EP0637301A1 - Oxazolidinones fongicides - Google Patents

Oxazolidinones fongicides

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Publication number
EP0637301A1
EP0637301A1 EP93909169A EP93909169A EP0637301A1 EP 0637301 A1 EP0637301 A1 EP 0637301A1 EP 93909169 A EP93909169 A EP 93909169A EP 93909169 A EP93909169 A EP 93909169A EP 0637301 A1 EP0637301 A1 EP 0637301A1
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EP
European Patent Office
Prior art keywords
phenyl
methyl
formula
furanyl
bonded
Prior art date
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EP93909169A
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German (de)
English (en)
Inventor
Carlton Lane Campbell
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EIDP Inc
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EI Du Pont de Nemours and Co
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Publication of EP0637301A1 publication Critical patent/EP0637301A1/fr
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
    • C07D263/44—Two oxygen 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
    • A01N43/72—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
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
    • C07D263/48—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Definitions

  • This invention relates to particular oxazolidinone compounds useful as fungicides, agriculturally suitable compositions containing such compounds, and methods of use of such compounds or compositions as fungicides in crop plants.
  • WO90/12791 is drawn to the use of fungicidal compounds of Formula i
  • A is O orNR 4 ; and W is O orS.
  • WO90/12791 generically discloses compounds of Formula i wherein R 2 is phenyl substituted with benzyloxy and the phenyl of the benzyloxy is optionally substituted.
  • WO90/12791 specifically discloses a compound of Formula i wherein W is O, A is NH, R 1 is methyl, R 3 is phenyl, and R 2 is 4-benzyloxy- phenyl. This compound is not within the scope of the instant application.
  • US92/01224 generically discloses compounds wherein A is NH and R 2 is phenyl substituted with benzyloxy or phenoxymethyl. US92/01224 specifically discloses several compounds wherein A is NH, W is O, R 1 is methyl, R 3 is phenyl, R 4 is H, and R 2 is phenyl substituted with benzyloxy or phenoxymethyl, and said benzyloxy and henoxymethyl groups are substituted on the phenyl ring. Compounds specifically disclosed in US92/01224 are not within the scope of the instant application.
  • This invention comprises compounds of Formula I including all geometric and stereoisomers, agricultural compositions containing them and the use of the compounds or said compositions as fungicides.
  • the compounds of Formula I are:
  • R 1 is H; methyl; or ethyl
  • R 3 is phenyl optionally substituted with R 5 ;
  • R 4 is H or methyl;
  • R 5 is F; Cl; or C 1 -C4 a]kyl;
  • R 2 is selected from the group consisting of substituents of Formulae A, B andC:
  • G is a phenyl, naphthalenyl, pyridinyl, furanyl, thienyl, indolyl,
  • N-methylindolyl benzo[fr]furanyl, benzo[i-]t--ienyl, quinolinyl, isoquinolinyl, pyrrolyl, N-methylpyirolyl or N-ethylpyrrolyl each optionally substituted with R 7 , R 8 , or R 7 and R 8 ; such that the point of attachment to X is a carbon atom of G;
  • T is CH or N; U is O; S; NH; orNCH 3 ; R 6 is H; methyl; or ethyl;
  • R 7 is halogen; C r C 6 alkyl; C 2 -C 6 alkenyl; ⁇ -Cg haloalkyl; C r C alkylthio; allylthio; allyloxy; C1-C4 haloalkoxy; cyano; carbomethoxy; carboethoxy; phenoxy; nitro; amino; C j -Cg alkoxy; or dime ⁇ ylam-no; R 8 is F; Cl; Br; C r C 3 alkyl; or trifluoromethyl; R ⁇ is H or F; R 10 is hydrogen; halogen; C r C 6 alkyl; C 2 -C 6 alkenyl; C r C 6 haloalkyl;
  • R 7 and R 8 when R 7 and R. 8 are bonded to adjacent carbons, then R 7 and R 8 can be taken together to form R 7 -R 8 which is CH2CH2W, WCH 2 CH 2 , orWCH 2 CH 2 CH 2 ; or ( ⁇ ) when R 8 is bonded to C-2 of G, and X is CHR 6 Q, then R 8 and
  • R 8 and R 9 can be taken together to form R 8 -R 9 which is CH 2 , CH(CH 3 ), or CH 2 CH 2 ; J, W, and Z are each independently CH 2 , 0, or S; provided that
  • te ⁇ n "a-kyl”, used either alone or in compound words such as "alkylthio” or “haloalkyl” denotes straight-chain or branched alkyl; e.g., methyl, ethyl, n-propyl, t-propyl, or the different butyl, pentyl or hexyl isomers.
