WO2005122761A1 - Bactericidal composition - Google Patents

Abstract

Disclosed is a bactericidal composition containing an amide compound represented by the formula (1) below and an ethylenebisdithiocarbamate compound as active ingredients. Also disclosed is a method for controlling plant diseases wherein the amide compound represented by the formula (1) below and the ethylenebisdithiocarbamate compound are applied to a plant or the soil where the plant grows.

Description

 P T / JP2005 / 011214

Fungicidal composition technical field

 TECHNICAL FIELD The present invention relates to a bactericidal composition, particularly to a bactericidal composition which is excellent in controlling plant diseases caused by algae (egg fungi). Light

Background art

 Conventionally, many fungicides have been developed to control plant disease caused by algae (egg fungi). However, there is always a need for fungicides with even higher writing effects. Disclosure of the invention

 The present invention

 (I) Equation (1)

 [In the formula, X represents an oxygen atom or a sulfur atom,

R ¹ is a hydrogen atom, a halogen atom, a (1-4 alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group, a C 2 -C 4 alkynyl group, a CI -C 4 alkoxy group, a C 1 -C 4 Represents a haloalkoxy group or a cyano group,

R ² represents a hydrogen atom, a halogen atom, a (1--4alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group or a C 2 -C 4 alkynyl group, or R ¹ and R ² Together represent a C3-C5 polymethylene group or a 1,3-butadiene-1,4-diyl group,

R ³ represents a hydrogen atom, a C 1 -C 3 alkyl group or a cyano group,

R ⁴ represents a C 1 -C 3 alkyl group,

R ⁵ is a C 1 -C 4 alkyl group, a C 3 -C 4 alkenyl group or a C 3 -C 4 alkynyl P2005 / 011214

2

Represents a group. ]

An amide compound represented by the following (hereinafter sometimes referred to as compound (I)):

 (I I) Ethylenebisdithiocarbamate compound

 (an ethylenebis (dithiocarbamate) compound) (hereinafter sometimes referred to as compound (II)) as an active ingredient (hereinafter sometimes referred to as the composition of the present invention). I do.

 Further, the present invention provides a method for controlling a plant disease, which comprises applying an effective amount of the compound (I) and the compound (II) to a plant or soil where the plant grows. First, the compound (I) will be described.

 In equation (1),

Examples of the halogen atom represented by R ¹ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and examples of the C 11 -C 4 alkyl group include a methyl group, an ethyl group, a propyl group, and an isopropyl group. Butyl group, isobutyl group, sec-butyl group and tert-butyl group; C1-C2 alkyl groups include methyl and ethyl groups; and C1-C4 haloalkyl groups include, for example, Examples include a fluoromethyl group, a difluoromethyl group and a trifluoromethyl group. Examples of the 02-4-alkenyl group include a vinyl group, a 1-methylvinyl group, a 1-propenyl group, a 2-propenyl group, and a 1-methyl- A 2-propenyl group, a 2-methyl-2-propyl group, a 2-butenyl group and a 3-butenyl group. Examples of the C 2 -C 4 alkynyl group include an ethynyl group, A C1-C4 alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group. Examples of the C1-C4 alkoxy group include a methoxy group, a ethoxy group, a propoxy group, and an isopropoxy group. Butoxy group, isobutoxy group, sec-butoxy group and tert-butoxy group. Examples of the C1-C4 haloalkoxy group include fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, Examples include a 2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group and a 2-fluoroethoxy group.

Examples of the halogen atom represented by R ² include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Examples of the C 1 -C 4 alkyl group include a methyl group, an ethyl group, a propyl group, and an isopropyl group. Butyl group, isobutyl group, sec-butyl group and tert-butyl group. Examples of the C1-C2 alkyl group include a methyl group and a tert-butyl group. PT / JP2005 / 011214

Three

A C1-C4 haloalkyl group, for example, a fluoromethyl group, a difluoromethyl group and a trifluoromethyl group; and a C2-C4 alkenyl group, for example, a vinyl group, 1-methylvinyl group. A 1-propenyl group, a 2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propyl group, a 2-butenyl group and a 3-butenyl group, Examples of the C 2 -C 4 alkynyl group include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-methyl-2-propynyl group, a 2-butynyl group and a 3-butynyl group.

The C 3- C 5 polymethylene group and R ¹ and R ² has decreased together, trimethylene group, and tetramethylene group and a pentamethylene group, the C 3- C 4 Porimechire down, trimethylene and tetramethylene And methylene groups.

