WO1998046583A1 - Derives de melithiazole fongicides - Google Patents

Derives de melithiazole fongicides Download PDF

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Publication number
WO1998046583A1
WO1998046583A1 PCT/US1998/006935 US9806935W WO9846583A1 WO 1998046583 A1 WO1998046583 A1 WO 1998046583A1 US 9806935 W US9806935 W US 9806935W WO 9846583 A1 WO9846583 A1 WO 9846583A1
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Prior art keywords
formula
group
compound
alkyl
hydrogen atom
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PCT/US1998/006935
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English (en)
Inventor
Gerhard Hoefle
Udo Soeker
Annerose Rehnig
Ewald Gerhard Sieverding
Original Assignee
Gesellschaft Für Biotechnologische Forschung, Mbh
American Cyanamid Company
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Priority claimed from DE19715290A external-priority patent/DE19715290A1/de
Application filed by Gesellschaft Für Biotechnologische Forschung, Mbh, American Cyanamid Company filed Critical Gesellschaft Für Biotechnologische Forschung, Mbh
Priority to US09/402,855 priority Critical patent/US6197802B1/en
Priority to AU68902/98A priority patent/AU6890298A/en
Priority to JP54400498A priority patent/JP2002510284A/ja
Priority to EP98914584A priority patent/EP0975613A1/fr
Publication of WO1998046583A1 publication Critical patent/WO1998046583A1/fr

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    • 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
    • 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
    • C07D277/22—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • 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
    • C07D277/22—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms

Definitions

  • This invention relates to novel meiithiazole derivatives, a process for their preparation, compositions containing such compounds, a method for combating a fungus at a locus comprising treating the locus with such compounds and their use as fungicides.
  • Fungicides are one of these agricultural technologies which are available to the world community. Fungicides are agrochemical compounds which protect crops and foods from fungus and fungal diseases. Crops and food are constantly threatened by a variety of fungal organisms, which, if left uncontrolled, can cause ruined crops and damaged harvests.
  • meiithiazole C by reductive cleavage of myxothiazol A with subsequent transformation of the resulting meiithiazole C amide into the corresponding methyl ester has been described by a poster of B. Bbhlendorf et al. presented at the Dechema Naturstofftagung in Irsee, Germany in 1996. Meiithiazole C disclosed on this poster shows weak in vitro activity against Bortrytis cinera.
  • the underlying problem of the present invention was to find novel meiithiazole derivatives having high in vivo activity against a broad range of phytopathogenic fungi.
  • the present invention provides novel meiithiazole derivatives of the general formula I
  • R 1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkyloxiranyl, alkanoyl, alkoxycarbonyl, formyl, hydroxyalkyl, alkoxyalkyl, alkanoyloxyalkyl, hydroximinoalkyl, alkoxyiminoalkyl, hydrazonoalkyl or alkylhydrazonoalkyl group;
  • R 2 represents an alkoxy group;
  • R 3 and R" each independently represent a hydrogen atom or an alkyl group
  • R 5 represents an alkyl group
  • R 6 represents a group of formula -COOR 7 or -CONR 7 R 8 , in which R 7 and R 8 each independently represent a hydrogen atom or an alkyl group; with the proviso that meiithiazole C or the corresponding amide of formula, OMe
  • the new compounds combine excellent fungicidal activities against a broad range of phytopathogenic fungi in various crops with comparably high systemicities.
  • R 1 through R 6 are as hereinbefore defined, and excluding meiithiazole C or the corresponding amide thereof, combine excellent fungicidal activity against diseases caused by phytopathogenic fungi even at low dose rates with high bioavailability due to their high systemicity.
  • Optionally substituted moieties may be unsubstituted or have from one up to the maximal possible number of substituents. Typically, 0 to 2 substituents are present.
  • Each optionally substituted group is independently substituted by one or more halogen atoms or nitro, cyano, cycloalkyl, preferably C 3 . 6 cycloalkyl, cycloalkenyl, preferably C 3 .
  • halogen may denote a bromine, iodine, chlorine or fluorine atom, and is preferably a bromine, chlorine or fluorine atom.
  • alkyl refers to a straight or branched chain radical or moiety.
