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WO1998004525A1 - Fungicidal n-aryl five-membered cyclic imides - Google Patents

Fungicidal n-aryl five-membered cyclic imides Download PDF

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Publication number
WO1998004525A1
WO1998004525A1 PCT/GB1997/002012 GB9702012W WO9804525A1 WO 1998004525 A1 WO1998004525 A1 WO 1998004525A1 GB 9702012 W GB9702012 W GB 9702012W WO 9804525 A1 WO9804525 A1 WO 9804525A1
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Prior art keywords
optionally substituted
hydrogen
compounds according
alkyl
compounds
Prior art date
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PCT/GB1997/002012
Other languages
French (fr)
Inventor
Peter John West
Clive Leonard Cornell
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Agrevo Uk Limited
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Publication date
Application filed by Agrevo Uk Limited filed Critical Agrevo Uk Limited
Priority to AU37002/97A priority Critical patent/AU3700297A/en
Publication of WO1998004525A1 publication Critical patent/WO1998004525A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
    • C07D207/408—Radicals containing only hydrogen and carbon atoms attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom 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
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
    • C07D233/72—Two oxygen atoms, e.g. hydantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • C07D271/07—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole 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
    • C07D277/34—Oxygen atoms

Definitions

  • This invention relates to compounds having pesticidal, especially fungicidal, insecticidal and acaricidal, activity.
  • the invention provides compounds of general formula I
  • A is O, S or NR ⁇ ; where R ⁇ is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
  • R 2 and R 3 which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
  • D is CR R 5 , CR 4 , NR 4 , N, 0 or S; where R 4 and R 5 , which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
  • E is O, S or NR6; where ⁇ is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl; provided that when B is NR 2 , then D is CR 4 R 5 , O or S; and when B is N, then where the dotted line signifies that a single or a double bond can be present as appropriate;
  • R9 to R ** 2 which may be the same or different, are hydrogen, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkoxy, or any two of R-** 1 to
  • R ⁇ 3 and R ⁇ 4 which may be the same or different, and are hydrogen or optionally substituted alkyl;
  • R 1 5 is hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted acyl or cyano, or R ⁇ and the carbon to which it is
  • heterocyclyl includes both aromatic and non-aromatic heterocyclyl groups.
  • Heterocyclyl groups are generally 5, 6 or 7-membered rings containing up to 4 hetero atoms selected from nitrogen, oxygen and sulfur.
  • Examples of heterocyclyl groups are furyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, dioxolanyl, oxazolyl, thiazolyl, imidazolyl, imidazolinyl, imidazoiidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyranyl, pyridyl, piperidinyl, dioxanyl, morpholino, dithianyl, thiomorpholino, pyridazinyl, pyr
  • Alkyl groups are preferably of 1 to 6 carbon atoms.
  • Alkenyl and alkynyl groups are generally of 3 to 6 carbon atoms.
  • Cycloalkyl or cycloalkenyl groups are preferably of 3 to 8 carbon atoms.
  • Substituents when present on any alkyl, cycloalkyl, cycloalkenyl, alkenyl or alkynyl moiety include, halogen, cyano, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted haloalkyl, hydroxy, nitro, optionally substituted amino, acyl, acyloxy, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted phenoxy and optionally substituted heterocyclyloxy.
  • Preferred substituents are halogen.
  • Cycloalkyl or cycloalkenyl groups may also be substituted by alkyl.
  • Amino groups may be substituted for example by one or two optionally substituted alkyl or acyl groups, or two substituents can form a ring, preferably a 5 to 7- membered ring, which may be substituted and may contain other hetero atoms, for example morpholine, thiomorpholine, or piperidine.
  • acyl includes the residue of sulfur and phosphorus-containing acids as well as carboxylic acids.
  • fused ring system when present, may be carbocyclic or heterocyclic, containing up to 3 heteroatoms; and include aromatic or non-aromatic 5, 6, or 7 membered rings.
  • Preferred fused ring systems include naphthalene and quinoline.
  • Substituents when present on any heterocyclyl group may for example be halogen, CN, NO2, acyl, O-acyl or a group T, OT or S(0) n T, where n is 0, 1 or 2 and T is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted acyl, optionally substituted phenyl, optionally substituted heterocyclyl or optionally substituted amino or two adjacent groups on the ring together with the atoms to which they are attached form a carbocyclic or heterocyclic ring, which may be similarly substituted.
  • Substituents when present on any phenyl group are preferably as defined above for the substituents on the heterocyclyl group.
  • particularly efficacious group of compounds are those of general formula I where A and E are 0.
  • B is CR 2 R 3 or NR 2 ; and/or D is CR 4 R 5 , NR 4 , 0, or S.
  • R 2 is preferably hydrogen or optionally substituted alkyl; and/or R 3 is preferably hydrogen; and/or R 4 is preferably hydrogen or optionally substituted alkyl; and/or R * -> is preferably hydrogen.
  • R " * -3 is preferably hydrogen or optionally substituted alkyl.
  • R "* ** * is preferably optionally substituted alkyl.
  • L is preferably an optionally substituted phenyl group or the group Si(R 22 >3.
  • L is a substituted phenyl, it is preferably substituted by one or more of the following groups C -I -CQ alkyl, C - ⁇ -CQ haloalkyl, C - ⁇ -CQ alkoxy, C -J -CQ alkylthio, C CQ haloalkoxy, halophenoxy, halogen, C3-C8 cycloalkyl, piperidino or pyrimidinyl.
  • R ⁇ to R ⁇ 2 are each hydrogen or halogen.
  • the invention includes individual isomers as well as mixtures thereof.