  • Alkenyl denotes straightchain or branched alkenes; e.g. 1-propenyl, 2- propenyl, 3-propenyl and the different butenyl, pentenyl and hexenyl isomers.
  • Alkenyl also denotes polyenes such as 13-hexadiene and 2,4,6-heptatriene.
  • Alkylthio denotes branched or straight-chain alkylthio moieties; e.g. methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
  • Alkoxy denotes, for example, methoxy, ethoxy, ⁇ -propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • halogen either alone or in compound words such as “haloalkyr', denotes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
  • haloalkyl include F3C, C1CH 2 , CF 3 CH 2 and CF 3 CF 2 .
  • haloalkoxy include CF 3 O, CCl 3 CH 2 O, CF 2 HCH 2 CH 2 O and CF 3 CH 2 O.
  • Cj-Cj The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are numbers from 1 to 6.
  • C j -C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl
  • C alkoxyalkoxy designates CH3OCH2O
  • C 3 alkoxyalkoxy designates, for example, CH 3 OCH 2 CH 2 O or CH 3 CH 2 OCH 2 O
  • C 4 alkoxyalkoxy designates the various isomers of an alkoxy group substituted with a second alkoxy group containing a total of 4 carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 O, and CH 3 CH 2 OCH 2 CH 2 O.
  • Preferred compounds, compositions containing them, and methods of their use for reasons of better activity and/or ease of synthesis are: Preferred 1.
  • R 2 is a substituent of Formula A and X is CHR 6 Q;
  • G is phenyl optionally substituted with R 7 or with R 7 and R 8 ;
  • R 7 is C 2 -C 5 alkenyl; C r C 5 haloalkyl; C r C 4 alkylthio; allylthio; allyloxy; Cj-C4 haloalkoxy; cyano; carbomethoxy; carboethoxy; or dimethylamino; or when R 7 and R 8 are bonded to adjacent carbons, they can be taken together to form -CH 2 CH 2 CH 2 - or -CH 2 CH 2 CH 2 CH 2 -; and provided that
  • R 2 is a substituent of Formula A;
  • R 3 is phenyl;
  • R 4 is H; R 9 is H; and
  • G is a phenyl, naphthalenyl, pyridinyl. or furanyl, each optionally substituted with R 7 , R 8 , or R 7 and R 8 .
  • Preferred 3 Compounds of Preferred 2 wherein: Xis CHR 6 Q; Q is O;
  • R 6 is H or methyl
  • G is a phenyl optionally substituted with R 7 , R 8 , or R 7 and R 8 .
  • Specifically preferred for greatest fungicidal activity and or ease of synthesis are:
  • Compounds of Formula I may exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers and geometric isomers.
  • One skilled in the art will appreciate that one stereoisomer may be the more active.
  • One skilled in the art knows how to separate said enantiomers, diastereomers, and geometric isomers. Accordingly, the present invention comprises racemic mixtures, individual stereoisomers, and optically active mixtures of compounds of Formula I.
  • the compounds of Formula I can be prepared as described below in Equations 1-5.
  • Substituted hydrazines of Formula 2 are either commercially available or can be prepared by literature methods (J. Timberlake; J. Stowell; The Chemistry of the Hydrazo, Azo, andAzoxy Groups (S. Patai, Ed.) John Wiley and Sons, Ltd., London (1975), p 69; Demers, J. P.; Klaubert, D. J.; Tetrahedron Lett. (1987), 4933.
  • 2-Thioxo-4-oxazolidinones of Formula 3 can be prepared by one or both of the methods described in detail in the literature (Geffken, D.; Z. Naturforsch, (1983), 38b, 1008; Geffken, D.; Arch. Pharm., (1982), 315, 802; WO90/12791 and U.S. 4,957,933).