  • such radicals have up to 10, in particular up to 6 carbon atoms.
  • an alkyl or alkoxy moiety has from 1 to 6 carbon atoms, preferably from 1 to 5 carbon atoms.
  • a preferred alkyl moiety is the methyl, ethyl, n-propyl, isopropyl or n-butyl group.
  • a preferred acyl moiety is acetyl or propionyl.
  • the invention especially relates to compounds of the general formula I in which any alkyl part of the groups R 1 through R 6 , which may be straight chained or branched, contains 1 to 10 carbon atoms, preferably 1 to 9 carbon atoms, more preferably 1 to 6 carbon atoms, and in which each optionally substituted group independently may be substituted by one or more halogen atoms or nitro, cyano, cycloalkyl, preferably C 3 . 6 cycloalkyl, cycloalkenyl, preferably C 3 . 6 cycloalkenyl, haloalkyl, preferably C ⁇ haloalkyl, halocycloalkyl, preferably C 3 .
  • halocycloalkyl alkoxy, preferably C . 6 alkoxy, haloalkoxy, preferably C,. 6 haloalkoxy, phenyl, or pyridyl groups, in which the phenyl moiety is optionally substituted by one to three substituents selected from halogen atoms, cyano, C ⁇ alkyl and C ⁇ alkoxy groups.
  • the invention especially relates to compounds of the general formula I in which R 1 represents a straight-chained or branched C ⁇ 0 alkoxyimino-C 2 . 10 alkyl, in particular a straight-chained ".-(C ⁇ alkoxyimino)- C 2 .
  • alkoxy moiety may be unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of halogen atoms, aryl, alkyl, alkoxy, haloalkyl and haloalkoxy groups, most preferably being a 1-(methoxyimino)-ethyl, 1-(methoxyimino)-n-propyl, 1- (ethoxyimino)-ethyl group or a 1-(benzyloxyimino)-ethyl group.
  • the invention especially relates to compounds of the general formula I in which R 2 represents a C... Q alkoxy group, in particular a methoxy group.
  • the meiithiazole derivatives of formula I are oils, gums, or, predominantly, crystalline solid materials and possess valuable fungicidal properties. Besides use as a fungicide for control of diseases in agronomic crops, the compound may be used as a biocide for the control of insect pests and nematodes, as a biocide of human/animal diseases/pests, and as a protectant or preservative for wood, leather or tissue.
  • the compounds of the present invention can protectively and curatively be used against a broad spectrum of diseases in plant and fruit production such as grain producing crops (wheat, barley, rice, rye, triticale, oat, maize, sorghum and others), grape vine plants and fruits, solanaceous crops (potato, tomato, tobacco, pepper and others) top fruit, stone fruits, soft fruits and fruit crops (apples, pears, citrus, mango, bananas, coffee, cocoa and others), oil producing crops (soybeans, sunflowers, groundnuts, rape, olives, palms and others), vegetables (like beans, lettuce, cucumbers, pumpkins, brassicas and others), horticultural plants, hops, sugarbeets, ornamentals, flowers, forestry trees and crops and others.
  • grain producing crops wheat, barley, rice, rye, triticale, oat, maize, sorghum and others
  • grape vine plants and fruits solanaceous crops (potato, tomato, tobacco, pepper and
  • the meiithiazole compounds of formula I possess a high fungicidal activity over a wide concentration range. Moreover, these compounds show enhanced curative and residual control of fungi and fungal diseases such as cereal, grape, apple and solanaceous crops diseases, and improved foliar systemicity compared with conventional fungicides. Good results in terms of control of diseases caused by phythopathogenic fungi are obtained with meiithiazole derivatives as defined in formula I, wherein
  • R represents an optionally substituted alkyl, alkenyl, alkyloxiranyl, hydroxyalkyl, alkoxyalkyl, alkanoyloxyalkyl, hydroximinoalkyl, alkoxyiminoalkyl, hydrazonoalkyl or alkylhydrazonoalkyl group;
  • R 2 represents a methoxy group,
  • R 3 represents a methyl group,
  • R 4 represents a hydrogen atom.