  • the compounds of the invention have activity as fungicides, especially against fungal diseases of plants, e.g. mildews and particularly barley powdery mildew (Erysiphe graminis) and vine downy mildew (Plasmopara viticola), rice blast (Pyricularia oryzae), cereal eyespot (Pseudocercosporei/a herpotrichoides) , rice sheath blight (PelHcularia sasakii), grey mould (Botrytis cinerea), damping off
  • rice blast Pyricularia oryzae
  • cereal eyespot Pseudocercosporei/a herpotrichoides
  • rice sheath blight PelHcularia sasakii
  • grey mould Botrytis cinerea
  • fungi against which the compounds may be active include other powdery mildews, other rusts, and general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidomycete origin.
  • the invention thus also provides a method of combating pests (i.e. fungi, insects, nematodes, acarids and weeds) at a locus infested or liable to be infested therewith, which comprises applying to the locus a compound of formula I.
  • pests i.e. fungi, insects, nematodes, acarids and weeds
  • the invention also provides an agricultural composition
  • an agricultural composition comprising a compound of formula I in admixture with an agriculturally acceptable diluent or carrier.
  • composition of the invention may of course include more than one compound of the invention.
  • composition can comprise one or more additional active ingredients, for example compounds known to possess plant-growth regulant, herbicidal, fungicidal, insecticidal or acaricidal properties.
  • additional active ingredients for example compounds known to possess plant-growth regulant, herbicidal, fungicidal, insecticidal or acaricidal properties.
  • the compound of the invention can be used in sequence with the other active ingredient.
  • the diluent or carrier in the composition of the invention can be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent.
  • Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or salts of such esters; fatty alcohol sulfates such as sodium dodecyl sulfate, sodium octadecyl sulfate or sodium cetyl sulfate; ethoxylated fatty alcohol sulfates; ethoxylated alkylphenol sulfates; lignin suifonates; petroleum suifonates; alkyl-aryl suifonates such as alkyl-benzene suifonates or lower alky
  • butyl-naphthalene sulfonate salts of sulfonated naphthalene-formaldehyde condensates; salts of sulfonated phenol-formaldehyde condensates; or more complex suifonates such as the amide suifonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate.
  • amide suifonates e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate.
  • Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alkyl- or alkenyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide, e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, or ethoxylated acetylenic glycols.
  • a cationic surface-active agent examples include, for instance, an aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such as an amine oxide or polyoxyethylene alkylamine; an amide-linked amine prepared by the condensation of a carboxyiic acid with a di- or polyamine; or a quaternary ammonium salt.
  • compositions of the invention can take any form known in the art for the formulation of agrochemicals, for example, a solution, a dispersion, an aqueous emulsion, a dusting powder, a seed dressing, a fumigant, a smoke, a dispersible powder, an emulsifiable concentrate or granules. Moreover it can be in a suitable form for direct application or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.
  • An emulsifiable concentrate comprises a compound of the invention dissolved in a water-immiscible solvent which is formed into an emulsion with water in the presence of an emulsifying agent.
  • a dusting powder comprises a compound of the invention intimately mixed and ground with a solid pulverulent diluent, for example, kaolin.
  • a granular solid comprises a compound of the invention associated with similar diluents to those which may be employed in dusting powders, but the mixture is granulated by known methods. Alternatively it comprises the active ingredient absorbed or adsorbed on a pre-granular diluent, for example, Fuller's earth, attapulgite or limestone grit.
  • Wettable powders, granules or grains usually comprise the active ingredient in admixture with a suitable surfactant and an inert powder diluent such as china clay.
  • Another suitable concentrate is a fiowable suspension concentrate which is formed by grinding the compound with water or other liquid, a wetting agent and a suspending agent.
  • the concentration of the active ingredient in the composition of the present invention, as applied to plants is preferably within the range of 0.0001 to 1.0 per cent by weight, especially 0.0001 to 0.01 per cent by weight.
  • the amount of active ingredient can vary widely and can be, for example, from 5 to 95 per cent by weight of the composition.
  • the compound is generally applied to seeds, plants or their habitat.
  • the compound can be applied directly to the soil before, at or after drilling so that the presence of active compound in the soil can control the growth of fungi which may attack seeds.
  • the active compound can be applied in any manner which allows it to be intimately mixed with the soil such as by spraying, by broadcasting a solid form of granules, or by applying the active ingredient at the same time as drilling by inserting it in the same drill as the seeds.
  • a suitable application rate is within the range of from 5 to 1000 g per hectare, more preferably from 10 to 500 g per hectare.
  • the active compound can be applied directly to the plant by, for example, spraying or dusting either at the time when the fungus has begun to appear on the plant or before the appearance of fungus as a protective measure.
  • the preferred mode of application is by foliar spraying. It is generally important to obtain good control of fungi in the early stages of plant growth as this is the time when the plant can be most severely damaged.
  • the spray or dust can conveniently contain a pre- or post-emergence herbicide if this is thought necessary.
  • a suitable rate of application is from 0.025 to 5 kg per hectare, preferably from 0.05 to 1 kg per hectare.
  • B in CR 2 R 3 ; D is NR 4 and E is 0; may be prepared in two steps by reacting amines VI with isocyanate VII, where Q is a leaving group, followed by cyclisation.
  • Construction of the group -K-L can be performed using a number of strategies either before or after construction of the 5-membered heterocyclyl group.
  • compounds of formula Ik i.e. compounds of general formula I where K is -CH(R ⁇ 3 )-, can be prepared by reacting hydroxy compound IX, which is preferably a phenolic compound, with potassium re -butoxide followed by addition of VII.
  • the title compound was prepared in analogous fashion to Example 1 replacing the 3-trifluoromethylphenylacetyl oxime with o-cresol in stage a). The title compound was obtained as a solid, m.p. 94-5 °C.
  • the title compound was prepared in known manner from o-aminobenzyl alcohol and te/ ⁇ -butyldimethylsiiyl chloride
  • the title compound was prepared in analogous fashion to Example 2 using ⁇ -(o- tolyloxy)-o-toluidine instead of ferf-butyldimethylsilyloxy)-o-toluidine.
