WO1996036229A1 - Fungicidal cyclic amides - Google Patents

Fungicidal cyclic amides Download PDF

Info

Publication number
WO1996036229A1
WO1996036229A1 PCT/US1996/006507 US9606507W WO9636229A1 WO 1996036229 A1 WO1996036229 A1 WO 1996036229A1 US 9606507 W US9606507 W US 9606507W WO 9636229 A1 WO9636229 A1 WO 9636229A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
chr
diyl
optionally substituted
phenyl
Prior art date
Application number
PCT/US1996/006507
Other languages
French (fr)
Inventor
Tariq Arthur Andrea
Richard James Brown
Reed Aaron Coats
Dilon Jancey Daniel
Deborah Ann Frasier
Michael Henry Howard, Jr.
Gerard Michael Koether
Morris Padgett Rorer
Michael Paul Walker
Simon Lingqi Xu
Thomas Paul Selby
Original Assignee
E.I. Du Pont De Nemours And Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by E.I. Du Pont De Nemours And Company filed Critical E.I. Du Pont De Nemours And Company
Publication of WO1996036229A1 publication Critical patent/WO1996036229A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N43/713—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with four or more nitrogen atoms as the only ring hetero 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/24—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing the groups, or; Thio analogues thereof
    • 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
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • 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
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A01N55/02—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing metal atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/28—Two oxygen or sulfur atoms
    • C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
    • C07D231/32—Oxygen atoms
    • 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
    • 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
    • C07D249/14—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/30—Germanium compounds

Definitions

  • This invention relates to certain cyclic amides, their N-oxides, agriculturally suitable salts and compositions, and methods of their use as fungicides.
  • WO 85/01939 discloses tetrazolones of Formula i as herbicides:
  • W is O or S
  • R is alkyl, haloalkyl, alkoxyalkyl, alkylthioalkyl, cyanoalkyl, haloalkoxy alkyl,
  • X 1 and X 2 are F, Cl, or Br and the other is F, Cl, Br, alkyl, or haloalkyl; or when X 1 is F, Cl, or Br, X 2 may be selected from the substituents above and nitro; and
  • Z is H; F; Cl; Br; cyano; nitro; alkyl; alkyl substituted with F, Cl, Br, or alkoxy; and alkynyl.
  • EP 679,643 and J. Heterocyclic Chem. (1988), 25, 1307-1310 teach various heterocyclic compounds including 1,2,4-triazolinones, pyrazolinones, tetrazolinones and tetrazoles.
  • the cyclic amides of the present invention are not disclosed in any of these publications.
  • 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:
  • G is selected from the group
  • E is selected from:
  • A is N or CR 14 ;
  • B is O; S; or NR 5 ;
  • each W is independently O; S; NH; N(C 1 -C 6 alkyl); or NO(C 1 -C 6 alkyl);
  • X is H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 3 -C 6 cycloalkyl; cyano; NH 2 ; NHR 1 ;
  • X 1 is C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy; C 2 -C 6 alkenyloxy; C 2 -C 6 haloalkenyloxy;
  • each R 1 is independently C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6
  • R 2 is H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 3 -C 6 cycloalkyl; C 2 -C 4 alkylcarbonyl; C 2 -C 4 alkoxycarbonyl; hydroxy; C 1 -C 2 alkoxy; or acetyloxy;
  • R 3 and R 4 are each independently halogen; cyano; nitro; hydroxy; C 1 -C 6 alkyl;
  • C 1 -C 6 haloalkyl C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy; C 2 -C 6 alkenyloxy; C 2 -C 6 alkynyloxy; C 1 -C 6 alkylthio; C 1 -C 6 alkylsulfinyl; C 1 -C 6 alkylsulfonyl; formyl;
  • R 25 3 Si-C ⁇ C-; or phenyl, phenylethynyl, benzoyl, or phenylsulfonyl each substituted with R 8 and optionally substituted with one or more R 10 ; or when E is 1,2-phenylene and R 3 and R 4 are attached to adjacent atoms, R 3 and R 4 can be taken together as C 3 -C 5 alkylene, C 3 -C 5 haloalkylene, C 3 -C 5 alkenylene or C 3 -C5 haloalkenylene each optionally substituted with 1-2 C 1 -C 3 alkyl;
  • R 5 is H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 3 -C 6 cycloalkyl; C 2 -C 4 alkylcarbonyl; or C 2 -C 4 alkoxycarbonyl;
  • -CR 6 CR 6 -; -C ⁇ C-; -CHR 15 O-; -OCHR 15 -; -CHR 15 S(O) n -; -S(O) n CHR 15 -;
  • Z 1 is H or -A 3 -Z
  • W 1 is O or S
  • a 1 is O; S; NR 15 ; or a direct bond;
  • a 2 is O; NR 15 ; or a direct bond;
  • each R 6 is independently H; 1-2 CH 3 ; C 2 -C 3 alkyl; C 1 -C 3 alkoxy; C 3 -C 6
  • alkoxycarbonylamino NH 2 C(O)NH; (C 1 -C 3 alkyl)NHC(O)NH;
  • each R 7 is independently H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy; C 1 -C 6 alkylthio; C 1 -C 6 alkylsulfinyl; C 1 -C 6 alkylsulfonyl; C 1 -C 6 haloalkylthio; C 1 -C 6 haloalkylsulfinyl; C 1 -C 6 haloalkylsulfonyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 3 -C 6 cycloalkyl; C 2 -C 4 alkylcarbonyl; C 2 -C 4 alkoxycarbonyl; halogen; cyano; nitro; hydroxy
  • a ring system selected from 3 to 14-membered monocyclic, fused bicyclic and fused tricyclic nonaromatic heterocyclic ring systems and 5 to
  • each heterocyclic ring system containing 1 to 6 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 4 nitrogens, no more than 2 oxygens, and no more than 2 sulfurs, each nonaromatic or aromatic heterocyclic ring system substituted with R 9 and optionally substituted with one or more R 10 ;
  • each Q is independently selected from the group -CHR 13 -, -NR 13 -, -O-, and
  • R 8 is H; 1-2 halogen; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy; C 1 -C 6
  • C 3 -C 6 cycloalkyl C 3 -C 6 alkenyloxy; CO 2 (C 1 -C 6 alkyl); NH(C 1 -C 6 alkyl);
  • N(C 1 -C 6 alkyl) 2 cyano; nitro; SiR 19 R 20 R 21 ; or GeR 19 R 20 R 21 ;
  • R 9 is H; 1-2 halogen; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6
  • haloalkenyl C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 3 -C 6 cycloalkyl or C 3 -C 6 cycloalkenyl each optionally substituted with at least one member selected from 1-2 halogen, 1-2 C 1 -C 3 alkyl, 1-2 C 1 -C 3 alkoxy, and one phenyl optionally substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, nitro or cyano; C 2 -C 6 alkoxyalkyl; C 2 -C 6 alkylthioalkyl; C 3 -C 6 alkoxy alkynyl; C 7 -C 10 tetrahydropyranyloxy alkynyl; benzyloxymethyl; C 1 -C 6 alkoxy; C 1
  • CO 2 (C 1 -C 6 alkyl); NH(C 1 -C 6 alkyl); N(C 1 -C 6 alkyl) 2 ; -C(R 18 ) NOR 17 ; cyano; nitro; SF 5 ; SiR 22 R 23 R 24 ; or GeR 22 R 23 R 24 ; or R 9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
  • each R 10 is independently halogen; C 1 -C 4 alkyl optionally substituted with 1-3
  • R 9 and an R 10 when R 9 and an R 10 are attached to adjacent atoms on Z, R 9 and said adjacently attached R 10 can be taken together as -OCH 2 O- or -OCH 2 CH 2 O-; each CH 2 group of said taken together R 9 and R 10 optionally substituted with 1-2 halogen; or
  • R 7 and said adjacently attached R 10 can be taken together as -(CH 2 ) r -J- such that J is attached to Z;
  • J is -CH 2 -; -CH 2 CH 2 -; -OCH 2 -; -CH 2 O-; -SCH 2 -; -CH 2 S-; -N(R 16 )CH 2 -; or
  • R 11 and R 12 are each independently 1-2 halogen; C 1 -C 4 alkyl; C 1 -C 4 haloalkyl;
  • haloalkylsulfonyl C 3 -C 6 alkenylthio; C 3 -C 6 haloalkenylthio; C 2 -C 6 alkylthioalkylthio; nitro; cyano; thiocyanato; hydroxy; N(R 26 ) 2 ; SF 5 ;
  • each R 13 is independently H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; or phenyl optionally substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, nitro or cyano;
  • R 14 is H; halogen; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl;
  • R 7 and the adjacently attached R 15 can be taken together as -CH 2 -(CH 2 ) s -; -O-(CH 2 ) s -; -S-(CH 2 ) s -; or
  • R 16 , R 17 , and R 18 are each independently H; C 1 -C 3 alkyl; C 3 -C 6 cycloalkyl; or phenyl optionally substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl,
  • R 19 , R 20 , R 21 , R 22 , R 23 , and R 24 are each independently C 1 -C 6 alkyl; C 1 -C 4
  • haloalkyl C 2 -C 6 alkenyl; C 1 -C 4 alkoxy; or phenyl;
  • each R 25 is independently C 1 -C 4 alkyl; C 1 -C 4 haloalkyl; C 2 -C 4 alkenyl; C 1 -C 4 alkoxy; or phenyl;
  • each R 26 is independently H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkynyl; C 3 -C 6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, nitro or cyano; each R 27 is independently C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 2 -C 6 alkenyl; C 2 -C 6 haloalkenyl; C 2 -C 6 alkynyl; C 2 -C 6 haloalkyn
  • r is 0 or 1 ;
  • s is 2 or 3; provided that
  • R 9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of R 1 1 , R 12 , or both R 1 1 and R 12 ;
  • R 9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
  • R 9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring
  • G is G-3
  • B is NR 5
  • X is NH 2 , NHR 1 or N(C 1 -C 6 alkyl .
  • R 1 and Y is O or a direct bond, then Z is other than phenyl substituted with R 9 and optionally substituted with one or more R 10 .
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers.
  • 1-2 CH 3 indicates that the substituent can be methyl or, when there is a hydrogen attached to the same atom, the substituent and said hydrogen can both be methyl.
  • 1-2 alkyl indicates that one or two of the available positions for that substituent may be alkyl which are independently selected.
  • 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
  • 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, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • the term “1-3 alkoxy” indicates that one to three of the available positions for that substituent may be alkoxy which are independently selected; and the term “1-2 alkoxy” is defined analogously.
  • Alkoxyalkyl denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • Alkoxyalkoxy denotes alkoxy substitution on alkoxy.
  • Alkenyloxy includes straight-chain or branched alkenyloxy moieties. Examples of “alkenyloxy” include
  • Alkynyloxy includes straight-chain or branched alkynyloxy moieties. Examples of “alkynyloxy” include HC ⁇ CCH 2 O, CH 3 C ⁇ CCH 2 O and
  • 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 CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 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 hexylsulfinyl 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) 2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.
  • Alkenylthio alkenylsulfinyl
  • alkenylsulfonyl alkynylthio
  • alkynylsulfinyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • cycloalkoxy includes the same groups linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy.
  • Cycloalkenyl includes groups such as cyclopentenyl and cyclohexenyl as well as groups with more than one double bond such as 1,3- and 1,4-cyclohexadienyl.
  • Trialkylsilylalkoxyalkoxy denotes trialkylsilylalkoxy substitution on alkoxy.
  • Examples of “trialkylsilylalkoxyalkoxy” includes, for example, (CH 3 ) 3 SiCH 2 CH 2 OCH 2 O.
  • aromatic carbocyclic ring system includes fully aromatic carbocycles and carbocycles in which at least one ring of a polycyclic ring system is aromatic (where aromatic indicates that the Hückel rule is satisfied).
  • nonaromatic carbocyclic ring system denotes fully saturated carbocycles as well as partially or fully unsaturated carbocycles where the Hückel rule is not satisfied by any of the rings in the ring system.
  • aromatic heterocyclic ring system includes fully aromatic heterocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where aromatic indicates that the Hückel rule is satisfied).
  • nonaromatic heterocyclic ring system denotes fully saturated heterocycles as well as partially or fully unsaturated heterocycles where the Hückel rule is not satisfied by any of the rings in the ring system.
  • the heterocyclic ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • 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, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 .
  • haloalkenyl “haloalkynyl", “haloalkoxy", and the like, are defined analogously to the term “haloalkyl”.
  • CF 3 CH 2 CH CHCH 2 .
  • haloalkoxy include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio include CCl 3 S, CF 3 S, CCl 3 CH 2 S and ClCH 2 CH 2 CH 2 S.
  • haloalkylsulfinyl 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 .
  • the total number of carbon atoms in a substituent group is indicated by the "C i -C j " prefix where i and j are numbers from 1 to 10.
  • C 1 -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl.
  • alkylcarbonyl examples include C(O)CH 3 , C(O)CH 2 CH 2 CH 3 and C(O)CH(CH 3 ) 2 .
  • alkoxycarbonyl when a compound of Formula I is comprised of one or more heterocyclic rings, all substituents are attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • 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.
  • E is selected from the group 1,2-phenylene; 1,5-, 1,6-, 1,7-, 1,8-, 2,6-, 2,7-, 1,2-, and 2,3-naphthalenediyl; 1H-pyrrole-1,2-, 2,3- and 3,4-diyl; 2,3- and 3,4-furandiyl; 2,3- and 3,4-thiophenediyl;
  • 6,7- and 7,8-quinazolinediyl 2,5-, 2,6-, 2,7-, 2,8-, 2,3-, 5,6-, 6,7- and 7,8-quinoxalinediyl; 1,8,-naphthyridine-2,5-, 2,6-, 2,7-, 3,5-, 3,6-, 4,5-, 2,3- and 3,4-diyl; 2,6-, 2,7-, 4,6-, 4,7-, 6,7-pteridinediyl; pyrazolo[5,1-b]thiazole-2,6-, 2,7-, 3,6-, 3,7-, 2,3- and 6,7-diyl; thiazolo[2,3-c]-1,2,4-triazole-2,5-, 2,6-, 5,6-diyl;
  • each aromatic ring system optionally substituted with one of R 3 , R 4 , or both R 3 and R 4 ;
  • W is O
  • R 1 is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl
  • R 2 is ⁇ ; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; or C 3 -C 6 cycloalkyl;
  • R 3 and R 4 are each independently halogen; cyano; nitro; C 1 -C 6 alkyl;
  • C 1 -C 6 haloalkyl C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy; C 1 -C 6 alkylthio; C 1 -C 6 alkylsulfonyl; C 2 -C 6 alkylcarbonyl; C 2 -C 6 alkoxycarbonyl; (C 1 -C 4 alkyl)N ⁇ C(O); (C 1 -C 4 alkyl) 2 NC(O); benzoyl; or phenylsulfonyl;
  • R 7 is H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy; C 1 -C 6 alkylthio;
  • R 7 and said adjacently attached R 10 can be taken together as -(CH 2 ) r -J- such that J is attached to Z;
  • Z is selected from the group C 1 -C 10 alkyl; C 3 -C 6 cycloalkyl; phenyl;
  • pyridazinyl pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; 1,2,4,5-tetrazinyl; 1H-indolyl; benzofuranyl; benzo[b]thiophenyl; 1H-indazolyl; 1H-benzimidazolyl; benzoxazolyl; benzothiazolyl; quinolinyl; isoquinolinyl; cinnolinyl; phthalazinyl; quinazoUnyl;
  • R 9 is ⁇ ; 1-2 halogen; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy; C 1 -C 6 alkylthio; cyano; CO 2 (C 1 -C 6 alkyl);
  • each R 15 is independently H; C 1 -C 3 alkyl; or C 3 -C 6 cycloalkyl.
  • Preferred 2 Compounds of Preferred 1 wherein:
  • E is selected from the group 1,2-phenylene; 1,6-, 1,7-, 1,2-, and 2,3-naphthalenediyl; 2,3- and 3,4-furandiyl; 2,3- and 3,4-thiophenediyl; 2,3- and 3,4-pyridinediyl; 4,5-pyrimidinediyl; 2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and 6,7-benzofurandiyl; and benzo[b]thiophene-2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and 6,7-diyl; each aromatic ring system optionally substituted with one of R 3 , R 4 , or both R 3 and R 4 ;
  • Z is selected from the group phenyl; pyridinyl; pyrimidinyl; and naphthalenyl; each group substituted with R 9 and optionally substituted with one or more R 10 ;
  • R 7 is H; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy; C 1 -C 6 alkylthio;
  • J is -CH 2 - or -CH 2 CH 2 -;
  • E is selected from the group 1,2-phenylene; 2,3- and 3,4-thiophenediyl; and 2,3- and 3,4-pyridinediyl; each aromatic ring system optionally substituted with one of R 3 , R 4 , or both R 3 and R 4 ;
  • B is O or NR 5 ;
  • X is C 1 -C 3 alkyl; NHR 1 ; or N(C 1 -C 3 alkyl)R 1 ;
  • R 1 is C 1 -C 3 alkyl
  • R 2 is H or C 1 -C 2 alkyl
  • R 7 is H; C 1 -C 3 alkyl; C 1 -C 3 haloalkyl; C 1 -C 3 alkoxy; C 1 -C 3 alkylthio; or cyclopropyl; and
  • each R 15 is independently H; C 1 -C 3 alkyl; or cyclopropyl.
  • G is G-1;
  • A is N.
  • G is G-2;
  • A is N;
  • X is NHR 1 or N(C 1 -C 6 alkyl . R 1 .
  • R 1 is methyl
  • R 2 is methyl
  • 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.
  • 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.
  • G is G-1, G-2 or G-3; embodiments where X is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, cyano, N ⁇ 2 , NHR 1 or
  • R 1 N(C 1 -C 6 alkyl .
  • R 7 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkylcarbonyl,
  • Z is other than C 3 -C 6 cycloalkenyl and adamantyl each substituted with R 9 and optionally substituted with one or more R 10 ; embodiments where R 9 is H, 1-2 halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 6 alkenyloxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl,
  • R 11 and R 12 are each independently halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 3 -C 6 alkenyloxy, C 3 -C 6 haloalkenyloxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulf
  • the compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-35.
  • Compounds of Formula 2 can be reduced to compounds of Formula 1 in protic solvents (Scheme 1) such as aliphatic alcohols or water, or aliphatic alcohol and water mixtures using metal hydrides such as sodium borohydride (for additional references using different conditions see Larock, Comprehensive Organic Transformations, R. C. Larock: New York, (1989), pp. 528-534).
  • protic solvents such as aliphatic alcohols or water, or aliphatic alcohol and water mixtures using metal hydrides such as sodium borohydride
  • Compounds of Formula 2a can be prepared by reacting N,N-drn ⁇ emylformarnide with an aryl metal species of Formula 4 (Scheme 2) generated in situ by reacting an aryl halide of Formula 3 with metallic magnesium to form an aryl Grignard intermediate or with an alkyllithium to generate an aryllithium intermediate.
  • Scheme 2 aryl metal species of Formula 4
  • metallic magnesium to form an aryl Grignard intermediate or with an alkyllithium to generate an aryllithium intermediate.
  • organometallic compounds to carbonyl groups is well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), pp. 920-929).
  • Compounds of Formula 5, 5a, and 5b can be prepared by treating compounds of Formula 6, 6a, 6b, and 6c with the appropriate alkyl transfer reagent in an inert solvent with or without additional acidic or basic reagents or other reagents (Scheme 3).
  • Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide; ethers such as
  • ketones such as acetone or
  • trimethylsilyldiazomethane (CH 3 ) 3 Si) on carbonyl compounds of Formula 6 (Method 1).
  • a protic cosolvent such as methanol.
  • compounds of Formula 5 can also be prepared by contacting carbonyl compounds of Formula 6 with alkyl trichloroacetimidates of
  • 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 5 can also be prepared from compounds of Formula 6 by treatment with a trialkyloxonium tetrafluoroborate (i.e. Meerwein's salt) of Formula 9 (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. Schöllkopf, U. Groth, C. Deng, Angew. Chem., Int. Ed. Engl.,
  • alkylating agents which can convert carbonyl compounds of Formula 6 to compounds of Formula 5 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,
  • DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
  • Two sequential applications of Methods 1-4 to compounds of Formula 6a can be used to prepare compounds of Formula 5a, via compounds of Formula 6b.
  • compounds of Formula 5a have equivalent R 1 groups, they can be prepared by reacting compounds of Formula 6a with two equivalents of the appropriate alkylating agents according to Methods 1-4.
  • Compounds of Formula 5b can be prepared from compounds of Formula 6c by appropriate applications of Methods 1-4. See G. Zvilichovsky, M. David,
  • the nucleophiles of Formula 12 are N- substituted hydroxylamines (HO- ⁇ HR 2 ) and substituted hydrazines (H ⁇ (R 5 )- ⁇ HR 2 ).
  • esters of Formula 11 can be prepared by methods described hereinafter.
  • Esters of Formula 11 or 11c can be prepared from copper (I)-catalyzed reaction of compounds of Formula 13 or 13a with substituted aryl halides of Formula 14 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,
  • Esters of Formula 11 or 11c can also be prepared from compounds of Formula 11d after modification of the carboxylic acid functional group to the appropriate Y and Z group.
  • the malonate esters of Formula 11e can be prepared by treating aryl acetic acid esters of Formula 15 with a dialkyl carbonate or alkyl chloroformate in the presence of a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 7).
  • a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 7).
  • Compounds of Formula 11f can be prepared from compounds of Formula 11e by alkylation with a suitable alkylating agent in an inert solvent.
  • Suitable alkylating agents include dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl
  • 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 alkali metal amides such as lithium diisopropylamide.
  • Suitable solvents include polar aprotic solvents such as N,N-dimethylformamide or ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether. Alkylations of this type are well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), p 412, and references therein).
  • esters of Formula 15 can be alkylated to provide esters of
  • Suitable alkylating agents include dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane. 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 alkali metal amides such as lithium diisopropylamide.
  • Suitable solvents include polar aprotic solvents such as
  • N,N-dimethylformamide or ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether. Alkylations of this type are well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), p 416-418, and references therein).