  • compounds of Formula la can be prepared by the methods outlined in Equation 2. These procedures involve treatment of a 2-hydroxycarboxylic acid ester of Formula 4 with a carbonylating agent of Formula 6 to produce compounds of Formula 5, followed by conversion of 5 to la by treatment with a substituted h-ydrazine 2.
  • U can be chlorine, 1-imidazolyl, or other suitable leaving group.
  • the ester group containing Z in compounds of Formula 4 can be alkyl (C1-C4), alkenyl (C 3 -C4), cycloalkyl (C Ci ⁇ , cycloalkylalkyl (Cg-C ), alkoxyalkyl C 2 -C4), and phenylmethyl.
  • Z C I j -Q ⁇ alkyl, C3-C4 alkenyl, C 3 -C 12 cycloaHcyl, Cg-Cy cycloalkylalkyl, C 2 -C 4
  • the 2-hydroxycarbo- ⁇ lic acid esters of Formula 4 can be prepared by a number of methods known in the literature.
  • the 2-hydroxycarboxylic acids can be formed from the corresponding 2-hydroxycarboxylic acids by esterification as is well known in the literature.
  • the 2-hydroxycarboxylic acids can be prepared from ketones or aldehydes by formation of cyanohydrins, then hydrolysis, as is also known.
  • cyanohydrins For example, Org. Syntheses. Coll. Vol. 4, 58 (1968) teaches the preparation of atrolactic acid from acetophenone.
  • the esters can also be synthesized from aldehyde and ketone cyanohydrins by treatment with alcohols in the presence of HQ to afford the iminoether hydrochlorides, followed by hydrolysis.
  • a third method known for preparing 2-hydroxycarboxylic acids and esters involves treating 2-keto-acids or 2-keto-esters with nucleophilic-organometallic reagents such as Grignard reagents, and alkyl- and aryl-lithium reagents.
  • nucleophilic-organometallic reagents such as Grignard reagents, and alkyl- and aryl-lithium reagents.
  • R. G. Salomon et al. teaches the preparation of some esters of Formula 4 by the addition of aryl-Grignard reagents to pyruvate esters (J. Org. Chem. (1982), 47, 4692).
  • some 2-hydroxycarboxylic acids may be prepared by the regioselective nucleophilic addition of an aryl organometallic reagent to the metal salt (e.g., sodium salt) of pyruvic acid.
  • Carbonyl compounds known to undergo this reaction include pyruvate esters and acids, glyoxylate esters and acids, and diesters of oxomalonates.
  • the acids used in the acylation reaction can either be protic in nature, for example, a mixture of acetic and sulfuric acid, or a Lewis acid such as aluminum chloride, tin tetrachloride, titanium tetrachloride, or other Lewis acid known to effect Friedel- Crafts-type reactions.
  • the acid can be used either catalytically or in excess. In some cases, the acid may react destructively with the carbonyl substrate and excess carbonyl compound must be used.
  • the acylation can be conducted neat or in a solvent known by one skilled in the art to be suitable for Friedel-Crafts reactions, for example, methylene chloride, carbon disulfide, and nitrobenzene.
  • the reaction may be conducted from -50 to 100°C.
  • the specific choice of acid, solvent, temperature, and reaction time will depend on the carbonyl and aromatic substrates to be reacted.
  • the compounds of Fo ⁇ nula 5 can be prepared by the method illustrated in Step 1, Equation 2.
  • the alcohols of Formula 4 are dissolved in an inert solvent such as methylene chloride or 1-chlorobutane, and treated with a tertiaty-amine base such as triethylamine, pyridine, and N-N-diisopropylethylamine, at a temperature from -60 to +30°C.
  • phosgene (6a) to provide chloroformates of Formula 5a.
  • the phosgene can be added as a gas or dissolved in a inert solvent such as toluene and added in solution.
  • Step 1 When the reaction of Step 1 is complete, the resulting mixture is poured into a water-immiscible solvent and washed with dilute aqueous mineral acid, water, and brine. The organic liquid phase is dried and evaporated to yield products of Formula 5a.
  • CDI l.l'-carbonyldiimidazole
  • the alcohols of Formula 4 are dissolved in an inert solvent in which the CDI has sufficient solubility at the reaction temperature.
  • 1-chlorobutane and toluene are three of many suitable inert solvents.
  • the CDI is added as a solid or as a solution in an inert solvent at temperatures from 0 to 100°C.