  • the product was obtained as a 55:45 mixture of rotamers, ⁇ H N.M.R. ⁇ (ppm) 1 .26 and 1 .50 (3H, d, -CH-Me); 2.20(3H, s, Ph e); 4.10 and 4.20 (1 H, q, -CHMe); 4.90-5.10 (2H, m, -0-CH 2 Ph); and 6.80-7.65 (8H, m, Ar-H).
  • the title compound was prepared in analogous fashion to Example 2 using ethyl isocyanatoethanoate instead of ethyl 2-isocyanatopropionate and the product from Example 1 , stage c), instead of ⁇ -(ferf-butyldimethylsilyloxy)-o-toluidine.
  • the product was obtained as a mixture of rotamers, 1 H N.M.R.
  • the title compound was prepared in similar fashion to Example 1 using ethyl 2- mercaptopropionate instead of N-methylhydroxylamine hydrochloride.
  • Example 3 The title compound was prepared in similar fashion to Example 1 using ethyl mercaptoethanoate instead of ethyl 2-mercaptopropionate.
  • Example 3 Example 3
  • Erysiphe graminis f. sp. hordei barley powdery mildew Erysiphe graminis f. sp. tritici: wheat powdery mildew Pyricularia oryzae: rice blast PelHcularia sasakii: rice sheath blight Botrytis cinerea: grey mould
  • Venturia inaequalis apple scab Leptosphaeria nodorum: glume blotch
  • Aqueous solutions or dispersions of the compounds at the desired concentration, including a wetting agent, were applied by spray or by drenching the stem base of the test plants, as appropriate. Plants or plant parts were then inoculated with appropriate test pathogens and kept under controlled environment conditions suitable for maintaining plant growth and development of the disease. After an appropriate time, the degree of infection of the affected part of the plant was visually estimated. Compounds were considered active if they gave greater than 50% control of the disease at a concentration of 500 ppm (w/v) or less.
  • Compounds 1 and 6 showed activity against Plasmopara viticola; Compounds 4 and 7 showed activity against Pyricularia oryzae; Compound 1 showed activity against PelHcularia sasakii; Compounds 4 and 3 showed activity against Botrytis cinerea; Compound 4 showed activity against Venturia inaequalis; Compounds 1 and 5 showed activity against Erysiphe graminis f. sp. tritici

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  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Compounds of general formula (I) wherein A is O, S or NR1; B is CR?2R3, CR2, NR2¿, or N; D is CR?4R5, CR4, NR4¿, N, O or S; E is O, S or NR6; provided that when B is NR2, then D is CR45, O or S; and when B is N, then D is CR4; where the dotted line signifies that a single or a double bond can be present as appropriate; K is -O-, -S(O)¿n?-, -CHR?13-, -CHR13CHR14-, -CR13=CR14¿-, -C=C-, -CHR13O-, -OCHR?13-, -CHR13S(O)¿n-, -S(O)nCHR13-, -CH(R13)O-N=C(R15)-, -C(R15)=N-OCH(R13)-, -C(R15)=N-O-, -O-N=C(R15)-, -CHR15OC(=O)N(R20), -CH(R?13)N(R21)N=C(R15¿)- or a direct bond; where the moiety depicted on the rigt side of the linkage is attached to L; L is optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted cycloalkyl; optionally substituted cycloalkenyl; optionally substituted heterocyclyl; optionally substituted phenyl; or Si(R22)3; or R9, K, and L together with the phenyl ring M, can form an optionally substituted fused ring system. These compounds have pesticidal, especially fungicidal, insecticidal and acaricidal activity.

Description

FUNGTCIDAL N-ARYL FIVE-MEMBERED CYCLIC IMIDES
This invention relates to compounds having pesticidal, especially fungicidal, insecticidal and acaricidal, activity.
The invention provides compounds of general formula I
Figure imgf000003_0001
wherein A is O, S or NR^ ; where R^ is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
B is CR2R3, CR2, NR2 or N; where R2 and R3, which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
D is CR R5, CR4, NR4, N, 0 or S; where R4 and R5, which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
E is O, S or NR6; where ^ is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl; provided that when B is NR2, then D is CR4R5, O or S; and when B is N, then
Figure imgf000003_0002
where the dotted line signifies that a single or a double bond can be present as appropriate;
R9 to R** 2, which may be the same or different, are hydrogen, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkoxy, or any two of R-**1 to
R^ together with the phenyl ring form an optionally substituted fused ring system;
K is -0-, -S(0)n-, -CHR1 3-, -CHR1 3CHR14-, -CR1 =CR1 4-, -C=C-, -CHR1 0-, -OCHR1 3-, -CHR1 3S(0)n-, -S(0)nCHRl -, -CH(R1 )0-N = C(R15)-,
-C(R1 5) = N-OCH{R1 3)-, -C(R1 5) = N-0-, -O-N = C(R1 5)-, -CHR1 5OC( = 0)N(R20), -CH(R1 3)N{R 1 )N = C(R1 5)- or a direct bond; where the moiety depicted on the right side of the linkage is attached to L; R^ 3 and R^ 4, which may be the same or different, and are hydrogen or optionally substituted alkyl; R1 5 is hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted acyl or cyano, or R^ and the carbon to which it is attached form a ring, which ring is optionally substituted; R2^ is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted cycloalkyl; R21 is acyl; and n is 0, 1 , or 2; L is optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted cycloalkyl; optionally substituted cycloalkenyl; optionally substituted heterocyclyl; optionally substituted phenyl; or Si(R22>3, where R22 is optionally substituted alkyl; or R9, K, and L together with the phenyl ring M, can form an optionally substituted fused ring system.