  • Esters of Formula 15a can be treated with a carbonylating agent of Formula 34 to provide compounds of Formula 11g.
  • the compounds of Formula 34 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,
  • ketones such as acetone or 2-butanone
  • hydrocarbons such as toluene or benzene
  • halocarbons such as dichloromethane or chloroform.
  • Compounds of Formula 6c can be prepared from compounds of Formula 11g by reaction with an ambident nucleophile of Formula 12a.
  • An example of nucleophiles of Formula 12a An example of nucleophiles of Formula 12a.
  • Formula 12a is methylhydrazine.
  • Nitrile esters of Formula 11aa (Scheme 7b) can be prepared by reacting
  • Esters of Formula 15 can be prepared from acid-catalyzed alcoholysis of aryl acetonitriles of Formula 16 or esterification of aryl acetic acids of Formula 17 as illustrated in Scheme 8 (see Org. Synth., Coll. Vol. I, (1941), 270).
  • esters of Formula 15 can be prepared by palladium (O)-catalyzed cross coupling reaction of aryl iodides of Formula 14 with a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 8).
  • a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 8).
  • Scheme 8 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 15b can also be prepared by copper (I)-catalyzed condensation of aryl halides of Formula 18 with compounds of Formula 19 as described in EP-A-307,103 and illustrated below in Scheme 9.
  • esters of Formula 15 can also be prepared by forming the Y 2 bridge using conventional nucleophilic substitution chemistry (Scheme 10).
  • Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 21 or 22 with a nucleophilic ester of Formula 20 affords compounds of Formula 15c.
  • a base for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 20.
  • esters of Formula 15 can also be prepared by forming the Y 3 bridge from substituted hydroxylamine 15e and carbonyl compounds 22a.
  • the hydroxylamine 15e is in turn prepared from esters 15d. This method has been described in EP-A-600,835 and illustrated in Scheme 11.
  • the leaving group Lg 1 in the amides of Formula 24 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.
  • compounds of Formula 23a can be prepared from compounds of 24a.
  • Compounds of Formula 23b and 23c can be prepared by reaction of compounds of 24 or 24a, respectively, with alkali or transition metal cyanide salts. Displacements of this type are well established in the art. The reactions are usually conducted in polar, aprotic solvents such as N,N- dimethylformamide, with or without additional catalysts. For an example, see A.
  • Compounds of Formula 24b can be prepared from compounds of Formula 25 by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding ⁇ -halo-substituted derivatives (Scheme 13).
  • halogenating agents such as thionyl chloride or phosphorus oxybromide
  • compounds of Formula 25 can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methanesulfonyl chloride, p-toluenesulfonyl chloride, and
  • sulfonyl compounds of Formula 24d can be prepared by oxidation of the corresponding thio compound of Formula 26 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-chloro-peroxybenzoic acid, hydrogen peroxide and Oxone ® (KHSO 5 ).
  • compounds of Formula 26a can be oxidized to compounds of Formula 24e with one or two equivalents of oxidizing reagent.
  • the diacyl compound of Formula 27 is treated with excess thionyl halide, for example excess thionyl chloride.
  • the product formed first is the ring-closed compound of Formula 28 which can be isolated or converted in situ to the compound of Formula 24f; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
  • the hydrazides of Formula 27 can be prepared as illustrated in Scheme 16.
  • compounds of Formula 30 can be prepared by treating a ketenedithioacetal of Formula 31 with an ambident nucleophile of Formula 12 (Scheme 17).
  • the nucleophiles of Formula 12 are described above.
  • Ketene dithioacetals of Formula 31a can be prepared by condensing arylacetic acid esters of Formula 15 with carbon disulfide in the presence of a suitable base, followed by reaction with two equivalents of an V-halide, such as iodomethane or propargyl bromide (Scheme 18).
  • Compounds of Formula 32 can be prepared by condensation of N-amino-ureas of Formula 33 with a carbonylating agent of Formula 34 (Scheme 19).
  • the compounds of Formula 34 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
  • 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.
  • compounds of Formula 32a can be prepared by reacting compounds of Formula 33a with alkylamidines in solvents such as n-butanol or N,N-dimethylformamide in the presence of a base, followed by N-alkylation (in the presence of a base) with an alkylhalide as demonstrated by J. Heeves, et al., J. Med. Chem., 1984, 27, 894-900 (Scheme 19).
  • N-Amino-ureas of Formula 33 can be prepared as illustrated in Scheme 20.
  • N, N'-carbonyldiimidazole, or N, N'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 36.
  • 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 33.
  • Formula 33a compounds can be prepared by reaction of Formula 36 iso(thiocyanates) as outlined in Scheme 20a.
  • Compounds of Formula 37 can be prepared by either method illustrated in Scheme 21.
  • Ureas of Formula 38 are reacted with activated 2-halocarboxylic acid derivatives 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 37 compounds can be prepared by reaction of Formula 36 isocyanates with Formula 39a esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula 37 compounds.
  • the ureas of Formula 38 can be prepared by either of the methods illustrated in Scheme 22.
  • an isocyanate or isothiocyanate of Formula 36 can be condensed with an amine of Formula R 2 -NH 2 to form the urea.
  • the arylamine and iso(thio)cyanates of Formulae 35 and 36, 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. Advanced Organic
  • thionating reagents such as P 2 S 5 or Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane- 2,4-disulfide) as illustrated in Scheme 23 (see Bull. Soc. Chim. Belg., (1978), 87, 229; and Tetrahedron Lett.
  • 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.
  • aryl halides of Formula 44 can be prepared by radical halogenation of the corresponding alkyl compound (i.e., H instead of halogen in Formula 44), or by acidic cleavage of the corresponding methylether (i.e., OMe instead of halogen in Formula 44).
  • Other aryl halides of Formula 44 can be prepared from the appropriate alcohols of Formula 45 by well known halogenation methods in the art (see Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry; 3rd ed., Part B, Plenum: New York, (1990), p 122).
  • the olefins of Formula 46 can be converted to the saturated compounds of Formula 47 by hydrogenation over a metal catalyst such as palladium on carbon as is well-known in the art (Rylander, Catalytic Hydrogenation in Organic Synthesis;
  • Formula 48 alkynes can be prepared by halogenation/dehalogenation of
  • Formula 46 olefins using procedures well-known in the art (March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), p 924). Additionally, Formula 48 alkynes can be prepared by well-known reaction of aryl halides with alkyne derivatives in the presence of catalysts such as nickel or palladium (see J. Organomet. Chem., (1975), 93 253-257).
  • the olefin of Formula 46 can also be prepared by reversing the reactivity of the reactants in the Wittig or Horner-Emmons condensation.
  • 2-alkylaryl derivatives of Formula 51 can be converted into the corresponding dibromo-compound of Formula 52 as illustrated in Scheme 26 (see Synthesis, (1988), 330).
  • the dibromo- compound can be hydrolyzed to the carbonyl compound of Formula 53, which in turn can be condensed with a phosphorus-containing nucleophile of Formula 54 or 55 to afford the olefin of Formula 46.
  • compounds of Formula 53 can be prepared by oxidation of the corresponding alcohols of Formula 30.
  • Vinylhalides of Formula 56 can be prepared by reacting phosphorus reagents of Formulae 55a or 55b with carbonyl compounds of Formula 53 (Scheme 26).
  • the preparations of halides of Formula 55a from the appropriate diethylphosphonoacetate are described by McKenna and Khawli in J. Org. Chem., (1986), 51, 5467.
  • the thiono esters of Formula 55b can be prepared from esters of Formula 55a by converting the carbonyl oxygen of the ester to a thiocarbonyl (see Chem. Rev., (1984), 84, 17 and Tetrahedron Lett., (1984), 25, 2639).
  • the O-substituted hydroxylamine can be condensed with the carbonyl compound of Formula 58 to yield oximes of Formula 57 directly.
  • Carbamates of Formula 59 can be prepared by reacting aryl alcohols of Formula 45 with isocyanates of Formula 61 (Scheme 28). A base such as triethylamine can be added to catalyze the reaction. As shown, carbamates of Formula 59 can be further alkylated to provide the carbamates of Formula 60.
  • the compounds of the present invention are prepared by combinations of reactions as illustrated in the Schemes 1-28 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 L can be accomplished by one skilled in the art by the appropriate combination of reagents and reaction sequences for a particular Z-L.
  • 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 L is defined in individual schemes, and the preparation of representative Z-L examples.
  • Compounds of Formula 63 in Scheme 29 can be prepared from compounds of
  • Compounds of Formula 62 can be prepared from compounds of Formula 61a (Scheme 30) by Friedel-Crafts acylation with compounds of Formula 64. (See
  • Compounds of Formula 62 may also be prepared by reaction of acyl halides, anhydrides, esters, or amides of Formula 67 with organometallic reagents of Formula 66. (See March, J.
  • the organometallic compounds of Formula 66 may be prepared by reductive metallation or halogen-metal exchange of a halogen-containing compound of Formula 65 using, for example, magnesium or an organolithium reagent, or by deprotonation of compounds of Formula 61a using a strong base such as a lithioamide or an organolithium reagent, followed by transmetallation.
  • Compounds of Formula 65 may be prepared by reaction of compounds of
  • N-halosuccinimides, tert-butyl hypohalites or SO 2 CI 2 my also be used .
  • electrophilic substitutions see de la Mare, "Electrophilic Halogenation," Cambridge University Press, London (1976).
  • Compounds of Formula 69 can be prepared from compounds of Formula 68 by similar procedures.
  • Compounds of Formula 54 or 55 in Scheme 26 can be prepared by reaction of compounds of
  • Compounds of Formula 70 can be prepared from compounds of Formula 62b by treatment with peracids such as perbenzoic or peracetic acid, or with other peroxy compounds in the presence of an acid catalysts, followed by hydrolysis of the resultant ester.
  • peracids such as perbenzoic or peracetic acid
  • acid catalysts such as sodium bicarbonate
  • Formula 70 corresponds to
  • Formula 19 in Scheme 9 when Y 1 O and reagent HO-Z in Scheme 24.
  • Compounds of Formula 74 can be prepared from compounds of Formula 70 by conversion to the dialkylthiocarbamates of Formula 72 followed by rearrangement to Formula 73 and subsequent hydrolysis. See M. S. Newman and H. A. Karnes, J. Org. Chem. (1966), 31, 3980-4.
  • Compounds of Formula 75 can be prepared from compounds of Formula 61a by nitration, followed by reduction (Scheme 34).
  • a wide variety of nitrating agents is available (see Schofield, Aromatic Nitration, Cambridge University Press, Cambridge (1980)). Reduction of nitro compounds can be accomplished in a number of ways (see March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 1103-4 and references therein).
  • Iodides of Formula 14 can be prepared from compounds of Formula 80 by the methods described above in Schemes 24-28 for various Y-Z combinations.
  • Compounds of Formula 80 can in turn be prepared from compounds of Formula 79 by functional group interconversions which are well known to one skilled in the art.
  • the compounds of Formula 79 can be prepared by treating compounds of Formula 78 with an
  • organolithium reagent such as n-BuLi or LDA followed by trapping the intermediate with iodine (Beak, P., Snieckus, V. Ace. Chem. Res., (1982), 15, 306). Additionally, lithiation via halogen metal exchange of compounds of Formula 78, where H is replaced by Br, will produce an intermediate which can be trapped with iodine to prepare compounds of Formula 79 (Parham, W E., Bradsher, C. K. Ace. Chem. Res., (1982), 15, 300 (Scheme 32).
  • 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.
  • o-Tolyl isocyanate (50.4 g) and 75.2 g of N-bromosuccinimide in 800 mL of carbon tetrachloride were heated to reflux. Benzoyl peroxide (1.1 g) was added and the mixture was heated at reflux for 1.5 h. The solution was cooled to room temperature and the precipitate was removed by filtration. The filtrate was concentrated in vacuo and redissolved in 500 mL of toluene and cooled to 5°C. 1,1-Dimethylhydrazine (30 mL) in 20 mL of toluene was added dropwise. The reaction mixture was stirred at room temperature overnight. The precipitated solid was collected by filtration and redissolved in 1 L of dichloromethane.
  • Step B Preparation of 5-cMoro-4-[2-(chloromethyl)phenyl]-2,4-dihydro-2- methyl-3H-1,2,4-triazol-3-one
  • Step C Preparation of 1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethanone oxime
  • Step D Preparation of 5-chloro-2,4-dihydro-2-methyl-4-[2-[[ [[1-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethylidenelamino]oxylmethyl]phenyl]-3H-1,2,4-triazol-3- one
  • Step E Preparation of 2,4-dihydro-2-methyl-5-(methylamino)-4-[2-[[[[[1-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol-3- one
  • Step D The title compound of Step D (1 g) was dissolved/suspended in 5 mL methanol and then 5 g of methylamine was added. The container was closed (sealed) and heated at approximately 90°C for 36 h. The reaction was allowed to cool and the vessel was evacuated. The solution/suspension was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with distilled water and then saturated aqueous sodium chloride solution. The organic phase was dried (MgSO 4 ), filtered and concentrated under reduced pressure.
  • o-Tolylhydrazine hydrochloride (10 g, 63.0 mmol) was ground to a fine powder and suspended in a mixed solvent of 60 mL of ethanol and 60 mL of 10% aqueous HCl. The suspension turned into a clear solution after heating at 60°C. To this solution was added dropwise pyruvic acid (5.3 mL, 75.7 mmol). The mixture was stirred at room temperature for 1 h and 100 mL of water was added. The orange precipitate was collected via filtration. After drying overnight (55°C, 10 h) in the vacuum oven, the title compound of Step D (8.8 g, 73%) was obtained as a light orange solid melting at 155-157°C.
  • Step F Preparation of 2,4-dihydro-4,5-dimethyl-2-(2-methylphenyl)-3H-1,2,4- triazol-3-one
  • N-bromosuccinimide (0.86 g, 4.9 mmol)
  • benzoyl peroxide (30 mg) in 20 mL of carbon tetrachloride was heated at reflux for 10 h.
  • the solvent was removed in vacuo and the residue purified by chromatography to give, along with 5-(bromomethyl)-2,4- dihydro-4-methyl-2-(2-methylphenyl)-3H-1,2,4-triazol-3-one, the title compound of Step G (0.67 g, 54%) as a colorless oil.
  • Step H Preparation of 2,4-dihydro-4,5-dimethyl-2-[2-[[[[[[ 1-[3- (trimethylgermyl)phenyl]ethylidene]a m ino]oxy]methyl]phenyl]-3H-1,2,4- triazol-3-one
  • Step B Preparation of 1,4-dihydro-1-methyl-4-(2-bromophenyl)-5H-tetrazol-5-one
  • Step C Preparation of 2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde
  • Step D Preparation of 1,4-dihydro-1-[2-(hydroxymethyl)phenyl]-4-methyl-5H- tetrazol-5-one
  • Step F Preparation of 1-[3-(trifluorom ethyl)phenyl]ethanone oxime
  • Step A Preparation of 2-(1,4-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde oxime
  • Step B Preparation of 2-(1,4-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde O-[[3-(trifluoromethyl)phenyl]methyl]oxime Under nitrogen, to a suspension of sodium hydride (0.17 g of 60% oil dispersion,
  • Step A Preparation of 1-13-(trifluoromethoxy.phenyllethanone oxime
  • Step B Preparation of 1-methyl-4-[2-[ [[ [ 1-[3-(trifluoromethoxy)phenyl]- ethylidene]amino]oxy]methyl]phenyl]-1,2,4-triazolidine-3,5-dione
  • Step A Preparation of 1-[3-(trifluoromethyl)phenyllethanone oxime
  • Step D The title compound of Step D (1.25 g) was dissolved in 5 mL of trimethyl orthoacetate and to this solution was added 3 drops of acetic acid and the solution was heated at reflux overnight. The reaction mixture was then concentrated under reduced pressure and dissolved in ethyl acetate. The ethyl acetate solution was washed successively with 1 N aqueous ⁇ Cl, saturated aqueous Na ⁇ CO 3 and saturated aqueous NaCl. The organic layer was dried over MgSU4 and then was concentrated under reduced pressure. Column chromatography using 60-70% ethyl acetate in hexanes as eluant gave 0.42 g of the title compound of Step E, a compound of the invention, as an oil.
  • Step C Preparation of 1-[3-(trimethylsilyl)phenyl]ethanone oxime
  • Step C Under N 2 , the title compound of Step C (0.39 g; 1.85 mol) was added to a stirred suspension of sodium hydride (0.08 g 60% oil dispersion; 2.03 mmol) in 25 mL of dry DMF. The reaction mixture was stirred at room temperature for 1 h. The title compound of Step E in Example 3 (0.50 g; 1.76 mmol) was then added. The reaction mixture was stirred at room temperature for 16 h and was then poured into H 2 O (100 mL) and the aqueous mixture was extracted twice with diethyl ether. The combined organic layers were washed with saturated aqueous NaCl and dried with magnesium sulfate.
  • Step C Preparation of methyl ⁇ -methyl-2-[(2- methylphenoxy)methyl]benzeneacetate
  • Step D Preparation 2,4-dimethyl-4-[2-[(2-methylphenoxy)methyl]phenyl]-3,5- pyrrolidinedione
  • Step E Preparation 2,4-dihydro-5-methoxy-2,4-dimethyl-4-[2-[(2- methylphenoxy)methyl]phenyl]-3H-pyrazol-3-one
  • Step E Chromatography of the residue, an oil, on silica gel with 4: 1 hexane-ethyl acetate afforded the title compound of Step E as an oil.
  • the oil was triturated in hexane/1-chlorobutane to afford the title compound of Step E, a compound of the invention, (340 mg) as a solid melting at 147-150 °C.
  • 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
  • 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;
  • 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.
  • 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, N,N-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and
  • 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- ⁇ Umethylformamide 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
  • 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, Altemaria 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, Sphaerothecafuliginea, Fusarium oxysporum, Verticillium dahliae, Pyth
  • 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.
  • insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, esfenvalerate, fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion,
  • insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, deltame
  • metaldehyde methamidophos, methidathion, methomyl, methoprene, methoxychlor, 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 (ICIA5504), benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride, copper
  • Preferred for better control of plant diseases caused by fungal plant pathogens e.g., lower use rate or broader spectrum of plant pathogens controlled
  • resistance management are mixtures of a compound of this invention with a fungicide selected from the group cyproconazole, cyprodinil (CGA 219417), epoxyconazole (BAS 480F), fenpropidin, fenpropimorph, flusilazole and tebuconazole.
  • a fungicide selected from the group cyproconazole, cyprodinil (CGA 219417), epoxyconazole (BAS 480F), fenpropidin, fenpropimorph, flusilazole and tebuconazole.
  • a fungicide selected from the group cyproconazole, cyprodinil (CGA 219417), epoxyconazole (BAS 480F), fenpropidin, fenpropimorph, flusilazole and
  • CGA 219417 compound 6 and epoxyconazole (BAS 480F); compound 6 and fenpropidin; compound 6 and fenpropimorph; compound 6 and flusilazole; compound 6 and tebuconazole; compound 12 and cyproconazole; compound 12 and cyprodinil (CGA 219417); compound 12 and epoxyconazole (BAS 480F); compound 12 and fenpropidin; compound 12 and fenpropimorph; compound 12 and flusilazole;
  • compound 12 and tebuconazole compound 18 and cyproconazole; compound 18 and cyprodinil (CGA 219417); compound 18 and epoxyconazole (BAS 480F); compound 18 and fenpropidin; compound 18 and fenpropimorph; compound 18 and flusilazole;
  • compound 18 and tebuconazole compound 26 and cyproconazole; compound 26 and cyprodinil (CGA 219417); compound 26 and epoxyconazole (BAS 480F); compound 26 and fenpropidin; compound 26 and fenpropimorph; compound 26 and flusilazole; and compound 26 and tebuconazole.
  • 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.
  • 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.
  • Trem® 014 polyhydric alcohol esters
  • 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 suspension was sprayed to the point of run-off on wheat seedlings.
  • 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 suspension was sprayed to the point of run-off on rice seedlings.
  • 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 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.
  • Phytophthora infestans the causal agent of potato and tomato late blight
  • test suspension was sprayed to the point of run-off on grape seedlings.
  • 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 suspension was sprayed to the point of run-off on cucumber seedlings.
  • Results for Tests A-F are given in Table A.
  • a rating of 100 indicates