  • R 1 represents an iminoalkyl group of formula
  • X represents O or NR 11 ;
  • R 9 , R 10 and R 1 each independently represent a hydrogen atom or an alkyl, aryl or heteroaryl group, preferably wherein R 1 represents a 1-
  • R 1 represents an alkenyl group of formula wherein
  • R 9 and R 10 each independently represent a hydrogen atom or an alkyl, aryl or heteroaryl group, and R 11 is a hydrogen atom or an alkyl, aryl, acyl or heteroaryl group, in particular wherein R 9 represents a C ⁇ e alkyl group, one of R 10 and R 1 represents a hydrogen atom or a C,. 6 alkyl group and the other represents a hydrogen atom; or c) R represents a hydroxyalkyl group of formula
  • R 9 and R 10 each independently represent a hydrogen atom or an alkyl, aryl, or heteroaryl group, and R is a hydrogen atom or an alkyl, aryl, acyl or heteroaryl group, in particular wherein R 9 represents a C ⁇ e alkyl group, R 10 represents a hydrogen atom and R 11 represents a C ⁇ alkyl or C ⁇ acyl group.
  • the present invention provides a process for preparing a meiithiazole derivative of the general formula I
  • R 1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkyloxiranyl, alkanoyl, alkoxycarbonyl, formyl, hydroxyalkyl, alkoxyalkyl, alkanoyloxyalkyl, hydroximinoalkyl, alkoxyiminoalkyl, hydrazonoalkyl or alkylhydrazonoalkyl group;
  • R 2 represents an alkoxy group
  • R 3 and R 4 each independently represent a hydrogen atom or an alkyl group
  • R 5 represents an alkyl group
  • R 6 represents a group of formula -COOR 7 or -CONR 7 R 8 , in which R 7 and
  • R 8 each independently represent a hydrogen atom or an alkyl group; with the proviso that meiithiazole C or the corresponding amide thereof of formula,
  • Y represents NH 2 or OCH 3 , are excluded which comprises one of the following:
  • R 10 is a hydrogen atom or an alkyl, aryl or heteroaryl group and X is O or NR 1 1 where R 11 is a hydrogen atom or an alkyl, aryl or heteroaryl group, to give a compound of formula I wherein R 1 represents an iminoalkyl group of formula R 10 X ⁇ N
  • R 10 and R 11 are as hereinbefore defined, and R' represents an alkyl or alkoxy group, and n is 0 or 1 to give a corresponding compound of formula I wherein R 1 represents an alkenyl group of formula
  • R 9 , R 10 and R 11 are as hereinbefore defined;
  • the present invention provides a process for the preparation of a compound of formula I, wherein R 1 represents an acetyl group and R 6 represents a group of formula -COOR 7 , in which R 7 represents an alkyl group other than methyl, which comprises treating the amide of meiithiazole C with a compound of formula II,
  • the present invention further provides a process for the preparation of a compound of formula I, wherein R 1 represents an acetyl group and R 6 represents a group of formula -CONR 7 R 8 , in which R 7 represents an alkyl group and R 8 represents a hydrogen atom or an alkyl group, which comprises treating meiithiazole C with an amine of formula III,
  • R 7 R 8 NH (III) in the presence of a trialkylaluminium compound can be prepared by a process which comprises the steps of:
  • the present invention also provides a process for the preparation of a compound of formula I, wherein R 1 represents an iminoalkyl group of formula
  • R 9 , R 10 and X are as hereinbefore defined, ' which comprises reacting a compound of formula I, in which R 1 represents an acyl group of formula R 9 -CO-, with an amino derivative of formula VII,
  • the present invention further provides a process for the preparation of a compound of formula I, wherein R 1 represents an alkenyl group of formula
  • the present invention further relates to compounds of formula V
  • R 6 is as hereinbefore defined.
  • Meiithiazole C, the amide thereof and the compounds of formulae II, VII and VIII are known products, and may themselves be prepared according to established methods or routine adaptations thereof. Substituents which are not compatible with the selected reaction conditions may be introduced afterwards. They can be generated by known methods such as subsequent derivatization or substitution of a suitable group or by cleavage of a suitable protecting group.