The term heterocyclyl includes both aromatic and non-aromatic heterocyclyl groups. Heterocyclyl groups are generally 5, 6 or 7-membered rings containing up to 4 hetero atoms selected from nitrogen, oxygen and sulfur. Examples of heterocyclyl groups are furyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, dioxolanyl, oxazolyl, thiazolyl, imidazolyl, imidazolinyl, imidazoiidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyranyl, pyridyl, piperidinyl, dioxanyl, morpholino, dithianyl, thiomorpholino, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, triazinyl, thiazolinyl, benzimidazolyl, tetrazolyl, benzoxazolyl, imidazopyridinyl, 1 ,3-benzoxazinyl, 1 ,3-benzothiazinyl, oxazolopyridinyl, benzofuranyl, quinoliπyl, quinazolinyl, quinoxalinyl, sulfolanyl, dihydroquinazolinyl, benzothiazolyl, phthalimido, benzofuranyl, azepinyl, oxazepinyl, thiazepinyl, diazepinyl and benzodiazepinyl.
Alkyl groups are preferably of 1 to 6 carbon atoms. Alkenyl and alkynyl groups are generally of 3 to 6 carbon atoms. Cycloalkyl or cycloalkenyl groups are preferably of 3 to 8 carbon atoms.
Substituents, when present on any alkyl, cycloalkyl, cycloalkenyl, alkenyl or alkynyl moiety include, halogen, cyano, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted haloalkyl, hydroxy, nitro, optionally substituted amino, acyl, acyloxy, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted phenoxy and optionally substituted heterocyclyloxy. Preferred substituents are halogen.
Cycloalkyl or cycloalkenyl groups may also be substituted by alkyl.
Amino groups may be substituted for example by one or two optionally substituted alkyl or acyl groups, or two substituents can form a ring, preferably a 5 to 7- membered ring, which may be substituted and may contain other hetero atoms, for example morpholine, thiomorpholine, or piperidine.
The term acyl includes the residue of sulfur and phosphorus-containing acids as well as carboxylic acids. Examples of acyl groups are thus -C( = 0)R^, -C( = 0)OR1 6, -C( = X)NR1 6R1 7, -C( = 0)N(R1 6)OR1 7, -C( = 0)ONR1 6R1 7, -C( =0)N(R1 6)NR 7R1 8, -C( = 0)SR1 6, -C( =S)SR1 6, -S{0)pR1 6, -S(0)2OR1 6, -S(0)pNR1 6R1 7, -P( = X)(OR 6)(OR1 7), -C( = 0)-C( = 0)OR1 6, where R1 6, R 1 7 and R^ which may be the same or different, are hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted phenyl or optionally substituted heterocyclyl or R1 7 and R1 *** together with the atom(s) to which they are attached can form a ring; p is 1 or 2; and X is O or S.
Any fused ring system, when present, may be carbocyclic or heterocyclic, containing up to 3 heteroatoms; and include aromatic or non-aromatic 5, 6, or 7 membered rings. Preferred fused ring systems include naphthalene and quinoline.
Substituents when present on any heterocyclyl group may for example be halogen, CN, NO2, acyl, O-acyl or a group T, OT or S(0)nT, where n is 0, 1 or 2 and T is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted acyl, optionally substituted phenyl, optionally substituted heterocyclyl or optionally substituted amino or two adjacent groups on the ring together with the atoms to which they are attached form a carbocyclic or heterocyclic ring, which may be similarly substituted.
Substituents when present on any phenyl group are preferably as defined above for the substituents on the heterocyclyl group.
We have found that particularly efficacious group of compounds are those of general formula I where A and E are 0. Preferably B is CR2R3 or NR2; and/or D is CR4R5, NR4, 0, or S.
R2 is preferably hydrogen or optionally substituted alkyl; and/or R3 is preferably hydrogen; and/or R4 is preferably hydrogen or optionally substituted alkyl; and/or R*-> is preferably hydrogen.
Preferably K is -CHR1 30- or -CH(R1 3)0-N = C(R1 5)-.
R "* -3 is preferably hydrogen or optionally substituted alkyl. R"* *** is preferably optionally substituted alkyl.
L is preferably an optionally substituted phenyl group or the group Si(R22>3. When L is a substituted phenyl, it is preferably substituted by one or more of the following groups C -I -CQ alkyl, C -\ -CQ haloalkyl, C -\ -CQ alkoxy, C -J -CQ alkylthio, C CQ haloalkoxy, halophenoxy, halogen, C3-C8 cycloalkyl, piperidino or pyrimidinyl.
Preferably R^ to R^ 2 are each hydrogen or halogen.
In cases where the compounds of the invention exist as the E and Z isomers, the invention includes individual isomers as well as mixtures thereof.
The compounds of the invention have activity as fungicides, especially against fungal diseases of plants, e.g. mildews and particularly barley powdery mildew (Erysiphe graminis) and vine downy mildew (Plasmopara viticola), rice blast (Pyricularia oryzae), cereal eyespot (Pseudocercosporei/a herpotrichoides) , rice sheath blight (PelHcularia sasakii), grey mould (Botrytis cinerea), damping off
(Rhizoctonia solani), wheat brown rust (Pυccinia recondita), late tomato or potato blight (Phytophthora infestans), apple scab ( Venturia inaequalis), glume blotch (Leptosphaeria nodorum). Other fungi against which the compounds may be active include other powdery mildews, other rusts, and general pathogens of Deuteromycete, Ascomycete, Phycomycete and Basidomycete origin.
The invention thus also provides a method of combating pests (i.e. fungi, insects, nematodes, acarids and weeds) at a locus infested or liable to be infested therewith, which comprises applying to the locus a compound of formula I.
The invention also provides an agricultural composition comprising a compound of formula I in admixture with an agriculturally acceptable diluent or carrier.
The composition of the invention may of course include more than one compound of the invention.
In addition the composition can comprise one or more additional active ingredients, for example compounds known to possess plant-growth regulant, herbicidal, fungicidal, insecticidal or acaricidal properties. Alternatively the compound of the invention can be used in sequence with the other active ingredient.