The C 1 one C 3 alkyl group represented by R ^3, methyl, Echiru group, a propyl group and a Isopuropiru group.

The C 1 one C 3 alkyl group represented by R ^4, a methyl group, Echiru group, and a propyl group and isopropyl group, and the C 1 one C 2 alkyl group, methyl Moto及beauty Echiru group.

Examples of the C 1 -C 4 alkyl group represented by R ⁵ include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group. Examples of the 2 alkyl group include a methyl group and an ethyl group, and examples of the C 3 -C 4 alkenyl group include a 2-propenyl group, a 1-methyl-2-propenyl group, and a 2-methyl-2-propyl group. And the C 3 -alkenyl group includes a 2-propenyl group, and the C 3 -C 4 alkynyl group includes a 2-propenyl group, a 1-methyl-2-propynyl group, and a 2-propynyl group. — A butyl group and a 3-butynyl group; and a C 3 alkynyl group include a 2-propenyl group. As an embodiment of the compound (I), for example, in the formula (1), X is an oxygen atom or a sulfur atom, R ¹ is a halogen atom or a C 1 -C 2 alkyl group, R ² is a hydrogen atom, A halogen atom or a C 1 -C 2 alkyl group, or R ¹ and R ^{2 taken} together to form a C 3 -C 4 polymethylene group or 1,3-butadiene-1,4-diyl group, ^An amide compound in which ^{3 is a} hydrogen atom, R ⁴ is a C 1 -C 2 alkyl group, and R ⁵ is a C 3 alkynyl group; and in the formula (1), X is an oxygen atom, and R ¹ is hydrogen Atom, halogen atom or C1-C2 alkyl group, R ² is a hydrogen atom or a halogen atom, or R ¹ and R ² are taken together to form a C 3 -C 4 polymethylene group or 1,3-butadiene 1,4-diyl group, and R ³ is a cyano group. Amide compounds wherein R ⁴ is a C 1 -C 2 alkyl group; and R ⁵ is a CI—C 2 alkyl group, a C 3 alkenyl group or a C 3 alkynyl group. Table 1 shows specific examples of the compound (I) together with the compound number.

table 1

次に、 化合物 （I) の製造例方法を示す。

Next, a production example method of compound (I) will be described.

Among the compounds (I), a compound represented by the formula (2-1) wherein X is an oxygen atom and a compound represented by the formula (2-2) wherein X is a sulfur atom are produced, for example, according to the following scheme. can do.

 [Where,

R ¹ is a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group, a C 2 -C 4 alkynyl group, a C 1 -C 4 alkoxy Represents a C 1 -C 4 haloalkoxy group or a cyano group,

R ² represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group or a C 2 -C 4 alkynyl group, or R ¹ and R ² represent Together represent a C3-C5 polymethylene group or a 1,3-butadiene-1,4-diyl group,

R ³ represents a hydrogen atom, a C 1 -C 3 alkyl group or a cyano group,

R ⁴ represents a C 1 -C 3 alkyl group,

R ⁵ represents a C 1 -C 4 alkyl group, a C 3 -C 4 alkenyl group or a C 3 -C 4 alkynyl group,

R ⁶ represents a methyl group, an ethyl group or a propyl group,

L ¹ represents a chlorine atom or a bromine atom, and L ² represents a halogen atom. ] Process ((1) 1 1)

 The compound represented by the formula (5) can be produced by reacting the compound represented by the formula (3) with the compound represented by the formula (4).

 The reaction is carried out in the presence or absence of a solvent, usually in the presence of a base. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, and aliphatic hydrocarbons such as hexane, heptane, and octane; Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as benzene and the like, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butylonitrile, N, N-dimethylformamide And sulfoxides such as dimethyl sulfoxide and mixtures thereof.

 Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride and potassium hydride, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5 . 4.0] Pendeck 7-ene, 1,5-diazabicyclo [4.3.0] Tertiary amines such as non-5-ene and nitrogen-containing aromatics such as pyridine and 4-dimethylaminopyridine Group compounds.

The amount of the reagent used in the reaction is usually 1 to 10 mol of the base and 1 to 5 mol of the compound of the formula (4) per 1 mol of the compound of the formula (3). is there. The reaction temperature of the reaction is usually in the range of 0 to 100 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

 After completion of the reaction, the compound represented by the formula (5) is isolated by pouring the reaction mixture into water, extracting with an organic solvent, and performing a post-treatment operation such as drying and concentration of the organic layer. Can be. The isolated compound represented by the formula (5) can be further purified by operations such as chromatography and recrystallization. Process ((1)-2)

 The compound represented by the formula (7) can be produced by reacting the compound represented by the formula (5) with the compound represented by the formula (6).