  • the reaction between the amide of meiithiazole C and the trialkoxonium tetrafluoroborate of formula II is preferably carried out analogously to known methods, e.g. Kiesling et al., Synth. Commun. 1997, 27, 923-937. As a rule it is carried out in the presence of an inert solvent, such as an optionally halogenated hydrocarbon like tetrachloromethane or dichloromethane, or an alcohol of formula R 7 -OH or in mixtures of these solvents.
  • the molar ratio between the amide and formula II is in the range of 0.3 to 1.9.
  • the reaction is preferably carried out at a temperature between 0 and 150 °C, in particular, at ambient temperature.
  • the first step of this reaction is carried out with trimethoxonium tetrafluoroborate and the alcoholysis is carried out in the presence of an alcohol other than methanol.
  • the alkyliminoester is preferably hydrolysed in a buffer system at a pH of 3 to 6, preferably 4 to 5, in particular at about pH 4.5.
  • the compounds of formula IV are preferably hydrolysed using a carboxylic acid, in particular trifluoroacetic acid, with traces of water in an inert solvent such as optionally halogenated hydrocarbons like tetrachloromethane or dichloromethane.
  • an inert solvent such as optionally halogenated hydrocarbons like tetrachloromethane or dichloromethane.
  • the resulting 3-oxo-compounds are treated with an ortho-ester of formula VI analogously to known methods, e.g. W. J. Le Noble, Synthesis 1970, 1-6.
  • the processes described below can analogously be applied to other starting compounds, if desired. Due to excellent fungicidal activity, the compounds of formula I can be used in cultivation of all plants where infection by phytopathogenic fungi is undesirable, e.g. cereals, solanaceous crops, vegetables, legumes, apples, vine.
  • the compounds of general formula I have been found to have fungicidal activity. Accordingly, the invention further provides a fungicidal composition which comprises, as an active ingredient, at least one compound of formula I, together with one or more carriers. A method of making such a composition is also provided which comprises bringing a compound of formula I as defined above into association with the carrier(s). Such a composition may contain a single active ingredient or a mixture of several active ingredients of the present invention. It is also envisaged that different isomers or mixtures of isomers may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixtures of isomers.
  • a fungicidal composition according to the invention preferably contains from 0.5% to 95% by weight (w/w) of the active ingredients], together with a carrier therefor.
  • a carrier in the composition of the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed, soil, or water in which a plant grows, or to facilitate storage, transport or handling.
  • a carrier may be a solid or a liquid, including material which is normally a gas but which has been compressed to form a liquid.
  • compositions may be manufactured into e.g. emulsion concentrates, solutions, oil in water emulsions, wettable powders, soluble powders, suspension concentrates, dusts, granules, water dispersible granules, micro-capsules, gels, tablets and other formulation types by well- established procedures. These procedures include intensive mixing and/or milling of the active ingredients with other substances, such as fillers, solvents, solid carriers, surface active compounds (surfactants), and optionally, solid and/or liquid auxiliaries and/or adjuvants.
  • the form of application such as spraying, atomizing, dispersing or pouring may be chosen, like the compositions according, to the desired objectives and the given circumstances.
  • Suitable solvents are those such as aromatic hydrocarbons, e.g. Solvesso ® 200, substituted naphthalenes, phthalic acid esters, such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons, e.g. cyclohexane or paraffins, alcohols and glycols as well as their ethers and esters, e.g. ethanol, ethyleneglycol mono- and dimethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methyl-2-pyrrolidone, or ⁇ -butyrolactone, higher alkyl pyrrolidones, e.g.
  • aromatic hydrocarbons e.g. Solvesso ® 200
  • substituted naphthalenes such as dibutyl or dioctyl phthalate
  • aliphatic hydrocarbons e.g. cyclohexane or paraffins
  • n-octylpyrrolidone or cyclohexylpyrrolidone epoxidized plant oil esters, e.g. methylated coconut or soybean oil ester and water. Mixtures of different liquids are often suitable as solvents.
  • Solid carriers which can be used for dusts, wettable powders, water dispersible granules, or granules, can be mineral fillers, such as calcite, talc, kaolin, montmorillonite or attapulgite. The physical properties may be improved by addition of highly dispersed silica gel or polymers.
  • Carriers for granules can be porous material, e.g. pumice, kaolin, sepiolite, bentonite; non-sorptive carriers can be calcite or sand. Additionally, a multitude of pre- granulated inorganic or organic materials can be used, such as dolomite or crushed plant residues.
