCl-Ph oil*
64 H CH2S 3,4-diMe-Ph 61-72
65 H CH2S 2,4-diCl-Ph 56-62
66 H CH2S 2,4-diF-Ph oil*
*See Index Table E for !H NMR data.
INDEX TABLE E
Cmpd. No. *H NMR Data (CDC1 solution unless indicated otherwise)a 1 δ 2.26 (s,3H), 3.38 (s,3H), 3.83 (s,3H), 6.6-6.7 (m,3H), 6.8-7.0 (m,3H),
7.0-7.1 (m,2H), 7.2-7.3 (m,2H)
2 δ 3.29 (s,3H), 3.79 (s,3H), 7.01 (m,lH), 7.50 (m,5H), 8.71 (m,lH), 9.59 (s,lH) 7 δ 3.37 (s,3H), 3.78 (s,3H), 6.49 (d,lH, J=0.6), 6.94-7.00 (m,2H), 7.20 (m,lH),
7.30-7.52 (m,4H), 8.38 (s,lH)
10 δ 3.37 (s,3H), 3.78 (s,3H), 6.50 (d,lH, J=0.8), 6.9-7.0 (m,2H), 7.1-7.2 (m, lH),
7.30-7.60 (m,4H), 8.39 (d,lH, J=0.6) 32 δ 3.36 (s,3H), 3.87 (s,3H), 3.96 (s,3H), 7.10-7.50 (m,7H)
61 δ 2.30 (s,3H), 3.30 (s,3H), 3.81 (s,3H), 7.28 (m,2H), 7.45 (t,lH,J=8.0)
66 δ 3.40 (s,3H),3.94 (s,3H), 7.02 (m,2H), 7.40 (m,3H),7.64 (m,lH), 8.22(m,lH),
9.45 (s,lH) a H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (m)-multiplet. J values indicate coupling constants and are reported in Hz.
BIOLOGICAL EXAMPLES OF THE INVENTION Test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests. Spraying these
200 ppm test suspensions to the point of run-off on the test plants is the equivalent of a rate of 500 g/ha.
TEST A The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20°C for 7 days, after which disease ratings were made.
TEST B The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.
TEST C The test suspension was sprayed to the point of run-off on rice seedlings. The following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 h, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made. TEST D
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made. TEST E The test suspension was sprayed to the point of run-off on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20°C for 24 h, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 h, after which disease ratings were made.
TEST F The test suspension was sprayed to the point of run-off on cucumber seedlings. The following day the seedlings were inoculated with a spore suspension oϊBotrytis cinerea (the causal agent of gray mold on many crops) and incubated in a saturated atmosphere at 20°C for 48 h, and moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.
Results for Tests A-F are given in Table A. In the table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results. ND indicates disease control not determined due to phytotoxicity.
Table A
Cmpd No. Test A TestB TestC TestD TestE TestF
1 100 100 99 100a 100* 0
2 92 99 94 100a 100* 0
3 100 100 86 100 100* 0
4 99 99 86 0 100* 0
5 - 100 82** 75 100* 0
6 98 100 94 96a 100* 0
7 98 100 91 96a 100* 98
8 100 100 53 100a 95* 0
9 100 100 86 100a 100* 0
10 100 100 32 92 77* 0
11 100 100 86 100a 100* 0
12 98 100 94 97a 100* 0
13 63 100 91 92 100* 0
14 79 99 86 81 97* 0
15 100 99 94 100 59* 10
16 100 100 97 100 100* 0
17 98 100 74 81 11* 70
18 100 100 94 100 100* 0
19 100 100 99 100 100* 0 Cmpd No. Test A TestB TestC TestD TestE TestF
20 98 99 86 100 44* 0
21 100 100 97 100 100* 0
22 99 97 53 97 97* 0
23 77 97 74 - 100* 0
24 100 100 91 76 68* 0
25 99 100 32 0 1* 0
26 99 100 32 100a 100* 0
27 98 97 0 91 - 0
28 92 0 0 57 - 0
29 92 86 0 57 - 0
30 100 100 74 26 13* 0