  • the resulting mixture is poured into a water- immiscible solvent and washed successively with dilute mineral acid, water, and brine.
  • the organic liquid phase of this mixture is separated, dried, and evaporated to isolate the product.
  • isolation of compounds of Formula 5 is not necessary.
  • the compounds can be treated in situ with a hydrazine of Formula 2 as described below for Step 2.
  • CDI can be first prepared, for example by treatment of a solution of imidazole in an inert solvent with phosgene as described by Staab and Wendel (Org. Syntheses. Coll. Vol. J, 201, (1973)), and then treated in situ with alcohols 4 to afford 5b.
  • compounds of Formula 5 can be dissolved in an inert solvent such as methylene chloride, 1-chlorobutane, or THF and treated with a hydrazine of Formula 2 at a temperature from 0 to 80°C.
  • an inert solvent such as methylene chloride, 1-chlorobutane, or THF
  • a hydrazine of Formula 2 at a temperature from 0 to 80°C.
  • U Cl as shown in Formula 5a
  • a tertiary-amine base such as triethylamine, N ⁇ -diethylaniline, N ⁇ -diisopropylethylamine, or a second equivalent of a hydrazine 2
  • Suitable carboxylic acids include acetic acid, pivalic acid, and benzoic acid.
  • the product of Formula la can be isolated by evaporation of the aforementioned inert solvent, and purified by dissolving the residue in a water-immiscible solvent such as ether or methylene chloride, washing with mineral acid, aqueous base, and water, drying, and evaporating the extraction solvent. Crystallization or chromatography can be utilized for additional purification if desired.
  • 4-Imino-2-oxazolid-nones of Formula lb can be prepared by sequential conversion of cyanohydrins of Formula 7 to their respective chloroformates of Formula 8 or O-(-midazolylcarbonyl) derivatives of Formula 9, treatment of a compound 8 or 9 with a substituted hydrazine which produces the carbazates of Formula 109, then cyclization of a caibazate 10 to the product of Formula lb.
  • This sequence is schematically illustrated in Equation 3.
  • the 9-(imidazolylcarbonyl) derivatives of Formula 9 will be the intermediates of choice over the chloroformates of Formula 8 for those cyanohydrins 7 which fail to react, or react only poorly, with phosgene.
  • the cyanohydrins which react poorly with phosgene tend to be those derived from electron-rich-aryl alkyl ketones. Methodology for preparation of ketone cyanohydrins is well known to those skilled in the art. See, for example, Org.
  • Conversion of cyanohydrins to chloroformates is generally accomplished by mixing the cy anohydrin with phosgene and an acid acceptor in an inert solvent.
  • Typical acid acceptors include the tertiary-amine bases (such as pyridine, NJI- dimemylaniline, N ⁇ -diethyla line).
  • Typical inert solvents include the aromatic hydrocarbons (such as benzene, toluene, xylenes), ethers (such as THF, dioxane, diethyl ether), and chlorinated hydrocarbons (such as methylene chloride, chloroform). Temperatures are typically -20 to +40°C.
  • the chloroformates can be used direcdy in solution or be isolated by filtration of the reaction mixture and evaporation of the solvent from the filtrate; further purification can be accomplished by dissolution of the chloroformate in an inert, water-immiscible solvent (such as ether, benzene, toluene, xylenes, ethyl acetate, methylene chloride, chloroform, 1-chlorobutane), washing the solution with cold, dilute mineral acid, cold water, drying the solution, and evaporation of the solvent.
  • Conversion of cyanohydrins to their chloroformates is known in the literature (e.g., N. Kondratenko et al., Probl. Poluch.
  • cyanohydrins to their 0-imidazolyl carbonates can be accomplished by mixing the cyanohydrin with l, -carbonyldiimidazole (CDI) in an inert solvent until the reaction is substantially complete [optionally the CDI can be generated in situ from phosgene and imidazole as described by Staab and Wendel, Org. Synthesis Coll. Vol.5, 201, (1973)].
  • CDI l, -carbonyldiimidazole
  • the progress of the reaction can be conveniently followed by thin-layer chromatography, or by noting evolution of CO 2 (or lack thereof) on treatment of a sample of the reaction mixture with water, which reacts quickly with any unreacted CDI.
  • the reaction is generally over within a few minutes to a few days; typical times are about 2 h to an overnight period.