  • Fungicidal pesticidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application.
  • a carrier which is a surfactant facilitates this process of dilution.
  • at least one carrier in a composition according to the invention is a surfactant.
  • the composition may contain at two or more carriers, at least one of which is a surfactant.
  • Surfactants may be nonionic, anionic, cationic or zwitterionic substances with good dispersing, emulsifying and wetting properties depending on the nature of the compound according to general formula I to be formulated. Surfactants may also include mixtures of individual surfactants.
  • the fungicidal compositions of the invention may, for example, be formulated as wettable powders, water dispersible granules, dusts, granules, tablets, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols.
  • Wettable powders usually contain 5 to 90% w/w of active ingredient and usually contain in addition to solid inert carrier, 3 to10% w/w of dispersing and wetting agents and, where necessary, 0 to 10% w/w of stabilizer(s) and/or other additives such as penetrants or stickers.
  • Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and may be diluted in the field with further solid carrier to give a composition usually containing 0.5 to 10% w/w of active ingredient.
  • Water dispersible granules and granules are usually prepared to have a size between 0.15 mm and 2.0 mm and may be manufactured by a variety of techniques. Generally, these types of granules will contain 0.5 to 90% w/w active ingredient and 0 to 20% w/w of additives such as stabilizer, surfactants, slow release modifiers and binding agents.
  • the so-called "dry flowables" consist of relatively small granules having a relatively high concentration of active ingredient.
  • Emulsifiable concentrates usually contain, in addition to a solvent or a mixture of solvents, 1 to 80% w/v active ingredient, 2 to 20% w/v emulsifiers and 0 to 20% w/v of other additives such as stabilizers, penetrants and corrosion inhibitors.
  • Suspension concentrates are usually milled so as to obtain a stable, non-sedimenting flowable product and usually contain 5 to 75% w/v active ingredient, 0.5 to 15% w/v of dispersing agents, 0.1 to 10% w/v of suspending agents such as protective colloids and thixotropic agents, 0 to 10% w/v of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation and crystalization or as antifreeze agents for water.
  • Aqueous dispersions and emulsions for example compositions obtained by diluting the formulated product according to the invention with water, also lie within the scope of the invention.
  • the biological activity of the active ingredient can also be increased by including an adjuvant in the spray dilution.
  • An adjuvant is defined here as a substance which can increase the biological activity of an active ingredient but is not itself significantly biologically active
  • the adjuvant can either be included in the formulation as a coformulant or carrier, or can be added to the spray tank together with the formulation containing the active ingredient.
  • the compositions may preferably be in a coficentrated form whereas the end user generally employs diluted compositions
  • the compositions may be diluted to a concentration down to 0.001% of active ingredient
  • the doses usually are in the range from 0 01 to 10 kg a.i./ha.
  • Solvent Shellsol ® A 2 to 1000 ml (mixture of C 9 - C 10 aromatic hydrocarbons)
  • SC Suspension Concentrate
  • Carrier / Filler Kaolin 35 % (w/w) Water Dispersible Granules (WG) Active Ingredient MCM 50 % (w/w)
  • Binding agent (mixture of sodium salts of condensed naphthalene sulfonic acid and alkyl sulfonates) Wetting agent Morwet ® EFW 6) 2 % (w/w)
  • compositions of this invention can also comprise other compounds having biological activity, e.g. compounds having similar or complementary pesticidal activity or compounds having plant growth regulating, fungicidal or insecticidal activity.
  • These mixtures of pesticides can have a broader spectrum of activity than the compound of general formula I alone
  • the other pesticide can have a synergistic effect on the pesticidal activity of the compound of general formula I.
  • the other fungicidal compound can be, for example, one which is also capable of combating diseases of cereals (e.g. wheat) such as those caused by Erysipha, Puccinia, Septona, Gibberella and Helminthosporium spp., seed and soil borne diseases and downy and powdery mildews on vines, early and late blight on solanaceous crops, and powdery mildew and scab on apples etc.
