WO2006118155A1 - Biphenyl derivative or salt thereof, and bactericide for agricultural and horticultural use containing same as active ingredient - Google Patents

Biphenyl derivative or salt thereof, and bactericide for agricultural and horticultural use containing same as active ingredient Download PDF

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Publication number
WO2006118155A1
WO2006118155A1 PCT/JP2006/308764 JP2006308764W WO2006118155A1 WO 2006118155 A1 WO2006118155 A1 WO 2006118155A1 JP 2006308764 W JP2006308764 W JP 2006308764W WO 2006118155 A1 WO2006118155 A1 WO 2006118155A1
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group
substituted
alkyl
formula
halogen
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PCT/JP2006/308764
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French (fr)
Japanese (ja)
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Shigeru Mitani
Hitoshi Nakayama
Koji Sugimoto
Munekazu Ogawa
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Ishihara Sangyo Kaisha, Ltd.
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Publication of WO2006118155A1 publication Critical patent/WO2006118155A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
    • C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C07C233/15—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/90—Carboxylic acid amides having nitrogen atoms of carboxamide groups further acylated
    • C07C233/92—Carboxylic acid amides having nitrogen atoms of carboxamide groups further acylated with at least one carbon atom of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08—Hydroxylamino compounds or their ethers or esters
    • C07C239/14—Hydroxylamino compounds or their ethers or esters having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms

Definitions

  • the present invention relates to an agricultural and horticultural fungicide containing a novel biphenyl derivative or a salt thereof as an active ingredient.
  • Known agricultural and horticultural fungicides having a biphenyl structure include those described in European Patent Publication No. 101 0690, which may be branched between a biphenyl group and a substituted amino group. Since it has C alkylene, its chemical structure is different from the compound of the present invention.
  • Patent Document 1 European Published Patent Publication No. 1010690
  • Patent Document 2 International Publication WO05Z44007
  • halogen atom contained in the formula (I) fluorine, chlorine, bromine or iodine is used.
  • fluorine, chlorine or bromine is used.
  • alkyl moiety contained in the formula (I) examples include C alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tbutyl.
  • alkoxy moiety contained in the formula (I) examples include C alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like.
  • alkell moiety contained in the formula (I) examples include C alkell such as bulle, valyl, isopropyl and 3-methyl-2-butyr.
  • alkyl moiety contained in the formula (I) examples include C alkyl such as ethynyl, 1-propyl, 2-propyl (propargyl) and the like.
  • Examples of the cycloalkyl contained in the formula (I) include c cycloalkyl such as cyclopropyl, cyclopentyl, cyclohexyl and the like.
  • the aryl part contained in the formula (I) is, for example, a C aryl such as a file or naphthyl.
  • examples of the heterocyclic moiety contained in the formula (I) include pyridyl, chael, fuller, thiazolyl and the like.
  • examples of the substituent of the substitutable filer and the substitutable heterocycle included in the formula (I) include halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and the like.
  • the biphenyl derivative represented by the formula (I) or a salt thereof exhibits an excellent effect as an active ingredient of an agricultural and horticultural fungicide.
  • the compound of the formula (I) or a salt thereof can be produced by various known synthesis methods using characteristics based on the basic skeleton or the type of substituent.
  • a substituent such as an amino group, a hydroxyl group, or a carboxyl group
  • the substituent is protected with an appropriate protecting group at the stage of the raw material or intermediate, or the substituent can be easily added.
  • Substitution with a convertible substituent group may enable efficient production.
  • Examples of the protecting group described above include the protecting groups described in Examples X ⁇ i, .W. Greene, P.tj.M.Wuts, Protective Groups in urganic Syntnesis (3rd Edition, 1999).
  • a desired compound can be obtained by carrying out a reaction using the protecting group and then removing the protecting group or converting to a desired group as necessary. it can.
  • the method using a protecting group can be carried out by applying methods well known by those skilled in the art, such as ordinary hydrolysis, esterification, amidation, dehydration, diazotization, oxidation and the like.
  • the compound of formula (I) is obtained by coupling a compound of formula (II) and a compound of formula (III) in the presence of a suitable transition metal catalyst, or by formula (VII) And a compound of formula (VI) can be produced by coupling in the presence of a suitable transition metal catalyst.
  • the reaction can be carried out by a known method (for example, 5th edition, Experimental Chemistry Course 18—Synthesis of Organic Compounds VI, pp.327-352 “Section 3.2 Cross Coupling Reaction” (Maruzen), Comprehensive Organic Synthesis, Volume 3, 481,1991 or Synthetic Communications, Volumell, 513, 1981 etc.).
  • the leaving group represented by L in formula (II) or formula (VII) includes halogen, trifluoromethanesulfo-loxy isotonic as a metal represented by M in formula (III) or formula (VI) Examples thereof include magnesium halide, zinc halide, alkyl tin, alkyl silicon, alkoxy silicon, silicon halide, alkyl aluminum, and aluminum halide.
  • the transition metal catalyst used in the reaction means a transition metal compound or a complex of a transition metal compound and an arbitrary ligand.
  • palladium-carbon Pd / C
  • tetra Kis triphenylphosphine
  • bis dibenzylideneacetone
  • tris dipalladium (0)
  • palladium acetate II) triphenylphosphine
  • palladium (II) acetate Tricyclohexylphosphine
  • dichloropalladium (II) -ethylenediamine- ⁇ , ⁇ , ⁇ ', ⁇ '-tetraacetic acid palladium (II) bis (dicyclohexylamine), dichloropalladium ( ⁇ ) - ⁇ , ⁇ '-Bis (dicyclohexylphosphino) pheucene, -Keckel carbon (Ni / C), tetrakis (triphenylphosphine) nickel (0), bis (1,5-cycloo
  • iron and copper catalysts can be used when the power lacks generality and M is magnesium halide.
  • M is magnesium halide.
  • a previously isolated one may be used, or a transition metal compound and a ligand may be mixed in an arbitrary reaction solvent and used without isolation.
  • the transition metal catalyst is used in a proportion of 0.001 to 0.2 equivalents, preferably 0.01 equivalents to 0.1 equivalents, relative to the compound of formula (IV).
  • the reaction is carried out, for example, with ketones such as acetone, methyl ethyl ketone, and cyclohexanone; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4 dioxane, dimethoxetane, and diethylene glycol dimethyl ether; ethyl acetate, acetic acid Esters such as methyl; Ananolones such as methanol, ethanol, n-propanol, and isopropanol; Aromatic hydrocarbons such as benzene, black benzene, nitrobenzene, and tolylene; -Tolyls such as acetonitrile; ⁇ , ⁇ -dimethyl Formamide; ⁇ , ⁇ -dimethylacetamide; ⁇ -methyl-2-pyrrolidone; dimethyl sulfoxide; polyethylene glycols; water or other solvent that does not inhibit the progress
  • the compound of formula (II) or the compound of formula (VII) and the compound of formula (III) or the compound of formula (VI) can be used in an equivalent amount or in excess.
  • the reaction is generally performed in the presence of an appropriate base.
  • bases include alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate; sodium hydroxide , Alkaline metal hydroxides such as potassium hydroxide, alkaline earths such as calcium hydroxide Metal hydroxides; Phosphate salts such as potassium phosphate; Inorganic salts such as cesium fluoride and potassium fluoride; Amines such as triethylamine; Pyridines such as pyridine and 4- ( ⁇ , ⁇ -dimethylamino) pyridine Can be mentioned.
  • the base is usually used in a proportion of 1.0 to 20 equivalents, preferably 1.0 to 3.0 equivalents, relative to the compound of formula (II) or the compound of formula (VII).
  • Additives include alkenes such as 1,3-butadiene and aryloxybenzene; inorganic salts such as lithium chloride; quaternary ammonium salts such as tetrabutyl ammonium bromide; 1,4-diazabicyclo And organic bases such as [2,2,2] octane.
  • the additive is used in a proportion of 0.001 to 2 equivalents, preferably 0.01 equivalents to 1 equivalent, relative to the compound of formula (II).
  • the reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used.
  • the reaction time is not constant depending on the reaction temperature, reaction amount, reaction pressure, etc., but generally it can be selected from the range of 1 to 72 hours.
  • a compound of formula (I 1) in which A in formula (I) is a carbonyl group can also be prepared by the following method
  • the compound of the formula (I 1) can be produced by an amidy reaction between the compound of the formula (V) and the compound represented by HNR 2 .
  • the protecting group for the carboxyl group represented by Q in the compound of the formula (V) is preferably an alkyl group, although it may be substituted with a phenyl or pyridyl group.
  • the compound of formula (V) is represented by HNR 2 in the presence of a condensing agent as necessary.
  • a condensing agent examples include dicyclohexyl carbodiimide, diisopropyl carbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and the like.
  • solvents examples include aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as jetyl ether, tetrahydrofuran, 1,4-dioxane, and dimethoxyethane; dichloromethane, 1,2-dichloroethane, and chloroform.
  • Halogenated hydrocarbons such as: alcohols such as methanol and ethanol; ⁇ , ⁇ -dimethylformamide, ⁇ -methyl-2-pyrrolidone, pyridine and the like.
  • two or more kinds of these solvents can be used as a mixed solvent in some cases.
  • the reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used.
  • the reaction time varies depending on the reaction temperature, reaction volume, reaction pressure, etc. Generally, it is only necessary to select a force within the range of 1 to 72 hours.
  • the compound of the formula (I 1) can also be produced by a method using a reactive derivative of the compound of the formula (V) in place of the compound of the formula (V) in the amidation reaction.
  • a reactive derivative of the compound of the formula (V) an acid halide, an acid anhydride, an active ester and the like can be used.
  • the reaction can be performed, for example, according to the method described in “Chemical Experiment Course (4th edition)” edited by The Chemical Society of Japan, 22 (1992) (Maruzen). An example of such a reaction is shown in the following flow.
  • the compound of formula (V) which is the starting material of production method 2 can be produced by the following method.
  • the protective group Q can be applied with the protective group for a carboxyl group described in the above-mentioned ⁇ Protective Groups in Organic Synthesis (3rd Edition, 1999) ''. Or by hydrolysis.
  • a compound in which Q is a hydrogen atom can be prepared by hydrolyzing a compound in which Q is a carboxyl protecting group.
  • the compound of the formula (V) is obtained by coupling the compound of the formula (IV) and the compound of the formula (III) in the presence of a transition metal catalyst, or the compound of the formula (VII) and the compound of the formula (VIII). It can be produced by coupling a compound with a transition metal catalyst.
  • a transition metal catalyst a transition metal compound used in Production Method 1 or a complex of a transition metal compound and an arbitrary ligand can be used.
  • the transition metal catalyst is used in a proportion of 0.001 to 0.2 equivalent, desirably 0.01 equivalent to 0.1 equivalent, relative to the compound of formula (IV) or formula (VII).
  • the reaction may be carried out, for example, with ketones such as acetone, methyl ethyl ketone, and cyclohexanone; ethers such as jetyl ether, diisopropyl ether, tetrahydrofuran, 1,4 dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; Esters such as ethyl and methyl acetate; Alcohols such as methanol, ethanol, n-propanol, and isopropanol; Aromatic hydrocarbons such as benzene, black benzene, nitrobenzene, and toluene; Acetonitrile, etc.
  • ketones such as acetone, methyl ethyl ketone, and cyclohexanone
  • ethers such as jetyl ether, diisopropyl ether, tetrahydrofuran, 1,4 dioxane, dimethoxyethane, and di
  • the compound of formula (IV) or formula (VII) and the compound of formula (III) or formula (VIII) can be used in an equivalent amount or in excess.
  • the reaction in the presence of bases may be advantageous for the smooth progress of the reaction.
  • bases include alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate; , Alkali metal hydroxides such as potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, inorganic salts such as cesium fluoride and potassium fluoride, and amines such as triethylamine And pyridines such as pyridine and 4- ( ⁇ , ⁇ -dimethylamino) pyridine.
  • the base is usually used in a proportion of 1.0 to 20 equivalents, preferably 1.0 to 3.0 equivalents, relative to the compound of formula (IV) or formula (VII).
  • the reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used.
  • the reaction time is not constant depending on the reaction temperature, reaction volume, reaction pressure, etc. Generally, you can select a force ranging from 1 hour to 72 hours.
  • the compound of formula (V-1) when Q is a hydrogen atom can also be produced by the following method.
  • the compound of the formula (V-1) can be produced by acidifying the compound of the formula (XI) by an ordinary method using an oxidizing agent such as manganese diacid and potassium permanganate.
  • the compound of formula (XI) is obtained by coupling a compound of formula (IX) and a compound of formula (III) in the presence of a transition metal catalyst, or a compound of formula (VII) and formula (X).
  • This compound can be produced by the use of force coupling in the presence of a transition metal catalyst. Both coupling reactions can be carried out in the same manner as in Production Method 1 described above.
  • a compound of formula (XV) can be produced by halogenating a compound of formula (V-1). For this reaction, the usual acid halogenated reaction can be applied.
  • This reaction is preferably carried out at a reaction temperature of O to 200 ° C. in the presence or absence of an inert solvent such as dichloroethane.
  • an inert solvent such as dichloroethane.
  • the halogenating agent used in this reaction include a fluorinating agent, a chlorinating agent, and a brominating agent, but a chlorinating agent such as chlorothionyl, oxylin chloride, and chlorooxalyl is used. Hope to do.
  • the compound of formula (I2) can be produced by subjecting the compound of formula (XIV) to a usual reduction reaction such as catalytic reduction or iron reduction.
  • the compound of formula (XIV) is obtained by coupling a compound of formula (XII) and a compound of formula (III) in the presence of a transition metal catalyst, or a compound of formula (VII) and It can be produced by coupling a compound with a transition metal catalyst.
  • the reaction for producing the compound of the formula (XIV) can be carried out according to the reaction described in production method 1. Further, the compound of the formula (XIV) can be subjected to the production reaction of the compound of the formula (I2) with or without isolation and purification.
  • X ′ and ⁇ are each independently a halogen atom; a hydroxyl group; a formyl group; a substituent that is substituted with a norogen, an alkoxy group, or an alkylthio; an alkyl group, a tro group; Group substituted by halogen or alkoxy, alkoxy group substituted by halogen or haloalkyl, aryloxy group; substituted by halogen or haloalkyl, heterocyclic oxy group; substituted by halogen or haloalkyl A heterocyclic group; an alkyl group, an alkyl carbo group; an alkyl carbo group; an alkyl carbo group; an alkylthio group; an alkyl sulpho group; A group; an alkyl sulfier group or an imino group optionally substituted by alkyl or alkoxy ⁇ , is a halogen atom; a formyl group; may be substituted with
  • a ′ is a carbo group; a thio group; an alkylene group or a single bond, R 1 and R 2 are each independently a hydrogen atom; halogen, cycloalkyl, substituted phenyl, substituted heterocycle An alkyl group which may be substituted with alkylthio, alkoxy or cyan; a alkenyl group which may be substituted with norogen, cycloalkyl, fur or cyan; a norogen, cycloalkyl, phenol or cyan May be substituted !, an alkyl group; a cycloalkyl group that may be substituted with halogen or alkyl; Well, alkoxy group; may be substituted with halogen, alkyl or haloalkyl!
  • Aryl group may be substituted with halogen, alkyl or haloalkyl, heterocyclic group; may be substituted with halogen, alkylcarbo -Alkyl group; alkenyl group; imino group; may be substituted with alkyl !, amino group; may be substituted with alkyl !, aminocarbol group; alkylcarbo-lamino group; formyl group or cyano And m and ⁇ are each independently 0, 1, 2, 3 or 4].
  • the biphenyl derivative of the formula (I) is one of the biphenyl derivatives of the formula ( ⁇ ), especially for preventing plant diseases.
  • the present inventors have specifically found a substituent pattern of a compound having an excellent removal effect.
  • the compound of the formula (I ′) is a method according to the compound of the formula (I), that is, in the production methods 1 to 3 described above.
  • the biphenyl derivative represented by the formula (I) or a salt thereof include an agricultural and horticultural fungicide and It is useful as an active ingredient in pest control agents such as Z or antifungal agents, but is particularly useful as an active ingredient in agricultural and horticultural fungicides.
  • Agricultural and horticultural fungicides include, for example, rice blast, sesame leaf blight, coat blight; wheat powdery mildew, red mold, rust, snow rot, naked smut, eye coat disease, leaves Blight, dry blight; citrus sunspot disease, common scab; apple moyulia disease, powdery mildew, spotted leaf disease, black star disease; pear black star disease, black spot disease; peach ash star disease, black star disease, Phomopsis rot; grape black rot, rot, powdery mildew, downy mildew; power anthracnose, leaf deciduous; cucurbit anthracnose, powdery mildew, vine blight, downy mildew Tomato ring mold disease, leaf mold disease, plague; black crab disease of cruciferous vegetables; summer plague of potato; plague; strawberry powdery mildew; gray mold disease of various crops; Although it is effective in controlling diseases, it exhibits excellent control effects especially for powdery mildew and rice blast of wheat
  • Candida It is effective against the genus, Talytococcus, Aspergillus, Staphylococcus and Trichophyton.
  • the compound of the present invention is usually prepared by mixing the compound with various agricultural adjuvants, powder, granules, granule wettable powder, wettable powder, aqueous suspension, oily suspension, aqueous solvent, emulsion, It can be used in various forms such as liquids, pastes, aerosols, microdispersions, etc., but it should be in the form of any formulation that is usually used in the field as long as it meets the purpose of the present invention. Can do.
  • Adjuvants used in the formulation include solid forms such as diatomaceous earth, slaked lime, calcium carbonate, tark, white carbon, kaolin, bentonite, kaolinite and sericite, clay, sodium carbonate, sodium bicarbonate, sodium sulfate, zeolite, starch, etc.
  • Carrier water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, black benzene, cyclohexane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, Solvents such as alcohols; fatty acid salts, benzoates, alkylsulfosuccinates, dialkylsulfosuccinates, polycarboxylic acids, alkyl sulfate esters, alkyl sulfates, alkyl aryl sulfates, alkyl diglycol ether sulfates , Arco Sulfate ester salt, alkyl sulfonate salt, alkyl aryl sulfonate salt, aryl sulfonate salt, ligne sulfonate salt, alkyl diphenyl ether disulf
  • adjuvants can be selected from those known in the art without departing from the object of the present invention.
  • various commonly used adjuvants such as extenders, thickeners, anti-settling agents, antifreezing agents, dispersion stabilizers, safeners, and antifungal agents can also be used.
  • the blending ratio of the compound of the present invention to various adjuvants is generally 0.005: 99.995 to 95: 5, preferably 0.2: 99.8 to 90:10, by weight. In actual use of these preparations, they can be used as they are, or diluted to a predetermined concentration with a diluent such as water, and various spreading agents can be added as necessary.
  • the concentration of the compound of the present invention varies depending on the target crop, method of use, formulation, application rate, etc., and cannot be generally defined. However, in the case of foliage treatment, it is usually 0.1 to 10,000 ppm, preferably L to 2,000 ppm. In the case of soil treatment, it is usually 10 to 100,000 g / ha, preferably 200 to 20,000 g / ha.
  • the compound of the present invention is generally applied for application of its various preparations or dilutions thereof, that is, spraying (eg spraying, spraying, misting, atomizing, dusting, water surface application, etc.) , Soil application (mixing, irrigation, etc.), surface application (application, powder coating, covering, etc.). It can also be applied by the so-called ultra-low-volume spray method. In this method, it is possible to contain 100% of the active ingredient.
  • the compound of the present invention may contain other agricultural chemicals such as bactericides, insecticides, acaricides, nematicides, antiviral agents, attractants, herbicides, plant growth preparations, etc., if necessary. They can be mixed and used together, and in this case, even better effects may be shown.
  • fungicide for example, mepa-pyrim (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (Mepanipyrim), pyrimethanil, cyprozil (
  • Pyridinamine compounds such as Fluazinam; Triadimefon, Bitertanol, Triflumi zole, Etaconazole, Propiconazole, Penconazo, Penconazole, Flusilazole, Micro Butaninole (Myclobutanil), Cyproconazonore (Cyproconazole), Tebuconazonole (Tebuconazole), Hexaconazo Monore (Hexaconazole), Farconazonore (Furconazole-cis), Prochloraz (Prochl oraz), Metoconazonole Epoxy Epoxiconazole), Tetraconazole, Oxpoconazole ftimarate, Sipconazole, Prothioconazole, Triazimenol, Flutriafol, Difeno conazole, Norequinconazole, Fenbuconaz ole, Bromuconazole, Diniconazole, Tricyclazole, Probenazo
  • Dithio carbamate compounds such as Maneb, Zineb, Mancozeb, Polycarbamate, Metiram, Propineb, thiram;
  • Organochlorine compounds such as Fthalide, Chlorothalonil, Quintozene;
  • Imidazole compounds such as Benomyl, Thiophanate-Methyl, Carbendazim, Thiabendazole, Foveriazole, Cyazofamid;
  • Cyanoacetamide compounds such as Cymoxanil
  • Copper-based compounds such as cupric hydroxide and organic copper (Oxine Copper); isoxazole-based compounds such as hymexazol;
  • N-nologenothioalkyl compounds such as Captan, Captafol, Folpet;
  • Dicanolevoxiimide compounds such as Procymidone, Iprodione, Vinclozolin;
  • Benzalide compounds such as Flutolanil, Mepronil, Zoxamid, Tiadinil;
  • Carboxin Carboxin
  • Oxycarboxin Monocarboxin
  • Thifluzamid Thifluzamid (Thifluza mide)
  • MTF-753 Penthiopyrad, Penthiopyrad
  • Boscalid Boscalid
  • Piperazine compounds such as Triforine
  • Pyridine compounds such as Pyrifenox
  • Carbinol compounds such as Fenarimol and Flutriafol
  • Piperidine compounds such as Fenpropidine
  • Morpholine compounds such as Fenpropimorph, Spiroxamine, Tridemorph;
  • Organotin compounds such as Fentin Hydroxide and Fentin Acetate
  • Urea compounds such as Pencycuron
  • Synamic acid compounds such as Dimethomorph, Flumorph; Ferrocarbamate compounds such as Dietofencarb; Cyanopyrrole compounds such as Fludioxonil and Fenpiclonil;
  • Azoxystrobin Kresoxim-Methyl, Metominofen, Trifloxystrobin, Picoxystrobin, Oryzastrobin, Dimoxystrobin (Dimoxystrobin), pyraclostrobin, and strutovirin compounds such as Fluoxastrobin;
  • Oxazolidinone compounds such as Famoxadone
  • Thiazole carboxamide compounds such as ethaboxam
  • Silylamide compounds such as Silthiopham
  • Amino acid amide carbamate compounds such as Iprovalicarb, benchthiavalicar b-isopropyl;
  • Imidazolidine compounds such as Fenamidone
  • Hydoxyxanilide compounds such as fenhexamid
  • Benzenesulfonamide compounds such as Flusulfamid
  • Oxime ether compounds such as cyflufenamid
  • Phenoxy amide compounds such as Fenoxanil
  • Antibiotics such as Noridamycin, Kasugamycin, Polyoxins;
  • Guazine compounds such as iminoctadine
  • pesticides insecticides, acaricides, or nematicides
  • active compound compounds for example, Profenofos, Dichlorvos, Fenamiphos, Fenitr othion, EPN, Diazinon, Chlorpyrifos-methyl, Acephate, Prothiofos, Phoschiazate (Fosthiazate) Organophosphates such as Phosphocarb, Cadusafos, Dislufoton, Chlorpyrifos, Demeton-S-methyl, Dimethhoate, Methamidophos Compounds: Power Barbaryl, Propoxur, Aldicarb, Carboforan, Chi Carnots such as Thiodicarb, Methomyl, Oxamyl (0 xamyl), Ethiofencarb, Pirimicarb, Fenobucarb, Carbosul
  • active compound compounds for example, Profenofos, Dichlorvos, Fenamiphos, Fenit
  • Nereistoxin derivatives such as Cartap, Thiocyclam, Bensultap;
  • Organochlorine compounds such as Dicofol, Tetradifon, Endosulfan;
  • Organometallic compounds such as Fenbutatin Oxide
  • Penolemethrin Permethrin
  • Penolemethrin Permethrin
  • Deltamethrin Cyperme thrin
  • Cyhalothrin Cyhalothrin
  • Teflut hrin Cyhalothrin
  • Ethofenprox Flufenprox
  • Flufenprox Flufenprox Pyrethroid compounds such as Fenpropathrin, Bifenthrin, and Imidate
  • Juvenile hormone-like compounds such as methoprene
  • Pyridazinone compounds such as Pyridaben
  • Pyrazole compounds such as Fenpyroximate, Fipronil, Te bufenpyrad, Ethiprole, Tolfenpyrad, Acetoprole;
  • Hydrazine compounds such as Tebufenozide, Methoxyfenozide, Chromafenozide, Halofenozide; Pyridine compounds such as Pyridaryl, Flonicamid A tetronic acid compound such as Spirodiclofen; a streptavirline compound such as Fluacrypyrin;
  • Dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, hydrazine compounds, and other compounds include Buprofezin, Hexythiazox, Amitraz, Chlorimeform, Silafluofen, Triazamate, Pymetrozine, Pyrimidifen, Chlorfenapyr, Indoxac arb, Acequinocyl, Etoxazole, C ine), 1,3-dichloropropene, 1,3-dichloropropene, Diafenthiuron, Benclothiaz, Flufenerim, Pyridal yl, Spirodiclofen, Bifenazate, spirotetra Pine (spirotetramat), propanoregit (Propargite), benolevbutin (Verbutin), spiromesifen (Spiromesifen), thiazolyl cinano-tolyl (Thiazolylcinnanonitrile), amide-flumeme And compounds such as Amido
  • microbial pesticides such as BT agents, entomopathogenic virus agents, Avermectin, Milbemycin, Spinosad, Emamectin Benzoate, Ivermectin, Lepimectin ), Antibiotics such as Azadirachtin, and natural products such as Rotenone.
  • the ratio of developing solvent is a volume ratio
  • 1H-NMR uses CDC1 as the solvent.
  • N-methyl-3- (2, -chloro-6, -methyl-3, -trifluoromethylphenol) benzamide obtained in Synthesis Example 2 0.2 g in 10 ml of anhydrous tetrahydrofuran at 10 ° C 60% sodium hydride (0.1 lg) was added in several portions, and the mixture was stirred at the same temperature for 10 minutes. Subsequently, 0.14 ml of propargyl bromide was added at 5 ° C, and the mixture was stirred at 15 ° C for 4 hours.
  • the mixture was heated to 60 ° C and stirred at the same temperature for 4 hours. After allowing to cool, the insoluble material was filtered off, and ethyl acetate was added to the filtrate, followed by washing with a 10% aqueous solution of ammonium chloride and then with saturated saline.
  • Table 1 shows the compounds of the formula (I) produced by the method according to Synthesis Examples 1 to 13.
  • Table 2 shows compounds of the formula (V) that are intermediates for producing the compound of the formula (I) produced by the methods according to the synthesis examples 1 to 5, 7 and 12 to 13.
  • Me represents methyl
  • Et represents ethyl
  • n-Pr represents normal propyl
  • c-Pr represents cyclopropyl
  • i-Pr represents isopyl pill.
  • the substitution position of Z in Tables 1 and 2 is represented by the numbers 1 to 6 in the formulas in Table 1.
  • the mp (melting point) in the physical properties column was measured using an automatic melting point measuring apparatus (METTLER FP62 manufactured by METTLER TOLEDO).
  • reaction solution was subjected to silica gel (Kanto Chemical Co., Silica Gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane) to give crude 3-amino- After obtaining 17 g of 2,4-dichlorodibenzotrifluoride, it was purified by distillation under reduced pressure. The boiling point was 72-75 ° CZ4 mmHg.
  • the NMR of this product was as follows.
  • Table 3 shows the compounds of formula ( ⁇ ) produced according to the methods of Reference Example Intermediate Synthesis Examples 1 and 2, the method of Reference Example 1, and the production method described above.
  • Table 4 shows compounds of the formula (V ′) which are intermediates for the production of the compound of the formula ( ⁇ ).
  • Me represents methyl
  • Et represents ethyl
  • n-Pr represents normal propyl
  • i-Bu represents isobutyl
  • c-Pr represents cyclopropyl
  • Pr represents isopropyl.
  • the mp (melting point) in the physical properties column is the automatic melting point. It measured using the measuring apparatus (METTLER FP62 by METTLER TOLEDO).
  • the lesion area, number of lesions or spore formation area is less than 10% of the untreated area 3: Spot area, number of lesions or spore formation area is less than 40% of untreated area 2: Disease area, number of lesions or spore formation area is less than 70% of untreated area 1: Disease area, The number of lesions or sporulation area is 70% or more of the untreated area
  • Test Example 1 Wheat powdery mildew prevention effect test
  • Wheat (variety: Norin 61) was cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution adjusted to a predetermined concentration of the present compound was sprayed with a spray gun. After the chemical solution was dried (on the day of treatment), conidia of powdery mildew fungus were sprinkled and inoculated in a constant temperature room at 20 ° C. The spore formation area was investigated 6 to 7 days after the inoculation, and the control index was determined according to the above evaluation criteria.
  • Test Example 2 Test for prevention of mildew powdery mildew
  • Cucumbers (variety: Sagamihanjiro) were cultivated in a plastic pot with a diameter of 7.5 cm, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution prepared by adjusting the compound of the present invention to a predetermined concentration was sprayed with a spray gun. After the chemical solution was dried (on the day of treatment or the next day), a conidial spore suspension of powdery mildew and powdery mildew was sprayed and kept in a constant temperature room at 20 ° C. The spore formation area was investigated 6 to 7 days after the inoculation, and the control index was determined according to the above evaluation criteria.
  • Rice (variety: Nipponbare) was cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution prepared by adjusting the compound of the present invention to a predetermined concentration was sprayed with a spray gun. After the drug solution was dried (on the day of treatment or the next day), a conidial spore suspension of blast fungus was spray-inoculated, kept in an inoculation box at 20 ° C for 24 hours, and then kept in a constant temperature room at 20 ° C. The number of lesions was investigated 6 to 11 days after the inoculation, and the control index was determined according to the above evaluation criteria. As a result, 1-2, 1-21 and 1-62 in the compound showed an effect of controlling the control index of 4 or more at 400 ppm.
  • the above is uniformly mixed to form a powder.
  • the mixture of the above components and the compound of the present invention are mixed at a weight ratio of 4: 1 to obtain a wettable powder.
  • the above is uniformly mixed and pulverized to obtain an aqueous suspension.
  • the compound of the present invention has an excellent effect for controlling plant pathogens and can be used as a bactericidal agent for agricultural and horticultural use.
  • the entire contents of the specification, claims, drawings, and abstract of Japanese Patent Application No. 2005-129320 filed on April 27, 2005 are hereby incorporated herein by reference. As it is incorporated.

Abstract

Disclosed is a bactericide for agricultural and horticultural use having a high and stable plant disease control effect. Specifically disclosed is a biphenyl derivative represented by the formula (I) below or a salt thereof. (I) (In the formula, X and Y1 independently represent a halogen atom, an alkyl group or the like; Y2 represents a haloalkyl group, a haloalkoxy group or a bromine atom; Z represents a halogen atom, a formyl group or an alkyl group which may be substituted by a halogen; A represents a carbonyl group, a thiocarbonyl group or a single bond; R1 and R2 independently represent a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted alkoxy group, an optionally substituted aryl group, an optionally substituted alkylcarbonyl group, an optionally substituted alkenylcarbonyl group, a formyl group or the like; and n represents an integer of 0-4.)