The diluent or carrier in the composition of the invention can be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent. Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or salts of such esters; fatty alcohol sulfates such as sodium dodecyl sulfate, sodium octadecyl sulfate or sodium cetyl sulfate; ethoxylated fatty alcohol sulfates; ethoxylated alkylphenol sulfates; lignin suifonates; petroleum suifonates; alkyl-aryl suifonates such as alkyl-benzene suifonates or lower alkylnaphthalene suifonates, e.g. butyl-naphthalene sulfonate; salts of sulfonated naphthalene-formaldehyde condensates; salts of sulfonated phenol-formaldehyde condensates; or more complex suifonates such as the amide suifonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate. Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alkyl- or alkenyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide, e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, or ethoxylated acetylenic glycols.
Examples of a cationic surface-active agent include, for instance, an aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such as an amine oxide or polyoxyethylene alkylamine; an amide-linked amine prepared by the condensation of a carboxyiic acid with a di- or polyamine; or a quaternary ammonium salt.
The compositions of the invention can take any form known in the art for the formulation of agrochemicals, for example, a solution, a dispersion, an aqueous emulsion, a dusting powder, a seed dressing, a fumigant, a smoke, a dispersible powder, an emulsifiable concentrate or granules. Moreover it can be in a suitable form for direct application or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.
An emulsifiable concentrate comprises a compound of the invention dissolved in a water-immiscible solvent which is formed into an emulsion with water in the presence of an emulsifying agent.
A dusting powder comprises a compound of the invention intimately mixed and ground with a solid pulverulent diluent, for example, kaolin.
A granular solid comprises a compound of the invention associated with similar diluents to those which may be employed in dusting powders, but the mixture is granulated by known methods. Alternatively it comprises the active ingredient absorbed or adsorbed on a pre-granular diluent, for example, Fuller's earth, attapulgite or limestone grit.
Wettable powders, granules or grains usually comprise the active ingredient in admixture with a suitable surfactant and an inert powder diluent such as china clay.
Another suitable concentrate is a fiowable suspension concentrate which is formed by grinding the compound with water or other liquid, a wetting agent and a suspending agent.
The concentration of the active ingredient in the composition of the present invention, as applied to plants is preferably within the range of 0.0001 to 1.0 per cent by weight, especially 0.0001 to 0.01 per cent by weight. In a primary composition, the amount of active ingredient can vary widely and can be, for example, from 5 to 95 per cent by weight of the composition.
In the method of the invention the compound is generally applied to seeds, plants or their habitat. Thus, the compound can be applied directly to the soil before, at or after drilling so that the presence of active compound in the soil can control the growth of fungi which may attack seeds. When the soil is treated directly the active compound can be applied in any manner which allows it to be intimately mixed with the soil such as by spraying, by broadcasting a solid form of granules, or by applying the active ingredient at the same time as drilling by inserting it in the same drill as the seeds. A suitable application rate is within the range of from 5 to 1000 g per hectare, more preferably from 10 to 500 g per hectare.
Alternatively the active compound can be applied directly to the plant by, for example, spraying or dusting either at the time when the fungus has begun to appear on the plant or before the appearance of fungus as a protective measure. In both such cases the preferred mode of application is by foliar spraying. It is generally important to obtain good control of fungi in the early stages of plant growth as this is the time when the plant can be most severely damaged. The spray or dust can conveniently contain a pre- or post-emergence herbicide if this is thought necessary. Sometimes, it is practicable to treat the roots of a plant before or during planting, for example, by dipping the roots in a suitable liquid or solid composition. When the active compound is applied directly to the plant a suitable rate of application is from 0.025 to 5 kg per hectare, preferably from 0.05 to 1 kg per hectare.
Compounds of the invention may be prepared, in known manner, in a variety of ways.
Compounds of general formula la; i.e. compounds of general formula I where A is
0; B is NR2; D is CR R5, and E is NR6, where R6 is hydrogen; can be prepared according to the following reaction scheme, by reacting compounds of formula II with compounds of general formula III.
Figure imgf000010_0001
Compounds of formula lb; i.e. compounds of general formula I where A is 0; B is
NR2; D is CR4R5; and E is O; may be prepared according to the following reaction scheme by treating aforementioned compounds la with hydrochloric acid.
Figure imgf000011_0001
Compounds of general formula 1 d, i.e. compounds of general formula I where A is
0; B in CR2R3; D is NR4 and E is 0; may be prepared in two steps by reacting amines VI with isocyanate VII, where Q is a leaving group, followed by cyclisation.
Figure imgf000011_0002
(VI) (Id)
Compounds of general formula le; i.e. compounds of general formula I where A is O; B is NR2; D is O, and E is O; can be prepared according to the following reaction scheme, by reacting compounds of formula II with compounds of general formula VII, followed by cyclisation of the resulting intermediate.
Figure imgf000012_0001
(ID (If)
Compounds of general formula If, i.e. compounds of general formula I where A is O; B in CR2R3; D is CR4R**** and E is 0; may be prepared in two steps by reacting amines VI with a succinic anhydride (X) , followed by cyclisation.
Figure imgf000012_0003
Figure imgf000012_0002
Similarly compounds of formula Ii, where R3 and R*-*1 form a bond, can be formed using the appropriate maieic anhydride.
Construction of the group -K-L can be performed using a number of strategies either before or after construction of the 5-membered heterocyclyl group.
Compounds of formula Ij, i.e. compounds of general formula I where K is -CH(R1 3)0N = C(R1 5)-, can be prepared from the benzylic compound VII, where X is a leaving group preferably halogen, and oxime VIII. Preferred reaction conditions comprise treating the oxime VIII will potassium ferf-butoxide followed by addition of VII. In similar fashion, compounds of formula Ik, i.e. compounds of general formula I where K is -CH(R^ 3)-, can be prepared by reacting hydroxy compound IX, which is preferably a phenolic compound, with potassium re -butoxide followed by addition of VII.