Abstract

Compounds of Formula (I), and their N-oxides and agriculturally suitable salts, are disclosed which are useful as fungicides, wherein G is selected from the group (G-1), (G-2), (G-3), (G-4), and (G-5). A is N or CR14; B is O; S; or NR5; each W is independently O; S; NH; N(C¿1?-C6 alkyl); or NO(C1-C6alkyl); X is H; C1-C6alkyl; C1-C6haloalkyl; C3-C6cycloalkyl; cyano; NH2; NHR?1; N(C¿1-C6alkyl)R1; NH(C¿1?-C6alkoxy); or N(C1-C6alkoxy)R?1¿; and E, X?1, R1, R2, R5, R14¿, Y, and Z are as defined in the disclosure. 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 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.
WO 85/01939 discloses tetrazolones of Formula i as herbicides:
Figure imgf000003_0001
wherein
W is O or S;
R is alkyl, haloalkyl, alkoxyalkyl, alkylthioalkyl, cyanoalkyl, haloalkoxy alkyl,
trifluoromethylthio, alkenyl, or haloalkenyl;
one of X1 and X2 is F, Cl, or Br and the other is F, Cl, Br, alkyl, or haloalkyl; or when X1 is F, Cl, or Br, X2 may be selected from the substituents above and nitro; and
Z is H; F; Cl; Br; cyano; nitro; alkyl; alkyl substituted with F, Cl, Br, or alkoxy; and alkynyl.
However, no utility as fungicides is alleged and the cyclic amides of the present invention are not disclosed therein.
U.S. 5,108,486, U.S. 5,064,845, U.S. 5,138,068, U.S. 4,059,703, U.S. 5,035,740,
EP 679,643 and J. Heterocyclic Chem. (1988), 25, 1307-1310 teach various heterocyclic compounds including 1,2,4-triazolinones, pyrazolinones, tetrazolinones and tetrazoles. The cyclic amides of the present invention are not disclosed in any of these publications.
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:
Figure imgf000004_0002
wherein
G is selected from the group
Figure imgf000004_0001
E is selected from:
i) 1,2-phenylene optionally substituted with one of R3, R4, or both R3 and
R4;
ii) a naphthalene ring, provided that when G and Y are attached to the same ring, then G and Y are attached to adjacent ring members, the naphthalene ring optionally substituted with one of R3, R4, or both R3 and R4; and iii) a ring system selected from 5 to 12-membered monocyclic and fused bicyclic aromatic heterocyclic ring systems, each heterocyclic ring system containing 1 to 6 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 4 nitrogens, no more than 2 oxygens, and no more than 2 sulfurs, each fused bicyclic ring system optionally containing one nonaromatic ring that optionally includes one or two Q as ring members and optionally includes one or two ring members independently selected from C(=O) and S(O)2, provided that G is attached to an aromatic ring, and when G and Y are attached to the same ring, then G and Y are attached to adjacent ring members, each aromatic heterocyclic ring system optionally substituted with one of R3, R4, or both R3 and R4;
A is N or CR14;
B is O; S; or NR5;
each W is independently O; S; NH; N(C 1-C6 alkyl); or NO(C1-C6 alkyl);
X is H; C1-C6 alkyl; C1-C6 haloalkyl; C3-C6 cycloalkyl; cyano; NH2; NHR1 ;
N(C1-C6 alkyl. R1; NH(C1-C6 alkoxy); or N(C1-C6 alkoxy)R1;
X1 is C1-C6 alkoxy; C1-C6 haloalkoxy; C2-C6 alkenyloxy; C2-C6 haloalkenyloxy;
C2-C6 alkynyloxy; C2-C6 haloalkynyloxy; C3-C6 cycloalkoxy; C1-C6 alkylthio; C1-C6 haloalkylthio; C2-C6 alkenylthio; C2-C6 haloalkenylthio;
C2-C6 alkynylthio; C2-C6 haloalkynylthio; C3-C6 cycloalkylthio; C1-C6 alkylsulfinyl; C1-C6 haloalkylsulfinyl; C2-C6 alkenylsulfinyl; C2-C6 haloalkenylsulfinyl; C2-C6 alkynylsulfinyl; C2-C6 haloalkynylsulfinyl; C3-C6 cycloalkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylsulfonyl; C2-C6 alkenylsulfonyl; C2-C6 haloalkenylsulfonyl; C2-C6 alkynylsulfonyl; C2-C6 haloalkynylsulfonyl; C3-C6 cycloalkylsulfonyl; halogen; or X;
each R1 is independently C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6
haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C1-C6 alkoxy; formyl; C2-C4 alkylcarbonyl; or C2-C4 alkoxycarbonyl; provided that when G is G-4, then only one of R1 can be C1-C6 alkoxy;
R2 is H; C1-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;
R3 and R4 are each independently halogen; cyano; nitro; hydroxy; C1-C6 alkyl;
C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C2-C6 alkenyloxy; C2-C6 alkynyloxy; C1-C6 alkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl; formyl;
C2-C6 alkylcarbonyl; C2-C6 alkoxycarbonyl; NH2C(O); (C1-C4 alkyl)NHC(O); (C1-C4 alkyl)2NC(O); Si(R25)3; Ge(R25)3;
(R25)3Si-C≡C-; or phenyl, phenylethynyl, benzoyl, or phenylsulfonyl each substituted with R8 and optionally substituted with one or more R10; or when E is 1,2-phenylene and 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 C1-C3 alkyl;
R5 is H; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C4 alkylcarbonyl; or C2-C4 alkoxycarbonyl;
Y is -O-; -S(O)n-; -NR15-; -C(=O)-; -CH(OR15)-; -CHR6-; -CHR6CHR6-;
-CR6=CR6-; -C≡C-; -CHR15O-; -OCHR15-; -CHR15S(O)n-; -S(O)nCHR15-;
-CHR15O-N=C(R7)-; -(R7)C=N-OCH(R15)-; -C(R7)=N-O-; -O-N=C(R7)-;
-CHR15OC(=O)N(R15)-; -CHR15OC(=S)N(R15)-; -CHR15OC(=O)O-; -CHR15OC(=S)O-; -CHR15OC(=O)S-; -CHR15OC(=S)S-;
-CHR15SC(=O)N(R15)-; -CHR15SC(=S)N(R15)-; -CHR15SC(=O)O-;
-CHR15SC(=S)O-; -CHR15SC(=O)S-; -CHR15SC(=S)S-;
-CHR15SC(=NR15)S-; -CHR15N(R15)C(=O)N(R15)-;
-CHR15O-N(R15)C(=O)N(R15)-; -CHR15O-N(R15)C(=S)N(R15)-;
-CHR15O-N=C(R7)NR15-; -CHR15O-N=C(R7)OCH2-;
-CHR15O-N=C(R7)-N=N-; -CHR15O-N=C(R7)-C(=O)-;
-CHR15O-N=C(R7)-C(=N-A2-Z1)-A1-;
-CHR15O-N=C(R7)-C(R7)=N-A2-A3-; -CHR15O-N=C(-C(R7)=N-A2-Z1)-;
-CHR15O-N=C(R7)-CH2O-; -CHR15O-N=C(R7)-CH2S-;
-O-CH2CH2O-N=C(R7)-; -CHR15O-C(R15)=C(R7)-; -CHR15O-C(R7)=N-;
-CHR15S-C(R7)=N-; -C(R7)=N-NR15-; -CH=N-N=C(R7)-;
-CHR15N(R15)-N=C(R7)-; -CHR15N(COCH3)-N=C(R7)-;
-OC(=S)NR15C(=O)-; -CHR6-C(=W1)-A1-; -CHR6CHR6-C(=W1)-A1-;
-CR6=CR6-C(=W1)-A1-; -C≡C-C(=W1)-A1-; -N=CR6-C(=W1)-A1-; 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;
Z1 is H or -A3-Z;
W1 is O or S;
A1 is O; S; NR15; or a direct bond;
A2 is O; NR15; or a direct bond; A3 is -C(=O)-; -S(O)2-; or a direct bond;
each R6 is independently H; 1-2 CH3; C2-C3 alkyl; C1-C3 alkoxy; C3-C6
cycloalkyl; formylamino; C2-C4 alkylcarbonylamino; C2-C4
alkoxycarbonylamino; NH2C(O)NH; (C1-C3 alkyl)NHC(O)NH;
(C1-C3 alkyl)2NC(O)NH; N(C1-C3 alkyl)2; piperidinyl; morpholinyl;
1-2 halogen; cyano; or nitro;
each R7 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 alkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylthio; C1-C6 haloalkylsulfinyl; C1-C6 haloalkylsulfonyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C4 alkylcarbonyl; C2-C4 alkoxycarbonyl; halogen; cyano; nitro; hydroxy; amino; NH(C1-C6 alkyl); N(C1-C6 alkyl)2; or morpholinyl; each Z is independently selected from:
i) C1-C10 alkyl, C2-C10 alkenyl, and C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10;
ii) C3-C6 cycloalkyl, C3-C6 cycloalkenyl and phenyl each substituted with R9 and optionally substituted with one or more R10;
iii) a ring system selected from 3 to 14-membered monocyclic, fused bicyclic and fused tricyclic nonaromatic heterocyclic ring systems and 5 to
14-membered monocyclic, fused bicyclic and fused tricyclic aromatic heterocyclic ring systems, each heterocyclic ring system containing 1 to 6 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 4 nitrogens, no more than 2 oxygens, and no more than 2 sulfurs, each nonaromatic or aromatic heterocyclic ring system substituted with R9 and optionally substituted with one or more R10;
iv) a multicyclic ring system selected from 8 to 14-membered fused-bicyclic and fused-tricyclic ring systems which are an aromatic carbocyclic ring system, a nonaromatic carbocyclic ring system, or a ring system containing one or two nonaromatic rings that each include one or two Q as ring members and one or two ring members independently selected from C(=O) and S(O)2, and any remaining rings as aromatic carbocyclic rings, each multicyclic ring system substituted with R9 and optionally substituted with one or more R10; and
v) adamantyl substituted with R9 and optionally substituted with one or more
R10; each Q is independently selected from the group -CHR13-, -NR13-, -O-, and
-S(O)p-;
R8 is H; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6
haloalkoxy; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C1-C6 alkylthio; C1-C6 haloalkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl;
C3-C6 cycloalkyl; C3-C6 alkenyloxy; CO2(C1-C6 alkyl); NH(C1-C6 alkyl);
N(C1-C6 alkyl)2; cyano; nitro; SiR19R20R21; or GeR19R20R21;
R9 is H; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6
haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl or C3-C6 cycloalkenyl each optionally substituted with at least one member selected from 1-2 halogen, 1-2 C1-C3 alkyl, 1-2 C1-C3 alkoxy, and one phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; C2-C6 alkoxyalkyl; C2-C6 alkylthioalkyl; C3-C6 alkoxy alkynyl; C7-C10 tetrahydropyranyloxy alkynyl; benzyloxymethyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C3-C6 alkenyloxy; C3-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C1-C6 cycloalkoxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxy alkoxy; C2-C6 alkylthioalkoxy; C1-C6 alkylthio; C1-C6 haloalkylthio; C1-C6 alkylsulfinyl; C1-C6 haloalkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio;
CO2(C1-C6 alkyl); NH(C1-C6 alkyl); N(C1-C6 alkyl)2; -C(R18)=NOR17; cyano; nitro; SF5; SiR22R23R24; or GeR22R23R24; or R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
R11, R12, or both R11 and R12;
each R10 is independently halogen; C1-C4 alkyl optionally substituted with 1-3
C1-C3 alkoxy; C1-C4 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C6 alkoxyalkyl; C2-C6 alkylthioalkyl; C3-C6 alkoxyalkynyl; C7-C10 tetrahydropyranyloxy alkynyl; benzyloxymethyl; C1-C4 alkoxy; C1-C4 haloalkoxy; C3-C6 alkenyloxy;
C3-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C1-C6 cycloalkoxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxy alkoxy; C2-C6 alkylthioalkoxy; C1-C4 alkylthio; C1-C4 haloalkylthio; C1-C4 alkylsulfinyl; C1-C4 haloalkylsulfinyl; C1-C4 alkylsulfonyl; C1-C4 haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio; nitro; cyano; thiocyanato; hydroxy; N(R26)2; SF5; Si(R25)3; Ge(R25)3; (R25)3Si-C=C-;
OSi(R25)3; OGe(R25)3; C(=O)R26; C(=S)R26; C(=O)OR26; C(=S)OR26;
C(=O)SR26; C(=S)SR26; C(=O)N(R26)2; C(=S)N(R26)2; OC(=O)R26;
OC(=S)R26; SC(=O)R26; SC(=S)R26; N(R26)C(=O)R26; N(R26)C(=S)R26;
OC(=O)OR27; OC(=O)SR27; OC(=O)N(R26)2; SC(=O)OR27; SC(=O)SR27;
S(O)2OR26; S(O)2N(R26)2; OS(O)2R27; or N(R26)S(O)2R27; or
when R9 and an R10 are attached to adjacent atoms on Z, R9 and said adjacently attached R10 can be taken together as -OCH2O- or -OCH2CH2O-; each CH2 group of said taken together R9 and R10 optionally substituted with 1-2 halogen; or
when Y and an R10 are attached to adjacent atoms on Z and Y is
-CHR15O-N=C(R7)-, -O-N=C(R7)-, -O-CH2CH2O-N=C(R7)-,
-CHR15O-C(R15)=C(R7)-, -CH=N-N=C(R7)-, -CHR15N(R15)-N=C(R7)- or -CHR15N(COCH3)-N=C(R7)-, R7 and said adjacently attached R10 can be taken together as -(CH2)r-J- such that J is attached to Z;
J is -CH2-; -CH2CH2-; -OCH2-; -CH2O-; -SCH2-; -CH2S-; -N(R16)CH2-; or
-CH2N(R16)-; each CH2 group of said J optionally substituted with 1 to 2
CH3;
R11 and R12 are each independently 1-2 halogen; C1-C4 alkyl; C1-C4 haloalkyl;
C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C2-C6 alkoxyalkyl; C2-C6 alkylthioalkyl; C3-C6 alkoxyalkynyl; C1-C10
tetrahydropyranyloxyalkynyl; benzyloxymethyl; C1-C4 alkoxy; C1-C4 haloalkoxy; C3-C6 alkenyloxy; C3-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxyalkoxy;
C2-C6 alkylthioalkoxy; C1-C4 alkylthio; C1-C4 haloalkylthio; C1-C4 alkylsulfinyl; C1-C4 haloalkylsulfinyl; C1-C4 alkylsulfonyl; C1-C4
haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio; nitro; cyano; thiocyanato; hydroxy; N(R26)2; SF5;
Si(R25)3; Ge(R25)3; (R25)3Si-C≡C-; OSi(R25)3; OGe(R25)3; C(=O)R26;
C(=S)R26; C(=O)OR26; C(=S)OR26; C(=O)SR26; C(=S)SR26;
C(=O)N(R26)2; C(=S)N(R26)2; OC(=O)R26; OC(=S)R26; SC(=O)R26;
SC(=S)R26; N(R26)C(=O)R26; N(R26)C(=S)R26; OC(=O)OR27;
OC(=O)SR27; OC(=O)N(R26)2; SC(=O)OR27; SC(=O)SR27; S(O)2OR26; S(O)2N(R26)2; OS(O)2R27; N(R26)S(O)2R27; or phenyl, phenoxy, benzyl, benzyloxy, phenylsulfonyl, phenylethynyl or pyridinylethynyl, each optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
each R13 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; or phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
R14 is H; halogen; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl;
C2-C6 alkynyl; C2-C6 haloalkynyl; or C3-C6 cycloalkyl;
each R15 is independently H; C1-C3 alkyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; or when Y is -CHR15N(R15)C(=O)N(R15)-, the two R15 attached to nitrogen atoms on said group can be taken together as -(CH2)s-; or
when Y is -CHR15O-N=C(R7)NR15-, R7 and the adjacently attached R15 can be taken together as -CH2-(CH2)s-; -O-(CH2)s-; -S-(CH2)s-; or
-N(C!-C3 alkyl)-(CH2)s-; with the directionality of said linkage defined such that the moiety depicted on the left side of the linkage is bonded to the carbon and the moiety on the right side of the linkage is bonded to the nitrogen;
R16, R17, and R18 are each independently H; C1-C3 alkyl; C3-C6 cycloalkyl; or phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl,
C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
R19, R20, R21, R22, R23, and R24 are each independently C1-C6 alkyl; C1-C4
haloalkyl; C2-C6 alkenyl; C1-C4 alkoxy; or phenyl;
each R25 is independently C1-C4 alkyl; C1-C4 haloalkyl; C2-C4 alkenyl; C1-C4 alkoxy; or phenyl;
each R26 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; each R27 is independently C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; n and p are each independently 0, 1 or 2;
r is 0 or 1 ; and
s is 2 or 3; provided that
(i) when G is G-1 or G-4 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of R1 1, R12, or both R1 1 and R12;
(ii) when G is G-2, X is H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl or NH2 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with
R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
R11, R12, or both R11 and R12;
(hi) when G is G-1 and A is N, then Y is other than -O-, -S(O)n-, -NR15-, -CHR6-,
-CHR6CHR6-, -CR6=CR6-, -C≡C-, and a direct bond;
(iv) when G is G-1, A is N and W is S, NH or N(C1-C6 alkyl), then R2 is other than H;
(v) when G is G-3, B is NR5, X is H, NH2, NHR1 or N(C1-C6 alkyl)R1 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of R11, R12, or both R11 and R12; and
(vi) when G is G-3, B is NR5, X is NH2, NHR1 or N(C1-C6 alkyl.R1 and Y is O or a direct bond, then Z is other than phenyl substituted with R9 and optionally substituted with one or more R10.
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, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. The term "1-2 CH3" indicates that the substituent can be methyl or, when there is a hydrogen attached to the same atom, the substituent and said hydrogen can both be methyl. The term "1-2 alkyl" indicates that one or two of the available positions for that substituent may be alkyl which are independently selected. "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 olefinic bond. Examples of "alkenylene" include CH2CH=CH, CH2CH2CH=CH, CH2CH=CHCH2 and CH2CH=CHCH2CH2. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. The term "1-3 alkoxy" indicates that one to three of the available positions for that substituent may be alkoxy which are independently selected; and the term "1-2 alkoxy" is defined analogously. "Alkoxyalkyl" 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 hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2, CH3CH2S(O)2, CH3CH2CH2S(O)2, (CH3)2CHS(O)2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkenylthio", "alkenylsulfinyl", "alkenylsulfonyl", "alkynylthio",
"alkynylsulfinyl", "alkynylsulfonyl", and the like, are defined analogously to the above examples. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkoxy" includes the same groups linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy. "Cycloalkenyl" includes groups such as cyclopentenyl and cyclohexenyl as well as groups with more than one double bond such as 1,3- and 1,4-cyclohexadienyl. "Trialkylsilylalkoxyalkoxy" denotes trialkylsilylalkoxy substitution on alkoxy. Examples of "trialkylsilylalkoxyalkoxy" includes, for example, (CH3)3SiCH2CH2OCH2O. The term "aromatic carbocyclic ring system" includes fully aromatic carbocycles and carbocycles in which at least one ring of a polycyclic ring system is aromatic (where aromatic indicates that the Hückel rule is satisfied). The term "nonaromatic carbocyclic ring system" denotes fully saturated carbocycles as well as partially or fully unsaturated carbocycles where the Hückel rule is not satisfied by any of the rings in the ring system. The term "aromatic heterocyclic ring system" includes fully aromatic heterocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where aromatic indicates that the Hückel rule is satisfied). The term "nonaromatic heterocyclic ring system" denotes fully saturated heterocycles as well as partially or fully unsaturated heterocycles where the Hückel rule is not satisfied by any of the rings in the ring system. The heterocyclic ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen. 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, ClCH2, CF3CH2 and CF3CCl2. The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (Cl)2C=CHCH2 and
CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HC≡CCHCl, CF3C=C, CCl3C≡C and FCH2C≡CCH2. Examples of "haloalkoxy" include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O. Examples of "haloalkylthio" include CCl3S, CF3S, CCl3CH2S and ClCH2CH2CH2S. 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 "Ci-Cj" prefix where i and j are numbers from 1 to 10. For example, C1-C3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl. Examples of "alkylcarbonyl" include C(O)CH3, C(O)CH2CH2CH3 and C(O)CH(CH3)2. 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 heterocyclic rings, all substituents are attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
When a group contains a substituent which can be hydrogen, for example R9 or
R13, 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). 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 N-oxides and agriculturally
suitable salts thereof, wherein:
E is selected from the group 1,2-phenylene; 1,5-, 1,6-, 1,7-, 1,8-, 2,6-, 2,7-, 1,2-, and 2,3-naphthalenediyl; 1H-pyrrole-1,2-, 2,3- and 3,4-diyl; 2,3- and 3,4-furandiyl; 2,3- and 3,4-thiophenediyl;
1H-pyrazole-1,5-, 3,4- and 4,5-diyl; 1H-imidazole-1,2-, 4,5- and 1,5-diyl; 3,4- and 4,5-isoxazolediyl; 4,5-oxazolediyl; 3,4- and 4,5-isothiazolediyl; 4,5-thiazolediyl; 1H-1,2,3-triazole-1,5- and 4,5-diyl; 2H-1,2,3-triazole-4,5-diyl; 1H-1,2,4-triazole- 1,5-diyl; 4H-1,2,4-triazole-3,4-diyl; 1,2,3-oxadiazole-4,5-diyl;
1,2,5-oxadiazole-3,4-diyl; 1,2,3-thiadiazole-4,5-diyl;
1,2,5-thiadiazole-3,4-diyl; 1H-tetrazole- 1,5-diyl; 2,3- and
3,4-pyridinediyl; 3,4- and 4,5-pyridazinediyl; 4,5-pyrimidinediyl; 2,3-pyrazinediyl; 1,2,3-triazine-4,5-diyl; 1,2,4-triazine-5,6-diyl; 1H-indole-1,4-, 1,5-, 1,6-, 1,7-, 2,4-, 2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 1,2-, 2,3-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-,
3,4-, 3,5-, 3,6-, 3,7-, 2,3-, 4,5-, 5,6- and 6,7-benzofurandiyl;
benzo[b]thiophene-2,4-, 2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 2,3-, 4,5-, 5,6- and 6,7-diyl; 1H-indazole-1,4-, 1,5-, 1,6-, 1,7-, 3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl; 1H-benzimidazole-1,4-, 1,5-, 1,6-, 1,7-, 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-diyl;
1,2-benzisoxazole-3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-benzoxazolediyl;
1,2-benzisothiazole-3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-benzothiazolediyl; 2,5-, 2,6-, 2,7-, 2,8-, 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 2,3-, 3,4-,
5,6-, 6,7- and 7,8-quinolinediyl; 1,5-, 1,6-, 1,7-, 1,8-, 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 3,4-, 5,6-, 6,7- and
7,8-isoquinolinediyl; 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 3,4-, 5,6-, 6,7- and 7,8-cinnolinediyl; 1,5-, 1,6-, 1,7-, 1,8-, 5,6-, 6,7- and 7,8-phthalazinediyl; 2,5-, 2,6-, 2,7-, 2,8-, 4,5-, 4,6-, 4,7-, 4,8-, 5,6-,
6,7- and 7,8-quinazolinediyl; 2,5-, 2,6-, 2,7-, 2,8-, 2,3-, 5,6-, 6,7- and 7,8-quinoxalinediyl; 1,8,-naphthyridine-2,5-, 2,6-, 2,7-, 3,5-, 3,6-, 4,5-, 2,3- and 3,4-diyl; 2,6-, 2,7-, 4,6-, 4,7-, 6,7-pteridinediyl; pyrazolo[5,1-b]thiazole-2,6-, 2,7-, 3,6-, 3,7-, 2,3- and 6,7-diyl; thiazolo[2,3-c]-1,2,4-triazole-2,5-, 2,6-, 5,6-diyl;
2-oxo-1,3-benzodioxole-4,5- and 5,6-diyl;
1,3-dioxo-1H-isoindole-2,4-, 2,5-, 4,5- and 5,6-diyl;
2-oxo-2H-1-benzopyran-3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 5,6-, 6,7- and 7,8-diyl; [1,2,4]triazolo[1,5-α]pyridine-2,5-, 2,6-, 2,7-, 2,8-, 5,6-, 6,7- and 7,8-diyl;
3,4-dihydro-2,4-dioxo-2H-1,3-benzoxazine-3,5-, 3,6-, 3,7-, 3,8-, 5,6-, 6,7- and 7,8-diyl; 2,3-dihydro-2-oxo-3,4-, 3,5-, 3,6-, 3,7-,
4,5-, 5,6- and 6,7-benzofurandiyl; thieno[3,2- d]thiazole-2,5-, 2,6-, and 5,6-diyl; 5,6,7,8-tetrahydro-2,5-, 2,6-, 2,7-, 2,8-, 3,5-, 3,6-,
3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 2,3- and 3,4-quinolinediyl;
2,3-dihydro-l,1,3-trioxo-1,2-benzisothiazole-2,4-, 2,5-, 2,6-, 2,7-,
4,5-, 5,6- and 6,7-diyl; 1,3-benzodioxole-2,4-, 2,5-, 4,5- and
5,6-diyl; 2,3-dihydro-2,4-, 2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-,
4,5-, 5,6- and 6,7-benzofurandiyl;
2,3-dihydro-1,4-benzodioxin-2,5-, 2,6-, 2,7-, 2,8-, 5,6- and 6,7-diyl; and 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2,4-, 2,5-, 2,6-,
2,7-, 2,8-, 3,4-, 3,5-, 3,6-, 3,7-, 3,8-, and 2,3-diyl; each aromatic ring system optionally substituted with one of R3, R4, or both R3 and R4;
W is O;
R1 is C1-C3 alkyl or C1-C3 haloalkyl;
R2 is Η; C1-C6 alkyl; C1-C6 haloalkyl; or C3-C6 cycloalkyl;
R3 and R4 are each independently halogen; cyano; nitro; C1-C6 alkyl;
C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 alkylthio; C1-C6 alkylsulfonyl; C2-C6 alkylcarbonyl; C2-C6 alkoxycarbonyl; (C1-C4 alkyl)NΗC(O); (C1-C4 alkyl)2NC(O); benzoyl; or phenylsulfonyl;
Y is -O-; -CH=CH-; -C≡C-; -CH2O-; -OCH2-; -CH2S(O)n-;
-CH2O-N=C(R7)-; -(R7)C=N-OCH(R15)-; -C(R7)=N-O-;
-CH2OC(O)NH-; -CH2S-C(R7)=N-; -CH=CR6-C(=W1)-A1-; or a direct bond;
R7 is H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 alkylthio;
C2-C6 alkenyl; C2-C6 alkynyl; C3-C6 cycloalkyl; halogen; or cyano; or
when Y and an R10 are attached to adjacent atoms on Z and Y is
-CH2O-N=C(R7)-, R7 and said adjacently attached R 10 can be taken together as -(CH2)r-J- such that J is attached to Z;
Z is selected from the group C1-C10 alkyl; C3-C6 cycloalkyl; phenyl;
naphthalenyl; anthracenyl; phenanthrenyl; 1H-pyrrolyl; furanyl; thienyl; 1H-pyrazolyl; 1H-imidazolyl; isoxazolyl; oxazolyl;
isothiazolyl; thiazolyl; 1H- 1 ,2,3-triazolyl; 2H- 1 ,2,3-triazolyl;
1H-1,2,4-triazolyl; 4H-1,2,4-triazolyl; 1,2,3-oxadiazolyl; 1,2,4-oxadiazolyl; 1,2,5-oxadiazolyl; 1,3,4-oxadiazolyl;
1,2,3-thiadiazolyl; 1,2,4-thiadiazolyl; 1,2,5-thiadiazolyl;
1,3,4-thiadiazolyl; 1H-tetrazolyl; 2H-tetrazolyl; pyridinyl;
pyridazinyl; pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; 1,2,4,5-tetrazinyl; 1H-indolyl; benzofuranyl; benzo[b]thiophenyl; 1H-indazolyl; 1H-benzimidazolyl; benzoxazolyl; benzothiazolyl; quinolinyl; isoquinolinyl; cinnolinyl; phthalazinyl; quinazoUnyl;
quinoxalinyl; 1,8-naphthyridinyl; pteridinyl; 2,3-dihydro-1H-indenyl;
1,2,3,4-tetrahydronaphthalenyl;
6,7,8,9-tetrahydro-5H-benzocycloheptenyl;
5,6,7,8,9,10-hexahydrobenzocyclooctenyl;
2,3-dihydro-3-oxobenzofuranyl; 1,3-dihydro-1-oxoisobenzofuranyl;
2,3-dihydro-2-oxobenzofuranyl;
3,4-dihydro-4-oxo-2H-1-benzopyranyl;
3 ,4-dihydro-1-oxo-1H-2-benzopyranyl ;
3,4-dihydro-3-oxo-1H-2-benzopyranyl;
3,4-dihydro-2-oxo-2H-1-benzopyranyl; 4-oxo-4H-1-benzopyranyl ;
2-OXO-2H-1-benzopyranyl;
2,3,4,5-tetrahydro-5-oxo-1-benzoxepinyl;
2,3,4,5-tetrahydro-2-oxo-1-benzoxepinyl;
2,3-dihydro-1,3-dioxo-1H-isoindolyl;
1,2,3,4-tetrahydro-1,3-dioxoisoquinolinyl;
3 ,4-dihydro-2,4-dioxo-2H-1,3-benzoxazinyl;
2-oxo- 1,3-benzodioxyl;
2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazolyl; 9H-fluorenyl;
azulenyl; and thiazolo[2,3-c]-1,2,4-triazolyl; each group substituted with R9 and optionally substituted with one or more R10;
R9 is Η; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 alkylthio; cyano; CO2(C1-C6 alkyl);
NΗ(C1-C6 alkyl); N(C1-C6 alkyl)2; SiR22R23R24; or GeR22R23R24; or R9 is C3-C6 cycloalkyl, phenyl, phenoxy, pyridinyl, pyridinyloxy, pyrimidinyl, or pyrimidinyloxy, each optionally substituted with one of R11, R12, or both R1 1 and R12; and
each R15 is independently H; C1-C3 alkyl; or C3-C6 cycloalkyl. Preferred 2. Compounds of Preferred 1 wherein:
E is selected from the group 1,2-phenylene; 1,6-, 1,7-, 1,2-, and 2,3-naphthalenediyl; 2,3- and 3,4-furandiyl; 2,3- and 3,4-thiophenediyl; 2,3- and 3,4-pyridinediyl; 4,5-pyrimidinediyl; 2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and 6,7-benzofurandiyl; and benzo[b]thiophene-2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and 6,7-diyl; each aromatic ring system optionally substituted with one of R3, R4, or both R3 and R4;
