JP2005225860A - Biphenyl derivative or salt thereof, pest control agent containing the same as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a pest control agent that has stable and high pest-controlling effect on cultivated crops that are infected with plant diseases. <P>SOLUTION: The pest control agent comprises a biphenyl derivative represented by formula (I) or a salt thereof (wherein X, Y and Z are each independently a halogen atom, hydroxy, formyl, an alkyl which may be substituted, an alkoxy which may be substituted, an alkylthio, an alkylsulfonyl, an alkylsulfinyl; A is carbonyl, thiocarbonyl, an alkylene or a single bond; R<SP>1</SP>and R<SP>2</SP>are each independently H, an alkyl which may be substituted, an alkenyl which may be substituted, an alkynyl which may be substituted, an aryl which may be substituted, formyl, an alkylcarbonyl, cyano, and the like; (m) and (n) are each independently 0, 1, 2, 3 or 4). <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a pest control agent containing a novel biphenyl derivative or a salt thereof as an active ingredient.

  WO98 / 37068, page 106, compound table includes N- (3,3-dimethylbutyl) -3- (2-methoxyphenyl) benzamide and N- (3,3-dimethylbutyl) -3- (2-fluorophenyl) ) Benzamide is described. WO99 / 23073, WO2003 / 99776, and WO2004 / 039753 describe compounds having a biphenyl structure. However, these are not compounds for agricultural and horticultural fungicides and / or antifungal agents.

International Publication WO98 / 37068 International Publication No. WO99 / 23073 International Publication WO2003 / 99776 International Publication WO2004 / 039753

  Many agricultural and horticultural fungicides provided in the past have their characteristics in controlling the phytopathogenic fungi, and some of them have a slightly inferior therapeutic effect or a relatively residual effect compared to the preventive effect. Depending on the application situation, it may show only a practically insufficient control effect against phytopathogenic fungi. Accordingly, there is a demand for the creation of new compounds having a strong phytopathogenic fungi control effect.

As a result of researches to solve the above-mentioned problems, the present inventors have used various compounds represented by the formula (I) as an active ingredient, so that various diseases, particularly wheat, vegetables, fruits and florets, can be obtained. The present invention has been completed by finding that it exhibits excellent control effects against powdery mildews, downy mildews such as vegetables and fruits, and rice blast.
That is, the present invention relates to the formula (I):

[Wherein X and Y are each independently a halogen atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino group which may be substituted with alkyl; a halogen or alkoxy; An aryloxy group which may be substituted with halogen or haloalkyl; a heterocyclic oxy group which may be substituted with halogen or haloalkyl; a heterocyclic group which may be substituted with halogen or haloalkyl; An alkylcarbonylamino group; an alkylcarbonyl group optionally substituted with a halogen; an alkylthio group; an alkylsulfonyl group; an alkylsulfinyl group or an imino group optionally substituted with alkyl or alkoxy; Z A halogen atom; a formyl group; an alkyl group which may be substituted with halogen; an alkoxy group which may be substituted with alkoxy; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group, wherein A is a carbonyl group; a thiocarbonyl group; an alkylene group Or R ¹ and R ² are each independently a hydrogen atom; halogen, cycloalkyl, substituted phenyl, substituted heterocycle, alkyl group optionally substituted with alkylthio, alkoxy or cyano; halogen, cycloalkyl Alkenyl group optionally substituted with phenyl, cyano; alkynyl group optionally substituted with halogen, cycloalkyl, phenyl or cyano; cycloalkyl group optionally substituted with halogen or alkyl; substituted with halogen, alkyl or haloalkyl The An aryl group which may be substituted with halogen, alkyl or haloalkyl; an alkylcarbonyl group which may be substituted with halogen; an alkenylcarbonyl group; an imino group; an amino group which may be substituted with alkyl; An aminocarbonyl group which may be substituted with; an alkylcarbonylamino group; a formyl group or a cyano group, and m and n are each independently 0, 1, 2, 3 or 4] or a biphenyl derivative thereof The present invention relates to a pest control agent containing a salt as an active ingredient.

  As the halogen atom contained in the formula (I), fluorine, chlorine, bromine and iodine are used, and for example, fluorine, chlorine and bromine are preferably used.

Examples of the alkyl moiety contained in the formula (I) include C _1-6 alkyl (eg, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, etc.).

Examples of the alkenyl moiety contained in the formula (I) include C _2-6 alkenyl (eg, vinyl, allyl, isopropenyl, 3-methyl-2-butenyl, etc.).

Examples of the alkynyl moiety contained in the formula (I) include C _2-6 alkynyl (eg, 2-propynyl, 2-butynyl, etc.).

Examples of the cycloalkyl contained in the formula (I) include C _3-6 cycloalkyl (eg, cyclopropyl, cyclopentyl, cyclohexyl, etc.).

Examples of the aryl moiety contained in the formula (I) include C _6-10 aryl (eg, phenyl, naphthyl, etc.). In addition, examples of the heterocyclic moiety contained in the formula (I) include pyridyl, thienyl, furanyl, thiazolyl and the like. In addition, examples of the substituent of the substituted phenyl and the substituted heterocycle included in the formula (I) include halogen, alkyl, haloalkyl, alkoxy, haloalkoxy and the like.

  When there are a plurality of substituents Y included in the formula (I), each of Y may be the same or different. M indicating the number of Y substituents is preferably 2. Among them, one Y is substituted at the para position with respect to X, and the other Y is ortho position with respect to the bonding position of the two phenyl rings. It is more desirable to substitute with

  When there are a plurality of substituents Z contained in the formula (I), each of Z may be the same or different. N representing the number of Z substituents is preferably 0.

  The biphenyl derivative represented by the formula (I) or a salt thereof exhibits an excellent effect as an active ingredient of a pest control agent such as an agricultural / horticultural fungicide or an antifungal agent.

Among the biphenyl derivatives of the formula (I) or salts thereof, desirable embodiments are described below.
(1) In the formula (I), X is a chlorine atom; a bromine atom; an iodine atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino which may be substituted with alkyl. Aryloxy group which may be substituted with halogen or haloalkyl; heterocyclic oxy group which may be substituted with halogen or haloalkyl; heterocyclic group which may be substituted with halogen or haloalkyl; amino which may be substituted with alkyl Alkylcarbonylamino group; alkylcarbonyl group optionally substituted with halogen; alkylthio group; alkylsulfonyl group or alkylsulfinyl group, Y is halogen atom; hydroxyl group; formyl group; substituted with halogen, alkoxy or alkylthio May Nitro group; amino group optionally substituted with alkyl; aryloxy group optionally substituted with halogen or haloalkyl; heterocyclic oxy group optionally substituted with halogen or haloalkyl; substituted with halogen or haloalkyl An aminocarbonyl group which may be substituted with alkyl; an alkylcarbonylamino group; an alkylcarbonyl group which may be substituted with halogen; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group, and Z is a halogen atom A biphenyl wherein A is a carbonyl group; a thiocarbonyl group or a single bond, and m and n are each independently 0, 1, 2, 3 or 4; Derivatives or salts thereof.
(2) In the formula (I), m is 2 and one Y is substituted at the para position with respect to X, and the other Y is substituted at the ortho position with respect to the bonding position of the two phenyl rings Derivatives or salts thereof.
(3) The biphenyl derivative according to (1), wherein m is 2, one Y is substituted at the para position with respect to X, and the other Y is substituted at the ortho position with respect to the bonding position of the two phenyl rings Its salt.

(4) In the formula (I), X is a chlorine atom; a bromine atom; an iodine atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino which may be substituted with alkyl. Aryloxy group which may be substituted with halogen or haloalkyl; heterocyclic oxy group which may be substituted with halogen or haloalkyl; heterocyclic group which may be substituted with halogen or haloalkyl; amino which may be substituted with alkyl Alkylcarbonylamino group; alkylcarbonyl group optionally substituted with halogen; alkylthio group; alkylsulfonyl group or alkylsulfinyl group, Y is halogen atom; hydroxyl group; formyl group; substituted with halogen, alkoxy or alkylthio May Nitro group; amino group optionally substituted with alkyl; aryloxy group optionally substituted with halogen or haloalkyl; heterocyclic oxy group optionally substituted with halogen or haloalkyl; substituted with halogen or haloalkyl An aminocarbonyl group which may be substituted with alkyl; an alkylcarbonylamino group; an alkylcarbonyl group which may be substituted with halogen; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group, wherein A is thiocarbonyl A biphenyl derivative or a salt thereof which is a group or a single bond.
(5) X is a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino group which may be substituted with alkyl; an aryloxy group which may be substituted with halogen or haloalkyl; Heterocyclic oxy group optionally substituted with halogen or haloalkyl; heterocyclic group optionally substituted with halogen or haloalkyl; aminocarbonyl group optionally substituted with alkyl; alkylcarbonylamino group; optionally substituted with halogen The biphenyl derivative of (1) or a salt thereof, which is an alkylcarbonyl group; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group.

(6) In the formula (I), X and Y are each independently a halogen atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino group which may be substituted with alkyl An alkoxy group which may be substituted with alkoxy; an aryloxy group which may be substituted with halogen or haloalkyl; a heterocyclic oxy group which may be substituted with halogen or haloalkyl; a heterocyclic group which may be substituted with halogen or haloalkyl; An aminocarbonyl group which may be substituted with alkyl; an alkylcarbonylamino group; an alkylcarbonyl group which may be substituted with halogen; an alkylthio group; an alkylsulfonyl group; an alkylsulfinyl group or an imino group which may be substituted with alkyl or alkoxy; And Z is halo Formyl group; alkyl group which may be substituted with halogen; alkoxy group which may be substituted with alkoxy; alkylthio group; alkylsulfonyl group or alkylsulfinyl group, and A is a carbonyl group; thiocarbonyl group or single bond And R ¹ and R ² are each independently an alkyl group optionally substituted with halogen, cycloalkyl, substituted phenyl, substituted heterocycle, alkylthio, alkoxy or cyano; substituted with halogen, cycloalkyl, phenyl or cyano An alkynyl group optionally substituted with halogen, cycloalkyl, phenyl or cyano; a cycloalkyl group optionally substituted with halogen or alkyl; an aryl group optionally substituted with halogen, alkyl or haloalkyl ;halogen Heterocyclic group which may be substituted with alkyl or haloalkyl; alkylcarbonyl group which may be substituted with halogen; alkenylcarbonyl group; imino group; amino group which may be substituted with alkyl; aminocarbonyl which may be substituted with alkyl Group; alkylcarbonylamino group; biphenyl derivative or salt thereof which is formyl group or cyano group.
(7) The biphenyl derivative or a salt thereof according to (6), wherein Z is a halogen atom; a formyl group or an alkyl group which may be substituted with a halogen.
(8) X is a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino group which may be substituted with alkyl; an aryloxy group which may be substituted with halogen or haloalkyl; Heterocyclic oxy group optionally substituted with halogen or haloalkyl; heterocyclic group optionally substituted with halogen or haloalkyl; aminocarbonyl group optionally substituted with alkyl; alkylcarbonylamino group; optionally substituted with halogen The biphenyl derivative of (7) or a salt thereof, which is an alkylcarbonyl group; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group.