  • Suitable inert solvents include those mentioned above for preparation of the chloroformates. Reaction temperatures can vary from about -20°C up to the boiling point of the solvent, with ambient temperatures preferred for convenience.
  • reaction mixtures can be used directly for the next step (reaction with a substituted hydrazine), or the intermediate 0-(imidazolylcarbonyl) compounds can be purified and even isolated prior to use.
  • solvent in the reaction mixture is evaporated (if water-immiscible), and the residue is treated with cold water and water- ⁇ nmiscible solvent (e.g., diethyl ether, benzene, toluene, 1-chlorobutane, methylene chloride, chloroform, ethyl acetate); the layers are separated, and the organic layer is dried and evaporated to the ( -(imidazolylcarbonyl) compound.
  • solvent in the reaction mixture is evaporated (if water-immiscible), and the residue is treated with cold water and water- ⁇ nmiscible solvent (e.g., diethyl ether, benzene, toluene, 1-chlorobutane, methylene chloride, chloroform, e
  • Conversion of the cyanohydrin chloroformates to the carbazates comprises mixing the chloroformate with a substituted hydrazine in an inert solvent, with either some of a substituted hydrazine or an added tertiary-amine base [e.g., pyridine, N-N-diethylaniline, NN-dimethylaniline, triethylamine. (NN-d--sopropyl)eihyla ⁇ nine] acting as an acid acceptor.
  • Suitable solvents include those suitable for preparation of the chloroformate. The reaction is generally rapid and complete within a few minutes in the usual temperature range (about -20°C to ambient).
  • the intermediate carbazate can be isolated by evaporating the solvent in vacuo (if water-immiscible) and washing a solution of the residue in a water-immiscible solvent [such as mentioned for the preparation of an O-(imidazolylcarbonyl) compound] with dilute mineral acid and water, drying, and evaporation of the solvent.
  • a water-immiscible solvent such as mentioned for the preparation of an O-(imidazolylcarbonyl) compound
  • cyclization can be effected by treatment of a solution of the carbazate in an inert solvent (e.g., toluene, benzene, 1-chlorobutane, THF, chloroform) with imidazole or atertiary-aminebase [e.g., triethylamine, (N ⁇ -diisopropyl)ethylamine, pyridine] and optionally heating the mixture up to the boiling point of the solvent; for example, cyclization is typically effected by boiling a toluene solution of the carbazate in the presence of triethylamine at reflux for 2 h.
  • an inert solvent e.g., toluene, benzene, 1-chlorobutane, THF, chloroform
  • imidazole or atertiary-aminebase e.g., triethylamine, (N ⁇ -diisopropyl)ethylamine, pyridine
  • Conversion of an O-(imidazolylcarbonyl) derivative to a carbazate is effected by mixing an 0-(imidazolyl- carbonyl) derivative with a substituted hydrazine in an inert solvent (such as those mentioned for preparation of the chloroformate). Reaction is generally complete within a few minutes to an hour. Purification of the products can be effected by washing the reaction mixtures (if a water-immiscible solvent was used) with water, drying, and evaporation of the solvent.
  • Ease of isolation of the imino compound of Formula lb can sometimes be enhanced by conversion of it to a salt, for example by addition of a strong acid HX, wherein HX is HBr, HC1, HI, HNO 3 , H 2 SO 4 , H 3 PO 4 , or an organic acid such as alkyl- and arylsulfonic acids, to a solution of compound lb in an inert organic solvent (such as those mentioned for preparation of the chloroformate above). Crystallization of the salt of Formula Ib-HX can then often be effected from the same or different organic solvent, or the salt can be recovered by evaporation of the solvent.
  • Some of the -mine salts offer advantage of formulation or enhanced fungicidal activity over the free-base forms.
  • compounds of Formula Ib-HX can be converted to the corresponding 2,4-oxazolidinedione of Formula la by reaction with water; typically the salt (or lb plus an acid) is mixed with water, optionally in the presence of a cosolvent (e.g., acetone, butanone, THF) and optionally heated until conversion to the 4-oxo compound la is substantially complete (Equation 4).