Z is selected from the group phenyl; pyridinyl; pyrimidinyl; and naphthalenyl; each group substituted with R9 and optionally substituted with one or more R10;
R7 is H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 alkylthio;
C2-C6 alkenyl; C2-C6 alkynyl; cyclopropyl; halogen; or cyano; or when Y and an R10 are attached to adjacent atoms on Z and Y is -CH2O-N=C(R7)-, R7 and said adjacently attached R10 can be taken together as -(CH2)r-J- such that J is attached to Z;
J is -CH2- or -CH2CH2-; and
r is 1.
Preferred 3. Compounds of Preferred 2 wherein:
E is selected from the group 1,2-phenylene; 2,3- and 3,4-thiophenediyl; and 2,3- and 3,4-pyridinediyl; each aromatic ring system optionally substituted with one of R3, R4, or both R3 and R4;
B is O or NR5;
X is C1-C3 alkyl; NHR1; or N(C1-C3 alkyl)R1;
R1 is C1-C3 alkyl;
R2 is H or C1-C2 alkyl;
Y is -O-; -CH=CH-; -CH2O-; -CH2O-N=C(R7)-; -(R7)C=N-OCH(R15)-;
-CH2OC(=O)NH-; -CH2S-C(R7)=N-; or -CH=CR6-C(=W1)-A1-; R7 is H; C1-C3 alkyl; C1-C3 haloalkyl; C1-C3 alkoxy; C1-C3 alkylthio; or cyclopropyl; and
each R15 is independently H; C1-C3 alkyl; or cyclopropyl.
Preferred 4. Compounds of Preferred 3 wherein:
G is G-1; and
A is N.
Preferred 5. Compounds of Preferred 4 wherein:
R2 is methyl. Preferred 6. Compounds of Preferred 3 wherein:
G is G-2;
A is N; and
X is NHR1 or N(C1-C6 alkyl.R1.
Preferred 7. Compounds of Preferred 6 wherein:
R1 is methyl; and
R2 is methyl.
Most preferred are compounds of Preferred 3 selected from the group:
1,4-dihydro-1-methyl-4-[2-[[[[1-[3- (trifluoromethyl)phenyl]ethyhdene]amino]oxy]methyl]phenyl]-5H-tetrazol-5- one;
1,4-dihydro-1-methyl-4-[2-[[[[1-[3-
(trimethylsilyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-5H-tetrazol-5-one; 2,4-dihydro-2-methyl-5-(methylamino)-4-[2-[[[[1-[3- (trimethylsilyl)phenyl]ethyhdene]amino]oxy]methyl]phenyl]-3H- 1 ,2,4-triazol-3- one; and
2,4-dihydro-2,5-dimethyl-4-[2-[[[[1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol- 3-one.
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.
Of note are embodiments where G is G-1, G-2 or G-3; embodiments where X is C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, cyano, NΗ2, NHR1 or
N(C1-C6 alkyl.R1; embodiments where R2 is H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl or C2-C4 alkoxycarbonyl; embodiments where Y is -O-, -S(O)n-, -NR15-, -C(=O)-, -CH(OR15)-, -CHR6-, -CHR6CHR6-, -CR6=CR6-, -C≡C-, -CHR15O-, -OCHR15-, -CHR15S(O)n-, -S(O)nCHR15-, -CHR15O-N=C(R7)-,
-(R7)C=N-OCH(R15)-, -C(R7)=N-O-, -O-N=C(R7)-, -CHR15OC(=O)N(R15)-, -CHR15OC(=S)N(R15)-, -CHR15O-N(R15)C(=O)N(R15)-,
-CHR15O-N(R15)C(=S)N(R15)-, -CHR15O-N=C(R7)NR15-,
-CHR15O-N=C(R7)OCH2-, -CHR15O-N=C(R7)-N=N-, -CHR15O-N=C(R7)-C(=O)-, -CHR15S-C(R7)=N-, -C(R7)=N-NR15-, -CH=N-N=C(R7)-,
-CHR15N(COCH3)-N=C(R7)-, -OC(=S)NR15C(=O)-, -CHR6-C(=W1)-A1-,
-CHR6CHR6-C(=W1)-A1-, -CR6=CR6-C(=W1)-A1-, -C≡C-C(=W1)-A1-,
-N=CR6-C(=W1)-A1- or a direct bond; embodiments where R7 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylthio, C1-C6 haloalkylsulfinyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, halogen, cyano or morpholinyl;
embodiments where Z is other than C3-C6 cycloalkenyl and adamantyl each substituted with R9 and optionally substituted with one or more R10; embodiments where R9 is H, 1-2 halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 alkenyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl,
CO2(C1-C6 alkyl), NH(C1-C6 alkyl), N(C1-C6 alkyl)2, -C(R18)=NOR17, cyano, nitro, SF5, SiR22R23R24, GeR22R23R24, or phenyl, benzyl, benzoyl, phenoxy, pyridinyl, pyridinyloxy, thienyl, thienyloxy, furanyl, pyrimidinyl, or pyrimidinyloxy each optionally substituted with one of R11, R12, or both R1 1 and R 12 ; embodiments where each R10 is independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, nitro or cyano; embodiments where, when Y and an R10 are attached to adjacent atoms on Z and Y is -CHR15O-N=C(R7)-, -O-N=C(R7)-, -CH=N-N=C(R7)- or
-CHR15N(COCH3)-N=C(R7)-, R7 and said adjacently attached R10 are taken together as -(CH2)r-J- such that J is attached to Z; embodiments where R11 and R12 are each independently halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C3-C6 alkenyloxy, C3-C6 haloalkenyloxy, C1-C4 alkylthio, C1-C4 haloalkylthio, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C3-C6 alkenylthio, C3-C6 haloalkenylthio, nitro, cyano, SF5, Si(R25)3 or Ge(R25)3; embodiments where R19, R20, R21, R22, R23, and R24 are each independently C1-C6 alkyl, C1-C4 alkoxy or phenyl; embodiments where each R25 is independently C1-C4 alkyl or phenyl; and embodiments where R3 and R4 are each independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylsulfonyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, (C1-C4 alkyl)NHC(O), (C1-C4 alkyl)2NC(O), benzoyl or phenylsulfonyl. The compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-35. The definitions of G, E, A, B, W, X, X1, R1-R27, Y, Z1, W1, A1-A3, Z, Q, J, n, p, r and s in the compounds of
Formulae 1-80 below are as defined above in the Summary of the Invention.
One skilled in the art will recognize that some compounds of Formula I can exist in one or more tautomeric forms. The present invention comprises all tautomeric forms of compounds of Formula I.
The compounds of Formula I can be prepared as described below in Procedures 1-4. Procedure 1 describes the syntheses of compounds of Formula I in which a final alkylation is used to prepare compounds of Formula I in which G = G-1, G-4 and G-5. Procedure 2) describes the syntheses of compounds of Formula I in which G = G-2 or G-3 and procedures for intermediates leading to compounds of Formula I in which G = G-4 and G-5. Procedures 3) and 4) describe syntheses that are applicable to compounds of Formula I in which G = G-1, G-2, G-3, G-4 and G-5, including the syntheses of the aryl moiety (E-Y-Z) before and after the constructions of G.
1) Synthesis of G-1, G-4 and G-5
Compounds of Formula 2 can be reduced to compounds of Formula 1 in protic solvents (Scheme 1) such as aliphatic alcohols or water, or aliphatic alcohol and water mixtures using metal hydrides such as sodium borohydride (for additional references using different conditions see Larock, Comprehensive Organic Transformations, R. C. Larock: New York, (1989), pp. 528-534).
Figure imgf000021_0001
Compounds of Formula 2a can be prepared by reacting N,N-drnιemylformarnide with an aryl metal species of Formula 4 (Scheme 2) generated in situ by reacting an aryl halide of Formula 3 with metallic magnesium to form an aryl Grignard intermediate or with an alkyllithium to generate an aryllithium intermediate. The addition of organometallic compounds to carbonyl groups is well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), pp. 920-929).
Figure imgf000022_0001
Compounds of Formula 5, 5a, and 5b can be prepared by treating compounds of Formula 6, 6a, 6b, and 6c with the appropriate alkyl transfer reagent in an inert solvent with or without additional acidic or basic reagents or other reagents (Scheme 3).
Suitable solvents are selected from the group consisting of polar aprotic solvents such as acetonitrile, N,N-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; and halocarbons such as dichloromethane or chloroform.
Figure imgf000022_0002
Figure imgf000023_0001
For example, compounds of Formula 5 can be prepared by the action of diazoalkane reagents of Formula 7 such as diazomethane (U = H) or
trimethylsilyldiazomethane (U = (CH3)3Si) on carbonyl compounds of Formula 6 (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 5 can also be prepared by contacting carbonyl compounds of Formula 6 with alkyl trichloroacetimidates of
Formula 8 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 5 can also be prepared from compounds of Formula 6 by treatment with a trialkyloxonium tetrafluoroborate (i.e. Meerwein's salt) of Formula 9 (Method 3). The use of trialkyloxonium salts as powerful alkylating agents is well known in the art (see U. Schöllkopf, U. Groth, C. Deng, Angew. Chem., Int. Ed. Engl.,
(1981), 20, 798).
Other alkylating agents which can convert carbonyl compounds of Formula 6 to compounds of Formula 5 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,
1,8-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.
Two sequential applications of Methods 1-4 to compounds of Formula 6a can be used to prepare compounds of Formula 5a, via compounds of Formula 6b. When compounds of Formula 5a have equivalent R1 groups, they can be prepared by reacting compounds of Formula 6a with two equivalents of the appropriate alkylating agents according to Methods 1-4.
Compounds of Formula 5b can be prepared from compounds of Formula 6c by appropriate applications of Methods 1-4. See G. Zvilichovsky, M. David,
J. Heterocyclic Chem., (1988) 25, 1307 for alkylation examples applied to compound
6d, leading to, among others, compound 5c (not a compound of the present invention).
Compounds of Formula 6e can be synthesized as outlined in Scheme 4. An isocyanate or isothiocyanate (Formula 36) as prepared in Scheme 20 below is reacted with trimethylsilyl azide (TMS-azide) with or without solvent followed by contacting the crude product with water. For examples of these and other procedures to effect this kind of transformation, see O. Tsuge, et al, J. Org. Chem., 45, 5130 (1980).
Figure imgf000025_0001
2) Syntheses of G-2 and G-3, and Intermediates leading to G-4 and G-5
Compounds of Formula 10 or 10a (compounds of Formula I wherein G = G-3 and W = O can be prepared by condensation of malonate derivatives (U1 = T) or β-keto esters (U1 = C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl), respectively, of Formula 11 with an ambident nucleophile of Formula 12 (Scheme 5). The nucleophiles of Formula 12 are N- substituted hydroxylamines (HO-ΝHR2) and substituted hydrazines (HΝ(R5)-ΝHR2). Compounds of Formula 6c can be prepared from compounds of Formula 11a (when U1 = T) by reaction with an ambident nucleophile of Formula 12a. Compounds of Formula 10b (compounds of Formula I, wherein G = G-5) can be prepared from compounds of Formula 11a (U1 = C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl). Examples of nucleophiles of Formulae 12 and 12a are
N-methylhydroxylamine and methylhydrazine. Compounds of Formula 11 and 11a can be prepared by methods described hereinafter. The esters of Formula 11 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. In cases where U1 equals alkyl in Formula 11 the carbonyl may need protecting. For examples of this type of chemistry, see B. Ruhland and G. Leclerc, J. Heterocyclic Chem., 26, 469 (1989).
1 1 m 1 C1-C6 C1-C6 C1-C6
Figure imgf000026_0001
Compounds of Formula 10aa can be prepared by reaction of nitrile esters of Formula 11aa with ambident nucleophiles of Formula 12 (Scheme 5a). Alkylation of 10aa with alkyl halides in the presence of base provides compounds of Formula 10ab. Alternatively, treatment of 10aa with alkylamines or alkoxy amines provides compounds of Formula 10ab.
Figure imgf000027_0001
Esters of Formula 11 or 11c can be prepared from copper (I)-catalyzed reaction of compounds of Formula 13 or 13a with substituted aryl halides of Formula 14 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 6. Procedures to prepare compounds of
Formula 14 are described below (see Scheme 35).
Esters of Formula 11 or 11c can also be prepared from compounds of Formula 11d after modification of the carboxylic acid functional group to the appropriate Y and Z group. A copper (I)-catalyzed coupling of compounds of Formula 13 or 13a with
ort ho-bromocarboxylic acids of Formula 14a (see A. Bruggink, A. McKillop, Tetrahedron, (1975), 31, 2607) can be used to prepare compounds of Formula 11b or 11d as shown in Scheme 6. Methods to prepare compounds of Formula 14a 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).
Figure imgf000028_0001
Figure imgf000029_0001
Additionally, the malonate esters of Formula 11e can be prepared by treating aryl acetic acid esters of Formula 15 with a dialkyl carbonate or alkyl chloroformate in the presence of a suitable base such as, but not limited to, sodium metal or sodium hydride (Scheme 7). For example, see J. Am. Chem. Soc, (1928), 50, 2758. Compounds of Formula 11f can be prepared from compounds of Formula 11e by alkylation with a suitable alkylating agent in an inert solvent. Suitable alkylating agents include dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl
trifluoromethanesulfonate, and alkyl halides such as iodomethane. 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 alkali metal amides such as lithium diisopropylamide. Suitable solvents include polar aprotic solvents such as N,N-dimethylformamide or ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether. Alkylations of this type are well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), p 412, and references therein).
Figure imgf000030_0001
Alternatively, esters of Formula 15 can be alkylated to provide esters of
Formula 15a by alkylation with a suitable alkylating agent in an inert solvent
(Scheme 7a). Suitable alkylating agents include dialkyl sulfates such as dimethyl sulfate, haloalkyl sulfonates such as methyl trifluoromethanesulfonate, and alkyl halides such as iodomethane. 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 alkali metal amides such as lithium diisopropylamide. Suitable solvents include polar aprotic solvents such as
N,N-dimethylformamide or ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether. Alkylations of this type are well known in the art (see March, J. Advanced Organic Chemistry; 4th ed., John Wiley: New York, (1992), p 416-418, and references therein).
Esters of Formula 15a can be treated with a carbonylating agent of Formula 34 to provide compounds of Formula 11g. The carbonylating agents of Formula 34 are carbonyl or thiocarbonyl transfer reagents such as phosgene, thiophosgene, diphosgene (ClC(=O)OCCl3), triphosgene (Cl3COC(=O)OCCl3), N, N'-carbonyldiimidazole, N,N'-thiocarbonyldiimidazole, and 1,1'-carbonyldi(1,2,4-triazole). Alternatively, the compounds of Formula 34 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.
Compounds of Formula 6c can be prepared from compounds of Formula 11g by reaction with an ambident nucleophile of Formula 12a. An example of nucleophiles of
Formula 12a is methylhydrazine.
) 4
Figure imgf000031_0001
Nitrile esters of Formula 11aa (Scheme 7b) can be prepared by reacting
compounds of Formula 16 under similar conditions outlined in Scheme 7a.
Figure imgf000032_0001
Esters of Formula 15 can be prepared from acid-catalyzed alcoholysis of aryl acetonitriles of Formula 16 or esterification of aryl acetic acids of Formula 17 as illustrated in Scheme 8 (see Org. Synth., Coll. Vol. I, (1941), 270).
Additionally, esters of Formula 15 can be prepared by palladium (O)-catalyzed cross coupling reaction of aryl iodides of Formula 14 with a Reformatsky reagent or an alkoxy(trialkylstannyl)acetylene followed by hydration (Scheme 8). 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.
I
Figure imgf000032_0002
Aryl acetic acid esters of Formula 15b can also be prepared by copper (I)-catalyzed condensation of aryl halides of Formula 18 with compounds of Formula 19 as described in EP-A-307,103 and illustrated below in Scheme 9.
Figure imgf000033_0001
Some esters of Formula 15 (Formula 15c) can also be prepared by forming the Y2 bridge using conventional nucleophilic substitution chemistry (Scheme 10).
Displacement of an appropriate leaving group (Lg) in electrophiles of Formula 21 or 22 with a nucleophilic ester of Formula 20 affords compounds of Formula 15c. A base, for example sodium hydride, is used to generate the corresponding alkoxide or thioalkoxide of the compound of Formula 20.
5
Figure imgf000033_0002
Some esters of Formula 15 (Formula 15f) can also be prepared by forming the Y3 bridge from substituted hydroxylamine 15e and carbonyl compounds 22a. The hydroxylamine 15e is in turn prepared from esters 15d. This method has been described in EP-A-600,835 and illustrated in Scheme 11.
A
Figure imgf000034_0001
Compounds of Formula 23 (compounds of Formula I in which G = G-2 or G-3, G' = C or N, and A' = A or B) can be prepared by reaction of Formula 24 compounds with lower alkyl amines in a suitable solvent such as methanol or dioxane (Scheme 12). The leaving group Lg1 in the amides of Formula 24 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. Similarly, compounds of Formula 23a can be prepared from compounds of 24a. Compounds of Formula 23b and 23c can be prepared by reaction of compounds of 24 or 24a, respectively, with alkali or transition metal cyanide salts. Displacements of this type are well established in the art. The reactions are usually conducted in polar, aprotic solvents such as N,N- dimethylformamide, with or without additional catalysts. For an example, see A.
Miyashita, y. Suzuki, K. Ohta, T. Higashino, Heterocycles, (1994) 39, 345.
Figure imgf000035_0001
Compounds of Formula 24b can be prepared from compounds of Formula 25 by reaction with halogenating agents such as thionyl chloride or phosphorus oxybromide to form the corresponding β-halo-substituted derivatives (Scheme 13). Alternatively, compounds of Formula 25 can be treated with an alkylsulfonyl halide or haloalkylsulfonyl anhydride, such as methanesulfonyl chloride, p-toluenesulfonyl chloride, and
trifluoromethanesulfonyl anhydride, to form the corresponding β-alkylsulfonate of Formula 24b. The reaction with the sulfonyl halides may be performed in the presence of a suitable base (e.g., triethylamine). In a similar manner, compounds of Formula 24c can be prepared from compounds of Formula 6c.
g
Figure imgf000036_0001
As illustrated in Scheme 14, sulfonyl compounds of Formula 24d can be prepared by oxidation of the corresponding thio compound of Formula 26 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-chloro-peroxybenzoic acid, hydrogen peroxide and Oxone® (KHSO5). Similarly, compounds of Formula 26a can be oxidized to compounds of Formula 24e with one or two equivalents of oxidizing reagent.
Figure imgf000037_0001
Alternatively, halo-compounds of Formula 24f (compounds of Formula 24b wherein A' = A = N, G' = N, and W = O) can be prepared from hydrazides of Formula 27 as illustrated in Scheme 15. When R27 = C(=S)S(C1-C4 alkyl), the diacyl compound of Formula 27 is treated with excess thionyl halide, for example excess thionyl chloride. The product formed first is the ring-closed compound of Formula 28 which can be isolated or converted in situ to the compound of Formula 24f; see P. Molina, A. Tarraga, A. Espinosa, Synthesis, (1989), 923 for a description of this process.
Alternatively, when R27 = R2 as defined above, the hydrazide of Formula 27 is cyclized with phosgene to form the cyclic urea of Formula 24f wherein hal = Cl. This procedure is described in detail in J. Org. Chem., (1989), 54, 1048.
Figure imgf000038_0001
The hydrazides of Formula 27 can be prepared as illustrated in Scheme 16.
Condensation of the isocyanate of Formula 29 with the hydrazine of
Formula H2NNR2R27 in an inert solvent such as tetrahydrofuran affords the hydrazide.
Figure imgf000038_0002
7
In addition to the methods disclosed above, compounds of Formula 30 can be prepared by treating a ketenedithioacetal of Formula 31 with an ambident nucleophile of Formula 12 (Scheme 17). The nucleophiles of Formula 12 are described above.
Figure imgf000039_0001
Ketene dithioacetals of Formula 31a can be prepared by condensing arylacetic acid esters of Formula 15 with carbon disulfide in the presence of a suitable base, followed by reaction with two equivalents of an V-halide, such as iodomethane or propargyl bromide (Scheme 18).
Figure imgf000039_0002
Compounds of Formula 32 can be prepared by condensation of N-amino-ureas of Formula 33 with a carbonylating agent of Formula 34 (Scheme 19). The carbonylating agents of Formula 34 are carbonyl or thiocarbonyl transfer reagents such as phosgene, thiophosgene, diphosgene (ClC(=O)OCCl3), triphosgene (Cl3COC(=O)OCCl3),
N, N'-carbonyldiimidazole, N, N'-thiocarbonyldiimidazole, and
1,1'-carbonyldi(1,2,4-triazole). Alternatively, the compounds of Formula 34 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. Also, compounds of Formula 32a can be prepared by reacting compounds of Formula 33a with alkylamidines in solvents such as n-butanol or N,N-dimethylformamide in the presence of a base, followed by N-alkylation (in the presence of a base) with an alkylhalide as demonstrated by J. Heeves, et al., J. Med. Chem., 1984, 27, 894-900 (Scheme 19).
Figure imgf000040_0001
N-Amino-ureas of Formula 33 can be prepared as illustrated in Scheme 20.
Treatment of an arylamine of Formula 35 with phosgene, thiophosgene,
N, N'-carbonyldiimidazole, or N, N'-thiocarbonyldiimidazole produces the isocyanate or isothiocyanate of Formula 36. 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 33.
Figure imgf000041_0001
Additionally, Formula 33a compounds can be prepared by reaction of Formula 36 iso(thiocyanates) as outlined in Scheme 20a.
Figure imgf000042_0001
Compounds of Formula 37 can be prepared by either method illustrated in Scheme 21. Ureas of Formula 38 are reacted with activated 2-halocarboxylic acid derivatives 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 37 compounds can be prepared by reaction of Formula 36 isocyanates with Formula 39a esters. As described above, base may be added to accelerate the reaction and subsequent cyclization to Formula 37 compounds.
Figure imgf000043_0001
The ureas of Formula 38 can be prepared by either of the methods illustrated in Scheme 22. The arylamine of Formula 35 can be contacted with an isocyanate or isothiocyanate of Formula R2N=C=W as described above. Alternatively, an isocyanate or isothiocyanate of Formula 36 can be condensed with an amine of Formula R2-NH2 to form the urea. The arylamine and iso(thio)cyanates of Formulae 35 and 36, 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), 23(3), 335 and references therein. For methods describing the preparation of arylamines of Formula 35 that are not commercially available, see M. S. Gibson in The Chemistry oftheAmino Group; Patai, S., Ed.; Interscience Publishers, (1968); p 37 and Tetrahedron Lett. (1982), 23(7), 699 and references therein.
Figure imgf000044_0001
3) Thionation Procedures
Compounds of Formula 39 (compounds of Formula I wherein G = G- 1 , W = S) can be prepared by treating compounds of Formula 40 with thionating reagents such as P2S5 or Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane- 2,4-disulfide) as illustrated in Scheme 23 (see Bull. Soc. Chim. Belg., (1978), 87, 229; and Tetrahedron Lett., (1983), 24, 3815). Under similar conditions, compounds of Formula 41 (compounds of Formula I wherein G = G-2 or G-3, G' = C or N, and A' = A or B) can be prepared from compounds of Formula 42. Compounds of Formula 41a (compounds of formula I wherein G = G-5, W = S) can be prepared from compounds of Formula 42a.
Figure imgf000045_0001
4) Aryl Moiety (E-Y-Z) Synthesis Procedures
Compounds of Formula 43 (compounds of Formula I wherein Y is CHR15O, CHR15S, or CHR15O-N=CR7) can be prepared by contacting halides of Formula 44 with various nucleophiles (Scheme 24). 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.
5 5
Figure imgf000046_0001
Some aryl halides of Formula 44 can be prepared by radical halogenation of the corresponding alkyl compound (i.e., H instead of halogen in Formula 44), or by acidic cleavage of the corresponding methylether (i.e., OMe instead of halogen in Formula 44). Other aryl halides of Formula 44 can be prepared from the appropriate alcohols of Formula 45 by well known halogenation methods in the art (see Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry; 3rd ed., Part B, Plenum: New York, (1990), p 122).
Compounds of Formula I wherein Y is CR6=CR6 or CHR6-CHR6 (Formula 46 and 47, respectively) can be prepared as illustrated in Scheme 25. Treatment of the halides of Formula 44 with triphenylphosphine or a trialkylphosphite produces the corresponding phosphonium salt (Formula 49) or phosphonate (Formula 50), respectively. Condensation of the phosphorus compound with a base and a carbonyl compound of Formula Z(R6)C=O affords the olefin of Formula 46.
Figure imgf000047_0001
The olefins of Formula 46 can be converted to the saturated compounds of Formula 47 by hydrogenation over a metal catalyst such as palladium on carbon as is well-known in the art (Rylander, Catalytic Hydrogenation in Organic Synthesis;
Academic: New York, (1979)).
Formula 48 alkynes can be prepared by halogenation/dehalogenation of