  • cereals e.g. wheat
  • wheat e.g. wheat
  • fungicidal compounds utilizable in the compositions of the present invention are anilazine, azoxystrobin, benalaxyl, benomyl, bethoxazin, binapacryl, bitertanol, blasticidin S, Bordeaux mixture, bromuconazole, bupirimate, captafol, captan, carbendazim, carboxin, carpropamid, chlorbenzthiazon, chlorothalonil, chlozolinate, copper-containing compounds such as copper oxychioride, and copper sulfate, cycloheximide, cymoxanil, cypofuram, cyproconazole, cyprodinil, dichlofluanid, dichlone, dichloran, diclobutrazol, diclocymet, diclomezine, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dim
  • the co-formulations according to the invention may contain at least one compound of formula I and a chemical agent that induces the systemic acquired resistance in plants such as, for example, nicotinic acid or derivatives thereof or BION.
  • the compounds of general formula I can be mixed with soil, peat or other rooting media for the protection of the plants against seed-borne, soil-borne or foliar fungal diseases.
  • the invention still further provides the use as a fungicide of a compound of the general formula I as defined above or a composition as defined above, and a method for combating fungus at a locus, which comprises treating the locus, which may be, for example, plants subject to or subjected to fungal attack, seeds of such plants or the medium in which such plants are growing or are to be grown, with such a compound or composition.
  • the present invention is of wide applicability in the protection of crop and ornamental plants against fungal attack.
  • Typical crops which may be protected include vines, grain crops such as wheat and barley, rice, sugar beet, top fruit, peanuts, potatoes, vegetables and tomatoes.
  • the duration of the protection is normally dependent on the individual compound selected, and also a variety of external factors, such as climate, whose impact is normally mitigated by the use of a suitable formulation.
  • the compounds according to the invention have curative, protective and residual activity and are systemic in plants.
  • the compounds control diseases after foliar, soil, into water or seed application. They can be applied in different formulations.
  • the compounds have better curative and systemic properties than current commercialized strobilurine derivatives.
  • reaction mixture is concentrated and extracted with ether (3 times).
  • organic phase is separated, dried and concentrated in vacuo.
  • the residue is purified by MPL chromatography (column: Eurosil Bioselect 100-20-C-18, 15-25 ⁇ m, 32 x 3 cm, eluent: methanol/water) yielding the pure product, 209 mg (56 %).
  • aqueous phase is extracted with ether four times, the organic phases are combined and dried with sodium sulfate.
  • the solvent is removed of in vacuo and the residue is purified by HPLC (methanol/water 60/40). 23 mg (55%) of meiithiazole C, having a melting point 106°C, (re-crystallized from ethanol) are obtained.
  • a mixture of trimethylaluminium and hexane (75 ⁇ l, 150 ⁇ mol) is added to a mixture of methylamine and dichloromethane (obtained by introduction of methylamine into 1 ml of dichloromethane within 1 minute) and stirred at room temperature for 20 minutes.
  • a mixture of 15 mg (44.2 ⁇ mol) meiithiazole C as obtained in Example 2 and 300 ⁇ l of dichloromethane is added to the reaction mixture.
  • the mixture is stirred for 2 hours at room temperature and acidified with 0.1 M hydrochloric acid.
  • the phases are separated and the organic phase is washed with a saturated sodium bicarbonate solution and dried with sodium sulfate.
  • the solvent is removed of in vacuo and the residue is purified by PSC (dichloromethane/methanol 9 : 1). 11 mg (74%) of the desired product are obtained.
  • N C-CH 3 (s) 2.44 2.33
  • IR (KBr): (E/Z)-MCM: v 826 cm-1 (w), 898 (w), 927 (w), 973 (w), 992 (w), 1049 (s), 1071 (s), 1094 (s), 1126 (m), 1194 (m), 1223 (w), 1263 (m), 1305 (w), 1383 (m), 1438 (m), 1456 (w), 1487 (w), ' l625 (s), 1712 (s), 2879 (w), 2902 (w), 2938 (m), 2973 (w).
  • a ready-to-use mixture of 25 mg (60.0 ⁇ mol) methyltriphenyl- phosphonium bromide / sodium amide (commercially available from Fluka, Art. No. 69500) is diluted with 400 ml of tetrahydrofuran at room temperature with stirring.