Description

明 細 書  Specification
ビフエニル誘導体又はその塩、並びにそれらを有効成分として含有する 農園芸用殺菌剤  Biphenyl derivatives or salts thereof, and agricultural and horticultural fungicides containing these as active ingredients
技術分野  Technical field
[0001] 本発明は、新規なビフエ-ル誘導体又はその塩を有効成分として含有する農園芸 用殺菌剤に関する。  [0001] The present invention relates to an agricultural and horticultural fungicide containing a novel biphenyl derivative or a salt thereof as an active ingredient.
背景技術  Background art
[0002] ビフエニル構造を有する農園芸用殺菌剤としては、ヨーロッパ公開特許公報第 101 0690号に記載のものが知られている力 このものはビフエニル基と置換アミノ基の間 に分岐してもよい C アルキレンを有するので、本発明化合物とは化学構造が相違  [0002] Known agricultural and horticultural fungicides having a biphenyl structure include those described in European Patent Publication No. 101 0690, which may be branched between a biphenyl group and a substituted amino group. Since it has C alkylene, its chemical structure is different from the compound of the present invention.
1-7  1-7
する。この化学構造の相違によって、特定の植物病害に対して特に優れた防除効果 を発揮する。本発明化合物の化学構造は WO05Z44007に上位概念で記載されて いるが、同公報には特定の置換基パターンをもつ本発明化合物は具体的に記載さ れていない。この置換基パターンの相違により、本発明化合物は WO05Z44007に 具体的に記載の化合物よりさらに優れた植物病害防除効果を発揮する。  To do. Due to this difference in chemical structure, it exhibits a particularly excellent control effect against specific plant diseases. Although the chemical structure of the compound of the present invention is described in a superordinate concept in WO05Z44007, the compound of the present invention having a specific substituent pattern is not specifically described in the publication. Due to the difference in the substituent pattern, the compound of the present invention exhibits a superior plant disease control effect than the compound specifically described in WO05Z44007.
[0003] 特許文献 1：ヨーロッパ公開特許公報第 1010690号 [0003] Patent Document 1: European Published Patent Publication No. 1010690
特許文献 2：国際公開公報 WO05Z44007  Patent Document 2: International Publication WO05Z44007
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0004] 従来から提供された多くの農園芸用殺菌剤は、各々その植物病原菌防除効果に おいて特徴を有しており、あるものは予防効果に比べて治療効果がやや劣ったり、或 いは残効性が比較的短力つたりし、施用場面によっては、植物病原菌に対し実用上 不十分な防除効果しか示さないことがある。従って、強力な植物病原菌防除効果を 有する新規化合物の創製が希求されて ヽる。 [0004] Many agricultural and horticultural fungicides provided in the past have characteristics in controlling phytopathogenic fungi, and some of them have a slightly inferior therapeutic effect or preventive effect. May have a relatively short residual effect, and depending on the application situation, it may have a practically insufficient control effect against phytopathogenic fungi. Therefore, there is a demand for the creation of new compounds having a strong phytopathogenic fungi control effect.
課題を解決するための手段  Means for solving the problem
[0005] 本発明者らは、前述の問題点を解決すべく研究した結果、式 (I)で表される新規な ビフエニル誘導体又はその塩を有効成分として使用することにより、種々の病害特に ムギ類、野菜類、果実類及び花卉類のうどんこ病やイネいもち病に対して優れた植 物病原菌防除効果を発揮することを見い出し、本発明を完成した。 [0005] As a result of researches aimed at solving the above-mentioned problems, the present inventors have found that various novel diseases, in particular, by using a novel biphenyl derivative represented by the formula (I) or a salt thereof as an active ingredient, The present invention has been completed by finding that it exhibits excellent plant pathogen control effects against powdery mildew and rice blast of wheat, vegetables, fruits and flowers.
すなわち、本発明は、式 (I) :  That is, the present invention provides a compound of formula (I):
[0006] [化 1]  [0006] [Chemical 1]
〔式中、 X及び Y1は各々独立にハロゲン原子；水酸基；ホルミル基;ノヽロゲン、アルコ キシ若しくはアルキルチオで置換されてもょ 、アルキル基 トロ基；アルキルで置換 されてもょ 、ァミノ基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基； アルキルチオ基；アルキルスルホ -ル基又はアルキルスルフィエル基であり、 Y2はハ 口アルキル基、ハロアルコキシ基又は臭素原子であり、 Zはハロゲン原子；ホルミル基 又はハロゲンで置換されてもよいアルキル基であり、 Aはカルボ-ル基；チォカルボ -ル基又は単結合であり、 R1及び R2は各々独立に水素原子;ノヽロゲン、シクロアルキ ル、置換可フヱ-ル、置換可複素環、アルキルチオ、アルコキシ若しくはシァノで置 換されてもよいアルキル基;ノヽロゲン、シクロアルキル、フエ-ル若しくはシァノで置換 されてもよいァルケ-ル基;ノヽロゲン、シクロアルキル、フエ-ル若しくはシァノで置換 されてもょ 、アルキ-ル基；ハロゲン若しくはアルキルで置換されてもよ!、シクロアル キル基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基；ハロゲン、アル キル若しくはハロアルキルで置換されてもよいァリール基;ノヽロゲン、アルキル若しく はハロアルキルで置換されてもょ 、複素環基；ハロゲンで置換されてもょ 、アルキル カルボ-ル基；ァルケ-ルカルポ-ル基;イミノ基；アルキルで置換されてもょ 、ァミノ 基；アルキルで置換されてもょ 、ァミノカルボ-ル基；アルキルカルボ-ルァミノ基；ホ ルミル基又はシァノ基であり、 nは 0〜4の整数である（但し、 Xと Y1が同時に塩素原子 である場合は除く）〕で表されるビフエニル誘導体又はその塩、並びにそれらを有効 成分として含有する農園芸用殺菌剤に関する。 [In the formula, X and Y 1 are each independently a halogen atom; a hydroxyl group; a formyl group; a substituent that is substituted with a norogen, an alkoxy group, or an alkylthio; an alkyl group; a tro group; an amino group that is substituted with an alkyl; an amino group; Alkyl group, which may be substituted with halogen or alkoxy; alkylthio group; alkylsulfol group or alkylsulfier group; Y 2 is a haloalkyl group, haloalkoxy group or bromine atom; Z is a halogen atom A formyl group or an alkyl group which may be substituted with halogen; A is a carbo group; a thio group or a single bond; R 1 and R 2 are each independently a hydrogen atom; a norogen, a cycloalkyl; , Substituted file, substituted heterocycle, alkylthio, alkoxy or alkyl group optionally substituted by cyan; An alkenyl group optionally substituted with benzene, phenol or cyan; may be substituted with a norogen, cycloalkyl, phenol or cyan; an alkyl group; may be substituted with halogen or alkyl; !, Cycloalkyl group; substituted with halogen or alkoxy; alkoxy group; aryl group optionally substituted with halogen, alkyl or haloalkyl; substituted with norogen, alkyl or haloalkyl; Ring group: substituted with halogen, alkyl carbo group; alkenyl group; imino group; substituted with alkyl, amino group; substituted with alkyl, amino carbo group ; alkylcarbonyl - Ruamino group; an e mill group or Shiano group, n is an integer from 0 to 4 (provided that, X and Y 1 is a chlorine atom der simultaneously If biphenyl derivative or a salt thereof represented by the excluded)], and to agricultural and horticultural fungicides containing them as active ingredient.
[0007] 式 (I)中に含まれるハロゲン原子としては、フッ素、塩素、臭素又はヨウ素が用いら れ、望ましくはフッ素、塩素又は臭素が用いられる。 [0007] As the halogen atom contained in the formula (I), fluorine, chlorine, bromine or iodine is used. Preferably, fluorine, chlorine or bromine is used.
[0008] 式 (I)中に含まれるアルキル部分としては、例えばメチル、ェチル、プロピル、イソプ 口ピル、ブチル、イソブチル、 t ブチル等の C アルキルが挙げられる。  [0008] Examples of the alkyl moiety contained in the formula (I) include C alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tbutyl.
1-6  1-6
[0009] 式 (I)中に含まれるアルコキシ部分としては、例えばメトキシ、エトキシ、プロポキシ、 イソプロポキシ、ブトキシ、イソブトキシ、 t—ブトキシ等の C アルコキシが挙げられる  [0009] Examples of the alkoxy moiety contained in the formula (I) include C alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like.
1-6  1-6
[0010] 式 (I)中に含まれるァルケ-ル部分としては、例えばビュル、ァリル、イソプロべ-ル 、 3—メチルー 2 ブテュル等の C ァルケ-ルが挙げられる。 [0010] Examples of the alkell moiety contained in the formula (I) include C alkell such as bulle, valyl, isopropyl and 3-methyl-2-butyr.
2-6  2-6
式 (I)中に含まれるアルキ-ル部分としては、例えばェチニル、 1 プロビュル、 2— プロピ-ル（プロパルギル）等の C アルキ-ルが挙げられる。  Examples of the alkyl moiety contained in the formula (I) include C alkyl such as ethynyl, 1-propyl, 2-propyl (propargyl) and the like.
2-6  2-6
[0011] 式（I)中に含まれるシクロアルキルとしては、例えばシクロプロピル、シクロペンチル 、シクロへキシル等の c シクロアルキルが挙げられる。  [0011] Examples of the cycloalkyl contained in the formula (I) include c cycloalkyl such as cyclopropyl, cyclopentyl, cyclohexyl and the like.
3-6  3-6
[0012] 式 (I)中に含まれるァリール部分としては、例えばフエ-ル、ナフチル等の C ァリ  [0012] The aryl part contained in the formula (I) is, for example, a C aryl such as a file or naphthyl.
6-10 ールが挙げられる。また、式 (I)中に含まれる複素環部分としては、ピリジル、チェ- ル、フラ -ル、チアゾリル等が挙げられる。なお、式 (I)中に含まれる置換可フエ-ル 及び置換可複素環の置換基としては、ハロゲン、アルキル、ハロアルキル、アルコキ シ、ハロアルコキシ等が挙げられる。  6-10 rules. Further, examples of the heterocyclic moiety contained in the formula (I) include pyridyl, chael, fuller, thiazolyl and the like. In addition, examples of the substituent of the substitutable filer and the substitutable heterocycle included in the formula (I) include halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and the like.
発明の効果  The invention's effect
[0013] 式 (I)で表されるビフ ニル誘導体又はその塩は、農園芸用殺菌剤の有効成分とし て優れた効果を示す。  [0013] The biphenyl derivative represented by the formula (I) or a salt thereof exhibits an excellent effect as an active ingredient of an agricultural and horticultural fungicide.
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0014] 本発明のビフヱ-ル誘導体又はその塩のうち、望ましい態様を以下に記載する。 [0014] Preferred embodiments of the biphenyl derivative or salt thereof of the present invention are described below.
(1)式 (I)のビフヱニル誘導体又はその塩。  (1) A biphenyl derivative of the formula (I) or a salt thereof.
(2) Aがカルボ-ル基又はチォカルボ-ル基である（1)に記載のビフエ-ル誘導体 又はその塩。  (2) The biphenyl derivative or a salt thereof according to (1), wherein A is a carbo group or a thio group.
[0015] (3) Xが臭素原子又はアルキル基である（1)又は（2)に記載のビフヱ-ル誘導体又 はその塩。  [0015] (3) The biphenyl derivative or salt thereof according to (1) or (2), wherein X is a bromine atom or an alkyl group.
(4) Y2がハロアルキル基である（1)、 (2)又は（3)に記載のビフヱニル誘導体又はそ の塩 (4) The biphenyl derivative according to (1), (2) or (3) wherein Y 2 is a haloalkyl group, or Salt of
(5) Y2がモノフルォロメチル基、ジフルォロメチル基又はトリフルォロメチル基である（ 1)、 (2)、 (3)又は (4)に記載のビフ ニル誘導体又はその塩。 (5) The biphenyl derivative or a salt thereof according to (1), (2), (3) or (4), wherein Y 2 is a monofluoromethyl group, a difluoromethyl group or a trifluoromethyl group.
[0016] 式 (I)の化合物又はその塩は、その基本骨格或いは置換基の種類に基づく特徴を 利用し、種々の公知の合成法にて製造できる。例えば、式 (I)の化合物がアミノ基、 水酸基、カルボキシル基等の置換基を有する場合、原料乃至中間体の段階で当該 置換基を適当な保護基で保護するか或いは当該置換基に容易に変換可能な置換 基に置換しておくと、効率的な製造が行える場合がある。前記した保護基としては、 例 X·ば i，.W. Greene, P.tj.M.Wuts着、 Protective Groups in urganic Syntnesis(3rd Edition,1999)に記載の保護基が挙げられ、これら保護基を反応条件に応じて適宜 選択して用いれば良い。保護基を用いる方法では、当該保護基を用いて反応を行つ た後、必要に応じて保護基を除去、或いは所望の基に転ィ匕することにより、所望の化 合物を得ることができる。保護基を用いた方法では、通常の加水分解、エステル化、 アミド化、脱水、ジァゾ化、酸化等、当業者により周知の方法を適用することにより行う ことができる。 [0016] The compound of the formula (I) or a salt thereof can be produced by various known synthesis methods using characteristics based on the basic skeleton or the type of substituent. For example, when the compound of formula (I) has a substituent such as an amino group, a hydroxyl group, or a carboxyl group, the substituent is protected with an appropriate protecting group at the stage of the raw material or intermediate, or the substituent can be easily added. Substitution with a convertible substituent group may enable efficient production. Examples of the protecting group described above include the protecting groups described in Examples X · i, .W. Greene, P.tj.M.Wuts, Protective Groups in urganic Syntnesis (3rd Edition, 1999). May be appropriately selected according to the reaction conditions. In the method using a protecting group, a desired compound can be obtained by carrying out a reaction using the protecting group and then removing the protecting group or converting to a desired group as necessary. it can. The method using a protecting group can be carried out by applying methods well known by those skilled in the art, such as ordinary hydrolysis, esterification, amidation, dehydration, diazotization, oxidation and the like.
[0017] 式 (I)の化合物の望ましい製造方法の態様を以下に記載する。  [0017] Embodiments of desirable production methods of the compound of formula (I) are described below.
(製法 1)  (Manufacturing method 1)
[0018] [化 2] [0018] [Chemical 2]
(反応式中、 X、 R2及び ηは前述の通りであり、 Lは脱離基であり、 Μは金属又は BR 4基であり、 R3及び R4は各々独立に水酸基、アルキル基又はァ ルコキシ基である） (In the reaction formula, X, R 2 and η are as described above, L is a leaving group, Μ is a metal or BR 4 group, and R 3 and R 4 are each independently a hydroxyl group, an alkyl group, or an alkoxy group)
上記フローに示したように式 (I)の化合物は、式 (II)の化合物と式 (III)の化合物とを 適切な遷移金属触媒の存在下で、カップリングさせるか又は、式 (VII)の化合物と式 (V I)の化合物とを適切な遷移金属触媒の存在下で、カップリングさせることにより製造で きる。反応は、公知の方法 (例えば第 5版実験化学講座 18—有機化合物の合成 VI, p .327〜352「3.2節 クロスカップリング反応」（丸善）、 Comprehensive Organic Synthe sis, Volume3, 481,1991或いは Synthetic Communications, Volumell,513,1981など )に準じて行うことができる。式 (II)又は式 (VII)中の Lで表される脱離基としてはハロゲ ン、トリフルォロメタンスルホ -ルォキシ等力 式 (III)又は式 (VI)中の Mで表される金属 としては、ハロゲン化マグネシウム、ハロゲン化亜鉛、アルキルスズ、アルキル珪素、 アルコキシ珪素、ハロゲン化珪素、アルキルアルミニウム、ハロゲン化アルミニウム等 が挙げられる。反応で使用する遷移金属触媒とは、遷移金属化合物又は遷移金属 化合物と任意の配位子との錯体を意味する。例えばパラジウム-炭素 (Pd/C)、テトラ キス（トリフエ-ルホスフィン）パラジウム (0)、ビス (ジベンジリデンアセトン)パラジウム (0) 、トリス (ジベンジリデンアセトン)ジパラジウム (0)、酢酸パラジウム (II) トリフエ-ルホス フィン、酢酸パラジウム (II) トリシクロへキシルホスフィン、ジクロロパラジウム (II)-ェチ レンジァミン- Ν,Ν,Ν',Ν'-テトラ酢酸、酢酸パラジウム (II) ビス（ジシクロへキシルアミ ン）、ジクロロパラジウム (Π)-Ι,Ι'-ビス（ジシクロへキシルホスフイノ）フエ口セン、 -ッケ ルー炭素（Ni/C)、テトラキス（トリフエ-ルホスフィン）ニッケル (0)、ビス（1,5-シクロオタ タジェン）ニッケル (0)、ニッケルァセチルァセトナート (11)、ジクロロビス（トリフエ-ルホ スフイン）ニッケル (11)、ジクロロ [1,2-ビス（ジフエ-ルホスフイノ）プロパン]ニッケル (11)、 テトラキス（トリフエ-ルホスフィン）白金 (0)等が挙げられる。また、鉄や銅触媒は一般 性に欠ける力 おもに Mがハロゲン化マグネシウムの場合に利用出来る。錯体の場 合、予め単離したものを使用しても良いし、また任意の反応溶媒中で遷移金属化合 物と配位子を混合して単離せずに使用しても良い。遷移金属触媒は、式 (Π)の化合 物に対して 0.001〜0.2当量、望ましくは 0.01当量〜 0.1当量の割合で使用される。ま た、反応は、例えば、アセトン、メチルェチルケトン、シクロへキサノン等のケトン類;ジ ェチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン、 1,4 ジォキサン、ジメ トキシェタン、ジエチレングリコールジメチルエーテル等のエーテル類；酢酸ェチル、 酢酸メチル等のエステル類；メタノール、エタノール、 n-プロパノール、イソプロパノー ノレ等のァノレコーノレ類；ベンゼン、クロ口ベンゼン、ニトロベンゼン、トノレェン等の芳香 族炭化水素類；ァセトニトリル等の-トリル類； Ν,Ν-ジメチルホルムアミド； Ν,Ν-ジメチ ルァセトアミド； Ν-メチル -2-ピロリドン；ジメチルスルホキシド；ポリエチレングリコール 類;水など本反応の進行を阻害しない溶媒中又は無溶媒下で行われる。また、これら の溶媒は場合により 2種類以上を混合溶媒として用いることもできる。 As shown in the above flow, the compound of formula (I) is obtained by coupling a compound of formula (II) and a compound of formula (III) in the presence of a suitable transition metal catalyst, or by formula (VII) And a compound of formula (VI) can be produced by coupling in the presence of a suitable transition metal catalyst. The reaction can be carried out by a known method (for example, 5th edition, Experimental Chemistry Course 18—Synthesis of Organic Compounds VI, pp.327-352 “Section 3.2 Cross Coupling Reaction” (Maruzen), Comprehensive Organic Synthesis, Volume 3, 481,1991 or Synthetic Communications, Volumell, 513, 1981 etc.). The leaving group represented by L in formula (II) or formula (VII) includes halogen, trifluoromethanesulfo-loxy isotonic as a metal represented by M in formula (III) or formula (VI) Examples thereof include magnesium halide, zinc halide, alkyl tin, alkyl silicon, alkoxy silicon, silicon halide, alkyl aluminum, and aluminum halide. The transition metal catalyst used in the reaction means a transition metal compound or a complex of a transition metal compound and an arbitrary ligand. For example, palladium-carbon (Pd / C), tetra Kis (triphenylphosphine) palladium (0), bis (dibenzylideneacetone) palladium (0), tris (dibenzylideneacetone) dipalladium (0), palladium acetate (II) triphenylphosphine, palladium (II) acetate Tricyclohexylphosphine, dichloropalladium (II) -ethylenediamine- Ν, Ν, Ν ', Ν'-tetraacetic acid, palladium (II) bis (dicyclohexylamine), dichloropalladium (Π) -Ι, Ι '-Bis (dicyclohexylphosphino) pheucene, -Keckel carbon (Ni / C), tetrakis (triphenylphosphine) nickel (0), bis (1,5-cyclootatagene) nickel (0), nickel Acetyl casenerate (11), dichlorobis (triphenylphosphine) nickel (11), dichloro [1,2-bis (diphenylphosphino) propane] nickel (11), Rakisu (bird whistle - Le phosphine) platinum (0), and the like. Also, iron and copper catalysts can be used when the power lacks generality and M is magnesium halide. In the case of a complex, a previously isolated one may be used, or a transition metal compound and a ligand may be mixed in an arbitrary reaction solvent and used without isolation. The transition metal catalyst is used in a proportion of 0.001 to 0.2 equivalents, preferably 0.01 equivalents to 0.1 equivalents, relative to the compound of formula (IV). In addition, the reaction is carried out, for example, with ketones such as acetone, methyl ethyl ketone, and cyclohexanone; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 1,4 dioxane, dimethoxetane, and diethylene glycol dimethyl ether; ethyl acetate, acetic acid Esters such as methyl; Ananolones such as methanol, ethanol, n-propanol, and isopropanol; Aromatic hydrocarbons such as benzene, black benzene, nitrobenzene, and tolylene; -Tolyls such as acetonitrile; Ν, Ν-dimethyl Formamide; Ν, Ν-dimethylacetamide; Ν-methyl-2-pyrrolidone; dimethyl sulfoxide; polyethylene glycols; water or other solvent that does not inhibit the progress of this reaction or without solvent. In addition, two or more kinds of these solvents can be used as a mixed solvent in some cases.
反応に際しては、式 (II)の化合物又は式 (VII)の化合物と、式 (III)の化合物又は式（ VI)の化合物を当量若しくは一方を過剰に用いることができる。また、適切な塩基類の 存在下に反応させるのが一般的である。塩基類としては、例えば炭酸ナトリウム、炭 酸カリウム、炭酸セシウム等のアルカリ金属炭酸塩;炭酸水素ナトリウム等のアルカリ 金属の炭酸水素塩；炭酸カルシウム等のアルカリ土類金属の炭酸塩；水酸化ナトリゥ ム、水酸ィ匕カリウム等のアルカリ金属水酸ィ匕物；水酸ィ匕カルシウム等のアルカリ土類 金属水酸化物；燐酸カリウム等の燐酸塩；フッ化セシウム、フッ化カリウム等の無機塩 類；トリェチルァミン等のアミン類；ピリジン、 4- (Ν,Ν-ジメチルァミノ）ピリジン等のピリ ジン類などが挙げられる。塩基類は、式 (II)の化合物又は式 (VII)の化合物に対して、 通常 1.0〜20当量、望ましくは 1.0〜3.0当量の割合で使用される。また、適切な添カロ 剤の存在下に反応させるの力 反応を円滑に進行させる上で有利な場合がある。添 加剤としては、 1,3-ブタジエン、ァリルォキシベンゼン等のアルケン類;塩化リチウム 等の無機塩類；テトラブチルアンモ-ゥムブロミド等の 4級アンモ-ゥム塩； 1 ,4-ジァザ ビシクロ [2,2,2]オクタン等の有機塩基類などが挙げられる。添加剤は、式 (II)の化合 物に対して 0.001〜2当量、望ましくは 0.01当量〜 1当量の割合で使用される。 In the reaction, the compound of formula (II) or the compound of formula (VII) and the compound of formula (III) or the compound of formula (VI) can be used in an equivalent amount or in excess. The reaction is generally performed in the presence of an appropriate base. Examples of bases include alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate; sodium hydroxide , Alkaline metal hydroxides such as potassium hydroxide, alkaline earths such as calcium hydroxide Metal hydroxides; Phosphate salts such as potassium phosphate; Inorganic salts such as cesium fluoride and potassium fluoride; Amines such as triethylamine; Pyridines such as pyridine and 4- (Ν, Ν-dimethylamino) pyridine Can be mentioned. The base is usually used in a proportion of 1.0 to 20 equivalents, preferably 1.0 to 3.0 equivalents, relative to the compound of formula (II) or the compound of formula (VII). In addition, the reaction force in the presence of an appropriate additive may be advantageous for smoothly progressing the reaction. Additives include alkenes such as 1,3-butadiene and aryloxybenzene; inorganic salts such as lithium chloride; quaternary ammonium salts such as tetrabutyl ammonium bromide; 1,4-diazabicyclo And organic bases such as [2,2,2] octane. The additive is used in a proportion of 0.001 to 2 equivalents, preferably 0.01 equivalents to 1 equivalent, relative to the compound of formula (II).
[0021] 反応温度は 70°C〜300°Cであり、望ましくは 0°C〜使用する溶媒の沸点域が良い 。反応時間は反応温度、反応量、反応圧力等により一定しないが一般的には 1時間 〜72時間の範囲から選択すれば良 、。  [0021] The reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used. The reaction time is not constant depending on the reaction temperature, reaction amount, reaction pressure, etc., but generally it can be selected from the range of 1 to 72 hours.
[0022] (製法 2)  [0022] (Manufacturing method 2)
式 (I)中の Aがカルボニル基である式 (I 1)の化合物は、次の方法でも製造できる  A compound of formula (I 1) in which A in formula (I) is a carbonyl group can also be prepared by the following method
[0023] [化 3] [0023] [Chemical 3]
[0024] (反応式中、 X、 R2及び nは前述の通りであり、 Qは水素原子又は力 ルボキシル基の保護基である） [0024] (In the reaction formula, X, R 2 and n are as described above, Q is a hydrogen atom or a protecting group for a force ruxyl group)
上記フローに示したように式 (I 1)の化合物は、式 (V)の化合物と HNR 2で表さ れる化合物とのアミドィ匕反応により製造できる。式 (V)の化合物中の Qで表されるカル ボキシル基の保護基は、フエ-ル又はピリジルで置換されてもょ 、アルキル基である のが望ましい。 As shown in the above flow, the compound of the formula (I 1) can be produced by an amidy reaction between the compound of the formula (V) and the compound represented by HNR 2 . The protecting group for the carboxyl group represented by Q in the compound of the formula (V) is preferably an alkyl group, although it may be substituted with a phenyl or pyridyl group.
[0025] アミド化反応は、必要に応じ縮合剤の存在下、式 (V)の化合物を HNR 2で表され る化合物と縮合することにより行うことができる。縮合剤としては、例えば、ジシクロへ キシルカルボジイミド、ジイソプロピルカルボジイミド、 1-ェチル -3-(3-ジメチルァミノ プロピル)カルポジイミド等が挙げられる。使用できる溶媒としては、例えば、ベンゼン 、トルエン、キシレン等の芳香族炭化水素；ジェチルエーテル、テトラヒドロフラン、 1,4 -ジォキサン、ジメトキシェタン等のエーテル類；ジクロロメタン、 1,2-ジクロロェタン、ク ロロホルム等のハロゲン化炭化水素；メタノール、エタノール等のアルコール類； Ν,Ν- ジメチルホルムアミド、 Ν-メチル -2-ピロリドン、ピリジン等が挙げられる。また、これら の溶媒は場合により 2種類以上を混合溶媒として用いることもできる。 [0025] In the amidation reaction, the compound of formula (V) is represented by HNR 2 in the presence of a condensing agent as necessary. Can be carried out by condensation with a compound. Examples of the condensing agent include dicyclohexyl carbodiimide, diisopropyl carbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and the like. Examples of solvents that can be used include aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as jetyl ether, tetrahydrofuran, 1,4-dioxane, and dimethoxyethane; dichloromethane, 1,2-dichloroethane, and chloroform. Halogenated hydrocarbons such as: alcohols such as methanol and ethanol; Ν, Ν-dimethylformamide, Ν-methyl-2-pyrrolidone, pyridine and the like. In addition, two or more kinds of these solvents can be used as a mixed solvent in some cases.
[0026] 反応温度は 70°C〜300°Cであり、望ましくは 0°C〜使用する溶媒の沸点がよい。ま た、反応時間は反応温度、反応量、反応圧力等により異なるが一般的には 1時間〜 7 2時間の範囲力 選択すればょ 、。  [0026] The reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used. In addition, the reaction time varies depending on the reaction temperature, reaction volume, reaction pressure, etc. Generally, it is only necessary to select a force within the range of 1 to 72 hours.
[0027] また、式 (I 1)の化合物は、上記アミド化反応で、式 (V)の化合物に代えて式 (V) の化合物の反応性誘導体を使用する方法によっても製造できる。式 (V)の化合物の 反応性誘導体としては、酸ハライド、酸無水物、活性エステル等が使用できる。反応 は、例えば日本化学会編「実験化学講座 (第 4版)」 22卷 (1992年) (丸善)等に記載の 方法に準じて行うことができる。そのような反応の一例を下記フローに示す。  [0027] The compound of the formula (I 1) can also be produced by a method using a reactive derivative of the compound of the formula (V) in place of the compound of the formula (V) in the amidation reaction. As the reactive derivative of the compound of the formula (V), an acid halide, an acid anhydride, an active ester and the like can be used. The reaction can be performed, for example, according to the method described in “Chemical Experiment Course (4th edition)” edited by The Chemical Society of Japan, 22 (1992) (Maruzen). An example of such a reaction is shown in the following flow.
[0028] [化 4]  [0028] [Chemical 4]
[0029] (反応式中、 X、 R2及び nは前述の通りであり、 Halはハロゲン原子で ある） [0029] (In the reaction formula, X, R 2 and n are as described above, and Hal is a halogen atom)
[0030] (原料製法 I)  [0030] (Raw material manufacturing method I)
製法 2の出発原料である式 (V)の化合物は次の方法で製造できる。  The compound of formula (V) which is the starting material of production method 2 can be produced by the following method.
[0031] [化 5] [0031] [Chemical 5]
(VI I  (VI I
[0032] (反応式中、 X、 Ζ、 η、 Μ及び Lは前述の通りであり、 Qは水素原子又はカル ボキシル基の保護基である） [0032] (In the reaction formula, X, Ζ, η, Μ and L are as described above, and Q is a hydrogen atom or a protecting group for a carboxyl group)
Qがカルボキシル基の保護基の時、保護基 Qは前述の「Protective Groups in Or ganic Synthesis(3rd Edition,1999)」に記載のカルボキシル基の保護基を適用でき、 同文献に記載の脱保護反応や加水分解等により除去することができる。また、 Qが水 素原子の場合の化合物は、 Qがカルボキシル基の保護基である化合物を加水分解 して製造することちでさる。  When Q is a protective group for a carboxyl group, the protective group Q can be applied with the protective group for a carboxyl group described in the above-mentioned `` Protective Groups in Organic Synthesis (3rd Edition, 1999) ''. Or by hydrolysis. A compound in which Q is a hydrogen atom can be prepared by hydrolyzing a compound in which Q is a carboxyl protecting group.