Formula 46 olefins using procedures well-known in the art (March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), p 924). Additionally, Formula 48 alkynes can be prepared by well-known reaction of aryl halides with alkyne derivatives in the presence of catalysts such as nickel or palladium (see J. Organomet. Chem., (1975), 93 253-257).
The olefin of Formula 46 can also be prepared by reversing the reactivity of the reactants in the Wittig or Horner-Emmons condensation. For example, 2-alkylaryl derivatives of Formula 51 can be converted into the corresponding dibromo-compound of Formula 52 as illustrated in Scheme 26 (see Synthesis, (1988), 330). The dibromo- compound can be hydrolyzed to the carbonyl compound of Formula 53, which in turn can be condensed with a phosphorus-containing nucleophile of Formula 54 or 55 to afford the olefin of Formula 46. Additionally, compounds of Formula 53 can be prepared by oxidation of the corresponding alcohols of Formula 30.
Vinylhalides of Formula 56 can be prepared by reacting phosphorus reagents of Formulae 55a or 55b with carbonyl compounds of Formula 53 (Scheme 26). The preparations of halides of Formula 55a from the appropriate diethylphosphonoacetate are described by McKenna and Khawli in J. Org. Chem., (1986), 51, 5467. The thiono esters of Formula 55b can be prepared from esters of Formula 55a by converting the carbonyl oxygen of the ester to a thiocarbonyl (see Chem. Rev., (1984), 84, 17 and Tetrahedron Lett., (1984), 25, 2639).
Figure imgf000048_0001
Oximes of Formula 57 (Formula I wherein Y is C(R7) = N-O) can be prepared from carbonyl compounds of Formula 58 by condensation with hydroxylamine, followed by O-alkylation with electrophiles of Formula Z-(C1, Br, or I) (Scheme 27).
Alternatively, the O-substituted hydroxylamine can be condensed with the carbonyl compound of Formula 58 to yield oximes of Formula 57 directly. X
Figure imgf000049_0001
,
Carbamates of Formula 59 can be prepared by reacting aryl alcohols of Formula 45 with isocyanates of Formula 61 (Scheme 28). A base such as triethylamine can be added to catalyze the reaction. As shown, carbamates of Formula 59 can be further alkylated to provide the carbamates of Formula 60.
Figure imgf000049_0002
Compounds of Formula I wherein Y is -CHR15O-N=C(R7)-C(=N-A2-Z1)-A1-,
-CHR15O-N=C(R7)-C(R7)=N-A2-A3- or -CHR15O-N=C(-C(R7)=N-A2-Z1)- can be prepared by methods known in the art (see, for example, WO 95/18789, WO 95/21153, and references therein) together with the methods disclosed herein.
The compounds of the present invention are prepared by combinations of reactions as illustrated in the Schemes 1-28 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 L (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-L. 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 L is defined in individual schemes, and the preparation of representative Z-L examples. Compounds of Formula 63 in Scheme 29 can be prepared from compounds of
Formula 62 by reaction with hydroxylamine or hydroxylamine salts. See Sandier and
Karo, "Organic Functional Group Preparations," Vol. 3 Academic Press, New York,
(1972) 372-381 for a review of methods. Compounds of Formula 63 correspond to compounds of Formula 19 in Scheme 9 when Y1 = O-N=C(R7) and in Scheme 24, reagent HO-N=CR7.
Figure imgf000050_0001
Compounds of Formula 62 can be prepared from compounds of Formula 61a (Scheme 30) by Friedel-Crafts acylation with compounds of Formula 64. (See
Olah, G. Friedel-Crafts and Related Reactions, Interscience, New York (1963-1964) for a general review). Compounds of Formula 62 may also be prepared by reaction of acyl halides, anhydrides, esters, or amides of Formula 67 with organometallic reagents of Formula 66. (See March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 433-435 and references therein.) The organometallic compounds of Formula 66 may be prepared by reductive metallation or halogen-metal exchange of a halogen-containing compound of Formula 65 using, for example, magnesium or an organolithium reagent, or by deprotonation of compounds of Formula 61a using a strong base such as a lithioamide or an organolithium reagent, followed by transmetallation. Compound 62 corresponds to Compound 17a in Scheme 11, while Compound 62a corresponds to O = C(R6)Z in Scheme 25.
Figure imgf000051_0001
Compounds of Formula 65 may be prepared by reaction of compounds of
Formula 61a (Scheme 31) with, for example, bromine or chlorine, with or without additional catalysts, under free-radical or aromatic electrophilic halogenation conditions, depending on the nature of Z. Alternative sources of halogen, such as
N-halosuccinimides, tert-butyl hypohalites or SO2CI2, my also be used . (See March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 476-479, 620-626, and references therein.) For a review of free-radical halogenation, see Huyser, in Patai," The Chemistry of the Carbon-Halogen Bond," Part 1 , Wiley, New York (1973) pp 549-607. For electrophilic substitutions, see de la Mare, "Electrophilic Halogenation," Cambridge University Press, London (1976). Compounds of Formula 65 correspond to compounds of Formula 21 in Scheme 10 where Lg = Br, Cl, or I and reagent Z-hal in Scheme 27. Compounds of Formula 69 can be prepared from compounds of Formula 68 by similar procedures. Compounds of Formula 69 correspond to compounds of Formula 22 in Scheme 10 where Lg = Br, Cl, or I. Compounds of Formula 54 or 55 in Scheme 26 can be prepared by reaction of compounds of
Formula 69 with triphenylphosphine or trialkyl phosphites, respectively, followed by deprotonation with base. See Cadogen, "Organophosphorus Reagents in Organic Synthesis," Academic Press, New York (1979) for a general treatise on these reagents.
Figure imgf000052_0001
Compounds of Formula 70 can be prepared from compounds of Formula 62b by treatment with peracids such as perbenzoic or peracetic acid, or with other peroxy compounds in the presence of an acid catalysts, followed by hydrolysis of the resultant ester. For a review, see Plesnicar, in Trahanovsky, "Oxidation in Organic Chemistry, pt. C, Academic Press, New York (1978) pp 254-267. Formula 70 corresponds to
Formula 19 in Scheme 9 when Y1 = O and reagent HO-Z in Scheme 24. Compounds of Formula 74 can be prepared from compounds of Formula 70 by conversion to the dialkylthiocarbamates of Formula 72 followed by rearrangement to Formula 73 and subsequent hydrolysis. See M. S. Newman and H. A. Karnes, J. Org. Chem. (1966), 31, 3980-4. Formula 74 corresponds to Formula 19 in Scheme 9 when Y1 = S and reagent HS-Z in Scheme 24.
Figure imgf000053_0001
Compounds of Formula 75 can be converted to compounds of
Formulae 65, 70 or 74 via the diazonium compounds 76, by treatment with nitrous acid followed by subsequent reaction (Scheme 33). See reviews by Hegarty , pt. 2, pp 511-91 and Schank, pt. 2, pp 645-657, in Patai, "The Chemistry of Diazonium and
Diazo Groups," Wiley, New York (1978). Treatment of Formula 76 compounds with cuprous halides or iodide ions yield compounds of Formula 65. Treatment of
Formula 76 compounds with cuprous oxide in the presence of excess cupric nitrate provides compounds of Formula 70. (Cohen, Dietz, and Miser, J. Org. Chem, (1977),
42, 2053). Treatment of Formula 76 compounds with (S2)-2 yields compounds of
Formula 74.
Figure imgf000053_0002
74
Compounds of Formula 75 can be prepared from compounds of Formula 61a by nitration, followed by reduction (Scheme 34). A wide variety of nitrating agents is available (see Schofield, Aromatic Nitration, Cambridge University Press, Cambridge (1980)). Reduction of nitro compounds can be accomplished in a number of ways (see March, J. Advanced Organic Chemistry; 3rd ed., John Wiley: New York, (1985), pp 1103-4 and references therein). Formula 75 corresponds to Formula 19 in Scheme 9 when Y1 = NR15 and R15 = H.
Figure imgf000054_0001
Iodides of Formula 14 can be prepared from compounds of Formula 80 by the methods described above in Schemes 24-28 for various Y-Z combinations. Compounds of Formula 80 can in turn be prepared from compounds of Formula 79 by functional group interconversions which are well known to one skilled in the art. The compounds of Formula 79 can be prepared by treating compounds of Formula 78 with an
organolithium reagent such as n-BuLi or LDA followed by trapping the intermediate with iodine (Beak, P., Snieckus, V. Ace. Chem. Res., (1982), 15, 306). Additionally, lithiation via halogen metal exchange of compounds of Formula 78, where H is replaced by Br, will produce an intermediate which can be trapped with iodine to prepare compounds of Formula 79 (Parham, W E., Bradsher, C. K. Ace. Chem. Res., (1982), 15, 300 (Scheme 32).
Figure imgf000054_0002
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.
1H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br s = broad singlet.
EXAMPLE 1
Step A: Preparation of N-[2-(bromomethyl)phenyl]-2,2- dimethylhydrazinecarboxamide
o-Tolyl isocyanate (50.4 g) and 75.2 g of N-bromosuccinimide in 800 mL of carbon tetrachloride were heated to reflux. Benzoyl peroxide (1.1 g) was added and the mixture was heated at reflux for 1.5 h. The solution was cooled to room temperature and the precipitate was removed by filtration. The filtrate was concentrated in vacuo and redissolved in 500 mL of toluene and cooled to 5°C. 1,1-Dimethylhydrazine (30 mL) in 20 mL of toluene was added dropwise. The reaction mixture was stirred at room temperature overnight. The precipitated solid was collected by filtration and redissolved in 1 L of dichloromethane. The organic solution was washed with 500 mL of water and then with 500 mL of saturated aqueous sodium chloride solution. The organic phase was dried (MgSO4), filtered and concentrated to give 58 g (56% yield) of the title compound of Step A as a beige solid. 1H NMR (CDCl3): δ 8.6 (br s.1H), 8.00 (d,1H), 7.30 (m,2H), 7.04 (t,1H), 5.70 (br s,1H), 4.52 (s,2H), 2.67 (s,6H). The material was used in the next step without further characterization.
Step B: Preparation of 5-cMoro-4-[2-(chloromethyl)phenyl]-2,4-dihydro-2- methyl-3H-1,2,4-triazol-3-one
The title compound of Step A (58 g) was dissolved in 800 mL of
dichloromethane and 86 g of triphosgene was added in one portion. A slight exotherm was observed, and then the mixture was heated to reflux overnight. The reaction mixture was cooled and the solvent removed in vacuo. The resulting solid was dissolved in 1 L of ethyl acetate and washed with 500 mL of water, 500 mL of saturated aqueous sodium bicarbonate, and then 500 mL of saturated aqueous sodium chloride solution. The organic phase was dried (MgSO4), filtered and concentrated to give a dark oil which solidified on standing. The solid was triturated in 2: 1 hexane: n -butyl chloride to yield 32 g of a beige solid. Recrystallization of the solid from 150 mL of hot methanol yielded 21 g of the title compound of Step B as a white, fluffy solid melting at 122-124°C. A second crop was obtained from recrystallization of the mother liquors. 1Η NMR
(CDCl3): δ 7.45-7.6 (m,3H), 7.25 (m,1H), 4.68 (d,1H), 4.46 (d,1H), 3.56 (s,3H).
Approximately 10% of 5-chloro-4-[2-(bromomethyl)phenyl]-2,4-dihydro-2-methyl-3H- 1,2,4-triazol-3-one was observed in the 1Η NMR spectrum.
Step C: Preparation of 1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethanone oxime
To a stirred solution of 5.0 g of 7-acetyl- 1,2,3 ,4-tetrahydro- 1,1,4,4- tetramethylnaphthalene in 20 mL of methanol under a nitrogen atmosphere was added 1.65 g of hydroxylamine hydrochloride and then 1.96 g of sodium acetate. The reaction was allowed to stir overnight, then was diluted with diethyl ether, washed twice with distilled water and then saturated aqueous sodium chloride solution. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The resulting solid was triturated with a small amount of hexanes to afford 4.25 g of the title compound of Step C as a white solid. 1H NMR (CDCl3): δ 7.57 (s,1H), 7.36 (m,2H), 2.28 (s,3H), 1.69 (s,4H), 1.31 (s,6H), 1.28 (s,6H). Step D: Preparation of 5-chloro-2,4-dihydro-2-methyl-4-[2-[[ [[1-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethylidenelamino]oxylmethyl]phenyl]-3H-1,2,4-triazol-3- one
To a stirred solution of 1.71 g of the title compound of Step C in 12 mL of TΗF under a nitrogen atmosphere was added 0.85 g of potassium t-butoxide. Another 6 mL of TΗF and 6 mL of DMF was added (to enable stirring) and then 1.5 g of the title compound of Step B was added. The reaction mixture was allowed to stir for 3 h, then was diluted with diethyl ether and washed with distilled water. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The resulting material was purified by flash chromatography (20-30% ethyl acetate/hexanes as eluant) to give 2.05 g of the title compound of Step D as a gum (approximately 80% pure). 1Η NMR (CDCI3): δ 7.60 (m,1H), 7.50 (m,3H), 7.3-7.2 (m,3H), 5.25 (d,1H), 5.17 (d,1H), 3.47 (s,3H), 2.16 (s,3H), 1.69 (m,4H), 1.28 (m,12H).
Step E: Preparation of 2,4-dihydro-2-methyl-5-(methylamino)-4-[2-[[[[1-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol-3- one
The title compound of Step D (1 g) was dissolved/suspended in 5 mL methanol and then 5 g of methylamine was added. The container was closed (sealed) and heated at approximately 90°C for 36 h. The reaction was allowed to cool and the vessel was evacuated. The solution/suspension was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed with distilled water and then saturated aqueous sodium chloride solution. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (80-100% ethyl acetate/hexanes as eluant) to afford 300 mg of the title compound of Step E, a compound of the invention, as a solid (85% pure). 1Η NMR (CDCI3): δ 7.65 (d,lΗ), 7.6-7.1 (m,6H), 5.15 (m,2H), 3.95 (m,1H), 3.45 (s,3H), 2.6 (d,3H), 2.2 (s,3H), 1.65 (s,4H), 1.25 (s,12H).
EXAMPLE 2
Step A: Preparation of 2-(3-bromophenyl)-2-methyl-1,3-dioxolane
1-(3-Bromophenyl)ethanone (60.6 g, 0.3 mole), ethylene glycol (83.7 mL, 1.5 mole), and p-toluenesulfonic acid (0.15 g) were dissolved in benzene (250 mL) and heated to reflux overnight using a Dean-Stark apparatus. Water and some ethylene glycol had separated and the cooled (room temperature) mixture was poured into water (300 mL) and extracted with diethyl ether (2 x 100 mL). The combined organic phases were dried (MgSO4) and concentrated to give the crude product as an oil (62.05 g, 85%). 31.7 g of the oil was vacuum distilled and 29.54 g of the title compound of Step A was isolated as the fraction boiling between 64-73°C (24-27 Pa).
Step B: Preparation of 1-[3-(trimethylgermyl)phenyllethanone
A 250 mL 4-neck flask was charged with a suspension of magnesium pieces
(0.8 g, 0.033 mole) in 5 mL of THF. A solution of the title compound of Step A dissolved in 20 mL of THF was added dropwise (a few crystals of iodine were added to the mixture after a small portion of the solution had been added). Heating to 60°C was required to initiate the reaction; the temperature was then maintained between 62-67°C during the remainder of the addition and then the mixture was heated to reflux for 1.5 h. After cooling the mixture to 60°C, a solution of trimethylgermanium bromide (6.52 g, 0.033 mole) dissolved in THF (7 mL) was added in small aliquots, allowing the exotherm from each addition to keep the temperature between 65-67°C. The mixture was refluxed a total of 2 h, cooled, and poured into a saturated ammonium chloride solution (40 mL). Following separation of the organic layer, the aqueous layer was extracted with diethyl ether. The combined organic layers were dried (MgSO4) and concentrated to give 8.75 g of an oil which slowly crystallized. This solid was then dissolved in acetone (70 mL) and 1 N HCl (2 mL) was added. The resulting solution was refluxed for 3 h. The reaction mixture was concentrated and the residue was partitioned between water and diethyl ether. After drying (MgSO4), the organic phase was concentrated to yield 6.95 g (89% overall for both steps) of the title compound of Step B as a yellow oil. 1H NMR
(CDCl3): δ 8.063 (s,1H), 7.9 (d,1H), 7.7 (d,1H), 7.4 (t,1H), 2.62 (s,3H), 0.43 (s,7H). Step C: Preparation of 1-[3-(trimethylgermyl)phenyllethanone oxime
Sodium acetate trihydrate (4.09 g, 0.03 mole) was added to a solution of hydroxylamine hydrochloride (2.09 g, 0.03 mole) in water (25 mL), and this solution was added to a solution of the title compound of Step B (4.87 g, 0.021 mole) in methanol (40 mL). The mixture was then refluxed overnight and concentrated in vacuo. The mixture was treated with water and then extracted with methylene chloride (2 x 120 mL). The combined organic layers were dried (MgSO4) and concentrated to yield an oil.
Filtration through a 1.5 inch column of silica gel (25% ethyl acetate/hexanes) yielded two fractions, the second of which was chromatographed using a medium pressure liquid chromatograph (MPLC) (10% ethyl acetate/hexanes). The two fractions obtained corresponded to both isomers of the title compound of Step C. On standing at room temperature one of the products isomerized to a mixture. The predominant isomer was used in further preparations (1.2 g, 23%). 1H NMR (CDCl3): δ 9.112 (s,1H), 7.73 (s,1H), 7.545 (d,1H), 7.48 (d,1H), 7.393 (t,1H), 2.312 (s,3H), 0.405 (s,8H). Step D: Preparation of 2-[(2-methylphenyl)hydrazono]propanoic acid
o-Tolylhydrazine hydrochloride (10 g, 63.0 mmol) was ground to a fine powder and suspended in a mixed solvent of 60 mL of ethanol and 60 mL of 10% aqueous HCl. The suspension turned into a clear solution after heating at 60°C. To this solution was added dropwise pyruvic acid (5.3 mL, 75.7 mmol). The mixture was stirred at room temperature for 1 h and 100 mL of water was added. The orange precipitate was collected via filtration. After drying overnight (55°C, 10 h) in the vacuum oven, the title compound of Step D (8.8 g, 73%) was obtained as a light orange solid melting at 155-157°C. 1H NMR (CDCl3): δ 2.16 (s,3H), 2.30 (s,3H), 6.99 (t,1H), 7.17 (d,1H), 7.26 (t,1H), 7.42 (d,1H), 7.56 (s,1H).
Step E: Preparation of 2,4-dihydro-5-methyl-2-(2-methylphenyl)-3H-1,2,4- triazol-3-one
To a solution of the title compound of Step D (5.0 g, 26.0 mmol) and
diphenylphosphoryl azide (6.2 mL, 28.6 mmol) in 130 mL of toluene at room
temperature under a nitrogen atmosphere was added triethylamine (4.0 mL, 28.6 mmol). The resulting solution was heated at reflux for 6 h and then was stirred at room temperature overnight (14 h). The solvent was removed in vacuo and the dark orange oil thus obtained was purified by chromatography to give the title compound of Step E (4.5 g, 91%) as a light brown solid melting at 145-147°C. 1H NMR (CDCI3): δ 2.28 (s,3Η), 2.33 (s,3H), 7.30-7.44 (m,4H).
Step F: Preparation of 2,4-dihydro-4,5-dimethyl-2-(2-methylphenyl)-3H-1,2,4- triazol-3-one
To a solution of the title compound of Step E (1.2 g, 6.3 mmol) and iodomethane (1.0 mL, 16.1 mmol) in 150 mL of TΗF under a nitrogen atmosphere at 0°C was added sodium hydride (0.75 g, 60% oil dispersion, 18.8 mmol). The resulting mixture was stirred at room temperature for 3 h and worked up by quenching with ice. The aqueous phase was extracted with ethyl acetate (3 x 100 mL). The combined organic extracts were dried (MgSO4) and filtered, and the solvent was removed in vacuo to afford the title compound of Step F (1.20 g, 93%). 1H NMR (CDCI3): δ 2.29 (s,3Η), 2.31 (s,3H), 3.37 (s,3H), 7.23-7.34 (m,4H).
Step G: Preparation of 2-[2-(bromomethyl)phenyl]-2,4-dihydro-4,5-dimethyl-3H-
1,2,4-triazol-3-one
A solution of the title compound of Step F (0.9 g , 4.4 mmol),
N-bromosuccinimide (0.86 g, 4.9 mmol), and benzoyl peroxide (30 mg) in 20 mL of carbon tetrachloride was heated at reflux for 10 h. The solvent was removed in vacuo and the residue purified by chromatography to give, along with 5-(bromomethyl)-2,4- dihydro-4-methyl-2-(2-methylphenyl)-3H-1,2,4-triazol-3-one, the title compound of Step G (0.67 g, 54%) as a colorless oil. 1H NMR (CDCl3): δ 2.31 (s,3H), 3.32 (s,3H), 4.68 (s,2H), 7.30-7.48 (m,4H).
Step H: Preparation of 2,4-dihydro-4,5-dimethyl-2-[2-[[[[ 1-[3- (trimethylgermyl)phenyl]ethylidene]a m ino]oxy]methyl]phenyl]-3H-1,2,4- triazol-3-one
To a solution of the title compound of Step G (100 mg, 0.3 mmol) and the title compound of Step C (90 mg, 0.3 mmol) in 7 mL of DMF under a nitrogen atmosphere at 0°C was added sodium hydride (21 mg, 60% dispersion in oil, 0.5 mmol). The resulting suspension was stirred at room temperature for 5 h. The reaction mixture was then quenched with ice (20 g) and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were dried (MgSO4) and filtered, and the solvent removed in vacuo. The residue was purified by column chromatography to give 80 mg of the title compound of Step Η, a compound of the invention, as a colorless oil. 1Η NMR
(CDCI3): δ 0.39 (s,9Η), 2.23 (s,3H), 2.24 (s,3H), 3.24 (s,3H), 5.36 (s,2H), 7.29-7.46 (m,5H), 7.53-7.60 (m,2H), 7.66 (s,1H).
EXAMPLE 3
Step A: Preparation of 1-(2-bromophenyl)-1,4-dihydro-5H-tetrazol-5-one
2-Bromophenyl isocyanate (8.6 g, 43.4 mmol) was added to azidotrimethylsilane (10 g, 86.9 mmol) at room temperature. The reaction mixture was then heated at reflux for 20 h, cooled to room temperature, and poured onto ice. The precipitates were filtered and washed twice with water. The solids were then recrystallized from
9: 1/n-butyl chloride:acetonitrile to yield 4.7 g of the title compound of Step A as a solid melting at 143-145°C. 1H NMR (Me2SO-d6; 300 MHz): δ 7.5-7.7 (m,3H), 7.9 (m,1H), 14.7 (br s,1H).
Step B: Preparation of 1,4-dihydro-1-methyl-4-(2-bromophenyl)-5H-tetrazol-5- one
Potassium carbonate (2.51 g, 18.2 mmol) was added portionwise to a solution of the title compound of Step A (4.4 g, 18.2 mmol) in 50 mL of dry
N-N-dimethylformamide at room temperature. The mixture was then stirred at room temperature for 0.5 h. Iodomethane (3.11 g, 21.9 mmol) was then added at room temperature and the mixture was stirred at room temperature for 20 h. The reaction mixture was poured into water, extracted twice with diethyl ether and the combined extracts were dried over magnesium sulfate. The solvent was then removed by distillation under reduced pressure to give an oil. The oil was purified by silica gel chromatography using 2:l/hexanes:ethyl acetate as the eluent to yield 3.6 g of the title compound of Step B as an oil. 1H NMR (CDCl3; 300 MHz): δ 3.73 (s,3H), 7.35-7.50 (m,3H), 7.76 (d,1H, J=7.9 Hz).
Step C: Preparation of 2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde
Under nitrogen, n-butyllithium (14.5 mL of a 2.5 M solution in hexanes,
36.3 mmol) was added dropwise to a solution of the title compound of Step B (8.4 g, 33 mmol) in 100 mL of dry tetrahydrofuran at -65°C. The mixture was then stirred at -65°C for 0.5 h. N, N-Dimethylformamide (2.64 g, 36 mmol) was then added at -65°C. The reaction mixture was gradually warmed to room temperature over 20 h. Water (50 mL) was added dropwise at room temperature. The reaction mixture was then extracted twice with diethyl ether and dried over magnesium sulfate. The solvent was then removed by distillation under reduced pressure to give a solid which was triturated twice with n -butyl chloride, and the solid was suction-dried to yield 2.85 g of the title compound of Step C. The filtrate was concentrated under reduced pressure to an oil which was purified by silica gel chromatography using 4: l/hexanes:ethyl acetate as the eluent to yield an additional 0.85 g of the title compound of Step C melting at
102-104°C. 1H ΝMR (CDCl3; 300 MHz): δ 3.75 (s,3H), 7.61 (d,1H, J=7.7Hz), 7.65 (t,1H, J=7.6Hz), 7.78 (t,1H, J=7.6Hz), 8.06 (d,1H, J=7.7Hz), 10.05 (s,1H).
Step D: Preparation of 1,4-dihydro-1-[2-(hydroxymethyl)phenyl]-4-methyl-5H- tetrazol-5-one
To a stirred solution of the title compound of Step C (0.5 g, 2.45 mmol) in 25 mL of ethanol was added sodium borohydride (0.06 g, 1.47 mmol) in one portion at 10°C. The mixture was stirred at room temperature for 20 h. The solvent was removed by distillation under reduced pressure to give an oil which was diluted with water (30 mL) and extracted twice with methylene chloride. The combined extracts were dried over magnesium sulfate and the solvent was removed by distillation under reduced pressure to give 0.44 g of the title compound of Step D. 1Η ΝMR (CDCl3; 300 MHz): δ 3.49 (t,1H, J=7.0Hz), 3.75 (s,3H), 4.54 (d,1H, J=6.9Hz), 7.40-7.60 (m,3H), 7.65 (m,1H).
Step E: Preparation of 1,4-dihydro-1-methyl-4-[2-
[[(methylsulfonyl)oxy]methyl]phenyl]-5H-tetrazol-5-one Under nitrogen, to a solution of the title compound of Step D (2 g, 9.71 mmol) and triethylamine (1.18 g, 11.7 mmol) in 25 mL of dry tetrahydrofuran was added dropwise methanesulfonyl chloride (1.20 g, 11.7 mmol) at 0°C. The resulting suspension was stirred at room temperature for 3 h and was then heated at reflux for 2 h. The reaction mixture was then cooled to room temperature and the solvent was removed by distillation under reduced pressure to give an oil. The oil was diluted with water (25 mL), extracted twice with methylene chloride and the combined extracts were dried over magnesium sulfate. The solvent was then removed by distillation under reduced pressure to give 2 g of the title compound of Step E as an oil. 1H NMR (CDCl3;