Figure imgf000013_0001
Various R groups can be modified in known manner to give compounds with other desirable groups. Examples of such modifications are given in the preparative examples below.
Other methods will be apparent to the chemist skilled in the art as will be the methods for preparing starting materials and intermediates.
The following Examples also make apparent various methods of preparing compounds of the invention as well as starting materials and intermediates of the invention. Structures of isolated novel compounds were confirmed by elemental and/or other appropriate analyses. Where "■ H N.M.R. spectra were used to confirm chemical structure, these were performed in CDCI3. Example 1
2-Methvl-4-{α-M -(3-trifluoromethvlDhenvl)Bthylidenflaminooxyl-o-tolyl}-1 .?.4- oxadiazolidine-3.5-dione (Compound 1 )
Figure imgf000014_0001
To an ice-cooled solution of the product from stage d) (2.0 g) in 2N sodium hydroxide (2.6 ml) and dioxane (6.5 ml) was added ethyl chloroformate (0.55 ml).
After addition, the solution was allowed to warm to room temperature, whereupon the solution was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried and evaporated to give an oil which was purified by chromatography (ethyl acetate : light petroleum b.p. 40-60°C) to give a colourless oil, 1 H N.M.R. δ(ppm) 2.20 (3H, s, N = C(Me)Ph); 3.40 (3H, s, NMe); 5.20-5.40 (2H, m, PhCH2); 7.30-7.90 (8H, m, Ar-H).
Preparation of Starting Materials a) α-ri -f3-TrifluoromethvlDhenvl)ethvlideneaminooxvl-o-nitrotoluene
A solution containing 3'-trifluoromethylphenylacetophenone oxime (2.0 g), potassium carbonate (0.68 g) and 2-nitrobenzyl bromide (2.15 g) in ethylmethylketone (10 ml) was heated under reflux for 16 hours. The solution was then cooled, filtered, and the filtrate was evaporated to dryness. The resulting solid was dissolved in dichloromethane and the solution washed with water and then brine. The solution was dried (MgSO_*ι) and evaporated to give the title compound as an oil.
b) -f 1-(3-TrifluoromethvlDhenvl)ethvlideneaminonχv1-r,-toltιidine
To a solution of the product from stage a) (20 g) and palladium on charcoal (1 g, 10%) was added hy*~'- -.zine hydrate (8.5 ml) over a 20 minute period whilst maintaining the re i temperature at 20-25 °C. The resulting suspension was stirred fo. -> further 30 minutes at room temperature. The solution was then filtered through silica, washing through with dichloromethane, and the filtrate and washings were evaporated to dryness. The resulting solid was dissolved in diethyl ether, dried (Na2S0 > and evaporated to give a solid which was used in stage c) without further purification.
c) nt-ri -(3-Trifluoromethylnhenvnethvlideneaminooxvl-o-tolyl isor.vRnatp
To a solution of the product from stage c) (16.23 g) in dry dichloromethane ( 1 50 ml) at room temperature was added triphosgene (5.1 6 g) over a 5 minute period. The solution was stirred for a further 4 hours at room temperature and evaporated to dryness. Trituration with diethyl ether and filtration removed the solid, which was washed with diethyl ether. The combined filtrates were then evaporated to give the title compound, - N.M.R. δ(ppm) 2.25 (3H, s), 5.30 (2H, s), 7.10-7.35 (3H, m), 7.40-7.55 (2H, dd), 7.60 (1 H, d), 7.80 (1 H, d) and 7.90 (1 H, s).
d) 1 -Hvdroxy-1 -mRthyl-3-{nt-n -(3-trifluoromethvlphenvl)ethvlideneaminooxy1--.- tolyl}urea
To a stirred suspension of N-methylhydroxylamine hydrochloride ( 1 .43 g) in diethyl ether (50 ml) at room temperature was added triethylamine (3.35 ml) and stirring was continued overnight. The suspension was filtered and the residue was washed with diethyl ether (50 ml). The product from stage c) (4 g) in diethyl ether (5 ml) was then added to the filtrate and the solution was stirred at room temperature for 7.5 hours. The solution was evaporated to dryness and the residue was purified by flash chromatography (ethyl acetate : light petroleum b.p. 40-60 °C) to yield a colourless viscous oil which solidified on standing to give the title compound as a white solid, m.p. 1 13-1 1 5 °C. ?.Methvl-4-{α-.o-tolvloxv)-o-tolvl}-1 .2.4-oxadiazolidine-3.5-dione (Compound 2.
Figure imgf000016_0001
The title compound was prepared in analogous fashion to Example 1 replacing the 3-trifluoromethylphenylacetyl oxime with o-cresol in stage a). The title compound was obtained as a solid, m.p. 94-5 °C.
Example 2
3-rr-t-(f-.rf-Butvldimethvlsilvloxv)--.-tolvll-5-methvlimidazolidine-2.4-dione (Compound 3)
Figure imgf000016_0002
A solution of ethyl 2-{3-[α-(te/?-butyldimethylsilyloxy)-o-tolyl]ureido}propionate ( 1 7.62 g) in dry methanol (500 ml) was heated under reflux for 3 hours. The reaction mixture was then concentrated to dryness to give the title product as an oil, Η N.M.R. δ(ppm) 0.05 (6H, s, Si(Me)2); 0.91 (9H, s, SiC(Mβ)3); 1 .54 (3H, d,
CHMe); 4.22 (1 H, m, CHMe); 4,60-4.69 (2H, m, PhCH20-); 6.68 (1 H, br.d, NH);
7.20 (1 H, t, Ar); 7.37-7.48 (2H, m, Ar); and 7.63 (1 H, t, Ar).