31 100 100 53 100 100* 0
32 9* 15* 0* - 42* -
33 0 85 0 20 4* 0
34 92 93 53 20 o* 0
35 82 86 0 22 13* 0
36 92 94 0 21 7* 0
37 86 97 0 21 7* 0
38 97 97 52 92 1* 0
39 97 94 73 61 1* 0
40 96 99 53 100a 97* 94
41 98 97 53 ND 100* 0
42 100 100 97 85 27* 0
43 86 100 0 ND 100* 69
44 98 100 94 92 100* 0
45 100 100 91 97 100* 0
46 100 100 53 92 100* 0
47 98** 100** 74** 75** 100* 0
48 99 100 94 100 98* 0
49 100 100 94 100 100* 0
50 94 100 99 100 100* 0
51 95 99 99 0 100* 0
52 95 99 94 90 100* 0
53 98 99 94 ND 100* 0
54 95 99 74 0 98* 48
55 100 100 99 96 - 98
57 86 100 91 0 98* 73 Cmpd No. Test A TestB TestC TestD TestE TestF
58 100 99 94 100 88* 0
59 98 99 97 ND 100* 0
60 98 99 86 100 100* 97
61 10* 98* 29* - 100* -
62 98 100 99 0 90* 94
63 100 100 91 0 89* 82
64 61 94 74 45 26* 0
65 0 97 0 62 64* 0
66 91 94 74 0 24* 0
67 22 97 53a 56 1* 3 a Phytotoxicity rating of 20%.
* Tested at 10] ppm.
** Tested at 4C Ippm l.

Claims

CLAIMS What is claimed is:
1. A compound selected from Formula I, N-oxides and agriculturally suitable salts thereof,
wherein
E is 1 ,2-phenylene optionally substituted with R3 or both R3 and R4; A is O, S, Ν, ΝR5 or CR6; G is C or Ν; provided that when G is C, then A is O, S or ΝR5 and the floating double bond is attached to G; and when G is Ν, then A is Ν or CR6 and the floating double bond is attached to A; W is O, S, ΝH, Ν(CrC6 alkyl) or NO(CrC6 alkyl); X is OR1, S OjmR1 or halogen; R1 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C -Cg alkynyl, C2-C$ haloalkynyl, C3-C6 cycloalkyl, C2-C alkylcarbonyl or C2-C4 alkoxycarbonyl; R2 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C2-C6 alkynyl, C2-C£ haloalkynyl, C3-Cg cycloalkyl, C2-C4 alkylcarbonyl, C2-C alkoxycarbonyl, hydroxy, Cj-C alkoxy or acetyloxy;
R3 and R4 are each independently halogen, cyano, nitro, hydroxy, C C6 alkyl, Ct-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C - haloalkynyl, CrC6 alkoxy, CrC6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, CrC6 alkylthio, CrC6 alkylsulfinyl, CrC6 alkylsulfonyl, formyl, C2-C6 alkylcarbonyl, C -C6 alkoxycarbonyl,
NH2C(O), (CrC4 alkyl)NHC(O), (CrC4 alkyl)2NC(O), (R13)3Si, (R13)3Ge, (R13)3Si-C≡C, phenyl, phenylethynyl, benzoyl or phenylsulfonyl, each phenyl, phenylethynyl, benzoyl and phenylsulfonyl substituted with R8 and optionally substituted with one or more R10; or when R3 and R4 are attached to adjacent atoms, R3 and R4 can be taken together as C3-C5 alkylene, C3-C5 haloalkylene, C3-C5 alkenylene or C3-C5 haloalkenylene, each optionally substituted with 1-2 CrC3 alkyl; R5 is H, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl,
C2-C6 alkynyl, C -C6 haloalkynyl, C3-C6 cycloalkyl, C2-C alkylcarbonyl or C2-C alkoxycarbonyl; Y is -O-, -S(O)n-, -NR7-, -CH2O-, -CH2NR7-, -CH2S(O)n- or a direct bond; and the directionality of the Y linkage is defined such that the moiety depicted on the left side of the linkage is bonded to E and the moiety on the right side of the linkage is bonded to Z; Z is phenyl, pyrimidinyl or triazinyl, each substituted with R9 and optionally substituted with one or more R10; R6 is H, halogen, CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2- alkynyl, C2-Cg haloalkynyl or C3-Cg cycloalkyl; R7 is H, Ci-C3 alkyl or C3-C6 cycloalkyl; or R7 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C J-C4 alkyl, CJ-C4 haloalkyl, CJ-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; R8 is H, 1 -2 halogen, C λ -C6 alkyl, C } -C6 haloalkyl, C { -C6 alkoxy,