[0033] 式 (V)の化合物は、式 (IV)の化合物と式 (III)の化合物とを遷移金属触媒存在下で カップリングさせるか又は、式 (VII)の化合物と式 (VIII)の化合物とを遷移金属触媒の 存在下でカップリングさせることにより製造できる。遷移金属触媒としては、製法 1で 使用の遷移金属化合物又は遷移金属化合物と任意の配位子との錯体を用いること ができる。遷移金属触媒は、式 (IV)又は式 (VII)の化合物に対して 0.001〜0.2当量、 望ましくは 0.01当量〜 0.1当量の割合で使用される。また、反応は、例えば、アセトン、 メチルェチルケトン、シクロへキサノン等のケトン類；ジェチルエーテル、ジイソプロピ ルエーテル、テトラヒドロフラン、 1,4 ジォキサン、ジメトキシェタン、ジエチレングリコ ールジメチルエーテル等のエーテル類；酢酸ェチル、酢酸メチル等のエステル類;メ タノール、エタノール、 n-プロパノール、イソプロパノール等のアルコール類；ベンゼン 、クロ口ベンゼン、ニトロベンゼン、トルエン等の芳香族炭化水素類；ァセトニトリル等 の-トリル類； Ν,Ν-ジメチルホルムアミド； Ν,Ν-ジメチルァセトアミド；ジメチルスルホキ シド;水など本反応の進行を阻害しない溶媒中又は無溶媒下で行われる。また、これ らの溶媒は場合により 2種類以上を混合溶媒として用いることもできる。 [0033] The compound of the formula (V) is obtained by coupling the compound of the formula (IV) and the compound of the formula (III) in the presence of a transition metal catalyst, or the compound of the formula (VII) and the compound of the formula (VIII). It can be produced by coupling a compound with a transition metal catalyst. As the transition metal catalyst, a transition metal compound used in Production Method 1 or a complex of a transition metal compound and an arbitrary ligand can be used. The transition metal catalyst is used in a proportion of 0.001 to 0.2 equivalent, desirably 0.01 equivalent to 0.1 equivalent, relative to the compound of formula (IV) or formula (VII). The reaction may be carried out, for example, with ketones such as acetone, methyl ethyl ketone, and cyclohexanone; ethers such as jetyl ether, diisopropyl ether, tetrahydrofuran, 1,4 dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; Esters such as ethyl and methyl acetate; Alcohols such as methanol, ethanol, n-propanol, and isopropanol; Aromatic hydrocarbons such as benzene, black benzene, nitrobenzene, and toluene; Acetonitrile, etc. -Tolyls;, Ν-dimethylformamide; Ν, Ν-dimethylacetamide; dimethyl sulfoxide; water or the like in a solvent that does not inhibit the progress of this reaction or in the absence of a solvent. In addition, two or more kinds of these solvents can be used as a mixed solvent in some cases.
[0034] 反応に際しては、式 (IV)又は式 (VII)の化合物と、式 (III)又は式 (VIII)の化合物を 当量若しくは一方を過剰に用いることができる。また、塩基類の存在下に反応させる のが、反応を円滑に進行させる上で有利な場合がある。塩基類としては、例えば炭酸 ナトリウム、炭酸カリウム、炭酸セシウム等のアルカリ金属炭酸塩;炭酸水素ナトリウム 等のアルカリ金属の炭酸水素塩；炭酸カルシウム等のアルカリ土類金属の炭酸塩；水 酸ィ匕ナトリウム、水酸ィ匕カリウム等のアルカリ金属水酸ィ匕物；水酸ィ匕カルシウム等のァ ルカリ土類金属水酸化物；フッ化セシウム、フッ化カリウム等の無機塩類；トリェチルァ ミン等のアミン類;ピリジン、 4- (Ν,Ν-ジメチルァミノ）ピリジン等のピリジン類などが挙 げられる。塩基類は、式 (IV)又は式 (VII)の化合物に対して、通常 1.0〜20当量、望 ましくは 1.0〜3.0当量の割合で使用される。  In the reaction, the compound of formula (IV) or formula (VII) and the compound of formula (III) or formula (VIII) can be used in an equivalent amount or in excess. In addition, the reaction in the presence of bases may be advantageous for the smooth progress of the reaction. Examples of bases include alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate; , Alkali metal hydroxides such as potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, inorganic salts such as cesium fluoride and potassium fluoride, and amines such as triethylamine And pyridines such as pyridine and 4- (Ν, Ν-dimethylamino) pyridine. The base is usually used in a proportion of 1.0 to 20 equivalents, preferably 1.0 to 3.0 equivalents, relative to the compound of formula (IV) or formula (VII).
[0035] 反応温度は 70°C〜300°Cであり、望ましくは 0°C〜使用する溶媒の沸点がよい。ま た、反応時間は反応温度、反応量、反応圧力等により一定しないが一般的には 1時 間〜 72時間の範囲力 選択すればょ 、。  [0035] The reaction temperature is 70 ° C to 300 ° C, preferably 0 ° C to the boiling point of the solvent used. In addition, the reaction time is not constant depending on the reaction temperature, reaction volume, reaction pressure, etc. Generally, you can select a force ranging from 1 hour to 72 hours.
[0036] (原料製法 Π)  [0036] (Raw material manufacturing method Π)
製法 2の出発原料である式 (V)の化合物のうち、 Qが水素原子である場合の式 (V-1 )の化合物は次の方法でも製造できる。  Of the compounds of formula (V) which are starting materials of production method 2, the compound of formula (V-1) when Q is a hydrogen atom can also be produced by the following method.
[0037] [化 6] [0037] [Chemical 6]
(VI I (X ) (VI I (X)
[0038] (反応式中、 X、 Ζ、 η、 Μ及び Lは前述の通りであり、 Meはメチル基であり、 H alはハロゲン原子である） [0038] (In the reaction formula, X, Ζ, η, Μ and L are as described above, Me is a methyl group, and Hal is a halogen atom)
式 (V— 1)の化合物は、式 (XI)の化合物を二酸ィ匕マンガン、過マンガン酸カリウム等 の酸化剤を用いて、通常の方法によって酸ィ匕させることにより製造できる。式 (XI)の化 合物は、式 (IX)の化合物と式 (III)の化合物とを遷移金属触媒の存在下でカップリン グさせるか又は、式 (VII)の化合物と式 (X)の化合物とを遷移金属触媒の存在下で力 ップリングさせること〖こより製造できる。両カップリング反応は前述の製法 1と同様にし て行うことができる。また、式 (V—1)の化合物をハロゲンィ匕することにより、式 (XV)の 化合物を製造することができる。この反応には、通常の酸ハロゲンィ匕反応が適用でき る。この反応は、ジクロロェタン等の不活性溶媒の存在下または非存在下で、 O〜200 °Cの反応温度で行われるのが望ましい。この反応で使用されるハロゲン化剤としては 、フッ素化剤、塩素化剤、臭素化剤等が挙げられるが、塩ィ匕チォニル、ォキシ塩化リ ン、塩ィ匕ォキサリル等の塩素化剤を使用するのが望ま 、。  The compound of the formula (V-1) can be produced by acidifying the compound of the formula (XI) by an ordinary method using an oxidizing agent such as manganese diacid and potassium permanganate. The compound of formula (XI) is obtained by coupling a compound of formula (IX) and a compound of formula (III) in the presence of a transition metal catalyst, or a compound of formula (VII) and formula (X). This compound can be produced by the use of force coupling in the presence of a transition metal catalyst. Both coupling reactions can be carried out in the same manner as in Production Method 1 described above. In addition, a compound of formula (XV) can be produced by halogenating a compound of formula (V-1). For this reaction, the usual acid halogenated reaction can be applied. This reaction is preferably carried out at a reaction temperature of O to 200 ° C. in the presence or absence of an inert solvent such as dichloroethane. Examples of the halogenating agent used in this reaction include a fluorinating agent, a chlorinating agent, and a brominating agent, but a chlorinating agent such as chlorothionyl, oxylin chloride, and chlorooxalyl is used. Hope to do.
[0039] (製法 3)  [0039] (Manufacturing method 3)
[0040] 式 (I)中の R1及び R2が水素原子であり、 Aが単結合である式 (I 2)の化合物は、 次の方法でも製造できる。 [0041] [化 7] [0040] The compound of the formula (I 2) in which R 1 and R 2 in the formula (I) are hydrogen atoms and A is a single bond can also be produced by the following method. [0041] [Chemical 7]
(νπ ) (XI I I) (νπ) (XI I I)
[0042] (反応式中、 X、 Ζ、 Α、 η、 L及び Μは前述の通りである） [0042] (In the reaction formula, X, Ζ, Α, η, L and Μ are as described above)
上記フローに示したように式 (I 2)の化合物は、式 (XIV)の化合物を接触還元、鉄 還元などの通常の還元反応により製造できる。また、式 (XIV)の化合物は、式 (XII) の化合物と式 (III)の化合物とを遷移金属触媒の存在下でカップリングさせるか又は、 式 (VII)の化合物と式 (ΧΙΠ)の化合物とを遷移金属触媒の存在下でカップリングさせる ことにより製造できる。式 (XIV)の化合物を製造する反応は、製法 1に記載の反応に 準じて行うことができる。また、式 (XIV)の化合物は単離精製して或いは単離精製せ ず、式 (I 2)の化合物の製造反応に供することができる。  As shown in the above flow, the compound of formula (I2) can be produced by subjecting the compound of formula (XIV) to a usual reduction reaction such as catalytic reduction or iron reduction. In addition, the compound of formula (XIV) is obtained by coupling a compound of formula (XII) and a compound of formula (III) in the presence of a transition metal catalyst, or a compound of formula (VII) and It can be produced by coupling a compound with a transition metal catalyst. The reaction for producing the compound of the formula (XIV) can be carried out according to the reaction described in production method 1. Further, the compound of the formula (XIV) can be subjected to the production reaction of the compound of the formula (I2) with or without isolation and purification.
[0043] 製法 1〜3の方法によって製造された式 (I)の化合物及びその製造用中間体は、抽 出、濃縮、結晶化、濾過、再結晶、各種クロマトグラフィー等通常の化学操作を適用 して単離、精製できる。  [0043] Production Method The compounds of formula (I) produced by the methods 1 to 3 and intermediates for production thereof are subjected to usual chemical operations such as extraction, concentration, crystallization, filtration, recrystallization, and various chromatography. And can be isolated and purified.
[0044] 前記した式 (I)のビフヱ-ル誘導体は、上位概念化合物である WO 05/44007 記載の式 (Γ ) :  [0044] The biphenyl derivative of the above formula (I) is a superordinate conceptual compound represented by the formula (Γ) in WO 05/44007:
[0045] [化 8] [0045] [Chemical 8]
〔式中、 X '及び Υ，は各々独立にハロゲン原子；水酸基；ホルミル基；ノヽロゲン、アル コキシ若しくはアルキルチオで置換されてもょ 、アルキル基 トロ基；アルキルで置 換されてもょ 、ァミノ基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基 ；ハロゲン若しくはハロアルキルで置換されてもょ 、ァリールォキシ基；ハロゲン若しく はハロアルキルで置換されてもょ 、複素環ォキシ基；ハロゲン若しくはハロアルキル で置換されてもょ 、複素環基；アルキルで置換されてもょ 、ァミノカルボ-ル基；アル キルカルボ-ルァミノ基；ハロゲンで置換されてもょ 、アルキルカルボ-ル基；アルキ ルチオ基；アルキルスルホ -ル基；アルキルスルフィエル基又はアルキル若しくはァ ルコキシで置換されてもよいイミノ基であり、 ζ，はハロゲン原子；ホルミル基;ノヽロゲン で置換されてもょ 、アルキル基；アルコキシで置換されてもよ!、アルコキシ基；アルキ ルチオ基；アルキルスルホ -ル基又はアルキルスルフィエル基であり、 A'はカルボ- ル基；チォカルボ-ル基；アルキレン基又は単結合であり、 R1及び R2は各々独立に 水素原子；ハロゲン、シクロアルキル、置換可フエ-ル、置換可複素環、アルキルチ ォ、アルコキシ若しくはシァノで置換されてもよいアルキル基;ノヽロゲン、シクロアルキ ル、フ -ル若しくはシァノで置換されてもよいァルケ-ル基;ノヽロゲン、シクロアルキ ル、フエ-ル若しくはシァノで置換されてもよ!、アルキ-ル基；ハロゲン若しくはアル キルで置換されてもよいシクロアルキル基;ノヽロゲン若しくはアルコキシで置換されて もよ 、アルコキシ基；ハロゲン、アルキル若しくはハロアルキルで置換されてもよ!ヽァリ ール基；ハロゲン、アルキル若しくはハロアルキルで置換されてもよ 、複素環基；ハロ ゲンで置換されてもょ 、アルキルカルボ-ル基；ァルケ-ルカルポ-ル基；イミノ基； アルキルで置換されてもよ!、ァミノ基；アルキルで置換されてもよ!、ァミノカルボ-ル 基；アルキルカルボ-ルァミノ基；ホルミル基又はシァノ基であり、 m及び ηは各々独 立に 0、 1、 2、 3又は 4である〕で表されるビフエ二ル誘導体に包含される化合物であ る。式 (I)のビフ ニル誘導体は、式 (Γ )のビフ ニル誘導体中、特に植物病害の防 除効果が優れたィ匕合物の置換基パターンを具体的に見出したものである。前記式 (I ' )の化合物は、式 (I)の化合物に準じた方法すなわち、前記した製法 1〜3において [In the formula, X ′ and 独立 are each independently a halogen atom; a hydroxyl group; a formyl group; a substituent that is substituted with a norogen, an alkoxy group, or an alkylthio; an alkyl group, a tro group; Group substituted by halogen or alkoxy, alkoxy group substituted by halogen or haloalkyl, aryloxy group; substituted by halogen or haloalkyl, heterocyclic oxy group; substituted by halogen or haloalkyl A heterocyclic group; an alkyl group, an alkyl carbo group; an alkyl carbo group; an alkyl carbo group; an alkylthio group; an alkyl sulpho group; A group; an alkyl sulfier group or an imino group optionally substituted by alkyl or alkoxy Ζ, is a halogen atom; a formyl group; may be substituted with a norogen, an alkyl group; may be substituted with an alkoxy !, an alkoxy group; an alkylthio group; an alkylsulfol group or an alkylsulfiel group. A ′ is a carbo group; a thio group; an alkylene group or a single bond, R 1 and R 2 are each independently a hydrogen atom; halogen, cycloalkyl, substituted phenyl, substituted heterocycle An alkyl group which may be substituted with alkylthio, alkoxy or cyan; a alkenyl group which may be substituted with norogen, cycloalkyl, fur or cyan; a norogen, cycloalkyl, phenol or cyan May be substituted !, an alkyl group; a cycloalkyl group that may be substituted with halogen or alkyl; Well, alkoxy group; may be substituted with halogen, alkyl or haloalkyl! Aryl group; may be substituted with halogen, alkyl or haloalkyl, heterocyclic group; may be substituted with halogen, alkylcarbo -Alkyl group; alkenyl group; imino group; may be substituted with alkyl !, amino group; may be substituted with alkyl !, aminocarbol group; alkylcarbo-lamino group; formyl group or cyano And m and η are each independently 0, 1, 2, 3 or 4]. The biphenyl derivative of the formula (I) is one of the biphenyl derivatives of the formula (Γ), especially for preventing plant diseases. The present inventors have specifically found a substituent pattern of a compound having an excellent removal effect. The compound of the formula (I ′) is a method according to the compound of the formula (I), that is, in the production methods 1 to 3 described above.
[0046] [化 9] [0046] [Chemical 9]
部分を Part
[0047] [化 10]  [0047] [Chemical 10]
部分に、 Aを A，に、 Zを Z，に代えた場合の方法によって、製造することができる。 It can be manufactured by the method in which A is replaced with A and Z is replaced with Z.
[0048] 前記式 (I)で表されるビフ ニル誘導体又はその塩 (以下、本発明化合物と略す） 及び式 (Γ )で表されるビフ ニル誘導体又はその塩は、農園芸用殺菌剤及び Z又 は抗真菌剤といった有害生物防除剤の有効成分として有用であるが、特に農園芸用 殺菌剤の有効成分として有用である。農園芸用殺菌剤としては、例えばイネのいもち 病、ごま葉枯病、紋枯病；ムギ類のうどんこ病、赤かび病、さび病、雪腐病、裸黒穂病 、眼紋病、葉枯病、ふ枯病;カンキッの黒点病、そうか病；リンゴのモユリア病、うどん こ病、斑点落葉病、黒星病；ナシの黒星病、黒斑病；モモの灰星病、黒星病、フォモ プシス腐敗病；ブドウの黒とう病、晚腐病、うどんこ病、ベと病；力キの炭そ病、落葉病 ；ゥリ類の炭そ病、うどんこ病、つる枯病、ベと病；トマトの輪紋病、葉かび病、疫病；ァ ブラナ科野菜の黒斑病、バレイショの夏疫病、疫病;イチゴのうどんこ病;種々の作物 の灰色かび病、菌核病等の病害の防除に有効であるが、特にムギ類、野菜類のうど んこ病及びイネいもち病に優れた防除効果を示す。また、フザリウム菌、ピシゥム菌、 リゾクトニア菌、バーティシリウム菌、ブラズモディォホーラ菌等の植物病原菌によって 引き起こされる土壌病害の防除にも有効である。抗真菌剤としては、例えばカンジダ 属菌、タリプトコッカス属菌、ァスペルギルス属菌、スタフイロコッカス属菌ゃトリコフイト ン属菌などに対して有効である。 [0048] The biphenyl derivative represented by the formula (I) or a salt thereof (hereinafter abbreviated as the compound of the present invention) and the biphenyl derivative represented by the formula (Γ) or a salt thereof include an agricultural and horticultural fungicide and It is useful as an active ingredient in pest control agents such as Z or antifungal agents, but is particularly useful as an active ingredient in agricultural and horticultural fungicides. Agricultural and horticultural fungicides include, for example, rice blast, sesame leaf blight, coat blight; wheat powdery mildew, red mold, rust, snow rot, naked smut, eye coat disease, leaves Blight, dry blight; citrus sunspot disease, common scab; apple moyulia disease, powdery mildew, spotted leaf disease, black star disease; pear black star disease, black spot disease; peach ash star disease, black star disease, Phomopsis rot; grape black rot, rot, powdery mildew, downy mildew; power anthracnose, leaf deciduous; cucurbit anthracnose, powdery mildew, vine blight, downy mildew Tomato ring mold disease, leaf mold disease, plague; black crab disease of cruciferous vegetables; summer plague of potato; plague; strawberry powdery mildew; gray mold disease of various crops; Although it is effective in controlling diseases, it exhibits excellent control effects especially for powdery mildew and rice blast of wheat and vegetables. It is also effective for controlling soil diseases caused by phytopathogenic fungi such as Fusarium, Pythium, Rhizoctonia, Verticillium, and Brasmodhora. As an antifungal agent, for example, Candida It is effective against the genus, Talytococcus, Aspergillus, Staphylococcus and Trichophyton.
本発明化合物は、通常、該化合物と各種農業上の補助剤とを混合して粉剤、粒剤 、顆粒水和剤、水和剤、水性懸濁剤、油性懸濁剤、水溶剤、乳剤、液剤、ペースト剤 、エアゾール剤、微量散布剤などの種々の形態に製剤して使用されるが、本発明の 目的に適合する力ぎり、通常の当該分野で用いられているあらゆる製剤形態にする ことができる。製剤に使用する補助剤としては、珪藻土、消石灰、炭酸カルシウム、タ ルク、ホワイトカーボン、カオリン、ベントナイト、カオリナイト及びセリサイトの混合物、 クレー、炭酸ナトリウム、重曹、芒硝、ゼォライト、澱粉などの固型担体;水、トルエン、 キシレン、ソルベントナフサ、ジォキサン、アセトン、イソホロン、メチルイソブチルケト ン、クロ口ベンゼン、シクロへキサン、ジメチルスルホキシド、ジメチルホルムアミド、ジ メチルァセトアミド、 N—メチル—2—ピロリドン、アルコールなどの溶剤；脂肪酸塩、安 息香酸塩、アルキルスルホコハク酸塩、ジアルキルスルホコハク酸塩、ポリカルボン酸 塩、アルキル硫酸エステル塩、アルキル硫酸塩、アルキルァリール硫酸塩、アルキル ジグリコールエーテル硫酸塩、アルコール硫酸エステル塩、アルキルスルホン酸塩、 アルキルァリールスルホン酸塩、ァリールスルホン酸塩、リグ-ンスルホン酸塩、アル キルジフヱ-ルエーテルジスルホン酸塩、ポリスチレンスルホン酸塩、アルキルリン酸 エステル塩、アルキルァリールリン酸塩、スチリルァリールリン酸塩、ポリオキシェチレ ンアルキルエーテル硫酸エステル塩、ポリオキシエチレンアルキルァリールエーテル 硫酸塩、ポリオキシエチレンアルキルァリールエーテル硫酸エステル塩、ポリオキシ エチレンアルキルエーテルリン酸塩、ポリオキシエチレンアルキルァリールリン酸エス テル塩、ナフタレンスルホン酸ホルマリン縮合物の塩のような陰イオン系の界面活性 剤ゃ展着剤;ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、脂肪酸ポリダリ セライド、脂肪酸アルコールポリグリコールエーテル、アセチレングリコール、ァセチレ ンアルコール、ォキシアルキレンブロックポリマー、ポリオキシエチレンアルキルエー テル、ポリオキシエチレンアルキルァリールエーテル、ポリオキシエチレンスチリルァリ ールエーテル、ポリオキシエチレングリコールアルキルエーテル、ポリオキシエチレン 脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン グリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、ポリオキシプロピレン脂 肪酸エステルのような非イオン系の界面活性剤ゃ展着剤;ォリーブ油、カポック油、 ひまし油、シュロ油、椿油、ヤシ油、ごま油、トウモロコシ油、米ぬか油、落花生油、綿 実油、大豆油、菜種油、亜麻仁油、きり油、液状パラフィンなどの植物油や鉱物油な どが挙げられる。これら補助剤は本発明の目的力も逸脱しないかぎり、当該分野で知 られたものの中から選んで用いることができる。また、増量剤、増粘剤、沈降防止剤、 凍結防止剤、分散安定剤、薬害軽減剤、防黴剤など通常使用される各種補助剤も 使用することができる。本発明化合物と各種補助剤との配合割合は重量比で、一般 に 0.005： 99.995〜95 : 5、望ましくは 0.2 : 99.8〜90 : 10である。これら製剤の実際の 使用に際しては、そのまま使用するか、又は水等の希釈剤で所定濃度に希釈し、必 要に応じて各種展着剤を添加して使用することができる。 The compound of the present invention is usually prepared by mixing the compound with various agricultural adjuvants, powder, granules, granule wettable powder, wettable powder, aqueous suspension, oily suspension, aqueous solvent, emulsion, It can be used in various forms such as liquids, pastes, aerosols, microdispersions, etc., but it should be in the form of any formulation that is usually used in the field as long as it meets the purpose of the present invention. Can do. Adjuvants used in the formulation include solid forms such as diatomaceous earth, slaked lime, calcium carbonate, tark, white carbon, kaolin, bentonite, kaolinite and sericite, clay, sodium carbonate, sodium bicarbonate, sodium sulfate, zeolite, starch, etc. Carrier; water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, black benzene, cyclohexane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, Solvents such as alcohols; fatty acid salts, benzoates, alkylsulfosuccinates, dialkylsulfosuccinates, polycarboxylic acids, alkyl sulfate esters, alkyl sulfates, alkyl aryl sulfates, alkyl diglycol ether sulfates , Arco Sulfate ester salt, alkyl sulfonate salt, alkyl aryl sulfonate salt, aryl sulfonate salt, ligne sulfonate salt, alkyl diphenyl ether disulfonate salt, polystyrene sulfonate salt, alkyl phosphate ester salt, alkyl sulfonate salt Lille phosphate, styryl aryl phosphate, polyoxyethylene alkyl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl ether phosphate, poly Anionic surfactants such as oxyethylene alkyl aryl phosphate ester salts and naphthalene sulfonic acid formalin condensate salts; sorbitan fatty acid esters, glycerin fatty acid esters, fatty acid polyglycerides Id, fatty acid alcohol polyglycol ether, acetylene glycol, acetylene alcohol, oxyalkylene block polymer, polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene styryl aryl ether, polyoxyethylene glycol alkyl ether , Polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene Nonionic surfactant spreading agents such as glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxypropylene fatty acid ester; olive oil, kapok oil, castor oil, palm oil, straw oil, coconut oil, sesame oil Corn oil, rice bran oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, linseed oil, cutting oil, liquid paraffin and other vegetable oils and mineral oils. These adjuvants can be selected from those known in the art without departing from the object of the present invention. In addition, various commonly used adjuvants such as extenders, thickeners, anti-settling agents, antifreezing agents, dispersion stabilizers, safeners, and antifungal agents can also be used. The blending ratio of the compound of the present invention to various adjuvants is generally 0.005: 99.995 to 95: 5, preferably 0.2: 99.8 to 90:10, by weight. In actual use of these preparations, they can be used as they are, or diluted to a predetermined concentration with a diluent such as water, and various spreading agents can be added as necessary.
[0050] 本発明化合物の使用濃度は、対象作物、使用方法、製剤形態、施用量などの違い によって異なり、一概に規定できないが、茎葉処理の場合、有効成分当たり普通 0.1 〜10,000ppm、望ましくは、 l〜2,000ppmである。土壌処理の場合には、普通 10〜10 0,000g/ha、望ましくは、 200〜20,000g/haである。  [0050] The concentration of the compound of the present invention varies depending on the target crop, method of use, formulation, application rate, etc., and cannot be generally defined. However, in the case of foliage treatment, it is usually 0.1 to 10,000 ppm, preferably L to 2,000 ppm. In the case of soil treatment, it is usually 10 to 100,000 g / ha, preferably 200 to 20,000 g / ha.
[0051] 本発明化合物は、その種々の製剤又はその希釈物の施用に関して、通常一般に 行なわれている施用方法すなわち、散布 (例えば散布、噴霧、ミスティング、アトマイ ジング、散粒、水面施用等)、土壌施用（混入、灌注等)、表面施用（塗布、粉衣、被 覆等)等により行うことができる。また、いわゆる超高濃度少量散布法 (ultra low volu me)により施用することもできる。この方法においては、活性成分を 100%含有するこ とが可能である。  [0051] The compound of the present invention is generally applied for application of its various preparations or dilutions thereof, that is, spraying (eg spraying, spraying, misting, atomizing, dusting, water surface application, etc.) , Soil application (mixing, irrigation, etc.), surface application (application, powder coating, covering, etc.). It can also be applied by the so-called ultra-low-volume spray method. In this method, it is possible to contain 100% of the active ingredient.
[0052] 本発明化合物は、必要に応じて他の農薬、例えば、殺菌剤、殺虫剤、殺ダニ剤、殺 線虫剤、抗ウィルス剤、誘引剤、除草剤、植物成長調製剤などと、混用、併用するこ とができ、この場合には一層優れた効果を示すこともある。  [0052] The compound of the present invention may contain other agricultural chemicals such as bactericides, insecticides, acaricides, nematicides, antiviral agents, attractants, herbicides, plant growth preparations, etc., if necessary. They can be mixed and used together, and in this case, even better effects may be shown.
