WO1998016517A1 - Procede permettant de produire des derives d'isoxazole et produits intermediaires pour produire ceux-ci - Google Patents

Procede permettant de produire des derives d'isoxazole et produits intermediaires pour produire ceux-ci Download PDF

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WO1998016517A1
WO1998016517A1 PCT/JP1997/003584 JP9703584W WO9816517A1 WO 1998016517 A1 WO1998016517 A1 WO 1998016517A1 JP 9703584 W JP9703584 W JP 9703584W WO 9816517 A1 WO9816517 A1 WO 9816517A1
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general formula
compound represented
compound
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PCT/JP1997/003584
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English (en)
Japanese (ja)
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Hiroyuki Kai
Akira Takase
Minoru Tomida
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Shionogi & Co., Ltd.
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Priority to AU44003/97A priority Critical patent/AU4400397A/en
Publication of WO1998016517A1 publication Critical patent/WO1998016517A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/36—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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

Definitions

  • the present invention relates to 3—benzoylisoxazoles, which are important intermediates such as antifungal agents and agricultural germicides, and more particularly to unsubstituted 3-benzoyl rings at the 4- and 5-positions of the isoxazole ring.
  • the present invention relates to a novel method for producing soxazole, an intermediate for producing the same, and a novel method for producing a 3-((1-alkoxyminobenzyl) isoxazole derivative which is useful as an agricultural fungicide using the same as a raw material.
  • 3-Benzyl isoxazoles which are unsubstituted in the 4- and 5-positions of the isoxazole ring, are isoxazolyl ethanol derivatives that are useful as antifungals and fungicides for agriculture. 5 — 6 9 8 3 5) and 3 — ( ⁇ -alkoxysiminobenzil) isoxoxazole derivative (W095Z26695) useful as an agricultural fungicide (See No. 6).
  • a method for producing the intermediate there is a method based on a Freedel-Craft reaction of 3-isoxazole carboxylic acid chloride and substituted benzene (Japanese Patent Publication No. 5-69835).
  • An object of the present invention is to provide an industrially advantageous method for producing 3-benzoylisoxazole in which the 4- and 5-positions of the isoxazole ring are unsubstituted, and an intermediate for the production thereof. Further, the present invention has an object to provide a novel method for producing a 3— ( ⁇ -alkoxyiminobenzyl) isosoxazole derivative which is useful as an agricultural germicide using them as a raw material. I do.
  • the present inventors have conducted intensive studies in order to achieve the above object, and as a result, reacted benzohydroxamic acid chloride produced from substituted acetophenone with acetylene in the presence of a base.
  • phenol is added to this to react with ketoxime etc. for the purpose of 3-benzoynoleic soxazole. It was Heading a way to elephants.
  • the present inventors have found a method for producing a 3- ( ⁇ -alkoxyiminobenzyl) isosoxazole derivative by oxidizing 3-benzoyl-5-alkoxy-1-2-isosoxazoline to complete the present invention. did. That is, the present invention
  • ⁇ 2 each independently represent a hydrogen atom, an alkyl, Anoreko alkoxy, Nono b Gen atoms, Application Benefits off Noreoro methyltransferase or a (CH 2)
  • R 6 represents a hydrogen atom or an alkyl.
  • lower used in the present specification for the process for producing the compound represented by the formula (wherein each symbol is as defined above), unless otherwise specified, preferably has 1 to 8 carbon atoms. Or a group having 1 to 6 carbon atoms, more preferably a group having 1 to 4 carbon atoms.
  • alkyl represented by R 1 and R 2 examples include, for example,