Cj-Cβ haloalkoxy, C2-C6 alkenyl, C2-C6 haloalkenyl, C -C6 alkynyl, CrC6 alkylthio, CrC6 haloalkylthio, CrC6 alkylsulfinyl, Cj-Cg alkylsulfonyl, C3-C6 cycloalkyl, C3-C6 alkenyloxy, CO2(CrC6 alkyl), NH(CrC6 alkyl), N(CrC6 alkyl)2, cyano, nitro, SiR14R15R16 or GeR14R15R16;
R9 is phenyl, phenylmethyl, phenoxy, benzoyl, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with one or more R1 1 and with one R12; each R10 is independently halogen, C1-C4 alkyl, Cj-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, nitro or cyano; each R11 is independently halogen, cyano, nitro, Cj-C4 alkyl, Cj-C4 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, Cj-C4 alkylthio, Cj-C4 alkylsulfinyl or C1-C4 alkylsulfonyl; R12 is halogen, CrC4 alkyl, CrC4 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 alkylthioalkyl, C3-C6 alkoxyalkynyl, C7-C10 tetrahydropyranyloxyalkynyl, benzyloxymethyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 alkenyloxy, C3-Cg haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C5-C9 trialkylsilylalkoxyalkoxy, C2-C6 alkylthioalkoxy, C1-C4 alkylthio, CrC4 haloalkylthio, CrC4 alkylsulfinyl, CrC4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C3-Cg alkenylthio, C3-C6 haloalkenylthio, C2-Cg alkylthioalkylthio, nitro, cyano, thiocyanato, hydroxy, N(Rl7)2, SF5, Si(R13)3, Ge(Rl )3, (Rl3)3Si-C≡C-, OSi(R13)3, OGe(Rl3)3, C(=O)R17, C(=S)Rl7, C(=O)OR*7, C(=S)OR17, C(=O)SR17, C(=S)SR17, C(=O)N(R1 )2, C(=S)N(Rl7)2, OC(=O)R17, OC(=S)R17, SC(=O)Rl7, SC(=S)R17, N(R17)C(=O)Rl , N(R17)C(=S)R17, OC(=O)OR18, OC(=O)SR18, OC(=O)N(R17)2, SC(=O)OR18, SC(=O)SR18, S(O)2ORl7, S(O)2N(R1 )2, OS(O)2R18 or N(R17)S(O)2R18; or Rl2 is phenyl, phenoxy, benzyl, benzyloxy, phenylsulfonyl, phenylethynyl or pyridinylethynyl, each optionally substituted on the aromatic ring with halogen, Cj-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; each R13 is independently C1-C4 alkyl, C]-C4 haloalkyl, C2-C4 alkenyl,
C1-C4 alkoxy or phenyl; R14, R15, and R16 are each independently CrC6 alkyl, C2-C6 alkenyl,
CJ-C4 alkoxy or phenyl; each R17 is independently H, Cj-Cs alkyl, Cj-Cg haloalkyl, C2-Cg alkenyl, C2-Cg haloalkenyl, C2-Cg alkynyl, C2-Cg haloalkynyl, C3-Cg cycloalkyl, phenyl or benzyl, each phenyl and benzyl optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, Cj-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; R18 is CrC6 alkyl, CrC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-Cg alkynyl, C2-Cg haloalkynyl or C3-Cg cycloalkyl; or R18 is phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C]-C alkyl, Cj-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; and m and n are each independently 0, 1 or 2; provided that i) when E is 1 ,2-phenylene, A is N, G is N, W is O, X is OMe, R2 is CH3 and Z substituted with R9 is 6- [3 , 5 -bis(trifluoromethyl)phenyl] -4-pyrimidiny 1 , 6-(2,4-dichlorophenyl)-4-pyrimidinyl, 4-[3,5-bis(trifluoromethyl)phenyl]-2-pyrimidinyl,