[0053] 上記他の農薬中の、殺菌剤の有効成分化合物 (一般名；一部申請中を含む)として は、例えば、メパ-ピリム（Mepanipyrim)、ピリメサ-ル（Pyrimethanil)、シプロジ-ル（[0053] In the above-mentioned other agricultural chemicals, as an active ingredient compound of a fungicide (generic name; including some pending applications), for example, mepa-pyrim (Mepanipyrim), pyrimethanil, cyprozil (
Cyprodinil)のようなピリミジナミン系化合物； Pyrimidinamine compounds such as Cyprodinil);
フルアジナム（Fluazinam)のようなピリジナミン系化合物； トリアジメホン（Triadimefon)、ビテルタノール（Bitertanol)、トリフルミゾール（Triflumi zole)、エタコナゾ一ノレ (Etaconazole)、プロピコナゾーノレ (Propiconazole)、ペンコナゾ 一ノレ (Penconazole)、フノレシラゾーノレ (Flusilazole)、マイクロブタニノレ (Myclobutanil)、 シプロコナゾ一ノレ (Cyproconazole)、テブコナゾーノレ (Tebuconazole)、へキサコナゾ 一ノレ (Hexaconazole)、ファーコナゾ一ノレシス (Furconazole- cis)、プロクロラズ (Prochl oraz)、メトコナゾーノレ (Metconazole)、エポキシコナゾ一ノレ (Epoxiconazole)、テトラコ ナゾーノレ (Tetraconazole)、ォキスポコナゾーノレフマノレ酸塩 (Oxpoconazole ftimarate)シプコナゾーノレ (Sipconazole)、プロチォコナゾーノレ (Prothioconazole)、トリ アジメノール（Triadimenol)、フルトリアホール（Flutriafol)、ジフエノコナゾール（Difeno conazole)、フノレキンコナゾ一ノレ (Fluquinconazole)、フェンブコナン一ノレ (Fenbuconaz ole)、ブロムコナゾ一ノレ (Bromuconazole)、ジニコナゾール (Diniconazole)、トリシクラ ゾール (Tricyclazole)、プロべナゾーノレ (Probenazole)、シメコナゾーノレ (Simeconazole )、ぺフラゾエート (Pefijrazoate)、ィプコナゾーノレ (Ipconazole)、イミベンコナゾ一ノレ (I mibenconazole)のようなァゾール系化合物； Pyridinamine compounds such as Fluazinam; Triadimefon, Bitertanol, Triflumi zole, Etaconazole, Propiconazole, Penconazo, Penconazole, Flusilazole, Micro Butaninole (Myclobutanil), Cyproconazonore (Cyproconazole), Tebuconazonole (Tebuconazole), Hexaconazo Monore (Hexaconazole), Farconazonore (Furconazole-cis), Prochloraz (Prochl oraz), Metoconazonole Epoxy Epoxiconazole), Tetraconazole, Oxpoconazole ftimarate, Sipconazole, Prothioconazole, Triazimenol, Flutriafol, Difeno conazole, Norequinconazole, Fenbuconaz ole, Bromuconazole, Diniconazole, Tricyclazole, Probenazole, Pimeconazolate, Pimeconazolate Azole compounds such as Ipconazole, I mibenconazole;
キノメチォネート (Quinomethionate)のようなキノキサリン系化合物；  Quinoxaline compounds such as quinomethionate;
マンネブ（Maneb)、ジネブ（Zineb)、マンゼブ（Mancozeb)、ポリカーバメート（Polyca rbamate)、メチラム（Metiram)、プロピネブ（Propineb)、チラム (thiram)のようなジチォ カーバメート系化合物；  Dithio carbamate compounds such as Maneb, Zineb, Mancozeb, Polycarbamate, Metiram, Propineb, thiram;
フサライド（Fthalide)、クロロタ口-ル（Chlorothalonil)、キントゼン（Quintozene)のよ うな有機塩素系化合物；  Organochlorine compounds such as Fthalide, Chlorothalonil, Quintozene;
べノミノレ（Benomyl)、チオファネートメチノレ（Thiophanate-Methyl)、カーベンダジム（ Carbendazim)、チアベンダゾール (Thiabendazole)、フベリアゾール (foberiazole)、シァ ゾフアミド（Cyazofamid)のようなイミダゾール系化合物；  Imidazole compounds such as Benomyl, Thiophanate-Methyl, Carbendazim, Thiabendazole, Foveriazole, Cyazofamid;
シモキサニル (Cymoxanil)のようなシァノアセトアミド系化合物；  Cyanoacetamide compounds such as Cymoxanil;
メタラキシル（Metalaxyl)、メタラキシノレ一 M (Metalaxyl- M)、メフエノキサム (Mefenox am)、ォキサジキシル (Oxadixyl)、オフレース（Oforace)、ベナラキシル (Benalaxyl)、 ベナラキシル M (Benalaxy卜 M、別名キララキシル (Kiralaxyl、 Chiralaxyl))、フララキ シル（Furalaxyl)、シプロフラム（Cyproforam)のようなフエニルアミド系化合物； ジクロフルアニド（Dichlofluanid)のようなスルフ ン酸系化合物； Metalaxyl, Metalaxyl-M, Mefenox am, Oxadixyl, Offace, Benalaxyl, Benalaxy 卜 M, also known as Kiraxyl, Chiralxyl ), Phenylamides such as Furalaxyl, Cyproforam; Sulfuric acid compounds such as Dichlofluanid;
水酸化第二銅（Cupric hydroxide)、有機銅（Oxine Copper)のような銅系化合物； ヒメキサゾール（Hymexazol)のようなイソキサゾール系化合物；  Copper-based compounds such as cupric hydroxide and organic copper (Oxine Copper); isoxazole-based compounds such as hymexazol;
ホセチルアルミニウム（FosetW-Al)、トルコホスメチル（Tolcofos- Methyl)、 S—ベン ジル O, O—ジイソプロピルホスホロチォエート、 O—ェチル S, S—ジフエ-ルホス ホロジチォエート、アルミニウムェチルハイドロゲンホスホネートのような有機リン系化 合物；  Like fosetyl aluminum (FosetW-Al), Turkish phosmethyl (Tolcofos-Methyl), S-benzyl O, O-diisopropyl phosphorothioate, O-ethyl S, S-diphenyl-phosphorodithioate, aluminum ethyl hydrogen phosphonate Organic phosphorus compounds;
キヤプタン（Captan)、キヤプタホル（Captafol)、フオルペット（Folpet)のような N—ノヽ ロゲノチォアルキル系化合物；  N-nologenothioalkyl compounds such as Captan, Captafol, Folpet;
プロシミドン（Procymidone)、ィプロジオン（Iprodione)、ビンクロゾリン（Vinclozolin) のようなジカノレボキシイミド系ィヒ合物；  Dicanolevoxiimide compounds such as Procymidone, Iprodione, Vinclozolin;
フルトラ-ル（Flutolanil)、メプロ-ル (Mepronil)、ゾキサミド（Zoxamid)、チアジ-ル (Tiadinil)のようなベンズァ-リド系化合物；  Benzalide compounds such as Flutolanil, Mepronil, Zoxamid, Tiadinil;
カルボキシン (Carboxin)、ォキシカルボキシン (Oxycarboxin)、チフルザミド (Thifluza mide)、 MTF- 753(ペンチォピラド、 Penthiopyrad),ボスカリド (Boscalid)  Carboxin (Carboxin), Oxycarboxin, Thifluzamid (Thifluza mide), MTF-753 (Penthiopyrad, Penthiopyrad), Boscalid (Boscalid)
のようなァ-リド系化合物； Amide compounds such as
トリホリン（Triforine)のようなピペラジン系化合物；  Piperazine compounds such as Triforine;
ピリフエノックス（Pyrifenox)のようなピリジン系化合物；  Pyridine compounds such as Pyrifenox;
フエナリモル（Fenarimol)、フルトリアフオル（Flutriafol)のようなカルビノール系化合 物；  Carbinol compounds such as Fenarimol and Flutriafol;
フェンプロピデイン（Fenpropidine)のようなピペリジン系化合物；  Piperidine compounds such as Fenpropidine;
フェンプロピモルフ（Fenpropimorph)、スピロキサミン（Spiroxamine)、トリデモルフ (T ridemorph)のようなモルフオリン系化合物；  Morpholine compounds such as Fenpropimorph, Spiroxamine, Tridemorph;
フェンチンヒドロキシド（Fentin Hydroxide)、フェンチンアセテート（Fentin Acetate )のような有機スズ系化合物；  Organotin compounds such as Fentin Hydroxide and Fentin Acetate;
ペンシキュロン（Pencycuron)のような尿素系化合物；  Urea compounds such as Pencycuron;
ジメトモルフ（Dimethomorph)、フルモルフ（Flumorph)のようなシンナミック酸系化合 物； ジエトフェンカルプ（Diethofencarb)のようなフエ-ルカーバメート系化合物； フルジォキソ-ル（Fludioxonil)、フェンピクロ-ル（Fenpiclonil)のようなシァノピロ一 ル系化合物； Synamic acid compounds such as Dimethomorph, Flumorph; Ferrocarbamate compounds such as Dietofencarb; Cyanopyrrole compounds such as Fludioxonil and Fenpiclonil;
ァゾキシストロビン（Azoxystrobin)、クレソキシムメチル（Kresoxim- Methyl)、メトミノ フェン（Metominofen)、トリフロキシストロビン（Trifloxystrobin)、ピコキシストロビン（Pic oxystrobin)、オリザストロビン（Oryzastrobin)、ジモキシストロビン（Dimoxystrobin)、ピ ラクロストロビン (Pyraclostrobin)、フノレォキサストロビン（Fluoxastrobin)のようなスト口 ビルリン系化合物；  Azoxystrobin, Kresoxim-Methyl, Metominofen, Trifloxystrobin, Picoxystrobin, Oryzastrobin, Dimoxystrobin (Dimoxystrobin), pyraclostrobin, and strutovirin compounds such as Fluoxastrobin;
ファモキサドン（Famoxadone)のようなォキサゾリジノン系化合物；  Oxazolidinone compounds such as Famoxadone;
エタボキサム（Ethaboxam)のようなチアゾールカルボキサミド系化合物；  Thiazole carboxamide compounds such as ethaboxam;
シルチオファム（Silthiopham)のようなシリルアミド系化合物；  Silylamide compounds such as Silthiopham;
ィプロバリカルプ（Iprovalicarb)、ベンチアバリカルブーイソプロピル (benthiavalicar b-isopropyl)のようなァミノアシッドアミドカーバメート系化合物；  Amino acid amide carbamate compounds such as Iprovalicarb, benchthiavalicar b-isopropyl;
フエナミドン（Fenamidone)のようなイミダゾリジン系化合物；  Imidazolidine compounds such as Fenamidone;
フェンへキサミド（Fenhexamid)のようなハイド口キシァ二リド系化合物；  Hydoxyxanilide compounds such as fenhexamid;
フルスルフアミド（Flusulfamid)のようなベンゼンスルホンアミド系化合物；  Benzenesulfonamide compounds such as Flusulfamid;
シフルフエナミド（Cyflufenamid)のようなォキシムエーテル系化合物；  Oxime ether compounds such as cyflufenamid;
フエノキサ-ル（Fenoxanil)のようなフエノキシアミド系化合物；  Phenoxy amide compounds such as Fenoxanil;
アトラキノン系化合物；  Atraquinone compounds;
クロトン酸系化合物；  Crotonic acid compounds;
ノ リダマイシン（Validamycin)、カスガマイシン（Kasugamycin)、ポリオキシン (Polyoxi ns)のような抗生物質；  Antibiotics such as Noridamycin, Kasugamycin, Polyoxins;
ィミノクタジン（Iminoctadine)のようなグァ-ジン系化合物；  Guazine compounds such as iminoctadine;
その他の化合物として、イソプロチオラン（Isoprothiolane)、ピロキロン（Pyroquilon) 、ジクロメジン（Diclomezine)、キノキシフェン（Quinoxyfen)、プロパモカルブ塩酸塩（P ropamocarb Hydrochloride)クロノレヒクリン (Chloropicrin)、タンメット (Dazomet)、メタ ムナトリウム塩（Metam- sodium)、ニコビフェン（Nicobifen)、メトラフエノン（Metrafenone )、 MTF- 753、 UBF- 307、ジクロシメット（Diclocymet)、プロキンアジド（Proquinazid)、 アミスルブロム（Amisulbrom；別名アミブロドール（Am¾romdole) )、 KIF-7767 (KUF- 1 204、 Pyribencarb methyl、 Mepyricarb)、 ¾yngenta 446510 (Mandipropamid^ dipro mandamid)などが挙げられる。 Other compounds include Isoprothiolane, Pyroquilon, Diclomezine, Quinoxyfen, Propamocarb Hydrochloride, Chloropicrin, Dazomet, Sodium sodium ( Metam-sodium), Nicobifen, Metrafenone, MTF-753, UBF-307, Diclocymet, Proquinazid, Examples include Amisulbrom (also known as Am¾romdole), KIF-7767 (KUF-1 204, Pyribencarb methyl, Mepyricarb), and ¾yngenta 446510 (Mandipropamid ^ dipro mandamid).
上記他の農薬中の、殺虫剤、殺ダニ剤、或いは殺線虫剤、すなわち殺害虫剤の有 効成分化合物（一般名；一部申請中を含む）としては、例えばプロフエノホス (Profenof os)、ジクロルボス (Dichlorvos)、フエナミホス (Fenamiphos)、フエ-トロチオン（Fenitr othion)、 EPN、ダイアジノン（Diazinon)、クロルピリホスメチル（Chlorpyrifos- methyl) 、ァセフェート（Acephate)、プロチォホス（Prothiofos)、ホスチアゼート（Fosthiazate) 、ホスホカルブ（Phosphocarb)、カズサホス（Cadusafos)、ジスルホトン（Dislufoton)、ク ロルピリホス（Chlorpyrifos)、デメトン- S-メチル（Demeton-S- methyl)、ジメトエート（Di methoate)、メタミドホス（Methamidophos)のような有機リン酸エステル系化合物； 力ルバリル（Carbaryl)、プロボキスル（Propoxur)、アルジカルプ（Aldicarb)、カルボ フラン（Carboforan)、チォジカルプ（Thiodicarb)、メソミル (Methomyl)、ォキサミル（0 xamyl)、ェチォフェンカルプ（Ethiofencarb)、ピリミカルブ（Pirimicarb)、フエノブカル ブ（Fenobucarb)、カルボスルファン（Carbosulfan)、ベンフラカルブ (Benluracarb)の ようなカーノメート系化合物；  In the above-mentioned other pesticides, insecticides, acaricides, or nematicides, that is, active compound compounds (generic name; including some pending applications) of pesticides, for example, Profenofos, Dichlorvos, Fenamiphos, Fenitr othion, EPN, Diazinon, Chlorpyrifos-methyl, Acephate, Prothiofos, Phoschiazate (Fosthiazate) Organophosphates such as Phosphocarb, Cadusafos, Dislufoton, Chlorpyrifos, Demeton-S-methyl, Dimethhoate, Methamidophos Compounds: Power Barbaryl, Propoxur, Aldicarb, Carboforan, Chi Carnots such as Thiodicarb, Methomyl, Oxamyl (0 xamyl), Ethiofencarb, Pirimicarb, Fenobucarb, Carbosulfan, Benluracarb Compounds;
カルタップ (Cartap)、チオシクラム（Thiocyclam)、ベンスルタップ (Bensultap)のよう なネライストキシン誘導体；  Nereistoxin derivatives such as Cartap, Thiocyclam, Bensultap;
ジコホル (Dicofol)、テトラジホン（Tetradifon)、エンドスルファン（Endosulfan)のよう な有機塩素系化合物；  Organochlorine compounds such as Dicofol, Tetradifon, Endosulfan;
酸化フェンブタスズ (Fenbutatin Oxide)のような有機金属系化合物；  Organometallic compounds such as Fenbutatin Oxide;
フェンノ レレート (Fenvalerate)、ぺノレメトリン (Permethrin)ゝシぺノレメトリン (Cyperme thrin)、デルタメトリン（Deltamethrin)、シハロトリン（Cyhalothrin)、テフルトリン（Teflut hrin)、エトフェンプロックス (Ethofenprox)、フルフェンプロックス（Flufenprox)、フェン プロパトリン（Fenpropathrin)、ビフェントリン（Bifenthrin)、イミデート（Imidate)のような ピレスロイド系化合物；  Fenvalerate, Penolemethrin (Permethrin) ゝ Cyperme thrin, Deltamethrin, Cyhalothrin, Teflut hrin, Ethofenprox, Flufenprox, Flufenprox Pyrethroid compounds such as Fenpropathrin, Bifenthrin, and Imidate;
ジフルべンズロン（Diflubenzuron)、クロルフルァズロン（Chlorfluazuron)、テフルべ ンズロン（Teflubenzuron)、フルフエノクスロン（Flufenoxuron)、ルフェヌロン（Lufenuro n)、ノバルロン（Novaluron)、ビストリフルロン（Bistrifluron)、ノビフルムロン（Noviflumu ron)のようなべンゾィルゥレア系化合物； Diflubenzuron, Chlorfluazuron, Teflubenzuron, Flufenoxuron, Lufenuro n) Benzoylurea compounds such as Novaluron, Bistrifluron, Noviflumuron;
メトプレン（Methoprene)のような幼若ホルモン様化合物；  Juvenile hormone-like compounds such as methoprene;
ピリダベン（Pyridaben)のようなピリダジノン系化合物；  Pyridazinone compounds such as Pyridaben;
フェンピロキシメート（Fenpyroximate)、フィプロ-ル（Fipronil)、テブフェンピラド（Te bufenpyrad)、ェチピロール（Ethiprole)、トルフェンピラド（Tolfenpyrad)、ァセトプロ一 ル（Acetoprole)のようなピラゾール系化合物；  Pyrazole compounds such as Fenpyroximate, Fipronil, Te bufenpyrad, Ethiprole, Tolfenpyrad, Acetoprole;
イミダクロプリド（Imidacloprid)、二テンビラム（Nitenpyram)、ァセタミプリド（Acetamip rid)、チアクロプリド（Thiacloprid)、チアメトキサム（Thiamethoxam)、クロチア-ジン（C lothianidin)、 -ジノテフラン（Nidinoteforan)、ジノテフラン（Dinoteforan)などのネオ- 3チノイド、；  Imidacloprid, Nitenpyram, Acetamip rid, Thiacloprid, Thiamethoxam, Crothiadin, Clothianidin, Dinotefuran, Dinotefuran, Dinotean Tinoids;
テブフエノジド（Tebufenozide)、メトキシフエノジド（Methoxyfenozide)、クロマフエノジ ド（Chromafenozide)、ノヽロフエノジド（Halofenozide)などのヒドラジン系化合物； ピリダリル (Pyridaryl)、フ口-力ミド（Flonicamid)などのようなピリジン系化合物； スピロディクロフェン（Spirodiclofen)などのようなテトロニック酸系化合物； フルアタリピリム（Fluacrypyrin)などのようなスト口ビルリン系化合物；  Hydrazine compounds such as Tebufenozide, Methoxyfenozide, Chromafenozide, Halofenozide; Pyridine compounds such as Pyridaryl, Flonicamid A tetronic acid compound such as Spirodiclofen; a streptavirline compound such as Fluacrypyrin;
フルフエネリム（Flufenerim)などのようなピリジナミン系化合物；  Pyridinamine compounds such as Flufenerim;
ジニトロ系化合物、有機硫黄化合物、尿素系化合物、トリアジン系化合物、ヒドラゾ ン系化合物、また、その他の化合物として、ブプロフエジン（Buprofezin)、へキシチア ゾクス（Hexythiazox)、アミトラズ（Amitraz)、クロルジメホルム（Chlordimeform)、シラフ ルォフェン（Silafluofen)、トリァザメイト（Triazamate)、ピメトロジン（Pymetrozine)、ピリ ミジフェン（Pyrimidifen)、クロルフエナビル（Chlorfenapyr)、インドキサカルブ（Indoxac arb)ゝァセキノシノレ (Acequinocyl)、エトキサゾ一ノレ (Etoxazole)、シロマジン (Cyromaz ine)、 1, 3—ジクロロプロペン（1, 3- dichloropropene)、ジァフェンチウロン（Diafenthi uron)、ベンクロチアズ（Benclothiaz)、フルフェンリム（Flufenerim)、ピリダリル（Pyridal yl)、スピロジクロフェン（Spirodiclofen)、ビフエナゼート（Bifenazate)、スピロテトラマツ ト（spirotetramat)、プロパノレギット（Propargite)、べノレブチン（Verbutin)、スピロメシフ ェン（Spiromesifen)、チアゾリルシナノ-トリル（Thiazolylcinnanonitrile)、アミドフルメッ ト（Amidoflumet)、フルべンジアミド（Flubendiamide)のような化合物； AKD- 1022、 IKA -2000などが挙げられる。更に、 BT剤、昆虫病原ウィルス剤などのような微生物農薬 、アベルメクチン（Avermectin)、ミルべマイシン（Milbemycin)、スピノサッド（Spinosad) 、エマメクチンべンゾエート (Emamectin Benzoate)、ィベノレメクチン (Ivermectin)、レ ピメクチン（Lepimectin)のような抗生物質、ァザデイラクチン (Azadirachtin)、ロテノン (Rotenone)のような天然物などと、混用、併用することもできる。 Dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, hydrazine compounds, and other compounds include Buprofezin, Hexythiazox, Amitraz, Chlorimeform, Silafluofen, Triazamate, Pymetrozine, Pyrimidifen, Chlorfenapyr, Indoxac arb, Acequinocyl, Etoxazole, C ine), 1,3-dichloropropene, 1,3-dichloropropene, Diafenthiuron, Benclothiaz, Flufenerim, Pyridal yl, Spirodiclofen, Bifenazate, spirotetra Pine (spirotetramat), propanoregit (Propargite), benolevbutin (Verbutin), spiromesifen (Spiromesifen), thiazolyl cinano-tolyl (Thiazolylcinnanonitrile), amide-flumeme And compounds such as Amidoflumet and Flubendiamide; AKD-1022 and IKA-2000. In addition, microbial pesticides such as BT agents, entomopathogenic virus agents, Avermectin, Milbemycin, Spinosad, Emamectin Benzoate, Ivermectin, Lepimectin ), Antibiotics such as Azadirachtin, and natural products such as Rotenone.
実施例  Example
[0055] 次に式 (I)のビフエニル誘導体及びその製造用中間体の具体的合成例を記載する 。なお、各合成例中で、展開溶媒の比は容量比であり、 1H-NMRは CDC1を溶媒に用  [0055] Next, specific synthesis examples of the biphenyl derivative of the formula (I) and the intermediate for production thereof will be described. In each synthesis example, the ratio of developing solvent is a volume ratio, and 1H-NMR uses CDC1 as the solvent.
3 いて VARIAN社製 300MHz (MERCURY plus)で測定した。  3 and measured at 300 MHz (MERCURY plus) manufactured by VARIAN.
合成例 1  Synthesis example 1
N-メチル -3- (6'-ブロモ -2'-クロ口- 3'-トリフルォロメチルフエ-ル)ベンズアミド (ィ匕合 物 No.I— 1)の合成  Synthesis of N-methyl-3- (6'-bromo-2'-black mouth-3'-trifluoromethylphenol) benzamide (Compound No.I-1)
(1) 3-ァミノ- 4-ブロモベンゾトリフルオリド 37gのベンゼン 300ml溶液中へ、 N-クロ口 スクシンイミド 20. 6gを室温にて数回に分けて投入した後、 50〜60°Cにて 40時間緩 やかに攪拌した。ガスクロマトグラフィーにて反応終了を確認した後氷冷し、反応系 中へ約 50gの無水硫酸ナトリウムをカ卩えてしばらく攪拌し、セライトろ過した。ろ液から 減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性） カラムクロマトグラフィー (展開溶媒 n-へキサン）にて精製し、さらに減圧蒸留にて沸 点 88— 91°C/5mmHgの 3-ァミノ- 4-ブロモ - 2-クロ口べンゾトリフルオリド 16gを得た 。このものの NMRは以下の通りであった。  (1) 3-Amino-4-bromobenzotrifluoride Into a solution of 37 g of benzene in 300 ml of benzene, N-closuccinic succinimide (20. 6 g) was added in several portions at room temperature, then at 50-60 ° C. Stir gently for a period of time. After confirming the completion of the reaction by gas chromatography, it was cooled with ice, and about 50 g of anhydrous sodium sulfate was added to the reaction system and stirred for a while, followed by Celite filtration. The solvent was distilled off from the filtrate under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical / neutral) column chromatography (developing solvent n-hexane) and further distilled under reduced pressure. 16 g of 3-amino-4-bromo-2-chromobenzobenzofluoride having a boiling point of 88-91 ° C / 5 mmHg was obtained. The NMR of this product was as follows.
1H-NMR δ (ppm) 4.78(bs,2H),6.94(d,lH;J=8.4Hz),7.43(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 4.78 (bs, 2H), 6.94 (d, lH; J = 8.4Hz), 7.43 (d, lH; J = 8.4Hz)
[0056] (2) (1)で得た 3-ァミノ- 4-ブロモ -2-クロ口べンゾトリフルオリド 32gとヨウ素 19. 3gを ベンゼン 350mlに溶解し、攪拌しながら亜硝酸 t-ブチル 18. 5mlを 15〜19°Cにて 2 5分間を要して滴下した。 17〜18°Cにてさらに 30分間攪拌した後、反応系中へ氷片 約 50gと酢酸ェチル 200mlを加え、さらに 5%亜硫酸水素ナトリウム水溶液 300mlを 加えてしばらく攪拌した。得られた有機層を氷冷 5%水酸ィ匕カリウム水溶液 200mlで 洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（ 関東ィ匕学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へ キサン）にて精製し、油状の 4-ブロモ -2-クロ口- 3-ョードベンゾトリフルオリド 28. 5gを 得た。また、このものの NMRは以下の通りであった。 [0056] (2) 32 g of 3-amino-4-bromo-2-chlorobenzobenzotrifluoride obtained in (1) and 19.3 g of iodine were dissolved in 350 ml of benzene, and t-butyl nitrite with stirring. 18. 5ml was added dropwise at 15-19 ° C over 25 minutes. After further stirring for 30 minutes at 17 to 18 ° C, about 50 g of ice pieces and 200 ml of ethyl acetate were added to the reaction system, and further 300 ml of 5% aqueous sodium hydrogensulfite solution was added and stirred for a while. The obtained organic layer was washed with 200 ml of ice-cold 5% potassium hydroxide aqueous solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. Purified by column chromatography (developing solvent: n-hexane), silica gel 60N manufactured by Kanto Chemical Co., Ltd .; spherical, neutral; oily 4-bromo-2-chloro-3-3-iodobenzotrifluoride 28 Obtained 5 g. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 7.55(d,lH;J=8.7Hz),7.65(d,lH;J=8.7Hz)  1H-NMR δ (ppm) 7.55 (d, lH; J = 8.7 Hz), 7.65 (d, lH; J = 8.7 Hz)
[0057] (3) (2)で得た 4-ブロモ -2-クロ口- 3-ョードベンゾトリフルオリド 1. 93gと 3-エトキシカ ルボユルフェ-ルボロン酸 1. 2gをエタノール 20mlに溶解し、 5%パラジウム炭素（we t、 Degussa製品 E101Type) O. 43gをカ卩えて室温にて 10分間攪拌した。反応系を 0°C に冷却し、炭酸ナトリウム粉末 1. 6gを加え、同温度で反応系内を窒素置換した後、 1 3時間加熱還流した。放冷後、酢酸ェチル 80ml及び無水硫酸ナトリウム約 50gをカロ え、 5分間攪拌した後、セライトろ過した。ろ液力も減圧下溶媒を留去し、残渣をシリカ ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル = 16 : 1)にて精製し、 3- (6'-ブロモ -2'-クロ口- 3'-トリフルォ ロメチルフエ-ル)-安息香酸ェチル (ィ匕合物 No.V— 3) 0. 82gを無定形個体として得 た。また、このものの NMRは以下の通りであった。 [0057] (3) 4-Bromo-2-chloro-3-iodobenzotrifluoride (1.93 g) obtained in (2) and 1.2 g of 3-ethoxycarboxyl boronic acid were dissolved in 20 ml of ethanol. 43 g of 5% palladium on carbon (wet, Degussa product E101Type) O. was added and stirred at room temperature for 10 minutes. The reaction system was cooled to 0 ° C., 1.6 g of sodium carbonate powder was added, the inside of the reaction system was purged with nitrogen at the same temperature, and the mixture was heated to reflux for 13 hours. After allowing to cool, 80 ml of ethyl acetate and about 50 g of anhydrous sodium sulfate were added, stirred for 5 minutes, and filtered through Celite. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) (developing solvent n-hexane: ethyl acetate = 16: 1). To obtain 3- (6'-bromo-2'-black mouth-3'-trifluoromethylphenol) -ethyl benzoate (Compound No.V-3) as an amorphous solid. It was. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 1.40(t,3H;J=7.2Hz),4.39(q,2H;J=7.2Hz),7.40(d,lH;J=7.8Hz),7.5 4-7.61(m,2H),7.72(d,lH;J=8.4Hz),7.91(s,lH),8.14(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 1.40 (t, 3H; J = 7.2Hz), 4.39 (q, 2H; J = 7.2Hz), 7.40 (d, lH; J = 7.8Hz), 7.5 4-7.61 (m, 2H), 7.72 (d, lH; J = 8.4Hz), 7.91 (s, lH), 8.14 (d, lH; J = 8.4Hz)
[0058] (4) (3)で得た 3- (6'-ブロモ - 2'-クロ口- 3'-トリフルォロメチルフエ-ル)-安息香酸ェ チノレ 0. 41gを 400/0メチノレ ミン メタノーノレ溶液 7. 2ml【こ溶解し、 40〜60oC【こて 3 . 5時間攪拌した。放冷後、減圧下メタノールと過剰のメチルアミンを留去し、残渣を シリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性)カラムクロマトグラフィー（展開 溶媒 n-へキサン:酢酸ェチル = 1 : 1)にて精製し、融点 146. 3°Cの目的化合物 0. 27gを得た。また、このものの NMRは以下の通りであった。 [0058] (4) (3) was obtained in 3 (6'-bromo - 2'black port - 3'triflate Ruo Russia methyl Hue - Le) - benzoic Sane Chinore 0. 41 g of 40 0/0 Metinoremine methanol solution 7.2 ml [dissolved and stirred at 40-60 ° C. trowel for 3.5 hours. After standing to cool, methanol and excess methylamine were distilled off under reduced pressure, and the residue was subjected to silica gel (silica gel 60N, spherical, neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 1). The product was purified in 1) to obtain 0.27 g of the objective compound having a melting point of 146.3 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 3.01(d,3H;J=4.8Hz),6.30(bs,lH),7.31-7.36(m,lH),7.52-7.62(m, 3H),7.71(d,lH;J=8.4Hz),7.83-7.88(m,lH)  1H-NMR δ (ppm) 3.01 (d, 3H; J = 4.8Hz), 6.30 (bs, lH), 7.31-7.36 (m, lH), 7.52-7.62 (m, 3H), 7.71 (d, lH; J = 8.4Hz), 7.83-7.88 (m, lH)
[0059] 合成例 2 [0059] Synthesis Example 2
N-メチル -3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)ベンズアミド (ィ匕合 物 No.I— 16)の合成  Synthesis of N-methyl-3- (2'-black-6-methyl-3'-trifluoromethylphenol) benzamide (Compound No.I-16)
(1)合成例 1 (1)で得た 3-ァミノ- 4-ブロモ -2-クロ口べンゾトリフルオリド 27. 5gの 1,4- ジォキサン 400ml溶液中へ、テトラキストリフエ-ルフォスフィンパラジウム 5. 8gを室 温にてカ卩え、 10分間攪拌した。 0°Cに冷却し、 50%トリメチルボロキシンのテトラヒドロ フラン溶液 47ml及び炭酸カリウム粉末 41. 5gを加え、反応系中を窒素置換した後、 18時間加熱還流した。 (1) Synthesis Example 1 3-Amino-4-bromo-2-chlorodibenzotrifluoride obtained in (1) 27.5 g of 1,4- In a 400 ml solution of dioxane, 5.8 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. After cooling to 0 ° C., 47 ml of a 50% trimethylboroxine tetrahydrofuran solution and 41.5 g of potassium carbonate powder were added, and the reaction system was purged with nitrogen, followed by heating to reflux for 18 hours.
放冷後、酢酸ェチル 300ml及び無水硫酸ナトリウム約 200gを加えしばらく攪拌し た後、不溶物をセライトろ過にて濾別した。ろ液力 減圧下溶媒を留去し、残渣をシリ 力ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル = 12 : 1)にて精製し、油状の 3-ァミノ- 2-クロ口- 4-メチル ベンゾトリフノレオリド 18. 2gを得た。また、このものの NMRは以下の通りであった。 1H-NMR δ (ppm) 2.25(s,3H),4.29(bs,2H),7.00(d,lH;J=8.4Hz),7.03(d,lH;J=8.4Hz) [0060] (2)臭ィ匕銅 (II) 9. 2gをァセトニトリル 150mlに溶解し、 0°Cに冷却後、亜硝酸 t-プチ ル 6. 5mlをカ卩ぇ（1)で得た 3-ァミノ- 2-クロ口- 4-メチルベンゾトリフルオリド 7. 9gのァ セトニトリル 50ml溶液を— 2〜7°Cにて 20分間を要して滴下した後、さらに 15〜20 °Cにて 3時間攪拌した。  After allowing to cool, 300 ml of ethyl acetate and about 200 g of anhydrous sodium sulfate were added and stirred for a while, and then insoluble matter was filtered off through Celite filtration. Filtration force The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) (developing solvent n-hexane: ethyl acetate = 12: 1). To obtain 18.2 g of oily 3-amino-2-chromo-4-methylbenzotrifunoleolide. Moreover, NMR of this product was as follows. 1H-NMR δ (ppm) 2.25 (s, 3H), 4.29 (bs, 2H), 7.00 (d, lH; J = 8.4Hz), 7.03 (d, lH; J = 8.4Hz) [0060] (2) Odory copper (II) 9.2g dissolved in acetonitrile 150ml, cooled to 0 ° C, 6.5ml nitrous acid t-butyl obtained in cake (1) 3-amino-2-chloro Methyl 4-methylbenzotrifluoride (7.9 g) in 50 ml of acetonitrile was added dropwise at −2 to 7 ° C. over 20 minutes, and the mixture was further stirred at 15 to 20 ° C. for 3 hours.