(9) The biphenyl derivative of (1) or a salt thereof, wherein A is a carbonyl group or a single bond in the formula (I) {provided that N- (3,3-dimethylbutyl) -3- (2-methoxyphenyl) benzamide And N- (3,3-dimethylbutyl) -3- (2-fluorophenyl) benzamide}.
(10) In the formula (I), A is a carbonyl group or a single bond, and R ¹ and R ² are each independently an alkyl group which may be substituted with halogen, cycloalkyl, phenyl, alkylthio, alkoxy or cyano; halogen An alkenyl group optionally substituted with cycloalkyl, phenyl or cyano; an alkynyl group optionally substituted with halogen, cycloalkyl, phenyl or cyano; an aryl group optionally substituted with halogen, alkyl or haloalkyl; an alkylcarbonyl group A biphenyl derivative or a salt thereof when it is a formyl group or a cyano group;

  The compound of the formula (I) or a salt thereof can be produced by various known synthesis methods utilizing characteristics based on the basic skeleton or the type of substituent. For example, when the compound of the 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 may allow efficient production. Examples of the protecting group described above include the protecting groups described in Protective Groups in Organic Synthesis (3rd Edition, 1999) by TWGreene, PGMWuts, and these protecting groups may be appropriately selected and used depending on the reaction conditions. good. In the method using a protecting group, a desired compound can be obtained by carrying out the reaction using the protecting group and then removing the protecting group as necessary or converting it to a desired group. The reaction can be carried out by applying a method known by those skilled in the art, such as ordinary esterification, amidation, dehydration, diazotization, oxidation and the like.

Embodiments of desirable production methods for the compounds of formula (I) are described below.
(Production method 1)

(In the reaction formula, X, Y, Z, m, n, A, R ¹ and R ² are as described above, L is a leaving group, and M is a metal)
As shown in the above flow, the compound of the formula (I) can be produced by coupling the compound of the formula (II) and the compound of the formula (III) in the presence of a transition metal catalyst. The reaction can be performed according to a known method (for example, Comprehensive Organic Synthesis, Volume3,481,1991 or Synthetic Communications, Volume11,513,1981). The leaving group represented by L in the formula (II) is halogen, trifluoromethanesulfonyloxy and the like, and the metal represented by M in the formula (III) is hydroxyboron, alkylboron, alkoxyboron, halogen Examples thereof include magnesium halide, zinc halide, alkyltin, alkylsilicon, alkoxysilicon, silicon halide, alkylaluminum, 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), tetrakis (triphenylphosphine) palladium (0), bis (dibenzylideneacetone) palladium (0), tetrakis (dibenzylideneacetone) dipalladium (0), palladium (II)- Triphenylphosphine, palladium (II) acetate-tricyclohexylphosphine, dichloropalladium (II) -1,1'-bis (dicyclohexylphosphino) ferrocene, tetrakis (triphenylphosphine) nickel (0), bis (1,5- And cyclooctadiene) nickel (0), nickel acetylacetonate (II), dichlorobis (triphenylphosphine) nickel (II), tetrakis (triphenylphosphine) platinum (0), and the like. In the case of a complex, one previously isolated 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 (II). The reaction may be 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, dimethoxyethane, and diethylene glycol dimethyl ether; esters such as ethyl acetate and methyl acetate. Alcohols such as methanol, ethanol, n-propanol and isopropanol; aromatic hydrocarbons such as benzene, chlorobenzene, nitrobenzene and toluene; nitriles such as acetonitrile; N, N-dimethylformamide; N, N-dimethylacetamide; Dimethyl sulfoxide: The reaction is carried out in a solvent such as water that does not inhibit the progress of this reaction or in the absence of a solvent. In addition, two or more of these solvents can be used as a mixed solvent depending on circumstances.

  In the reaction, the compound of formula (II) and the compound of formula (III) can be used in an equivalent amount or in excess of one. In addition, the reaction in the presence of bases may be advantageous for smoothly proceeding 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; sodium hydroxide, water Alkali metal hydroxides such as potassium oxide; alkaline earth metal hydroxides such as calcium hydroxide; inorganic salts such as cesium fluoride and potassium fluoride; or triethylamine, pyridine, 4- (N, N-dimethylamino) Examples include 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 (II).

  The reaction temperature is -70 ° C to 300 ° C, preferably 0 ° C to the boiling point range of the solvent used. The reaction time is not constant depending on the reaction temperature, reaction amount, reaction pressure, etc., but it is generally selected from the range of 1 hour to 72 hours.

(Manufacturing method 2)
The compound of the formula (I-1) in which A in the formula (I) is a carbonyl group can also be produced by the following method.

(In the reaction formula, X, Y, Z, m, n, R ¹ and R ² are as described above.)
As shown in the above flow, the compound of the formula (I-1) can be produced by an amidation reaction between the compound of the formula (VI) and the compound of the formula (VII).

  The amidation reaction can be performed by condensing the compound of formula (VI) with the compound of formula (VII) in the presence of a condensing agent. Examples of the condensing agent include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIPC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (WSC), 1,1′-carbonylbis-1H-imidazole (CDI). ) And the like. Examples of solvents that can be used include aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran (THF), 1,4-dioxane and dimethoxyethane, dichloromethane, 1,2-dichloroethane and chloroform. And halogenated hydrocarbons such as N, N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and pyridine. In addition, two or more of these solvents can be used as a mixed solvent depending on circumstances.

The compound of formula (I-1) can also be produced by a method using a reactive derivative of the compound of formula (VI) instead of the compound of formula (VI) in the amidation reaction. As the reactive derivative of the compound of the formula (VI), an acid halide, an acid anhydride, an active ester or the like can be used. The reaction can be performed, for example, according to the method described in “Chemical Experiment Course (4th edition)” volume 22 (1992) (Maruzen) edited by the Chemical Society of Japan.
(Raw material manufacturing method I)
The compound of the formula (VI) that is the starting material of production method 2 can be produced by the following method.

(In the reaction formula, X, Y, Z, m, n, M and L are as described above, and Q is a protecting group for a hydrogen atom or a carboxyl group)
The compound of formula (VI) can be produced by hydrolyzing the compound of formula (V). When Q is a hydrogen atom, the compound of formula (V) becomes the compound of formula (VI) itself, so that the hydrolysis step can be omitted. When Q is a protecting group for a carboxyl group, the protecting group Q can be applied with the protecting group for a carboxyl group described in the above-mentioned “Protective Groups in Organic Synthesis (3rd Edition, 1999)”. It can be removed by hydrolysis or the like.

  The compound of the formula (V) can be produced by coupling the compound of the formula (IV) and the compound of the formula (III) in the presence of a transition metal catalyst. The compound of formula (V) can be produced by coupling a compound of formula (VII) and a compound of formula (VIII) in the presence of a transition metal catalyst. The reaction can be carried out in the same manner as in Production Method 1 described above.

(Raw material production method II)
The compound of formula (VI) which is the starting material of production method 2 can also be produced by the following method.

(In the reaction formula, X, Y, Z, m, n, M and L are as described above.)
The compound of the formula (VI) can be produced by oxidizing the compound of the formula (XI) by an ordinary method using an oxidizing agent such as manganese dioxide and potassium permanganate. The compound of the formula (XI) can be produced by coupling the compound of the formula (IX) and the compound of the formula (III) in the presence of a transition metal catalyst. The compound of formula (XI) can be produced by coupling a compound of formula (VII) and a compound of formula (X) 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.

(Manufacturing method 3)

(In the reaction formula, X, Y, Z, m, n, A, R ¹ and R ² are as described above, L is a leaving group, and M is a metal)
As shown in the above flow, the compound of the formula (I) can be produced by coupling the compound of the formula (VII) and the compound of the formula (XII) in the presence of a transition metal catalyst. The reaction can be carried out according to the reaction described in Process 1.

  The compound of formula (I) and its production intermediate produced by the methods 1 to 3 are subjected to usual chemical operations such as extraction, concentration, distillation, crystallization, filtration, recrystallization, and various chromatography. Can be isolated and purified.

  The biphenyl derivative or a salt thereof (hereinafter abbreviated as the compound of the present invention) is useful as an active ingredient of a pesticide such as an agricultural and horticultural fungicide and / or an antifungal agent. Useful as an active ingredient. Examples of agricultural and horticultural fungicides include rice blast disease, sesame leaf blight, coat blight; wheat powdery mildew, red mold disease, rust disease, snow rot, naked smut, eye coat disease, leaves Blight, dry blight; citrus black spot, common scab; apple monilia, powdery mildew, spotted leaf disease, black scab; pear black scab, black spot; peach ash, black spot, Phomopsis rot; grape black rot, late rot, powdery mildew, downy mildew; oyster anthracnose, leaf fall; cucurbit anthracnose, powdery mildew, vine blight, downy mildew; Tomato ring mold disease, leaf mold disease, plague; black spot disease of cruciferous vegetables, summer plague of potato, plague; strawberry powdery mildew; for the control of diseases such as gray mold disease and mycorrhizal disease of various crops Although effective, it exhibits an excellent control effect especially against powdery mildew of wheat and vegetables and downy mildew of vegetables. It is also effective for controlling soil diseases caused by phytopathogenic fungi such as Fusarium, Psium, Rhizoctonia, Verticillium, and Plasmodiohora. Antifungal agents are effective against, for example, Candida, Cryptococcus, Aspergillus, Staphylococcus, and Trichophyton.

  The compound of the present invention is usually prepared by mixing the compound with various agricultural adjuvants, powders, granules, granule wettable powders, wettable powders, aqueous suspensions, oily suspensions, aqueous solvents, emulsions, It can be formulated into various forms such as liquids, pastes, aerosols, microdispersions, etc., but can be made into any conventional form used in the art as long as it meets the purpose of the present invention. it can. Adjuvants used in the formulation include solid carriers such as diatomaceous earth, slaked lime, calcium carbonate, talc, white carbon, kaolin, bentonite, kaolinite and sericite, clay, sodium carbonate, sodium bicarbonate, sodium sulfate, zeolite, starch, etc. Solvent such as water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, chlorobenzene, cyclohexane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, alcohol; fatty acid salt, benzoic acid Acid salt, alkylsulfosuccinate, dialkylsulfosuccinate, polycarboxylate, alkylsulfate, alkylsulfate, alkylarylsulfate, alkyldiglycolethersulfate, alcohol Sulfate ester, alkyl sulfonate, alkyl aryl sulfonate, aryl sulfonate, lignin sulfonate, alkyl diphenyl ether disulfonate, polystyrene sulfonate, alkyl phosphate ester, alkyl aryl phosphate, styryl aryl Phosphate, polyoxyethylene alkyl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl aryl ether sulfate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl aryl phosphate , Anionic surfactants such as naphthalenesulfonic acid formalin condensate salts and spreading agents; sorbitan fatty acid esters, glycerin fatty acid esters, fatty acid polyglycerides , 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 , Nonionic surfactants and spreading agents such as polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxypropylene fatty acid ester; olive oil, kapok oil, castor oil, palm Oil, coconut oil, coconut oil, sesame oil, corn oil, rice bran oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, linseed oil, cutting oil, liquid Examples include vegetable oils such as paraffin 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 a bulking agent, thickener, anti-settling agent, antifreezing agent, dispersion stabilizer, safener, and antifungal agent can also be used. The compounding ratio of the compound of the present invention and various adjuvants is generally 0.005: 99.995 to 95: 5, preferably 0.2: 99.8 to 90:10. 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 spreaders 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 defined unconditionally, but in the case of foliar treatment, it is usually 0.1 to 10,000 ppm, preferably 1 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, coating, etc.) can be performed. It can also be applied by the so-called ultra low volume application method (ultra low volume). In this method, it is possible to contain 100% of the active ingredient.