2- [3 , 5 -bis(trifluoromethy l)phenyl] -4-pyrimidiny 1, 3 - [2-(methoxycarbonyl)-6-nitrophenoxy]phenyl, 3 -(2,6-dicyanophenoxy)phenyl, 3-(6-chloro-5-nitro-4-pyrimidinyloxy)phenyl, 3-[4-nitro-2-(trifluoromethyl)phenoxy]phenyl,
3 -(2,6-dimethylphenoxy)phenyl, 3-(2-cyano-3-fluorophenoxy)phenyl, 3-(2-cyano-6-fluorophenoxy)phenyl, 3-(2,6-dinitrophenoxy)phenyl, 3-(2,5-difluorophenoxy)phenyl, 3-(2,5-dimethylphenoxy)phenyl, 3-(2,5-dichlorophenoxy)phenyl, 3-(3,5-dichlorophenoxy)phenyl, 3-(2,3-difluorophenoxy)phenyl, 3-(2,4-difluorophenoxy)phenyl, 3 ',5 '-bis(trifluoromethyl) [1,1 '-biphenyl] -3 -yl or 3',5'-dichloro-[l, -biphenyl]-3-yl, then Y is other than -O-; and ii) when E is 1 ,2-phenylene, A is N, G is N, W is O, X is OMe, R2 is CH3 and Z substituted with R9 is
3-(3,5-dichlorophenyl)-5-methyl-l,2,4-triazin-6-yl, then Y is other than -CH2S-; and iii) when A is N, G is N, W is O, X is OMe and EYZ is [2-[[6-[3,5- bis(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-6-methylphenyl] or [2-[3-(2,6-difluorophenoxy)phenoxy]-6-methylphenyl], then R2 is other than CH3.
2. A compound of Claim 1 wherein: A is O, S or NR5;
G is C;
R9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl or pyrimidinyloxy, each substituted on the aromatic ring with two or more R1 ! and with one R12; and
R12 is halogen, C1-C4 alkyl, Cj-C haloalkyl, C1-C4 alkoxy, CrC haloalkoxy, Cι-C alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, CJ-C4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or N(R17)2; or R12 is phenyl optionally substituted with halogen, CJ-C4 alkyl,
C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano.
3. A compound of Claim 2 wherein:
A is O;
W is O; X is OR1;
R1 is CH3;
R2 is CH3;
R3 and R4 are each independently halogen or Cι-C3 alkyl; and
Y is O, CH2O or CH2S(O)n.
4. The compound of Claim 1 which is selected from the group:
A is N or CR6;
G is N; R9 is phenyl, phenylmethyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl; or pyrimidinyloxy each substituted on the aromatic ring with two or more R1 1 and with one Rl2; and R12 is halogen, CrC4 alkyl, CrC4 haloalkyl, CrC4 alkoxy, CrC4 haloalkoxy, Cj-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, Cj-C4 haloalkylsulfinyl, Cj-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, nitro, cyano, thiocyanato, hydroxy or N(R17)2; or R12 is phenyl optionally substituted with halogen, C1-C4 alkyl, j-C4 haloalkyl, C1-C4 alkoxy, Cj-C4 haloalkoxy, nitro or cyano.
5. The compound of Claim 4 which is selected from the group:
A is N; W is O; X is OR1; RUs CH^
R2 is CH3;
R3 and R4 are each independently halogen or Cj-C3 alkyl; and Y is O, CH2O or CH2S(O)n.
6. A fungicidal composition comprising a fungicidally effective amount of a compound of Claim 1 and at least one of a surfactant, a solid diluent or a liquid diluent.
7. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
EP97945385A 1996-11-01 1997-10-01 Fungicidal cyclic amides Withdrawn EP0937051A1 (en)

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US7122544B2 (en) 2000-12-06 2006-10-17 Signal Pharmaceuticals, Llc Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto
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