Patent Application
20050192359
The present invention relates to N-biphenylamide compounds and fungicidal compositions containing the same.
Some of N-biphenylamide compounds are disclosed in International Patent Application published under the Patent Cooperation Treaty WO97/08148, European Patent Published Application 0545099 and the like.
The object of the present invention is to provide a novel N-biphenylamide compound having excellent controlling activity against plant diseases.
The present inventor has earnestly studied, and found that the N-biphenylamide compound of the formula (1) has excellent plant diseases controlling effect to complete the present invention.
Namely, the present invention provides the N-biphenylamide compound (hereinafter, referred to as the present compound) of the following formula (1):
wherein R1, R2, R3, R4 and R5 independently represent a hydrogen atom, halogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-6 haloalkynyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 alkenyloxy, C3-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C6 cycloalkyl, C3-C6 cycloalkoxy, tri(C1-C6 alkyl)silyl or cyano,
In the present invention, a specific example of each substituent in the formula (1) is shown in the following.
In R1, R2, R3, R4 and R5;
The phenyl substituted with R1, R2, R3, R4 and R5 includes, for example, the phenyl wherein R1, R2 and R3 are independently a hydrogen atom, halogen atom, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 alkenyloxy, C3-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C6 cycloalkyl, C3-C6 cycloalkoxy, tri(C1-C6 alkyl)silyl or cyano, and R4 and R5 are hydrogen atoms;
In R6;
In R7, the C1-C3 alkyl includes, for example, methyl, ethyl and propyl.
In R8, the C1-C3 alkyl includes, for example, methyl, ethyl and propyl.
In R9 and R10;
In R11, R12 and R13;
The phenyl substituted with R9, R10, R11, R12 and R13 includes, for example, the phenyl wherein R9 and R10 are C1-C6 alkoxy, and R11, R12 and R13 are a hydrogen atom, halogen atom or C1-C3 alkyl;
In R14, R15, R16 and R17;
The o-phenylene substituted with R14, R15, R16 and R17 includes, for example, the o-phenylene wherein R14, R15, R16 and R17 are independently a hydrogen atom, halogen atom or C1-C3 alkyl;
The embodiments of the present compounds include, for example, the following compounds.
The compound of the formula (1) wherein X1 is an oxygen atom;
The following describes a production process for the present compound.
The present compound can be produced by, for example, (Production Process A), (Production Process B), (Production Process C) or (Production Process D).
(Production Process A)
The present compound of the formula (4) can be produced by making the compound of the formula (2) react with the compound of the formula (3).
wherein L1 represents a chlorine atom, bromine atom or methanesulfonyloxy, and R1 to R17 have the same meaning as described above.
The reaction is carried out in the presence or absence of a solvent, and usually in the presence of base.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethyl acetate, butyl acetate and the like; nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used in the reaction includes, for example, carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; nitrogen containing aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
Concerning the ratio of the compound used in the reaction, the amount of the compound of the formula (3) is usually 1 to 10 mole, and the amount of the base is usually 1 to 10 mole, based on 1 mole of the compound of the formula (2).
The reaction time is usually in the range of 0.1 to 24 hours, and the reaction temperature is usually in the range of 0 to 150° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (4). Even more, the isolated present compound of the formula (4) can be purified by a technique such as chromatography, recrystallization and the like.
(Production Process B)
The present compound of the formula (6) can be produced by making the compound of the formula (5) react with
The reaction is usually carried out in solvents. The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; nitrites such as acetonitrile, butyronitrile and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The amount of Lawesson's reagent is usually 1 to 10 mole based on 1 mole of the compound of the formula (5).
The reaction time is usually in the range of 0.5 to 24 hours, and the reaction temperature is usually in the range of 50 to 150° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (6). Even more, the isolated present compound of the formula (6) can be purified by a technique such as chromatography, recrystallization and the like.
(Production Process C)
The present compound of the formula (9) can be produced by making the compound of the formula (7) react with the compound of the formula (8).
wherein L2 represents a bromine atom, iodine atom or methanesulfonyloxy, R8a represents C1-C3 alkyl, R1 to R7, R9 to R17, X1 and X2 have the same meaning as described above.
The reaction is carried out in the presence or absence of a solvent, and usually in the presence of base.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethyl acetate, butyl acetate and the like; nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used in the reaction includes, for example, carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like.
Concerning the ratio of the compound used in the reaction, the amount of the compound of the formula (8) is usually 1 to 10 mole, and the amount of the base is usually 1 to 10 mole, based on 1 mole of the compound of the formula (7).
The reaction time is usually in the range of 0.5 to 24 hours, and the reaction temperature is usually in the range of 0 to 120° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (9). Even more, the isolated present compound of the formula (9) can be purified by a technique such as chromatography, recrystallization and the like.
(Production Process D)
The present compound of the formula (13) can be produced by making the compound of the formula (10) react with methanesulfonyl chloride, and subsequently making react with the compound of the formula (12).
wherein R1 to R7, R9 to R12 and X2 have the same meaning as described above.
[Step 1]: The Process of Making the Compound of the Formula (10) React with Methanesulfonyl Chloride.
The reaction is carried out usually in a solvent, and usually in the presence of base.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethyl acetate, butyl acetate and the like; nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used in the reaction includes, for example, carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydrides such as sodium hydride and the like; tertiary amines such as triethylamine, diisopropylethamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; nitrogen containing aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
Concerning the ratio of the compound used in the reaction, the amount of the base is usually 1 to 10 mole, and the amount of methanesulfonyl chloride is usually 1 to 3 mole, based on 1 mole of the compound of the formula (10).
The reaction time is usually in the range of 1 to 24 hours, and the reaction temperature is usually in the range of −20 to 100° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (11). Even more, the isolated present compound of the formula (11) can be purified by a technique such as chromatography, recrystallization and the like.
[Step 2]: The Process of Making the Compound of the Formula (11) React with the Compound of the Formula (12).
The reaction is carried out in the presence or absence of a solvent, and in the presence or absence of base.
The solvent used in the reaction, if required, includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethyl acetate, butyl acetate and the like; nitrites such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide and the like; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used in the reaction, if required, includes, for example, carbonates such as sodium carbonate, potassium carbonate and the like; tertiary amines such as triethylamine, diisopropylethamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; nitrogen containing aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
The amount of the compound of the formula (12) is usually 1 to 10 mole based on 1 mole of the compound of the formula (11).
The reaction time is usually in the range of 1 to 24 hours, and the reaction temperature is usually in the range of 0 to 150° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (13). Even more, the isolated present compound of the formula (13) can be purified by a technique such as chromatography, recrystallization and the like.