  The compound of the present invention may be used in combination with other agricultural chemicals such as fungicides, insecticides, acaricides, nematicides, antiviral agents, attractants, herbicides, plant growth preparations, etc. In this case, a more excellent effect may be exhibited.

In the above-mentioned other agricultural chemicals, as an active ingredient compound of a fungicide (generic name; including some applications), for example, pyrimidinamine compounds such as mepanipyrim, pyrimethanil, and cyprodinil;
Pyridinamine compounds such as Fluazinam;
Triadimefon, Bitertanol, Triflumizole, Etaconazole, Propiconazole, Penconazole, Flusilazole, Microbutanil, Cyproconazole Cyproconazole), Tebuconazole, Hexaconazole, Furconazole-cis, Prochloraz, Metconazole, Epoxiconazole, Tetraconazole, O Oxpoconazole fumarate, Sipconazole, Prothioconazole, Triadimenol, Flutriafol, Difenoconazole Azole compounds such as Fluquinconazole, Fenbuconazole, Bromuconazole, Diniconazole, Tricyclazole, Probenazole, Simeconazole;
Quinoxaline compounds such as quinomethionate;
Dithiocarbamate compounds such as Maneb, Zineb, Mancozeb, Polycarbamate, Metiram, Propineb;
Organochlorine compounds such as Fthalide, Chlorothalonil, Quintozene;
Imidazole compounds such as Benomyl, Thiophanate-Methyl, Carbendazim, Cyazofamid;
Cyanoacetamide compounds such as Cymoxanil;
Phenylamide compounds such as Metalaxyl, Metalaxyl M, Oxadixyl, Offurace, Benalaxyl, Furalaxyl, Cyprofuram;
Sulfenic acid compounds such as Dichlofluanid;
Copper compounds such as cuprichydroxide and organic copper (Oxine Copper);
Isoxazole compounds such as hymexazol;
Organophosphorus such as fosetyl-aluminum, turfos-methyl, S-benzyl O, O-diisopropyl phosphorothioate, O-ethyl S, S-diphenyl phosphorodithioate, aluminum ethyl hydrogen phosphonate Compound;
N-halogenothioalkyl compounds such as Captan, Captafol, Folpet;
Dicarboximide compounds such as Procymidone, Iprodione, Vinclozolin;
Benzanilide compounds such as Flutolanil, Mepronil, Zoxamid, Tiadinil;
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 and Spiroxamine;
Organotin compounds such as Fentin Hydroxide and Fentin Acetate;
Urea compounds such as Pencycuron;
Synamic acid compounds such as Dimethomorph and Flumorph;
Phenyl carbamate compounds such as Dietofencarb;
Cyanopyrrole compounds such as fludioxonil and fenpiclonil;
Azoxystrobin, Kresoxim-Methyl, Metominofen, Trifloxystrobin, Picoxystrobin, Oryzastrobin, Dimoxystrobin A strobilurin-based compound 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, benchthiavalicarb;
An imidazolidine-based compound such as fenamidone;
Hydroxyanilide compounds such as Fenhexamid;
Benzenesulfonamide compounds such as flusulfamid; oxime ether compounds such as cyflufenamid;
Phenoxyamide-based compounds such as phenoxanil;
Atraquinone compounds;
Crotonic acid compounds;
Antibiotics such as polyoxins;
Guanidine-based compounds such as iminoctadine;
Other compounds include Isoprothiolane, Pyroquilon, Diclomezine, Quinoxyfen, Propamocarb Hydrochloride, Chloropicrin, Dazomet, and Carmsodium salt. ), Nicobifen, Metrafenone, MTF-753, UBF-307, Diclocymet, Proquinazid and the like.

In the above-mentioned other agricultural chemicals, insecticide, acaricide, or nematicide, that is, an active ingredient compound of a pesticide (generic name; including some pending applications), for example, Profenofos, Dichlorvos ( Dichlorvos, Fenamiphos, Fenitrothion, EPN, Diazinon, Chlorpyrifos-methyl, Acephate, Prothiofos, Fosthiazate, Phosphocarb, Phosphocarb, Phosphocarb Organophosphate compounds such as Cadusafos) and disulfoton;
Carbaryl (Carbaryl), Propoxur, Aldicarb, Carbofuran, Thiodicarb, Methomyl, Oxamyl, Ethiofencarb, Pirimicarb, Fenobucarb Carbamate compounds such as Carbosulfan and Benfuracarb;
Nereistoxin derivatives such as Cartap and Thiocyclam;
Organochlorine compounds such as Dicofol and Tetradifon;
Organometallic compounds such as Fenbutatin Oxide;
Fenvalerate, Permethrin, Cypermethrin, Deltamethrin, Cyhalothrin, Tefluthrin, Etofenprox, Flufenprox, Imidate Pyrethroid compounds such as
Benzoyl urea compounds such as diflubenzuron, chlorfluazuron, teflubenzuron, flufenoxuron, bistrifluron, noviflumuron;
Juvenile hormone-like compounds such as methoprene;
Pyridazinone compounds such as Pyridaben;
Pyrazole compounds such as Fenpyroximate, Fipronil, Tebufenpyrad, Ethiprole, Tolfenpyrad, Acetoprole;
Imidacloprid, Nitenpyram, Acetamiprid, Thiacloprid, Thiamethoxam, Clothianidin, Nidinotefuran, Dinotefur, Dinotefuran
Hydrazine compounds such as Tebufenozide, Methoxyfenozide, Chromafenozide;
Pyridine compounds such as Pyridaryl, Flonicamid, etc .;
Tetronic acid compounds such as Spirodiclofen;
Strobilurin compounds such as fluacrypyrin;
Pyridinamine compounds such as flufenerim;
Dinitro compounds, organic sulfur compounds, urea compounds, triazine compounds, hydrazone compounds, and other compounds such as Buprofezin, Hexythiazox, Amitraz, Chlorimeform, Silafluofen ), Triazamate, Pymetrozine, Pyrimidifen, Chlorfenapyr, Indoxacarb, Acequinocyl, Etoxazole, Cyromazine, 3-Cyromazine (1,3-dichloropropene), Verbutin, Spiromesifen, Thiazolylcinnanonitrile, Amidoflumet; AKD-1022, IKA-2000 And the like. In addition, mixed with microbial pesticides such as BT agents and entomopathogenic virus agents, antibiotics such as Avermectin, Milbemycin, Spinosad, Emamectin Benzoate, etc. You can also.

Next, specific synthesis examples of the biphenyl derivative of the present invention and the intermediate for production thereof will be described.
Synthesis example 1
Synthesis of N, N-diethyl-3- (2 ', 4', 6'-trimethylphenyl) benzamide (Compound No. 1-1)
To a solution of 0.26 g of 3-bromo-N, N-diethylbenzamide in 10 ml of toluene, 0.05 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto, 0.25 g of 2,4,6-trimethylphenylboronic acid, 2 ml of ethanol, and 3 ml of 2 molar sodium carbonate water were successively added, and the reaction system was purged with nitrogen, followed by heating under reflux for 2 hours.
After allowing to cool, 50 ml of cold water was added, followed by extraction with ethyl acetate (50 ml, twice). The obtained organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. 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 = 2: 1), 0.28 g of oily target compound was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.15 (bs, 6H), 1.98 (s, 6H), 2.31 (s, 3H), 3.30 (bs, 2H), 3.48 (bs, 2H), 6.92 (s, 2H), 7.11 (s, 1H), 7.16 (dd, 1H; J = 1.6 & 6.4 Hz),
7.34 (dd, 1H; J = 1.6 & 6.4 Hz), 7.43 (dd, 1H; J = 6.4 & 6.4 Hz)

Synthesis example 2
Synthesis of N-methyl-3- (2 ', 4', 6'-trimethylphenyl) -benzamide (Compound No. 1-22) (1) Ethyl 3-bromo-benzoate into a 20 ml toluene solution Then, 180 mg of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto, 4 ml of ethanol, 5.5 ml of 2 molar sodium carbonate water, and then 0.98 g of 2,4,6-trimethylphenylboronic acid were sequentially added, and the reaction system was purged with nitrogen, followed by heating under reflux for 5 hours. .
After allowing to cool, 50 ml of cold water and 50 ml of ethyl acetate were added, and the insoluble material was filtered off. The organic layer was separated and extracted from the aqueous layer again with 50 ml of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical and neutral) (developing solvent n-hexane). : Ethyl acetate = 16: 1), and 1.2 g of ethyl 3- (2 ′, 4 ′, 6′-trimethylphenyl) -benzoate having a melting point of 62.9 ° C. was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.40 (t, 3H; J = 7.2Hz), 2.00 (s, 6H), 2.35 (s, 3H), 4.38 (q, 2H: J = 7.2Hz), 6.96 (s, 2H), 7.40 (dd, 1H; J = 1.2 & 7.5 Hz), 7.50 (t, 1H; J = 7.5 Hz), 7.86 (d, 1H; J = 1.2 Hz), 8.03 (dd, 1H; J = 1.2 & 7.5 Hz)

(2) 6 ml of 1 molar sodium hydroxide solution into 10 ml of 1,4-dioxane in 1.07 g of 3- (2 ′, 4 ′, 6′-trimethylphenyl) -benzoic acid ethyl ester obtained in (1) Was added at 10 ° C. and stirred for 1 hour, followed by heating and stirring at 60 to 70 ° C. overnight.
After allowing to cool, 1,4-dioxane was distilled off under reduced pressure, 50 ml of ethyl acetate and 30 ml of 10% aqueous ammonium chloride solution were added, and the mixture was stirred for a while and then extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was dried under reduced pressure to give 3- (2 ′, 4 ′, 6′-trimethylphenyl) -benzoate having a melting point of 150.2 ° C. 0.70 g of acid was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.99 (s, 6H), 2.34 (s, 3H), 6.95 (s, 2H), 7.38 (d, 1H; J = 7.5 Hz), 7.51 (t, 1H; J = 7.5 Hz), 7.91 (s, 1H), 8.08 (d, 1H; J = 7.5 Hz)

(3) Into a 60 ml 1,2-dichloroethane solution of 1-2.0 g of 3- (2 ', 4', 6'-trimethylphenyl) -benzoic acid obtained in (2), 7.9 ml of thionyl chloride was cooled with ice. In addition, 5 drops of N, N-dimethylformamide was added, followed by heating to reflux for 5 hours.
After cooling, 50 ml of toluene was added and the solvent was distilled off. Further, 50 ml of toluene was added twice and the solvent was repeatedly distilled off, followed by vacuum drying to obtain 11 g of crude 3- (2 ′, 4 ′, 6′-trimethylphenyl) -benzoic acid chloride. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.01 (s, 6H), 2.36 (s, 3H), 6.98 (s, 2H), 7.1-7.3 (m, 1H), 7.4-7.6 (m, 2H), 7.97 (s , 1H), 8.1-8.2 (m, 1H)