Preparation of starting materials a) Ethvl 2-{3-I«-(fer butvldimethvl-silyloxy)-o-tolyl1ureido}propionate α-(fevτ-Butyldimethylsilyloxy)-σ-toluidine (8.84 g) was added to a stirred solution of ethyl 2-isocyanatopropionate ( 1 3.33 g) in dry diethyl ether (300 ml) and the solution stirred for 2 hours. The reaction mixture was concentrated to dryness to give a crude oil which was purified by flash chromatography on silica gel (ethyl acetate: light petroleum b.p. 40-60 °C) to give the title compound as an oil, 1 H N.M.R. δ(ppm) 0.10 (s, 6H); 0.94 (s, 9H) 1 .30 (t, 3H); 1 .47 (d, 3H); 4.26 (q, 2H); 4.58 (dq, 1 H); 4.72 (s, 2H); 5.14 (br.d, 1 H); 7.02 (dd, 1 H), 7.1 6 (d, 1 H) 7.30 (dd, 1 H); 7.66 (br.s 1 H); and 7.87 (d, 1 H).
b) α-(fe -ButyldimethvlsiMoxv)-o-to!uidine
The title compound was prepared in known manner from o-aminobenzyl alcohol and te/τ-butyldimethylsiiyl chloride
5-Methyl-3-rfi-(o-tolvloxv)-o-tolvll-imidazolidine-2.4-dione (Compound 4)
Figure imgf000017_0001
Me
The title compound was prepared in analogous fashion to Example 2 using α-(o- tolyloxy)-o-toluidine instead of ferf-butyldimethylsilyloxy)-o-toluidine. The product was obtained as a 55:45 mixture of rotamers, ^ H N.M.R. δ(ppm) 1 .26 and 1 .50 (3H, d, -CH-Me); 2.20(3H, s, Ph e); 4.10 and 4.20 (1 H, q, -CHMe); 4.90-5.10 (2H, m, -0-CH2Ph); and 6.80-7.65 (8H, m, Ar-H).
3-fα-(o-Tolyloxy)-o-tolynimidazolidine-2.4-dione (Compound 5)
Figure imgf000017_0002
The title compound was prepared in similar fashion to Example 2 using ethyl isocyanatoethanoate instead of ethyl 2-isocyanatopropionate, and α-(o-tolyloxy)-o- toluidine instead of α-(fe ?-butyldimethylsilyloxy)-σ-toluidine. The product was obtained as a solid, m.p. 130-1 °C. 3-{α-n -(3-TrifluoromethvlDhenvl)ethvlideneaminooxvl-o-tolvl.imida7nline-2.4-dinnR (Compound 6)
Figure imgf000018_0001
The title compound was prepared in analogous fashion to Example 2 using ethyl isocyanatoethanoate instead of ethyl 2-isocyanatopropionate and the product from Example 1 , stage c), instead of α-(ferf-butyldimethylsilyloxy)-o-toluidine. The product was obtained as a mixture of rotamers, 1 H N.M.R. δ(ppm) 2.20 (3H, s, N = C(Me)Ph); 1 .26 and 1 .50 (3H, d, -CH-Mβ); 2.20(3H, s, PhMe); 4.10 and 4.20 (1 H, q, -CHMe); 4.90-5.10 (2H, m, -0-CH2Ph); and 6.80-7.65 (8H, m, Ar-H).
5-Methyl-3-fα-(o-tolyloxv)-o-tolvnthiazolidin-2.4-dione (Compound 7)
Figure imgf000018_0002
The title compound was prepared in similar fashion to Example 1 using o- methylphenol instead of 3'-trifluoromethylacetophenone oxime, and ethyl 2- mercaptopropionate instead of N-methylhydroxylamine hydrochloride. The title product was obtained as a solid, m.p. 124-5 °C. 5-Methvl-3-{α-π -(3-trifluoromethvlphenvl)ethvlideneaminooxvl-o-tolyl)thia7θliriin- 2.4-dione (Compound 8)
Figure imgf000019_0001
The title compound was prepared in similar fashion to Example 1 using ethyl 2- mercaptopropionate instead of N-methylhydroxylamine hydrochloride. The title product was obtained as a mixture of rotamers, "Η Ν.M.R. δ(ppm) 1 .70 (3H, d, CHMe); 2.1 5 (3H, s, Ν = C(Me)Ph); 4.2-4.3 (1 H, m, -CH-Me); 5.00-5.1 5 (2H, m, -0-CH2Ph); and 7.05-7.80 (8H, m, Ar-H).
3-{rt-f 1 -(3-Trifluoromethvlphenvl)ethvlideneaminooxvl-o-tolvl}thiazolidin-2.4-dione (Compound 9)
Figure imgf000019_0002
The title compound was prepared in similar fashion to Example 1 using ethyl mercaptoethanoate instead of ethyl 2-mercaptopropionate. The title product was obtained as a mixture of rotamers, - H N.M.R. δ(ppm) 2.20 (3H, s, N = C(Me)Ph); 3.90-4.10 (2H, q, -SCH2CON); 5.05-5.1 5 (2H, m, -0-CH2Ph); and 7.1 5-7.90 (8H, m, Ar-H). Example 3
3-Methvl-1 -(«-(o-tolvloxvl-c-)-tolvnDvrrolidine-2.5-dione (Compound 101
Figure imgf000020_0001
A solution containing the product of stage a) (1 .5 g) and CDI (0.77 g) in tetrahydrofuran (70 ml) was stirred at room temperature for 20 hours. The reaction mixture was concentrated to dryness and then purified by flash chromatography to give the title compound as a solid, m.p. 106-107 °C.