300 MHz): δ 2.88 (s,3H), 3.73 (s,3H), 5.33 (s,2H), 7.5-7.7 (m,4H).
Step F: Preparation of 1-[3-(trifluorom ethyl)phenyl]ethanone oxime
1-[3-(Trifluoromethyl)phenyl]ethanone (25 g, 13.3 mmol) was combined in a single neck round bottom flask with hydroxylamine hydrochloride (15.3 g, 22.0 mmol) in 200 mL of methanol under a nitrogen atmosphere. To this stirred mixture at room temperature was added sodium acetate (36.4 g, 44.4 mmol) portionwise. A white precipitate formed after the addition of sodium acetate. The mixture was heated under reflux for two hours and was then cooled to room temperature. The solvent was removed under reduced pressure and the resulting white solid was partitioned between saturated ammonium chloride solution (200 mL) and methylene chloride (300 mL). The organic layer was separated and washed with water (200 mL). After drying over
MgSO4, the organic layer was concentrated under reduced pressure to afford 26.6 g of the title compound of Step F as a white solid melting at 56-62 °C. 1H NMR (CDCI3): δ 8.36 (br s,1H), 7.89 (d,1H, J=0.5Hz), 7.81 (d,1H, J=8.0Hz), 7.63 (d,1H, J=8.0Hz), 7.53-7.49 (m,1H), 2.32 (s,3H).
Step G: Preparation of 1,4-dihydro-1-methyl-4-[2-[[ [[1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-5H- tetrazol-5-one
Under nitrogen, to a solution of the title compound of Step F (0.79 g, 3.9 mmol) in 25 mL of dry N,N-dimethylformamide was added sodium hydride (0.15 g of 60% oil dispersion, 3.9 mmol) portionwise at room temperature. The reaction mixture was stirred at room temperature for 0.5 h. The title compound of Step E (1 g, 3.52 mmol) was then added at room temperature and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was then poured into water (25 mL), extracted twice with diethyl ether and the combined extracts were dried over magnesium sulfate. The solvent was then removed by distillation under reduced pressure to give an oil which was purified by silica gel chromatography using 4: l/hexanes:ethyl acetate as the eluent to yield 0.85 g of the title compound of Step G, a compound of the invention, as an oil. 1Η ΝMR (CDCI3; 300 MHz): δ 2.18 (s,3H), 3.64 (s,3H), 5.34 (s,2H), 7.40-7.60 (m,4H), 7.60-7.65 (m,2H), 7.76 (d,1H, J=7.9Hz). EXAMPLE 4
Step A: Preparation of 2-(1,4-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde oxime
To a stirred solution of the title compound of Step C in Example 3 ( 1.14 g, 5.59 mmol) in 25 mL of methanol was added hydroxylamine hydrochloride (0.47 g, 6.71 mmol). The reaction mixture was heated at reflux for 2 h and then cooled to room temperature. The solvent was removed by distillation under reduced pressure to give an oily solid which was diluted with water (30 mL), extracted twice with methylene chloride and the combined extracts were dried over magnesium sulfate. The solvent was removed by distillation under reduced pressure to yield 1.2 g of the title compound of Step A as an oil. 1Η NMR (CDCl3; 300 MHz): δ 3.73 (s,3H), 7.4-7.6 (m,3H), 7.8 (m,2H), 8.12 (s,1H).
Step B: Preparation of 2-(1,4-dihydro-4-methyl-5-oxo-1H-tetrazol-1- yl)benzaldehyde O-[[3-(trifluoromethyl)phenyl]methyl]oxime Under nitrogen, to a suspension of sodium hydride (0.17 g of 60% oil dispersion,
4.07 mmol) in 25 mL of N,N-dimethylformamide was added the title compound of Step A (0.81 g, 3.70 mmol) at room temperature. The reaction mixture was stirred at room temperature for 0.5 h. Then α'-bromo-α,α,α-trifluoro-m-xylene (0.97 g,
4.07 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was poured into water (25 mL), extracted twice with diethyl ether and the combined extracts were dried over magnesium sulfate. The solvent was then removed by distillation under reduced pressure to give an oil which was purified by silica gel chromatography using 1:1/hexanes:ethyl acetate as the eluent to yield 0.80 g of the title compound of Step B, a compound of the invention. 1Η ΝMR (CDCI3; 300 MHz): δ 3.67 (s,3H), 5.21 (s,2H), 7.4-7.6 (m,6H), 7.63 (s,1H), 7.95 (m,1H), 8.15 (s,1H).
EXAMPLE 5
Step A: Preparation of 1-13-(trifluoromethoxy.phenyllethanone oxime
To a stirring solution of 70.0 g of 3-(trifluoromethoxy)acetophenone in 350 mL of methanol under Ν2 was added 26.04 g of hydroxylamine hydrochloride and 30.91 g of sodium acetate. The reaction mixture was stirred overnight, and then was concentrated under reduced pressure. The resulting material was diluted with diethyl ether, washed successively with distilled water, saturated aqueous NaHCO3, and saturated aqueous NaCl. The organic layer was dried over MgSO4, and then concentrated under reduced pressure to give 73 g of the title compound of Step A as an oil. (1H NMR shows this oil to be approximately 87% pure containing approximately 13% of the dimethyl acetal.) 1H NMR (CDCl3): δ 8.75 (s,1H), 7.55 (d,1H), 7.5 (s,1H), 7.45 (t,1H), 7.25 (d,1H), 2.30 (s,3H).
Step B: Preparation of 1-methyl-4-[2-[ [[ [ 1-[3-(trifluoromethoxy)phenyl]- ethylidene]amino]oxy]methyl]phenyl]-1,2,4-triazolidine-3,5-dione
The title compound of Step A (73.0 g) was dissolved in 500 mL of
tetrahydrofuran under N2 and to this with stirring was added portionwise, over
15 minutes, 13.32 g of 60% sodium hydride. The reaction mixture was allowed to stir for 5 minutes, and then 65.79 g of the title compound of Step B in Example 1 was added portionwise over 10 minutes. The reaction mixture was stirred overnight, and then heated at reflux for 1 hour. To this mixture was then added 97 mL of 30% sodium methoxide in methanol and the reaction was refluxed another 1.5 hours. After cooling, the reaction mixture was partitioned between diethyl ether and distilled water, the aqueous layer (now basic) was collected, washed with methylene chloride, neutralized with 6N aqueous HCl, and then extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous NaCl, dried over MgSO4, and then concentrated under reduced pressure to give 12.85 g, of the title compound of Step B. 1H NMR (CDCI3): δ 7.4-7.65 (m,5H), 7.25-7.4 (m,2H), 7.2 (d,1H), 5.27 (s,2H), 3.12 (s,3H), 2.19 (s,3H). Step C: Preparation of 1-methyl-2-(2-propyn-1-yl)-4-[2-[[[ [1-[3-
(trifluoromethoxy)phenyl]ethylidene]amino]oxy]methyl]phenyl]-1,2,4- triazolidine-3,5-dione
To a stirring solution of 1.0 g of the title compound of Step B in 10 mL of tetrahydrofuran under N2 was added 0.11 g of 60% sodium hydride and then 0.31 mL of 80% propargyl bromide (in toluene). The reaction mixture was stirred overnight, and then was washed successively with distilled water and saturated aqueous NaCl. The organic layer was dried over MgSO4 and then was concentrated under reduced pressure. Column chromatography gave 0.52 g of the title compound of Step C, a compound of the invention, as an oil. 1H NMR (CDCl3): δ 7.25-7.6 (m,7H), 7.2 (d,1H), 5.25 (s,2H), 4.35 (d,2H), 3.25 (s,3H), 2.3 (t,1H), 2.19 (s,3H).
EXAMPLE 6
Step A: Preparation of 1-[3-(trifluoromethyl)phenyllethanone oxime
To a solution of 25 g of 3-(trifluoromethyl)acetophenone in 200 mL of pyridine under a nitrogen atmosphere was added 10.2 g of hydroxylamine hydrochloride. The solution was heated under reflux for 6 h and then the solvent was removed in vacuo. The resulting residue was taken up in 10% aqueous HCl and extracted with three 150 mL portion of ethyl acetate. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo to provide an oil which solidified on standing. Trituration of this solid in hexanes provided 24.9 g of the title compound of Step A as a white solid melting at 65-66 °C.
Step B: Preparation of 1-[3-(trifluoromethyl)phenyl]ethanone
O-[(2-nitrophenyl)methylloxime
To a suspension of 4.92 g of NaH (60% oil dispersion) in 150 mL of
tetrahydrofuran was added portionwise 24.9 g of the title compound of Step A. Gas evolution occurred and the resulting mixture was stirred at room temperature for 4.5 h. Then, 25.2 g of o-nitrobenzyl chloride was added. The solids dissolved to give a solution and then a new precipitate formed. The mixture was stirred overnight at room temperature. The solvent was removed in vacuo and the residue was taken up in ice water and ether, 30 mL of IN NaOH was then added and the phases were separated. The organic phase was dried (MgSO4), filtered and concentrated in vacuo to provide 39.4 g of the title compound of Step B as a pale reddish oil. 1H NMR (CDCl3): δ 8.05 (d,1H), 7.85 (s,1H), 7.8 (d,1H), 7.6 (m,2H), 7.45 (m,2H), 5.7 (s,2H), 2.3 and 2.35 (2s,3H total).
Step C: Preparation of 1-[3-(trifluoromethyl)phenyl]ethanone
O -[(2-aminophenyl)methyl]oxime
To a solution of 39.2 g of the title compound of Step B in 500 mL of acetic acid and 50 mL of water at >75 °C was added portionwise 21.4 g of iron powder while keeping the reaction temperature between 80-90 °C. The reaction mixture was stirred at 80-90° C for 5 min, filtered hot through filter paper onto ice, diluted with 500 mL of water and extracted twice with 500 mL portions of dichloromethane. The combined organic extracts were washed twice with 500 mL portions of water, twice with 500 mL portions of saturated NaHCO3 solution, dried (MgSO4), filtered and concentrated in vacuo to provide 32 g of an oil. This crude oil was dissolved in 300 mL of
tetrahydrofuran and 110 mL of 1N HCl in ether was added dropwise resulting in formation of a precipitate. The mixture was stirred for 30 min and then filtered.
Additional precipitate was obtained by removing the solvents and slurrying the residue in ether. The combined precipitates were suspended in dichloromethane and treated with 120 mL of IN NaOH and the solids dissolved. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo to provide 24.9 g of an amber oil which solidified on standing. This solid was recrystallized from hexane to give 18.7 g of the title compound of Step C as a tan solid melting at 67-69 °C. Step D: Preparation of 1-methyl-N-[2-[[[[1-1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]hydrazine- carboxamide
To a stirring solution of 5.0 g of the title compound of Step C in 35 mL of ethyl acetate at 5 °C under Ν2 was added 2.41 g of triphosgene. The reaction mixture was heated at reflux for 2 h, and then was allowed to cool. The reaction was then
concentrated under reduced pressure and the residue was dissolved in 35 mL of toluene. The resulting solution was cooled to 5 °C and 0.84 mL of methylhydrazine was slowly added. After the addition, the ice bath was removed, and the reaction was allowed to stir for 10 min and then was again concentrated under reduced pressure. Column
chromatography on silica gel using 50-70% ethyl acetate in hexanes as eluant gave 5.05 g of the title compound of Step D as a solid. 1H NMR (CDCl3): δ 9.3 (s, 1H), 8.05 (d,1H), 7.95 (s,1H), 7.8 (d,1H), 7.6 (d,1H), 7.5 (t,1H), 7.35 (m,2H), 7.05 (t,1H), 5.23 (s,2H), 3.69, (s,2H), 3.23 (s,3H), 2.26 (s,3H).
Step E: Preparation of 2,4-dihydro-2,5-dimethyl-4-[2-[[[[1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4- triazol-3-one
The title compound of Step D (1.25 g) was dissolved in 5 mL of trimethyl orthoacetate and to this solution was added 3 drops of acetic acid and the solution was heated at reflux overnight. The reaction mixture was then concentrated under reduced pressure and dissolved in ethyl acetate. The ethyl acetate solution was washed successively with 1 N aqueous ΗCl, saturated aqueous NaΗCO3 and saturated aqueous NaCl. The organic layer was dried over MgSU4 and then was concentrated under reduced pressure. Column chromatography using 60-70% ethyl acetate in hexanes as eluant gave 0.42 g of the title compound of Step E, a compound of the invention, as an oil. (This desired product has the same Rf as the starting material). 1H NMR (CDCl3): δ 7.85 (s,1H), 7.75 (d,1H), 7.6 (m,2H), 7.45 (m,3H), 7.2 (d,1H), 5.2 (m,2H), 3.5 (s,3H), 2.2 (s,3H), 2.0 (s,3H).
EXAMPLE 7
Step A: Preparation of 2-(3-bromophenyl)-2-methyl-1,3-dioxolane
1-(3-Bromophenyl)ethanone (35 g, 0.18 mol), ethylene glycol (39 mL, 0.70 mol), and p-toluenesulfonic acid (0.5 g) were dissolved in toluene (300 mL) and heated to reflux in a Dean-Stark apparatus. After six hours, water and some ethylene glycol had separated and the mixture was cooled and washed with water and saturated aqueous sodium bicarbonate solution. Drying (MgSO4) and concentrating the organic phase gave the title compound of Step A as an oil (44 g, 99% yield). 1H NMR (CDCl3):
δ 7.64 (m,1H), 7.39 (m,2H), 7.21 (t,1H), 4.04 (m,2H), 3.76 (m,2H), 1.63 (s,3H).
Step B: Preparation of 1-[3-(trimethylsilyl)phenyl]ethanone
A flame-dried flask was charged with magnesium pieces (5.3 g, 0.22 mole) and tetrahydrofuran (50 mL) under a nitrogen atmosphere. To this vigorously stirred slurry was added dropwise the title compound of Step A (44 g, 0.18 mole) in THF (150 mL). The reaction mixture was warmed to 40°C during the addition and then to 65°C for 1.5 hours after the addition was complete. After cooling the solution to room
temperature, trimethylsilyl chloride (28 mL, 0.22 mole) was added dropwise over 15 minutes and the reaction was allowed to stir for 16 hours. The reaction suspension was cooled to 10°C and was then treated with saturated aqueous ammonium chloride solution and extracted with diethyl ether. The combined organic phases were dried (MgSO4) and concentrated to give the intermediate silylated ketal. This crude intermediate was dissolved in acetone (180 mL) and treated with 1N hydrochloric acid solution (18 mL) at reflux for 2 hours. After cooling, saturated aqueous sodium bicarbonate solution (180 mL) was added carefully and the mixture was extracted with methylene chloride. The combined organic phases were dried (MgSO4) and
concentrated to give the title compound of Step B as a yellow oil (34 g, 99% yield). 1H NMR (CDCI3): δ 8.10 (s,1H), 7.91 (m,1H), 7.73 (m,1H), 7.45 (t,1H), 2.62 (s,3H), 0.30 (s,9H).
Step C: Preparation of 1-[3-(trimethylsilyl)phenyl]ethanone oxime
The title compound of Step B (34 g, 0.18 mol) was dissolved in methanol
(175 mL) and treated with a solution of hydroxylamine hydrochloride (19 g, 0.28 mol) and sodium acetate (38 g, 0.28 mol) in water (130 mL). The mixture was heated at reflux for 2.5 hours, cooled, and extracted with methylene chloride. The combined organic phases were dried (MgSO4), concentrated, and the resulting residue was chromatographed on silica gel with 10% ethyl acetate/hexane as eluent. The title compound of Step C was isolated as a colorless oil (30 g, 80% yield). 1H NMR
(CDCI3): δ 9.27 (s,1H), 7.77 (s,1H), 7.56 (m,2H), 7.37 (t,1H), 2.32 (s,3H), 0.29 (s,9H). Step D: Preparation of 1,4-dihydro-1-methyl-4-[2-[[[[1-[3-
(trimethylsilyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-5H-tetrazol- 5-one
Under N2, the title compound of Step C (0.39 g; 1.85 mol) was added to a stirred suspension of sodium hydride (0.08 g 60% oil dispersion; 2.03 mmol) in 25 mL of dry DMF. The reaction mixture was stirred at room temperature for 1 h. The title compound of Step E in Example 3 (0.50 g; 1.76 mmol) was then added. The reaction mixture was stirred at room temperature for 16 h and was then poured into H2O (100 mL) and the aqueous mixture was extracted twice with diethyl ether. The combined organic layers were washed with saturated aqueous NaCl and dried with magnesium sulfate. The organic solvent was removed under reduced pressure to afford an oil which was purified by column chromatography using 4: l/hexanes:ethyl acetate as eluent to afford 0.37 g of the title compound of Step D, a compound of the invention, as an oil. 1H NMR (CDCl3): δ 0.27 (s,9H), 2.17 (s,3H), 3.61 (s,3H), 5.32 (s,2H), 7.35 (m,1H), 7.4-7.6 (m,5H), 7.60 (m,1H), 7.68 (s,1H).
EXAMPLE 8
Step A: Preparation of 1-(Bromomethyl)-2-iodobenzene
To a stirred solution of 2-iodobenzyl alcohol (50 g, 214 mmol) in diethyl ether (500 mL) cooled in an ice water bath was added via addition funnel phosphorus tribromide (26 mL, 277 mmol) and the resulting mixture was chilled in a refrigerator for 3.5 h. The reaction mixture was quenched by the addition of 50 mL of methanol and washed with water, saturated sodium bicarbonate solution and then water. The organic phase was dried (MgSO4) and concentrated under reduced pressure to afford a white solid. The solid was triturated with hexane and collected by filtration to afford the title compound of Step A (57.95 g) as a solid melting at 55-57 °C.
Step B: Preparation of 1-iodo-2-[(2-methylphenoxy)methyl]benzene
To a solution of σ-cresol (21.1 g, 195 mmol) in tetrahydrofuran (500 mL) was added portionwise sodium hydride (7.8 g, 240 mmol, 60% oil dispersion, washed with hexanes) with ice water bath cooling. The resulting mixture was stirred at room temperature 20 min, the title compound of Step A (57.95 g, 195 mmol) was added and the mixture was then heated to 60 °C overnight. An additional portion of sodium hydride (2 g) was added and heating was resumed for 3 h. The reaction mixture was cooled, quenched with water and the phases were separated. The aqueous phase was extracted twice with diethyl ether and the combined organic phases, after drying
(MgSO4), were concentrated under reduced pressure. The residue was triturated in hexanes to afford the title compound of Step B (59.14 g) as a solid melting at 45-48 °C. Step C: Preparation of methyl α-methyl-2-[(2- methylphenoxy)methyl]benzeneacetate
To a suspension of sodium hydride (14.5 g, 363 mmol, 60% oil dispersion, washed with hexanes) in N, N-dimethylpropyleneurea (200 mL) was added dimethyl malonate (41.6 mL, 363 mmol) dropwise with ice water bath cooling. The resulting mixture was stirred at room temperature for 20 min and then the title compound of Step B (59.1 g, 182 mmol) and cuprous iodide (69 g, 363 mmol) were added. The mixture was heated to 140 °C overnight and was then stirred at room temperature for 24 h. The reaction mixture was diluted with 400 mL of 1N C1 and extracted four times with diethyl ether. The combined extracts were dried (MgSO4) and concentrated under reduced pressure. Chromatography of the residue, an oil, on silica gel with 7: 1 hexane- ethyl acetate afforded the title compound of Step C, the fourth-eluting component,
(5.45 g) as an oil. 300 MHz 1H NMR (CDCl3): δ 1.52(d,3H), 2.24(s,3H), 3.63(s,3H), 4.07(q,1H), 5.03(d,1H), 5.21(d,1H), 6.9(m,2H), 7.17(d,2H).
Step D: Preparation 2,4-dimethyl-4-[2-[(2-methylphenoxy)methyl]phenyl]-3,5- pyrrolidinedione
To a solution of the title compound of Step C (2.84 g, 10 mmol) in
tetrahydrofuran (75 mL) was added, with ice water bath cooling, lithium diisopropyl amide (6.7 mL of a 1.5 M solution in cyclohexane/tetrahydrofuran, 10 mmol). The reaction mixture was stirred lh and l,r-carbonyldiimidazole (1.62 g, 10 mmol) was added which resulted in formation of a precipitate, the mixture was stirred 1 h, and methylhydrazine (461 mg, 10 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with 1N HCl, the phases were separated, and the aqueous phases were extracted with ethyl acetate. The
combined extracts were dried (MgSO4) and concentrated under reduced pressure. The residue was triturated in 1-chlorobutane which afforded the title compound of Step D (1.35 g) as a tan solid melting at 125-129 °C.
Step E: Preparation 2,4-dihydro-5-methoxy-2,4-dimethyl-4-[2-[(2- methylphenoxy)methyl]phenyl]-3H-pyrazol-3-one
To a solution of the title compound of Step D (960 mg, 3 mmol) in dichloromethane (50 mL) was added, with ice water bath cooling, tetramethyloxonium tetrafluoroborate (1.5 g, 10 mmol). The mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was washed twice with saturated sodium bicarbonate solution. The aqueous phases were back-extracted with dichloromethane. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure.
Chromatography of the residue, an oil, on silica gel with 4: 1 hexane-ethyl acetate afforded the title compound of Step E as an oil. The oil was triturated in hexane/1-chlorobutane to afford the title compound of Step E, a compound of the invention, (340 mg) as a solid melting at 147-150 °C.
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 62 can be prepared. The following abbreviations are used in the Tables which follow: t = tertiary, n = normal, i = iso, c = cyclo,
Me = methyl, Et = ethyl, Pr = propyl, i-Pr = isopropyl, Bu = butyl, hex = hexyl, Ph = phenyl, nap = naphthalenyl, MeO and OMe = methoxy, EtO = ethoxy, PhO and OPh = phenoxy, MeS and SMe = methylthio, CN = cyano, NO2 = nitro, TMS = trimethylsilyl, TBDMS = t-BuMe2Si, and SO2Me = methylsulfonyl.
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0001
Figure imgf000083_0001
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
Figure imgf000087_0001
Figure imgf000088_0001
Figure imgf000089_0001
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
Figure imgf000105_0001
Figure imgf000106_0001
Figure imgf000107_0001
Figure imgf000108_0001
Figure imgf000109_0001
Figure imgf000110_0001
Figure imgf000111_0001
Figure imgf000112_0001
Figure imgf000113_0001
Figure imgf000114_0001
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
Figure imgf000132_0001
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0001
Figure imgf000136_0001
Figure imgf000137_0001
Figure imgf000138_0001
Figure imgf000139_0001
Figure imgf000140_0001
Figure imgf000141_0001
Figure imgf000142_0001
Figure imgf000143_0001
Figure imgf000144_0001
Figure imgf000145_0001
Figure imgf000146_0001
Figure imgf000147_0001
Figure imgf000148_0001
Figure imgf000149_0001
Figure imgf000150_0001
Formulation/Ut ility
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.
Figure imgf000151_0001
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, N,N-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-αUmethylformamide, 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-E.
Figure imgf000152_0001
Figure imgf000153_0001
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, Altemaria 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, Sphaerothecafuliginea, Fusarium oxysporum, Verticillium dahliae, Pythium aphanidermatum, Phytophthora megasperma, Sclerotinia sclerotiorum, Sclerotium rolfsii, Erysiphe polygoni, 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, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, esfenvalerate, fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion,
metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, 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 (ICIA5504), benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole, cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph, diniconazole, diniconazole-M, dodine, edifenphos, epoxyconazole (BAS 480F), fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimorph, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl (BAS 490F), mancozeb, maneb, mepronil, metalaxyl, metconazole, myclobutanil, neo-asozin (ferric methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propiconazole, pyrifenox, pyroquilon, sulfur, tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon, triadimenol, tricyclazole, triticonazole, uniconazole, validamycin and vinclozolin; nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, 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 cyproconazole, cyprodinil (CGA 219417), epoxyconazole (BAS 480F), fenpropidin, fenpropimorph, flusilazole and tebuconazole. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-E) are selected from the group: compound 6 and cyproconazole; compound 6 and cyprodinil
(CGA 219417); compound 6 and epoxyconazole (BAS 480F); compound 6 and fenpropidin; compound 6 and fenpropimorph; compound 6 and flusilazole; compound 6 and tebuconazole; compound 12 and cyproconazole; compound 12 and cyprodinil (CGA 219417); compound 12 and epoxyconazole (BAS 480F); compound 12 and fenpropidin; compound 12 and fenpropimorph; compound 12 and flusilazole;
compound 12 and tebuconazole; compound 18 and cyproconazole; compound 18 and cyprodinil (CGA 219417); compound 18 and epoxyconazole (BAS 480F); compound 18 and fenpropidin; compound 18 and fenpropimorph; compound 18 and flusilazole;
compound 18 and tebuconazole; compound 26 and cyproconazole; compound 26 and cyprodinil (CGA 219417); compound 26 and epoxyconazole (BAS 480F); compound 26 and fenpropidin; compound 26 and fenpropimorph; compound 26 and flusilazole; and compound 26 and tebuconazole.
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: Ph = phenyl, PhO = phenoxy, and CN = cyano. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared.
Figure imgf000156_0001
Figure imgf000157_0001
Figure imgf000158_0001
Figure imgf000159_0001
Figure imgf000160_0001
a 1H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets. 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 of 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.
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.
Figure imgf000161_0001
Figure imgf000162_0001