(4) 3- (2 ′, 4 ′, 6′-trimethylphenyl) -benzoic acid chloride 1.3 g obtained in (3) was added to 25 ml of tetrahydrofuran containing 1.3 g of 40% methylamine in methanol. It was charged in several batches at ℃. After completion of the addition, the mixture was stirred overnight at room temperature. 50 ml of ethyl acetate and 30 ml of 10% aqueous ammonium chloride solution were added and stirred for a while, followed by extraction twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained solid was washed with n-hexane to obtain 1.04 g of the target compound having a melting point of 142.9 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.96 (s, 6H), 2.33 (s, 3H), 3.01 (d, 3H; J = 4.8 Hz), 6.21 (bs, 1H), 6.94 (s, 2H), 7.25- 7.30 (m, 1H), 7.48 (t, 1H; J = 7.5 Hz), 7.52-7.53 (m, 1H), 7.73-7.77 (m, 1H)

Synthesis example 3
Synthesis of N-methyl-Nn-propyl-3- (2 ′, 4 ′, 6′-trimethylphenyl) benzamide (Compound No. 1-4) N-methyl-3- (2 ′, To a solution of 4 ′, 6′-trimethylphenyl) benzamide in 0.25 g of anhydrous tetrahydrofuran was added ice-cooled 60% sodium hydride in several portions, and the mixture was stirred at the same temperature for 20 minutes. Subsequently, 0.29 ml of 1-iodopropane was added under ice cooling, and the mixture was stirred overnight at room temperature. The reaction solution was ice-cooled, 50 ml of ethyl acetate and 30 ml of 10% aqueous ammonium chloride solution were added, and the mixture was stirred for a while and extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical and neutral) (developing solvent n-hexane). : Ethyl acetate = 2: 1), 0.19 g of the oily target compound was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 0.77 & 0.99 (bs each, 3H), 1.58 & 1.68 (bs each, 2H), 2.02 (s, 6H), 2.34 (s, 3H), 2.97 & 3.08 (bs each, 3H ), 3.24 (bs, 1H), 3.52 (bs, 1H), 6.95 (s, 2H), 7.15-7.20 (m, 2H), 7.39 (bs, 1H), 7.46 (t, 1H; J = 7.5 Hz)

Synthesis example 4
N-methyl-3- (4'-chloro-2 ', 6'-dimethylphenyl) benzamide (Compound No. 1-23)
200 mg of tetrakistriphenylphosphine palladium was added to a mixed solution of 0.86 g of N-methyl-3-bromobenzamide in 10 ml of toluene and 3 ml of ethanol under ice cooling, and the mixture was stirred for 20 minutes. Thereto was added 0.93 g of 4-chloro-2,6-dimethylbenzeneboronic acid, 4.5 ml of 2 molar sodium carbonate water, and the reaction system was purged with nitrogen, followed by heating under reflux for 9 hours.
After allowing to cool, 50 ml of cold water was added, followed by 50 ml of ethyl acetate, the precipitate was filtered off, and the organic layer was separated from the filtrate. The aqueous layer was extracted again with 50 ml of ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was a silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; spherical / neutral) column. Purification by chromatography (developing solvent n-hexane: ethyl acetate = 1: 1) gave 0.40 g of the desired compound having a melting point of 137.1 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.98 (s, 6H), 3.02 (d, 3H; J = 5.1 Hz), 6.18 (bs, 1H), 7.10 (s, 2H), 7.24 (d, 1H; J = 7.5 Hz), 7.49 (t, 1H; J = 7.5 Hz), 7.51 (s, 1H), 7.75 (d, 1H; J = 7.5 Hz)

Synthesis example 5
Synthesis of N-methyl-N-propargyl-3- (4′-chloro-2 ′, 6′-dimethylphenyl) benzamide (Compound No. 1-14) N-methyl-3- (4 obtained in Synthesis Example 4 To a solution of 0.28 g of '-chloro-2', 6'-dimethylphenyl) benzamide in 10 ml of anhydrous tetrahydrofuran was added 0.08 g of 60% sodium hydride under ice cooling, and the mixture was stirred at the same temperature for 10 minutes. Subsequently, 0.20 ml of propargyl bromide was added under ice cooling, and the mixture was stirred overnight at room temperature. Cold water was added to the reaction system, and the mixture was extracted twice with 50 ml of ethyl acetate. The combined organic layers were washed again with water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Chemical, silica gel 60N; spherical / neutral) column chromatography (developing solvent n-hexane: Purified with ethyl acetate = 2: 1). 0.23 g of the target compound was obtained as an amorphous solid. Moreover, NMR of this product was as follows:
¹ H-NMR δ (ppm) 2.00 (s, 6H), 2.29 (s, 1H), 3.10 (bs, 3H), 4.02 (bs, 1H), 4.36 (bs, 1H), 7.09 (s, 2H), 7.16-7.20 (m, 2H), 7.47 (s, 1H), 7.48 (d, 1H; J = 5 Hz)

Synthesis Example 6
Synthesis of N-methyl-3- (2 ', 4', 6'-trimethylphenyl) benzylamine (Compound No. 1-27)
To a solution of 0.8 g of N-methyl-3-bromobenzylamine dissolved in 10 ml of toluene, 0.15 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 5 minutes. To this solution, 0.76 g of 2,4,6-trimethylphenylboronic acid, 3 ml of ethanol, and 4.5 ml of 2 mol aqueous sodium carbonate solution were sequentially added, and the mixture was stirred for 4 hours while heating under reflux. After allowing to cool, 50 ml of ethyl acetate and 50 ml of 5% aqueous ammonium chloride were added, and the mixture was stirred for a while and then separated. The aqueous layer was further extracted with 30 ml of ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel (Kanto Chemical Co., Silica Gel 60N; spherical / neutral) column chromatography (developing solvent n-hexane: ethyl acetate = 1: 1) to give 0.55 g of the oily desired compound. Got. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.00 (s, 6H), 2.08 (bs, 1H), 2.33 (s, 3H), 2.46 (s, 3H), 3.80 (s, 3H), 6.93 (s, 2H), 7.41 (d, 1H; J = 7.5 Hz), 7.08 (s, 1H), 7.29 (d, 1H; J = 7.5 Hz), 7.38 (t, 1H; J = 7.5 Hz)

Synthesis example 7
Synthesis of N-methyl-N-propargyl-3- (2 ′, 4 ′, 6′-trimethylphenyl) benzylamine (Compound No. 1-28) N-methyl-3- (2 ′ obtained in Synthesis Example 6 , 4 ′, 6′-trimethylphenyl) benzylamine (0.17 g) was dissolved in anhydrous tetrahydrofuran (10 ml), and 60% sodium hydride (57 mg) was added under ice cooling, followed by stirring for 20 minutes. After slowly dropping 0.14 ml of propargyl bromide at 5 ° C. or lower, the mixture was stirred overnight at room temperature. The reaction mixture was quenched with 20 ml of cold water and extracted with 50 ml of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained crude product was subjected to silica gel (manufactured by Kanto Chemical, silica gel 60N; spherical / neutral) column chromatography (developing solvent n-hexane: acetic acid). Purification by ethyl = 4: 1) gave 0.20 g of the target compound as an oil. Moreover, NMR of this product was as follows:
¹ H-NMR δ (ppm) 2.09 (s, 6H), 2.40 (s, 3H), 2.43 (s, 3H), 3.39 (s, 2H), 3.69 (s, 2H), 7.00 (s, 2H), 7.12 (d, 1H; J = 7.5 Hz), 7.21 (s, 1H), 7.38 (d, 1H; J = 7.5 Hz), 7.44 (t, 1H; J = 7.5 Hz)

Synthesis example 8
Synthesis of N-methyl-6-chloro-3- (2 ′, 4 ′, 6′-trimethylphenyl) benzamide (Compound No. 2-12) (1) 4.8 g of 5-bromo-2-chlorobenzoic acid After dissolving in 50 ml of 1,2-dichloroethane, 2.2 ml of thionyl chloride and 3 drops of N, N-dimethylformamide were added at room temperature, and the mixture was stirred for 4 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. 30 ml of toluene was again added to the residual oil and concentrated to obtain 5.0 g of crude 5-bromo-2-chlorobenzoic acid chloride.
To a solution of this in 70 ml of tetrahydrofuran was added dropwise 40 ml of a 40% methylamine methanol solution at 0 ° C., followed by stirring at room temperature for 2 hours. 50 ml of ice water and 100 ml of ethyl acetate were added to the reaction solution, and after stirring for a while, liquid separation was performed. The obtained organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained solid was finely pulverized in a mixed solvent of 30 ml of n-hexane and 5 ml of diethyl ether, filtered and dried to obtain 4.8 g of crude N-methyl-6-chloro-3-bromobenzamide. . Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.92 (d, 3H: J = 2.0 Hz), 6.36 (bs, 1H), 7.17 (d, 1H; J = 8.4 Hz), 7.38 (dd, 1H; J = 2.4 & 8.4 Hz), 7.66 (d, 1H; J = 2.4 Hz)

(2) To a solution of 1.0 g of N-methyl-6-chloro-3-bromobenzamide obtained in (1) in 15 ml of toluene, 0.15 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto, 0.76 g of 2,4,6-trimethylphenylboronic acid, 3 ml of ethanol, 4.5 ml of 2 molar sodium carbonate water were sequentially added, and the reaction system was purged with nitrogen, followed by stirring for 2 hours while heating under reflux. .
After allowing to cool, 50 ml of cold water was added, followed by 50 ml of ethyl acetate, the precipitate was filtered off, and the organic layer was separated from the filtrate. The aqueous layer was extracted again with 50 ml of ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was a silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; spherical / neutral) column. Purification by chromatography (developing solvent n-hexane: ethyl acetate = 2: 1) gave 0.25 g of the desired compound having a melting point of 130.0 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.97 (s, 6H), 2.31 (s, 3H), 2.94 (d, 1H; J = 4.8 Hz), 6.54 (bs, 1H), 6.91 (s, 2H), 7.11 ( dd, 1H; J = 2.0 & 4.8 Hz), 7.39 (d, 1H; J = 2.0 Hz), 7.39 (d, 1H; J = 4.8 Hz)

Synthesis Example 9
Synthesis of 3- (2 ′, 4 ′, 6′-trimethylphenyl) acetanilide (Compound No. 1-44) (1) Triethylamine 3 in a solution of 3.5 g of 3-bromoaniline in 50 ml of tetrahydrofuran was stirred under ice-cooling. After adding .35 ml, 1.57 ml of acetyl chloride was slowly added dropwise at 0 to 5 ° C. After completion of dropping, the mixture was stirred at room temperature for 0.5 hour. 50 ml of ice water and 100 ml of ethyl acetate were added to the reaction solution, and after stirring for a while, liquid separation was performed. The obtained organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained 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 = 2: 1) to give 3-bromoacetanilide 3 as white crystals. 0.6 g was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.18 (s, 3H), 7.20-7.40 (m, 3H), 7.41 (d, 1H; J = 7.8 Hz), 7.75 (s, 1H)

(2) To a solution of 0.21 g of 3-bromoacetanilide obtained in (1) dissolved in 5 ml of toluene, 0.05 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 15 minutes. Thereto, 0.25 g of 2,4,6-trimethylphenylboronic acid, 2 ml of ethanol, 3 ml of 2 molar sodium carbonate water were successively added, and the reaction system was purged with nitrogen, followed by stirring for 12 hours while heating under reflux.
After allowing to cool, 10 ml of cold water was added and extracted with 15 ml and 10 ml of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical and neutral) (developing solvent n-hexane). : Ethyl acetate = 2: 1), and 0.15 g of the target compound having a melting point of 173.8 ° C. was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.98 (s, 6H), 2.15 (s, 3H), 2.30 (s, 3H), 6.85 (d, 1H; J = 8.0 Hz), 6.90 (s, 2H), 7.16 ( s, 1H), 7.33 (t, 1H; J = 8.0 Hz), 7.41 (bs, 1H), 7.57 (d, 1H; J = 8.0 Hz)

Synthesis Example 10
Synthesis of N-methyl-N-3- (2 ′, 4 ′, 6′-trimethylphenyl) benzylacetamide (Compound No. 1-41) (1) 30 ml of tetrahydrofuran solution of 2.25 g of 3-bromobenzylamine hydrochloride To the solution, 3.4 ml of triethylamine was added with stirring under ice cooling, followed by stirring at room temperature for 40 minutes, and 0.86 ml of acetyl chloride was slowly added dropwise at 10 ° C. After completion of dropping, the mixture was stirred at room temperature for 1 hour. 50 ml of ice water and 100 ml of ethyl acetate were added to the reaction solution, and after stirring for a while, liquid separation was performed. The obtained organic layer was washed with 2% aqueous ammonia chloride and saturated brine, dried over anhydrous sodium sulfate, and then the solvent under reduced pressure. Distilled off. The obtained 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 = 1: 4), and white crystals of N-3- 2.05 g of bromobenzylacetamide was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.03 (s, 3H), 4.38 (d, 2H; J = 5.7 Hz), 6.07 (bs, 1H), 7.17-7.2 (m, 2H), 7.36-7.41 (m, 2H )

(2) To a solution of 1.15 g of N-3-bromobenzylacetamide obtained in (1) in 20 ml of anhydrous tetrahydrofuran was added 0.23 g of 60% sodium hydride under ice cooling, followed by stirring at the same temperature for 10 minutes. Subsequently, 0.63 ml of iodomethane was added under ice cooling, and the mixture was stirred at room temperature for 3.5 hours. Cold water was added to the reaction system, and the mixture was extracted twice with 50 ml of ethyl acetate. The combined organic layer was washed again with water and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel (manufactured by Kanto Chemical, silica gel 60N; spherical and neutral) column chromatography (developing solvent n-hexane: acetic acid). Purified with ethyl = 1: 3). 0.95 g of yellow oily N-3-bromobenzyl-N-methylacetamide was obtained. Moreover, NMR of this product was as follows:
¹ H-NMR δ (ppm) 2.14 & 2.17 (s each, 3H), 2.94 (s, 3H), 4.50 & 4.55 (s each, 2H), 7.09 & 7.18 (d each, 1H; J = 7.8 Hz), 7.10-7.30 (m, 1H), 7.31-7.37 (s each, 1H), 7.35-7.45 (m, 1H)

(3) To a solution of 0.24 g of N-3-bromobenzyl-N-methylacetamide obtained in (2) dissolved in 5 ml of toluene, 0.05 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 15 minutes. . Thereto, 0.25 g of 2,4,6-trimethylphenylboronic acid, 2 ml of ethanol, 3 ml of 2 molar sodium carbonate water were successively added, and the reaction system was purged with nitrogen, followed by stirring for 12 hours while heating under reflux.
After allowing to cool, 10 ml of cold water was added and extracted with 15 ml and 10 ml of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, 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. 0.2 g was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.97 (s, 6H), 2.14 (s, 3H), 2.31 & 2.32 (s each, 3H), 2.91 & 2.93 (s each, 3H), 4.54 & 4.62 (s each, 2H ), 6.92 & 6.93 (s each, 2H), 6.94 & 6.97 (s each, 1H), 7.03 & 7.07 (d each, 1H; J = 7.6 Hz), 7.14 & 7.20 (d each, 1H; J = 7.6 Hz ), 7.36 & 7.40 (t each, 1H; J = 7.6 Hz)

Synthesis Example 11
Synthesis of 3- (2 ', 6'-dichloro-4'-methylthiophenyl) aniline (Compound No. 1-207)
To a 50 ml toluene solution of 2.2 g of 4-bromo-3,5-dichlorothioanisole, 0.05 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto was added 1.4 g of 3-aminophenylboronic acid, 8 ml of ethanol, and 9.5 ml of 2 molar sodium carbonate water, and the reaction system was purged with nitrogen, followed by stirring under heating and refluxing for 3.5 hours.
After allowing to cool, cold water was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. To obtain 0.91 g of the oily target compound. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.51 (s, 3H), 3.79 (bs, 2H), 6.57 (s, 1H), 6.64 (d, 1H; J = 7.8 Hz), 6.75 (d, 1H; J = 7.8 Hz), 7.22 (s, 2H), 7.24 (t, 1H; J = 7.8 Hz)

Synthesis Example 12
Synthesis of 4- (3'-aminophenyl) -3,5-dimethylphenyl 5-trifluoromethyl-2-pyridyl ether (Compound No.1-57) (1) 4-Bromo-3,5-synthesized separately To a 40 ml toluene solution of 1.56 g dimethylphenyl 5-trifluoromethyl-2-pyridyl ether, 0.16 g tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto, 0.83 g of 3-nitrophenylboronic acid, 5 ml of ethanol, 5.4 ml of 2 molar sodium carbonate water were added, and the reaction system was purged with nitrogen, followed by stirring for about 3 hours while heating under reflux.
After allowing to cool, cold water was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. To obtain 0.48 g of 4- (3′-nitrophenyl) -3,5-dimethylphenyl 5-trifluoromethyl-2-pyridyl ether having a melting point of 100.6 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.97 (s, 6H), 6.86 (s, 2H), 6.98 (d, 1H; J = 7.8 Hz), 7.47 (d, 1H; J = 7.8 Hz), 7.56 (t, 1H; J = 7.8 Hz), 7.85 (dd, 1H; J = 8.7 & 2.4 Hz), 8.01 (s, 1H), 8.17 (d, 1H; J = 7.8 Hz), 8.42 (d, 1H; J = 2.4 Hz)

(2) Into a 20 ml solution of 1.64 g of 4- (3′-nitrophenyl) -3,5-dimethylphenyl 5-trifluoromethyl-2-pyridyl ether obtained in (1), 10% palladium on carbon .14 g was added in several portions with stirring at 10 ° C. The reaction system was replaced with hydrogen, and the mixture was vigorously stirred overnight at room temperature under pressure of a hydrogen balloon. The reaction product was filtered through Celite and washed well with methanol. The filtrate was dried over anhydrous sodium sulfate, and methanol was distilled off under reduced pressure to obtain 0.36 g of the target compound having a melting point of 200.3 ° C.
Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.02 (s, 6H), 3.47 (s, 2H), 6.87 (s, 2H), 7.02 (d, 1H; J = 8.7 Hz), 7.24 (d, 1H; J = 7.5 Hz), 7.36 (s, 1H), 7.50 (t, 1H; J = 7.5Hz), 7.54 (d, 1H; J = 7.5 Hz), 7.89 (dd, 1H; J = 8.7 & 2.4 Hz), 8.45 ( d, 1H; J = 2.4 Hz)

Synthesis Example 13
Synthesis of 3- (2 ′, 6′-dimethyl-4 ′-(5-trifluoromethyl-2-pyridyl) oxyphenyl) acetanilide (Compound No. 1-56) 4- (3 ′ -Aminophenyl) -3,5-dimethylphenyl 5-trifluoromethyl-2-pyridyl ether (Compound No. 1-57) 0.18 g of anhydrous tetrahydrofuran in 10 ml was added at 0 ° C. with 0.11 ml of triethylamine. Thereafter, 0.05 ml of acetyl chloride was added dropwise at −5 ° C., and the mixture was gradually warmed to room temperature with stirring for 2 hours. Cold water was added and the mixture was extracted with ethyl acetate. The organic layer obtained 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. By purification by chromatography, 0.10 g of the target compound having a melting point of 174.7 ° C. was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.05 (s, 6H), 2.20 (s, 3H), 6.88 (s, 2H), 6.92 (d, 1H; J = 7.5 Hz), 7.03 (d, 1H; J = 8.7 Hz), 7.24 (bs, 1H), 7.30 (s, 1H), 7.38 (t, 1H; J = 7.5Hz), 7.53 (d, 1H; J = 7.5 Hz), 7.91 (dd, 1H; J = 8.7 & 2.4 Hz), 8.50 (d, 1H; J = 2.4 Hz)

Synthesis Example 14
Synthesis of 3- (2 ', 6'-dichlorophenyl) aniline (Compound No. 1-268) (1) Tetrakistriphenylphosphine palladium into 50 ml toluene solution of 0.9 g 1-bromo-2,6-dichlorobenzene 0.14 g was added at room temperature and stirred for 10 minutes. Thereto was added 0.8 g of 3-nitrophenylboronic acid, 5 ml of ethanol, and 4.2 ml of 2 molar sodium carbonate water, and the reaction system was purged with nitrogen, followed by stirring for 15 hours while heating under reflux.
After allowing to cool, the reaction solution was filtered through Celite, and washed well with ethyl acetate from above. Cold water was added to the filtrate, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical / neutral) column chromatography. By purification, 0.98 g of oily 3- (2,6-dichlorophenyl) nitrobenzene was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 7.30 (t, 1H; J = 8.1 Hz), 7.42 (d, 2H; J = 8.1 Hz), 7.61 (d, 1H; J = 7.8 Hz), 7.65 (t, 1H; J = 7.8 Hz), 8.18 (s, 1H), 8.29 (d, 1H; J = 7.8 Hz)

(2) 0.2 g of 10% palladium on carbon was added in portions to a solution of 1.9 g of 3- (2 ', 6'-dichlorophenyl) nitrobenzene obtained in (1) in 40 ml of methanol while stirring at 0 ° C. It was. The reaction system was replaced with hydrogen, and the mixture was stirred overnight at 10-15 ° C. under pressure with a hydrogen balloon. The reaction product was filtered through celite and washed thoroughly with methanol. The filtrate was dried over anhydrous sodium sulfate, and the residue obtained by evaporating methanol under reduced pressure was subjected to silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical / neutral) column chromatography. To obtain 0.53 g of the target compound having a melting point of 102.0 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 6.70 (s, 1H), 6.74 (d, 1H; J = 7.5 Hz), 6.87 (d, 1H; J = 7.5 Hz), 7.20 (t, 1H; J = 7.5 Hz) , 7.25 (s, 2H), 7.29 (t, 1H; J = 8.1 Hz), 7.38 (d, 2H; J = 8.1 Hz)

Synthesis Example 15
Synthesis of 3- (2 ′, 6′-dichlorophenyl) -N-formanilide (Compound No. 1-209) 3- (2 ′, 6′-dichlorophenyl) aniline (Compound No.1- 268) 0.36 g was dissolved in 3 ml of formic acid and stirred for 2.5 hours under heating to reflux. After allowing to cool, cold water was added, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. To obtain 0.30 g of the objective compound having a melting point of 114.0 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 7.02 (s, 1H), 7.07-7.23 (m, 2H), 7.25-7.47 (m, 3H), 7.45 & 7.66 (d each, 1H; J = 8.0 Hz), 8.17 & 8.37 (s each, 1H), 8.73 & 9.11 (d each, 1H; J = 11.0 Hz)

Synthesis Example 16
Synthesis of 3- (2 ′, 6′-dichlorophenyl) -N-formyl-N-propargylanilide (Compound No. 1-216) 3- (2 ′, 6′-dichlorophenyl) -N— obtained in Synthesis Example 15 0.27 g of formanilide (Compound No. 1-209) was dissolved in 5 ml of N, N-dimethylformamide, 60 mg of 60% sodium hydride was added at 5 ° C., and the mixture was stirred at the same temperature for 10 minutes. Propargyl bromide 0.18g was dripped there at 5 degreeC there, Then, it stirred at room temperature overnight. Since the reaction was not completed, 60 mg of sodium hydride (60 mg) was added at room temperature, and the mixture was stirred at the same temperature for 1 hour. The raw material 3- (2 ', 6'-dichlorophenyl) -N-formanilide almost disappeared. did. Add cold water, extract with ethyl acetate, dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and purify the residue by column chromatography on silica gel (silica gel 60N; spherical / neutral). As a result, 0.20 g of the target compound of amorphous solid was obtained. Further, NMR of this product was as follows.