The following describes a production process for the intermediate compound of the present compound.
The compound of the formula (19) can be produced by, for example, the following scheme.
wherein L3 represents a chlorine atom or bromine atom, L4 represents a chlorine atom, bromine atom, iodine atom or trifluoromethanesulfonyloxy, L5 represents B(OH)2, B(OR19)2 or SnR20, R19 and R20 represent C1-C10 alkyl, and R1 to R5, R7 and R9 to R17 have the same meaning as the described above.
[Step5-1]
The compound of the formula (16) can be produced by making the compound of the formula (14) react with the compound of the formula (15).
The reaction is carried out usually in solvents, and usually in the presence of base.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as ethyl acetate, butyl acetate and the like; nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The base used in the reaction includes, for example, carbonates such as sodium carbonate, potassium carbonate and the like; tertiary amines such as triethylamine, diisopropylethamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene and the like; nitrogen containing aromatic compounds such as pyridine, 4-dimethylaminopyridine and the like.
Concerning the ratio of the compound used in the reaction, the amount of the base is usually 1 to 10 mole, and the amount of the compound of the formula (15) is usually 1 to 3 mole, based on 1 mole of the compound of the formula (14).
The reaction time is usually in the range of 1 to 24 hours, and the reaction temperature is usually in the range of −20 to 100° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (16). Even more, the isolated present compound of the formula (16) can be purified by a technique such as chromatography, recrystallization and the like.
[Step5-2]
The compound of the formula (17) wherein R7 is a hydrogen atom can be produced by making the compound of the formula (16) react with a reducing agent.
The reaction is carried out usually in solvents.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; water; and the mixture thereof.
The reducing agent used in the reaction includes, for example, sodium borohydride and potassium borohydride.
The amount of the reducing agent is usually 0.25 to 3 mole based on 1 mole of the compound of the formula (16).
The reaction time is usually in the range of instant to 24 hours, and the reaction temperature is usually in the range of −20 to 100° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (17). Even more, the isolated present compound of the formula (17) can be purified by a technique such as chromatography, recrystallization and the like.
The compound of the formula (17) wherein R7 is C1-C3 alkyl can be produced by making the compound of the formula (16) react with an organic metal compound such as Grignard reagent, alkyl lithium and the like.
The reaction is carried out usually in solvents.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like.
The amount of the organic metal compound is usually 1 to 3 mole based on 1 mole of the compound of the formula (16).
The reaction time is usually in the range of instant to 24 hours, and the reaction temperature is usually in the range of −80 to 50° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (17). Even more, the isolated present compound of the formula (17) can be purified by a technique such as chromatography, recrystallization and the like.
[Step5-3]
The compound of the formula (19) can be produced by making the compound of the formula (17) react with the compound of the formula (18) in the presence of a catalyst.
The reaction is carried out usually in a solvent, and usually in the presence of base.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; nitrites such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The catalyst used in the reaction includes, for example, palladium compounds such as palladium acetate, tetrakis(triphenylphosphine) palladium, {1,1-bis(diphenylphosphino)ferrocene}palladium dichloride methylene chloride complex, bis(triphenylphosphine)palladium dichloride and the like.
Concerning the ratio of the compound used in the reaction, the amount of the compound of the formula (17) is usually 1 to 5 mole, and the amount of the catalyst is usually 0.001 to 0.1 mole, based on 1 mole of the compound of the formula (18).
As the need arises, the reaction may be carried out in the presence of a base (for example, an inorganic base such as sodium acetate, potassium acetate, potassium phosphate, sodium hydrogencarbonate and the like) and/or phase transfer catalyst (for example, tertiary ammonium salt such as tetrafluorobenzyl bromide, benzyl triethylammonium bromide and the like).
The reaction time is usually in the range of 0.2 to 24 hours, and the reaction temperature is usually in the range of 50 to 120° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (19). Even more, the isolated present compound of the formula (19) can be purified by a technique such as chromatography, recrystallization and the like.
The compound of the formula (14) can be produced by, for example, the following scheme.
wherein R1 to R5 and L3 have the same meaning as the described above.
[Step 6-1]
The compound of the formula (22) can be produced by making the compound of the formula (21) react with a cyanide compound.
The reaction is carried out usually in solvents.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; nitriles such as acetonitrile, butyronitrile and the like; acid amides such as N,N-dimethylformamide; sulfoxides such as dimethylsulfoxide and the like; and the mixture thereof.
The cyanide compound used in the reaction includes, for example, alkali metal cyanide such as sodium cyanide, potassium cyanide and the like; and cupric cyanide.
The amount of the cyanide compound is usually 1 to 5 mole based on 1 mole of the compound of the formula (21).
The reaction time is usually in the range of 1 to 24 hours, and the reaction temperature is usually in the range of 50 to 100° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (22). Even more, the isolated present compound of the formula (22) can be purified by a technique such as chromatography, recrystallization and the like.
[Step 6-2]
The compound of the formula (23) can be produced by making the compound of the formula (22) hydrolyze under acidic condition.
The reaction is carried out usually in the presence of an acid and water, and, if necessary, in a organic solvents.
The acid used in the reaction includes, for example, hydrochloric acid, hydrobromic acid and sulfuric acid.
The amount of the acid is usually 1 mole to excess amount based on 1 mole of the compound of the formula (22).
The reaction time is usually in the range of 1 to 40 hours, and the reaction temperature is usually in the range of 40 to 100° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (23). Even more, the isolated present compound of the formula (23) can be purified by a technique such as chromatography, recrystallization and the like.
[Step 6-3]
The compound of the formula (14) can be produced by making the compound of the formula (23) react with a chlorinating agent or brominating agent.
The reaction is carried out usually in the presence or absence of a solvent.
The solvent used in the reaction includes, for example, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether and the like; aliphatic hydrocarbons such as hexane, heptane, octane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; nitriles such as acetonitrile, butyronitrile and the like; and the mixture thereof.
The chlorinating agent and brominating agent used in the reaction includes, for example, thionyl chloride, phosphorous oxychloride, phosphorous chloride and thionyl bromide.
The amount of the chlorinating agent or brominating agent used in the reaction is usually 1 to 5 mole based on 1 mole of the compound of the formula (23).
The reaction time is usually in the range of 0.1 to 24 hours, and the reaction temperature is usually in the range of 50 to 150° C.
After completion of the reaction, the reaction mixture is subjected to usual post treatment procedure such as extracting with organic solvent, subsequently drying and concentrating the organic layer, to isolate the present compound of the formula (14). Even more, the isolated present compound of the formula (14) can be purified by a technique such as chromatography, recrystallization and the like.
Examples of the plant diseases to be controlled by the present compound include, for example,
When the present compound is used for controlling plant diseases by applying the present compound, it can be used as the present compound itself, but usually as a fungicidal composition containing the present compound and an appropriate carrier. The fungicidal composition of the present invention is usually formulated to emulsifiable concentrates, wettable powders, water dispersible granules, flowables, dusts, granules and so on by mixing with solid carrier, liquid carrier, surfactant or the other auxiliaries. These formulations usually contain 0.1 to 90% by weight of the present compound.
Examples of the solid carrier utilized for the formulation include fine powders or granules of minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, terra alba, pyrophyllite, talc, diatomaceous earth and calcite; natural organic substances such as corncob and walnut shell; synthetic organic substances such as urea; salts such as calcium carbonate and ammonium sulfate; and synthetic inorganic substances such as synthetic hydrous silicon oxide. Examples of the liquid carrier include aromatic hydrocarbons such as xylene, alkylbenzene and methylnaphthalene; alcohols such as isopropanol, ethylene glycol, propylene glycol and cellosolve; ketones such as acetone, cyclohexanone and isophorone; vegetable oils such as soybean oil and cottonseed oil; paraffin type aliphatic hydrocarbons; esters; dimethyl sulfoxide; acetonitrile and water.
Examples of the surfactant include anionic surfactants such as alkylsulfate ester salts, alkylarylsulfonate salts, dialkyl sulfosaccinate salts, polyoxyethylenealkylary ether phosphate salts, ligninsulfonate salts and naphthalenesulfonate formaldehyde condensate; nonionic surfactants such as polyoxyethylenealkylary ether, polyoxyethylenealkylpolyoxypropylene block copolymers and sorbitan fatty acid esters.
Examples of the auxiliaries for formulation include water soluble polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polysaccharides such as gum arabic, alginic acid and its salts, CMC (carboxymethylcellulose) and xanthan gum; inorganic substances such as aluminium magnesium silicate and alumina sol; preservatives; coloring agent; PAP (isopropyl acid phosphate) and stabilizers such as BHT.
By applying the fungicidal composition of the present invention to a plant, the plant can be protected from plant diseases, namely the plant diseases can be controlled. By applying the fungicidal composition of the present invention to a soil, the plant growing on the soil can be protected from plant diseases, namely the plant diseases can be controlled.
When the plant disease controlling composition of the present invention is used with foliar application to a plant or soil application, the application amount, although it may vary with a kind of crops, a kind of plant disease to be controlled, an extent of breaking out plant disease to be controlled, formulation types, the time of application, the weather conditions and the like, is usually in the range of 1 to 5,000 g, preferably 5 to 1,000 g, 10,000 m2.
The emulsifiable concentrates, wettable powders, flowables and the like are usually applied by spraying after diluted with water. In this case, the concentrate of the present compound is usually in the range of 0.0001 to 3 weight %, preferably 0.0005 to 1 weight %. The dusts, granules and the like are usually applied as such without any dilution.
The present fungicidal composition of the present invention can be used with the other application such as seed treatment. The method includes, for example, soaking seeds in the fungicidal composition of the present invention of 1 to 1000 ppm, spraying or daubing the fungicidal composition of the present invention of 1 to 1000 ppm on seeds, and powder coating seeds with the fungicidal composition of the present invention.
The method for controlling plant diseases of the present invention is usually carried out by applying an effective amount of the present compound on the plant wherein occurrence of a plant disease is predictable, and/or the soil wherein the plant is growing.
The fungicidal composition of the present invention can be used as agricultural/horticultural plant diseases controlling composition, namely plant diseases controlling composition in the plowed fields, paddy fields, orchards, tea plantations, pastures, lawns and the like.
Also, the fungicidal composition of the present invention can be used with other plant diseases controlling composition, insecticides, acaricides, nematocides, herbicides, plant growth regulators and/or fertilizers.
Examples of such other plant diseases controlling composition include: chlorothalonil; fluazinam; dichlofluanid; fosetyl-Al; cyclic imide derivatives such as captan, captafol, folpet and the like; dithiocarbamate derivatives such as maneb, mancozeb, thiuram, ziram, zineb, propineb and the like; inorganic or organic copper derivatives such as basic copper sulfate, basic copper chloride, copper hydroxide, copper-oxinate and the like; acylalanine derivatives such as metalaxyl, furalaxyl, ofurace, cyprofuram, benalaxyl, oxadixyl and the like; strobilurine compound such as kresoxim-methyl, azoxystrobin, trifloxystrobin, picoxystrobin, pyraclostrobin, dimoxystrobin and the like; anilinopyrimidine derivatives such as cyprodinil, pyrimethanil, mepanipyrim and the like; phenyl pyrrole derivatives such as fenpiclonil, fludioxonil and the like; imide derivatives such as procymidone, iprodione, vinclozolin and the like; benzimidazole derivatives such as carbendazim, benomyl, thiabendazole, thiophanate methyl and the like; amine derivatives such as fenpropimorph, tridemorph, fenpropidin, spiroxamine and the like; azole derivatives such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromuconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, myclobutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol, imazalil, flutriafol and the like; cymoxanil; dimethomorph; famoxyadone, fenamidone; iprovalicarb; benthiavalicarb; cyazofamid, zoxamide, ethaboxam; nicobifen; fenhexamid; quinoxyfen; diethofencarb and acibenzolar S-methyl.
The following production examples, formulation examples and test examples and the like describe the invention further in detail below, but do not limit the scope of the invention.
At first the production examples of the present compound is shown. In addition, a number of the present compound is a compound number as described in the following tables.
In 10 ml of diethyl ether were added 3.64 g of N-3′,4′-dimethoxybiphenyl-2-yl)-2-hydroxy-2-(4-methylphenyl)acetamide and 0.30 ml of triethylamine, and 0.15 ml of methanesulfonyl chloride was added dropwise at about 0° C. The mixture was stirred at room temperature for 1 hour. After the addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed two times with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue and 2 ml of 2-propyN-1-ol were mixed, and stirred at about 80° C. for 30 minutes. The reaction mixture was cooled to room temperature, and extracted with ethyl acetate after the addition of water. The organic layer was successively washed with water, a saturated sodium bicarbonate aqueous solution, and a saturated sodium chloride aqueous solution; dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 311 mg of N-3′,4′-dimethoxybiphenyl-2-yl)-2-(propynyloxy)-2-(4-methylphenyl)acetamide (the present compound 1-063).
1H-NMR (CDCl3, TMS) d (ppm): 8.79 (1H, s), 8.38 (1H, d, J=8.4 Hz), 7.13-7.35 (7H, m), 7.01 (1H, d, J=8.0 Hz), 6.95 (1H, dd, J=8.4, 2.0 Hz), 6.90 (1H, d, J=2.0 Hz), 5.01 (1H, s), 3.88-4.05 (8H, m), 2.44 (1H, t, J=2.4 Hz), 2.33 (3H, s)
From 2-(4-ethylphenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol, N-(3′,4′-dimethoxybiphenyl-2-yl)-2-(4-ethylphenyl)-2-(2-propynyloxy)acetamide (the present compound 1-064) was obtained by the similar method of Production Example 1.
1H-NMR (CDCl3, TMS) d (ppm): 8.80 (1H, br), 8.38 (1H, dd, J=1.2, 8.3 Hz), 7.1-7.4 (7H, m), 7.00 (1H, d, J=8.0 Hz), 6.96 (1H, dd, J=2.0, 8.0 Hz), 6.91 (1H, d, J=2.0 Hz), 5.01 (1H, s), 4.07 (1H, dd, J=2.4, 15.8 Hz), 3.96 (3H, s), 3.90 (1H, dd, J=2.4, 15.6 Hz), 3.90 (3H, s), 2.63 (2H, q, J=7.7, 15.2 Hz), 2.44 (1H, t, J=2.4 Hz), 1.21 (3H, t, J=7.7 Hz)
From 2-(4-methoxyphenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol, N-(3′,4′-dimethoxybiphenyl-2-yl)-2-(4-methoxyphenyl)-2-(2-propynyloxy)acetamide (the present compound 1-080) was obtained by the similar method of Production Example 1.
1H-NMR (CDCl3, TMS) d (ppm): 8.78 (1H, br), 8.38 (1H, d, J=8.7 Hz), 7.2-7.4 (4H, m), 7.1-7.2 (1H, m), 6.8-7.0 (5H, m), 4.99 (1H, s), 4.0-4.1 (1H, m), 3.95 (3H, s), 3.90 (3H, s), 3.8-3.9 (1H, m), 3.79 (3H, s), 2.44 (1H, t, J=2.4 Hz)
From 2-(4-methylphenyl)-N-(3′,4′-dimethoxy-4-methylbiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol, N-(3′,4′-dimethoxy-4-methylbiphenyl-2-yl)-2-(2-propynyloxy)-2-(4-methylphenyl)acetamide (the present compound 2-078) was obtained by the similar 10 method of Production Example 1.
1H-NMR (CDCl3, TMS) d (ppm): 8.75 (1H, br), 8.23 (1H, s), 7.1-7.3 (5H, m), 6.8-7.0 (4H, m), 5.00 (1H, s), 4.06 (1H, dd, J=2.4, 15.8 Hz), 3.94 (3H, s), 3.90 (1H, dd, J=2.2, 15.6 Hz), 3.89 (3H, s), 2.44 (1H, t, J=2.4 Hz), 2.35 (3H, s), 2.32 (3H, s)
From 2-(3-methylphenyl)-n-(3′,4′-dimethoxybiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol, N-(3′,4′-dimethoxybiphenyl-2-yl)-2-(2-propynyloxy)-2-(3-methylphenyl)acetamide (the present compound 1-098) was obtained by the similar method of Production Example 1.
1H-NMR (CDCl3, TMS) d (ppm): 8.80 (1H, br), 8.28 (1H, d, J=8.3 Hz), 7.1-7.4 (5H, m), 7.00 (1H, d, J=8.3 Hz), 6.95 (1H, dd, J=1.9, 8.2 Hz), 6.91 (1H, d, J=1.9 Hz), 5.00 (1H, s), 4.08 (1H, dd, J=2.4, 15.6 Hz), 3.95 (3H, s), 3.90 (1H, dd, J=2.4, 15.7 Hz), 3.90 (3H, s), 2.4-2.5 (1H, m)
In 6 ml of N,N-dimethylformamide were added 0.47 g of N-(3′-methoxy-4′-hydroxybiphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide, 0.30 g of 3-bromo-1-propyn and 0.92 g of cesium carbonate, and the reaction mixture was stirred at 0 to 5° C. for 1 hour, at room temperature for 1 hour, furthermore at 60° C. for 3 hour. The reaction mixture was cooled to room temperature, and extracted with ethyl acetate after addition of water. The organic layer was washed with 5% hydrochloric acid, and saturated sodium chloride aqueous solution successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 225 mg of N-(3 ′-methoxy-4′-(2-propynyloxy)biphenyl-2-yl)-2-(2-propynyloxy)-2-(4-methylphenyl)acetamide (the present compound 2-025).
1H-NMR (CDCl3, TMS) d (ppm): 8.78 (1H, s), 8.38 (1H, d, J=8.1 Hz), 7.13-7.35 (8H, m), 6.92-6.94 (2H, m), 5.01 (1H, s), 3.88-4.10 (5H, m), 2.55-2.56 (1H, m), 2.45-2.46 (1H, m), 2.33 (3H, s)
In 15 ml of ethylene glycol dimethyl ether were added 1.20 g of N-(3 ′,4′-dimethoxy-6-methylbiphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide, 1.22ml of 30% sodium hydroxide aqueous solution, 50 mg of tetrabutylammonium bromide and 543 mg 3-bromopropyne/5 ml of toluene solution at room temperature, the mixture was stirred at 40° C. for 6 hours. The reaction mixture was cooled to room temperature, and 10 extracted with ethyl acetate after addition of water. The organic layer was washed with saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 833 mg of N-(3′,4′-dimethoxy-6-methylbiphenyl-2-yl)-2-(2-propynyloxy)-2-(4-methylphenyl)acetamide (the present compound 2-046).
1H-NMR (CDCl3, TMS) d (ppm): 8.39 and 8.34 (1H in all, br), 8.1-8.3 (1H, m), 7.0-7.3 (7H, m), 6.6-6.9 (2H, m), 4.89 and 4.88 (1H in all, s), 3.8-4.0 (8H, m), 2.4-2.5 (1H, m), 2.32 and 2.31 (3H in all, s), 2.08 (3H, s)
In 5 ml of N,N-dimethylformamide were added 500 mg of N-(3′,4′-dimethoxy-5-methyl-biphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide, 667 mg of cesium carbonate and 226 mg of 3-bromopropyne, the mixture was stirred at 60° C. for 3.5 hours. The reaction mixture was cooled to room temperature, and extracted with ethyl acetate after addition of water. The organic layer was washed with saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 130 mg of N-(3′,4′-dimethoxy-5-methyl-biphenyl-2-yl)-2-(2-propynyloxy)-2-(4-methylphenyl)acetamide (the present compound 2-062).
1H-NMR (CDCl3, TMS) d (ppm): 8.68 (1H, br), 8.22 (1H, d, J=8.3 Hz), 7.0-7.3 (6H, m), 6.98 (1H, d, J=8.3 Hz), 6.93 (1H, dd, J=1.8, 8.2 Hz), 6.88 (1H, d, J=1.9 Hz), 4.99 (1H, s), 4.06 (1H, dd, J=2.4, 15.8 Hz), 3.95 (3H, s), 3.89 (1H, dd, J=2.4, 15.6 Hz), 3.89 (3H, s), 2.43 (1H, t, J=2.2 Hz), 2.33 (3H, s), 2.32 (3H, s)
In 10 ml of tetrahydrofuran were added 0.70 g of 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and 231 mg of triethylamine, and 241 mg of methanesulfonyl chloride was added dropwise at about 0° C. The mixture was stirred at the same temperature for 30 minutes and at room temperature for 60 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid and saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 3.43 g of a residue. 0.69 g of the obtained residue and 0.81 g 2-propyn-1-ol were mixed, and stirred at about 80° C. for 2 hours. The reaction mixture was cooled to room temperature, and extracted with ethyl acetate after addition of water. The organic layer was washed with saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 180 mg of 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-(2-propynyloxy)acetamide (the present compound 1-060).
1H-NMR (CDCl3, TMS) d (ppm): 8.74 (1H, br), 8.33 (1H, d, J=8.4 Hz), 7.2-7.4 (6H, m), 7.1-7.2 (1H, m), 6.8-7.1 (3H, m), 5.02 (1H, s), 3.9-4.2 (2H, m), 3.96 (3H, s), 3.89 (3H, s), 2.46 (1H, t, J=2.3 Hz)
From 2-phenyl-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol, N-(3′,4′-dimethoxybiphenyl-2-yl)-2-phenyl-2-(2-propynyloxy)acetamide (the present compound 1-058) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.77 (1H, br), 8.37 (1H, dd, J=0.97, 8.3 Hz), 7.2-7.5 (7H, m), 7.1-7.2 (1H, m), 7.00 (1H, d, J=8.0 Hz), 6.94 (1H, dd, J=2.0, 8.3 Hz), 6.90 (1H, d, J=2.0 Hz), 5.03 (1H, s), 3.8-4.2 (2H, m), 3.96 (3H, s), 3.89 (3H, s), 2.45 (1H, J=2.4 Hz)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and methanol, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-methoxyacetamide (the present compound 1-003) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.72 (1H, br), 8.31 (1H, d, J=8.0 Hz), 7.1-7.4 (7H, m), 6.98 (1H, d, J=7.8 Hz), 6.90 (1H, dd, J=2.0, 8.0 Hz), 6.87 (1H, d, J=1.9 Hz), 4.61 (1H, s), 3.97 (3H, s), 3.88 (3H, s), 3.25 (3H, s)
From 2-(4-fluorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and propargyl alcohol 2-(4-fluorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-(2-propynyloxy)acetamide (the present compound 1-059) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.77 (1H, br), 8.30 (1H, dd, J=8.3, 0.97 Hz), 7.2-7.4 (4H, m), 7.1-7.2 (1H, m), 7.0-7.1 (3H, m), 6.93 (1H, dd, J=1.9, 8.3 Hz), 6.89 (1H, d, J=1.9 Hz), 5.02 (1H, s), 4.08 (1H, dd, J=2.4, 15.6 Hz), 3.95 (3H, s), 3.91 (1H, dd, J=2.4, 15.6 Hz), 3.89 (3H, s), 2.46 (1H, t, J=2.4 Hz)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide ethyl alcohol, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-ethoxyacetamide (the present compound 1-111) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.77 (1H, br), 8.30 (1H, dd, J=8.3, 0.97 Hz), 7.2-7.4 (4H, m), 7.1-7.2 (1H, m), 7.0-7.1 (3H, m), 6.93 (1H, dd, J=1.9, 8.3 Hz), 6.89 (1H, d, J=1.9 Hz), 5.02 (1H, s), 4.08 (1H, dd, J=2.4, 15.6 Hz), 3.95 (3H, s), 3.91 (1H, dd, J=2.4, 15.6 Hz), 3.89 (3H, s), 2.46 (1H, t, J=2.4 Hz)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and isopropyl alcohol, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-isopropoxyacetamide (the present compound 1-252) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.94 (1H, br), 8.39 (1H, d, J=8.3 Hz), 7.1-7.4 (7H, m), 6.8-7.1 (3H, m), 4.78 (1H, s), 3.95 (3H, s), 3.89 (3H, s), 3.5-3.6 (1H, m), 0.96 (3H, d, J=6.1 Hz), 0.92 (3H, d, J=6.0 Hz)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and 2,2,2-trifluoroethyl alcohol, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-(2,2,2-trifluoroethoxy)acetamide (the present compound 1-234) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.60 (1H, br), 8.31 (1H, d, J=7.5), 7.2-7.4 (6H, m), 7.1-7.2 (1H, m), 6.98 (1H, d, J=8.0 Hz), 6.90 (1H, dd, J=1.9, 8.0 Hz), 6.82 (1H, d, J=1.9 Hz), 4.87 (1H, s), 3.95 (3H, s), 3.87 (3H, s), 3.6-3.8 (2H, s)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and 2-butyn-1-ol, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-(2-butynyloxy)acetamide (the present compound 1-241) was obtained by the similar method of Production Example 9.
1H-NMR (CDCl3, TMS) d (ppm): 8.76 (1H, br), 8.34 (1H, d, J=8.4), 7.2-7.4 (6H, m), 7.1-7.2 (1H, m), 6.99 (1H, d, J=8.0 Hz), 6.93 (1H, dd, J=1.9, 8.0 Hz), 6.89 (1H, d, J=1.9 Hz), 5.03 (1H, s), 4.0-4.1 (1H, m), 3.96 (3H, s), 3.8-3.9 (1H, m), 3.90 (3H, s), 1.81 (3H, t, J=2.0 Hz)
In 5 ml of tetrahydrofuran were dissolved 398 mg of 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and 131 mg of triethylamine, 94 mg of acetyl chloride was added dropwise. The mixture was stirred at room temperature for 1 hour and 30 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid and saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with N-hexane, subjected to filtration, and dried to obtain 403 mg of 2-acetyloxy-2-(4-chlorophenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)acetamide (the present compound 1-202)
1H-NMR (CDCl3, TMS) d (ppm): 8.35 (1H, d, J=8.3 Hz), 8.06 (1H, br), 7.1-7.4 (7H, m), 6.96 (1H, d, J=8.0 Hz), 6.85 (1H, dd, J=1.8, 8.1 Hz), 6.82 (1H, d, J=1.7 Hz), 6.03 (1H, s), 3.95 (3H, s), 3.87 (3H, s), 1.92 (3H, s)
From 2-(4-chlorophenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)-2-hydroxyacetamide and 2-methylpropionic chloride, 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-isobutyryloxyacetamide (the present compound 1-210) was obtained by the similar method of Production Example 12.
1H-NMR (CDCl3, TMS) d (ppm): 8.35 (1H, d, J=8.0 Hz), 8.09 (1H, br), 7.2-7.5 (7H, m), 7.1-7.4 (7H, m), 6.95 (1H, d, J=8.0 Hz), 6.86 (1H, dd, J=1.9, 8.0 Hz), 6.82 (1H, d, J=1.9 Hz), 6.03 (1H, s), 3.95 (3H, s), 3.86 (3H, s)2.3-2.4 (1H, m), 1.01 (6H, d, J=6.8 Hz)
From 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-hydroxyacetamide and 2,2-dimethylpropionic chloride, 403 mg of 2-(4-chlorophenyl)-N-(3′,4′-dihydroxybiphenyl-2-yl)-2-pyvaloyloxyacetamide (the present compound 1-214) was obtained by the similar method of Production Example 12.
1H-NMR (CDCl3, TMS) d (ppm): 8.34 (1H, d, J=8.4 Hz), 7.98 (1H, br), 7.1-7.4 (7H, m)6.95 (1H, d, J=8.3 Hz), 6.86 (1H, dd, J=1.9, 8.3 Hz), 6.81 (1H, d, J=1.7 Hz), 6.03 (1H, s), 3.95 (3H, s), 3.84 (3H, s), 1.00 (9H, s)
In 30 ml of tetrahydrofuran were added 1.75 g of N-(3′,4′-dimethoxybiphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide and 0.78 ml of triethylamine, and 0.38ml of methanesulfonyl chloride was added dropwise. The mixture was stirred at room temperature for 30 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue and 10ml of methanol were mixed, and stirred at about 65° C. for 1 hour. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and extracted with ethyl acetate after addition of water. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.3 g of N-(3′,4′-dimethoxybiphenyl-2-yl)-2-methoxy-2-(4-methylphenyl)acetamide (the present compound 1-006).
1H-NMR (CDCl3, TMS) d (ppm): 8.36 (1H, s), 8.35-8.37 (1H, m), 7.12-7.34 (7H, m), 6.99 (1H, d, J=8.0 Hz), 6.88-6.93 (2H, m), 4.60 (1H, s), 3.94 (3H, s), 3.89 (3H, s), 3.22 (3H, s), 2.33 (3H, s)
Next, the production examples of intermediate of the present compound are shown as the reference production example.
In a mixture of 8.00 g of aluminum chloride and 80 ml of dichloromethane was added 7.85 g of ethyl oxalyl chloride dropwide at 0° C. over stirring. After addition of 4.60 g of toluene at the same temperature, the mixture was stirred for 1 hour. The reaction mixture was poured in ice water, and extracted with chloroform. The organic layer was washed two times with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 9.3 g of ethyl 2-(4-methylphenyl)-2-oxoacetate in crude form.
1H-NMR (CDCl3, TMS) d (ppm): 7.91 (2H, d, J=8.2 Hz), 7.31 (2H, d, J=8.1 Hz), 4.44 (2H, q, J=7.1 Hz), 2.44 (3H, s), 1.42 (2H, t, J=7.0 Hz)
9.3 g of ethyl 2-(4-methylphenyl)-2-oxoacetate, 13 ml of 30% sodium hydroxide aqueous solution and 15 ml of ethanol were mixed, and heated under reflux condition for 2 hours. The reaction mixture was cooled to room temperature, acidified by addition of 5% hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed two times with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane, dried to obtain 5.2g of 2-(4-methylphenyl)-2-oxoacetic acid.
1H-NMR (CDCl3, TMS) d (ppm): 8.25 (2H, d, J=8.3 Hz), 7.32 (2H, d, J=8.0 Hz), 4.28 (1H, br), 2.45 (3H, s)
In 20 ml of toluene were added 2.08 g of 2-(4-methylphenyl)-2-oxoacetic acid, 1.5 ml of thionyl chloride and 49 mg of N,N-dimethylformamide, and stirred at 80° C. for 30 minutes and at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature, concentrated under reduce pressure to obtain 2-(4-methylphenyl)-2-oxoacetic chloride. The obtained 2-(4-methylphenyl)-2-oxoacetic chloride was added at 0 to 5° C. in the solution dissolved 2.91 g of 3′,4′-dimethoxy-2-aminobiphenyl and 2.6 ml of triethylamine in 30 ml of tetrahydrofuran, stirred at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution successively, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 3.57 g of N-(3′,4′-dimethoxybiphenyl-2-yl)-2-(4-methylphenyl)-2-oxoacetamide.
1H-NMR (CDCl3, TMS) d (ppm): 9.28 (1H, s), 8.56 (1H, d, J=7.2 Hz), 8.29 (2H, d, J=8.4 Hz), 7.40-7.44 (m, 1H), 7.22-7.35 (4H, m), 6.93-7.02 (m, 3H), 3.96 (3H, s), 3.91 (3H, s), 2.43 (3H, s)
In 10 ml of ethanol was dissolved 0.60 g of N-(3′,4′-dimethoxybiphenyl-2-yl)-2-(4-methylphenyl)-2-oxoacetamide, and 0.12 g of sodium borohydride was added. The mixture was stirred at room temperature for 4 hours, and then extracted with ethyl acetate after addition of water and 5% hydrochloric acid. The organic layer was washed with water, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution successively, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 285 mg of N-(3′,4′-dimethoxybiphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide.
1H-NMR (CDCl3, TMS) d (ppm): 8.37 (1H, d, J=4.4 Hz), 7.91 (1H, s), 7.32-7.37 (1H, m), 7.01-7.26 (m, 6H), 6.85 (1H, d, J=8.0 Hz), 6.70 (1H, dd, J=8.0, 2.0 Hz), 6.66 (1H, d, J=2.0 Hz), 4.98 (1H, d, J=3 Hz), 3.96 (3H, s), 3.79 (3H, s), 3.51 (1H, d, J=3 Hz), 2.34 (3H, s)
In 150 ml of toluene were added 15.0 g of 2-(4-methylphenyl)-2-oxoacetic acid, 10.7 ml of thionyl chloride and 0.3 ml of N,N-dimethylformamide, and stirred at 80° C. for 30 minutes and at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure to obtain 2-(4-methylphenyl)-2-oxoacetic chloride in crude form. Another hand, in 150 ml of tetrahydrofuran were dissolved 15.7 g of 2-bromaniline and 19 ml of triethylamine, and the 2-(4-methylphenyl)-2-oxoacetic chloride was added at 0 to 5° C. The mixture was stirred at room temperature for 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution successively, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane to obtain 21.9 g of N-(2-bromophenyl)-2-(4-methylphenyl)-2-oxoacetamide.
1H-NMR (CDCl3, TMS) d (ppm): 9.60 (1H, s), 8.51 (1H, dd, J=8.4, 1.2 Hz), 8.39 (2H, d, J=8.4 Hz), 7.61 (1H, dd, J=8.0, 1.2 Hz), 7.31-7.41 (3H, m), 7.04-7.26 (m, 1H), 2.46 (3H, s)
In 100 ml of ethanol were added 10.0 g of N-(2-bromophenyl)-2-(4-methylphenyl)-2-oxoacetamide and 0.36 g sodium borohydride, and stirred at room temperature for 8 hours. After addition of saturated ammonium chloride aqueous solution, the reaction mixture was concentrated under reduced pressure, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated to obtain 10.56 g of N-(2-bromophenyl)-2-hyrdoxy-2-(4-methylphenyl)acetamide.
1H-NMR (CDCl3, TMS) d (ppm): 8.70 (1H, s), 8.36 (1H, dd, J=8.4, 1.6 Hz), 7.52 (1H, dd, J=8.0, 1.2 Hz), 7.40 (2H, d, J=8.0 Hz), 7.19-7.32 (3H, m), 6.96-7.00 (m, 1H), 5.22 (1H, d, J=1.6 Hz), 3.30 (1H, s), 2.36 (3H, s)
In 25 ml of ethylene glycol dimethyl ether were added 2.33 g of N-(2-bromophenyl)-2-hyrdoxy-2-(4-methylphenyl)acetamide, 2.0 g of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenol, 4.6 g of potassium phosphate hydrate and 0.18 g of {1,1′-bis(diphenylphosphino)ferrocene}palladium(II) dichloride(II) methylene chloride complex, and stirred under nitrogen atmosphere at 80° C. for 3 hours. The reaction mixture was cooled at room temperature, and filtered. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 2.6 g of N-(3′-methoxy-4′-hydroxybiphenyl-2-yl)-2-hyrdoxy-2-(4-methylphenyl)acetamide.
1H-NMR (CDCl3, TMS) d (ppm): 8.36 (1H, d, J=8.4 Hz), 7.88 (1H, s), 7.32-7.35 (1H, m), 7.01-7.26 (m, 6H), 6.88 (1H, d, J=7.6 Hz), 6.61-6.64 (2H, m), 5.70 (1H, s), 4.98 (1H, d, J=2.8 Hz), 3.79 (3H, s), 3.61-3.63 (1H, m), 2.35 (3H, s)
In 140 ml of tetrahydrofuran were added 40.0 g of 4-bromochlorobenzene and 5.33 g of magnesium under nitrogen atmosphere, and stirred to prepare Grignard reagent. In 750 ml of tetrahydrofuran was dissolved 49.3 g of diethyl oxalyl, and the Grignard reagent was added dropwise at −70° C. over 30 minutes. The reaction mixture was warmed to room temperature over 2 hours, and stirred at room temperature for 2 hours. After addition of ice water and saturated ammonium chloride aqueous solution, the organic solvent was removed by distillation under reduce pressure from the reaction mixture. The residue was filtered, and the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 22.1 g of ethyl 2-(4-chlorophenyl)-2-oxoacetate.
1H-NMR (CDCl3, TMS) d (ppm): 7.98-8.01 (2H, m), 7.48-7.51 (2H, m), 3.98 (3H, s)
In 300 ml of ethanol were added 12.2 g of 2-(4-chlorophenyl)-2-oxoethyl acetate and 12.6 g of 20% sodium hydroxide aqueous solution, and stirred at room temperature for 3 hours. The reaction mixture was acidified by addition of 36% hydrochloric acid, and extracted three times with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane, and dried to obtain 5.2 g of 2-(4-chlorophenyl)-2-oxoacetic acid.
1H-NMR (CDCl3, TMS) d (ppm): 8.36-8.39 (1H, m), 8.0 (1H, br), 7.51-7.54 (2H, m)
In 12 ml of 1,4-dioxane were dissolved 1.12 g of 2-(4-chlorophenyl)-2-oxoacetic acid and 3 ml of N,N-dimethylformamide, and 1.18 g of 1,1′-carbonyldiimidazole was added at about 0° C. over stirring. After the mixture was stirred for 1.5 hours, 1.39 g of 3′,4′-dimethoxybiphenyl-2-ylamine was added dropwise in the mixture, and stirred at 0° C. for 30 minutes and at room temperature for 2 hours. The reaction mixture was extracted two times with ethyl acetate after addition of water. The organic layer was washed with 5% hydrochloric acid and saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with N-hexane, subjected to filtration, and dried to obtain 1.44 g of 2-(4-chlorophenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)-2-oxoacetamide.
1H-NMR (CDCl3, TMS) d (ppm): 9.30 (1H, br), 8.53 (1H, d, J=8.3 Hz), 8.36 (2H, d, J=8.5 Hz), 7.2-7.4 (5H, m), 6.9-7.1 (3H, m), 3.96 (3H, s), 3.91 (3H, s)
In 15 ml of methanol were dissolved 1.44 g of 2-(4-chlorophenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)-2-oxoacetamide, and 69 mg of sodium borohydride was added at about 0° C. After stirring for 1.5 hour, the reaction mixture was concentrated under reduced pressure. The obtained residue was extracted with ethyl acetate after addition of water. The organic layer was washed with 5% hydrochloric acid and saturated sodium chloride aqueous solution (two times) successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the obtained solid was washed with hexane to obtain 0.70 g of 2-(4-chlorophenyl)-N-(3′,4′-dimethoxybiphenyl-2-yl)-2-hydroxyacetamide.