0°Cに冷却し、 1規定塩酸 40mlを加えしばらく攪拌後、減圧下ァセトニトリルを留去 し、酢酸ェチルをカ卩ぇ抽出し、 10%塩ィ匕アンモ-ゥム水溶液、次いで飽和食塩水で 洗浄した。酢酸ェチル層を無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し、 残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性)カラムクロマトグラフィー (展開溶媒 n-へキサン:酢酸ェチル = 12 : 1)にて精製し、油状の 3-ブロモ -2-クロ口 -4-メチルベンゾトリフルオリド 8. 9gを得た。また、このものの NMRは以下の通りであ つた o  After cooling to 0 ° C and adding 40 ml of 1N hydrochloric acid and stirring for a while, the acetonitrile was distilled off under reduced pressure, and the ethyl acetate was extracted with a 10% aqueous solution of sodium chloride and saturated saline. Washed. After drying the ethyl acetate layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel 60N; spherical / neutral, manufactured by Kanto Yigaku) (developing solvent n-hexane: acetic acid). The product was purified by ethyl = 12: 1) to obtain 8.9 g of oily 3-bromo-2-chloro-4-methylbenzotrifluoride. The NMR of this product is as follows: o
1H-NMR δ (ppm) 2.52(s,3H),7.24(d, 1H;J=8. lHz),7.54(d, 1H;J=8.1Hz)  1H-NMR δ (ppm) 2.52 (s, 3H), 7.24 (d, 1H; J = 8 lHz), 7.54 (d, 1H; J = 8.1Hz)
[0061] (3) (2)で得た 3-ブロモ -2-クロ口- 4-メチルベンゾトリフルオリド 11. 8gのトルエン 30 Oml溶液中へ、テトラキストリフエニルフォスフィンパラジウム 1. 5gを室温にてカ卩え、 1 0分間攪拌した。 5°Cに冷却し、 3-メトキシカルボ-ルフエ-ルボロン酸 10. 5g、エタ ノール 30ml、 2モル濃度の炭酸ナトリウム水 43ml及び炭酸ナトリウム粉末 4. 6gを加 え、同温度で反応系内を窒素置換した後、 11時間加熱還流した。 放冷後、酢酸ェ チル 200mlをカ卩ぇ抽出し、 10%塩化アンモ-ゥム水溶液、次いで飽和食塩水で洗 浄した。有機層を無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し、残渣をシ リカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性)カラムクロマトグラフィー（展開溶 媒 n-へキサン：酢酸ェチル = 2 : 1)にて精製し、 3- (2'-クロ口- 6しメチル -3'-トリフル ォロメチルフエ-ル)-安息香酸メチル (ィ匕合物 No.V— 7) 9. 05gを無定形個体として 得た。また、このものの NMRは以下の通りであった。 [0061] (3) 3-Bromo-2-chloro-4-methylbenzotrifluoride obtained in (2) 1 .5 g of tetrakistriphenylphosphine palladium in room temperature 30 ml of toluene was brought to room temperature. The mixture was stirred and stirred for 10 minutes. Cool to 5 ° C, add 10.5 g of 3-methoxycarbolboronic acid, 30 ml of ethanol, 43 ml of 2 molar sodium carbonate water and 4.6 g of sodium carbonate powder, and leave the reaction system at the same temperature. After purging with nitrogen, the mixture was heated to reflux for 11 hours. After standing to cool, extract 200 ml of ethyl acetate and wash with 10% ammonium chloride aqueous solution and then with saturated saline. Purified. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Yigaku, silica gel 60N; spherical / neutral) column chromatography (developing solvent n-hexane: Purified with ethyl acetate = 2: 1), 3- (2'-black-6-methyl-3'-trifluoromethylphenol) -methyl benzoate (Compound No.V-7) 9. 05g was obtained as an amorphous individual. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.09(s,3H),3.92(s,3H),7.28(d,lH;J=8.4Hz),7.37(d,lH;J=7.5Hz),7 .53-7.63(m,2H),7.86(s,lH),8.10(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 2.09 (s, 3H), 3.92 (s, 3H), 7.28 (d, lH; J = 8.4Hz), 7.37 (d, lH; J = 7.5Hz), 7.53-7.63 (m, 2H), 7.86 (s, lH), 8.10 (d, lH; J = 8.4Hz)
[0062] (4) (3)で得た 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)-安息香酸メチ ノレ 8. 9gを 400/0メチノレ ミン メタノーノレ溶液 100ml【こ溶解し、 40oC【こて 1. 5時 攪拌した後、さらに室温にて 32時間攪拌した。減圧下メタノールと過剰のメチルアミ ンを留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラムクロ マトグラフィー（展開溶媒 n-へキサン:酢酸ェチル = 1 : 1)にて精製し、融点 132. 8 での目的化合物 8. Ogを得た。また、このものの NMRは以下の通りであった。 [0062] (4) (3) obtained in 3- (2'-black opening - 6 Mr. methyl-3'-triflate Ruo Russia methyl Hue - Le) - benzoic acid methylcarbamoyl Honoré 8.40 to 9 g 0/0 Mechinore Min methanol solution 100 ml [dissolved, 40 o C [trowel 1.5 hours] After stirring for 5 hours, the mixture was further stirred at room temperature for 32 hours. Methanol and excess methylamine were distilled off under reduced pressure, and the residue was purified on silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 1: 1). To obtain the target compound 8. Og having a melting point of 132.8. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.09(s,3H),3.02(d,3H;J=4.8Hz),6.22(bs,lH),7.26-7.32(m,2H),7. 55(t,lH;J=7.8Hz),7.57(s,lH),7.62(d,lH;J=8.1Hz),7.80-7.84(m,lH)  1H-NMR δ (ppm) 2.09 (s, 3H), 3.02 (d, 3H; J = 4.8Hz), 6.22 (bs, lH), 7.26-7.32 (m, 2H), 7.55 (t, lH; J = 7.8Hz), 7.57 (s, lH), 7.62 (d, lH; J = 8.1Hz), 7.80-7.84 (m, lH)
[0063] 合成例 3  [0063] Synthesis Example 3
N-メチル -N-プロパルギル- 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエニル） ベンズアミド (ィ匕合物 No.I— 21)の合成  Synthesis of N-methyl-N-propargyl-3- (2'-black-6-methyl-3'-trifluoromethylphenyl) benzamide (compound No.I-21)
合成例 2で得た N-メチル - 3-(2， -クロ口- 6， -メチル -3， -トリフルォロメチルフエ-ル） ベンズアミド 0. 2gの無水テトラヒドロフラン 10ml溶液中へ 10°Cで 60%水素化ナトリ ゥム 0. lgを数回に分けて投入後、同温度で 10分間攪拌した。続いて 5°Cにてプロ パルギルブロミド 0. 14mlを投入し、 15°Cにて 4時間攪拌した。反応溶液を 0°Cに冷 却後、酢酸ェチル 50ml及び 10%塩ィ匕アンモ-ゥム水溶液 30mlを加えてしばらく攪 拌し、酢酸ェチルで 2回抽出した。抽出した有機層を合わせ、無水硫酸ナトリウムを 加え乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 6 ON；球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン：酢酸ェチル = 2： 1 )にて精製し、無定形固体の目的化合物 0. 16gを得た。また、このものの NMRは以 下の通りであった。 Ή-NMR δ (ppm) 2.10(s,3H),2.28(bs,lH),3.09 & 3.14(bs,3H),4.03(bs,lH),4.37(bs,l H),7.2-7.3(m,3H),7.50-7.58(m,2H),7.60(d,lH;J=8.4Hz) N-methyl-3- (2, -chloro-6, -methyl-3, -trifluoromethylphenol) benzamide obtained in Synthesis Example 2 0.2 g in 10 ml of anhydrous tetrahydrofuran at 10 ° C 60% sodium hydride (0.1 lg) was added in several portions, and the mixture was stirred at the same temperature for 10 minutes. Subsequently, 0.14 ml of propargyl bromide was added at 5 ° C, and the mixture was stirred at 15 ° C for 4 hours. The reaction solution was cooled to 0 ° C., 50 ml of ethyl acetate and 30 ml of 10% aqueous solution of ammonium chloride were added and stirred for a while, and extracted twice with ethyl acetate. The extracted organic layers were combined, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 6 ON; spherical “neutral”) column chromatography (developing solvent n). Purification by -hexane: ethyl acetate = 2: 1) gave 0.16 g of the target compound as an amorphous solid. In addition, NMR of this product was as follows. Ή-NMR δ (ppm) 2.10 (s, 3H), 2.28 (bs, lH), 3.09 & 3.14 (bs, 3H), 4.03 (bs, lH), 4.37 (bs, l H), 7.2-7.3 (m , 3H), 7.50-7.58 (m, 2H), 7.60 (d, lH; J = 8.4Hz)
[0064] 合成例 4 [0064] Synthesis Example 4
N-ェチル -3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)ベンズアミド (ィ匕合 物 No.I— 18)の合成  Synthesis of N-ethyl-3- (2'-black-6-methyl-3'-trifluoromethylphenol) benzamide (Compound No.I-18)
(1)合成例 2 (3)に準じて 3-メトキシカルボ-ルフエ-ルボロン酸の代わりに 3-ェトキ シカルボ-ルフエ-ルボロン酸を用いて得た 3- (2'-クロ口- 6しメチル -3'-トリフルォロメ チルフエ-ル)-安息香酸ェチル（ィ匕合物 No. V— 8) 2. 4gの 1,4-ジォキサン 35ml溶 液中へ、 10°Cで苛性ソーダ 1. 5gの 20ml水溶液をカ卩えた後、室温にて 11時間攪拌 した。さらに 50°Cまで加温し、同温度にて 5時間攪拌した。酢酸ェチル 150mlを加え 、さらに氷冷 1規定塩酸 100mlを加えてしばらく攪拌した。有機層を無水硫酸ナトリウ ムにて乾燥後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60 N ;球状'中性)カラムクロマトグラフィーにて精製し (展開溶媒 n-へキサン:酢酸ェチ ル = 5： 3)、固体の 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)-安息香酸 (化合物 No.V—6) 1. 7gを得た。また、このものの NMRは以下の通りであった。  (1) Synthesis Example 2 3- (2'-Chrono-6-methyl) obtained by using 3-ethoxycarbolboronic acid instead of 3-methoxycarbolboronic acid according to Synthesis Example 2 (3) -3'-Trifluoromethyl propyl) -ethyl benzoate (Compound No. V—8) 2. Caustic soda at 10 ° C in 4 g of 1,4-dioxane 35 ml solution 1.5 g of 20 ml aqueous solution After stirring, the mixture was stirred at room temperature for 11 hours. The mixture was further heated to 50 ° C and stirred at the same temperature for 5 hours. Ethyl acetate (150 ml) was added, and ice-cold 1N hydrochloric acid (100 ml) was further added, followed by stirring for a while. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (silica gel 60 N; spherical 'neutral', manufactured by Kanto Yigaku) (developing solvent n -Hexane: ethyl acetate = 5: 3), solid 3- (2'-chloro-6-6-methyl-3'-trifluoromethylphenol) -benzoic acid (Compound No. V-6) ) 1. 7g was obtained. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.11(s,3H),7.30(d,lH;J=7.8Hz),7.44(d,lH;J=7.5Hz),7.58-7.65(m ,2H),7.95(s,lH),8.18(d,lH;J=7.8Hz)  1H-NMR δ (ppm) 2.11 (s, 3H), 7.30 (d, lH; J = 7.8Hz), 7.44 (d, lH; J = 7.5Hz), 7.58-7.65 (m, 2H), 7.95 (s , lH), 8.18 (d, lH; J = 7.8Hz)
[0065] (2) (1)で得た 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)-安息香酸 2. 1 gの 1,2-ジクロロェタン 30ml溶液中へ、塩化チォ -ル 0. 87ml、続いて Ν,Ν-ジメチル ホルムアミド 3滴を加え、加熱還流下に 3時間攪拌した。放冷後、反応溶液中へトル ェン 20mlを加え、減圧下、濃縮した。残渣オイルへ再度トルエン 30mlを加え、濃縮 (2回繰り返し)することにより、粗製の 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフ ェ -ル) -ベンゾイルクロリド 2. Ogを固体として得た。 [0065] (2) 3- (2'-Chromium-6-methyl-3'-trifluoromethylphenol) -benzoic acid obtained in (1) 2.1 g of 1,2-dichloroethane 30 ml To the solution was added 0.87 ml of thiol chloride, followed by 3 drops of Ν, Ν-dimethylformamide, and the mixture was stirred for 3 hours with heating under reflux. After allowing to cool, 20 ml of toluene was added to the reaction solution, and the mixture was concentrated under reduced pressure. Add 30 ml of toluene again to the residual oil and concentrate (repeat twice) to give crude 3- (2'-chloro-6-6 methyl-3'-trifluoromethylphenol) -benzoyl chloride 2 Og was obtained as a solid.
1H-NMR δ (ppm) 2.11(s,3H),7.32(d,lH;J=8.4Hz),7.50-7.54(m,lH),7.61-7.69(m,2 H),7.96(s,lH),8.18-8.22(m,lH)  1H-NMR δ (ppm) 2.11 (s, 3H), 7.32 (d, lH; J = 8.4Hz), 7.50-7.54 (m, lH), 7.61-7.69 (m, 2H), 7.96 (s, lH ), 8.18-8.22 (m, lH)
[0066] (3) 2モル濃度のェチルアミンーテトラヒドロフラン溶液 0. 6mlを無水 Ν,Ν-ジメチルホ ルムアミド 5mlで希釈し、 (2)で得た 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ -ル) -ベンゾイルクロリド 0. 2gのテトラヒドロフラン 2ml溶液を 0°Cにて加え、同温度で トリェチルァミン lmlの無水 Ν,Ν-ジメチルホルムアミド lml溶液を滴下した後、 20°Cに て 1時間、さらに 35°Cにて 4時間攪拌した。 0°Cに冷却し、酢酸ェチル 25mlをカロえ、 さらに水 10mlを加えてしばらく攪拌した後、有機層を無水硫酸ナトリウムにて乾燥後 、減圧下溶媒留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性)力 ラムクロマトグラフィー（展開溶媒 n-へキサン:酢酸ェチル = 1 : 1)にて精製し、無定 形固体の目的化合物 80mgを得た。また、このものの NMRは以下の通りであった。 1H-NMR δ (ppm) 1.24(t,3H;J=5.6Hz),2.08(s,3H),3.45-3.54(m,2H),6.13(bs,lH),7.2 7-7.30(m,2H),7.52-7.55(m,2H),7.60(d,lH;J=8.4Hz),7.81(d,lH;J=7.8Hz) [0066] (3) 0.6 ml of a 2 molar ethylamine-tetrahydrofuran solution was diluted with 5 ml of anhydrous Ν, Ν-dimethylformamide, and 3- (2′-chloro-6-6) obtained in (2) -3'-Trifluoromethylphenol) -benzoyl chloride 0.2 g of tetrahydrofuran 2 ml solution was added at 0 ° C, and at the same temperature A solution of lml triethylamine in 1 ml anhydrous Ν, ホ ル -dimethylformamide was added dropwise, followed by stirring at 20 ° C for 1 hour and further at 35 ° C for 4 hours. After cooling to 0 ° C., 25 ml of ethyl acetate was added, 10 ml of water was further added, and the mixture was stirred for a while. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Purified by ram chromatography (developing solvent n-hexane: ethyl acetate = 1: 1) to obtain 80 mg of the target compound as an amorphous solid. Moreover, NMR of this product was as follows. 1H-NMR δ (ppm) 1.24 (t, 3H; J = 5.6Hz), 2.08 (s, 3H), 3.45-3.54 (m, 2H), 6.13 (bs, lH), 7.2 7-7.30 (m, 2H ), 7.52-7.55 (m, 2H), 7.60 (d, lH; J = 8.4Hz), 7.81 (d, lH; J = 7.8Hz)
[0067] 合成例 5 [0067] Synthesis Example 5
N-メチル - 3- (2'-ブロモ - 6'-クロ口- 3'-トリフルォロメチルフエ-ル)ベンズアミド (ィ匕合 物 Νο.Ι— 62)の合成  Synthesis of N-methyl-3- (2'-bromo-6'-black mouth-3'-trifluoromethylphenol) benzamide (compound Νο.Ι— 62)
(1) 3-ァミノ- 4-クロ口べンゾトリフルオリド 13. 8mlのベンゼン 180ml溶液中へ、 N-ブ ロモこはく酸イミド 17. 8gを 10〜15°Cにて数回に分けて投入した後、室温にて 4時 間緩やかに攪拌した。ガスクロマトグラフィーにて反応終了を確認した後、氷冷し、反 応系中へ約 50gの無水硫酸ナトリウムを加えてしばらく攪拌した後、セライトろ過した 。ろ液力 減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N;球 状'中性)カラムクロマトグラフィー (展開溶媒 n-へキサン）にて精製し、油状の 3-アミ ノ- 2-ブロモ -4-クロ口べンゾトリフルオリド 10. 7gを得た。このものの NMRは以下の通 りであった。  (1) 3-Amino-4-chrome benzotrifluoride 13. Add 18.8 g of N-bromosuccinimide into 8 ml of 180 ml of benzene in several portions at 10-15 ° C. And then gently stirred at room temperature for 4 hours. After confirming the completion of the reaction by gas chromatography, it was ice-cooled, about 50 g of anhydrous sodium sulfate was added to the reaction system, and the mixture was stirred for a while and then filtered through Celite. Filtration force The solvent was distilled off under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane) to give an oily 3- 10.7 g of amino-2-bromo-4-clobenzotrifluoride was obtained. NMR of this product was as follows.
1H-NMR δ (ppm) 4.82(bs,2H),7.01(d,lH;J=8.4Hz),7.30(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 4.82 (bs, 2H), 7.01 (d, lH; J = 8.4Hz), 7.30 (d, lH; J = 8.4Hz)
[0068] (2) (1)で得た 3-ァミノ- 2-ブロモ -4-クロ口べンゾトリフルオリド 4. 7gとヨウ素 3gをベン ゼン 50mlに溶解し、攪拌しながら亜硝酸 t-ブチル 2. 7mlを 18〜20°Cにて 10分間 を要して滴下した後、 20〜25°Cにてさらに 1時間攪拌した。反応系中へ、氷片約 50 gと酢酸ェチル 200mlを加え、さらに 5%亜硫酸水素ナトリウム水溶液 100mlをカロえ てしばらく攪拌した。有機層を分離し、氷冷 5%水酸ィ匕カリウム水溶液 100mlで洗浄 後、無水硫酸ナトリウムにて乾燥し、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕 学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン） にて精製して、油状の 2-ブロモ -4-クロ口- 3-ョードベンゾトリフルオリド 4. 6gを得た。 また、このものの NMRは以下の通りであった。 [0068] (2) 4-Amino-2-bromo-4-chlorobenzoic trifluoride (4.7 g) obtained in (1) and 3 g of iodine were dissolved in 50 ml of benzene and stirred with nitrous acid t- After 2.7 ml of butyl was added dropwise at 18 to 20 ° C over 10 minutes, the mixture was further stirred at 20 to 25 ° C for 1 hour. About 50 g of ice pieces and 200 ml of ethyl acetate were added to the reaction system, and then 100 ml of 5% aqueous sodium hydrogen sulfite solution was added and stirred for a while. The organic layer was separated, washed with 100 ml of ice-cold 5% aqueous potassium hydroxide solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified on silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; Purification by spherical (neutral) column chromatography (developing solvent n-hexane) gave 4.6 g of oily 2-bromo-4-chloro-3-iodobenzotrifluoride. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 7.51(d, lH;J=8.4Hz),7.63(d, lH;J=8.4Hz)  1H-NMR δ (ppm) 7.51 (d, lH; J = 8.4 Hz), 7.63 (d, lH; J = 8.4 Hz)
[0069] (3) (2)で得た 2-ブロモ -4-クロ口- 3-ョードベンゾトリフルオリド 3. 9gと 3-エトキシカル ボユルフェ-ルボロン酸 2gをエタノール 50mlに溶解し、 5%パラジウム炭素（wet、 De gussa製品 E101Type) O. 33gをカ卩えて室温にて 10分間攪拌した。反応系を 0°Cに冷 却し、炭酸ナトリウム粉末 2. 45gを加え、反応系内を窒素置換した後、 12時間加熱 還流した。放冷後、酢酸ェチル 80ml及び無水硫酸ナトリウム約 80gを加え、しばらく 攪拌した後セライトろ過した。ろ液力 減圧下溶媒を留去し、残渣をシリカゲル（関東 化学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n_へキサン ：酢酸ェチル = 16 : 1)にて精製し、 3- (2'-ブロモ -6'-クロ口- 3'-トリフルォロメチルフエ -ル) -安息香酸ェチル (ィ匕合物 No.V— 13) 2. 2gを油状物として得た。また、このも のの NMRは以下の通りであった。 [0069] (3) 2-Bromo-4-chloro-3-iodobenzotrifluoride 3.9 g obtained in (2) and 2 g of 3-ethoxycarboxyl boronic acid were dissolved in 50 ml of ethanol, and 5% Palladium on carbon (wet, Degussa product E101Type) O. 33 g was added and stirred at room temperature for 10 minutes. The reaction system was cooled to 0 ° C, 2.45 g of sodium carbonate powder was added, and the inside of the reaction system was purged with nitrogen, and then heated to reflux for 12 hours. After allowing to cool, 80 ml of ethyl acetate and about 80 g of anhydrous sodium sulfate were added, and the mixture was stirred for a while and then filtered through Celite. Filtration force The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical 'neutral) (developing solvent n_hexane: ethyl acetate = 16: 1) 3- (2′-Bromo-6′-black mouth-3′-trifluoromethylphenol) -ethyl benzoate (Compound No. V-13) 2. 2 g was obtained as an oil. The NMR of this product was as follows.
1H-NMR δ (ppm) 1.39(t,3H;J=6.9Hz),4.41(q,2H;J=6.9Hz),7.38(d,lH;J=7.8Hz),7.5 8-7.69(m,2H),7.67(d,lH;J=8.4Hz),7.90(s,lH),8.14(d,lH;J=7.8Hz)  1H-NMR δ (ppm) 1.39 (t, 3H; J = 6.9Hz), 4.41 (q, 2H; J = 6.9Hz), 7.38 (d, lH; J = 7.8Hz), 7.5 8-7.69 (m, 2H), 7.67 (d, lH; J = 8.4 Hz), 7.90 (s, lH), 8.14 (d, lH; J = 7.8 Hz)
[0070] (4) (3)で得た 3- (2'-ブロモ -6'-クロ口- 3'-トリフルォロメチルフエ-ル)-安息香酸ェチ ノレ 1. 8gを 400/0メチノレ ミン メタノーノレ溶液 80ml【こ溶解し、 40〜60oC【こて 13時 間攪拌した。放冷後、減圧下メタノール及び過剰のメチルアミンを留去し、残渣をシリ 力ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン:酢酸ェチル = 3 : 2)にて精製し、融点 58. 2°Cの目的化合物 1. 5gを 得た。また、このものの NMRは以下の通りであった。 [0070] (4) 3- (2'-Bromo-6'-black mouth-3'-trifluoromethyl phenol) -benzoic acid ethyl alcohol obtained in (3) 1. 8 g 40 0 / 0 Mechinore Min Metanonore solution 80ml [and this dissolved, and the mixture was stirred between at 40~60 o C [trowel 13. After standing to cool, methanol and excess methylamine are distilled off under reduced pressure, and the residue is subjected to silica gel (silica gel 60N; spherical 'neutral', manufactured by Kanto Yigaku) column chromatography (developing solvent n-hexane: ethyl acetate). = 3 : 2) to obtain 1.5 g of the target compound having a melting point of 58.2 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.98(d,3H;J=4.8Hz),6.51(bs,lH),7.31(d,lH;J=7.8Hz),7.52-7.56( m,2H),7.61(s,lH),7.65(d,lH;J=8.4Hz),7.85(d,lH;J=7.8Hz)  1H-NMR δ (ppm) 2.98 (d, 3H; J = 4.8Hz), 6.51 (bs, lH), 7.31 (d, lH; J = 7.8Hz), 7.52-7.56 (m, 2H), 7.61 (s , lH), 7.65 (d, lH; J = 8.4Hz), 7.85 (d, lH; J = 7.8Hz)
[0071] 合成例 6 [0071] Synthesis Example 6
N-メチル -3- (2しメチル -6'-クロ口- 3'-トリフルォロメチルフエ-ル)ベンズアミド (ィ匕合 物 Νο.Ι— 74)の合成  Synthesis of N-methyl-3- (2-methyl-6'-black 3-3-trifluoromethylphenol) benzamide (compound Νο.Ι—74)
合成例 5で得た Ν-メチル -3- (2'-ブロモ -6'-クロ口- 3'-トリフルォロメチルフエ-ル)ベ ンズアミド 0. 9gの無水テトラヒドロフラン 30ml溶液中へテトラキストリフエ-ルフォスフ インパラジウム 0. 15gを加え、 5°Cにてジメチル亜鉛の n-へキサン 1モル溶液 4. 7ml を 5分間を要して滴下した。室温にて 15時間攪拌後、さらに 10°Cにてテトラキストリフ ェ-ルフォスフィンパラジウム 0. 15gとジメチル亜鉛の n-へキサン 1モル溶液 4. 7ml を追加した。 60°Cまで加熱し同温度にて 4時間攪拌した。放冷後、不溶物をろ別し、 ろ液に酢酸ェチルをカ卩え、 10%塩ィ匕アンモ-ゥム水溶液、次いで飽和食塩水で洗 浄した。有機層を無水硫酸ナトリウムにて乾燥した後、減圧下溶媒を留去し、残渣を シリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性)カラムクロマトグラフィー（展開 溶媒： n-へキサン:酢酸ェチル =4 : 3)にて精製し、融点 149. 6°Cの目的化合物 0 . 15gを得た。また、このものの NMRは以下の通りであった。 Ν-Methyl-3- (2'-bromo-6'-black mouth-3'-trifluoromethylphenol) benzamide obtained in Synthesis Example 5 0.9K of tetrakistriphenyl into 30 ml of anhydrous tetrahydrofuran -Add 0.15 g of Ruphosphinepalladium and add 1 mol of n-hexane in dimethylzinc at 5 ° C 4.7 ml Was dropped over 5 minutes. After stirring at room temperature for 15 hours, 0.15 g of tetrakis trifluorophosphine palladium and 4.7 ml of 1 molar solution of dimethylzinc in n-hexane were further added at 10 ° C. The mixture was heated to 60 ° C and stirred at the same temperature for 4 hours. After allowing to cool, the insoluble material was filtered off, and ethyl acetate was added to the filtrate, followed by washing with a 10% aqueous solution of ammonium chloride and then with saturated saline. After drying the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Yigaku, silica gel 60N; spherical and neutral) column chromatography (developing solvent: n-hexane: The product was purified by ethyl acetate = 4: 3) to obtain 0.15 g of the target compound having a melting point of 149.6 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.13(s,3H),2.96(d,3H;J=4.8Hz),6.58(bs,lH),7.25-7.29(m,lH),7. 1H-NMR δ (ppm) 2.13 (s, 3H), 2.96 (d, 3H; J = 4.8Hz), 6.58 (bs, lH), 7.25-7.29 (m, lH), 7.
39(d,lH;J=8.4Hz),7.50(t,lH;J=7.8Hz),7.57(d,lH;J=8.4Hz),7.58(s,lH),7.80-7.84(m,l39 (d, lH; J = 8.4 Hz), 7.50 (t, lH; J = 7.8 Hz), 7.57 (d, lH; J = 8.4 Hz), 7.58 (s, lH), 7.80-7.84 (m, l
H) H)
[0072] 合成例 7  [0072] Synthesis Example 7
N-メチル - N-プロパルギル- 3- (2'-クロ口- 6'-フルォロ- 3'-トリフルォロメチルフエ- ル)ベンズアミド (化合物 Νο.Ι— 90)の合成  Synthesis of N-methyl-N-propargyl-3- (2'-black mouth-6'-fluoro-3'-trifluoromethylphenol) benzamide (compound Νο.Ι— 90)
(1) 3-ァミノ- 4-フルォロベンゾトリフルオリド 13. 5gの四塩化炭素 30ml溶液中へ、 — 5°Cで次亜塩素酸 t-ブチル 8. 5mlを 15分間かけて滴下した後、 0°Cで 20分間緩 やかに攪拌した。ガスクロマトグラフィーにて反応終了を確認した後、反応溶液をシリ 力ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル =8 : 1)に付し、粗製の 3-ァミノ- 2-クロ口- 4-フルォロベン ゾトリフノレオリド 16gを得た。このものの NMRは以下の通りであった。  (1) 3-Amino-4-fluorobenzotrifluoride 13. In 5 ml of carbon tetrachloride in 30 ml solution — After dropwise addition of 8.5 ml of t-butyl hypochlorite at 5 ° C over 15 minutes The mixture was gently stirred at 0 ° C for 20 minutes. After confirming the completion of the reaction by gas chromatography, the reaction solution was subjected to silica gel (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) column chromatography (developing solvent n-hexane: ethyl acetate = 8: 1) ) To give 16 g of crude 3-amino-2-chromo-4-fluorobenzotrifureolide. The NMR of this product was as follows.
1H-NMR δ (ppm) 3.90(bs,2H),7.08(d,lH;J=9.0Hz),7.13(d,lH;J=9.0Hz)  1H-NMR δ (ppm) 3.90 (bs, 2H), 7.08 (d, lH; J = 9.0Hz), 7.13 (d, lH; J = 9.0Hz)
[0073] (2) (1)で得た 3-ァミノ- 2-クロ口- 4-フルォロベンゾトリフルオリド 10gとヨウ素 8. 3gを ベンゼン 100mlに溶解し、攪拌しながら亜硝酸 t-ブチル 7. 5mlを 5〜25°Cで 20分 間を要して滴下した後、 10〜15°Cで 30分間攪拌した。反応溶液を、氷冷 5%亜硫 酸水素ナトリウム水溶液 400mlへ注ぎ、ジェチルエーテルをカ卩えて抽出した。得られ た有機層を氷冷 5%水酸ィ匕カリウム水溶液 200ml、続いて飽和食塩水で洗浄し、無 水硫酸ナトリウムにて乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕 学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン） にて略精製し、油状の 2-クロ口- 4-フルォ口- 3-ョードベンゾトリフルオリド 2. 5gを得た[0073] (2) Dissolve 10 g of 3-amino-2-chloroguchi-4-fluorobenzotrifluoride obtained in (1) and 8.3 g of iodine in 100 ml of benzene, and add t-butyl nitrite while stirring. 7. After 5 ml was added dropwise at 5-25 ° C over 20 minutes, the mixture was stirred at 10-15 ° C for 30 minutes. The reaction solution was poured into 400 ml of ice-cold 5% aqueous sodium hydrogen sulfite solution, and extracted by adding jetyl ether. The obtained organic layer was washed with 200 ml of ice-cold 5% aqueous potassium hydroxide and then with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel (Kanto).匕 匕 学 匕, silica gel 60N; spherical 'neutral' column chromatography (developing solvent n-hexane) The oily 2-chrome mouth-4-fluoro mouth-3-iodobenzotrifluoride 2.5g was obtained.