¹ H-NMR δ (ppm) 2.23 (t, 1H; J = 2.7 Hz), 4.56 (d, 1H; J = 2.7 Hz), 7.17-7.26 (m, 3H), 7.32-7.41 (m, 3H), 7.50 (t, 1H; J = 7.8 Hz), 8.47 (s, 1H)

Synthesis Example 17
Synthesis of N-methyl-3- (2 ′, 6′-dichlorophenyl) -6-fluorobenzamide (Compound No. 2-22) (1) To a solution of 9.5 g of 5-bromo-2-fluorotoluene in 150 ml of toluene Then, 1.1 g of tetrakistriphenylphosphine palladium was added at room temperature and stirred for 10 minutes. Thereto was added 13.4 g of 2,6-dichlorophenylboronic acid, 30 ml of ethanol, 50 ml of a 2 molar sodium carbonate aqueous solution and 10.6 g of sodium carbonate powder, and the reaction system was purged with nitrogen, followed by stirring for 15 hours while heating under reflux. did. After allowing to cool, the reaction solution is filtered through Celite, and the filtrate is dried over anhydrous sodium sulfate, and then the solvent is distilled off under reduced pressure. The residue is subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. And purified (developing solvent n-hexane only) to obtain 6.5 g of oily 5- (2 ′, 6′-dichlorophenyl) -2-fluorotoluene. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.34 (d, 3H; J = 2.1 Hz), 7.05-7.13 (m, 3H), 7.21 (t, 1H; J = 7.5 Hz), 7.39 (d, 2H; J = 7.5 Hz)

(2) 6.4 g of 5- (2 ′, 6′-dichlorophenyl) -2-fluorotoluene obtained in (1) is dissolved in 20 ml of pyridine, 40 ml of water is added, and 20 g of 70 g is heated under stirring at 70-80 ° C. Potassium permanganate was added in several steps and stirred for 4.5 hours while heating under reflux. The mixture was cooled to 70 to 80 ° C., filtered through Celite, and washed 3 times with 100 ml of hot water from above. The aqueous layer obtained as a filtrate was ice-cooled, washed with diethyl ether, acidified with 2N hydrochloric acid while stirring, and the precipitated solid was filtered and sucked dry to give a melting point of 55.5 ° C. 1.5 g of-(2,6-dichlorophenyl) -2-fluorobenzoic acid was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 7.2-7.3 (m, 1H), 7.4-7.5 (m, 2H), 7.68 (bs, 1H), 7.95 (dd, 1H; J = 6.9 & 2.4 Hz), 8.10 (t , 1H; J = 7.5 Hz), 8.82 (bs, 1H)

(3) 1.2 g of 5- (2 ′, 6′-dichlorophenyl) -2-fluorobenzoic acid obtained in (2) was dissolved in 20 ml of 1,2-dichloroethane, and 0.67 ml of thionyl chloride and N, N, were dissolved at room temperature. 2 drops of N-dimethylformamide was added, and the mixture was stirred for 3 hours under reflux. After allowing to cool, 20 ml of toluene was added to the reaction solution, and the mixture was concentrated under reduced pressure. 20 ml of toluene was again added to the residual oil and concentrated to obtain 1.35 g of crude 5- (2 ′, 6′-dichlorophenyl) -2-fluorobenzoic acid chloride.
This was dissolved in 20 ml of tetrahydrofuran, and while stirring at 0 ° C., 1.4 ml of a 40% methylamine methanol solution was slowly added dropwise, followed by stirring at room temperature for 2 hours. To the reaction solution, 30 ml of ice water and 60 ml of ethyl acetate were added, and after stirring for a while, liquid separation was performed. The obtained organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained 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 = 2: 1) and the target compound 0 having a melting point of 142.5 ° C. .85 g was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 3.06 (d, 3H; J = 4.8 Hz), 6.80 (bs, 1H), 7.17-7.25 (m, 2H), 7.26 (d, 1H; J = 7.5 Hz), 7.33- 7.39 (m, 2H), 7.41 (s, 1H), 8.04 (dd, 1H; J = 7.5 & 2.4 Hz)

Synthesis Example 18
Synthesis of N-methyl-3- (2 ′, 6′-dichloro-3′-methylphenyl) benzamide (Compound No. 1-86) (1) In a solution of 25.9 ml of 2,4-dichlorotoluene in 350 ml of anhydrous tetrahydrofuran Then, under −75 to −62 ° C., 130 ml of 1.59 mol / l n-butyllithium was slowly dropped over 50 minutes, followed by stirring at −70 ° C. for 30 minutes. Under −75 to −65 ° C., 31.8 ml of trimethyl borate was gradually added dropwise and stirred for a while, then the ice bath was removed, and the mixture was stirred overnight while gradually warming to room temperature. Thereafter, the reaction system was cooled to 0 ° C., and ice water and 2N hydrochloric acid were gradually added with stirring, followed by stirring to room temperature for 2 hours. Extraction was performed with diethyl ether (500 ml × 2 times), and the combined organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, followed by suction drying to obtain 48 g of a composition. This was filtered using n-hexane to obtain 15 g of crude 2,6-dichloro-3-methylbenzeneboronic acid. This was used as a raw material for the next coupling reaction. The filtrate was also sucked and dried to obtain 22 g of powder mainly composed of the target product.

(2) N-methyl-3-bromobenzamide (2.15 g) and 2,6-dichloro-3-methylbenzeneboronic acid (2.5 g) obtained in (1) in a 25 ml ethanol solution with 5% palladium carbon under ice-cooling After adding 850 mg (type E101 NO / W; Aldrich reagent), 6.4 g of sodium carbonate powder was gradually added while cooling at 0 ° C., and the reaction system was purged with nitrogen, followed by stirring for 8 hours while heating under reflux. . After allowing to cool, 1.25 g of the boronic acid, 430 mg of 5% palladium carbon, and 5 ml of ethanol were added, and the reaction system was purged with nitrogen again, followed by further refluxing for 12 hours. After allowing to cool, the reaction solution is filtered through Celite, and the filtrate is dried over anhydrous sodium sulfate, and then the solvent is distilled off under reduced pressure. The residue is subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. (Developing solvent n-hexane: ethyl acetate = 2: 1 to 1: 1) to obtain 250 mg of the target compound having a melting point of 118.8 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.39 (s, 3H), 2.98 (d, 3H; J = 4.8 Hz), 6.41 (bs, 1H), 7.18 (d, 1H; J = 8.1 Hz), 7.28 (d, 1H; J = 8.1 Hz), 7.35 (d, 1H; J = 7.8 Hz), 7.50 (t, 1H; J = 7.8 Hz), 7.63 (s, 1H), 7.82 (d, 1H; J = 7.8 Hz)

Synthesis Example 19
Synthesis of N-ethyl-3- (2 ′, 6′-dichloro-3′-trifluoromethylphenyl) benzamide (Compound No. 1-127) (1) 1,4-mL of 2,4-dichlorobenzotrifluoride To a solution of 350 ml of tetrahydrofuran, 65 ml of 1.60 mol / l n-butyllithium was slowly dropped at −75 to −65 ° C. over 30 minutes, followed by stirring at −70 ° C. for 1 hour. Under −75 to −65 ° C., 15.9 ml of trimethyl borate was gradually added dropwise and stirred for a while, then the ice bath was removed, and the mixture was stirred for 1 hour while gradually warming to room temperature. Thereafter, the reaction system was cooled to 0 ° C., 70 ml of ice water and about 80 ml of 2N hydrochloric acid were gradually added with stirring, and the mixture was stirred overnight at room temperature. The mixture was extracted with diethyl ether (300 ml × 2 times), and the combined organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. By sufficiently sucking and drying, 28 g of crude 2,6-dichloro-3-trifluoromethylbenzeneboronic acid was obtained. This was used as a raw material for the next coupling reaction.

(2) After substituting the reaction system with nitrogen, 100 mg of tetrakistriphenylphosphine palladium was added to 10 ml of toluene in 0.46 g of N-ethyl-3-bromobenzamide under ice-cooling, followed by stirring at room temperature for 1 hour. did. Thereafter, under cooling at 0 ° C., a solution of 1.8 g of 2,6-dichloro-3-trifluoromethylbenzeneboronic acid obtained in (1) in 3 ml of ethanol was added, and further 3 ml of 2 molar sodium carbonate water was added. The mixture was stirred for 13 hours under reflux with heating while keeping the temperature of the oil bath at 90 ° C. .
After allowing to cool, 7 ml of cold water was added, the separated organic layer was taken, and then extracted from the aqueous layer with 50 ml of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical and neutral) (developing solvent n-hexane: ethyl acetate = 2: 1 to 1: 1) and the target compound having a melting point of 137.0 ° C. 325 mg was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.22-1.26 (m, 3H), 3.45-3.52 (m, 2H), 6.15 (bs, 1H), 7.35 (d, 1H; J = 7.6 Hz), 7.52-7.58 (m , 2H), 7.62 (s, 1H), 7.66 (d, 1H; J = 8.8 Hz), 7.85 (d, 1H; J = 6.8 Hz)

Synthesis Example 20
Synthesis of N-methyl-3- (2, '6'-dichloro-3'-trifluoromethylphenyl) benzamide (Compound No. 1-120)
The target compound having a melting point of 126.1 ° C. was obtained in the same manner as in Synthesis Example 19 except that N-ethyl-3-bromobenzamide was replaced with N-methyl-3-bromobenzamide. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 3.02 (d, 3H; J = 4.8 Hz), 6.22 (bs, 1H), 7.37 (d, 1H; J = 7.8 Hz), 7.52 (d, 1H; J = 8.4 Hz) , 7.56 (t, 1H; J = 7.8 Hz), 7.64 (s, 1H), 7.56 (t, 1H; J = 7.8 Hz), 7.67 (d, 1H; J = 8.4 Hz), 7.86 (d, 1H; (J = 7.8 Hz)

Synthesis Example 21
Synthesis of N-methyl-3- (2 ′, 4 ′, 6′-trimethylphenyl) thiobenzamide (Compound No. 1-142) N-methyl-3- (2 ′, 4 ′, 10 g of 6′-trimethylphenyl) -benzamide (Compound No. 1-22) was dissolved in 100 ml of toluene, 9.6 g of Lawesson's Reagent was added at room temperature, and the mixture was stirred for 3 hours while heating under reflux. Cold water was added and the mixture was extracted with ethyl acetate. The organic layer obtained 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. Purification by chromatography gave 1.1 g of the target compound having a melting point of 62.5 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.92 (s, 6H), 2.25 (s, 3H), 3.28 (d, 3H; J = 4.8 Hz), 6.87 (s, 2H), 7.19 (d, 1H; J = 7.5 Hz), 7.37 (t, 1H; J = 7.5 Hz), 7.44 (s, 1H), 7.71 (d, 1H; J = 7.5 Hz), 7.70 (bs, 1H)

Synthesis Example 22
Synthesis of N-methyl-3- (2 ', 6'-dichlorophenyl) benzamide (Compound No. 1-30)
The target compound having a melting point of 174.8 ° C. was obtained in the same manner as in Synthesis Example 4 except that 4-chloro-2,6-dimethylbenzeneboronic acid was replaced with 2,6-dichlorobenzeneboronic acid. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 3.01 (d, 3H; J = 4.8 Hz), 6.25 (bs, 1H), 7.24 (t, 1H; J = 7.5 Hz), 7.37-7.42 (m, 1H), 7.52 ( t, 1H; J = 7.5 Hz), 7.65 (s, 1H), 7.83 (d, 1H; J = 7.5 Hz)

Synthesis Example 23
Synthesis of N-methyl-3- (2 ′, 6′-dichloro-3′-nitrophenyl) benzamide (Compound No. 1-109) N-methyl-3- (2 ′, 6 ′) obtained in Synthesis Example 22 -Dichlorophenyl) benzamide (Compound No. 1-30) 0.56 g was dissolved in 5 ml of concentrated sulfuric acid, and 0.18 g of 70% nitric acid (d 1.42) was slowly added dropwise at 0-2 ° C. with stirring. Thereafter, the mixture was gradually warmed and stirred at room temperature for 2 hours. The reaction solution was poured into about 30 g of ice while stirring, and 50 ml of ethyl acetate was added and stirred 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 silica gel (Kanto Chemical, silica gel 60N; spherical / neutral) column chromatography. 0.61 g of compound was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.93 (d, 3H; J = 4.5 Hz), 6.94 (d, 1H; J = 4.5 Hz), 7.31 (d, 1H; J = 7.8 Hz), 7.49 (t, 1H; J = 7.8 Hz), 7.51 (d, 1H; J = 8.7 Hz), 7.66 (s, 1H), 7.73 (d, 1H; J = 8.7 Hz), 7.85 (d, 1H; J = 7.8 Hz)

Synthesis Example 24
Synthesis of N-methyl-3- (2 ′, 6′-dichloro-3′-aminophenyl) benzamide (Compound No. 1-108) N-methyl-3- (2 ′, 6 ′) obtained in Synthesis Example 23 -Dichloro-3'-nitrophenyl) benzamide (Compound No. 1-109) in a solution of 3.3 g of acetic acid in 25 ml of acetic acid at 50 to 57 ° C. with stirring at a temperature of 50 to 57 ° C., several times taking 15 minutes. Separately thrown in. Thereafter, the mixture was heated and stirred at 60 ° C. for 1 hour.
After allowing to cool to about 40 ° C., 50 ml of ethyl acetate was added to the system and stirred, and the filtrate obtained by celite filtration was washed with a dilute sodium bicarbonate aqueous solution and then with a saturated saline solution. 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 (manufactured by Kanto Chemical Co., Inc., silica gel 60N; spherical and neutral) (developing solvent n-hexane: acetic acid). Ethyl = 1: 1, containing 0.3% triethylamine), 2.5 g of the target compound having a melting point of 64.1 ° C. was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.92 (d, 3H; J = 4.5 Hz), 6.74 (d, 1H; J = 8.7 Hz), 7.02 (bs, 1H), 7.09 (d, 1H; J = 8.7 Hz) , 7.28 (d, 1H; J = 7.5 Hz), 7.43 (t, 1H; J = 7.5 Hz), 7.61 (s, 1H), 7.81 (d, 1H; J = 7.5 Hz)

Synthesis Example 25
Synthesis of N-methyl-3- (2 ', 6'-dichloro-3'-bromophenyl) benzamide (Compound No. 1-82)

To a solution of 1.34 g of cupric bromide in 40 ml of acetonitrile, 0.86 g of t-butyl nitrite (90%) was added at 0 ° C. Thereto was added a solution of N-methyl-3- (2 ′, 6′-dichloro-3′-aminophenyl) benzamide (Compound No. 1-108) 1.5 g obtained in Synthesis Example 24 in 20 ml of acetonitrile to −5 to 0. The mixture was added dropwise over 10 minutes with stirring at ° C. Then, it stirred at room temperature for 2.5 hours. 10 ml of cold water and 50 ml of ethyl acetate were added, the separated organic layer was taken, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography. Purification by chromatography (developing solvent n-hexane: ethyl acetate = 2: 1 to 1: 1) gave 1.45 g of the desired compound having a melting point of 158.0 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 3.02 (d, 3H; J = 4.8 Hz), 6.21 (bs, 1H), 7.28 (d, 1H; J = 8.7 Hz), 7.35 (d, 1H; J = 7.5 Hz) , 7.54 (t, 1H; J = 7.5 Hz), 7.59 (d, 1H; J = 8.7 Hz), 7.61 (s, 1H), 7.83 (d, 1H; J = 7.5 Hz)

Synthesis Example 26
Synthesis of N-methyl-3- (2 ', 3', 6'-trichlorophenyl) benzamide (Compound No.1-72) Except for using cupric chloride (anhydrous) instead of cupric bromide In the same manner as in Synthesis Example 25, the target compound having a melting point of 135.3 ° C. was obtained. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.95 (d, 3H; J = 4.5 Hz), 6.71 (bs, 1H), 7.30 (d, 1H; J = 7.5 Hz), 7.31 (d, 1H; J = 8.7 Hz) , 7.40 (d, 1H; J = 8.7 Hz), 7.50 (d, 1H; J = 7.5 Hz), 7.64 (s, 1H), 7.83 (d, 1H; J = 7.5 Hz)

Synthesis Example 27
Synthesis of N-methyl-N-propargyl-3- (2 ′, 3 ′, 6′-trichlorophenyl) benzamide (Compound No. 1-75) N-methyl-3- (2 ′, 3 ', 6'-Trichlorophenyl) benzamide (Compound No. 1-72) 0.2 g of anhydrous tetrahydrofuran 20 ml was charged with 0.14 g of 60% sodium hydride under ice cooling and then stirred at the same temperature for 20 minutes. did. Subsequently, 0.19 ml of propargyl bromide was added under ice cooling, and the mixture was stirred at room temperature for 3 hours. Cold water was added to the reaction system, and the mixture was extracted twice with 50 ml of ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel (silica gel 60N; spherical / neutral) column chromatography (developing solvent). Purified with n-hexane: ethyl acetate = 2: 1). 0.18 g of the target compound was obtained as an amorphous solid. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.29 (bs, 1H), 3.10 (bs, 3H), 4.05 & 4.36 (bs each, 2H), 7.23-7.57 (m, 6H)

Synthesis Example 28
Synthesis of N-methyl-3- (2 ′, 6′-dimethyl-4′-methoxyphenyl) benzamide (Compound No. 1-65) (1) 3,5-dimethyl-4-bromoanisole 2.2 g of toluene To a mixed solution of 50 ml and ethanol 8 ml, 0.35 g of tetrakistriphenylphosphine palladium was added under ice cooling and stirred for 20 minutes. Thereto was added 1.8 g of 3-carboxyphenylboronic acid and 12 ml of 2 molar sodium carbonate water, and the reaction system was purged with nitrogen, followed by heating under reflux for 22 hours.
After allowing to cool, 50 ml of cold water was added, followed by 100 ml of ethyl acetate, the precipitate was filtered off, and the organic layer was separated from the filtrate. The aqueous layer was extracted again with 50 ml of ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was a silica gel (manufactured by Kanto Chemical Co., Silica Gel 60N; spherical / neutral) column. Purification by chromatography (developing solvent n-hexane: ethyl acetate = 1: 1) gave 0.52 g of white crystalline 3- (2 ′, 6′-dimethyl-4′-methoxyphenyl) benzoic acid. . Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 2.01 (s, 6H), 3.83 (s, 3H), 6.68 (s, 2H), 7.40 (d, 1H; J = 7.5 Hz), 7.53 (t, 1H; J = 7.5 Hz), 7.91 (s, 1H), 8.08 (d, 1H; J = 7.5 Hz)

(2) 0.26 g of 3- (2 ′, 6′-dimethyl-4′-methoxyphenyl) benzoic acid obtained in (1) was dissolved in 5 ml of 1,2-dichloroethane, and 0.22 ml of thionyl chloride at room temperature. And 2 drops of N, N-dimethylformamide were added, and the mixture was stirred with heating under reflux for 2 hours. After allowing to cool, 30 ml of toluene was added to the reaction solution, and the mixture was concentrated under reduced pressure. 30 ml of toluene was added again to the residual oil and concentrated to obtain 0.34 g of crude 3- (2 ′, 6′-dimethyl-4′-methoxyphenyl) benzoic acid chloride. A solution of 0.4 g of 40% methylamine in methanol and 3 ml of anhydrous tetrahydrofuran was added dropwise to a solution of this in 7 ml of anhydrous tetrahydrofuran at 0 ° C., and the mixture was stirred at room temperature for 4 hours. To the reaction solution were added 10 ml of ice water and 20 ml of ethyl acetate, and the mixture was stirred for a while and collected. The obtained organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was finely pulverized in a mixed solvent of 10 ml of n-hexane and 2 ml of diethyl ether, filtered and dried to obtain 0.18 g of the target compound having a melting point of 139.6 ° C. Further, NMR of this product was as follows.
¹ H-NMR δ (ppm) 1.99 (s, 6H), 3.01 (d, 3H: J = 4.5 Hz), 3.82 (s, 3H), 6.19 (bs, 1H), 6.66 (s, 2H), 7.27 ( d, 1H; J = 7.8 Hz), 7.47 (t, 1H; J = 7.8 Hz), 7.52 (s, 1H), 7.74 (d, 1H; J = 7.8 Hz)

  The compounds of the formula (I) produced by the methods according to the above production methods 1 to 3 and synthesis examples 1 to 28 are shown in the following Tables 1 and 2. In the table, Me is methyl, Et is ethyl, n-Pr is normal propyl, i-Pr is isopropyl, n-Bu is normal butyl, c-Pr is cyclopropyl, and t-Bu is tertiary. Butyl, i-Bu represents isobutyl, and-represents a single bond. For convenience, the substitution position of Z in Table 2 is represented by a number from 1 to 6 in the formula in Table 2. The mp: melting point in the physical property column was measured using an automatic melting point measuring apparatus (MTTLER FP62 manufactured by METTLER TOLEDO).

Below, the test example of the pest control agent concerning this invention is described. In each test, the control index followed the following criteria.
[Control index] [Disease severity: Visual observation]
5: No lesion or sporulation is observed.
4: The lesion area, the number of lesions, or the spore formation area is less than 10% of the untreated group 3: The lesion area, the number of lesions or the spore formation area is less than 40% of the untreated group 2: The lesion area, The number of lesions or sporulation area is less than 70% of the untreated group 1: The lesion area, number of lesions or sporulation area is 70% or more of the untreated group

Test Example 1 Wheat powdery mildew prevention effect test Wheat (variety: Norin 61) was cultivated in a 7.5cm diameter plastic pot, and when the 1.5 leaf stage was reached, 10ml of a solution containing the compound of the present invention adjusted to a predetermined concentration was spray gun. It was sprayed with. 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, 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-9, 1-10, 1-11, 1-12 in the compound, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-25, 1- 27, 1-28, 1-29, 1-30, 1-31, 1-37, 1-41, 1-43, 1-44, 1-45, 1-46, 1-50, 1-58, 1-59, 1-60, 1-61, 1-64, 1-65, 1-66, 1-69, 1-70, 1-71, 1-72, 1-74, 1-75, 1- 76, 1-77, 1-78, 1-79, 1-81, 1-82, 1-85, 1-86, 1-99, 1-100, 1-101, 1-105, 1-107, 1-112, 1-113, 1-123, 1-135, 1-137, 1-138, 1-139, 1-141, 1-142, 1-149, 1-150, 1-151, 1- 152, 1-153, 1-154, 1-156, 1-157, 1-158, 1-159, 1-166, 1-169, 1-174, 1-175, 1-176, 1-177, 1-178, 1-179, 1-180, 1-181, 1-182, 1-183, 1-184, 1-185, 1-186, 1-187, 1-188, 1-189, 1- 190, 1-191, 1-192, 1-193, 1-194, 1-195, 1-196, 1-198, 1-199, 1-200, 1-201, 1-202, 1-204, 1-205, 1-206, 1-207, 1-208, 1-209, 1-210, 1-211, 1-212, 1-213, 1-214, 1-215, 1-216, 1- 217, 1-218, 1-220, 1-227, 1-228, 1-230, 1-234,1-235,1-236,1-237,1-238,1-239,1-240,1-241,1-242,1-243,1-244,1-245,1- 246, 1-250, 1-251, 1-253, 1-254, 1-254, 1-256, 1-257, 1-258, 1-259, 1-260, 1-261, 1-262, 1-263, 1-264, 1-265, 1-266, 1-267, 2-1, 2-2, 2-12, 2-19, 2-20, 2-22, and 2-23 are 400 ppm and the control index is 4 or more Showed the effect. 1-67, 1-80, 1-88, 1-120, 1-124, and 2-18 were 200 ppm, and the control index was 4 or more. 1-83, 1-84, 1-89, 1-90, 1-91, 1-92, 1-93, 1-121, 1-122, 1-124, 1-126 and 1-127 are 100 ppm The control index was 4 or more.

Test Example 2 Cucumber Powdery Mildew Prevention Effect Test Cucumber (variety: Sagamihanjiro) is cultivated in a plastic pot with a diameter of 7.5 cm, and when the 1.5 leaf stage is reached, 10 ml of the chemical solution adjusted to the prescribed concentration of the present compound is spray gun It was sprayed with. After the chemical solution was dried (on the day of treatment or the next day), a conidial spore suspension of 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, 1-4, 1-7, 1-10, 1-11, 1-13, 1-14, 1-17, 1-21, 1-29 , 1-30, 1-31, 1-68, 1-71, 1-72, 1-74, 1-75, 1-76, 1-77, 1-79, 1-80, 1-81, 1 -82, 1-86, 1-99, 1-100, 1-101, 1-109, 1-112, 1-113, 1-120, 1-123, 1-149, 1-150, 1-151 , 1-152, 1-156, 1-159, 1-174, 1-175, 1-179, 1-180, 1-181, 1-182, 1-183, 1-184, 1-185, 1 -188, 1-189, 1-192, 1-193, 1-194, 1-195, 1-207, 1-218, 1-228, 1-230, 1-231, 1-234, 1-235 , 1-236,1-237,1-238,1-242,1-251,1-253,1-256,1-259,1-260,1-266,2-2,2-22 and 2 -23 was 400 ppm, and the control index was 4 or more. 1-88 and 1-186 showed an effect of control index 4 or more at 200 ppm. 1-89, 1-90, 1-91, 1-93, 1-121, 1-122, 1-124, and 1-126 showed an effect of controlling the control index of 4 or more at 100 ppm.

Test Example 3 Cucumber downy mildew prevention effect test Cucumber (variety: Sagamihanjiro) is cultivated in a 7.5cm diameter plastic pot, and when reaching the 2nd leaf stage, 10ml of the drug solution with the compound of the present invention adjusted to the prescribed concentration is spray gun. It was sprayed with. After the chemical solution was dried (on the day of treatment), a conidial spore suspension of downy mildew was spray-inoculated and kept in a constant temperature room at 20 ° C. Seven days after inoculation, the spore formation area was examined, and the control index was determined according to the above evaluation criteria. As a result, 1-27, 1-56, 1-198, 1-204, and 1-267 in the compound showed an effect of controlling the control index of 4 or more at 400 ppm.

Test Example 4 Rice Blast Prevention Effect Test Rice (cultivar: Nipponbare) is cultivated in a 7.5 cm diameter plastic pot, and when the 1.5 leaf stage is reached, 10 ml of the chemical solution adjusted to the prescribed concentration is sprayed with a spray gun. did. After the drug solution was dried, the 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 evaluation criteria. As a result, among the compounds, 1-43, 1-70, 1-77, 1-86, 1-164, 1-198, 1-204, 1-206, 1-208, 1-209, 1-216 , 1-248, 1-250, 1-251, 1-252, 1-253, and 1-254 showed effects of 400 ppm or more at a control index of 4 or more.

  Next, although the formulation example of this invention is described, the formulation amount in this invention, a dosage form, etc. are not limited only to a description example.

Formulation Example 1
(1) Compound of the present invention 20 parts by weight (2) 72 parts by weight of clay (3) Sodium lignin sulfonate 8 parts by weight or more is uniformly mixed to obtain a wettable powder.

Formulation Example 2
(1) Compound of the present invention 5 parts by weight (2) Talc 95 parts by weight or more is uniformly mixed to obtain a powder.

Formulation Example 3
(1) Compound of the present invention 20 parts by weight (2) N, N'-dimethylacetamide 20 parts by weight (3) Polyoxyethylene alkylphenyl ether 10 parts by weight (4) Xylene 50 parts by weight or more are uniformly mixed and dissolved To make an emulsion.

Formulation Example 4
(1) Clay 68 parts by weight (2) Lignin sulfonic acid soda 2 parts by weight (3) Polyoxyethylene alkylaryl sulfate 5 parts by weight (4) Fine powder silica A mixture of each component of 25 parts by weight or more and the compound of the present invention Mix at a weight ratio of 4: 1 to make a wettable powder.

Formulation Example 5
(1) Compound of the present invention 50 parts by weight (2) Oxidated polyalkylphenyl phosphate-triethanolamine
2 parts by weight (3) 0.2 parts by weight of silicone (4) water 47.8 parts by weight or more of the mixture were uniformly mixed and pulverized into the stock solution. (5) sodium polycarboxylate 5 parts by weight (6) anhydrous sodium sulfate Add 42.8 parts by weight, uniformly mix, granulate, and dry to make granule wettable powder.

Formulation Example 6
(1) Compound of the present invention 5 parts by weight (2) Polyoxyethylene octylphenyl ether 1 part by weight (3) Polyoxyethylene phosphate ester 0.1 part by weight (4) Granular calcium carbonate 93.9 parts by weight (1)- (3) is uniformly mixed in advance and diluted with an appropriate amount of acetone, and then sprayed onto (4) to remove the acetone and form granules.

Formulation Example 7
(1) Compound of the present invention 2.5 parts by weight (2) N-methyl-2-pyrrolidone 2.5 parts by weight (3) Soybean oil 95.0 parts by weight or more are uniformly mixed and dissolved to give a trace amount of spray. (ultra low volume formulation).

Formulation Example 8
(1) Compound of the present invention 20 parts by weight (2) Oxidated polyalkylphenol phosphate triethanolamine 2 parts by weight (3) Silicone 0.2 part by weight (4) Xanthan gum 0.1 part by weight (5) Ethylene glycol 5 parts by weight Part (6) Water 72.7 parts by weight or more are uniformly mixed and pulverized to obtain an aqueous suspension.

Claims (6)

Formula (I):

[Wherein X and Y are each independently a halogen atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; an amino group which may be substituted with alkyl; a halogen or alkoxy; An aryloxy group which may be substituted with halogen or haloalkyl; a heterocyclic oxy group which may be substituted with halogen or haloalkyl; a heterocyclic group which may be substituted with halogen or haloalkyl; An alkylcarbonylamino group; an alkylcarbonyl group optionally substituted with a halogen; an alkylthio group; an alkylsulfonyl group; an alkylsulfinyl group or an imino group optionally substituted with alkyl or alkoxy; Z A halogen atom; a formyl group; an alkyl group which may be substituted with halogen; an alkoxy group which may be substituted with alkoxy; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group, wherein A is a carbonyl group; a thiocarbonyl group; an alkylene group Or R ¹ and R ² are each independently a hydrogen atom; halogen, cycloalkyl, substituted phenyl, substituted heterocycle, alkyl group optionally substituted with alkylthio, alkoxy or cyano; halogen, cycloalkyl Alkenyl group optionally substituted with phenyl, cyano; alkynyl group optionally substituted with halogen, cycloalkyl, phenyl or cyano; cycloalkyl group optionally substituted with halogen or alkyl; substituted with halogen, alkyl or haloalkyl The An aryl group which may be substituted with halogen, alkyl or haloalkyl; an alkylcarbonyl group which may be substituted with halogen; an alkenylcarbonyl group; an imino group; an amino group which may be substituted with alkyl; An aminocarbonyl group which may be substituted with; an alkylcarbonylamino group; a formyl group or a cyano group, and m and n are each independently 0, 1, 2, 3 or 4] or a biphenyl derivative thereof A pest control agent containing salt as an active ingredient. An agricultural and horticultural fungicide containing the biphenyl derivative represented by the formula (I) according to claim 1 or a salt thereof as an active ingredient. An antifungal agent comprising the biphenyl derivative represented by the formula (I) according to claim 1 or a salt thereof as an active ingredient. The formula (I) according to claim 1, wherein X is a chlorine atom; a bromine atom; an iodine atom; a hydroxyl group; a formyl group; an alkyl group which may be substituted with halogen, alkoxy or alkylthio; a nitro group; An aryloxy group which may be substituted with halogen or haloalkyl; a heterocyclic oxy group which may be substituted with halogen or haloalkyl; a heterocyclic group which may be substituted with halogen or haloalkyl; An alkylcarbonylamino group; an alkylcarbonyl group optionally substituted with halogen; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group, wherein Y is a halogen atom; a hydroxyl group; a formyl group; a halogen, alkoxy or alkylthio Replaced with An optionally substituted alkyl group; a nitro group; an amino group optionally substituted with alkyl; an aryloxy group optionally substituted with halogen or haloalkyl; a heterocyclic oxy group optionally substituted with halogen or haloalkyl; a halogen or haloalkyl A heterocyclic group which may be substituted; an aminocarbonyl group which may be substituted with alkyl; an alkylcarbonylamino group; an alkylcarbonyl group which may be substituted with halogen; an alkylthio group; an alkylsulfonyl group or an alkylsulfinyl group; Is a halogen atom; a formyl group or an alkyl group which may be substituted with a halogen atom, A is a carbonyl group; a thiocarbonyl group or a single bond, and m and n are each independently 0, 1, 2, 3 or 4 A biphenyl derivative or a salt thereof. The biphenyl derivative according to claim 4, wherein m is 2, one Y is substituted at the para position with respect to X, and the other Y is substituted at the ortho position with respect to the bonding position of the two phenyl rings. salt. A method for controlling plant diseases comprising applying the biphenyl derivative represented by the formula (I) according to claim 1 or a salt thereof to an agricultural or horticultural plant.