1H-NMR (CDCl3, TMS) d (ppm): 8.33 (1H, d, J=8.3 Hz), 7.95 (1H, br), 7.1-7.4 (7H, m), 6.83 (1H, d, J=8.0 Hz), 6.71 (1H, d, J=1.9 Hz), 6.65 (1H, dd, J=2.0, 7.9 Hzm), 4.99 (1H, br), 3.96 (3H, s), 3.82 (3H, s), 3.70 (1H, br)
In 100 ml of ethylene glycol dimethyl ether were added 10.1 g of 2-bromonitrobenzene, 10.0 g of 3,4-dimethoxyphenylboric acid, 31.8 g of potassium phosphate hydrate and 817 mg of {1,1′-bis(diphenylphosphino)ferrocene}palladium(II) dichloride(II) methylene chloride complex, and stirred under nitrogen atmosphere at 80° C. for 4.5 hours. The reaction mixture was cooled to room temperature, and subjected to filtration. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 10.0 g of 3,4-dimethoxy-2′-nitrobiphenyl.
1H-NMR (CDCl3, TMS) d (ppm): 7.4-7.9 (4H, m), 6.92 (1H, d, J=8.3 Hz), 6.88 (1H, dd, J=1.9, 8.3 Hz), 6.83 (1H, d, J=1.9 Hz), 3.91 (3H, s), 3.88 (3H, s)
In 100 ml of toluene were added 10.0 g of 3,4-dimethoxy-2′-nitrobiphenyl and 0.30 g of 5% Pt/C, furthermore 5.74g of hydrazine hydrate was added at 80 to 100° C., and stirred at the same temperature for 2 hours. The reaction mixture was cooled at room temperature, and filtered with Celite (registered trade name) after addition of toluene and water. The filtrate was separated, and the organic layer was concentrated under reduced pressure. The residue was washed with hexane, and collected by filtration to obtain 8.47 g of 3′,4′-dimethoxy-biphenyl-2-ylamine.
1H-NMR (CDCl3, TMS) d (ppm): 7.1-7.2 (2H, m), 6.9-7.1 (3H, m), 6.7-6.8 (2H, m) 3.92 (3H, s), 3.89 (3H, s), 3.77 (2H, br)
Next, examples of the present compound is shown with a numbers of the present compound.
The compound of the following formula wherein R3, R4, R5, R11, R12, R13, R14, R15, R16 and R17 in formula (1are hydrogen atoms, and R1, R2, R6, R7, R8, R9, R10, X1 and X2 are the atom or group described in Table 1.
In the table, “c-Pr” means cyclopropyl.
In the table, “c-Pr” means cyclopropyl.
The compound of the following formula wherein R2, R3, R4, R5, R7, R8, R11, R12 and R13 in the formula (1) are hydrogen atoms, and R1, R6, R9, R10, R14, R15 R16 and R17 are the atom or group described in Table 2.
In the table, “c-Pr” means cyclopropyl.
In the table, “c-Pr” means cyclopropyl.
Next formulation examples are shown. Parts represent parts by weight. The present compounds are described with the above-mentioned numbers.
Fifty parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142, 3 parts of calcium ligninsulfonate, 2 parts of magnesium laurylsulfate and 45 parts of synthetic hydrated silica are pulverized and mixed well to give wettable powders of each compound.
Twenty parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142 and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and wet-pulverized finely. To the obtained mixture, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminium magnesium silicate is added and further 10 parts of propylene glycol are added to give a flowable of each compound.
Two parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142, 88 parts of kaolin clay and 10 parts of talc are pulverized and mixed well to give dusts of each compound.
Five parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142, 14 parts of polyoxyethylenestyryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene are mixed well to give emulsifiable concentrates of each compound.
Two parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142, 1 part of synthetic hydrated silica, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are pulverized and mixed well, and water is added thereto and kneeded, granulated and dried to give granules of each compound.
Ten parts of each of the present compounds 1-001 to 1-257 and 2-001 to 1-142, 35 parts of white carbon containing 50% of ammonium polyoxyethylenealkyl ether sulfate and 55 parts of water are mixed and wet pulverized finely to give a formulation of each compound.
Next, it is shown that a present compounds are useful for controlling plant diseases. The present compounds are described with the above-mentioned numbers.
For comparison, a compound of number 4.1 described in European Patent Published Application 0545099, namely N- biphenyl-2-yl-2-methylbenzamide (hereinafter, refered to as the comparative compound A), was also subjected to the examination.
Additionally, the control effect was evaluated by visually observing the area of a lesion on a sample plant in investigation and comparing the area of a lesion on a non-treatment plant and the area of a lesion on a treated plant with the present compound.
Sand loam was compacted in a plastic pot, and a tomato (variety: Ponterosa) was seeded and grown in a green house for 20 days. The present compounds 1-006, 1-058, 1-059, 1-060, 1-063, 1-064, 1-080, 1-098, 1-111, 1-202, 1-210, 1-227, 1-234, 1-252, 2-025. 2-046, 2-062, 2-078 and the comparative compound A were formulated according to Formulation Example 6, then, diluted with water to provide given concentration of 500ppm, and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of the tomato leaves. After spraying, the liquid on the stem was air-dried, and a suspension of zoosporangiua of Phytophthora infestans was inoculated by spraying. After inoculation, the plant was first grown for one day at 23° C. under high humidity, then further grown for 4 days in the green house.
The areas of a lesion of the plants were visually obserbed. The lesion areas on plants on the plants treated with the present compound 1-006, 1-058, 1-059, 1-060, 1-063, 1-064, 1-080, 1-098, 1-111, 1-202, 1-210, 1-227, 1-234, 1-252, 2-025, 2-046, 2-062 and 2-078 were not more than 10% of the lesion area on a non-treatment plant. The lesion areas on plants on the plants treated with the comparative compound A was in a range of 76 to 100% of the lesion area on a non-treatment plant.
Sand loam was compacted in a plastic pot, and a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1-003, 1-006, 1-058, 1-059, 1-060, 1-063, 1-064, 1-080, 1-098, 1-111, 1-210, 1-214, 1-227, 1-252, 2-025, 2-046, 2-062 and 2-078 were formulated according to Formulation Example 6, then, diluted with water to provide given concentration of 200 ppm, and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the liquid on the stem was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first grown for one day at 23° C. under high humidity, then further grown for 6 days in the green house, then the control effect was checked.
The areas of a lesion of the plants were visually obserbed. The lesion areas on plants on the plants treated with the present compound 1-003, 1-006, 1-058, 1-059, 1-060, 1-063, 1-064, 1-080, 1-098, 1-111, 1-210, 1-214, 1-227, 1-252, 2-025, 2-046, 2-062 and 2-078 were not more than 10% of the lesion area on a non-treatment plant.
By using the present compound, plant diseases can be controlled.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2002-71627 | Mar 2002 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP03/02015 | 2/25/2003 | WO | 9/13/2004 |