。また、このものの NMRは以下の通りであった。 . Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 7.04— 7.10(m,lH),7.72(dd,lH;J=6.0&8.7Hz)  1H-NMR δ (ppm) 7.04-7.10 (m, lH), 7.72 (dd, lH; J = 6.0 & 8.7 Hz)
[0074] (3) (2)で得た 2-クロ口- 4-フルォロ- 3-ョードベンゾトリフルオリド 2. lgと 3-メトキシカ ルボユルフェ-ルボロン酸 1. 6gをエタノール 40mlに溶解し、 5%パラジウム炭素（we t、 Degussa製品 E101Type) O. 42gと炭酸ナトリウム粉末 1. 6gを 0°Cで加え、— 5°Cに て反応系内を窒素置換した後、 13時間加熱還流した。放冷後、酢酸ェチル及び無 水硫酸ナトリウム約 30gを加え 5分間攪拌した後、セライトろ過した。ろ液から減圧下 溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラムク 口マトグラフィー（展開溶媒 n-へキサン:酢酸ェチル = 16 : 1)にて精製し、融点 82. 9。Cの 3- (2'-クロ口- 6'-フルォロ- 3'-トリフルォロメチルフエ-ル)-安息香酸メチル (ィ匕 合物 No.V—22) 1. 2gを得た。また、このものの NMRは以下の通りであった。  [0074] (3) 2-chloro-2-4-fluoro-3-iodobenzotrifluoride 2. lg obtained in (2) and 1.6 g of 3-methoxycarbourelboronic acid were dissolved in 40 ml of ethanol, 5% palladium carbon (wet, Degussa product E101Type) O. 42g and sodium carbonate powder 1.6g were added at 0 ° C, and the reaction system was purged with nitrogen at -5 ° C, and then heated to reflux for 13 hours. After allowing to cool, about 30 g of ethyl acetate and anhydrous sodium sulfate were added and stirred for 5 minutes, and then filtered through Celite. The solvent was distilled off from the filtrate under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 16: 1). Purify and melt 82.9. C (3- (2′-Black) -6′-Fluoro-3′-trifluoromethylphenol) -methyl benzoate (Compound No. V-22) of C was obtained in an amount of 1.2 g. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 3.93(s,3H),7.20(t,lH;J=8.4Hz),7.50-7.60(m,2H),7.75(dd,lH;J=5 .7 & 9.0Hz),8.02(s,lH),8.12-8.16(m,lH)  1H-NMR δ (ppm) 3.93 (s, 3H), 7.20 (t, lH; J = 8.4Hz), 7.50-7.60 (m, 2H), 7.75 (dd, lH; J = 5.7 & 9.0Hz) , 8.02 (s, lH), 8.12-8.16 (m, lH)
[0075] (4) (3)で得た 3- (2'-クロ口- 6'-フルォロ- 3'-トリフルォロメチルフエ-ル)-安息香酸メ チル 0. 4gを 40%メチルァミンのメタノール溶液 7. 5mlに溶解し、 50。Cで 1. 5時間 攪拌した。同温度でさらに 40%メチルァミン一メタノール溶液 5mlをカ卩えて徐々に室 温まで放冷しながら 13時間攪拌した。減圧下メタノールと過剰のメチルアミンを留去 し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラムクロマトグラフ ィー（展開溶媒 n-へキサン:酢酸ェチル = 1 : 1)にて精製し、融点 125. 6°Cの N-メ チル- 3- (2'-クロ口- 6'-フルォロ- 3'-トリフルォロメチルフエ-ル)ベンズアミド (化合物 N 0.1-89) 0. 4gを得た。また、このものの NMRは以下の通りであった。  [0075] (4) 3- (2'-Chromium-6'-Fluoro-3'-trifluoromethylphenol) -methyl benzoate obtained in (3) 0.4 g of 40% methylamine 50. Dissolve in 7.5 ml of methanol solution. Stir at C for 1.5 hours. A further 5 ml of 40% methylamine-methanol solution was added at the same temperature, and the mixture was stirred for 13 hours while gradually cooling to room temperature. Methanol and excess methylamine were distilled off under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 1: 1). ) N-methyl-3- (2'-chloro-6'-fluoro-3'-trifluoromethylphenol) benzamide (compound N 0.1-89) with a melting point of 125.6 ° C 0.4 g was obtained. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.93(d,3H;J=4.8Hz),6.91(bs,lH),7.14(t,lH;J=8.7Hz),7.40(d,lH;J =7.5Hz),7.48(t,lH;J=7.5Hz),7.70(q,lH;J=5.4 & 8.7Hz),7.82-7.87(m,lH)  1H-NMR δ (ppm) 2.93 (d, 3H; J = 4.8Hz), 6.91 (bs, lH), 7.14 (t, lH; J = 8.7Hz), 7.40 (d, lH; J = 7.5Hz), 7.48 (t, lH; J = 7.5Hz), 7.70 (q, lH; J = 5.4 & 8.7Hz), 7.82-7.87 (m, lH)
[0076] (5) (4)で得た N-メチル -3- (2'-クロ口- 6'-フルォロ- 3'-トリフルォロメチルフエ-ル)ベ ンズアミド 0. 22gの無水テトラヒドロフラン 20ml溶液中へ、 5°Cで 60%水素化ナトリウ ム 0. 15gを数回に分けて投入後、同温度で 10分間攪拌した。同温度でプロパルギ ルブロミド 0. 18mlを投入し、室温で 12時間攪拌した。さらに 5°Cで 60%水素化ナト リウム 0. 15g及びプロパルギルブロミド 0. 18mlを投入した後、室温で 23時間攪拌し た。反応溶液を 0°Cに冷却後、酢酸ェチル 50ml及び 10%塩ィ匕アンモ-ゥム水溶液 30mlを加えてしばらく攪拌し、酢酸ェチルで 2回抽出した。抽出した有機層を合わ せ、無水硫酸ナトリウムを乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（関東 化学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン ：酢酸ェチル = 5 : 3)にて精製し、無定形固体の目的化合物 95mgを得た。また、こ のものの NMRは以下の通りであった。 [0076] (5) N-methyl-3- (2′-chloro-6′-fluoro-3′-trifluoromethylphenol) benzamide obtained in (4) 0.22 g of anhydrous tetrahydrofuran 20 ml To the solution, 0.15 g of 60% sodium hydride was added in several portions at 5 ° C, and then stirred at the same temperature for 10 minutes. At the same temperature, 0.18 ml of propargyl bromide was added and stirred at room temperature for 12 hours. 60% hydrogenated sodium at 5 ° C After adding 0.15 g of lithium and 0.18 ml of propargyl bromide, the mixture was stirred at room temperature for 23 hours. After cooling the reaction solution to 0 ° C., 50 ml of ethyl acetate and 30 ml of 10% aqueous solution of ammonium chloride were added and stirred for a while, followed by extraction twice with ethyl acetate. The extracted organic layers were combined and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (Kanto Chemical Co., Silica Gel 60N; spherical 'neutral') column chromatography (developing solvent n-hexane). : Ethyl acetate = 5: 3) to obtain 95 mg of the target compound as an amorphous solid. The NMR of this product was as follows.
1H-NMR δ (ppm) 2.29(bs,lH),3.11(bs,3H),4.06 & 4.38(bs,2H),7.19(t,lH;J=8.4Hz),7 .38— 7.50(m,2H),7.52— 7.60(m,2H),7.74(dd,lH;J=5.7 & 6.0Hz)  1H-NMR δ (ppm) 2.29 (bs, lH), 3.11 (bs, 3H), 4.06 & 4.38 (bs, 2H), 7.19 (t, lH; J = 8.4 Hz), 7.38-7.50 (m, 2H), 7.52-7.60 (m, 2H), 7.74 (dd, lH; J = 5.7 & 6.0Hz)
[0077] 合成例 8 [0077] Synthesis Example 8
3- (2'-クロ口- 6しメチル - 3'-トリフルォロメチルフエ-ル)-ァ-リン (ィ匕合物 No.I— 44) の合成  Synthesis of 3- (2'-Black-Methyl-6-3Methyl-3'-Trifluoromethylphenol) -Alin (Compound No.I—44)
(1)合成例 2 (1)で得た 3-ァミノ- 2-クロ口- 4-メチルベンゾトリフルオリド 21gの濃塩酸 150ml懸濁攪拌液中へ、 7〜10°Cにて 10分間を要して亜硝酸ナトリウム 7. 4gの 20 ml水溶液を滴下した。 30〜32°Cにて 2. 5時間攪拌後 5°Cまで冷却し、ヨウ化力リウ ム 25g及び尿素 1. 05gの 25ml水溶液を 5〜15°Cにて 15分間を要して滴下した。 2 5〜30°Cにて 5時間攪拌後、氷を加え酢酸ェチルで抽出した。得られた酢酸ェチル 層をチォ硫酸ナトリウム、飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減 圧下溶媒を留去した。残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性） カラムクロマトグラフィー（展開溶媒 n-へキサン）にて精製し、油状の 2-クロ口- 3-ョー ド -4-メチルベンゾトリフルオリド 20gを得た。また、このものの NMRは以下の通りであ つた o  (1) Synthesis Example 2 3-Amino-2-black mouth-4-methylbenzotrifluoride obtained in (1) 21 mL of concentrated hydrochloric acid in 150 ml suspension and stirring solution at 7-10 ° C, 10 minutes required Then, a 20 ml aqueous solution of 7.4 g of sodium nitrite was added dropwise. After stirring for 5 hours at 30 to 32 ° C, the mixture was cooled to 5 ° C, and 25 ml of an aqueous solution containing 25 g of rhodium iodide and 1.05 g of urea was added dropwise at 5 to 15 ° C over 15 minutes. . 2 After stirring at 5-30 ° C for 5 hours, ice was added and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with sodium thiosulfate and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral') column chromatography (developing solvent: n-hexane), and oily 2-chloro-3-3-iodo-4-methylbenzo 20 g of trifluoride was obtained. The NMR of this product is as follows: o
1H-NMR δ (ppm) 2.59(s,3H),7.23(d,lH;J=8.4Hz),7.58(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 2.59 (s, 3H), 7.23 (d, lH; J = 8.4Hz), 7.58 (d, lH; J = 8.4Hz)
[0078] (2) (1)で得た 2-クロ口- 3-ョード -4-メチルベンゾトリフルオリド 5. 7gのエタノール 10 0ml溶液中へ、室温で 3-ニトロフエ-ルボロン酸 3. 7gを加え、続いて 5%パラジウム 炭素 (wet、 Degussa製品 ElOlType . 8gを加えて室温にて 10分間攪拌した。反応 系を 5°Cに冷却し、炭酸ナトリウム粉末 5. 4gを加え、反応系内を窒素置換した後、 1 4時間加熱還流した。放冷後、酢酸ェチル 180ml及び無水硫酸ナトリウム約 100gを 加え 5分間攪拌した後セライトろ過した。ろ液力 減圧下溶媒を留去し、残渣をシリカ ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル = 16 : 1)にて精製し、 2'-クロ口- 6しメチル -3--トロ- 3'-トリフ ルォロメチルビフエ-ル 3. 6gを無定形個体として得た。また、このものの NMRは以下 の通りであった。 [0078] (2) 3.7 g of 3-nitrophenylboronic acid at room temperature was added to a solution of 5.7 g of ethanol obtained in (1) in 100 ml of ethanol. Then, 5% palladium on carbon (wet, Degussa product ElOlType. 8g was added and stirred for 10 minutes at room temperature. The reaction system was cooled to 5 ° C, 5.4 g of sodium carbonate powder was added, and After purging with nitrogen, the mixture was heated to reflux for 14 hours, and after standing to cool, 180 ml of ethyl acetate and about 100 g of anhydrous sodium sulfate were added. The mixture was stirred for 5 minutes and filtered through celite. Filtration force The solvent was distilled off under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Yigaku, silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 16: 1). After purification, 3.6 g of 2′-black-6-methyl-3--tro-3′-trifluoromethylbiphenyl was obtained as an amorphous solid. In addition, NMR of this product was as follows.
1H-NMR δ (ppm) 2.11(s,3H),7.33(d,lH;J=8.1Hz),7.51-7.55(m,lH),7.67(d,lH;J=8. lHz),7.65-7.71(m,lH),8.07-8.09(m,lH),8.28-8.32(m,lH)  1H-NMR δ (ppm) 2.11 (s, 3H), 7.33 (d, lH; J = 8.1Hz), 7.51-7.55 (m, lH), 7.67 (d, lH; J = 8.lHz), 7.65- 7.71 (m, lH), 8.07-8.09 (m, lH), 8.28-8.32 (m, lH)
[0079] (3) (2)で得た 2'-クロ口- 6しメチル -3-二トロ- 3'-トリフルォロメチルビフエ-ル 3. Ogを 酢酸ェチル 70mlに溶解し、 10°Cで 10%パラジウム炭素 (wet) O. 3gを攪拌しながら 数回に分けて加えた。反応系内を水素置換した後、 20°Cで 14時間激しく攪拌した。 セライトろ過した後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲ ル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン：酢酸ェチル = 3 : 2)にて精製し、油状の目的化合物 2. lgを得た。また、このものの NMRは以下の通 りであった。 [0079] (3) 2′-Black-6-methyl-3-nitro-3′-trifluoromethylbiphenyl obtained in (2) 3. Dissolve Og in 70 ml of ethyl acetate. At 0 ° C., 3 g of 10% palladium on carbon (wet) O. was added in several portions with stirring. After purging the reaction system with hydrogen, the mixture was vigorously stirred at 20 ° C. for 14 hours. After filtration through celite, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (Kanto Yigaku, silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 3: 2). To obtain 2.lg of the oily desired compound. In addition, NMR of this product was as follows.
1H-NMR δ (ppm) 2.13(s,3H),4.02(bs,2H),6.53(s,lH),6.58(d,lH;J=7.5Hz),6.78(d,l H;J=7.5Hz),7.22-7.27(m,2H),7.57(d,lH;J=8.1Hz)  1H-NMR δ (ppm) 2.13 (s, 3H), 4.02 (bs, 2H), 6.53 (s, lH), 6.58 (d, lH; J = 7.5Hz), 6.78 (d, lH; J = 7.5 Hz), 7.22-7.27 (m, 2H), 7.57 (d, lH; J = 8.1Hz)
[0080] 合成例 9 [0080] Synthesis Example 9
3- (2'-クロ口- 6しメチル - 3'-トリフルォロメチルフエ-ル)ァセトァ -リド (化合物 No.I— 4 6)の合成  Synthesis of 3- (2'-Black-6-Methyl-3'-trifluoromethylphenol) aceto-lide (Compound No. I— 4 6)
合成例 8で得た 3- (2'-クロ口- 6しメチル -3'-トリフルォロメチルフエ-ル)ァ-リン 0. 1 5g及びトリェチルァミン 0. lgの無水テトラヒドロフラン 15ml溶液中へ 10°Cで塩化ァ セチル 72mgを滴下後、室温で 3時間攪拌した。反応溶液を 0°Cに冷却し、酢酸ェチ ル 30ml及び 10%塩ィ匕アンモ-ゥム水溶液 20mlを加えてしばらく攪拌した。得られ た有機層を無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し、残渣をシリカゲ ル（関東ィ匕学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー (展開溶媒 n- へキサン：酢酸ェチル = 2 : 1)にて精製し、融点 49. 6°Cの目的化合物 0. 16gを得た 。また、このものの NMRは以下の通りであった。  To a solution of 3- (2'-black-6-methyl-3'-trifluoromethylphenol) phosphine 0.15 g and triethylamine 0. lg obtained in Synthesis Example 8 in 15 ml of anhydrous tetrahydrofuran 10 After 72 mg of acetyl chloride was added dropwise at ° C, the mixture was stirred at room temperature for 3 hours. The reaction solution was cooled to 0 ° C., 30 ml of ethyl acetate and 20 ml of 10% aqueous solution of ammonium chloride were added and stirred for a while. The obtained organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (silica gel 60N; spherical, neutral) column chromatography (developing solvent n- Purification by xane: ethyl acetate = 2: 1) gave 0.16 g of the target compound having a melting point of 49.6 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.08(s,3H),2.14(s,3H),6.84-6.89(m,lH),7.21-7.26(m,lH),7.32-7 .39(m,2H),7.54-7.59(m,2H),7.96(bs,lH) 1H-NMR δ (ppm) 2.08 (s, 3H), 2.14 (s, 3H), 6.84-6.89 (m, lH), 7.21-7.26 (m, lH), 7.32-7 .39 (m, 2H), 7.54-7.59 (m, 2H), 7.96 (bs, lH)
[0081] 合成例 10 [0081] Synthesis Example 10
N-メチル -3- (2しメチルチオ- 6'-クロ口- 3'-トリフルォロメチルフエ-ル)ベンズアミド（ 化合物 Νο.Ι— 229)の合成  Synthesis of N-methyl-3- (2 methylthio-6'-black mouth-3'-trifluoromethylphenol) benzamide (compound Νο.Ι—229)
合成例 5で得た Ν-メチル -3- (2'-ブロモ -6'-クロ口- 3'-トリフルォロメチルフエ-ル)ベ ンズアミド 0. 8gの無水 Ν,Ν-ジメチルホルムアミド 8ml溶液中へ、 15°Cにてメチルメル カプタンナトリウム塩の 15%水溶液 4mlをカ卩え、 60〜70°Cにて 15時間攪拌後、さら にメチルメルカプタンナトリウム塩の 15%水溶液 4mlをカ卩ぇ 100〜110°Cにて 4時間 攪拌した後、放冷した。冷水、酢酸ェチル 50ml及びジェチルエーテル 100mlをカロ え、得られた有機層を 10%塩ィ匕アンモ-ゥム水溶液、次いで飽和食塩水で洗浄した 。有機層を無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し、残渣をシリカゲ ル（関東ィ匕学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー (展開溶媒： n —へキサン：酢酸ェチル =4 : 3)にて精製し、融点 161. 8°Cの目的化合物 0. 31gを 得た。また、このものの NMRは以下の通りであった。  Ν-Methyl-3- (2'-bromo-6'-black mouth-3'-trifluoromethylphenol) benzamide obtained in Synthesis Example 5 0.8 g of anhydrous Ν, Ν-dimethylformamide in 8 ml solution Add 15 ml of 15% aqueous solution of methyl mercaptan at 15 ° C, stir at 60-70 ° C for 15 hours, and then add 4 ml of 15% aqueous solution of methyl mercaptan sodium salt. The mixture was stirred at 100 to 110 ° C for 4 hours and then allowed to cool. Cold water, 50 ml of ethyl acetate and 100 ml of jetyl ether were added, and the resulting organic layer was washed with a 10% aqueous solution of ammonium chloride and then with saturated saline. After drying the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (silica gel 60N; spherical, neutral) column chromatography (developing solvent: n-hexane: Purification by ethyl acetate = 4: 3) gave 0.31 g of the target compound having a melting point of 161.8 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.33(s,3H),2.95(d,3H;J=4.2Hz),6.65(bs,lH),7.17(d,lH;J=8.4Hz), 7.29(d,lH;J=7.8Hz),7.51(t,lH;J=7.8Hz),7.58(s,lH),7.64(d,lH;J=8.4Hz),7.88(d,lH;J =7.8Hz)  1H-NMR δ (ppm) 2.33 (s, 3H), 2.95 (d, 3H; J = 4.2Hz), 6.65 (bs, lH), 7.17 (d, lH; J = 8.4Hz), 7.29 (d, lH ; J = 7.8Hz), 7.51 (t, lH; J = 7.8Hz), 7.58 (s, lH), 7.64 (d, lH; J = 8.4Hz), 7.88 (d, lH; J = 7.8Hz)
[0082] 合成例 11 [0082] Synthesis Example 11
N-メチル - 3- (6'-ェチル - 2'-クロ口- 3'-トリフルォロメチルフエ-ル)ベンズアミド (化合 物 Νο.Ι— 256)の合成  Synthesis of N-Methyl-3- (6'-Ethyl-2'-Chloro-3-3-trifluoromethylphenol) benzamide (Compound Νο.Ι—256)
(1) 3-ァミノべンゾトリフルオリド 16. 2gの水 200ml懸濁液中へ、ヨウ素 25. 4g、炭酸 水素ナトリウム 16. 8gを室温にて投入し、 13時間攪拌した。酢酸ェチル 200mlをカロ え、さらにチォ硫酸ナトリウム水 150mlを加えてしばらく攪拌した後、有機層を飽和食 塩水で洗浄し、無水硫酸ナトリウムで乾燥後、減圧下溶媒を留去した。残渣をシリカ ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル =8 : 1〜4： 1)にて精製し、 3-ァミノ- 4-ョードベンゾトリフル オリド 9gを得た。このものの NMRは以下の通りであった。  (1) 3-Aminobenzotrifluoride 16.2 g of water in a 200 ml suspension was charged with 25.4 g of iodine and 16.8 g of sodium hydrogen carbonate at room temperature and stirred for 13 hours. After adding 200 ml of ethyl acetate and stirring for a while after adding 150 ml of sodium thiosulfate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel (silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 8: 1 to 4: 1), 3-amino- 9 g of 4-iodobenzotrifluoride was obtained. The NMR of this product was as follows.
1H-NMR δ (ppm) 4.30(bs,2H),6.69(d,lH;J=8.1Hz),6.93(s,lH),7.73(d,lH;J=8.1Hz) [0083] (2) (1)で得た 3-ァミノ- 4-ョードベンゾトリフルオリド 15. 8gのベンゼン 150ml溶液中 へ、 N-クロロスクシンイミド 7. 4gを室温にて数回に分けて投入した後、 40〜50°Cに て 15時間緩やかに攪拌した。ガスクロマトグラフィーにて反応終了を確認した後、氷 冷し、反応系中へ約 lOOgの無水硫酸ナトリウムを加えてしばらく攪拌し、セライトろ過 した。ろ液カゝら減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ；球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン）にて精製し、油状の 3- ァミノ- 2-クロ口- 4-ョードベンゾトリフルオリド 10. 9gを得た。このものの NMRは以下の 通りであった。 1H-NMR δ (ppm) 4.30 (bs, 2H), 6.69 (d, lH; J = 8.1Hz), 6.93 (s, lH), 7.73 (d, lH; J = 8.1Hz) [0083] (2) 3-Amino-4-iodobenzotrifluoride obtained in (1) 15. 8.4 g of N-chlorosuccinimide was divided into several portions at room temperature in 150 ml of benzene. After the addition, the mixture was gently stirred at 40-50 ° C for 15 hours. After confirming the completion of the reaction by gas chromatography, it was ice-cooled, about 10 g of anhydrous sodium sulfate was added to the reaction system, and the mixture was stirred for a while and filtered through celite. The solvent was removed from the filtrate under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane). -Amino-2-black mouth-4-oodobenzotrifluoride 10.9g was obtained. The NMR of this product was as follows.
1H-NMR δ (ppm) 4.80(bs,2H),6.79(d,lH;J=8.4Hz),7.65(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 4.80 (bs, 2H), 6.79 (d, lH; J = 8.4Hz), 7.65 (d, lH; J = 8.4Hz)
[0084] (3) (2)で得た 3-ァミノ- 2-クロ口- 4-ョードベンゾトリフルオリド 6. 5gの無水テトラヒドロ フラン 80ml溶液中へ、テトラキストリフエ-ルフォスフィンパラジウム 1. 2gを室温にて 加え、 10分間攪拌した。系内を窒素置換した後、反応系を 0°Cに冷却し、 5°Cにてジ ェチル亜鉛のテトラヒドロフラン 1モル溶液 26mlを 10分間を要して滴下した。室温に て 15時間攪拌後、酢酸ェチルをカ卩え、 10%塩ィ匕アンモ-ゥム水溶液、次いで飽和 食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥した後、減圧下溶媒を留去し 、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラムクロマトグラフィ 一（展開溶媒： n-へキサン:酢酸ェチル =8 : 1)にて精製し、油状の 3-ァミノ- 2-クロ 口- 4-ェチルベンゾトリフルオリド 1. 6gを得た。また、このものの NMRは以下の通りで めつに。 [0084] (3) Tetrakistriphenyl-phosphine palladium in 3-mlamino-2-chromo-4-iodobenzotrifluoride obtained in (2) in 80 ml of anhydrous tetrahydrofuran 80 ml 1. 2 g was added at room temperature and stirred for 10 minutes. After replacing the interior of the system with nitrogen, the reaction system was cooled to 0 ° C., and 26 ml of a 1 molar solution of dimethyl zinc in tetrahydrofuran was added dropwise at 5 ° C. over 10 minutes. After stirring at room temperature for 15 hours, ethyl acetate was added and washed with a 10% aqueous solution of ammonium chloride and then saturated brine. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Yigaku, silica gel 60N; spherical 'neutral) column chromatography (developing solvent: n-hexane: acetic acid). Ethyl = 8: 1) to obtain 1.6 g of oily 3-amino-2-chloro-4-ethylbenzotrifluoride. The NMR of this product is as follows.
1H-NMR δ (ppm) 1.27(t,3H;J=7.5Hz),2.56(q,2H;J=7.5Hz),4.1(bs,2H),7.05(s,2H) [0085] (4)臭化銅（11) 1. 72gをァセトニトリル 40mlに溶解し、 15°Cにて亜硝酸 t-ブチル 1.  1H-NMR δ (ppm) 1.27 (t, 3H; J = 7.5Hz), 2.56 (q, 2H; J = 7.5Hz), 4.1 (bs, 2H), 7.05 (s, 2H) [0085] (4) Copper bromide (11) 1. Dissolve 72 g in 40 ml of acetonitrile and tert-butyl nitrite at 15 ° C 1.
2mlをカ卩え、（3)で得た 3-ァミノ- 2-クロ口- 4-ェチルベンゾトリフルオリド 1. 57gのァセ トニトリル 10ml溶液を 15〜20°Cにて 5分間を要して滴下した後、 20°Cにて 1. 5時間 攪拌した。 0°Cに冷却し、 1規定塩酸 10mlを加えてしばらく攪拌後、減圧下ァセトニト リルを留去し、酢酸ェチルで抽出した。得られた酢酸ェチル層を 10%塩ィ匕アンモ- ゥム水溶液、次いで飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下 溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラムク 口マトグラフィー（展開溶媒 n-へキサン）にて精製し、油状の 3-ブロモ -2-クロ口- 4- ェチルベンゾトリフルオリド 1. 53gを得た。また、このものの NMRは以下の通りであつ た。 Prepare 2 ml of 3-amino-2-chloro-4-ethyl benzotrifluoride obtained in (3) 1. Add 57 g of acetonitrile solution in 10 ml at 15-20 ° C for 5 minutes. Then, the mixture was stirred at 20 ° C for 1.5 hours. After cooling to 0 ° C., 10 ml of 1N hydrochloric acid was added and stirred for a while, and then acetonitrile was distilled off under reduced pressure and extracted with ethyl acetate. The obtained ethyl acetate layer was washed with a 10% aqueous solution of ammonium chloride and then with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel (Kanto Chemicals). Made by silica gel 60N; spherical 'neutral' column chromatography (developing solvent n-hexane) and purified by oily 3-bromo-2-chromo-4- Ethylbenzotrifluoride 1.53 g was obtained. The NMR of this product was as follows.
1H-NMR δ (ppm) 1.25(t,3H;J=7.5Hz),2.87(q,2H;J=7.5Hz),7.23(d,lH;J=8.4Hz),7.5 9(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 1.25 (t, 3H; J = 7.5Hz), 2.87 (q, 2H; J = 7.5Hz), 7.23 (d, lH; J = 8.4Hz), 7.5 9 (d, lH; (J = 8.4Hz)
[0086] (5) (4)で得た 3-ブロモ -2-クロ口- 4-ェチルベンゾトリフルオリド 0. 62gのトルエン 25 ml溶液中へ、テトラキストリフエ-ルフォスフィンパラジウム 0. 12gを室温にてカロえ、 1 0分間攪拌した。 5°Cに冷却し、 3-エトキシカルボ-ルフエ-ルボロン酸 0. 7g、ェタノ ール 5ml及び 2モル濃度の炭酸ナトリウム水 4mlをカ卩え、同温度で反応系内を窒素 置換した後、 15時間加熱還流した。 放冷後、セライトろ過し、酢酸ェチルを加え抽 出し、 10%塩ィ匕アンモ-ゥム水溶液及び飽和食塩水で洗浄した。有機層を無水硫 酸ナトリウムで乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シ リカゲル 60N;球状'中性)カラムクロマトグラフィーにて精製して (展開溶媒 n_へキ サン：酢酸ェチル =8 : 1)、油状の 3- (2'-クロ口- 6'-ェチル -3'-トリフルォロメチルフエ -ル) -安息香酸ェチル (ィ匕合物 No.V— 33)0. 2gを得た。また、このものの NMRは以 下の通りであった。  [0086] (5) 3-Bromo-2-chloro-4-ethylbenzotrifluoride obtained in (4) 0.62 g of tetrakistriphenylphosphine palladium 0.12 g in 25 ml of toluene solution Calorie at room temperature and stirred for 10 minutes. After cooling to 5 ° C, 0.7 g of 3-ethoxycarbolboronic acid, 5 ml of ethanol and 4 ml of 2 molar sodium carbonate water were added, and the reaction system was purged with nitrogen at the same temperature. Heated to reflux for 15 hours. After allowing to cool, the mixture was filtered through Celite, extracted with ethyl acetate, and washed with a 10% aqueous solution of ammonium chloride and saturated brine. After drying the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; spherical 'neutral') (developing solvent). n_Hexane: Ethyl acetate = 8: 1), oily 3- (2'-black-6'-ethyl-3'-trifluoromethylphenol) -ethyl benzoate (compound) No. V—33) 0.2 g was obtained. In addition, NMR of this product was as follows.
1H-NMR δ (ppm) 1.04(t,3H;J=7.3Hz),1.39(t,3H;J=7.1Hz),2.39(q,2H;J=7.3Hz),4.3 9(q,2H;J=7.1Hz),7.32(d,lH;J=8.1Hz),7.36-7.39(m,lH),7.55(t,lH;J=7.7Hz),7.67(d,l H;J=8.1Hz),7.87-7.88(m,lH),8.10-8.14(m,lH)  1H-NMR δ (ppm) 1.04 (t, 3H; J = 7.3Hz), 1.39 (t, 3H; J = 7.1Hz), 2.39 (q, 2H; J = 7.3Hz), 4.39 (q, 2H; J = 7.1Hz), 7.32 (d, lH; J = 8.1Hz), 7.36-7.39 (m, lH), 7.55 (t, lH; J = 7.7Hz), 7.67 (d, l H; J = 8.1Hz ), 7.87-7.88 (m, lH), 8.10-8.14 (m, lH)
[0087] (6) (5)で得た 3- (2'-クロ口- 6'-ェチル -3'-トリフルォロメチルフエ-ル)-安息香酸ェ チノレ 0. 15gを 400/0メチノレ ミン メタノーノレ溶液 15ml【こ溶解し、室温【こて 13. 5時 間攪拌した。放冷後、減圧下メタノールと過剰のメチルアミンを留去し、残渣をシリカ ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン:酢酸ェチル = 1： 1)にて精製し、無定形固体の目的化合物 0. l lgを得 た。また、このものの NMRは以下の通りであった。 [0087] (6) (5) obtained in 3- (2'-black port - 6'Echiru 3'triflate Ruo Russia methyl Hue - Le) - benzoic Sane Chinore a 0. 15g 40 0/0 Methylolamine methanol solution 15 ml [dissolved, stirred at room temperature [trowel 13. 5 hours]. After standing to cool, methanol and excess methylamine were distilled off under reduced pressure, and the residue was subjected to silica gel (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) column chromatography (developing solvent n-hexane: ethyl acetate = The product was purified by 1: 1) to obtain 0. l lg of the target compound as an amorphous solid. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 1.01(t,3H;J=7.5Hz),2.36(q,2H;J=7.5Hz),2.96(d,3H;J=4.8Hz),6.5 9(bs,lH),7.27-7.31(m,2H),7.49(t,lH;J=7.8Hz),7.58-7.59(m,lH)7.65(d,lH;J=7.8Hz), 7.79-7.83(m,lH)  1H-NMR δ (ppm) 1.01 (t, 3H; J = 7.5Hz), 2.36 (q, 2H; J = 7.5Hz), 2.96 (d, 3H; J = 4.8Hz), 6.5 9 (bs, lH) , 7.27-7.31 (m, 2H), 7.49 (t, lH; J = 7.8Hz), 7.58-7.59 (m, lH) 7.65 (d, lH; J = 7.8Hz), 7.79-7.83 (m, lH)
[0088] 合成例 12 N-メチル - 3- (6しメチル - 2'-クロ口- 3'-ブロモフエ-ル)ベンズアミド (ィ匕合物 No.I—10 7)の合成 [0088] Synthesis Example 12 Synthesis of N-Methyl-3- (6Methyl-2'-Black-3-3-Bromophenol) benzamide (Compound No.I-10-7)
(1) 5-ブロモ -2-メチルァ-リン 6. lgのベンゼン 70ml溶液中へ、 N-クロロスクシンィ ミド 4. 5gを室温にて数回に分けて投入した後、 50〜55°Cにて 1. 5時間緩やかに攪 拌した。ガスクロマトグラフィーにてほぼ反応が終了したことを確認後、放冷し、反応 系中へ約 20gの無水硫酸ナトリウムを加えてしばらく攪拌し、ろ過した。ろ液から減圧 下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 '中性)カラム クロマトグラフィー（展開溶媒 n-へキサン:酢酸ェチル = 16 : 1)にて精製し、油状の 3-ブロモ -2-クロ口- 6-メチルァ-リン 1. 9gを得た。このものの NMRは以下の通りであ つた o  (1) 5-Bromo-2-methylaline 6. Into 70 ml of benzene in benzene, 4.5 g of N-chlorosuccinimide was added in several portions at room temperature. Stir gently for 5 hours. After confirming that the reaction was almost completed by gas chromatography, the mixture was allowed to cool, and about 20 g of anhydrous sodium sulfate was added to the reaction system, and the mixture was stirred for a while and filtered. The solvent was distilled off from the filtrate under reduced pressure, and the residue was purified by silica gel (Kanto Yigaku, silica gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 16: 1). As a result, 1.9 g of oily 3-bromo-2-chloro-6-methylaline was obtained. The NMR of this was as follows: o
1H-NMR δ (ppm) 2.17(s,3H),4.36(bs,2H),6.83(d,lH;J=8.1Hz),6.97(d,lH;J=8.1Hz) [0089] (2) (1)で得た 3-ブロモ -2-クロ口- 6-メチルァ-リン 1. 9gとヨウ素 1. 7gをベンゼン 70 mlに溶解し、攪拌しながら亜硝酸 t-ブチル 1. 35mlを 7〜10°Cにて 20分間を要して 滴下した。 14〜16°Cにてさらに 1. 5時間攪拌した後、反応系中へ氷片約 20gと酢酸 ェチル 80mlをカロえ、さらに 5%亜硫酸水素ナトリウム水溶液 80mlをカ卩えてしばらく攪 拌した。得られた有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、 減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状 ·中性） カラムクロマトグラフィー（展開溶媒 n-へキサン）にて精製し、融点 50. 4°Cの 4-プロ モ- 3-クロ口- 2-ョードトルエン 1. 15gを得た。また、このものの NMRは以下の通りであ つた o  1H-NMR δ (ppm) 2.17 (s, 3H), 4.36 (bs, 2H), 6.83 (d, lH; J = 8.1Hz), 6.97 (d, lH; J = 8.1Hz) [0089] (2) 3-Bromo-2-chloro-6-methylaline 1.9g and iodine 1.7g obtained in (1) are dissolved in 70 ml of benzene and stirred with stirring. It was added dropwise at 10 ° C for 20 minutes. After further stirring for 1.5 hours at 14 to 16 ° C, about 20 g of ice pieces and 80 ml of ethyl acetate were charged into the reaction system, and further 80 ml of 5% aqueous sodium hydrogen sulfite solution was added and stirred for a while. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Chemical Co., Ltd., silica gel 60N; spherical and neutral). Purification with (developing solvent n-hexane) gave 1.15 g of 4-promo-3-chloro-2--2-toluene having a melting point of 50.4 ° C. The NMR of this product is as follows: o
1H-NMR δ (ppm) 2.49(s,3H),6.99(d, 1H;J=8. lHz),7.49(d, 1H;J=8.1Hz)  1H-NMR δ (ppm) 2.49 (s, 3H), 6.99 (d, 1H; J = 8 lHz), 7.49 (d, 1H; J = 8.1Hz)
[0090] (3) (2)で得た 4-ブロモ -3-クロ口- 2-ョードトルエン 1. lgと 3-エトキシカルボ-ルフエ -ルボロン酸 0. 64gをエタノール 50mlに溶解し、 5%パラジウム炭素（wet、 Degussa 製品 E101Type) O. 5gをカ卩えて室温にて 10分間攪拌した。反応系を 0°Cに冷却し、 炭酸ナトリウム粉末 0. 88gを加え、同温度で反応系内を窒素置換した後、 13. 5時 間加熱還流した。放冷後、酢酸ェチル 50ml及び無水硫酸ナトリウム約 30gを加え 5 分間攪拌した後、セライトろ過した。ろ液力 減圧下溶媒を留去し、残渣をシリカゲル (関東ィ匕学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー (展開溶媒 n-へ キサン：酢酸ェチル =4 : 1)にて精製し、 3- (3'-ブロモ -2'-クロ口- 6しメチルフエ-ル） -安息香酸ェチル (ィ匕合物 No.V— 28)0. 53gを無定形個体として得た。また、このも のの NMRは以下の通りであった。 [0090] (3) 4-Bromo-3-chloro-2--2-toluene 1.lg obtained in (2) and 0.64 g of 3-ethoxycarbol-boroboronic acid were dissolved in 50 ml of ethanol, and 5% palladium was added. Carbon (wet, Degussa product E101Type) O. 5 g was added and stirred at room temperature for 10 minutes. The reaction system was cooled to 0 ° C, 0.88 g of sodium carbonate powder was added, the inside of the reaction system was purged with nitrogen at the same temperature, and the mixture was heated to reflux for 13.5 hours. After standing to cool, 50 ml of ethyl acetate and about 30 g of anhydrous sodium sulfate were added and stirred for 5 minutes, followed by filtration through Celite. Filtration force The solvent was distilled off under reduced pressure, and the residue was purified by silica gel (manufactured by Kanto Yigaku, silica gel 60N; spherical 'neutral) column chromatography (to developing solvent n- Purified with xylene: ethyl acetate = 4: 1), 3- (3'-bromo-2'-black-6-methylphenyl) -benzoyl benzoate (Compound No.V—28) 0 53 g was obtained as an amorphous individual. The NMR of this product was as follows.
1H-NMR δ (ppm) 1.39(t,3H;J=7.2Hz),2.01(s,3H),4.39(q,2H;J=7.2Hz),7.07(d,lH;J= 8.4Hz),7.33-7.38(m,lH),7.51-7.57(m,2H),7.84-7.86(m,lH),8.07-8.11(m,lH)  1H-NMR δ (ppm) 1.39 (t, 3H; J = 7.2Hz), 2.01 (s, 3H), 4.39 (q, 2H; J = 7.2Hz), 7.07 (d, lH; J = 8.4Hz), 7.33-7.38 (m, lH), 7.51-7.57 (m, 2H), 7.84-7.86 (m, lH), 8.07-8.11 (m, lH)
[0091] (4) (3)で得た 3- (3'-ブロモ -2'-クロ口- 6しメチルフエ-ル)-安息香酸ェチル 0. 13g を 40%メチルァミン一メタノール溶液 5mlに溶解し、 40°Cにて 15時間攪拌した。放 冷後、減圧下メタノールと過剰のメチルアミンを留去し、残渣をシリカゲル（関東化学 製、シリカゲル 60N ;球状 '中性)カラムクロマトグラフィー（展開溶媒 n_へキサン:酢 酸ェチル = 1： 1)にて精製し、融点 142. 2°Cの目的化合物 0. l lgを得た。また、こ のものの NMRは以下の通りであった。 [0091] (4) 0.13 g of 3- (3′-bromo-2′-black mouth-6-methylphenyl) -benzoate obtained in (3) was dissolved in 5 ml of 40% methylamine-methanol solution. The mixture was stirred at 40 ° C for 15 hours. After standing to cool, methanol and excess methylamine were distilled off under reduced pressure, and the residue was subjected to silica gel (Kanto Chemical Co., Silica Gel 60N; spherical 'neutral) column chromatography (developing solvent n_hexane: ethyl acetate = 1: Purification by 1) gave 0. l lg of the target compound having a melting point of 142.2 ° C. The NMR of this product was as follows.
1H-NMR δ (ppm) 2.00(S,3H),3.02(d,3H;J=4.8Hz),6.17(bs,lH),7.06(d,lH;J=8.1Hz) ,7.30(d,lH;J=7.5Hz),7.50-7.56(m,3H),7.80(d,lH;J=8.1Hz)  1H-NMR δ (ppm) 2.00 (S, 3H), 3.02 (d, 3H; J = 4.8Hz), 6.17 (bs, lH), 7.06 (d, lH; J = 8.1Hz), 7.30 (d, lH ; J = 7.5Hz), 7.50-7.56 (m, 3H), 7.80 (d, lH; J = 8.1Hz)
[0092] 合成例 13 [0092] Synthesis Example 13
N-シァノメチル - 3- (6'-ブロモ - 2'-クロ口- 3'-トリフルォロメチルフエニル)ベンズアミド (ィ匕合物 .1— 314)の合成  Synthesis of N-cyanomethyl-3- (6'-bromo-2'-chromo-3'-trifluoromethylphenyl) benzamide (compound .1-314)
(1)合成例 1 (2)で得た 4-ブロモ -2-クロ口- 3-ョードベンゾトリフルオリド 7. 7gのァセト 二トリル 80ml溶液中へ 5%パラジウム炭素（wet、 Degussa製品 ElOlType) 2. 2gをカロ えて室温にて 10分間攪拌した。反応系を 0°Cに冷却し、 3-カルボキシフエニルボロン 酸 3. 4g及び炭酸ナトリウム 6. 4gの 80ml水溶液を加え、同温度で反応系内を窒素 置換した後、 26時間加熱還流した。放冷後、氷片及び 2規定塩酸 80mlを加えてし ばらく攪拌し、セライトろ過した。ろ液力も減圧下溶媒を留去し、酢酸ェチル 80mlで 2 回抽出し、抽出した有機層を合わせ、飽和塩化アンモ-ゥム水溶液、水、飽和食塩 水で順次洗浄し、無水硫酸ナトリウムで乾燥した。減圧下溶媒を留去し、残渣をシリ 力ゲル（関東ィ匕学製、シリカゲル 60N;球状 '中性)カラムクロマトグラフィー (展開溶媒 n-へキサン：酢酸ェチル = 1 : 1)にて精製し、融点 104. 3。Cの 3- (6'-ブロモ - 2'-ク ロロ- 3'-トリフルォロメチルフエ-ル)-安息香酸 (ィ匕合物 No.V— 1)3. 7gを得た。また、 このものの NMRは以下の通りであった。 1H-NMR δ (ppm) 7.46-7.50(m,lH),7.59-7.66(m,2H),7.74(d,lH;J=8.4Hz),7.99-8.0 l(m,lH),8.20-8.24(m,lH) (1) Synthesis example 1 4-Bromo-2-chloro-3-3-iodobenzotrifluoride obtained in (2) 7.7 g of acetonitril in 80 ml solution 5% palladium on carbon (wet, Degussa product ElOlType ) 2. 2g was added and stirred at room temperature for 10 minutes. The reaction system was cooled to 0 ° C., added with 80 ml of an aqueous solution of 3.4 g of 3-carboxyphenylboronic acid and 6.4 g of sodium carbonate, purged the reaction system with nitrogen at the same temperature, and then heated to reflux for 26 hours. After allowing to cool, ice pieces and 80 ml of 2N hydrochloric acid were added, and the mixture was stirred briefly and filtered through Celite. The filtrate was distilled off under reduced pressure and the solvent was extracted twice with 80 ml of ethyl acetate. The extracted organic layers were combined, washed sequentially with saturated aqueous ammonium chloride, water and saturated brine, and then with anhydrous sodium sulfate. Dried. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) (developing solvent n-hexane: ethyl acetate = 1: 1). Mp 104.3. There was obtained 3.7 g of 3- (6′-bromo-2′-chloro-3′-trifluoromethylphenol) -benzoic acid (Compound No. V-1) of C. The NMR of this product was as follows. 1H-NMR δ (ppm) 7.46-7.50 (m, lH), 7.59-7.66 (m, 2H), 7.74 (d, lH; J = 8.4Hz), 7.99-8.0 l (m, lH), 8.20-8.24 (m, lH)
[0093] (2) (1)で得た 3- (6'-ブロモ -2 '-クロ口- 3 '-トリフルォロメチルフエ-ル)-安息香酸 0. [0093] (2) 3- (6′-Bromo-2′-cloguchi-3′-trifluoromethylphenol) -benzoic acid obtained in (1) 0.
8gの 1,2-ジクロロェタン 20ml溶液中へ、塩化チォ -ル 0. 44ml,続いて Ν,Ν-ジメチ ルホルムアミド 2滴を加え、加熱還流下に 3. 5時間攪拌した。放冷後、反応溶液中へ トルエン 30mlを加え、減圧下、濃縮した。残渣オイルへ再度トルエン 30mlをカロえ、 濃縮（2回繰り返し)することにより、粗製の 3- (6'-ブロモ -2'-クロ口- 3'-トリフルォロメチ ルフエ-ル)-ベンゾイルク口リドを得た。このものを無水テトラヒドロフラン 20mlに溶解 し、 0〜5°Cにてトリェチルァミン 0. 7ml及びアミノアセトニトリル硫酸塩 0. 43gを加え 、室温にて 13時間攪拌した。 0°Cに冷却し、酢酸ェチル 80ml及び塩ィ匕アンモ-ゥム 水溶液 50mlを加え、しばらく攪拌した。有機層を飽和食塩水で洗浄し、無水硫酸ナ トリウムにて乾燥後、減圧下溶媒を留去して、残渣をシリカゲル（関東ィ匕学製、シリカ ゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n_へキサン:酢酸ェチル = 1 : 1)にて精製し、融点 52. 0°Cの目的化合物 0. 51gを得た。また、このものの NM Rは以下の通りであった。  To a solution of 8 g of 1,2-dichloroethane in 20 ml, 0.44 ml of thiochloride and then 2 drops of Ν, Ν-dimethylformamide were added, and the mixture was stirred for 3.5 hours while heating under reflux. After allowing to cool, 30 ml of toluene was added to the reaction solution, and the mixture was concentrated under reduced pressure. Add 30 ml of toluene again to the residual oil and concentrate (repeat twice) to remove crude 3- (6'-bromo-2'-clo-3-3'-trifluoromethyl) -benzoyl chloride. Obtained. This was dissolved in 20 ml of anhydrous tetrahydrofuran, 0.7 ml of triethylamine and 0.43 g of aminoacetonitrile sulfate were added at 0-5 ° C, and the mixture was stirred at room temperature for 13 hours. After cooling to 0 ° C., 80 ml of ethyl acetate and 50 ml of an aqueous solution of ammonium chloride were added and stirred for a while. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel 60N; spherical 'neutral'). Purification was carried out using (developing solvent n_hexane: ethyl acetate = 1: 1) to obtain 0.51 g of the objective compound having a melting point of 52.0 ° C. The NMR of this product was as follows.
1H-NMR δ (ppm) 4.35(d,2H;J=5.7Hz),7.36-7.40(m,2H),7.55(t,lH;J=7.5Hz),7.58(d ,lH;J=8.4Hz),7.66-7.68(m,lH),7.71(d,lH;J=8.4Hz),7.86-7.90(m,lH)  1H-NMR δ (ppm) 4.35 (d, 2H; J = 5.7Hz), 7.36-7.40 (m, 2H), 7.55 (t, lH; J = 7.5Hz), 7.58 (d, lH; J = 8.4Hz ), 7.66-7.68 (m, lH), 7.71 (d, lH; J = 8.4Hz), 7.86-7.90 (m, lH)
[0094] 前記合成例 1〜 13に準じた方法で製造した前記式 (I)の化合物を第 1表に示した。  [0094] Table 1 shows the compounds of the formula (I) produced by the method according to Synthesis Examples 1 to 13.
また、前記合成例 1〜5、 7及び 12〜 13に準じた方法で製造した前記式 (I)の化合 物製造用中間体である前記式 (V)の化合物を第 2表に示した。各表中、 Meはメチル を、 Etはェチルを、 n-Prはノルマルプロピルを、 c-Prはシクロプロピルを、 i-Prはイソプ 口ピルを、を各々表すこととする。なお、第 1表及び第 2表中の Zの置換位置は、便宜 上、第 1表の式中の 1〜6の数字で表すこととした。また、物性欄の mp (融点）は、 自動 融点測定装置 (メトラートレド社製 METTLER FP62)を用いて測定した。  In addition, Table 2 shows compounds of the formula (V) that are intermediates for producing the compound of the formula (I) produced by the methods according to the synthesis examples 1 to 5, 7 and 12 to 13. In each table, Me represents methyl, Et represents ethyl, n-Pr represents normal propyl, c-Pr represents cyclopropyl, and i-Pr represents isopyl pill. For convenience, the substitution position of Z in Tables 1 and 2 is represented by the numbers 1 to 6 in the formulas in Table 1. The mp (melting point) in the physical properties column was measured using an automatic melting point measuring apparatus (METTLER FP62 manufactured by METTLER TOLEDO).
[0095] [表 1] (第 1表) [0095] [Table 1] (Table 1)
] (第 1表続き） ] (Continued from Table 1)
3] (第 1表続き) 3] (Continued from Table 1)
4] Four]
5] Five]
6] (第 1表続き） 6] (Continued from Table 1)
7] (第 1表続き) 7] (Continued from Table 1)
8] (第 1表続き) 8] (Continued from Table 1)
9] (第 1¾続き） 9] (1¾ continued)
10] (第 1表続き） Ten] (Continued from Table 1)
11] 12] (第 2表続き) 11] 12] (Continued in Table 2)
(参考例） (Reference example)
次に参考例として、前記式 (I)の化合物には包含されな!、前記式 (I ' )の化合物及 びその製造用中間体の具体的合成例を記載する。なお、各合成例中で、展開溶媒 の比は容量比であり、 H- NMRは CDC1を溶媒に用いて VARIAN社製 300MHz (MER Next, as reference examples, specific synthesis examples of the compound of the formula (I ′) and intermediates for production thereof will be described, which are not included in the compound of the formula (I)! In each synthesis example, the developing solvent Is the volume ratio, and H-NMR uses CDC1 as the solvent to produce 300MHz (MER
3  Three
CURY plus)で測定した。  CURY plus).
[0108] 参考例中間体合成例 1  [0108] Reference Example Intermediate Synthesis Example 1
(1) 3-ァミノ- 4-クロ口べンゾトリフルオリド 13. 8mlの四塩化炭素 40ml溶液中へ、一 20〜― 10°Cにて次亜塩素酸 t-ブチル 11. 4mlを 10分間かけて滴下した。徐々に室 温 (〜15°C)に戻しながら 2時間緩やかに攪拌した。ガスクロマトグラフィーにて反応 終了を確認した後、反応溶液をシリカゲル（関東化学製、シリカゲル 60N ;球状 '中性 )カラムクロマトグラフィー（展開溶媒 n-へキサン）に付し、粗製の 3-ァミノ- 2,4-ジクロ 口べンゾトリフルオリド 17gを得た後、減圧蒸留にて精製した。沸点は 72— 75°CZ4 mmHgであった。このものの NMRは以下の通りであった。  (1) 3-Amino-4-chlorobenzoic trifluoride 13. In 20 ml of carbon tetrachloride in 40 ml solution, t-butyl hypochlorite 11.4 ml for 10 minutes at 20--10 ° C It was dripped over. The mixture was gently stirred for 2 hours while gradually returning to room temperature (~ 15 ° C). After confirming the completion of the reaction by gas chromatography, the reaction solution was subjected to silica gel (Kanto Chemical Co., Silica Gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane) to give crude 3-amino- After obtaining 17 g of 2,4-dichlorodibenzotrifluoride, it was purified by distillation under reduced pressure. The boiling point was 72-75 ° CZ4 mmHg. The NMR of this product was as follows.
1H-NMR δ (ppm) 4.69(bs,2H),7.00(d,lH;J=8.4Hz),7.26(d,lH;J=8.4Hz)  1H-NMR δ (ppm) 4.69 (bs, 2H), 7.00 (d, lH; J = 8.4Hz), 7.26 (d, lH; J = 8.4Hz)
[0109] (2)臭化銅（II) 22. 9gをァセトニトリル 250mlに溶解して 0°Cに冷却し、亜硝酸 t-ブ チル 16mlをカ卩え、（1)で得た 3-ァミノ- 2,4-ジクロロべンゾトリフルオリド 21. 5gのァセ トニトリル 30ml溶液を— 5〜12°Cにて 10分間を要して滴下した後、さらに 10〜15°C にて 3時間攪拌した。  [0109] (2) Copper (II) bromide (22.9 g) was dissolved in acetonitrile (250 ml), cooled to 0 ° C, t-butyl nitrite (16 ml) was added, and the 3-amino compound obtained in (1) was obtained. -2,4-dichlorobenzotrifluoride 21.5 g of acetonitrile in 30 ml was added dropwise at 5-12 ° C over 10 minutes, then stirred at 10-15 ° C for 3 hours did.
0°Cに冷却後、 1規定塩酸 80mlを加えしばらく攪拌後、減圧下ァセトニトリルを留去 し、酢酸ェチルで抽出し、飽和食塩水で洗浄した。酢酸ェチル層を無水硫酸ナトリウ ムにて乾燥した後、減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲ ル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン：酢酸ェチル =8 ： 1)にて精製し、油状の 3-ブロモ -2,4-ジクロロべンゾトリフルオリド 27. 6gを得た。ま た、このものの NMRは以下の通りであった。  After cooling to 0 ° C., 80 ml of 1N hydrochloric acid was added and stirred for a while, then acetonitrile was distilled off under reduced pressure, extracted with ethyl acetate, and washed with saturated brine. After drying the ethyl acetate layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel 60N; spherical 'neutral', manufactured by Kanto Chemical Co., Ltd.) (developing solvent to n- Purification by xane: ethyl acetate = 8: 1) gave 27.6 g of oily 3-bromo-2,4-dichlorobenzotrifluoride. The NMR of this product was as follows.
1H-NMR δ (ppm) 7.49(d, lH;J=8.4Hz),7.60(d, lH;J=8.4Hz)  1H-NMR δ (ppm) 7.49 (d, lH; J = 8.4 Hz), 7.60 (d, lH; J = 8.4 Hz)
[0110] 参考例中間体合成例 2 [0110] Reference Example Intermediate Synthesis Example 2
3-ァミノ- 4-ブロモ 2-クロ口べンゾトリフルオリド 32gに代えて、参考例中間体合成 例一 1 (1)で得た 3-ァミノ- 2,4-ジクロロべンゾトリフルオリド 11.5gを用いて合成例 1 (2 )と同様の方法により合成し、シリカゲル（関東ィ匕学製、シリカゲル 60N;球状 ·中性)力 ラムクロマトグラフィーにて精製し (展開溶媒 n-へキサン)油状の 2,4-ジクロロ- 3-ョ ードベンゾトリフルオリド 10.2gを得た。また、このものの NMRは以下の通りであった。 Ή-NMR δ (ppm) 7.46(d, lH;J=8.4Hz),7.63(d, lH;J=8.4Hz) 3-Amino-4-bromo 2-Chlorobenzobenzotrifluoride Instead of 32g, Reference Example Intermediate Synthesis Example 1 3-Amino-2,4-dichlorobenzozotrifluoride obtained in (1) 11.5 Using g, synthesized by the same method as in Synthesis Example 1 (2), purified by silica gel (Kantoi Sakugaku, silica gel 60N; spherical and neutral) force chromatography (developing solvent n- hexane) 10.2 g of oily 2,4-dichloro-3-iodobenzotrifluoride was obtained. Moreover, NMR of this product was as follows. Ή-NMR δ (ppm) 7.46 (d, lH; J = 8.4Hz), 7.63 (d, lH; J = 8.4Hz)
[0111] 参考例 1 [0111] Reference Example 1
N-メチル -3- (3， -N-メチルカルバモイルフエ-ル)- 2-クロ口- 4-メチルベンズアミド（ 化合物 Νο.Γ— 243)の合成  Synthesis of N-Methyl-3- (3, -N-Methylcarbamoylphenol) -2-Chloromouth-4-methylbenzamide (Compound Νο.Γ—243)
(1) 3-ァミノ- 4-メチル安息香酸メチル 5. Ogのベンゼン 150ml溶液中へ、 14〜18°C で N-クロロスクシンイミド 4. Ogを数回に分けて投入した後、 28〜30°Cにて 15時間攪 拌した。ガスクロマトグラフィーにて反応終了を確認した後、氷冷し、ろ過にて析出物 を除いた。ろ液カゝら減圧下溶媒を留去し、残渣をシリカゲル（関東ィ匕学製、シリカゲル 60N ;球状'中性)カラムクロマトグラフィー（展開溶媒 n-へキサン〜 n-へキサン:酢 酸ェチル =6 : 1)にて精製し、 3-ァミノ- 2-クロ口- 4-メチル安息香酸メチル 3. 8gを得 た。このものの NMRは以下の通りであった。  (1) Methyl 3-amino-4-methylbenzoate 5. N-chlorosuccinimide at a temperature of 14-18 ° C in a solution of Og in 150 ml of benzene. The mixture was stirred at C for 15 hours. After confirming the completion of the reaction by gas chromatography, it was ice-cooled and the precipitate was removed by filtration. The solvent was distilled off from the filtrate under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; spherical 'neutral) column chromatography (developing solvent n-hexane to n-hexane: ethyl acetate). = 6: Purified in 1) to obtain 3.8 g of methyl 3-amino-2-chloromethyl-4-methylbenzoate. The NMR of this product was as follows.
1H-NMR δ (ppm) 2.21(s,3H),3.90(s,3H),4.01(bs,2H),6.98(d,lH;J=8.1Hz),7.14(d,l H;J=8.1Hz)  1H-NMR δ (ppm) 2.21 (s, 3H), 3.90 (s, 3H), 4.01 (bs, 2H), 6.98 (d, lH; J = 8.1Hz), 7.14 (d, lH; J = 8.1 Hz)
[0112] (2) (1)で得た 3-ァミノ- 2-クロ口- 4-メチル安息香酸メチル 20gに、攪拌下、 3規定濃 度の水酸ィ匕ナトリウム水溶液 34mlを室温にて 20分間を要して滴下し、 30mlの水を 加えた後、 0°Cまで冷却した。濃塩酸 150mlを攪拌しながら 10分間を要して 5〜 15 °Cにてカ卩えた後、亜硝酸ナトリウム 7. lgの 20ml水溶液を 5〜10°Cにて 10分間を要 して滴下した。強めに 3時間攪拌した後、ヨウ化カリウム 25gと尿素 1. lgの 25ml水溶 液を 10〜15°Cにて 15分間を要して滴下し、さらに室温にて 11時間攪拌した。氷を 加え、飽和チォ硫酸ナトリウム水溶液 100mlを少しづつ注ぎ、酢酸ェチルを加えて 抽出した。得られた有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後 、減圧下溶媒を留去し、真空乾燥して油状の 2-クロ口- 3-ョード -4-メチル安息香酸メ チノレ 23gを得た。また、このものの NMRは以下の通りであった。  [0112] (2) To 20 g of methyl 3-amino-2-chloro-4-methylbenzoate obtained in (1), with stirring, 34 ml of 3N aqueous sodium hydroxide solution at room temperature was added at room temperature. It was added dropwise over a period of 30 minutes, 30 ml of water was added, and then cooled to 0 ° C. After stirring 150 ml of concentrated hydrochloric acid for 10 minutes and stirring at 5 to 15 ° C, 20 ml aqueous solution of sodium nitrite 7.lg was added dropwise at 5 to 10 ° C for 10 minutes. . After strongly stirring for 3 hours, 25 g of potassium iodide and 1.1 g of urea (25 ml) in water were added dropwise at 10 to 15 ° C over 15 minutes, and further stirred at room temperature for 11 hours. Ice was added, 100 ml of saturated aqueous sodium thiosulfate solution was poured little by little, and extraction was performed by adding ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was dried under vacuum to give an oily 2-chloro-3--3-phenylbenzoic acid mesohydrate. 23 g of chinole was obtained. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.56(s,3H),3.92(s,3H),7.17(d,lH;J=8.1Hz),7.60(d,lH;J=8.1Hz) 1H-NMR δ (ppm) 2.56 (s, 3H), 3.92 (s, 3H), 7.17 (d, lH; J = 8.1Hz), 7.60 (d, lH; J = 8.1Hz)
[0113] (3) (2)で得た 2-クロ口- 3-ョード -4-メチル安息香酸メチル 3. lgの N-メチル - 2-ピロ リドン 60ml及び水 25ml溶液中へ、室温にて 5%パラジウム炭素（wet、 Degussa製品 E101Type) 2. lgをカ卩えて 10分間攪拌した後、 5°Cに冷却し、 3-カルボキシフエ-ル ボロン酸 2. 2g、続いて炭酸ナトリウム粉末 3. 2gを加え、—5°Cにて反応系内を窒素 置換した後、 12時間加熱還流した。放冷後、酢酸ェチル 50ml及びジェチルエーテ ル 150mlを加え、氷冷しながら2規定塩酸水を加えて酸性にした。得られた有機層を 飽和塩化アンモニゥム水溶液、水、飽和食塩水で順次十分に洗浄した後 [0113] (3) Methyl 2-chloro-3-3-iodo-4-methylbenzoate obtained in (2) 3. In a solution of 60 ml of N-methyl-2-pyrrolidone and 25 ml of water at room temperature 5% palladium on carbon (wet, Degussa product E101Type) 2. Add lg and stir for 10 minutes, then cool to 5 ° C, 3-carboxyphenol boronic acid 2.2g, followed by sodium carbonate powder 3. Add 2g and add nitrogen to the reaction system at -5 ° C. After the replacement, the mixture was heated to reflux for 12 hours. After cooling, the acetic acid Echiru 50ml and Jechiruete Le 150ml was added and acidified with 2 N aqueous hydrochloric acid with ice-cooling. The resulting organic layer was washed thoroughly with a saturated aqueous ammonium chloride solution, water and saturated brine successively.
、無水硫酸ナトリウムで乾燥した。減圧下溶媒留去し、残渣をシリカゲル（関東化学製 、シリカゲル 60N ;球状 ·中性)カラムクロマトグラフィー（展開溶媒 酢酸ェチル）にて 精製し、融点 262. 3°Cの 3-(3'-カルボキシフエ-ル)- 2-クロ口- 4-メチル安息香酸 (ィ匕 合物 No.V'-121)l. 7gを得た。また、このものの NMRは以下の通りであった。  And dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel (Kanto Chemical Co., Ltd., silica gel 60N; spherical / neutral) column chromatography (developing solvent: ethyl acetate), melting point 262.3 ° C 3- (3'- Carboxyphenol) -2-chloroguchi-4-methylbenzoic acid (Compound No. V′-121) l. 7 g was obtained. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.08(s,3H),7.33(d,lH;J=8.1Hz),7.39-7.42(m,lH),7.59(t,lH;J=7. 7Hz),7.72(d,lH;J=8.1Hz),7.80-7.82(m,lH),8.05-8.09(m,lH)  1H-NMR δ (ppm) 2.08 (s, 3H), 7.33 (d, lH; J = 8.1 Hz), 7.39-7.42 (m, lH), 7.59 (t, lH; J = 7.7 Hz), 7.72 ( d, lH; J = 8.1Hz), 7.80-7.82 (m, lH), 8.05-8.09 (m, lH)
[0114] (4) (3)で得た 3-(3'-カルボキシフエ-ル)- 2-クロ口- 4-メチル安息香酸 1. 45gの 1,2- ジクロロェタン 60ml溶液中へ、塩化チォ -ル 2. 2ml続いて Ν,Ν-ジメチルホルムアミ ド 3滴を加え、加熱還流下に 2. 5時間攪拌した。放冷後、反応溶液中へトルエン 40 mlをカ卩え、減圧下、濃縮した。残渣オイルへ再度トルエン 50mlを加え、濃縮（2回繰 り返し）することにより、粗製の 3-(3しクロ口カルボ-ルフエ-ル)- 2-クロ口- 4-メチルベ ンゾイルク口リドを得た。このものをテトラヒドロフラン 70mlに溶解し、 15°Cにてトリェチ ルァミン 7mlをカ卩え、 2モル濃度のメチルアミン―テトラヒドロフラン溶液 15mlを 5〜1 2°Cにて 5分間を要して滴下した。室温にて 9時間攪拌した後、 0°Cに冷却し、酢酸ェ チル 100mlを加え、さらに水 50mlを加えてしばらく攪拌した。有機層を飽和食塩水 で洗浄し、無水硫酸ナトリウムで乾燥後、減圧下溶媒を留去して粗製の結晶を得た。 酢酸ェチルと少量のメタノールと共によく粉碎後、ろ過して、融点 232. 0°Cの目的化 合物 1. Ogを得た。また、このものの NMRは以下の通りであった。  [0114] (4) 3- (3'-Carboxyphenol) -2-chloro-diethyl-4-methylbenzoic acid obtained in (3) 1. 45 g of 1,2-dichloroethane in 60 ml of solution -2 ml followed by 3 drops of Ν, ホ ル -dimethylformamide was added and stirred for 2.5 hours while heating under reflux. After allowing to cool, 40 ml of toluene was added to the reaction solution and concentrated under reduced pressure. Add 50 ml of toluene again to the residual oil and concentrate (repeated twice) to obtain crude 3- (3) black mouth carbonate--2-chloro mouth-4-methylbenzoyl mouthlid. It was. This was dissolved in 70 ml of tetrahydrofuran, 7 ml of triethylamine was added at 15 ° C., and 15 ml of a 2 molar methylamine-tetrahydrofuran solution was added dropwise at 5 to 12 ° C. over 5 minutes. After stirring at room temperature for 9 hours, the mixture was cooled to 0 ° C., 100 ml of ethyl acetate was added, 50 ml of water was further added, and the mixture was stirred for a while. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain crude crystals. After thoroughly dusting with ethyl acetate and a small amount of methanol, the mixture was filtered to obtain 1.Og of the desired compound having a melting point of 232.0 ° C. Moreover, NMR of this product was as follows.
1H-NMR δ (ppm) 2.08(s,3H),2.90(d,6H;J=8.7Hz),7.30-7.36(m,3H)7.57(t,lH;J=7.7 Hz),7.62-7.63(m,lH),7.84-7.87(m,lH)  1H-NMR δ (ppm) 2.08 (s, 3H), 2.90 (d, 6H; J = 8.7 Hz), 7.30-7.36 (m, 3H) 7.57 (t, lH; J = 7.7 Hz), 7.62-7.63 ( m, lH), 7.84-7.87 (m, lH)
[0115] 前記参考例中間体合成例 1及び 2の方法、参考例 1の方法並びに前記した製造方 法に準じて製造した式 (Γ)の化合物を第 3表に示した。また、式 (Γ)の化合物の製 造用中間体である式 (V' )の化合物を第 4表に示した。各表中、 Meはメチルを、 Etは ェチルを、 n-Prはノルマルプロピルを、 i-Buはイソブチルを、 c-Prはシクロプロピルを 、ト Prはイソプロピルをを各々表すこととする。また、物性欄の mp (融点）は、自動融点 測定装置 (メトラートレド社製 METTLER FP62)を用いて測定した。 [0115] Table 3 shows the compounds of formula (Γ) produced according to the methods of Reference Example Intermediate Synthesis Examples 1 and 2, the method of Reference Example 1, and the production method described above. Table 4 shows compounds of the formula (V ′) which are intermediates for the production of the compound of the formula (Γ). In each table, Me represents methyl, Et represents ethyl, n-Pr represents normal propyl, i-Bu represents isobutyl, c-Pr represents cyclopropyl, and Pr represents isopropyl. The mp (melting point) in the physical properties column is the automatic melting point. It measured using the measuring apparatus (METTLER FP62 by METTLER TOLEDO).
[0116] [表 13] [0116] [Table 13]
(第 3表) (Table 3)
[0117] [表 14] (第 3表続き） [0117] [Table 14] (Continued in Table 3)
15] (第 3表続き) 15] (Continued in Table 3)
16] (第 3表続き) 16] (Continued in Table 3)
17] (第 3表続き) 17] (Continued in Table 3)
18] (第 3表続き） 18] (Continued in Table 3)
19] (第 3表続き） 19] (Continued in Table 3)
20] (第 3表続き) 20] (Continued in Table 3)
21] twenty one]
22] (第 4表続き） twenty two] (Continued in Table 4)
23] (第 4表続き） twenty three] (Continued in Table 4)
24] (第 4表続き） twenty four] (Continued in Table 4)
以下に、本発明に係わる有害生物防除剤の試験例を記載する。各試験において、 防除指数は以下の基準に従った。 Below, the test example of the pest control agent concerning this invention is described. In each test, the control index followed the following criteria.
〔防除指数〕 〔発病程度：肉眼観察〕 [Control index] [Disease severity: Visual observation]
5 ： 病斑又は胞子形成が全く認められない。  5: No lesion or sporulation is observed.
4 ： 病斑面積、病斑数又は胞子形成面積が、無処理区の 10%未満 3 ： 病斑面積、病斑数又は胞子形成面積が、無処理区の 40%未満 2 ： 病斑面積、病斑数又は胞子形成面積が、無処理区の 70%未満 1 ： 病斑面積、病斑数又は胞子形成面積が、無処理区の 70%以上 4: The lesion area, number of lesions or spore formation area is less than 10% of the untreated area 3: Spot area, number of lesions or spore formation area is less than 40% of untreated area 2: Disease area, number of lesions or spore formation area is less than 70% of untreated area 1: Disease area, The number of lesions or sporulation area is 70% or more of the untreated area
[0129] 試験例 1 コムギうどんこ病予防効果試験 [0129] Test Example 1 Wheat powdery mildew prevention effect test
直径 7.5cmのポリ鉢でコムギ（品種:農林 61号)を栽培し、 1.5葉期に達した時に本発 明化合物を所定濃度に調整した薬液 10mlをスプレーガンにて散布した。薬液が乾燥 した後 (処理当日）に、うどんこ病菌の分生胞子を振り掛け接種し、 20°Cの恒温室内に 保った。接種 6から 7日後に胞子形成面積を調査し、前記評価基準に従って防除指 数を求めた。その結果、前記化合物中、 1-1、 1-2、 1-10、 1-16、 1-18、 1-20、 1-21、 1-22 、ト 23、 1-24、 1-25、 1-26、 1-27、 1-29、 1-30、 1-31、 1-33、 1-37、 1-38、 1-41、 1-43、 1-44 、 1-45、 1-46、 1-62、 1-74, 1-89, 1-90, 1-107及び 1-359が lOOppmで防除指数 4以上の 効果を示した。  Wheat (variety: Norin 61) was cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution adjusted to a predetermined concentration of the present compound was sprayed with a spray gun. After the chemical solution was dried (on the day of treatment), conidia of powdery mildew fungus were sprinkled and inoculated in a constant temperature room at 20 ° C. The spore formation area was investigated 6 to 7 days after the inoculation, and the control index was determined according to the above evaluation criteria. As a result, among the compounds, 1-1, 1-2, 1-10, 1-16, 1-18, 1-20, 1-21, 1-22, G 23, 1-24, 1-25, 1-26, 1-27, 1-29, 1-30, 1-31, 1-33, 1-37, 1-38, 1-41, 1-43, 1-44, 1-45, 1- 46, 1-62, 1-74, 1-89, 1-90, 1-107, and 1-359 showed an effect of control index 4 or more at lOOppm.
[0130] 試験例 2 キユウリうどんこ病予防効果試験 [0130] Test Example 2 Test for prevention of mildew powdery mildew
直径 7.5cmのポリ鉢でキユウリ（品種：相模半白）を栽培し、 1.5葉期に達した時に本 発明化合物を所定濃度に調整した薬液 10mlをスプレーガンにて散布した。薬液が乾 燥した後 (処理当日もしくは翌日）〖こ、うどんこ病菌の分生胞子懸濁液を噴霧接種し、 2 0°Cの恒温室内に保った。接種 6から 7日後に胞子形成面積を調査し、前記評価基 準に従って防除指数を求めた。その結果、前記化合物中、 1-1、 1-2、 1-16、 1-18、 1-21 、 1-23、 1-25、 1-26、 1-27、 1-30、 1-31、 1-37、 1-38、 1-41、 1-43、 1-46、 1-62、 1-74、 1-89 、 1-90、 1-107、 1-359及び 1-363が 400ppmで防除指数 4以上の効果を示した。  Cucumbers (variety: Sagamihanjiro) were cultivated in a plastic pot with a diameter of 7.5 cm, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution prepared by adjusting the compound of the present invention to a predetermined concentration was sprayed with a spray gun. After the chemical solution was dried (on the day of treatment or the next day), a conidial spore suspension of powdery mildew and powdery mildew was sprayed and kept in a constant temperature room at 20 ° C. The spore formation area was investigated 6 to 7 days after the inoculation, and the control index was determined according to the above evaluation criteria. As a result, among the above compounds, 1-1, 1-2, 1-16, 1-18, 1-21, 1-23, 1-25, 1-26, 1-27, 1-30, 1-31 , 1-37, 1-38, 1-41, 1-43, 1-46, 1-62, 1-74, 1-89, 1-90, 1-107, 1-359 and 1-363 Showed an effect of control index 4 or higher.
[0131] 試験例 3 稲いもち病予防効果試験 [0131] Test example 3 Rice blast prevention effect test
直径 7.5cmのポリ鉢で稲（品種：日本晴)を栽培し、 1.5葉期に達した時に本発明化 合物を所定濃度に調整した薬液 10mlをスプレーガンにて散布した。薬液が乾燥した 後 (処理当日もしくは翌日）、いもち病菌の分生胞子懸濁液を噴霧接種し、 24時間 20 °Cの接種箱に保ち、その後 20°Cの恒温室内に保った。接種 6から 11日後に病斑数 を調査し、前記評価基準に従って防除指数を求めた。その結果、前記化合物中、 1-2 、 1-21及び 1-62が 400ppmで防除指数 4以上の効果を示した。  Rice (variety: Nipponbare) was cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage was reached, 10 ml of a chemical solution prepared by adjusting the compound of the present invention to a predetermined concentration was sprayed with a spray gun. After the drug solution was dried (on the day of treatment or the next day), a conidial spore suspension of blast fungus was spray-inoculated, kept in an inoculation box at 20 ° C for 24 hours, and then kept in a constant temperature room at 20 ° C. The number of lesions was investigated 6 to 11 days after the inoculation, and the control index was determined according to the above evaluation criteria. As a result, 1-2, 1-21 and 1-62 in the compound showed an effect of controlling the control index of 4 or more at 400 ppm.
[0132] 次に本発明の製剤例を記載するが、本発明における製剤量、剤型等は記載例の みに限定されるものではない。 [0132] Next, formulation examples of the present invention will be described. It is not limited to only.
[0133] 製剤例 1  [0133] Formulation Example 1
(1)本発明化合物  (1) Compound of the present invention
(2)クレー 72重量部  (2) Clay 72 parts by weight
(3)リグ-ンスルホン酸ソーダ  (3) Sodium sulfonate sulfonate
以上のものを均一に混合して水和剤とする。  The above is uniformly mixed to obtain a wettable powder.
[0134] 製剤例 2  [0134] Formulation Example 2
(1)本発明化合物  (1) Compound of the present invention
(2)タルク  (2) Talc
以上のものを均一に混合して粉剤とする。  The above is uniformly mixed to form a powder.
[0135] 製剤例 3 [0135] Formulation Example 3
(1)本発明化合物  (1) Compound of the present invention
(2) N, N' —ジメチルァセトアミド  (2) N, N '—Dimethylacetamide
(3)ポリオキシエチレンアルキルフエ-ルエー -テル 1咅0重:！ I  (3) Polyoxyethylene alkylphenol-ter I
50重量部  50 parts by weight
以上のものを均一に混合、溶解して乳剤とする。  The above is uniformly mixed and dissolved to obtain an emulsion.
[0136] 製剤例 4 [0136] Formulation Example 4
(1)クレー 68重量部  (1) 68 parts by weight of clay
(2)リグニンスルホン酸ソーダ 2重量部  (2) 2 parts by weight of sodium lignin sulfonate
(3)ポリオキシエチレンアルキルァリールサルフェート 5重：！  (3) Polyoxyethylene alkyl aryl sulfate 5 layers!
(4)微粉シリカ 25重量部  (4) Fine silica 25 parts by weight
以上の各成分の混合物と、本発明化合物とを 4 : 1の重量割合で混合し、水和剤とす る。  The mixture of the above components and the compound of the present invention are mixed at a weight ratio of 4: 1 to obtain a wettable powder.
[0137] 製剤例 5  [0137] Formulation Example 5
(1)本発明化合物 50重量部  (1) 50 parts by weight of the compound of the present invention
(2)ォキシレーテッドポリアルキルフエニルフォスフェート-トリエタノールァミン  (2) Oxidated polyalkylphenyl phosphate-triethanolamine
2重量部  2 parts by weight
(3)シリコーン 0. 2重量部 (4)水 47. 8重量部 (3) Silicone 0.2 parts by weight (4) Water 47.8 parts by weight
以上のものを均一に混合、粉砕した原液に更に  In addition to the stock solution uniformly mixed and crushed
(5)ポリカルボン酸ナトリウム 5重量部  (5) Sodium polycarboxylate 5 parts by weight
(6)無水硫酸ナトリウム 42. 8重量部  (6) Anhydrous sodium sulfate 42.8 parts by weight
を加え均一に混合、造粒、乾燥して顆粒水和剤とする。  And uniformly mixed, granulated, and dried to obtain a wettable powder.
[0138] 製剤例 6  [0138] Formulation Example 6
(1)本発明化合物 5重量部  (1) Compound of the present invention 5 parts by weight
(2)ポリオキシエチレンォクチルフエ-ルエーテル 1重量部  (2) 1 part by weight of polyoxyethylene octyl ether
(3)ポリオキシエチレンの燐酸エステル 0. 1重量部  (3) Polyoxyethylene phosphate ester 0.1 parts by weight
(4)粒状炭酸カルシウム 93. 9重量部  (4) Granular calcium carbonate 93.9 parts by weight
(1)〜（3)を予め均一に混合し、適量のアセトンで希釈した後、（4)に吹付け、ァセト ンを除去して粒剤とする。  Mix (1) to (3) uniformly in advance and dilute with an appropriate amount of acetone, and spray onto (4) to remove the acetone to form granules.
[0139] 製剤例 7 [0139] Formulation Example 7
(1)本発明化合物 2. 5重量部  (1) Compound of the present invention 2.5 parts by weight
(2) N—メチルー 2—ピロリドン 2. 5重量部  (2) N-methyl-2-pyrrolidone 2.5 parts by weight
(3)大豆油 95. 0重量部  (3) Soybean oil 95.0 parts by weight
以上のものを均一に混合、溶解して微量散布剤 (ultra low volume formulation)とす る。  The above is mixed and dissolved uniformly to make an ultra low volume formulation.
[0140] 製剤例 8  [0140] Formulation Example 8
(1)本発明化合物 20重量部  (1) 20 parts by weight of the compound of the present invention
(2)ォキシレーテッドポリアルキルフエノール フォスフェートトリエタノールァミン  (2) Oxylated polyalkylphenol phosphate triethanolamine
2重量部  2 parts by weight
(3)シリコーン 0. 2重量部  (3) Silicone 0.2 parts by weight
(4)ザンサンガム 0. 1重量部  (4) Xanthan Gum 0.1 parts by weight
(5)エチレングリコール 5重量部  (5) 5 parts by weight of ethylene glycol
(6)水 72. 7重量部  (6) 72.7 parts by weight of water
以上のものを均一に混合、粉砕して水性懸濁剤とする。  The above is uniformly mixed and pulverized to obtain an aqueous suspension.
産業上の利用可能性 本発明の化合物は、植物病原菌防除に優れた効果を有するものであり、農園芸用 等における殺菌剤として利用可能である。 なお、 2005年 4月 27曰に出願された曰本特許出願 2005— 129320号の明細書 、特許請求の範囲、図面及び要約書の全内容をここに引用し、本発明の明細書の開 示として、取り入れるものである。 Industrial applicability The compound of the present invention has an excellent effect for controlling plant pathogens and can be used as a bactericidal agent for agricultural and horticultural use. The entire contents of the specification, claims, drawings, and abstract of Japanese Patent Application No. 2005-129320 filed on April 27, 2005 are hereby incorporated herein by reference. As it is incorporated.

Claims

請求の範囲 式 (I) Claim Formula (I)
[化 1]  [Chemical 1]
〔式中、 X及び Y1は各々独立にハロゲン原子；水酸基；ホルミル基;ノヽロゲン、アルコ キシ若しくはアルキルチオで置換されてもょ 、アルキル基 トロ基；アルキルで置換 されてもょ 、ァミノ基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基； アルキルチオ基；アルキルスルホ -ル基又はアルキルスルフィエル基であり、 Y2はハ 口アルキル基、ハロアルコキシ基又は臭素原子であり、 Zはハロゲン原子；ホルミル基 又はハロゲンで置換されてもよいアルキル基であり、 Aはカルボ-ル基；チォカルボ -ル基又は単結合であり、 R1及び R2は各々独立に水素原子;ノヽロゲン、シクロアルキ ル、置換可フヱ-ル、置換可複素環、アルキルチオ、アルコキシ若しくはシァノで置 換されてもよいアルキル基;ノヽロゲン、シクロアルキル、フエ-ル若しくはシァノで置換 されてもよいァルケ-ル基;ノヽロゲン、シクロアルキル、フエ-ル若しくはシァノで置換 されてもょ 、アルキ-ル基；ハロゲン若しくはアルキルで置換されてもよ!、シクロアル キル基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基；ハロゲン、アル キル若しくはハロアルキルで置換されてもよいァリール基;ノヽロゲン、アルキル若しく はハロアルキルで置換されてもょ 、複素環基；ハロゲンで置換されてもょ 、アルキル カルボ-ル基；ァルケ-ルカルポ-ル基;イミノ基；アルキルで置換されてもょ 、ァミノ 基；アルキルで置換されてもょ 、ァミノカルボ-ル基；アルキルカルボ-ルァミノ基；ホ ルミル基又はシァノ基であり、 nは 0〜4の整数である（但し、 Xと Y1が同時に塩素原子 である場合は除く）〕で表されるビフエニル誘導体又はその塩。 [In the formula, X and Y 1 are each independently a halogen atom; a hydroxyl group; a formyl group; a substituent that is substituted with a norogen, an alkoxy group, or an alkylthio; an alkyl group; a tro group; an amino group that is substituted with an alkyl; an amino group; Alkyl group, which may be substituted with halogen or alkoxy; alkylthio group; alkylsulfol group or alkylsulfier group; Y 2 is a haloalkyl group, haloalkoxy group or bromine atom; Z is a halogen atom A formyl group or an alkyl group which may be substituted with halogen; A is a carbo group; a thio group or a single bond; R 1 and R 2 are each independently a hydrogen atom; a norogen, a cycloalkyl; , Substituted file, substituted heterocycle, alkylthio, alkoxy or alkyl group optionally substituted by cyan; An alkenyl group optionally substituted with benzene, phenol or cyan; may be substituted with a norogen, cycloalkyl, phenol or cyan; an alkyl group; may be substituted with halogen or alkyl; !, Cycloalkyl group; substituted with halogen or alkoxy; alkoxy group; aryl group optionally substituted with halogen, alkyl or haloalkyl; substituted with norogen, alkyl or haloalkyl; Ring group: substituted with halogen, alkyl carbo group; alkenyl group; imino group; substituted with alkyl, amino group; substituted with alkyl, amino carbo group ; alkylcarbonyl - Ruamino group; an e mill group or Shiano group, n is an integer from 0 to 4 (provided that, X and Y 1 is a chlorine atom der simultaneously Biphenyl derivative or a salt thereof is excluded)] if.
[2] Aがカルボ-ル基又はチォカルボ-ル基である請求項 1に記載のビフエ-ル誘導体 又はその塩。 式 (I 1) [2] The biphenyl derivative or a salt thereof according to claim 1, wherein A is a carbo group or a thio group. Formula (I 1)
[化 2]  [Chemical 2]
〔式 R2及び nは前記請求項 1に記載の通りである〕で表される 請求項 1に記載のビフヱ-ル誘導体又はその塩。 〔formula The biphenyl derivative or a salt thereof according to claim 1, wherein R 2 and n are as defined in claim 1 above.
[4] Xが臭素原子又はアルキル基である請求項 1に記載のビフヱニル誘導体又はその塩 [4] The biphenyl derivative or a salt thereof according to claim 1, wherein X is a bromine atom or an alkyl group.
[5] Y2がハロアルキル基である請求項 1に記載のビフエ-ル誘導体又はその塩。 Le derivative or a salt thereof - [5] Bifue according to claim 1 Y 2 is a haloalkyl group.
[6] Y2がモノフルォロメチル基、ジフルォロメチル基又はトリフルォロメチル基である請求 項 1に記載のビフヱ-ル誘導体又はその塩。 6. The biphenyl derivative or a salt thereof according to claim 1, wherein Y 2 is a monofluoromethyl group, a difluoromethyl group or a trifluoromethyl group.
[7] nが 0又は 1である請求項 1に記載のビフエ二ル誘導体又はその塩。 [7] The biphenyl derivative or a salt thereof according to claim 1, wherein n is 0 or 1.
[8] 請求項 1に記載のビフエ-ル誘導体又はその塩を有効成分として含有する農園芸用 殺菌剤。 [8] An agricultural and horticultural fungicide containing the biphenyl derivative or a salt thereof according to claim 1 as an active ingredient.
[9] 請求項 1に記載のビフ ニル誘導体又はその塩を農園芸用植物に施用することから 成る植物病害の防除方法。  [9] A plant disease control method comprising applying the biphenyl derivative or salt thereof according to claim 1 to an agricultural or horticultural plant.
[10] 請求項 3に記載の式 (I 1)で表されるビフエニル誘導体又はその塩の製造方法で あって、式 (V)： [10] A method for producing a biphenyl derivative represented by the formula (I 1) or a salt thereof according to claim 3, wherein the formula (V):
[化 3] [Chemical 3]
〔式中、 X及び Y1は各々独立にハロゲン原子；水酸基；ホルミル基;ノヽロゲン、アルコ キシ若しくはアルキルチオで置換されてもょ 、アルキル基 トロ基；アルキルで置換 されてもょ 、ァミノ基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基； アルキルチオ基；アルキルスルホ -ル基又はアルキルスルフィエル基であり、 Y2はハ 口アルキル基、ハロアルコキシ基又は臭素原子であり、 Zはハロゲン原子；ホルミル基 又はハロゲンで置換されてもよいアルキル基であり、 nは 0〜4の整数であり、 Qは水 素原子又はカルボキシル基の保護基である（但し、 Xと Y1が同時に塩素原子である 場合は除く)〕で表される化合物と、 [In the formula, X and Y 1 are each independently a halogen atom; a hydroxyl group; a formyl group; a alkyl group, a tro group, or an alkylthio group; Or an amino group substituted by halogen or alkoxy; an alkylthio group; an alkylsulfol group or an alkylsulfiel group; Y 2 is a haloalkyl group, a haloalkoxy group, or bromine; An atom, Z is a halogen atom; a formyl group or an alkyl group which may be substituted with a halogen, n is an integer of 0 to 4, and Q is a hydrogen atom or a protecting group for a carboxyl group (provided that (Excluding the case where X and Y 1 are simultaneously chlorine atoms))),
式 HNR^"  Formula HNR ^ "
〔式中、 R1及び R2は各々独立に水素原子；ノヽロゲン、シクロアルキル、置換可フエ- ル、置換可複素環、アルキルチオ、アルコキシ若しくはシァノで置換されてもよいアル キル基;ノヽロゲン、シクロアルキル、フ -ル若しくはシァノで置換されてもよいアルケ -ル基；ノヽロゲン、シクロアルキル、フ -ル若しくはシァノで置換されてもよいアルキ -ル基；ハロゲン若しくはアルキルで置換されてもょ 、シクロアルキル基；ハロゲン若 しくはアルコキシで置換されてもょ 、アルコキシ基；ハロゲン、アルキル若しくはハロア ルキルで置換されてもよいァリール基;ノヽロゲン、アルキル若しくはハロアルキルで置 換されてもょ 、複素環基；ハロゲンで置換されてもょ 、アルキルカルボ-ル基；ァルケ 二ルカルボ-ル基;イミノ基；アルキルで置換されてもょ 、ァミノ基；アルキルで置換さ れてもよ!/、ァミノカルボ-ル基；アルキルカルボ-ルァミノ基；ホルミル基又はシァノ基 である〕で表される化合物とをアミドィ匕反応させることからなる前記ビフ 二ル誘導体 又はその塩の製造方法。 [Wherein, R 1 and R 2 are each independently a hydrogen atom; a norogen, a cycloalkyl, a substituted phenyl, a substituted heterocycle, an alkyl group optionally substituted with alkylthio, alkoxy or cyan; , An alkenyl group optionally substituted by cycloalkyl, fur or cyan; an alkyl group optionally substituted by halogeno, cycloalkyl, fur or cyan; optionally substituted by halogen or alkyl A cycloalkyl group; substituted with halogen or alkoxy; an alkoxy group; an aryl group which may be substituted with halogen, alkyl or haloalkyl; and substituted with norogen, alkyl or haloalkyl; Heterocyclic group; may be substituted with halogen; alkyl carbonyl group; alkenyl carbonyl group; imino group; alkyl Or amino group; may be substituted with alkyl! /, An aminocarbo group; an alkylcarbo-amino group; a formyl group or a cyano group]. A process for producing the bifuryl derivative or a salt thereof.
[11] アミド化反応を縮合剤の存在下で行う請求項 10に記載の方法。  [11] The method according to claim 10, wherein the amidation reaction is carried out in the presence of a condensing agent.
[12] 式 (V) :  [12] Formula (V):
[化 4] [Chemical 4]
〔式中、 X及び Y1は各々独立にハロゲン原子；水酸基；ホルミル基;ノヽロゲン、アルコ キシ若しくはアルキルチオで置換されてもょ 、アルキル基 トロ基；アルキルで置換 されてもょ 、ァミノ基；ハロゲン若しくはアルコキシで置換されてもょ 、アルコキシ基； アルキルチオ基；アルキルスルホ -ル基又はアルキルスルフィエル基であり、 Y2はノヽ 口アルキル基、ハロアルコキシ基又は臭素原子であり、 Zはハロゲン原子；ホルミル基 又はハロゲンで置換されてもよいアルキル基であり、 nは 0〜4の整数であり、 Qは水 素原子又はカルボキシル基の保護基である（但し、 Xと Y1が同時に塩素原子である 場合は除く)〕で表される化合物。 [In the formula, X and Y 1 are each independently a halogen atom; a hydroxyl group; a formyl group; a alkyl group, a tro group, or an alkylthio group; Or an amino group substituted by halogen or alkoxy; an alkylthio group; an alkylsulfol group or an alkylsulfiel group; Y 2 is a noble alkyl group, haloalkoxy group or bromine; An atom, Z is a halogen atom; a formyl group or an alkyl group which may be substituted with a halogen, n is an integer of 0 to 4, and Q is a hydrogen atom or a protecting group for a carboxyl group (provided that A compound represented by the above) except that X and Y 1 are simultaneously chlorine atoms.
Qで表されるカルボキシル基の保護基力 フエ-ル又はピリジルで置換されてもょ ヽ アルキル基である請求項 12に記載の化合物。  13. The compound according to claim 12, which is an alkyl group that is substituted with a phenyl or pyridyl protecting group for the carboxyl group represented by Q.
PCT/JP2006/308764 2005-04-27 2006-04-26 Biphenyl derivative or salt thereof, and bactericide for agricultural and horticultural use containing same as active ingredient WO2006118155A1 (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010032147A2 (en) * 2008-09-19 2010-03-25 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
JP2010523593A (en) * 2007-04-06 2010-07-15 ニューロクライン バイオサイエンシーズ，インコーポレイテッド Gonadotropin releasing hormone receptor antagonists and related methods
US8624034B2 (en) 2011-03-07 2014-01-07 Pfizer Inc. Fluoro-pyridinone derivatives useful as antibacterial agents
US8664401B2 (en) 2009-12-16 2014-03-04 Pfizer Inc. N-linked hydroxamic acid derivatives useful as antibacterial agents
US8748466B2 (en) 2011-04-08 2014-06-10 Pfizer Inc. Isoxazole derivatives useful as antibacterial agents
US8809333B2 (en) 2011-04-08 2014-08-19 Pfizer Inc. Imidazole, pyrazole, and triazole derivatives useful as antibacterial agents
CN109608341A (en) * 2018-12-28 2019-04-12 西南交通大学 A kind of aryl aniline compound and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11152259A (en) * 1997-08-26 1999-06-08 Kumiai Chem Ind Co Ltd Biarylalkylenecarbamic acid derivative, and fungicide for agriculture and horticulture
WO2005044007A1 (en) * 2003-11-11 2005-05-19 Ishihara Sangyo Kaisha, Ltd. Biphenyl derivative or its salt, and pesticide containing it as an active ingredient

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11152259A (en) * 1997-08-26 1999-06-08 Kumiai Chem Ind Co Ltd Biarylalkylenecarbamic acid derivative, and fungicide for agriculture and horticulture
WO2005044007A1 (en) * 2003-11-11 2005-05-19 Ishihara Sangyo Kaisha, Ltd. Biphenyl derivative or its salt, and pesticide containing it as an active ingredient

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8952161B2 (en) 2007-04-06 2015-02-10 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
JP2010523593A (en) * 2007-04-06 2010-07-15 ニューロクライン バイオサイエンシーズ，インコーポレイテッド Gonadotropin releasing hormone receptor antagonists and related methods
US11713324B2 (en) 2007-04-06 2023-08-01 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US10941159B2 (en) 2007-04-06 2021-03-09 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US10336769B2 (en) 2007-04-06 2019-07-02 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US9422310B2 (en) 2007-04-06 2016-08-23 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
WO2010032147A3 (en) * 2008-09-19 2010-06-03 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
US8722686B2 (en) 2008-09-19 2014-05-13 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
US9340493B2 (en) 2008-09-19 2016-05-17 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
WO2010032147A2 (en) * 2008-09-19 2010-03-25 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
US9180123B2 (en) 2009-12-16 2015-11-10 Pfizer Inc. N-link hydroxamic acid derivatives useful as antibacterial agents
US9018384B2 (en) 2009-12-16 2015-04-28 Pfizer Inc. N-link hydroxamic acid derivatives useful as antibacterial agents
US8846933B2 (en) 2009-12-16 2014-09-30 Pfizer Inc. N-link hydroxamic acid derivatives useful as antibacterial agents
US8664401B2 (en) 2009-12-16 2014-03-04 Pfizer Inc. N-linked hydroxamic acid derivatives useful as antibacterial agents
US8779148B2 (en) 2011-03-07 2014-07-15 Pfizer Inc. Fluoro-pyridinone derivatives useful as antibacterial agents
US8624034B2 (en) 2011-03-07 2014-01-07 Pfizer Inc. Fluoro-pyridinone derivatives useful as antibacterial agents
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