  • a cosolvent e.g., acetone, butanone, THF
  • the 4-oxo compound can be isolated in the usual ways, such as by filtration or evaporation of the reaction mixture, or by extraction of the product into an organic solvent and evaporation of that solvent. Equation 4
  • R 2 may be incompatible with the conditions in the methods described above for the preparation of the 2-hydroxyester functionality.
  • the constraction of the R 2 unit after the introduction of the hydroxy ester moiety may be desirable.
  • the formation of the bridge linking G with the R -substituted phenyl ring may be synthesized with the hydroxyester functionalities already in place (Equation 5). Equation 5
  • ethers and thioethers are well known in the chemical literature.
  • the classical method for the preparation of ethers, the Williamson ether synthesis involves reaction of an alkoxide, such as alkoxides derived from compounds of Formulae 11 and 15, with an electrophile, such as compounds of Formulae 12 and 14, in an inert solvent.
  • the same methodology can be used to form thioethers.
  • a variety of elecrrophiles of Formulae 12 and 14 are commercially available or can be prepared by known methods (e.g., see Hudlicky, M.; Hudlicky, T. In The Chemistry of Functional Groups, Patai, S; Rappoport, Z., Eds.; Supplement D, Pt 2; pp 1021-1172).
  • a base e.g., potassium carbonate
  • protecting groups may be necessary in order to prepare the hydroxyesters of Formulae 11 and 14.
  • a protecting group may be necessary to mask the acidic proton on Q during the introduction of the hydroxyester group.
  • THF tetrahydrofuran
  • Et 2 O diethyl ether
  • EtOAc ethyl acetate
  • DMF dimethyl formamide
  • Etl iodoethane
  • HO Ac acetic acid.
  • EXAMPLE 1 (a) Preparation of 2-(4-(t-butyldimethyls--lyloxy)phenyl)la ⁇ ic acid A round-bottom flask equipped with a magnetic stirbar, addition funnel, condenser and an N 2 inlet was charged with Mg (90 mg) and the apparatus was dried under a N 2 flow. Once cooled to room temperature, THF (1 mL) was added to the flask along with I 2 (1 mg) and BrCH 2 CH 2 Br (2 drops).
  • the filter cake was washed with Et 2 O (2 x 25 mL), allowed to air dry and was then transferred to a flask and suspended in H 2 O (10 mL). After stirring for 15 min., con. HQ (0.7 mL) was added along with EtOAc (25 mL) and the mixture was stirred until the phases cleared. The phases were separated and the aqueous phase was extracted with EtOAc (2 x 25 mL). All organic phases were washed with H 2 O (2 x 20 mL), brine (2 x 25 mL), combined and dried (Na 2 SO4).
  • the cyanohydrin was dissolved in THF (200 mL), treated with 1,1 '-carbonyldiimidazole, the mixture stirred overnight, and evaporated to a yellow grease.
  • the grease was dissolved in butyl chloride and the solution washed with ice-cold water (2X) and cold saturated brine, dried (MgSO4), and die filtered solution evaporated to an oil (64.2 g); the IR spectrum of the oil showed strong absorption at 1773 cm" 1 , due to die carbonyl group of the imidazolyl- carbonyl derivative of the cyanohydrin.
  • hetero atoms contained in the ring are given the lowest possible numbers using the accepted rules of heterocycle numbering.
  • the point of attachment of die radical is the position assigned die highest priority.
  • t- is tertiary OMe - is methoxy s - is secondary SMe - is methylti- ⁇ o n - is normal SEt - is ethylthio i - is iso NO 2 - is nitro M -is methyl CN - is cyano Et - is ethyl Ph - is phenyl
  • compositions of the present invention comprise an effective amount of at least one compound of Formula I as defined above and at least one of (a) a surfactant, (b) an organic solvent, and (c) at least one solid or liquid diluent.
  • Useful formulations can be prepared in conventional ways. They include dusts, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation.
  • the formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up 100 weight percent.
  • Typical solid diluents are described in Waikins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents and solvents are described in Marsden, Solvents Guide, 2nd Ed., I terscience, New York, (1950). McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, (1964), list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, etc.
  • compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer mill or fluid energy mill. Water- dispersible granules can be produced be agglomerating a fine powder composition; see for example, Cross et al., Pesticide Formulations, Washington, D.C., (1988), pp 251-259. Suspensions are prepared by wet-milling; see, for example, U.S.3,060,084. Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration".
  • Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in DE 3,246,493.