  • alkyls specifically methyl, ethyl propynole, isopropynole, butyl, isobutynole, sec-butyl, tert-butyl and the like.
  • Alkoxy represented by R 1 and R 2 includes, for example, alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, specifically, methoxy, ethoxy, and prooxy. Poxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy and the like.
  • Examples of the optionally substituted aryl represented by R 3 include aryl having 6 to 14 carbon atoms, such as phenyl and naphthyl. . T 5
  • Examples of the substituent of the substituted aryl represented by R 3 include lower alkyl (eg, methyl, ethyl, propyl, isopropyl, butyl, etc.) and lower alkoxy (eg, methoxy, Ethoxy, propoxy, isopropoxy, butoxy, etc.), cycloalkyl (eg, cyclopropyl, cyclopentyl, cyclohexyl, etc.), phenol, halogenated (lower) alkyl
  • Nodogenated (lower) alkyloxy e.g., difluoromethyoxy
  • trifluoromethyoxy e.g., trifluoromethyoxy
  • Phenyl, halogen atom e.g., fluorine, chlorine) Atom, bromine atom, iodine atom.
  • halogen atom e.g., fluorine, chlorine Atom, bromine atom, iodine atom.
  • lower alkyls, lower alkoxys, norogenated (lower) alkyls (especially trifluoromethyl), nordogenated (lower) alkoxys (especially difluoromethyoxy) and Halogen atoms are preferred.
  • substituents may be located at any substitutable position of the ring.
  • the number of the substituents is 1 to 5, preferably 1 to 4, and more preferably 1 to 3, and they may be the same or different.
  • R 3 include lower alkyl (preferably methyl), lower alkoxy (preferably methoxy), trifluoromethyl difluoromethylyloxy and halogen atoms
  • Examples of the alkyl represented by R 4 to R 6 include the same as those exemplified as the alkyl represented by R 1 and R 2 .
  • R 4 is methyl or ethyl
  • R 5 is alkyl having 2 to 5 carbon atoms (eg, ethyl, propynole, isopropynole, butyl, pentyl, etc.),
  • R 6 is preferably methyl.
  • alkylthio represented by R 4 examples include, for example, alkylthio having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, specifically, methylthio, ethylthio, propylthio, isopropylthio, Butylthio and the like. Of these, methylthio is preferred.
  • halogen atom represented by X examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • the compounds represented by the general formulas (VI) and (VII) include E-isomer and Z-isomer, and the present invention includes these isomers and a mixture of these isomers in any ratio. I do. In the present specification, this is indicated by using a wavy line ()) in the general formula.
  • the compound represented by the general formula (II) can be obtained by converting the compound (VIII) with alkyl nitrite and hydrogen chloride in a suitable solvent (single or mixed) by a known method, for example, the method described in Brachwitz, Z. Chera. , 6, 313 (1966).
  • Alkyl nitrite that can be used includes, for example, methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite, and the like.
  • the amount of use is 2 or more equivalents, preferably 2 to 6 equivalents, relative to compound (VIII).
  • Hydrogen chloride can be added by dissolving it in a suitable solvent as a gas to introduce it into the reaction solution.
  • the amount of use is 1 equivalent or more, preferably 1 to 6 equivalents, relative to the compound (VIII).
  • Solvents that can be used include, for example, ethers (eg, dimethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.), halogenated hydrocarbons (eg, , Dichloromethane, 1,2-dichloroethane, chlorohonolem, etc.) and mixed solvents of these solvents and aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.) Preference is preferred. .
  • ethers eg, dimethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.
  • the reaction temperature is between ⁇ 20 and 60 ° C., preferably between 0 and 40 ° C.
  • reaction time varies depending on the compound, but the reaction may be carried out for 1 to 72 hours.
  • the desired compound (II) obtained may be used as a reaction solution or in a crude form. Can be purified by recrystallization etc. and used in the next step Scheme 2
  • the compound represented by the general formula (IX) can be prepared by converting the compound (VIII) with an alkyl nitrite in a suitable solvent (single or mixed) in the presence of a base in a known manner, for example, in 0. Touster's review: Org. React., 7, 327 (1953).
  • alkyl nitrites that can be used include methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite, and the like.
  • the amount of use is 1 equivalent or more, preferably 1 to 1.2 equivalents, relative to compound (VIII).
  • Examples of the base that can be used include metal alkoxides (eg, sodium methoxide, sodium ethoxide, etc.), and the amount used is based on the compound (VIII).
  • metal alkoxides eg, sodium methoxide, sodium ethoxide, etc.
  • the amount used is based on the compound (VIII).
  • One or more equivalents, preferably one to two equivalents, can be used.
  • Solvents that can be used include, for example, ethers (eg, dimethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.), halogenated hydrocarbons (eg, Examples: dichloromethane, 1,2-dichloroethane, cross-linked form, etc., aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), alcohols (eg, Tano, Eno, Puno, Isopanol, Butano ), Water, and a mixed solvent thereof.
  • ethers eg, dimethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.
  • halogenated hydrocarbons eg, Examples: dichloromethane, 1,2-dichloroethane, cross-linked form, etc.
  • aromatic hydrocarbons eg, to
  • the reaction temperature is from 120 to 120 ° C, preferably from 0 to 50 ° C.
  • the reaction time varies depending on the compound, but the reaction may be carried out for 30 minutes to 24 hours.
  • the obtained compound (IX) can be used as is in the next step after purification, either as a reaction mixture or crude, or by a conventional method (eg, column chromatography, recrystallization, etc.). can do.
  • the compound represented by the general formula (II) can be produced by chlorinating the compound (IX) in an appropriate solvent (single or mixed).
  • Chlorinating agents that can be used are chlorine, nitrosyl chloride, N-chlorosuccinic acid imid / N, N—dimethylformamide, hydrogen chloride N-dimethylformamide /
  • OXONE registered trademark
  • OXONE registered trademark
  • the like can be used in an amount of 1 equivalent or more, preferably 1 to 2 equivalents, relative to compound (IX).
  • Solvents that can be used include, for example, ethers (eg, dimethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.), halogenated hydrocarbons (eg, Dichloromethane, 1,2-Dichloroethane, chloroform, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), N, N-dimethylforma And a mixed solvent thereof.
  • the reaction temperature is from 120 to 80 (:, preferably from 0 to 40 ° C.
  • reaction time varies depending on the compound, but the reaction may be carried out for 30 minutes to 24 hours.
  • the obtained desired compound (II) can be used as is in the next step after being purified as a reaction solution or a crude product, or by recrystallization or the like.
  • the compound represented by the general formula (II) can be produced by reacting the compound (X) with an alkyl nitrite in a suitable solvent (single or mixed) in the presence of hydrogen chloride. .
  • Alkyl nitrites that can be used include methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite, and the like.
  • One or more equivalents, preferably 1 to 3 equivalents, can be used relative to compound (X).
  • Hydrogen chloride can be introduced into the reaction solution as a gas or dissolved in a suitable solvent and added.
  • the amount of use is 0.1 equivalent or more, preferably 1 to 4 equivalents, relative to compound (X).
  • Solvents that can be used include, for example, ethers (eg, getyl ether, diisopropinoleether, dibutyl ether, tetrahydrofuran, dioxane, etc.), halogenated hydrocarbons (eg, , Dichloromethane, 1,2-dichloroethane, chloroform, etc.), aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.) and their mixed solutions Medium is preferred. .
  • ethers eg, getyl ether, diisopropinoleether, dibutyl ether, tetrahydrofuran, dioxane, etc.
  • halogenated hydrocarbons eg, Dichloromethane, 1,2-dichloroethane, chloroform, etc.
  • aromatic hydrocarbons eg, toluene, benzene, xylene, etc.
  • the reaction temperature is from 120 to 120 ° C, preferably from 0500C.
  • the reaction time varies depending on the compound, but it is sufficient to carry out the reaction for 17 2 hours.
  • the desired compound (II) obtained is purified as it is, in the form of a reaction solution or a crude product, or by recrystallization. Can be used in the next process.
  • the compound (X) has the ability to use a commercially available product, the chlorination of the corresponding compound (VIII), the corresponding Grignard reagent of a substituted benzene, and the commercially available product 2-chloro N-methoxy.
  • N easily prepared by methods known in the art, such as the reaction of methyl acetate amide or the Freedel-Crafts reaction of substituted benzene with chloroacetyl chloride.
  • R 7 and R 8 each independently represent a hydrogen atom, an alkyl, an alkoxy, a halogen atom or a trifluoromethyl.
  • Examples of the alkyl, alkoxy, and halogen atoms represented by R 7 and R 8 include the same groups as those exemplified as the groups represented by R 1 and R 2 .
  • the compound represented by the general formula (I) is produced by reacting the compound (II) with acetylene in a suitable solvent (single or mixed) under basic conditions. Can be done.
  • Acetylene is used as a gas or diluted with a suitable solvent.
  • the amount of use can be one equivalent or more with respect to the compound (II).
  • bases examples include metal bicarbonates (eg, sodium bicarbonate, potassium bicarbonate, etc.) and metal carbonates (eg, sodium bicarbonate, potassium carbonate) , Calcium carbonate, etc.), organic bases (eg, tertiary amines such as pyridin triethylamine) and the like, and the amount of use is 1 equivalent or 1 equivalent to the compound (II). More than one to five equivalents can be used, preferably.
  • Solvents that can be used include, for example, ethers (eg, dimethyl ether, diisopropinoleone tenor, dibutyl ether, tetrahydrofuran, dioxane, etc.), ketones (eg, Acetone, methylethyl ketone, etc., halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, carbon tetrachloride, etc.), aromatic hydrocarbons (eg, , Benzene, tosoleene, xylene, etc.), N, N-dimethylformamide, dimethylsulfoxide, alcohols (eg, methanol, ethanol, phenol, isopropanol) , Butanol) and their mixed solvents.
  • ethers eg, dimethyl ether, diisopropinoleone tenor, dibutyl ether, tetrahydrofuran, dioxane, etc.
  • the reaction temperature is between ⁇ 10 and 150 ° C., preferably between 0 and 100 ° C.
  • the reaction time varies depending on the compound, but the reaction may be carried out for 30 minutes to 120 hours.
  • the desired compound (I) thus obtained can be purified as it is, in the form of a crude reaction mixture, or by a conventional method (eg, column chromatography, recrystallization, etc.) and then purified in the next step. Can be used.
  • the compound represented by the general formula (IV) is produced by reacting the compound (II) with the compound (III) in a suitable solvent (single or mixed) under basic conditions. be able to.
  • Examples of the compound (III) include lower alkyl vinyl ethers such as ethyl vinyl ether and butyl vinyl ether.
  • the amount of the compound used is 1 equivalent or more, preferably 1 to 8 equivalents, based on the compound (II). Can be used.
  • bases examples include metal bicarbonates (eg, sodium bicarbonate, potassium bicarbonate, etc.) and metal carbonates (eg, sodium bicarbonate, potassium carbonate) , Calcium carbonate, etc.), organic bases (eg, tertiary amines such as pyridin triethylamine, etc.), and the amount of use is 1 equivalent or 1 equivalent relative to compound (II). More than one to five equivalents can be used, preferably.
  • Solvents that can be used include, for example, ethers (eg, getyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran) Lanthanum, dioxane, etc., ketones (eg, acetone, methylethylketone, etc.), halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane) , Carbon tetrachloride, etc.), aromatic hydrocarbons (eg, benzene, tonorenene, xylene, etc.), N, N-dimethylformamide, dimethylsnorreoxide, alcohols (eg, meta- And ethanol, ethanol, propylene, isopropanol, butanol, and the like, and mixed solvents thereof.
  • ethers eg, getyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran
  • the reaction temperature is from 110 to 150 ° C, preferably from 0 to 100 ° C.
  • the reaction time varies depending on the compound, but the reaction may be carried out for 30 minutes to 120 hours.
  • the desired compound (IV) obtained is purified as it is in the form of a reaction solution or in the form of a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.). Can be used.
  • the compound represented by the general formula (I) can be produced by reacting the compound (IV) with an acid in a suitable solvent (single or mixed).
  • Acids that can be used include hydrohalic acids (eg, hydrochloric acid, hydrobromic acid, etc.), hydrogen halides (eg, hydrogen chloride, hydrogen bromide, etc.), sulfuric acid, or aromatic sulfone Acids (eg, toluenesulfonic acid, etc.).
  • the amount of the acid to be used is 0.01 to 1 equivalent, preferably 0.1 to 1 equivalent, relative to compound (IV). Or 0.05 to 0.5 equivalent.
  • Solvents that can be used include, for example, aromatic hydrocarbons (eg, toluene, benzene, xylene), and saturated hydrocarbons (eg, cyclohexane, hexane, etc.). ), Halogenated hydrocarbons (eg, chloroform, 1,2-dichloroethane, etc.), and their mixed solvents.
  • the reaction temperature is from 20 to: L 80 ° C, preferably from 60 to: 130 ° C.
  • the reaction time varies depending on the compound, but if the reaction is performed for 0.5 to 48 hours,
  • the compound represented by the general formula (I) can also be produced by reacting the compound (IV) with a base in a suitable solvent (single or mixed).
  • a suitable solvent such as, but not limited to, benzyl alcohol, benzyl ether, benzyl ether, benzyl ether, benzyl ether, benzyl ether, benzyl ether, benzyl ether, benzyl ether ether, benzyl, benzyl, benzyl, benzyl, sulfonane, benzyl, benzyl, benzyl, sulfonate, benzyl ether, benzyl ether sulfate, benzyl ether sulfate, benzyl ether sulfonylurea sulfonylurea sulfonylurea sulfonylurea sulfonylurea sulfon
  • Solvents that can be used include, for example, ethers (eg, tetrahydrofuran, dioxane, etc.), alcohols (eg, methanol, ethanol, propanol) Etc.), water and a mixed solvent thereof.
  • ethers eg, tetrahydrofuran, dioxane, etc.
  • alcohols eg, methanol, ethanol, propanol
  • the reaction temperature is from 0 to 100 ° C, preferably from 10 to 50 ° C.
  • reaction time varies depending on the compound, but it is recommended that the reaction be performed for 5 to 48 hours.
  • the desired compound (I) obtained is purified as it is in the form of a reaction mixture or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.) and then purified in the next step. Can be used.
  • the compound represented by the general formula (XI) can be produced by subjecting the methyl group of the benzene ring of the compound (Ia) to nodogenation by a known method.
  • an inert solvent eg, carbon tetrachloride, cyclohexane, benzene benzene, etc.
  • chlorine, bromine, N-methyl succinate imide or N-promote If necessary, react with a halogenating agent such as succinic acid imidizer using a mercury lamp under light irradiation, or use a mercury lamp such as ⁇ , ⁇ '-azoisobutyryl nitrile or dibenzoyl peroxide. It can be produced by reacting in the presence of a dical initiator. In this reaction, the halogenating agent is used in an amount of 1 equivalent or more, preferably 1 to 1 equivalent to the compound (la).
  • a halogenating agent such as succinic acid imidizer using a mercury lamp under light irradiation, or use a mercury lamp such as ⁇ , ⁇ '-azoisobutyryl nitrile or dibenzoyl peroxide. It can be produced by reacting in the presence
  • the radical initiator can be used in an amount of 0.01 equivalent or more, preferably 0.05 to 0.5 equivalent, relative to the compound (Ia).
  • the reaction temperature is from 20 to 120 ° C, preferably from 50 to 90 ° C.
  • the reaction time varies depending on the compound, but the reaction may be carried out for 5 minutes to 3 hours.
  • the desired compound (XI) obtained is purified as it is in the form of a reaction solution or as a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.) and then purified.
  • a conventional method eg, column chromatography, recrystallization, etc.
  • the compound (Ia) used as a raw material in this reaction and the obtained compound (XI) are both novel compounds and are included in the present invention.
  • Compound (Ia) can be produced according to the method of Scheme 5 or 7 above. And can
  • the compound represented by the general formula (Ib) is produced by reacting the compound (XI) with the compound (XII) in the presence of a base without solvent or in an appropriate solvent (single or mixed). be able to.
  • compound (XII) can be used in one or more equivalents, preferably one to two equivalents, relative to compound (XI).
  • Bases that can be used include, for example, metal hydroxides (eg, sodium hydroxide, potassium hydroxide, etc.), metal carbonates (eg, sodium carbonate, Metal carbonate, etc.), metal alkoxide (eg, sodium methoxide, sodium ethoxide, potassium mono-ieri-butoxide, etc.), metal hydride (E.g., sodium hydride, potassium hydride, etc.).
  • metal hydroxides eg, sodium hydroxide, potassium hydroxide, etc.
  • metal carbonates eg, sodium carbonate, Metal carbonate, etc.
  • metal alkoxide eg, sodium methoxide, sodium ethoxide, potassium mono-ieri-butoxide, etc.
  • metal hydride E.g., sodium hydride, potassium hydride, etc.
  • solvent examples include N, N-dimethylformamide dimethylsulfoxide, aromatic hydrocarbons (eg, toluene, benzenexylene), and saturated hydrocarbons (eg, cyclohexane). Hexane, hexane, etc.), ethers (eg, tetrahydrofuran, dioxane, etc.), ketones (eg, acetate, methylethylketone, etc.), nitrile Water (eg, acetonitrile), water and their mixed solvents, and the like.
  • aromatic hydrocarbons eg, toluene, benzenexylene
  • saturated hydrocarbons eg, cyclohexane
  • Hexane, hexane, etc. ethers (eg, tetrahydrofuran, dioxane, etc.), ketones (eg, acetate, methylethylketone, etc.), nitrile Water (eg
  • the reaction temperature is from 120 to 130 ° C, preferably from 0 to 100 ° C.
  • the reaction time varies depending on the compound, but the desired compound (Ib) obtained by reacting for 10 minutes to 72 hours can be used as a reaction solution or in a crude form, or by a conventional method (eg, It can be purified by chromatography (eg, recrystallization) and used in the next step.
  • compound (VI) can be produced by reacting compound (IV) with compound (V) or a salt thereof in an appropriate solvent (single or mixed).
  • Compound (V) can be used in an amount of 1 equivalent or more, preferably 1 to 4 equivalents, relative to compound (IV).
  • Examples of the salt of the compound (V) include mineral salts such as hydrochloride and sulfate.
  • the reaction is carried out after neutralization with a base.
  • Bases that can be used include, for example, metal hydroxides (eg, sodium hydroxide, potassium hydroxide, etc.), metal carbonates (eg, sodium carbonate, carbonate) Such as calcium), metal alkoxides (eg, sodium methoxide, sodium ethoxide), and amines (eg, pyridin).
  • the amount is 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to the salt of compound (V).
  • Solvents that can be used include, for example, hydrocarbons (eg, benzene, Benzene, xylene, etc.), halogenated hydrocarbons (eg, chloro-form 1,2-dichloroethane), ethers (eg, tetrahydrofuran, dioxane) ), Alcohols (eg, methanol, ethanol propanol, butanol, etc.), water, and mixed solvents thereof.