  • a mixture of 8 mg (23.6 ⁇ mol) of meiithiazole C as obtained in Example 2 and 400 ml of tetrahydrofuran is added.
  • the resulting reaction mixture is stirred for 1.5 hours.
  • the solvent is removed of in vacuo and the residue is diluted with water and ether.
  • the aqueous phase is extracted with ether twice.
  • the combined organic phases are dried with sodium sulfate.
  • the solvent is removed of in vacuo and the residue is purified with preparative HPLC (methanol/water 65/35). 5 mg (63%) of the desired product are obtained.
  • a freshly prepared solution of diazomethane is added to a mixture of 5 mg (14.7 ⁇ mol) meiithiazole C as obtained in example 2 and ether at room temperature.
  • the mixture is stirred for 1 hour at room temperature and the solvent is removed of in vacuo.
  • the residue is diluted with ether and water and the aqueous phase is extracted with water twice.
  • the combined organic phases are dried with sodium sulfate.
  • the solvent is removed of in vacuo and the residue is purified by PSC (ether/petrol ether 50/50). 2 mg (39%) of the desired product are obtained.
  • a mixture of 100 mg (295 ⁇ mol) meiithiazole C as obtained in Example 2, 2 ml of dichloromethane and 200 ⁇ l of trifluoroacetic acid is kept at room temperature for 10 minutes.
  • a saturated sodium bicarbonate solution is added and the solvent is distilled of in vacuo.
  • the aqueous phase is extracted with water three times.
  • the combined organic phases are dried with sodium sulfate.
  • the solvent is removed of in vacuo to yield 94 mg (98%) of the desired product.
  • the MIC (Minimum inhibitory Concentration) value which indicates the lowest concentration of the active ingredient in the growth medium which causes a total inhibition of mycelial growth, is determined by serial dilution tests.
  • the compounds of the invention have been compared with known meiithiazole C, meiithiazole C-amide and with the commercially available strobilu ⁇ nes kresoxim-methyl (BASF AG) and azoxystrobin (ZEN EC A)
  • Test Plants Test plants were grown up in the greenhouse. Either seed, pregerminated seed or rooted vegetative plant material was planted in pots containing a fertilized soil/peat mixture. Test plants were used for treating them with the various fungicides when they were in the 3-4 leaf stage. The number of leaves of vegetatively propagated plant material was cut back to 3-4 leaves per plant. Application: Test plants were treated with fungicides either 1 or 3 days before (protective treatments) or 2 or 3 days after (curative treatments) the inoculation with a pathogen. The test compounds were applied to the test plants using a lateral-nozzle sprayer with a turntable rotating the pots, or the test compounds were applied with an hand-held airbrush. 2-4 plants were used per treatment.
  • Inoculations and culture conditions For the protective tests, treated plants were kept 1 or 3 days in the greenhouse and then inoculated with a pathogen. For inoculation an aqueous spore suspension was sprayed or spores were dusted onto the plants. Then the plants were kept in specific chambers for incubation if required, and then were moved to a greenhouse for disease development. For curative tests, plants were inoculated and, if required, incubated 2 or 3 days before the application of the compound, and then moved to a greenhouse after application of the compounds. The temperature in the greenhouse was between 18 and 25 degree C. The relative humidity was about 50-80% in the greenhouses and up to 100% in the incubation chambers. The plants were watered as required for good plant growth.
  • the % activity is given in the results (examples) or from the % activity at each dose rate an effective dose for 90% disease control (EP90) was calculated.
  • the results are shown in Tables VI to VIII.
  • Foliar systemicity When the primary leaves of wheat planted in 8 cm diameter pots in the greenhouse were fully expanded, the plants were cut back to four leaves in each pot of which two were marked with a permanent marker 5 cm below the leaf tip on the upper leaf surface. Thus there were two band-treated and two untreated plants in each pot.