  • Compound 3 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
  • Compound 3 20.0% blend of oil soluble sulfonates and poly oxyethylene ethers 10.0% isophorone 70.0%.
  • the compounds of this invention are useful as plant disease control agents.
  • the present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of Formula I as defined above or a fungicidal composition containing said compound.
  • the compounds and compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops.
  • Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection.
  • insecticides such as monocrotophos, carbofuran, tetrachlorvi ⁇ phos, malathion, parathio — methyl, methomyl, chlordimeform, diazinon, deltamethrin, oxamyl, fenvalerate, esfenvalerate, pe ⁇ nethrin, profenofos, sulprofos, triflumuron, difiubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphosmethyl, chlorpyrifos, dimethoate, fipronil, flufenprox, fonophos, isofenphos, methidathion, metha- midophos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, terbufos, trich
  • Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre — or post — infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing.
  • the compounds can also be applied to the seed to protect the seed and seedling. Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 10 g per kilogram of seed.
  • the following Tests demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions.
  • Test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests.
  • Trem® 014 polyhydric alcohol esters
  • test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.
  • Puccinia recondita the causal agent of wheat leaf rust
  • test suspension was sprayed to the point of run-off on rice seedlings. The following day the seedlings were inoculated with a spore suspension of Pyr ⁇ cularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 h, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made.
  • Pyr ⁇ cularia oryzae the causal agent of rice blast
  • TEST C The test suspension was sprayed to the point of run-off on tomato seedlings.
  • test suspension was sprayed to the point of run-off on potato seedlings.
  • seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.
  • Phytophthora infestans the causal agent of potato and tomato late blight
  • TEST E The test suspension was sprayed to the point of run-off on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20°C for 24 li, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 h, after which disease ratings were made.
  • Plasmopara viticola the causal agent of grape downy mildew

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne des oxazolidinones utiles en tant que fongicides, représentés par la formule (I) dans laquelle: A représente O ou NH; R3 représente phényle éventuellement substitué; R1 et R4 représentent chacun H ou alkyle; et R2 correspond à la formule (A), (B) ou (C).
EP93909169A 1992-04-24 1993-03-25 Oxazolidinones fongicides Withdrawn EP0637301A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US87330292A 1992-04-24 1992-04-24
PCT/US1993/002797 WO1993022299A1 (fr) 1992-04-24 1993-03-25 Oxazolidinones fongicides
US873302 1997-06-11

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EP0637301A1 true EP0637301A1 (fr) 1995-02-08

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EP (1) EP0637301A1 (fr)
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WO (1) WO1993022299A1 (fr)

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JP3356286B2 (ja) * 1992-11-13 2002-12-16 イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー ２，４−オキサゾリジンジオン類の製造方法
GB9607784D0 (en) * 1996-04-15 1996-06-19 Zeneca Ltd Fungicides
GB9607785D0 (en) * 1996-04-15 1996-06-19 Zeneca Ltd Fungicides
WO2005066135A2 (fr) * 2003-12-29 2005-07-21 Sepracor Inc. Inhibiteurs daao de pyrrole et de pyrazole
EP2963013A4 (fr) * 2013-02-27 2016-09-14 Shionogi & Co Dérivés d'indole et d'azaindole ayant chacun une activité d'activation d'ampk
CN110204505B (zh) * 2019-05-31 2023-02-03 荆门医药工业技术研究院 (s)-3-苄氧羰基-4-异丙基-2,5-恶唑烷二酮的制备工艺

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KR0148128B1 (ko) * 1989-04-21 1998-08-17 미리엄 디. 멕코나헤이 살진균성 옥사졸리디논
WO1991015480A1 (fr) * 1990-04-10 1991-10-17 E.I. Du Pont De Nemours And Company Oxazolidinones fongicides
EP0533734A1 (fr) * 1990-06-11 1993-03-31 E.I. Du Pont De Nemours And Company Iminooxazolidinones fongicides
EP0503798A1 (fr) * 1991-03-15 1992-09-16 E.I. Du Pont De Nemours And Company 4-Thioxooxazolidin-2-ones et 4-iminooxazoliden-2-ones fongicides

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Title
See references of WO9322299A1 *

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WO1993022299A1 (fr) 1993-11-11

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