Claims

CLAIMS What is claimed is:
1. A compound selected from Formula I, N-oxides and agriculturally suitable salts thereof,
wherein
Figure imgf000163_0002
G is selected from the group
Figure imgf000163_0001
E is selected from:
i) 1,2-phenylene optionally substituted with one of R3, R4, or both R3 and
R4;
ii) a naphthalene ring, provided that when G and Y are attached to the same ring, then G and Y are attached to adjacent ring members, the naphthalene ring optionally substituted with one of R3, R4, or both R3 and R4; and iii) a ring system selected from 5 to 12-membered monocyclic and fused bicyclic aromatic heterocyclic ring systems, each heterocyclic ring system containing 1 to 6 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 4 nitrogens, no more than 2 oxygens, and no more than 2 sulfurs, each fused bicyclic ring system optionally containing one nonaromatic ring that optionally includes one or two Q as ring members and optionally includes one or two ring members independently selected from C(=O) and S(O)2, provided that G is attached to an aromatic ring, and when
G and Y are attached to the same ring, then G and Y are attached to adjacent ring members, each aromatic heterocyclic ring system optionally substituted with one of R3, R4, or both R3 and R4;
A is N or CR14;
B is O; S; or NR5;
each W is independently O; S; NH; N(C1-C6 alkyl); or NO(C1-C6 alkyl);
X is H; C1-C6 alkyl; C1-C6 haloalkyl; C3-C6 cycloalkyl; cyano; NH2; NHR1;
N(C1-C6 alkyl)R1; NH(C1-C6 alkoxy); or N(C1-C6 alkoxy)R1;
X1 is C1-C6 alkoxy; C1-C6 haloalkoxy; C2-C6 alkenyloxy; C2-C6 haloalkenyloxy;
C2-C6 alkynyloxy; C2-C6 haloalkynyloxy; C3-C6 cycloalkoxy; C1-C6 alkylthio; C1-C6 haloalkylthio; C2-C6 alkenylthio; C2-C6 haloalkenylthio; C2-C6 alkynylthio; C2-C6 haloalkynylthio; C3-C6 cycloalkylthio; C1-C6 alkylsulfinyl; C1-C6 haloalkylsulfinyl; C2-C6 alkenylsulfinyl; C2-C6 haloalkenylsulfinyl; C2-C6 alkynylsulfinyl; C2-C6 haloalkynylsulfinyl; C3-C6 cycloalkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylsulfonyl; C2-C6 alkenylsulfonyl; C2-C6 haloalkenylsulfonyl; C2-C6 alkynylsulfonyl; C2-C6 haloalkynylsulfonyl; C3-C6 cycloalkylsulfonyl; halogen; or X;
each R1 is independently C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6
haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C1-C6 alkoxy; formyl; C2-C4 alkylcarbonyl; or C2-C4 alkoxycarbonyl; provided that when G is G-4, then only one of R1 can be C1-C6 alkoxy;
R2 is H; C1-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;
R3 and R4 are each independently halogen; cyano; nitro; hydroxy; C1-C6 alkyl;
C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C2-C6 alkenyloxy; C2-C6 alkynyloxy; C1-C6 alkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl; formyl; C2-C6 alkylcarbonyl; C2-C6 alkoxycarbonyl; NH2C(O);
(C1-C4 alkyl)NHC(O); (C1-C4 alkyl)2NC(O); Si(R25)3; Ge(R25)3; (R25)3Si-C=C-; or phenyl, phenylethynyl, benzoyl, or phenylsulfonyl each substituted with R8 and optionally substituted with one or more R10; or when E is 1,2-phenylene and 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 C1-C3 alkyl;
R5 is H; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C4 alkylcarbonyl; or C2-C4 alkoxycarbonyl;
Y is -O-; -S(O)n-; -NR15-; -C(=O)-; -CH(OR15)-; -CHR6-; -CHR6CHR6-;
-CR6=CR6-; -C≡C-; -CHR15O-; -OCHR15-; -CHR15S(O)n-; -S(O)nCHR15-;
-CHR15O-N=C(R7)-; -(R7)C=N-OCH(R15)-; -C(R7)=N-O-; -O-N=C(R7)-;
-CHR15OC(=O)N(R15)-; -CHR15OC(=S)N(R15)-; -CHR15OC(=O)O-;
-CHR15OC(=S)O-; -CHR15OC(=O)S-; -CHR15OC(=S)S-;
-CHR15SC(=O)N(R15)-; -CHR15SC(=S)N(R15)-; -CHR15SC(=O)O-;
-CHR15SC(=S)O-; -CHR15SC(=O)S-; -CHR15SC(=S)S-;
-CHR15SC(=NR15)S-; -CHR15N(R15)C(=O)N(R15)-;
-CHR15O-N(R15)C(=O)N(R15)-; -CHR15O-N(R15)C(=S)N(R15)-;
-CHR15O-N=C(R7)NR15-; -CHR15O-N=C(R7)OCH2-;
-CHR15O-N=C(R7)-N=N-; -CHR15O-N=C(R7)-C(=O)-;
-CHR15O-N=C(R7)-C(=N-A2-Z1)-A1-;
-CHR15O-N=C(R7)-C(R7)=N-A2-A3-; -CHR15O-N=C(-C(R7)=N-A2-Z1)-;
-CHR15O-N=C(R7)-CH2O-; -CHR15O-N=C(R7)-CH2S-;
-O-CH2CH2O-N=C(R7)-; -CHR15O-C(R15)=C(R7)-; -CHR15O-C(R7)=N-; -CHR15S-C(R7)=N-; -C(R7)=N-NR15-; -CH=N-N=C(R7)-;
-CHR15N(R15)-N=C(R7)-; -CHR15N(COCH3)-N=C(R7)-;
-OC(=S)NR15C(=O)-; -CHR6-C(=W1)-A1-; -CHR6CHR6-C(=W1)-A1-;
-CR6=CR6-C(=W1)-A1-; -C≡C-C(=W1)-A1-; -N=CR6-C(=W1)-A1-; 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;
Z1 is H or -A3-Z;
W1 is O or S;
A1 is O; S; NR15; or a direct bond;
A2 is O; NR15; or a direct bond;
A3 is -C(=O)-; -S(O)2-; or a direct bond; each R6 is independently H; 1-2 CH3; C2-C3 alkyl; C1-C3 alkoxy; C3-C6 cycloalkyl; formylamino; C2-C4 alkylcarbonylamino; C2-C4
alkoxycarbonylamino; NH2C(O)NH; (C1-C3 alkyl)NHC(O)NH;
(C1-C3 alkyl)2NC(O)NH; N(C1-C3 alkyl)2; piperidinyl; morpholinyl;
1-2 halogen ; cyano ; or nitro ;
each R7 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 alkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylthio; C1-C6 haloalkylsulfinyl; C1-C6 haloalkylsulfonyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C4 alkylcarbonyl; C2-C4 alkoxycarbonyl; halogen; cyano; nitro; hydroxy; amino; NH(C1-C6 alkyl); N(C1-C6 alkyl)2; or morpholinyl; each Z is independently selected from:
i) C1-C10 alkyl, C2-C10 alkenyl, and C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10;
ii) C3-C6 cycloalkyl, C3-C6 cycloalkenyl and phenyl each substituted with R9 and optionally substituted with one or more R10;
iii) a ring system selected from 3 to 14-membered monocyclic, fused bicyclic and fused tricyclic nonaromatic heterocyclic ring systems and 5 to
14-membered monocyclic, fused bicyclic and fused tricyclic aromatic heterocyclic ring systems, each heterocyclic ring system containing 1 to 6 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 4 nitrogens, no more than 2 oxygens, and no more than 2 sulfurs, each nonaromatic or aromatic heterocyclic ring system substituted with R9 and optionally substituted with one or more R10;
iv) a multicyclic ring system selected from 8 to 14-membered fused-bicyclic and fused-tricyclic ring systems which are an aromatic carbocyclic ring system, a nonaromatic carbocyclic ring system, or a ring system containing one or two nonaromatic rings that each include one or two Q as ring members and one or two ring members independently selected from C(=O) and S(O)2, and any remaining rings as aromatic carbocyclic rings, each multicyclic ring system substituted with R9 and optionally substituted with one or more R10; and
v) adamantyl substituted with R9 and optionally substituted with one or more R10; each Q is independently selected from the group -CHR13-, -NR13-, -O-, and
-S(O)p-;
R8 is H; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6
haloalkoxy; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C1-C6 alkylthio; C1-C6 haloalkylthio; C1-C6 alkylsulfinyl; C1-C6 alkylsulfonyl;
C3-C6 cycloalkyl; C3-C6 alkenyloxy; CO2(C1-C6 alkyl); NH(C1-C6 alkyl);
N(C1-C6 alkyl)2; cyano; nitro; SiR19R20R21; or GeR19R20R21;
R9 is H; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6
haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl or C3-C6 cycloalkenyl each optionally substituted with at least one member selected from 1-2 halogen, 1-2 C1-C3 alkyl, 1-2 C1-C3 alkoxy, and one phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; C2-C6 alkoxyalkyl; C2-C6 alkylthioalkyl; C3-C6 alkoxyalkynyl; C7-C10 tetrahydropyranyloxy alkynyl; benzyloxymethyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C3-C6 alkenyloxy;
C3-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C1-C6 cycloalkoxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxyalkoxy; C2-C6 alkylthioalkoxy; C1-C6 alkylthio; C1-C6 haloalkylthio; C1-C6 alkylsulfinyl; C1-C6 haloalkylsulfinyl; C1-C6 alkylsulfonyl; C1-C6 haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio;
CO2(C1-C6 alkyl); NH(C1-C6 alkyl); N(C1-C6 alkyl)2; -C(R18)=NOR17; cyano; nitro; SF5; SiR22R23R24; or GeR22R23R24; or R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
R11, R 12, or both R11 and R12;
each R10 is independently halogen; C1-C4 alkyl optionally substituted with 1-3 C1-C3 alkoxy; C1-C4 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; C2-C6 alkoxyalkyl; C2-C6 alkylthioalkyl; C3-C6 alkoxyalkynyl; C7-C10 tetrahydropyranyloxyalkynyl; benzyloxymethyl; C1-C4 alkoxy; C1-C4 haloalkoxy; C3-C6 alkenyloxy;
C3-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C1-C6 cycloalkoxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxyalkoxy; C2-C6 alkylthioalkoxy; C1-C4 alkylthio; C1-C4 haloalkylthio; C1-C4 alkylsulfinyl;
C1-C4 haloalkylsulfinyl; C1-C4 alkylsulfonyl; C1-C4 haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio; nitro; cyano; thiocyanato; hydroxy; N(R26)2; SF5; Si(R25)3; Ge(R25)3; (R25)3Si-C≡C-;
OSi(R25)3; OGe(R25)3; C(=O)R26; C(=S)R26; C(=O)OR26; C(=S)OR26;
C(=O)SR26; C(=S)SR26; C(=O)N(R26)2; C(=S)N(R26)2; OC(=O)R26;
OC(=S)R26; SC(=O)R26; SC(=S)R26; N(R26)C(=O)R26; N(R26)C(=S)R26;
OC(=O)OR27; OC(=O)SR27; OC(=O)N(R26)2; SC(=O)OR27; SC(=O)SR27;
S(O)2OR26; S(O)2N(R26)2; OS(O)2R27; or N(R26)S(O)2R27; or
when R9 and an R10 are attached to adjacent atoms on Z, R9 and said adjacently attached R10 can be taken together as -OCH2O- or -OCH2CH2O-; each CH2 group of said taken together R9 and R10 optionally substituted with 1-2 halogen; or
when Y and an R10 are attached to adjacent atoms on Z and Y is
-CHR15O-N=C(R7)-, -O-N=C(R7)-, -O-CH2CH2O-N=C(R7)-,
-CHR15O-C(R15)=C(R7)-, -CH=N-N=C(R7)-, -CHR15N(R15)-N=C(R7)- or -CHR15N(COCH3)-N=C(R7)-, R7 and said adjacently attached R10 can be taken together as -(CH2)r-J- such that J is attached to Z;
J is -CH2-; -CH2CH2-; -OCH2-; -CH2O-; -SCH2-; -CH2S-; -N(R16)CH2-; or
-CH2N(R16)-; each CH2 group of said J optionally substituted with 1 to 2
CH3;
R11 and R12 are each independently 1-2 halogen; C1-C4 alkyl; C1-C4 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-C6 haloalkenyloxy; C3-C6 alkynyloxy; C3-C6 haloalkynyloxy; C2-C6 alkoxyalkoxy; C5-C9 trialkylsilylalkoxyalkoxy;
C2-C6 alkylthioalkoxy; C1-C4 alkylthio; C1-C4 haloalkylthio; C1-C4 alkylsulfinyl; C1-C4 haloalkylsulfinyl; C1-C4 alkylsulfonyl; C1-C4
haloalkylsulfonyl; C3-C6 alkenylthio; C3-C6 haloalkenylthio; C2-C6 alkylthioalkylthio; nitro; cyano; thiocyanato; hydroxy; N(R26)2; SF5;
Si(R25)3; Ge(R25)3; (R25)3Si-C≡C-; OSi(R25)3; OGe(R25)3; C(=O)R26;
C(=S)R26; C(=O)OR26; C(=S)OR26; C(=O)SR26; C(=S)SR26;
C(=O)N(R26)2; C(=S)N(R26)2; OC(=O)R26; OC(=S)R26; SC(=O)R26;
SC(=S)R26; N(R26)C(=O)R26; N(R26)C(=S)R26; OC(=O)OR27;
OC(=O)SR27; OC(=O)N(R26)2; SC(=O)OR27; SC(=O)SR27; S(O)2OR26; S(O)2N(R26)2; OS(O)2R27; N(R26)S(O)2R27; or phenyl, phenoxy, benzyl, benzyloxy, phenylsulfonyl, phenylethynyl or pyridinylethynyl, each optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
each R13 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; or phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
R14 is H; halogen; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl;
C2-C6 alkynyl; C2-C6 haloalkynyl; or C3-C6 cycloalkyl;
each R15 is independently H; C1-C3 alkyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; or when Y is -CHR15N(R15)C(=O)N(R15)-, the two R15 attached to nitrogen atoms on said group can be taken together as -(CH2) s-; or
when Y is -CHR15O-N=C(R7)NR15-, R7 and the adjacently attached R15 can be taken together as -CH2-(CH2)s-; -O-(CH2)s-; -S-(CH2)s-; or
-N(C1-C3 alkyl)-(CH2)s-; with the directionality of said linkage defined such that the moiety depicted on the left side of the linkage is bonded to the carbon and the moiety on the right side of the linkage is bonded to the nitrogen;
R16, R17, and R18 are each independently H; C1-C3 alkyl; C3-C6 cycloalkyl; or phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 haloalkyl,
C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano;
R19, R20, R21, R22, R23, and R24 are each independently C1-C6 alkyl; C1-C4
haloalkyl; C2-C6 alkenyl; C1-C4 alkoxy; or phenyl;
each R25 is independently C1-C4 alkyl; C1-C4 haloalkyl; C2-C4 alkenyl; C1-C4
alkoxy; or phenyl;
each R26 is independently H; C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6 haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; each R27 is independendy C1-C6 alkyl; C1-C6 haloalkyl; C2-C6 alkenyl; C2-C6
haloalkenyl; C2-C6 alkynyl; C2-C6 haloalkynyl; C3-C6 cycloalkyl; or phenyl or benzyl, each optionally substituted on the phenyl ring with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, nitro or cyano; n and p are each independently 0, 1 or 2;
r is 0 or 1; and
s is 2 or 3; provided that
(i) when G is G-1 or G-4 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl,
pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of R11, R12, or both R11 and R12;
(ii) when G is G-2, X is H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl or NH2 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with
R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of
R11, R12 or both R11 and R12;
(iii) when G is G-1 and A is N, then Y is other than -O-, -S(O)n-, -NR15-, -CHR6-,
-CHR6CHR6-, -CR6=CR6-, -C≡C-, and a direct bond;
(iv) when G is G-1, A is N and W is S, NH or N(C1-C6 alkyl), then R2 is other than H;
(v) when G is G-3, B is NR5, X is H, NH2, NHR1 or N(C1-C6 alkyl)R1 and Z is C1-C10 alkyl, C2-C10 alkenyl or C2-C10 alkynyl each substituted with R9 and optionally substituted with one or more R10, then R9 is phenyl, benzyl, benzyloxy, benzoyl, phenoxy, phenylethynyl, phenylthio, phenylsulfonyl, pyridinyl, pyridinyloxy, pyridinylmethyloxy, pyridinylethynyl, pyridinylthio, thienyl, thienyloxy, furanyl, furanyloxy, pyrimidinyl, pyrimidinyloxy or pyrimidinylthio each optionally substituted on the aromatic ring with one of R11, R12, or both R11 and R12; and
(vi) when G is G-3, B is NR5, X is NH2, NHR1 or N(C1-C6 alkyl.R1 and Y is O or a direct bond, then Z is other than phenyl substituted with R9 and optionally substituted with one or more R10.
2. A compound of Claim 1 wherein:
E is selected from the group 1,2-phenylene; 1,5-, 1,6-, 1,7-, 1,8-, 2,6-, 2,7-, 1,2-, and 2,3-naphthalenediyl; 1H-pyrrole-1,2-, 2,3- and 3,4-diyl; 2,3- and
3,4-furandiyl; 2,3- and 3,4-thiophenediyl; 1H-pyrazole-1,5-, 3,4- and
4,5-diyl; 1H-imidazole-1,2-, 4,5- and 1,5-diyl; 3,4- and 4,5-isoxazolediyl; 4,5-oxazolediyl; 3,4- and 4,5-isothiazolediyl; 4,5-thiazolediyl;
1H-1,2,3-triazole-1,5- and 4,5-diyl; 2H-1,2,3-triazole-4,5-diyl;
1H-1,2,4-triazole-1,5-diyl; 4H-1,2,4-triazole-3,4-diyl;
1,2,3-oxadiazole-4,5-diyl; 1,2,5-oxadiazole-3,4-diyl;
1,2,3-thiadiazole-4,5-diyl; 1,2,5-thiadiazole-3,4-diyl; 1H-tetrazole-1,5-diyl;
2,3- and 3,4-pyridinediyl; 3,4- and 4,5-pyridazinediyl; 4,5-pyrimidinediyl; 2,3-pyrazinediyl; 1,2,3-triazine-4,5-diyl; 1,2,4-triazine-5,6-diyl;
1H-indole-1,4-, 1,5-, 1,6-, 1,7-, 2,4-, 2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 1,2-, 2,3-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 2,3-, 4,5-, 5,6- and 6,7-benzofurandiyl; benzo[b]thiophene-2,4-, 2,5-, 2,6-,
2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 2,3-, 4,5-, 5,6- and 6,7-diyl; 1H-indazole-1,4-, 1,5-, 1,6-, 1,7-, 3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl;
1H-benzimidazole-1,4-, 1,5-, 1,6-, 1,7-, 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-diyl; 1,2-benzisoxazole-3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-benzoxazolediyl; 1,2-benzisothiazole-3,4-,
3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-diyl; 2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-benzofhiazolediyl; 2,5-, 2,6-, 2,7-, 2,8-, 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 2,3-, 3,4-, 5,6-, 6,7- and 7,8-quinolinediyl; 1,5-, 1,6-, 1,7-, 1,8-, 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 3,4-, 5,6-, 6,7- and
7,8-isoquinolinediyl; 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 3,4-, 5,6-,
6,7- and 7,8-cinnolinediyl; 1,5-, 1,6-, 1,7-, 1,8-, 5,6-, 6,7- and
7,8-phthalazinediyl; 2,5-, 2,6-, 2,7-, 2,8-, 4,5-, 4,6-, 4,7-, 4,8-, 5,6-, 6,7- and 7,8-quinazolinediyl; 2,5-, 2,6-, 2,7-, 2,8-, 2,3-, 5,6-, 6,7- and
7,8-quinoxalinediyl; 1,8,-naphthyridine-2,5-, 2,6-, 2,7-, 3,5-, 3,6-, 4,5-, 2,3- and 3,4-diyl; 2,6-, 2,7-, 4,6-, 4,7-, 6,7-pteridinediyl;
pyrazolo[5,1-b]thiazole-2,6-, 2,7-, 3,6-, 3,7-, 2,3- and 6,7-diyl;
thiazolo[2,3-c]-1,2,4-triazole-2,5-, 2,6-, 5,6-diyl;
2-oxo-1,3-benzodioxole-4,5- and 5,6-diyl; 1,3-dioxo-1H-isoindole-2,4-, 2,5-, 4,5- and 5,6-diyl; 2-oxo-2H-1-benzopyran-3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-, 4,8-, 5,6-, 6,7- and 7,8-diyl; [1,2,4]triazolo[1,5-α]pyridine-2,5-, 2,6-, 2,7-, 2,8-, 5,6-, 6,7- and 7,8-diyl;
3,4-dihydro-2,4-dioxo-2H-1,3-benzoxazine-3,5-, 3,6-, 3,7-, 3,8-, 5,6-, 6,7- and 7,8-diyl; 2,3-dihydro-2-oxo-3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and
6,7-benzofurandiyl; thieno[3,2- d]thiazole-2,5-, 2,6-, and 5,6-diyl;
5,6,7,8-tetrahydro-2,5-, 2,6-, 2,7-, 2,8-, 3,5-, 3,6-, 3,7-, 3,8-, 4,5-, 4,6-, 4,7-,
4,8-, 2,3- and 3,4-quinolinediyl; 2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazole-2,4-, 2,5-, 2,6-, 2,7-, 4,5-, 5,6- and 6,7-diyl; 1,3-benzodioxole-2,4-, 2,5-, 4,5- and 5,6-diyl; 2,3-dihydro-2,4-,
2,5-, 2,6-, 2,7-, 3,4-, 3,5-, 3,6-, 3,7-, 4,5-, 5,6- and 6,7-benzofurandiyl;
2,3-dihydro-1,4-benzodioxin-2,5-, 2,6-, 2,7-, 2,8-, 5,6- and 6,7-diyl; and 5,6,7,8-tetrahydro-4H-cycloheρta[b]thiophene-2,4-, 2,5-, 2,6-, 2,7-, 2,8-,
3,4-, 3,5-, 3,6-, 3,7-, 3,8-, and 2,3-diyl; each aromatic ring system optionally substituted with one of R3, R4, or both R3 and R4;
W is O;
R1 is C1-C3 alkyl or C1-C3 haloalkyl;
R2 is Η; C1-C6 alkyl; C1-C6 haloalkyl; or C3-C6 cycloalkyl;
R3 and R4 are each independently halogen; cyano; nitro; C1-C6 alkyl; C1-C6
haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 alkylthio; C1-C6 alkylsulfonyl; C2-C6 alkylcarbonyl; C2-C6 alkoxycarbonyl; (C1-C4 alkyl)NΗC(O); (C1-C4 alkyl)2NC(O); benzoyl; or phenylsulfonyl;
Y is -O-; -CH=CH-; -C≡C-; -CH2O-; -OCH2-; -CH2S(O)n-; -CH2O-N=C(R7)-;
-(R7)C=N-OCH(R15)-; -C(R7)=N-O-; -CH2OC(O)NH-; -CH2S-C(R7)=N-;
-CH=CR6-C(=W1)-A1-; or a direct bond;
R7 is H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 alkylthio; C2-C6
alkenyl; C2-C6 alkynyl; C3-C6 cycloalkyl; halogen; or cyano; or
when Y and an R10 are attached to adjacent atoms on Z and Y is
-CH2O-N=C(R7)-, R7 and said adjacently attached R10 can be taken together as -(CH2)r-J- such that J is attached to Z;
Z is selected from the group C1-C10 alkyl; C3-C8 cycloalkyl; phenyl; naphthalenyl; anthracenyl; phenanthrenyl; 1H-pyrrolyl; furanyl; thienyl; 1H-pyrazolyl;
1H-imidazolyl; isoxazolyl; oxazolyl; isothiazolyl; thiazolyl;
1H-1,2,3-triazolyl; 2H-1,2,3-triazolyl; 1H-1,2,4-triazolyl; 4H-1,2,4-triazolyl;
1,2,3-oxadiazolyl; 1,2,4-oxadiazolyl; 1,2,5-oxadiazolyl; 1,3,4-oxadiazolyl;
1,2,3-thiadiazolyl; 1,2,4-thiadiazolyl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; 1H-tetrazolyl; 2H-tetrazolyl; pyridinyl; pyridazinyl; pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; 1,2,4,5-tetrazinyl; 1H-indolyl; benzofuranyl; benzo[b]thiophenyl; 1H-indazolyl; 1H-benzimidazolyl; benzoxazolyl;
benzothiazolyl; quinolinyl; isoquinolinyl; cinnolinyl; phthalazinyl;
quinazolinyl; quinoxalinyl; 1,8-naphthyridinyl; pteridinyl;
2,3-dihydro- 1H-indenyl; 1 ,2,3,4-tetrahydronaphthalenyl;
6,7,8,9-tetrahydro-5H-benzocycloheptenyl;
5,6,7,8,9,10-hexahydrobenzocyclooctenyl; 2,3-dihydro-3-oxobenzofuranyl; 1,3-dihydro-1-oxoisobenzofuranyl; 2,3-dihydro-2-oxobenzofuranyl;
3,4-dihydro-4-oxo-2H-1-benzopyranyl;
3,4-dihydro-1-oxo-1H-2-benzopyranyl;
3,4-dihydro-3-oxo-1H-2-benzopyranyl;
3,4-dihydro-2-oxo-2H-1-benzopyranyl; 4-oxo-4H-1-benzopyranyl;
2-oxo-2H- 1 -benzopyranyl; 2,3 ,4,5-tetrahydro-5-oxo-1-benzoxepinyl;
2,3,4,5-tetrahydro-2-oxo- 1 -benzoxepinyl;
2,3-dihydro-1,3-dioxo-1H-isoindolyl;
1,2,3,4-tetrahydro-1,3-dioxoisoquinolinyl;
3,4-dihydro-2,4-dioxo-2H-1,3-benzoxazinyl; 2-oxo-1,3-benzodioxyl;
2,3-dihydro-l,1,3-trioxo-1,2-benzisothiazolyl; 9H-fluorenyl; azulenyl; and thiazolo[2,3-c]-1,2,4-triazolyl; each group substituted with R9 and optionally substituted with one or more R10;
R9 is Η; 1-2 halogen; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6
haloalkoxy; C1-C6 alkylthio; cyano; CO2(C1-C6 alkyl); NΗ(C1-C6 alkyl);
N(C1-C6 alkyl)2; SiR22R23R24; or GeR22R23R24; or R9 is C3-C6 cycloalkyl, phenyl, phenoxy, pyridinyl, pyridinyloxy, pyrimidinyl, or pyrimidinyloxy, each optionally substituted with one of R11, R12, or both R11 and R12; and each R15 is independently H; C1-C3 alkyl; or C3-C6 cycloalkyl.
3. A compound of Claim 2 wherein:
E is selected from the group 1,2-phenylene; 1,6-, 1,7-, 1,2-, and
2,3-naphthalenediyl; 2,3- and 3,4-furandiyl; 2,3- and 3,4-thiophenediyl; 2,3- and 3,4-pyridinediyl; 4,5-pyrimidinediyl; 2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and
6,7-benzofurandiyl; and benzo[b]thiophene-2,4-, 2,7-, 3,5-, 2,3-, 4,5-, 5,6- and 6,7-diyl; each aromatic ring system optionally substituted with one of R3,
R4, or both R3 and R4;
Z is selected from the group phenyl; pyridinyl; pyrimidinyl; and naphthalenyl; each group substituted with R9 and optionally substituted with one or more R10; R7 is H; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 alkylthio; C2-C6
alkenyl; C2-C6 alkynyl; cyclopropyl; halogen; or cyano; or
when Y and an R10 are attached to adjacent atoms on Z and Y is
-CH2O-N=C(R7)-, R7 and said adjacently attached R10 can be taken together as -(CH2)r-J- such that J is attached to Z;
J is -CH2- or -CH2CH2-; and
r is 1.
4. A compound of Claim 3 wherein:
E is selected from the group 1,2-phenylene; 2,3- and 3,4-thiophenediyl; and 2,3- and 3,4-pyridinediyl; each aromatic ring system optionally substituted with one of R3, R4, or both R3 and R4;
B is O or NR5;
X is C1-C3 alkyl; NHR1; or N(C1-C3 alkyl)R1;
R1 is C1-C3 alkyl;
R2 is H or C1-C2 alkyl;
Y is -O-; -CH=CH-; -CH2O-; -CH2O-N=C(R7)-; -(R7)C=N-OCH(R15)-;
-CH2OC(=O)NH-; -CH2S-C(R7)=N-; or -CH=CR6-C(=W1)-A1-;
R7 is H; C1-C3 alkyl; C1-C3 haloalkyl; C1-C3 alkoxy; C1-C3 alkylthio; or
cyclopropyl; and
each R15 is independently H; C1-C3 alkyl; or cyclopropyl.
5. A compound of Claim 4 wherein G is G- 1 ; and A is N.
6. A compound of Claim 5 wherein R2 is methyl.
7. A compound of Claim 4 wherein G is G-2; A is N; and X is NHR1 or N(C1-C6 alkyl)R1.
8. A compound of Claim 7 wherein R1 is methyl; and R2 is methyl.
9. The compound of Claim 4 which is selected from the group:
1 ,4-dihydro- 1-methyl-4-[2-[[[[1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-5H-tetrazol-5- one;
1,4-dihydro-1-methyl-4-[2-[[[[1-[3-
(trimethylsilyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-5H-tetrazol-5-one; 2,4-dihydro-2-methyl-5-(methylamino)-4-[2-[[[[1-[3-
(trimemylsilyl)phenyl]emylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol-3- one; and
2,4-dihydro-2,5-dimethyl-4-[2-[[[[1-[3-
(trifluoromethyl)phenyl]ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,4-triazol- 3-one.
10. 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.
11. 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.
PCT/US1996/006507 1995-05-17 1996-05-08 Fungicidal cyclic amides WO1996036229A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US44329695A 1995-05-17 1995-05-17
US08/443,296 1995-05-17

Publications (1)

Publication Number Publication Date
WO1996036229A1 true WO1996036229A1 (en) 1996-11-21

Family

ID=23760233

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/006507 WO1996036229A1 (en) 1995-05-17 1996-05-08 Fungicidal cyclic amides

Country Status (1)

Country Link
WO (1) WO1996036229A1 (en)

Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997019935A1 (en) * 1995-12-01 1997-06-05 E.I. Du Pont De Nemours And Company Processes and compounds for preparing cyclic urea fungicides
WO1998005652A2 (en) * 1996-08-01 1998-02-12 E.I. Du Pont De Nemours And Company Arthropodicidal and fungicidal cyclic amides
WO1999005139A1 (en) * 1997-07-21 1999-02-04 Basf Aktiengesellschaft 2-[pyrazolyl and triazolyl-3'-oxymethylene]-phenyl-isoxazolones, triazolones and tetrazolones as pesticides and fungicides
WO1999031070A1 (en) * 1997-12-17 1999-06-24 Basf Aktiengesellschaft Substituted phenylpyrazolones, method and intermediate products for the production thereof, and their utilization for combating parasitic fungi and animal parasites
US5932583A (en) * 1995-07-04 1999-08-03 Novartis Crop Protection, Inc. Triazoline and isoxazoline bis-oxime derivatives and their use as pesticides
EP0934935A1 (en) * 1998-02-05 1999-08-11 Basf Aktiengesellschaft Heterocyclic substituted phenyl compounds, process and intermediates for their preparation and their use as fungicides and pesticides
US6057352A (en) * 1995-05-17 2000-05-02 E. I. Du Pont De Nemours And Company Fungicidal cyclic amides
US6096895A (en) * 1995-05-17 2000-08-01 E. I. Du Pont De Nemours And Company Heterocyclic dihydrazole compounds and their use for controlling fungal plant diseases
US6294567B1 (en) 1998-04-23 2001-09-25 Sumitomo Chemical Company, Limited Pyrazolinone derivatives
US6417370B1 (en) 1998-02-27 2002-07-09 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic keto-enols
US6451843B1 (en) 1998-04-27 2002-09-17 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic keto enols
US6458965B1 (en) 1998-03-26 2002-10-01 Bayer Aktiengesellschaft Aryl phenyl substituted cyclic ketoenols
US6489487B1 (en) 1998-08-03 2002-12-03 Sumitomo Chemical Company, Limited Triazolone derivatives, use thereof, and intermediates therefor
CN100430373C (en) * 2005-04-05 2008-11-05 湖南化工研究院 Biological active compound of methoxy acrylic ester containing bis trifluoromethyl phenyl and preparing process thereof
US20120029199A1 (en) * 2006-10-11 2012-02-02 President And Fellows Of Harvard College Synthesis of enone intermediate
US8119566B2 (en) 2003-08-14 2012-02-21 Bayer Cropscience Ag 4-biphenyl-substituted pyrazolidin-3,5-dione derivatives
WO2013092224A1 (en) 2011-12-21 2013-06-27 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi resistant to qo inhibitors
WO2013162077A1 (en) 2012-04-27 2013-10-31 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use
US8598148B2 (en) 2004-05-21 2013-12-03 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
US8722695B2 (en) 2009-12-11 2014-05-13 Autifony Therapeutics Limited Imidazolidinedione derivatives
WO2014175465A1 (en) 2013-04-26 2014-10-30 住友化学株式会社 Tetrazolinone compound and use of same
CN104245689A (en) * 2012-04-27 2014-12-24 住友化学株式会社 Tetrazolinone compounds and its use as pesticides
EP2815647A1 (en) 2013-06-18 2014-12-24 Basf Se Novel strobilurin-type compounds for combating phytopathogenic fungi
WO2015005499A1 (en) 2013-07-12 2015-01-15 住友化学株式会社 Tetrazolinone compound and use thereof
WO2015016373A1 (en) * 2013-07-31 2015-02-05 住友化学株式会社 Tetrazolinone compound, and use therefor
WO2015016372A1 (en) 2013-07-31 2015-02-05 住友化学株式会社 Tetrazolinone compound, and use therefor
WO2015030217A1 (en) 2013-08-29 2015-03-05 住友化学株式会社 Tetrazolinone compound and use of same
WO2015046480A1 (en) * 2013-09-25 2015-04-02 住友化学株式会社 Tetrazolinone compound and use thereof
WO2015056806A1 (en) 2013-10-17 2015-04-23 住友化学株式会社 Tetrazolinone compound and application for same
WO2015060461A1 (en) * 2013-10-25 2015-04-30 住友化学株式会社 Tetrazolinone compound and use thereof
WO2015064727A1 (en) * 2013-10-28 2015-05-07 住友化学株式会社 Tetrazolinone compound and application for same
CN104884442A (en) * 2012-12-27 2015-09-02 住友化学株式会社 Tetrazolinone compound and applications thereof
US9133175B2 (en) 2010-12-06 2015-09-15 Autifony Therapeutics Limited Compounds
WO2015146552A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Method for producing tetrazolinone compound
WO2015147332A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Tetrazolinone compound and application for same
WO2015147337A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Tetrazolinone compound and application for same
US20150299146A1 (en) * 2012-11-29 2015-10-22 Sumitomo Chemical Company, Limited Tetrazolinone compound and applications thereof
US9193704B2 (en) 2011-06-07 2015-11-24 Autifony Therapeutics Limited Hydantoin derivatives as KV3 inhibitors
US9314023B2 (en) 2012-09-28 2016-04-19 Sumitomo Chemical Company, Limited Tetrazolinone compounds and their use as pesticides
CN105636955A (en) * 2013-10-17 2016-06-01 住友化学株式会社 Tetrazolinone compound and application for same
WO2016088747A1 (en) * 2014-12-01 2016-06-09 日産化学工業株式会社 Hydrazone derivative and pest control agent
US9422252B2 (en) 2012-05-22 2016-08-23 Autifony Therapeutics Limited Triazoles as Kv3 inhibitors
CN106164069A (en) * 2014-03-28 2016-11-23 住友化学株式会社 Terazololine-one compound and application thereof
US9669030B2 (en) 2012-05-22 2017-06-06 Autifony Therapeutics Limited Hydantoin derivatives as Kv3 inhibitors
WO2018097318A1 (en) * 2016-11-28 2018-05-31 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use as pest control agents
US10053448B2 (en) 2015-03-31 2018-08-21 Sumitomo Chemical Company, Limited Substituted tetrazolinones for controlling plant diseases
US10375959B2 (en) 2015-01-22 2019-08-13 BASF Agro B.V. Ternary herbicidal combination comprising saflufenacil
CN110194749A (en) * 2019-07-08 2019-09-03 福州大学 3- trifluoro (difluoro) methyl-1, the synthetic method of 2,4- triazole -5- ketone compounds
CN114728951A (en) * 2019-11-15 2022-07-08 先正达农作物保护股份公司 Herbicidal thiazole compounds
EP4242199A1 (en) * 2022-03-07 2023-09-13 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors xii

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4059703A (en) * 1975-08-19 1977-11-22 Imperial Chemical Industries Limited Pesticidal compounds, processes and compositions
US5064845A (en) * 1990-05-29 1991-11-12 Rohm And Haas Company Fungicidal compositions and methods of use
US5108486A (en) * 1990-02-09 1992-04-28 Kanagawa Chemical Laboratory, Ltd. Herbicidal substituted-phenyl-1,2,4-triazol-5(1H)-thiones and -ones
US5136868A (en) * 1983-11-04 1992-08-11 Fmc Corporation Herbicidal 1-aryl-4-substituted-1,4-dihydro-5h-tetrazol-5-ones and sulfur analogs thereof
US5138068A (en) * 1989-06-26 1992-08-11 Ciba-Geigy Corporation 1-phenyl 5-oxotetrazolines

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4059703A (en) * 1975-08-19 1977-11-22 Imperial Chemical Industries Limited Pesticidal compounds, processes and compositions
US5136868A (en) * 1983-11-04 1992-08-11 Fmc Corporation Herbicidal 1-aryl-4-substituted-1,4-dihydro-5h-tetrazol-5-ones and sulfur analogs thereof
US5138068A (en) * 1989-06-26 1992-08-11 Ciba-Geigy Corporation 1-phenyl 5-oxotetrazolines
US5108486A (en) * 1990-02-09 1992-04-28 Kanagawa Chemical Laboratory, Ltd. Herbicidal substituted-phenyl-1,2,4-triazol-5(1H)-thiones and -ones
US5064845A (en) * 1990-05-29 1991-11-12 Rohm And Haas Company Fungicidal compositions and methods of use

Cited By (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6096895A (en) * 1995-05-17 2000-08-01 E. I. Du Pont De Nemours And Company Heterocyclic dihydrazole compounds and their use for controlling fungal plant diseases
US6057352A (en) * 1995-05-17 2000-05-02 E. I. Du Pont De Nemours And Company Fungicidal cyclic amides
US5932583A (en) * 1995-07-04 1999-08-03 Novartis Crop Protection, Inc. Triazoline and isoxazoline bis-oxime derivatives and their use as pesticides
WO1997019935A1 (en) * 1995-12-01 1997-06-05 E.I. Du Pont De Nemours And Company Processes and compounds for preparing cyclic urea fungicides
WO1998005652A3 (en) * 1996-08-01 1998-06-11 E I De Pount De Nemours And Co Arthropodicidal and fungicidal cyclic amides
WO1998005652A2 (en) * 1996-08-01 1998-02-12 E.I. Du Pont De Nemours And Company Arthropodicidal and fungicidal cyclic amides
WO1999005139A1 (en) * 1997-07-21 1999-02-04 Basf Aktiengesellschaft 2-[pyrazolyl and triazolyl-3'-oxymethylene]-phenyl-isoxazolones, triazolones and tetrazolones as pesticides and fungicides
US7056941B1 (en) 1997-07-21 2006-06-06 Basf Aktiengesellschaft 2-[pyrazolyl and triazolyl-3′-oxymethylene]-phenyl-isoxazolones, triazolones and tetrazolones as pesticides and fungicides
WO1999031070A1 (en) * 1997-12-17 1999-06-24 Basf Aktiengesellschaft Substituted phenylpyrazolones, method and intermediate products for the production thereof, and their utilization for combating parasitic fungi and animal parasites
EP0934935A1 (en) * 1998-02-05 1999-08-11 Basf Aktiengesellschaft Heterocyclic substituted phenyl compounds, process and intermediates for their preparation and their use as fungicides and pesticides
US6200997B1 (en) 1998-02-05 2001-03-13 Basf Aktiengesellschaft Heterocyclyl-substituted phenyl compounds, processes and intermediates for their preparation and their use for controlling harmful fungi and animal pests
US8058210B2 (en) 1998-02-27 2011-11-15 Bayer Cropscience Ag Arylphenyl-substituted cyclic keto-enols
US6417370B1 (en) 1998-02-27 2002-07-09 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic keto-enols
US7718706B2 (en) 1998-02-27 2010-05-18 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic keto-enols
US6716832B2 (en) 1998-02-27 2004-04-06 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic ketoenols
US7288676B2 (en) 1998-02-27 2007-10-30 Bayer Cropscience Ag Arylphenyl-substituted cyclic ketoenols
US7105471B2 (en) 1998-02-27 2006-09-12 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic ketoenols
US6458965B1 (en) 1998-03-26 2002-10-01 Bayer Aktiengesellschaft Aryl phenyl substituted cyclic ketoenols
US6693092B2 (en) 1998-03-26 2004-02-17 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic ketoenols
US6806264B2 (en) 1998-03-26 2004-10-19 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic ketoenols
US6294567B1 (en) 1998-04-23 2001-09-25 Sumitomo Chemical Company, Limited Pyrazolinone derivatives
US6451843B1 (en) 1998-04-27 2002-09-17 Bayer Aktiengesellschaft Arylphenyl-substituted cyclic keto enols
US6489487B1 (en) 1998-08-03 2002-12-03 Sumitomo Chemical Company, Limited Triazolone derivatives, use thereof, and intermediates therefor
US8119566B2 (en) 2003-08-14 2012-02-21 Bayer Cropscience Ag 4-biphenyl-substituted pyrazolidin-3,5-dione derivatives
US8987500B2 (en) 2003-08-14 2015-03-24 Bayer Cropscience Ag 4-biphenyl-substituted pyrazolidin-3,5-dione derivatives
US8586783B2 (en) 2003-08-14 2013-11-19 Bayer Cropscience Ag 4-biphenyl-substituted pyrazolidin-3,5-dione derivatives
US9884830B2 (en) 2004-05-21 2018-02-06 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
US10669244B2 (en) 2004-05-21 2020-06-02 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
US9365493B2 (en) 2004-05-21 2016-06-14 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
US11192866B2 (en) 2004-05-21 2021-12-07 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
US8598148B2 (en) 2004-05-21 2013-12-03 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
CN100430373C (en) * 2005-04-05 2008-11-05 湖南化工研究院 Biological active compound of methoxy acrylic ester containing bis trifluoromethyl phenyl and preparing process thereof
US8293920B2 (en) * 2006-10-11 2012-10-23 President And Fellows Of Harvard College Synthesis of enone intermediate
US8907104B2 (en) 2006-10-11 2014-12-09 President And Fellows Of Harvard College Synthesis of enone intermediate
US8580969B2 (en) 2006-10-11 2013-11-12 President And Fellows Of Harvard College Synthesis of enone intermediate
US20120029199A1 (en) * 2006-10-11 2012-02-02 President And Fellows Of Harvard College Synthesis of enone intermediate
US9849131B2 (en) 2009-12-11 2017-12-26 Autifony Therapeutics Limited Imidazolidinedione derivatives
US8722695B2 (en) 2009-12-11 2014-05-13 Autifony Therapeutics Limited Imidazolidinedione derivatives
US10058551B2 (en) 2009-12-11 2018-08-28 Autifony Therapeutics Limited Imidazolidinedione derivatives
US10632118B2 (en) 2009-12-11 2020-04-28 Autifony Therapeutics Limited Imidazolidinedione derivatives
US9216967B2 (en) 2009-12-11 2015-12-22 Autifony Therapeutics Limited Imidazolidinedione derivatives
US11583527B2 (en) 2010-12-06 2023-02-21 Autifony Therapeutics Limited Hydantoin derivatives useful as Kv3 inhibitors
US9422272B2 (en) 2010-12-06 2016-08-23 Autifony Therapeutics Limited Compounds
US10265316B2 (en) 2010-12-06 2019-04-23 Autifony Therapeuctics Limited Hydantoin derivatives useful as Kv3 inhibitors
US10098881B2 (en) 2010-12-06 2018-10-16 Autifony Therapeutics Limited Compounds
US10835534B2 (en) 2010-12-06 2020-11-17 Autifony Therapeutics Limited Compounds
US9346790B2 (en) 2010-12-06 2016-05-24 Autifony Therapeutics Limited Hydantoin derivatives useful as Kv3 inhibitors
US11197859B2 (en) 2010-12-06 2021-12-14 Autifony Therapeutics Limited Hydantoin derivatives useful as Kv3 inhibitors
US10555945B2 (en) 2010-12-06 2020-02-11 Autifony Therapeutics Limited Compounds
US11541052B2 (en) 2010-12-06 2023-01-03 Autifony Therapeutics Limited Compounds
US9833452B2 (en) 2010-12-06 2017-12-05 Autifony Therapeutics Limited Compounds
US9133175B2 (en) 2010-12-06 2015-09-15 Autifony Therapeutics Limited Compounds
US9193704B2 (en) 2011-06-07 2015-11-24 Autifony Therapeutics Limited Hydantoin derivatives as KV3 inhibitors
EA024331B1 (en) * 2011-12-21 2016-09-30 Басф Се USE OF STROBILURIN TYPE COMPOUNDS FOR COMBATING PHYTOPATHOGENIC FUNGI RESISTANT TO Qo INHIBITORS
CN104010502B (en) * 2011-12-21 2016-08-24 巴斯夫欧洲公司 Strobilurin-types compound purposes in the plant pathogenic fungi of preventing and treating tolerance Qo inhibitor
CN104010502A (en) * 2011-12-21 2014-08-27 巴斯夫欧洲公司 Use of strobilurin type compounds for combating phytopathogenic fungi resistant to Qo inhibitors
US9271501B2 (en) 2011-12-21 2016-03-01 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi resistant to QO inhibitors
WO2013092224A1 (en) 2011-12-21 2013-06-27 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi resistant to qo inhibitors
US10080365B2 (en) 2011-12-21 2018-09-25 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi resistant to Qo inhibitors
CN104245689A (en) * 2012-04-27 2014-12-24 住友化学株式会社 Tetrazolinone compounds and its use as pesticides
CN104271571B (en) * 2012-04-27 2017-07-07 住友化学株式会社 Terazololine-one compound and application thereof
WO2013162077A1 (en) 2012-04-27 2013-10-31 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use
US9565856B2 (en) 2012-04-27 2017-02-14 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use as pesticides
RU2646759C2 (en) * 2012-04-27 2018-03-07 Сумитомо Кемикал Компани, Лимитед Tetrazolinone compounds and their application as pesticides
JP2014101347A (en) * 2012-04-27 2014-06-05 Sumitomo Chemical Co Ltd Tetrazolinone compound and its use
CN104271571A (en) * 2012-04-27 2015-01-07 住友化学株式会社 Tetrazolinone compounds and its use
US9380782B2 (en) 2012-04-27 2016-07-05 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use
CN104245689B (en) * 2012-04-27 2017-06-06 住友化学株式会社 Terazololine-one compound and its purposes as insecticide
US9669030B2 (en) 2012-05-22 2017-06-06 Autifony Therapeutics Limited Hydantoin derivatives as Kv3 inhibitors
US10160730B2 (en) 2012-05-22 2018-12-25 Autifony Therapeutics Limited Triazoles as KV3 inhibitors
US11180461B2 (en) 2012-05-22 2021-11-23 Autifony Therapeutics Limited Triazoles as Kv3 inhibitors
US10611735B2 (en) 2012-05-22 2020-04-07 Autifony Therapeutics Limited Triazoles as Kv3 inhibitors
US9422252B2 (en) 2012-05-22 2016-08-23 Autifony Therapeutics Limited Triazoles as Kv3 inhibitors
US9314023B2 (en) 2012-09-28 2016-04-19 Sumitomo Chemical Company, Limited Tetrazolinone compounds and their use as pesticides
US9554576B2 (en) 2012-09-28 2017-01-31 Sumitomo Chemical Company, Limited Tetrazolinone compounds and their use as pesticides
US20150299146A1 (en) * 2012-11-29 2015-10-22 Sumitomo Chemical Company, Limited Tetrazolinone compound and applications thereof
US9725423B2 (en) 2012-11-29 2017-08-08 Sumitomo Chemical Company, Limited Tetrazolinone compound and applications thereof
US9560850B2 (en) 2012-12-27 2017-02-07 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
CN104884442B (en) * 2012-12-27 2016-11-02 住友化学株式会社 Terazololine-one compound and application thereof
CN104884442A (en) * 2012-12-27 2015-09-02 住友化学株式会社 Tetrazolinone compound and applications thereof
WO2014175465A1 (en) 2013-04-26 2014-10-30 住友化学株式会社 Tetrazolinone compound and use of same
JPWO2014175465A1 (en) * 2013-04-26 2017-02-23 住友化学株式会社 Tetrazolinone compounds and uses thereof
EP2990404A4 (en) * 2013-04-26 2016-09-07 Sumitomo Chemical Co Tetrazolinone compound and use of same
CN105339359A (en) * 2013-04-26 2016-02-17 住友化学株式会社 Tetrazolinone compound and use of same
US9867372B2 (en) 2013-04-26 2018-01-16 Sumitomo Chemical Company, Limited Tetrazolinone compound and use of same
EP2815647A1 (en) 2013-06-18 2014-12-24 Basf Se Novel strobilurin-type compounds for combating phytopathogenic fungi
EP2815648A1 (en) 2013-06-18 2014-12-24 Basf Se Novel strobilurin-type compounds for combating phytopathogenic fungi
US9888688B2 (en) 2013-07-12 2018-02-13 Sumitomo Chemical Company, Limited Tetrazolinone compounds and applications thereof
WO2015005499A1 (en) 2013-07-12 2015-01-15 住友化学株式会社 Tetrazolinone compound and use thereof
US20160150787A1 (en) * 2013-07-12 2016-06-02 Sumitomo Chemical Company, Limited Tetrazolinone compounds and applications thereof
US9521848B2 (en) 2013-07-31 2016-12-20 Sumitomo Chemical Company, Limited Tetrazolinone compound and use therefor
EP3029030A4 (en) * 2013-07-31 2017-03-08 Sumitomo Chemical Company, Limited Tetrazolinone compound, and use therefor
WO2015016372A1 (en) 2013-07-31 2015-02-05 住友化学株式会社 Tetrazolinone compound, and use therefor
WO2015016373A1 (en) * 2013-07-31 2015-02-05 住友化学株式会社 Tetrazolinone compound, and use therefor
CN105392779B (en) * 2013-07-31 2018-01-19 住友化学株式会社 Terazololine-one compound and application thereof
CN105492432A (en) * 2013-07-31 2016-04-13 住友化学株式会社 Tetrazolinone compound, and use therefor
US9512090B2 (en) 2013-07-31 2016-12-06 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
CN105392779A (en) * 2013-07-31 2016-03-09 住友化学株式会社 Tetrazolinone compound, and use therefor
JPWO2015016372A1 (en) * 2013-07-31 2017-03-02 住友化学株式会社 Tetrazolinone compounds and uses thereof
JPWO2015016373A1 (en) * 2013-07-31 2017-03-02 住友化学株式会社 Tetrazolinone compounds and uses thereof
JPWO2015030217A1 (en) * 2013-08-29 2017-03-02 住友化学株式会社 Tetrazolinone compounds and uses thereof
US9730448B2 (en) 2013-08-29 2017-08-15 Sumitomo Chemical Company, Limited Tetrazolinone compound and use of same
WO2015030217A1 (en) 2013-08-29 2015-03-05 住友化学株式会社 Tetrazolinone compound and use of same
WO2015046480A1 (en) * 2013-09-25 2015-04-02 住友化学株式会社 Tetrazolinone compound and use thereof
JPWO2015056806A1 (en) * 2013-10-17 2017-03-09 住友化学株式会社 Tetrazolinone compounds and uses thereof
US10085450B2 (en) 2013-10-17 2018-10-02 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
CN105636957A (en) * 2013-10-17 2016-06-01 住友化学株式会社 Tetrazolinone compound and application for same
US10077254B2 (en) 2013-10-17 2018-09-18 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
WO2015056806A1 (en) 2013-10-17 2015-04-23 住友化学株式会社 Tetrazolinone compound and application for same
CN105636955A (en) * 2013-10-17 2016-06-01 住友化学株式会社 Tetrazolinone compound and application for same
CN105636957B (en) * 2013-10-17 2018-05-11 住友化学株式会社 Terazololine-one compound and application thereof
CN105636955B (en) * 2013-10-17 2018-01-12 住友化学株式会社 Terazololine-one compound and application thereof
JPWO2015060461A1 (en) * 2013-10-25 2017-03-09 住友化学株式会社 Tetrazolinone compounds and uses thereof
US20160235065A1 (en) * 2013-10-25 2016-08-18 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
WO2015060461A1 (en) * 2013-10-25 2015-04-30 住友化学株式会社 Tetrazolinone compound and use thereof
US9635857B2 (en) 2013-10-25 2017-05-02 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
CN105658630A (en) * 2013-10-25 2016-06-08 住友化学株式会社 Tetrazolinone compound and use thereof
EP3061756A4 (en) * 2013-10-25 2017-06-21 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
US10091998B2 (en) 2013-10-28 2018-10-09 Sumitomo Chemical Company, Limited Tetrazolinone compound and use thereof
JPWO2015064727A1 (en) * 2013-10-28 2017-03-09 住友化学株式会社 Tetrazolinone compounds and uses thereof
WO2015064727A1 (en) * 2013-10-28 2015-05-07 住友化学株式会社 Tetrazolinone compound and application for same
CN105683169A (en) * 2013-10-28 2016-06-15 住友化学株式会社 Tetrazolinone compound and application for same
EP3064492A4 (en) * 2013-10-28 2017-06-21 Sumitomo Chemical Company, Limited Tetrazolinone compound and application for same
US9822085B2 (en) 2014-03-20 2017-11-21 Sumitomo Chemical Company, Limited Method for producing tetrazolinone compound
WO2015147332A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Tetrazolinone compound and application for same
JPWO2015147337A1 (en) * 2014-03-28 2017-04-13 住友化学株式会社 Tetrazolinone compounds and uses thereof
WO2015146552A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Method for producing tetrazolinone compound
CN106132952B (en) * 2014-03-28 2019-04-16 住友化学株式会社 Terazololine-one compound and its application
JPWO2015146552A1 (en) * 2014-03-28 2017-04-13 住友化学株式会社 Method for producing tetrazolinone compound
CN106132938B (en) * 2014-03-28 2019-05-17 住友化学株式会社 Terazololine-one compound and its application
JPWO2015147332A1 (en) * 2014-03-28 2017-04-13 住友化学株式会社 Tetrazolinone compounds and uses thereof
US9822095B2 (en) 2014-03-28 2017-11-21 Sumitomo Chemical Company, Limited Tetrazolinone compound and application thereof
US9826741B2 (en) 2014-03-28 2017-11-28 Sumitomo Chemical Company, Limited Tetrazolinone compound and application thereof
CN106132938A (en) * 2014-03-28 2016-11-16 住友化学株式会社 Terazololine-one compound and application thereof
CN106132952A (en) * 2014-03-28 2016-11-16 住友化学株式会社 Terazololine-one compound and application thereof
WO2015147337A1 (en) * 2014-03-28 2015-10-01 住友化学株式会社 Tetrazolinone compound and application for same
CN106164069A (en) * 2014-03-28 2016-11-23 住友化学株式会社 Terazololine-one compound and application thereof
WO2016088747A1 (en) * 2014-12-01 2016-06-09 日産化学工業株式会社 Hydrazone derivative and pest control agent
US10375959B2 (en) 2015-01-22 2019-08-13 BASF Agro B.V. Ternary herbicidal combination comprising saflufenacil
US10053448B2 (en) 2015-03-31 2018-08-21 Sumitomo Chemical Company, Limited Substituted tetrazolinones for controlling plant diseases
CN110023303B (en) * 2016-11-28 2022-01-18 住友化学株式会社 Tetrazolinone compounds and their use as pest control agents
US11225470B2 (en) 2016-11-28 2022-01-18 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use as pest control agents
CN110023303A (en) * 2016-11-28 2019-07-16 住友化学株式会社 Terazololine-one compound and its purposes as pest control agent
WO2018097318A1 (en) * 2016-11-28 2018-05-31 Sumitomo Chemical Company, Limited Tetrazolinone compounds and its use as pest control agents
CN110194749A (en) * 2019-07-08 2019-09-03 福州大学 3- trifluoro (difluoro) methyl-1, the synthetic method of 2,4- triazole -5- ketone compounds
CN110194749B (en) * 2019-07-08 2022-04-26 福州大学 Method for synthesizing 3-trifluoro (difluoro) methyl-1, 2, 4-triazole-5-ketone compound
CN114728951A (en) * 2019-11-15 2022-07-08 先正达农作物保护股份公司 Herbicidal thiazole compounds
EP4242199A1 (en) * 2022-03-07 2023-09-13 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors xii

Similar Documents

Publication Publication Date Title
WO1996036229A1 (en) Fungicidal cyclic amides
US6057352A (en) Fungicidal cyclic amides
US6096895A (en) Heterocyclic dihydrazole compounds and their use for controlling fungal plant diseases
AU677448B2 (en) Fungicidal cyclic amides
WO1997000612A1 (en) Arthropodicidal and fungicidal cyclic amides
JP2771334B2 (en) Fungicidal and fungicidal cyclic amides
JP2001506984A (en) Methyl-substituted fungicides and arthropodicides
WO1998023155A1 (en) Arthropodicidal and fungicidal cyclic amides
US5962436A (en) Fungicidal cyclic amides
JP2000516583A (en) Cyclic amides that are arthropodic and fungicidal and fungicidal
EP0630370A1 (en) Fungicidal oxazolidinones
WO1999028305A1 (en) Fungicidal cyclic amides
EP0869963A1 (en) Arthropodicidal and fungicidal organosilanes and organogermanes
WO1999011129A1 (en) Enantiomerically enriched compositions and their pesticidal use
WO1998020003A1 (en) Fungicidal cyclic amides
WO1998033382A1 (en) Fungicidal compositions
USH1401H (en) Fungicidal oxazolidinones
JP3378237B2 (en) Insecticidal dihydro-oxadiazines, -thiadiazines and -triazines
MXPA99004066A (en) Fungicidal cyclic amides
MXPA99001173A (en) Arthropodicidal and fungicidal cyclic amides

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase