WO1998046561A1 - Derives de benzene, derives de benzofurane et procedes de production de ces derives - Google Patents

Derives de benzene, derives de benzofurane et procedes de production de ces derives Download PDF

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Publication number
WO1998046561A1
WO1998046561A1 PCT/JP1998/001618 JP9801618W WO9846561A1 WO 1998046561 A1 WO1998046561 A1 WO 1998046561A1 JP 9801618 W JP9801618 W JP 9801618W WO 9846561 A1 WO9846561 A1 WO 9846561A1
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Prior art keywords
derivative
general formula
alkyl group
group
same
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PCT/JP1998/001618
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English (en)
Japanese (ja)
Inventor
Hirofumi Nakagawa
Yoshinori Endo
Mitsuyuki Murakami
Takeshi Gondo
Yasuhiro Endo
Masaki Abe
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Otsuka Chemical Co., Ltd.
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Priority to AU67470/98A priority Critical patent/AU6747098A/en
Publication of WO1998046561A1 publication Critical patent/WO1998046561A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • 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
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/52—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/62—Carboxylic acid nitriles containing cyano groups and oxygen atoms being part of oxyimino groups bound to the same carbon skeleton

Definitions

  • the present invention relates to a benzene derivative, a benzofuran derivative and a method for producing them.
  • 1 ⁇ 1 and 13 ⁇ 4 2 represents a halogen atom, a lower alkyl group, lower haloalkyl group, lower alkoxy group or Shiano group the same or different.
  • 3 and 5 are the same or different and represent a hydrogen atom or a lower alkyl group.
  • R 6 represents a lower alkyl group.
  • Y represents an oxygen atom or a sulfur atom.
  • the benzofuranyl triazole derivative represented by the formula is a compound useful as a herbicide. This benzofuranyl triazole derivative is a compound discovered by the present inventors for the first time. Patent applications have already been filed as Japanese Patent Application Laid-Open Nos. Hei 8-25083 and Hei 9-71583. JP Hei 8
  • the benzofuranyltriazole derivative of the general formula (6) can be prepared by the method shown in the following reaction formula-1. More manufactured.
  • the compound represented by the general formula (6) is derived from the (thio) semicarbazide derivative represented by the general formula (5) described in JP-A-8-20583 and JP-A-9-71583.
  • the method for producing the benzofurantriazole derivative described above is practical, there is still room for improvement. That is, trifluoroacetic anhydride used in this method has a low boiling point (40 ° C.), is highly hygroscopic, and reacts quickly with moisture to produce highly corrosive trifluoroacetic acid. Even if trifluoroacetic anhydride does not react with water, trifluoroacetic acid remains in the reaction mixture after completion of the reaction with the (thio) chemical pad'zide derivative. Need to be collected or treated and disposed of.
  • the present invention provides a novel benzene derivative and a benzofuran derivative which are intermediates for industrially advantageously producing the (thio) semicarbazide derivative of the general formula (5). Aim.
  • Another object of the present invention is to provide a method for producing such a benzene derivative and a benzofuran derivative.
  • Still another object of the present invention is to provide an industrially advantageous method for producing a benzofuranyl triazole derivative represented by the general formula (6). Disclosure of the invention
  • the benzene derivative and the benzofuran derivative of the present invention are novel compounds which have not been described in the literature, and are represented by the following general formulas (1), (2), (3) and (3), respectively. 4) in
  • 1 and 2 are the same or different and represent a halogen atom.
  • 1 3 and 1 ⁇ 4 the same or different One hydrogen atom or a lower alkyl group.
  • RRR 3 is the same as above.
  • R 5 represents hydrogen or a lower alkyl group.
  • RR 2 , R 3 , and R 5 are the same as above.
  • Y represents an oxygen atom or a sulfur atom.
  • the present invention relates to a novel benzene derivative represented by the general formula (1) and a novel benzofuran derivative represented by the general formulas (2), (3) and (4). It relates to these manufacturing methods.
  • the present invention relates to a method for producing a (thio) semicarbazide derivative represented by the general formula (5) and a benzofuranyl triazole derivative represented by the general formula (6) using these derivatives.
  • Examples of the halogen atom shown in the present specification include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • a straight or branched chain alkyl group having 1 to 6 carbon atoms preferably methyl, ethyl, propyl, isopropyl, butyl, i Seo heptyl, tert - 1 to 4 carbon atoms, such as butyl (C -! 4) of Ru can and this include linear or branched alkyl group.
  • Examples of the lower haloalkyl group shown in the present specification include, for example, triphenylenomethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, and fluoromethyl.
  • a straight-chain or branched-chain haloalkyl group having 1 to 4 carbon atoms having 1 to 3 carbon atoms can be exemplified.
  • the halogen atom those described above can be mentioned.
  • the lower alkoxy group shown in the present specification for example, a C 1 -C 4 group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy group, etc.
  • a straight-chain or branched-chain alkoxy group can be exemplified.
  • the benzene derivative represented by the general formula (1) is produced according to the method shown in the following reaction formula 12.
  • R 1 R 2 , R 3 and R 4 are as defined above.
  • X represents a halogen atom.
  • R 1 and X are each a halogen atom
  • R 2 , R 3 and R 4 are each a C- 4 alkyl group.
  • the benzene derivative of the general formula (1) is produced by reacting the benzene of the general formula (7) with the oxime of the general formula (8). You.
  • the reaction between the benzene derivative of the general formula (7) and the oxime of the general formula (8) is carried out in a two-phase solvent of water and a suitable hydrophobic solvent in the presence of a phase transfer catalyst and a base.
  • a suitable hydrophobic solvent include aromatic solvents such as benzene, toluene, chlorobenzene, etc .; dichloromethane, dichloroethane, and chlorofluoronom Halogen such as carbon tetrachloride System solvents; mixed solvents of these, and the like; among them, aromatic solvents are preferred.
  • phase transfer catalyst conventionally known ones can be widely used, and examples thereof include tetramethylammonium bromide, tetramethyl bromide-n-butynolemonium, and yo-i-dila tetran — Butynoleammonium, tetrachloride — n — Butylammonium, bromide tetra — n-pentylammonium, bromide tetra n — hexizoleammonium, bromide tetra — N — octyl ammonium, bromide tetra n — hexadecyl ammonium, benzylinoletriethyl ammonium, trichloride n — octyl methyl ammonium, etc.
  • Ammonium salt tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, methyltriphenylphosphonium bromide, tetrahydrochloride-n-butyl Quaternary phosphonium Honiu salt-free, such as a host Honiu beam, and the like.
  • the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; and carbonic acid. Examples of such metals include sodium hydroxide and metal hydroxides.
  • Such a base is usually used in the form of an aqueous solution or suspension, and its concentration is usually about 5 to 60%, preferably about 10 to 40%.
  • the reaction temperature of this reaction can be appropriately selected from the range of room temperature to 100 ° C, and is 50 to 8 Performing at 0 ° C is preferred in terms of reaction time and yield.
  • the ratio of the benzene derivative of the general formula (7) to the oxam of the general formula (8) is usually 1 to 5 moles, preferably 1.5 to 1 mole of the former. It is better to use up to 3.5 moles.
  • the phase transfer catalyst is used usually in an amount of 0.1 to 0.5 mol, preferably 0.15 to 0.3 mol, per 1 mol of the benzene derivative of the general formula (7).
  • the base is used in an amount of usually 1 to 4 mol, preferably 1.5 to 2.5 mol, per 1 mol of the benzene derivative of the general formula (7).
  • the amount of the reaction solvent used is 100 to 100 parts by weight of the benzene derivative of the general formula (7), usually 150 to 100 parts by weight, preferably 300 to 100 parts by weight. It is recommended to be 700 parts by weight.
  • the ratio of water and hydrophobic solvent used is preferably 0.5 to 20 and more preferably 1 to 10 with respect to water 1 by weight.
  • the benzene derivative of the general formula (1) can be produced with a high yield.
  • the benzene derivative of the general formula (7) which is a starting material for this reaction, is a known compound.
  • formula (7) is a known compound.
  • the oxime of the general formula (8) which is a starting material, can be easily produced from hydroxylamin or its hydrochloride and a ketone such as acetone.
  • the oxime of general formula (8) produced in this way may be used after purification, but the crude product obtained by distilling low-boiling substances from the reaction solution under reduced pressure may be used as it is. It is also possible.
  • hydroxylamine hydrochloride is used as a raw material, an oxime hydrochloride of the general formula (8) is obtained, but when this salt is used in Reaction Formula 12, the amount of base is adjusted to the amount of hydrochloric acid. It is desirable to increase the amount required for salt neutralization.
  • the benzene derivative of the general formula (7) is reacted with the oxime of the general formula (8) in dimethylformamide in the presence of sodium hydride, potassium butoxide and other bases.
  • the reaction system was By forming a two-phase system with a neutral solvent and reacting with a base using a phase transfer catalyst, it is possible to obtain the corresponding benzene derivative of the general formula (1) in good yield.
  • step 1 when the benzene derivative of the general formula (1) and hydrogen halide are mixed and heated, the 5-nitrobenzofuran derivative of the general formula (2) is produced.
  • the reaction solvent used in this reaction includes, for example, methanol, ethanol, n-prono, 0 -nor, 2-propanol, n-butanol, and methanol.
  • Alcohol-based solvents such as tilcello sonolev; carboxylic acid-based solvents such as acetic acid; mixed solvents thereof; among others, alcohol-based solvents are preferred.
  • the amount of the reaction solvent to be used is usually 100 to 300 parts by weight, preferably 400 to 300 parts by weight, per 100 parts by weight of the benzene derivative of the general formula (1). 150 parts by weight is preferred.
  • the hydrogen halide conventionally known ones can be widely used, and examples thereof include hydrogen chloride and hydrogen bromide. Such hydrogen halide can be used as it is dissolved in the reaction solvent as it is, but an aqueous solution of hydrogen halide can also be used by adding it to the reaction solvent.
  • the amount of hydrogen halide to be used is generally 1 to 15 mol, preferably 5 to 10 mol, per 1 mol of the benzene derivative of the general formula (1).
  • the reaction temperature can be appropriately selected from the range of 40 ° C. to the boiling point of the reaction solvent, but the reaction is preferably carried out at 60 to 100 ° C. from the viewpoint of the reaction time and the yield.
  • Hydrogen halide aqueous solution When used, the concentration thereof is not particularly limited, but usually an aqueous solution of 20 to 60% by weight is used, and more preferably, an aqueous solution of 30 to 50% by weight is used.
  • the 5-dibenzobenzofuran derivative represented by the general formula (2) can be produced by a method other than the above step 1 (for example, the 5-nitrobenzofuran derivative (2) can be produced by the following reaction.
  • the 5-nitrobenzofuran derivative (2) can be produced by the following reaction.
  • R 3b represents a lower alkyl group.
  • R 7 represents a hydrogen atom or a lower alkyl group.
  • C X 1 and X 2 each represent a nitrogen atom.
  • the inert solvent examples include non-protonic polar solvents such as aceton, acetonitril and dimethylformamide; ethers such as getyl ether and tetrahydrofuran; Solvents: alcohol solvents such as methanol and the like.
  • the amount of the solvent used is usually 100 to 200 parts by weight per 100 parts by weight of 2,5-disubstituted phenol (9), preferably 200 to 200 parts by weight; 0 0 0 parts by weight.
  • Examples of the base include carbonates such as potassium carbonate and sodium carbonate; hydroxides such as sodium hydroxide, calcium hydroxide and calcium hydroxide; and triethyla Tertiary amines such as mine, pyridin, triethylenediamine, etc .; metal hydrides such as sodium hydride, hydrogen hydride and the like.
  • the amount of the base to be used is generally 0.5 to 50 equivalents, preferably 1 to 10 equivalents, relative to 2,5-disubstituted phenol (9). 2, 3 —
  • the amount of the dihalogenopropene derivative (10) used is It is usually 1 to 10 mol, preferably 1 to 5 mol, per 1 mol of 2,5-disubstituted phenol (9).
  • the reaction temperature can be appropriately selected from the melting point to the boiling point of the solvent, but it is usually preferable to carry out the reaction within the range from room temperature to the boiling point of the solvent. The reaction usually completes in 1 to 100 hours.
  • a Claisen rearranged trisubstituted phenol derivative is obtained.
  • the high-boiling solvent include alkylanilines such as dimethylylaniline and getylaniline; tetralin, mesitylene, diphenylether, snoreholane, etc. However, among these, alkylanilines are preferred.
  • the amount of the high boiling point solvent to be used is generally 0 to 1000 parts by weight, preferably 20 to 200 parts by weight, per 100 parts by weight of the ether derivative (11). This reaction usually completes in 1 to 40 hours.
  • the nitration of the tri-substituted phenol derivative (12) gives the 412 phenol derivative (13).
  • the solvent include halogenated hydrocarbon solvents such as dichloromethane and chlorophonolem; acids such as sulfuric acid and acetic acid; water; and a mixed solvent thereof.
  • Is used in the general formula (1 2) 100 to 500 parts by weight, preferably 100 to 200 parts by weight, per 100 parts by weight of the trisubstituted phenol derivative.
  • the nitrifying agent nitric acid, acetyl chloride and the like are used. When nitric acid is used as the nitrating agent, its concentration is usually from 10 to L 0%, preferably from 50 to L 0%.
  • the amount of the nitrating agent used is usually 0.5 to 5 moles, preferably 0.9 to 1.5 moles per monolayer of the trisubstituted phenol derivative (12). Is good.
  • the reaction temperature can be appropriately selected from 130 ° C. to the boiling point of the solvent, but is usually preferably in the range of 0 to 50 ° C. This reaction is usually completed in 1 to 10 hours.
  • the 12-nitrobenzofuran derivative (2b) can be obtained by heating the 12-tropininol derivative (13) in an acidic solution.
  • the acid include mineral acids such as hydrogen chloride and hydrogen bromide.
  • the amount of the acid to be used is generally 0.5 to 100 mol, preferably 1 to 20 mol, per 1 mol of 4-nitrophenol derivative (13).
  • Solvents include carboxylic acids such as acetic acid; methanol, 2-prono. Alcohols such as ethanol; water and the like; these may be used alone or as a mixture of two or more.
  • hydrogen bromide is used as the acid and acetic acid is used as the solvent.
  • the amount of the solvent used is the 4-nitrophenol derivative (13) It is usually from 100 to 500 parts by weight, preferably from 100 to 100 parts by weight, per 100 parts by weight.
  • the reaction temperature is usually preferably in the range from room temperature to the boiling point of the solvent. This reaction is usually completed in 1 to 100 hours.
  • the inert solvent examples include non-protonic polar solvents such as aceton, acetonitril, dimethylformamide and the like; Etenole-based solvents such as jetinole ether and tetrahydrofuran; alcohol-based solvents such as methanol; and the like.
  • the amount of solvent used is 2,5-disubstituted-4-nitrophenol (14) 100 to 100 parts by weight Normally 100 to 200 parts by weight, preferably 100 parts by weight Or 200 to 100 parts by weight.
  • Examples of the base include carbonates such as potassium carbonate and sodium carbonate; hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide; Tertiary amines such as triethylamine, pyridin and triethylene diamine; metal hydrides such as sodium hydride and calcium hydride;
  • the amount of the base used is usually 0.5 to 50 equivalents, preferably 1 to 10 equivalents, based on 2,5-disubstituted-4- 4-nitrophenol (14). It is.
  • the amount of the propargyl halide derivative (15) to be used is usually 1 to 10 moles, preferably 1 to 10 moles, per mole of the 2,5-disubstituted-412 trophenol (14). Or 1 to 5 moles.
  • the reaction temperature is preferably in the range from room temperature to the boiling point of the solvent. This reaction usually completes in 1 to 50 hours.
  • the propargyl ether derivative (16) is rearranged and ring-closed in the presence or absence of a catalyst in the presence of an inert solvent to give the 5-nitrobenzofuran derivative (2b).
  • inert solvents include dimethylylaniline and getylaniline.
  • Alkylanilines such as phosphorus; tetralin, mesitylene, diphenyl ether, sulfolane, etc. can be used, but among these, alkylanilins are preferred.
  • the amount of the inert solvent used is usually from 0 to 100 parts by weight, preferably from 50 to 500 parts by weight, per 100 parts by weight of the propargyl-ter derivative of the general formula (16). It is. Cesium fluoride is used as the catalyst.
  • the amount of the catalyst used is usually 0.0001 to 50 moles, preferably 1 mole of prono and the argyl ether derivative (16). Or 0.01 to 5 moles.
  • the reaction temperature is preferably in the range of 100 to 300 ° C. The reaction is usually completed in 1 to 20 hours.
  • the 2,5-disubstituted phenol (9) is represented by the general formula (17) in the presence of sulfuric acid; 9 monoketo acid or 3—
  • a keto acid ester By reacting with a keto acid ester, a coumarin derivative (18) is obtained.
  • the 3-keto acid include acetoacetic acid and propionylacetic acid.
  • a 3-keto acid ester for example, acetate Ethyl acetate, propionyl acetate, and the like.
  • the / 3—keto acid or 3—keto acid ester of the general formula (17) is usually from 1 to 5 moles per mole of 2,5—disubstituted phenol (9). It is 10 moles, preferably 1 to 5 moles.
  • lingic acid may be used in place of the; 3—keto acid or / 3—keto acid ester of the general formula (17).
  • the amount of c- sulfuric acid, which is converted to 3-keto acid in the reaction system is 100 parts by weight of 2,5-disubstituted phenol of general formula (9). Usually 100 to 100 parts by weight, preferably 100 to 500 parts by weight.
  • the reaction temperature is usually in the range of room temperature to 200 ° C., preferably 100 to 160 ° C. This reaction usually completes in 1 to 10 hours.
  • the benzofuran carboxylic acid derivative (20) can be obtained by adding a 6-nitrocoumarin derivative (19) to a halogen and then reacting with a base.
  • a reaction solvent for the addition of halogen for example, dichloromethane, Halogenated hydrocarbons such as rum are used.
  • the amount of the solvent to be used is generally 100 to 500 parts by weight, preferably 200 to 200 parts by weight, per 100 parts by weight of the 6-dicyclomaline derivative of the general formula (19). 0 0 0 parts by weight.
  • the halogen for example, chlorine, bromine, or the like is used.
  • the amount of the halogen is usually 1 to 10 mol, preferably 1 to 1 mol of the 6-nitocumaline derivative (19). ⁇ 3 moles.
  • the reaction temperature can be selected from 0 ° C to the boiling point of the solvent, but it is usually preferable to carry out the reaction within the range of 0 to 50 ° C. This reaction usually completes in 1 to 50 hours.
  • a benzofurancarboxylic acid derivative (20) is obtained.
  • alcohol solvents include methanol, ethanol, and 2-prono. Knol and the like.
  • the amount of the alcohol-based solvent to be used is generally 100 to 500 parts by weight, preferably 200 to 500 parts by weight, per 100 parts by weight of the halogenated 6-nitrocoumarin derivative.
  • Examples of the aluminum hydroxide which is 200 parts by weight, include sodium hydroxide, potassium hydroxide, and the like. It is usually 3 to 30 mol, preferably 3 to 12 mol, per 1 mol of the trokumalin derivative.
  • the reaction temperature can be selected from 0 ° C to the boiling point of the solvent, but it is usually 0 to 5 It is preferable to carry out within the range of 0 ° C. This reaction is usually completed in 1 to 30 hours.
  • the benzofurancarboxylic acid derivative (20) is decarboxylated in a quinoline solvent by the action of a copper catalyst to give the 5-nitrobenzofuran derivative (2c).
  • the amount of quinoline used is usually 100 to 200 parts by weight, preferably 100 to 500 parts by weight, per 100 parts by weight of the benzofurancarboxylic acid derivative (20). It is.
  • the amount of the copper catalyst to be used is generally 0.05 to 10 mol, preferably 0.1 to 1 mol, per 1 mol of the benzofuran canolevonic acid derivative (20).
  • the copper catalyst can be used in various forms such as powder and granules, but is preferably used in powder form.
  • the reaction temperature is usually preferably in the range of 150 to 250 ° C. This reaction is usually completed in 0.5 to 10 hours.
  • the 5-nitrobenzofuran derivative represented by the general formula (2) thus obtained is used as an intermediate for producing the compounds of the general formulas (5) and (6). Importantly, it can itself be an intermediate for other pesticides, pharmaceuticals, etc.
  • Table 1 shows specific examples of the compound of the 5-nitrobenzofuran derivative (2), which was synthesized by any one of the methods of Step 1, Reaction Scheme 4, 5, and 6 of Reaction Scheme 13 above. . 1>
  • the 5-aminobenzobenzofuran derivative of the general formula (3) reduces the corresponding 5-dibenzobenzofuran derivative of the general formula (2) It is manufactured by this.
  • various methods for reducing a nitro group to an amino group for example, reduction of a nitro group using a metal noic acid, a metal hydride, a metal hydride complex compound, hydrazine, etc. Or the catalytic reduction method can be applied.
  • the reduction method using metal Z-acid is excellent in terms of industrial use from the viewpoint that inexpensive reagents can be used and no special equipment is required.
  • the reaction solvent is water; methanol, ethanol, or 2-prono.
  • examples include alcohol solvents such as ethanol; ether solvents such as tetrahydrofuran and dioxane; ester solvents such as ethyl acetate; acetic anhydride; and acetate.
  • alcohol solvents such as ethanol
  • ether solvents such as tetrahydrofuran and dioxane
  • ester solvents such as ethyl acetate
  • acetic anhydride acetic anhydride
  • acetate acetate
  • these solvents can be used alone or in combination of two or more.
  • a mixed solvent of alcoholic solvent and water is mentioned, and the mixing ratio is usually 1/1/10 to 10Z1, preferably IZSSZI.
  • the amount of the solvent to be used is as follows: 100 parts by weight of the 5-dibenzobenzofuran derivative of the general formula (2), usually 200 to 1000 parts by weight, preferably Is preferably 500 to 500 parts by weight.
  • the acid mineral acids such as hydrochloric acid and hydrobromic acid; and organic acids such as acetic acid are used. These acids may also be used as solvents.
  • the amount of the acid to be used is generally 0.5 to 100 mol, preferably 1.0 to 20 mol, per 1 mol of the 5-to-2-benzobenzofuran derivative of the general formula (2). Is good.
  • the metal include iron, zinc, and tin
  • examples of the metal salt include iron sulfate (11) and tin (II) chloride hydrate.
  • the amount of the metal or salt thereof to be used is generally 1.0 to 50 mol, preferably 2.0 to 10 mol, per 1 mol of the 5-dibenzobenzofuran derivative (2).
  • the temperature of this reduction reaction is preferably selected from the range of room temperature to the boiling point of the solvent, and is preferably from 50 ° C. to the boiling point of the solvent in view of the reaction time and the yield.
  • the order in which the solvent, substrate, acid and metal are added to the reaction vessel is not particularly limited. Since this reaction is exothermic, to control the reaction temperature and reaction rate, the substrate or metal should be added as a solid or in a solution or slurry using a solvent and then gradually added. You can do it.
  • Examples of a reaction solvent in the catalytic reduction method include methanol, ethanol, and 2-prono.
  • Alcohol solvents such as ethanol, butanol and methyl sorb; ether solvents such as getyl ether and tetrahydrofuran; cyclohexane, benzene Hydrocarbon solvents such as chlorofonolem, dichloroethane, cyclobenzene, dichlorobenzen, etc .; Any ester solvents and the like can be mentioned.
  • Preference is given to methanol, 2-propanol, tonolene, black mouth benzene, and the like.
  • the amount of the solvent used may be 5—nitrobenzene zofuran derivative (2), usually 100 to 100 parts by weight per 100 parts by weight, preferably 5 to 500 parts by weight.
  • the content is preferably from 0 to 500 parts by weight.
  • catalyst used in the catalytic reduction those widely known in the art can be widely used, such as Raney alloy, Raney catalyst, activated carbon-supported palladium, silica-supported palladium, and aluminum.
  • active Palladium on charcoal and platinum sulfide on activated carbon are listed.
  • the amount of these catalysts used is usually 0.0005 to 5 mol, preferably 1 mol, of 5-nitrobenzofuran derivative (2). 0.005 to 0.5 mol, for other catalysts, 5—2-benzobenzofuran derivative (2) Usually 0.000 to 0.05 to 0. It is preferably 5 moles, preferably 0.005 to 0.05 moles.
  • the temperature of the above reduction reaction can be appropriately selected from the range of 0 to 200 ° C, and preferably, the temperature is from room temperature to 100 ° C, in view of the reaction time and the yield. Preferred from. Further, the reduction reaction can be carried out at a hydrogen pressure of 1 to 300 kg / cm 2 . From the viewpoint of reaction time and yield, it is preferable to carry out the reaction in the range of 2 to 20 kg / cm 2 .
  • the 5-aminobenzobenzofuran derivative (3) can also be produced by a method other than the step 2 shown in Reaction Formula 13.
  • the 5-amino benzofuran derivative (3) can be produced by following the methods shown in the following reaction formulas -7 and -8.
  • the 4-substituted phenol derivative (13) obtained by di- or di-torosification of the tri-substituted phenol form (12) is a 4-to-12-phenol derivative (13 )
  • 4-nitrosophenol derivative (21) reduces to 4-aminophenol.
  • the derivative (22) is obtained, and the 4-aminophenol derivative (22) is heated in an acidic solution to give the 5-aminobenzobenzofuran derivative (3).
  • b) or a salt thereof is obtained.
  • Nitrosation of the trisubstituted phenol form (12) to a 412 torosophenol derivative (21) is carried out using nitrite and an acid.
  • the nitrite include sodium nitrite and potassium nitrite.
  • the amount of nitrite to be used is generally 1 to 10 mol, preferably 1 to 3 mol, per 1 mol of the trisubstituted phenol compound (12).
  • As the acid for example, hydrochloric acid, acetic acid or the like is used, and these can also serve as a solvent.
  • the amount of the acid to be used is generally 1 to: 100 mol, preferably 2 to 10 mol, per 1 mol of the trisubstituted phenol compound (12). May be used in larger quantities.
  • reaction solvent examples include phenol-based solvents such as methanol, ethanol, and 2-propanol; water; and the amount of tri-substituted phenol.
  • phenol-based solvents such as methanol, ethanol, and 2-propanol
  • water water
  • the amount of tri-substituted phenol usually 100 to 500 parts by weight, preferably 100 to 2000 parts by weight, per 100 parts by weight of the body (12). You. This reaction is usually carried out at a temperature of from 30 to 50 ° C, preferably at a temperature of 0 ° (: to room temperature.)
  • the reaction proceeds quickly after the addition of the reagents (nitrite and acid). Usually, it is preferable to react for about 0.5 to 10 hours after the introduction of the reagent.
  • the reduction of the 4—nitrophenol derivative (13) force to the 4—aminophenol derivative (22) is achieved by the reaction of 5—nitro in Reaction Scheme 13.
  • the reaction can be carried out under the same reaction conditions as in the reaction (step 2) for reducing the benzofuran derivative (2) to the 5- (aminobenzofuran derivative (3).
  • the reduction of the 42-nitrophenol derivative (21) to the 41-aminophenol derivative (22) is carried out by the reaction of 5-5-nitrobenzene in Reaction Formula 13
  • the same reaction conditions as in the reaction (Step 2) for the reduction of the benzofuran derivative (2) to the 5-amino benzobenzofuran derivative (3) can be used, and the same reducing agent is used.
  • the amount used may be two-thirds of the reducing agent used in the step 2.
  • the 4—aminophenol derivative (22) is ring-closed in a suitable solvent in the presence of an acid to give the 5—aminobenzofuran derivative (3b).
  • the acid include mineral acids such as hydrochloric acid and hydrobromic acid.
  • the amount of the acid to be used is usually 0.5 to: L00 mol, preferably 1 to 20 mol, per 1 mol of the -aminophenol derivative (22), Instead of these mineral acids, hydrogen chloride, hydrogen bromide, etc. may be added to the reaction system.
  • Solvents include carboxylic acids such as acetic acid; methanol, 2-proha. Alcohols such as ethanol; water and the like; these may be used alone or as a mixture of two or more.
  • the amount of the solvent used is usually from 100 to 500 parts by weight, preferably from 100 to 100 parts by weight, per 100 parts by weight of the 4-aminophenol derivative (22). 0 parts by weight.
  • the reaction temperature is usually preferably in the range from room temperature to the boiling point of the solvent. This reaction is usually completed in 1 to 100 hours.
  • the protecting group for the amino group of the 2,5-disubstituted-41-aminophenol derivative (23) is not limited to the acetyl group, but may be a honoleminole group or a chloroacetyl group.
  • Various commonly used protecting groups such as trichloroacetyl group, benzoyl group and the like can be used.
  • the 2,5-disubstituted-41-aminophenol derivative (23) is reacted with an acetylating agent in a solvent to form an acetoanilide derivative (24). Is obtained.
  • the reaction conditions for normal N-acetylation can be widely applied.
  • the acetylating agent those conventionally known can be widely used, and examples thereof include acetic anhydride, acetic halide, and acetic ester.
  • the amount of the acetic anhydride used is based on 1 mol of the 2,5-disubstituted-4-aminophenol derivative (23).
  • the solvent for example, aromatic solvents such as benzene, toluene, and benzene are preferable.
  • the amount of the solvent to be used is generally 100 to 500 parts by weight, preferably 100 to 500 parts by weight of 2,5-disubstituted-41-aminophenol derivative (23). H is 20 0 to 2000 parts by weight.
  • the reaction temperature is usually preferably in the range from room temperature to the boiling point of the solvent. This reaction usually completes in 1 to 50 hours.
  • ⁇ -Haloketone (25) is, for example, 3—Black mouth 2—Butanone, 3—Black mouth 2—Pentanone, 2—Black mouth 1— Pentannone and the like can be used in an amount of usually 0.5 to 10 mol, preferably 1 to 3 mol, per 1 mol of the acetoanilide derivative (24). is there.
  • the solvent include non-protonic polar solvents such as aceton, acetonitril, and dimethylformamide; ethers such as getylether and tetrahydrofuran; And the like.
  • the amount of the solvent used is usually 100 to 200 parts by weight per 100 parts by weight of the acetoanilide derivative (24), preferably 200 to 100 parts by weight. 0 parts by weight.
  • the base include carbonates such as potassium carbonate and sodium carbonate; hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide; Tertiary amines such as triethylamine, pyridin and triethylene diamine; sodium hydride; metal hydrides such as calcium hydride;
  • the amount of the base used is usually determined by deriving the acetate hydride of the general formula (24). It is usually 0.5 to 50 equivalents, preferably 1 to 10 equivalents, relative to the conductor.
  • the reaction temperature is usually preferably in the range from room temperature to the boiling point of the solvent. The reaction usually completes in 1 to 100 hours.
  • a benzofuranylamide derivative (27) is obtained by ring-closing the 3-ketoether derivative (26) in a solvent in the presence of an acid.
  • Concentrated sulfuric acid is preferable as the acid and the solvent, and the amount of the sulfuric acid used is usually from 100 to 500,000 parts by weight per 100 parts by weight of the / 3-ketoether derivative (26). Or 2000 to 2000 parts by weight.
  • the reaction temperature is preferably in the range of 0 to 150 ° C. This reaction is usually completed in 1 to 20 hours.
  • a 5-aminobenzobenzofuran derivative (3) is obtained.
  • the polar solvent include alcohol solvents such as methanol, ethanol, and 2-propanol, and water, and these may be used alone or in combination of two or more. it can.
  • the amount of the solvent used is generally 100 to 100,000 parts by weight, preferably 500 to 500 parts by weight, per 100 parts by weight of the benzofuranylamide derivative of the general formula (27). 0 parts by weight.
  • the base for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide are preferable. Better.
  • the amount of base used is benzofuranylamide derivative
  • reaction temperature is usually in the range of room temperature to the boiling point of the solvent. Heating is preferred to shorten the reaction time. This reaction is usually completed in 1 to 50 hours.
  • the thus obtained 5-amino benzofuran derivative of the general formula (3) is important as an intermediate for producing the compounds of the general formulas (5) and (6). It can itself be an intermediate for other pesticides, medicines and the like.
  • Table 2 shows specific examples of the 5-amino benzofuran derivative (3) obtained by the reaction of any one of Step 2, Reaction Formula 17 and Reaction Formula 18 in Reaction Formula 13. Table 2>
  • the benzofuranilyso (thio) cyanate derivative of the general formula (4) can be converted to Alternatively, it is produced by reacting with thiophosgene.
  • benzo in which Y is an oxygen atom
  • the furanyl isocyanate derivative is produced by reacting the corresponding 5-aminobenzofuran derivative (3) with phosphene, phosgene dimer or phosgene trimer.
  • the benzofuranilusisothiocyanate derivative in which Y is a sulfur atom is a thiophosgene in the corresponding 5-aminoaminobenzofuran derivative (3). It is produced by reacting
  • the reaction solvent that can be used in this reaction is not particularly limited as long as it is inactive under the reaction conditions, but specific examples include dichloromethane and chloroform.
  • Halogenated hydrocarbon solvents such as honolem, dichloroethane, and chlorobenzene; hydrocarbon solvents such as n-hexane, cyclohexane, benzene, and toluene; Examples include ester solvents such as ethyl acetate and water.
  • preferred solvents are dichloromethane, dichloroethane, toluene, ethyl acetate and the like. These solvents are used alone or in combination of two or more.
  • the amount of the solvent to be used is preferably from 200 to 100,000 parts by weight per 100 parts by weight of the 5- (aminobenzobenzofuran derivative) of the general formula (3), and is preferably used. Is preferably from 500 to 300 parts by weight.
  • Phosgene and tiophosgene also include these equivalents, for example, trichloromethanetinolechlorohonolate, Phosgene and the like can be mentioned.
  • the use ratio of the 5-aminobenzofuran derivative (3) and phosgene or tiophosgene is not particularly limited, but the latter is usually 0.5 equivalent to 1 equivalent of the former. ⁇ 2 equivalents, preferably 0.1 to 1.5 equivalents.
  • a base is not required, and the 5-aminobenzobenzofuran derivative (3) and phosgene or its equivalent may be heated in the presence of a solvent.
  • the reaction using thiophosgene is preferably performed in the presence of a base.
  • a base conventionally known bases can be widely used.
  • alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and the like, or sodium carbonate
  • alkali metal carbonates such as lime and potassium carbonate
  • tertiary amines such as triethylamine and pyridin.
  • it is an aqueous solution of an alkali metal hydroxide.
  • the concentration varies depending on the type of the base, but is usually 1 to 50% by weight, preferably 5 to 25% by weight. Good to use.
  • the amount of the base to be used is generally 1-10 mol, preferably 2-5 mol, per 1 mol of 5-aminobenzobenzofuran derivative (3). This reaction can be performed at a reaction temperature of 0 to 50 ° C.
  • Examples of the solvent used in the reaction to produce dithiocarbamate include hydrocarbon solvents such as benzene, tonolene, cyclohexane, and n-hexane; dichloromethan; Halogenated hydrocarbons such as chlorofluoronom, chlorochloroethane, trichloromethane, crozen benzene, crozen toluene, etc.
  • Medium Ether solvents such as ethynoleate and tetrahydrofuran, etc.
  • hydrocarbon solvents are preferable. These solvents can be used alone or in combination of two or more.
  • the amount of the solvent used is usually from 100 to 400 parts by weight, preferably from 200 to 100 parts by weight, based on 100 parts by weight of the 5-aminobenzobenzofuran derivative of the general formula (3). It is about 2000 parts by weight.
  • Examples of usable bases include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; sodium acetate, potassium acetate and the like. Acetates such as uranium; triethinoreamin, trimethinoreamin, diisopropyretinoreamin, 1-methinolebiperidine, 1-methinolemonorephorin, 1-methylpyroline , Lysine, 4-dimethinorea minopyridine, 4-pyrrolidinopyridin, 1,4_ diazabisik mouth [2.2.2] octane, 1 , 8 — Jaza Bisikro
  • phase transfer catalyst is preferably present in the reaction system.
  • the phase transfer catalyst include quaternary ammonium salts and quaternary phosphonium salts.
  • Quaternary Ammonium examples of the salt include tetramethylammonium bromide, tetramethyl bromide n-butynoleammonium, tetrachloroammonium n-butylammonium, and bromide tetrammonium.
  • Examples include butyl ammonium and benzyl triethyl ammonium chloride.
  • Examples of the quaternary phosphonium salts include tetraphenylphosphonium bromide, tetraphenylphosphonium chloride, methyltriphenylphosphonium bromide, and chloride chloride. Tetra-n-butylphosphonium etc. can be exemplified.
  • the amount of the base to be used is generally about 1 to 20 mol, preferably about 1 to 5 mol, per 1 mol of the 5-amino benzofuran derivative of the general formula (3).
  • the amount of carbon disulfide to be used is generally about 1 to 20 mol, preferably about 1 to 5 mol, per 1 mol of the 5-amino benzofuran derivative (3).
  • This reaction is usually performed at a temperature in the range of 0 to 50 ° C, and is generally completed in about 1 to 20 hours.
  • Solvents that can be used include, for example, cyclohexane, Hydrocarbon solvents such as toluene and toluene; halogenated hydrocarbon solvents such as dichloromethane, chlorophorenolem, dichloroethane, trichloroethane, and chlorobenzene; methanol Le, ethanol, 2-prono. And alcohol-based solvents such as ethanol; water and the like. Of these, halogenated hydrocarbon-based solvents are preferred.
  • the amount of the solvent to be used is generally about 200 to about 200 parts by weight, preferably about 500 to about 100 parts by weight, based on 100 parts by weight of the dithiolamine derivative salt.
  • halogen-based oxidizing agent examples include alkyl carbonates such as methyl methyl carbonate and potassium ethyl carbonate; phosgene, oxalyl chloride, sodium hypochlorite, and the like. However, among them, black carbonate alkyl esters are preferred.
  • the amount of the halogen-based oxidizing agent to be used is generally 1 to 10 mol, preferably 1 to 3 mol, per 1 mol of the dithiol rubbamate derivative salt.
  • This reaction is usually carried out at a temperature in the range of 0 to 50 ° C, and is generally completed in about 1 to 10 hours.
  • the halogenated oxidizing agent is added to the reaction solution without isolating the salt of the dithiocarboxylic acid derivative from the inside of the reaction system, whereby the compound represented by the general formula (4) is obtained.
  • Benzofuranyi sothiocyanate derivative where Y is a sulfur atom Can be obtained all at once.
  • Table 3 shows specific examples of the benzofuraniluiso (thio) cyanate derivative (4) obtained by step 3 of Reaction formula-3.
  • CH 3 is ° -C 3 H 7 CH 3
  • R 8 represents a lower alkyl group.
  • the reaction solvent that can be used in this reaction is not particularly limited as long as it is inert under the reaction conditions, and, specifically, dichloromethane, Halogenated hydrocarbon solvents such as chloro-honolem, dichloroethane, and black benzene, and aromatics such as n-hexane, cyclohexane, benzene, tonolenene Group hydrocarbon solvents and the like.
  • the amount of the solvent used is preferably from 200 to 100,000 parts by weight, per 100 parts by weight of the benzofuranyliso (thio) cyanate derivative of the general formula (4).
  • the amount is preferably 500 to 300 parts by weight.
  • alkyl hydrazine of the general formula (28) conventionally known alkyl hydrazines can be widely used, and examples thereof include methyl hydrazine, ethynole hydrazine, ⁇ -propynole hydrazine, Isopropynolehydrazine, n-butylhydrazine and the like.
  • the phenolic hydrazine (28) may not contain water, or may be in the form of an aqueous solution.
  • the use ratio of the benzofuranyliso (thio) cyanate derivative of (4) and the alkyl hydrazine of the general formula (28) is not particularly limited but is within a wide range. Although it can be appropriately selected from the above, it is usually preferable that the amount of the latter is 0.8 to 3 moles, preferably 1.0 to 2 moles per mole of the former. This reaction can be performed at a reaction temperature of 0 to 50 ° C.
  • an organic layer obtained by washing and separating the reaction solution of the benzofuraniliso (thio) cyanate derivative (4) produced in Step 3 of Reaction Scheme 13 is directly used in the step. It can also be used for 4.
  • Y is As a method for obtaining a semicarbazide derivative which is an oxygen atom, there is a method via a phenylcaprate derivative (29) (Steps 5 and 5 in Reaction Scheme-3). 6).
  • step 5 of Reaction formula-3 the reaction of 5-aminobenzofuran derivative of the general formula (3) with a phenylcycloformate in the presence of a base yields the general formula It is possible to produce the vinyl acetate derivative of (29).
  • Solvents used in this reaction include, for example, hydrocarbon solvents such as benzene, toluene, cyclohexane and n-hexane; dichloromethane, chloroform Halogenated hydrocarbon solvents such as honolem, dichloroethane, trichloroethane, black benzene, chlorotonolene, etc .; Jethyl ether, tetrahydrofuran Ether solvents such as lan; ester solvents such as ethyl acetate; These solvents can be used alone or in combination of two or more.
  • the amount of the solvent to be used is usually 100 to 400 parts by weight, preferably 200 to 200 parts by weight, per 100 parts by weight of the 5-amino benzofuran derivative (3). It is about 0 parts by weight.
  • Examples of usable bases include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; sodium acetate, and acetic acid. Acetates such as potassium; triethinoreamin, trimethinoreamin, 1-methinoreperi Gin, 1—Methylmonorephorin, 1—Methinolepyrrolidine, 4—Dimethinorea Minopyridine, 41 Pyrrolidinopyridin, 1,4—Zazabicyclo [2. 2.2] octane, 1,8- diazabicyclo [5.4.0] organic base such as indecen-17-ene. These bases can be used alone or in combination of two or more. The amount of the base to be used is generally about 1 to 20 mol, preferably about 1 to 5 mol, per 1 mol of the 5-aminobenzobenzofuran derivative (3).
  • the amount of phenylcycloform used is usually 1 to 20 mol, preferably about 1 to 5 mol, per 1 mol of the 5-amino benzobenzofuran derivative (3). is there.
  • This reaction is usually performed at a temperature in the range of 0 to 50 ° C, and is generally completed in about 1 to 20 hours.
  • step 6 of Reaction formula-3 by reacting the phenylcarbamate derivative of the general formula (29) with the alkylhydrazine of the general formula (28), In the general formula (5), a semicarbazide derivative in which Y is an oxygen atom is obtained.
  • Solvents that can be used include, for example, hydrocarbon solvents such as cyclohexane, benzene, and toluene; dichloromethane, chlorofluoronom, dichloroethane, and trichloromethane. Halogenated hydrocarbon solvents such as chloroethane and chlorobenzen; Ether solvents such as ether and tetrahydrofuran; ditrino solvents such as acetonitrile; methanol, ethanol, 2-propanol and the like; Alcohol solvents; water and the like.
  • the amount of the solvent used is usually from 100 to 400 parts by weight, preferably from 200 to 200 parts by weight, based on 100 parts by weight of the phenylcarbamate derivative (29). It is about parts by weight.
  • the amount of the alkynolehydrazine (28) to be used is generally 1 to 10 mol, preferably 1 to 5 mol, per 1 mol of the phenyl carbamate derivative.
  • This reaction is usually carried out within a range of room temperature to the boiling point of the solvent, and is generally completed in about 1 to 30 hours.
  • Step 7 of Reaction formula-3 the benzofuranylthiosemicarbazide derivative (5b) in which Y is a sulfur atom in the general formula (5) is converted into an inert solvent in the presence of a base.
  • Y is a sulfur atom in the general formula (5)
  • a base By reacting with trifluoroacetic acid alkyl ester, it is possible to obtain a benzofuran-l-oxotoxytriazole derivative (6b) in which Y is a sulfur atom in the general formula (6). .
  • Solvents that can be used in this reaction include, for example, alcoholic solvents such as methanol, ethanol, 2-prono, and 0 -nor; carbonized solvents such as cyclohexane, benzene, and toluene. Hydrogen solvents; dichloromethane, chlorophonolem, dichloroeta Halogenated hydrocarbon solvents such as benzene, trichloroethane, and chlorobenzene.
  • the amount of the solvent used is generally 100 to 200 parts by weight based on 100 parts by weight of the benzofuranylthiosemicarbazide derivative (5b) in which Y is a sulfur atom in the general formula (5). It is preferably about 200 to 100 parts by weight.
  • Bases that can be used in this reaction include, for example, alkali metal alcoholates such as sodium methoxide and potassium ethoxide; and alkali metals such as sodium hydroxide and potassium hydroxide.
  • alkali metal hydroxides alkaline metal hydroxides such as calcium hydroxide and magnesium hydroxide; and the like.
  • the amount of the base to be used is generally about 2 to 10 mol, preferably about 0.5 to 3 mol, per 1 mol of the benzofuranylthiosemicarbazide derivative (5b).
  • trifluoroacetic acid alkyl ester those conventionally known can be widely used.
  • methyl trifluoroacetate, ethyl tritrifluoroacetate, etc. are preferred.
  • the amount of the alkyl trifluoroacetate to be used is generally 1 to 10 mol, preferably 1 to 3 mol, per 1 mol of the benzofuranylthiosemicarbazide derivative (5b).
  • This reaction is usually performed in the range of room temperature to the boiling point of the solvent, Generally, it is completed in about 0.5 to 10 hours.
  • step 7 of Reaction Formula 13 from the semicarbazide derivative in which Y is an oxygen atom in the general formula (5), a benzofurantrile in which Y is an oxygen atom in the general formula (6)
  • a benzofurantrile in which Y is an oxygen atom in the general formula (6) In producing the azole derivative, for example, known methods described in JP-A-8-20583, JP-A-917583, and the like can be employed. That is, by heating a semicarbazide derivative in which Y is an oxygen atom in the general formula (5) in trifluoroacetic anhydride, Y should be an oxygen atom in the general formula (6). Nzofuranyl triazole derivatives can be produced.
  • a catalyst such as Lewis acids such as titanium tetrachloride, organic acids such as p-toluenesulfonic acid, and inorganic acids such as concentrated sulfuric acid.
  • the amount of the catalyst used is usually from 0.0001 to 10 mol, preferably from 0.01 to 1 mol, per mol of the semicarbazide derivative in which Y is an oxygen atom in the general formula (5). It may be 1 mole.
  • the reaction conditions such as the amount of trifluoroacetic anhydride used, the heating temperature and the time may be the same as those described in the above patent publication.
  • the reaction product obtained in each of the above reactions is isolated and purified from the reaction mixture by ordinary isolation and purification means.
  • isolation and purification means include, for example, extraction, filtration, distillation, and power.
  • Ram chromatograph etc. can be mentioned.
  • the benzene derivative (1), 5-nitrobenzofuran derivative (2), 5-amino benzobenzofuran derivative (3) and benzofuraniliso (chio) cyanate derivative (5) obtained above 4) is a benzofuran (thio) semicarbazide derivative of the general formula (5) and an intermediate for producing a benzofuranyl triazole derivative of the general formula (6) useful as a herbicide. However, it can also be an intermediate for other pesticides, medicines, etc. by itself.
  • the procedure of Example 1 was repeated except that acetic acid was used, to give 1.49 g of acetonoxime 0- (2-bromo-5-methyl_412-nitrophenyl) ether (1.49 g, yield 55%). %, Purity 95%).
  • 2-Prono2 was cooled in a 100 ml eggplant flask. Take 10 ml of the paste, and dissolve 1.10 g (30 mmol) of hydrogen chloride gas. To this solution was added 2.42 g (10 millimoles) of acetonoxime di- (2-cyclomethyl-5-methinole-4-nitrophenyl) ether, and the mixture was heated under reflux for 8 hours. After cooling the reaction mixture, the crude product was collected by filtration, washed twice with 20 ml of 2-propanol, twice with 30 ml of water, and once with 20 ml of 2-propanol.
  • Bromine was added to a solution of 5,8-dimethysol 6-nitrocyclomalin 2.19 g (10 mimol) obtained in [I] and 20 ml of 20 ml of cross-linked form. 4 g (15 mmol) was added little by little and stirred at room temperature for 1 day. Add 4% of 20% sodium sulfite aqueous solution, stir for 30 minutes, and then close the mouth form 30 m 1 was added, and the organic layer was washed with water. The organic layer was dried over magnesium sulfate, filtered, and evaporated under reduced pressure. When 5 ml of ethanol was added, a solid precipitated and became slurry.
  • the filtrate was separated, and the organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and filtered.
  • the organic layer was concentrated under reduced pressure, and n-hexane was added before drying to dryness.
  • the precipitated solid was filtered by suction, washed with n-hexane, and washed with 4—amino 2— (2—clo 5.60 g (yield 87%) of a yellow solid of 1 2 -propinole 1, 3,6 -dimethylphenol was obtained.
  • the benzene derivative represented by the general formula (1) and the benzofuran derivative represented by the general formulas (2), (3) and (4) of the present invention are represented by the general formula (5) And a benzofuranyltriazole derivative of the general formula (6), which are useful as intermediates for industrially advantageous production of the (thio) semicarbazide derivative represented by .
  • a method for producing a benzofuranyloxo-triazole derivative (6b) wherein Y is a sulfur atom does not require the use of trifluoroacetic anhydride, so that highly corrosive trifluoroacetic acid is not generated and trifluoroacetic acid remaining in the final reaction is not collected and discarded.
  • This method is useful in that it does not have the drawbacks of the conventional method that it does not work.

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Abstract

Cette invention concerne des composés qui sont utiles comme produits intermédiaires dans la production industrielle et à faible coût de dérivés de (thio)semicarbazides utilisés comme mélanges de base pour les herbicides. Ces dérivés de benzène et ces dérivés de benzofurane correspondent respectivement aux formules générales (I) et (II) où R1 et R2 peuvent être identiques ou différents et représentent chacun halogéno, un alkyle inférieur, un haloalkyle inférieur, un alcoxy inférieur ou cyano. R4 représente un alkyle inférieur tandis que R3 et R5 peuvent être identiques ou différents et représentent chacun hydrogène ou un alkyle inférieur. Z représente enfin nitro, amino ou un groupe YCN dans lequel Y représente soufre ou hydrogène.
PCT/JP1998/001618 1997-04-11 1998-04-08 Derives de benzene, derives de benzofurane et procedes de production de ces derives WO1998046561A1 (fr)

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EP1394155A2 (fr) * 2002-08-19 2004-03-03 Bayer Chemicals AG 5-Nitrobenzofuranes

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JP2002504535A (ja) * 1998-02-26 2002-02-12 マサチューセッツ インスティテュート オブ テクノロジー ヒドラジン、ヒドラゾン、ヒドロキシルアミンおよびオキシムの金属−触媒アリール化およびビニル化
JP4647780B2 (ja) * 1998-02-26 2011-03-09 マサチューセッツ インスティテュート オブ テクノロジー ヒドラジン、ヒドラゾン、ヒドロキシルアミンおよびオキシムの金属−触媒アリール化およびビニル化
EP1394155A2 (fr) * 2002-08-19 2004-03-03 Bayer Chemicals AG 5-Nitrobenzofuranes
EP1394155A3 (fr) * 2002-08-19 2004-03-24 Bayer Chemicals AG 5-Nitrobenzofuranes
US6984741B2 (en) 2002-08-19 2006-01-10 Bayer Aktiengesellschaft 5-Nitrobenzofurans

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