Preparation of starting material a) 2-Methyl-Λ/-fα-(o-tolyloxv)-o-tolvllsuccinamic acid and 3-mfithyl-Λ/-Ic*t-(n- tolyloxy)-o-tolyl1succinamic acid
A solution of the product from stage b) (3 g) and 2-methylsuccinic anhydride ( 1 .605 g) in dry toluene ( 1 50 ml) was heated under reflux for 5 hours. The reaction mixture was cooled to room temperature and concentrated to a crude oil, which was crystallised from ethyl acetate ( 10 ml) to give a mixture of the title compounds. This mixture was separated by HPLC, to give the first title compound, m.p. 1 39-41 °C and the second title compound, m.p. 142-4 °C.
b) α-.o-Tolyloxyl-o-tnluiriine
The title product was prepared in similar fashion to stages a) and b) of Example 1 , using o-cresol instead of 3'-trifluoromethylacetophenone oxime. Test Example
Compounds are assessed for activity against one or more of the following: Phytophthora infestans: late tomato blight Plasmopara viticola: vine downy mildew
Erysiphe graminis f. sp. hordei: barley powdery mildew Erysiphe graminis f. sp. tritici: wheat powdery mildew Pyricularia oryzae: rice blast PelHcularia sasakii: rice sheath blight Botrytis cinerea: grey mould
Venturia inaequalis: apple scab Leptosphaeria nodorum: glume blotch Aqueous solutions or dispersions of the compounds at the desired concentration, including a wetting agent, were applied by spray or by drenching the stem base of the test plants, as appropriate. Plants or plant parts were then inoculated with appropriate test pathogens and kept under controlled environment conditions suitable for maintaining plant growth and development of the disease. After an appropriate time, the degree of infection of the affected part of the plant was visually estimated. Compounds were considered active if they gave greater than 50% control of the disease at a concentration of 500 ppm (w/v) or less.
Compounds 1 and 6 showed activity against Plasmopara viticola; Compounds 4 and 7 showed activity against Pyricularia oryzae; Compound 1 showed activity against PelHcularia sasakii; Compounds 4 and 3 showed activity against Botrytis cinerea; Compound 4 showed activity against Venturia inaequalis; Compounds 1 and 5 showed activity against Erysiphe graminis f. sp. tritici

Claims

Compounds of general formula
Figure imgf000022_0001
wherein
A is 0, S or NR1 ; where R1 is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
B is CR R3, CR2, NR2 or N; where R2 and R3, which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
D is CR4R5, CR4, NR4, N, O or S; where R4 and R5, which may be the same or different, are hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl;
E is 0, S or ^; where R-**-* is hydrogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted acyl; provided that when B is NR2, then D is CR R5, O or S; and when B is N, then D is CR4; where the dotted line signifies that a single or a double bond can be present as appropriate;
R9 to R"* 2, which may be the same or different, are hydrogen, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkoxy, or any two of R9 to R1 2 together with the phenyl ring form an optionally substituted fused ring system;
K is -0-, -S(0)n-, -CHR 1 3-, -CHR1 3CHR1 4-, -CR1 3 = CR1 4-, -CsC-,
-CHR1 30-, -OCHR1 3-, -CHR 1 3S(0)n-, -S(0)nCHR1 3-, -CH(R 1 3)0-N = C(R1 5)-, -C(R 1 5) = N-OCH(R1 3)-, -C(R1 5) = N-0-,
-0-N = C(R1 5)-, -CHR1 50C( = 0)N(R20), -CH(R1 3)N(R21 )N = C(R1 5)- or a direct bond; where the moiety depicted on the right side of the linkage is attached to L; R1 3 and R1 4, which may be the same or different, and are hydrogen or optionally substituted alkyl; Rl 5 is hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted acyl or cyano, or R 1 5 and the carbon to which it is attached form a ring, which ring is optionally substituted; R2^ is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted cycloalkyl; R2^ is acyl; and n is 0, 1 , or 2; L is optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted cycloalkyl; optionally substituted cycloalkenyl; optionally substituted heterocyclyl; optionally substituted phenyl; or Si(R22)3, where R22 is optionally substituted alkyl; or R9, K, and L together with the phenyl ring M, can form an optionally substituted fused ring system.
Compounds according to claim 1 wherein A and E are O.
Compounds accoring to claim 1 or 2 wherein B is CR2R3 or NR2.
Compounds according to any preceding claim wherein D is CR4R5, NR4, O, or S. 5 Compounds according to any preceding claim wherein R2 is hydrogen or optionally substituted alkyl.
6 Compounds according to any preceding claim wherein R3 is hydrogen.
7 Compounds according to any preceding claim wherein R4 is hydrogen or optionally substituted alkyl.
8 Compounds according to any preceding claim wherein R-***- is hydrogen.
9 Compounds according to any preceding claim wherein K is -CHR^ 30- or
-CH(R1 3)0-N = C(R1 5)-.
10 Compounds according to any preceding claim wherein, when present, ^ 3 is hydrogen or optionally substituted alkyl.
1 1 Compounds according to any preceding claim wherein, where present, R^-** is optionally substituted alkyl.
12 Compounds according to any preceding claim wherein L is an optionally substituted phenyl group.
13 Compounds according to any preceding claim wherein L is a substituted phenyl group.
14 Compounds according to any preceding claim wherein L is a phenyl group substituted by one or more of the following groups: C-* -CQ alkyl, C-j -Cs haloalkyl, C-i -Cβ alkoxy, C1 -C5 alkylthio, C-j -Cβ haloalkoxy, halophenoxy, halogen, C3-C8 cycloalkyl, piperidino or pyrimidinyl.
1 5 Compounds according to any preceding claim wherein R9 to R^ are each hydrogen or halogen. 16 Compounds according to any one of claims 1 to 12 wherein L is Si(R )3.
17 Compounds according to claim 18 wherein R22 is alkyl.
18 A pesticidal composition comprising compounds as claimed in any preceding claim in admixture with an agriculturally acceptable diluent or carrier.
PCT/GB1997/002012 1996-07-27 1997-07-28 Fungicidal n-aryl five-membered cyclic imides WO1998004525A1 (en)

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