  • hydrocarbons eg, benzene, Benzene, xylene, etc.
  • halogenated hydrocarbons eg, chloro-form 1,2-dichloroethane
  • ethers eg, tetrahydrofuran, dioxane
  • Alcohols eg, methanol, ethanol propanol, butanol, etc.
  • the reaction temperature is 0 to 130 ° C, preferably 20 to 110 ° C.
  • the reaction time is usually about 15 minutes to 48 hours.
  • the resulting compound (VI) is used as is in the next step after purification, either as a reaction solution or in crude form, or by a conventional method (eg, column chromatography, recrystallization, etc.). can do.
  • the compound represented by the general formula (VII) can be produced by reacting the compound (VI) with an acid or a base in a suitable solvent (single or mixed) in the same manner as in the method described in the above scheme 7. it can.
  • the desired compound (VII) thus obtained can be purified, if necessary, by a conventional method (eg, Karamuk's mouth chromatography, recrystallization, etc.).
  • the compound represented by the general formula (VII) is obtained by converting a salt (eg, hydrochloride, sulfate, etc.) of the compound (IV) with the compound (V) into an appropriate solvent (single or mixed). During the reaction, it can be produced by reaction.
  • a salt eg, hydrochloride, sulfate, etc.
  • the salt of compound (V) can be used in an amount of 1 equivalent or more, preferably 1 to 4 equivalents, relative to compound (IV).
  • Solvents that can be used include, for example, aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, cyclohexane, hexane, etc.), alcohols (Eg, methanol, ethanol, propanol, butanol, etc.), water and mixed solvents thereof.
  • the reaction temperature is between 0 and 130 ° C, preferably between 20 and 110 ° C. Although the reaction time varies depending on the compound, the reaction may be performed for 15 minutes to 48 hours.
  • the desired compound (VII) thus obtained can be purified, if necessary, by a conventional method (eg, Karakku-guchi chromatography, recrystallization, etc.).
  • the compound (VII) obtained by the above schemes 11 and 12 has excellent bactericidal activity and is useful as an agricultural fungicide (W095 / 2695) 6).
  • a crude product of hydroxyiminoacetophenone was obtained.
  • the obtained crude product was subjected to isoprono. After dissolving in 60 ml of ethanol, 5.74 ml (0.06 mol) of ethyl vinyl ether and 5.04 g (0.06 mol) of sodium hydrogen carbonate were added. The mixture was stirred at 335 ° C. for 14 hours. After the reaction, 200 ml of ether was added, and the mixture was washed twice with 200 ml of saline, and the ether layer was dried over anhydrous magnesium sulfate. The residue obtained by concentration under reduced pressure was silica gel gel.
  • a crude product of acetophenone was obtained.
  • the obtained crude product was dissolved in 200 ml of isopropanol, 38.8 m 1 (0.3 monole) of petil vinyl ether and 16.80 g (0.2 mol) of sodium hydrogen carbonate were added, and the mixture was stirred at room temperature for 48 hours. After the reaction, add 400 ml of ether, wash twice with 400 ml of brine, dry the ether layer with anhydrous magnesium sulfate, and concentrate under reduced pressure to obtain a residue obtained by silica gel chromatography.
  • the obtained crude product was subjected to isoprono. Dissolved in 30 ml of ethanol 2.9 ml (0.03 monole) of 1 ter and 2.52 g (0.03 mol) of sodium hydrogen carbonate were added, and the mixture was stirred at 40 to 45 ° C for 6 hours. After the reaction, 15 O ml of ether was added, and the mixture was washed twice with 15 O ml of a saline solution. The ether layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a residue obtained by silica gel chromatography.
  • the process for producing 3-benzoyloxoxazole of the present invention is useful as an industrial process because the number of steps is small and raw materials are easily available as compared with the conventional process.

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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

L'invention concerne un procédé permettant de produire des composés représentés par la formule générale suivante (I): (où R1 et R2 représentent chacun hydrogène, alkyle, alcoxy, halogéno, ou -(CH¿2?)n-M-R?3¿, et où R3 représente un aryle éventuellement substitué, etc.; M représente oxygène, etc.; et n est égal à 0 ou 1). Ledit procédé se caractérise par la mise en réaction d'un composé représenté par la formule générale (II) (où R1 et R2 sont tels que définis plus haut), avec de l'acétylène, dans des conditions basiques; l'invention concerne également un procédé permettant de produire des composés représentés par la formule générale (VII), utiles en tant que germicides dans l'agriculture, à partir des composés représentés par les formules générales (I) et (II).
PCT/JP1997/003584 1996-10-11 1997-10-07 Procede permettant de produire des derives d'isoxazole et produits intermediaires pour produire ceux-ci WO1998016517A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU44003/97A AU4400397A (en) 1996-10-11 1997-10-07 Process for producing isoxazole derivatives and intermediates for producing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP8/270014 1996-10-11
JP27001496 1996-10-11

Publications (1)

Publication Number Publication Date
WO1998016517A1 true WO1998016517A1 (fr) 1998-04-23

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1997/003584 WO1998016517A1 (fr) 1996-10-11 1997-10-07 Procede permettant de produire des derives d'isoxazole et produits intermediaires pour produire ceux-ci

Country Status (2)

Country Link
AU (1) AU4400397A (fr)
WO (1) WO1998016517A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6809204B2 (en) 2001-10-12 2004-10-26 Onconova Therapeutics, Inc. Processes for the preparation of substituted isoxazoles and 2-isoxazolines
US7176795B2 (en) 2002-04-04 2007-02-13 National Oilwell Norway As Method and a device for protection of personnel
CN112028852A (zh) * 2020-09-29 2020-12-04 常州工程职业技术学院 一种3-酰基异噁唑类化合物及其制备方法

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FR2261260A1 (en) * 1974-02-18 1975-09-12 Roussel Uclaf Omega-isonitrosoacetophenone chloo derivs - obtd by reacting alkyl nitrite with omega-chloro acetophenone and used in germicides and bactericides
JPS61167673A (ja) * 1985-01-22 1986-07-29 ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド （イソキサゾール‐３‐イル）アリールメタノンおよびその製造方法
JPS6345277A (ja) * 1986-04-03 1988-02-26 Shionogi & Co Ltd イソオキサゾリルエタノ−ル誘導体、抗真菌剤および農業用殺菌剤
JPH02258754A (ja) * 1989-02-14 1990-10-19 Hoechst Celanese Corp α―クロロ―α―オキシイミノ―４ーヒドロキシアセトフェノンの製造
WO1995026956A1 (fr) * 1994-04-01 1995-10-12 Shionogi & Co., Ltd. Derive d'oxime et bactericide le contenant en tant qu'ingredient actif

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2261260A1 (en) * 1974-02-18 1975-09-12 Roussel Uclaf Omega-isonitrosoacetophenone chloo derivs - obtd by reacting alkyl nitrite with omega-chloro acetophenone and used in germicides and bactericides
JPS61167673A (ja) * 1985-01-22 1986-07-29 ヘキスト‐ルセル・フアーマシユウテイカルズ・インコーポレイテツド （イソキサゾール‐３‐イル）アリールメタノンおよびその製造方法
JPS6345277A (ja) * 1986-04-03 1988-02-26 Shionogi & Co Ltd イソオキサゾリルエタノ−ル誘導体、抗真菌剤および農業用殺菌剤
JPH02258754A (ja) * 1989-02-14 1990-10-19 Hoechst Celanese Corp α―クロロ―α―オキシイミノ―４ーヒドロキシアセトフェノンの製造
WO1995026956A1 (fr) * 1994-04-01 1995-10-12 Shionogi & Co., Ltd. Derive d'oxime et bactericide le contenant en tant qu'ingredient actif

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Title
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CHEMICAL ABSTRACTS, Vol. 75, (1971), Abstract No. 63350, page 417. *
J. CHEM. SOC. PERKIN TRANS. I, Vol. 3, (1983), pages 483-485. *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6809204B2 (en) 2001-10-12 2004-10-26 Onconova Therapeutics, Inc. Processes for the preparation of substituted isoxazoles and 2-isoxazolines
US7094903B2 (en) 2001-10-12 2006-08-22 Onconova Therapeutics, Inc. Processes for the preparation of substituted isoxazoles and 2-isoxazolines
US7176795B2 (en) 2002-04-04 2007-02-13 National Oilwell Norway As Method and a device for protection of personnel
CN112028852A (zh) * 2020-09-29 2020-12-04 常州工程职业技术学院 一种3-酰基异噁唑类化合物及其制备方法
CN112028852B (zh) * 2020-09-29 2022-07-26 常州工程职业技术学院 一种3-酰基异噁唑类化合物及其制备方法

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