  • Table VI Examples of curative activity of MCM expressed as EP 90 values (ppm a.i.) for the control of barley powdery mildew (BPM - Erysiphe graminis on barley), grape vines powdery mildew (GPM - Uncinula necator on grape) and apple scab (AS - Venturia inaequalis on apple):
  • Table VII Examples of 3 day protective activity of MCM expressed as EP 90 values (ppm a.i.) against wheat septoriosis (WSN - Lepthosphaeria nodorum), wheat powdery mildew (WPM - Erysiphe graminis), wheat rust (WLR - Puccinia recondita), apple powdery mildew (APM - Podosphaera leucotricha), bean rust (BR - Uromyces appendiculata on phaseolus beans)
  • Table VIII Curative (2 d cur) and protective (1 d res) activity (%) of MCM against grape downy mildew (GPM - Plasmopara viticola), tomato late blight (TLB - Phytophthora infestans) and barley net blotch (BNB - Pyrenophora teres)
  • Table IX Systemicity of MCM in wheat leaves (in mm) after foliar application using wheat powdery mildew as the indicator disease:

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Abstract

L'invention concerne des composés de formule Dans ladite formule, R1 représente un atome d'hydrogène ou bien un groupe éventuellement substitué: alkyle, alcényle, alkyloxiranyle, alcanoyle, alcoxycarbonyle, formyle, hydroxyalkyle, alcoxyalkyle, alcanoyloxyalkyle, hydroximinoalkyle, alcoxyiminoalkyle, hydrazonoalkyle ou alkylhydrazonoalkyle; R2 est un groupe alcoxy; R3 et R4 sont chacun indépendamment un atome d'hydrogène ou un groupe alkyle; R5 est un groupe alkyle; et R6 est un groupe de formule -COOR7 ou -CONR?7R8, où R7 et R8¿ ont une excellente activité fongicide et systémique. Lesdits composés sont donc utiles pour différentes applications agricoles.
PCT/US1998/006935 1997-04-11 1998-04-08 Derives de melithiazole fongicides WO1998046583A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US09/402,855 US6197802B1 (en) 1997-04-11 1998-04-08 Fungicidal melithiazole derivatives
AU68902/98A AU6890298A (en) 1997-04-11 1998-04-08 Fungicidal melithiazole derivatives
JP54400498A JP2002510284A (ja) 1998-04-08 1998-04-08 殺菌・殺カビ性のメリチアゾール誘導体
EP98914584A EP0975613A1 (fr) 1997-04-11 1998-04-08 Derives de melithiazole fongicides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19715290A DE19715290A1 (de) 1997-04-11 1997-04-11 Melithiazol C-Derivate
DE19715290.2 1997-04-11
EP98101365.9 1998-01-27
EP98101365 1998-01-27

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001012615A2 (fr) * 1999-08-12 2001-02-22 Gesellschaft Fur Biotechnologische Forschung Mbh Derives d'acide heteroaryl hepta-2,6-dienoique fongicides
WO2001038317A2 (fr) * 1999-11-24 2001-05-31 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Derives de melitthiazol fongicides

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4410449A1 (de) * 1994-03-25 1995-09-28 Biotechnolog Forschung Gmbh Melithiazole, Herstellungsverfahren, Mittel mit einem Gehalt an Melithiazol und Melittangium lichenicola DSM 9004 mit der Fähigkeit, Melithiazole zu bilden

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4410449A1 (de) * 1994-03-25 1995-09-28 Biotechnolog Forschung Gmbh Melithiazole, Herstellungsverfahren, Mittel mit einem Gehalt an Melithiazol und Melittangium lichenicola DSM 9004 mit der Fähigkeit, Melithiazole zu bilden

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRUCE J. MARTIN ET AL: "Total synthesis of the beta-methoxyacrylate-based fungicide myxothiazol", TETRAHEDRON LETTERS., vol. 34, no. 32, 1993, OXFORD GB, pages 5151 - 5154, XP002070974 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001012615A2 (fr) * 1999-08-12 2001-02-22 Gesellschaft Fur Biotechnologische Forschung Mbh Derives d'acide heteroaryl hepta-2,6-dienoique fongicides
WO2001012615A3 (fr) * 1999-08-12 2001-09-13 American Cyanamid Co Derives d'acide heteroaryl hepta-2,6-dienoique fongicides
WO2001038317A2 (fr) * 1999-11-24 2001-05-31 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Derives de melitthiazol fongicides
WO2001038317A3 (fr) * 1999-11-24 2001-11-08 Basf Corp Derives de melitthiazol fongicides

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