 The reaction is performed in the presence of a base in the presence of a solvent.

 Examples of the solvent used for the reaction include 1,4-dioxane, tetrahydrofuran, ethers such as ethylene glycol dimethyl ether, tert-butyl methyl ether, and aliphatic hydrocarbons such as hexane, heptane, and octane. Aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as chlorobenzene; acid amides such as N, N-dimethylformamide; sulfoxides such as dimethyl sulfoxide; water; and mixtures thereof. No.

 Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride and potassium hydride, sodium methoxide, sodium ethoxide and potassium tert-butoxide. Metal alkoxides.

 The amount of the reagent used in the reaction is usually a ratio of 1 to 10 mol of the base to 1 mol of the compound of the formula (5), and a ratio of 1 to 5 mol of the compound of the formula (6). It is.

 The reaction temperature of the reaction is usually in the range of 120 to 100 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

After completion of the reaction, the compound represented by the formula (7) is isolated by pouring the reaction mixture into water, extracting the organic solvent, and performing a post-treatment operation such as drying and concentration of the organic layer. Can be. The isolated compound represented by the formula (7) can be further purified by operations such as chromatography and recrystallization. Process ((1) 1 3) The compound represented by the formula (8) can be produced by reacting the compound represented by the formula (7) with hydrogen in the presence of a hydrogenation catalyst.

 The reaction is usually performed in a hydrogen atmosphere, usually in the presence of a solvent.

 Examples of the solvent used in the reaction include alcohols such as methanol, ethanol, and propanol, esters such as ethyl acetate and butyl acetate, tetrahydrofuran, ethers such as 1,4-dioxane, and mixtures thereof. Is mentioned. Examples of the hydrogenation catalyst used in the reaction include transition metal compounds such as palladium carbon, palladium hydroxide, Raney nickel®, and platinum oxide.

 The amount of the hydrogenation catalyst used in the reaction is usually 0.001 to 0.5 mol per 1 mol of the compound represented by the formula (7).

 The reaction is usually performed under a hydrogen atmosphere at 1 to 100 atm.

 The reaction can be carried out in the presence of an acid (such as hydrochloric acid) if necessary.

 The reaction temperature of the reaction is usually in the range of 120 to 100 ° C., and the reaction time is usually 0.20.

The range is 1-2 hours.

 After completion of the reaction, the compound represented by the formula (8) can be isolated by performing post-treatment operations such as filtering the reaction mixture and drying and concentrating the filtrate. The isolated compound represented by the formula (8) can be further purified by operations such as chromatography and recrystallization. Process ((1)-4)

 The compound represented by the formula (10) can be produced by reacting a compound represented by the formula (8) with a compound represented by the formula (9).

 The reaction is carried out in the presence or absence of a solvent, usually in the presence of a base.

 Examples of the solvent used for the reaction include 1,4-dioxane, tetrahydrofuran, ethers such as ethylene glycol dimethyl ether and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane and octane, and toluene. And aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as ethyl benzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, N, N-dimethylformamide and the like Examples include acid amides, sulfoxides such as dimethyl sulfoxide, and mixtures thereof.

Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diaza Tertiary amines such as bicyclo [5.4.0] pendec 7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine Group compounds.

 The amount of the reagent used in the reaction is usually 1 to 10 mol of the base and 1 to 5 mol of the compound of the formula (9) per 1 mol of the compound of the formula (8). is there.

 The reaction temperature of the reaction is usually in the range of 0 to 100 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

 After the completion of the reaction, the compound represented by the formula (10) can be isolated by performing post-treatment operations such as adding an organic solvent to the reaction mixture, if necessary, followed by filtration and concentration of the filtrate. . The isolated compound represented by the formula (10) can be further purified by an operation such as distillation, chromatography, and recrystallization. Process ((1) 1-5)

 The compound represented by the formula (11) can be produced by reacting the compound represented by the formula (10) with water in the presence of a base.

 The reaction is usually performed in the presence of water and an organic solvent.

 Examples of the organic solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether; aromatic hydrocarbons such as toluene and xylene; Examples include halogenated hydrocarbons such as benzene, nitriles such as acetonitrile and ptyronitrile, alcohols such as methanol, ethanol, and propanol, and mixtures thereof.

 Examples of the base used in the reaction include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide.

 The amount of the base used in the reaction is usually 1 to 10 mol per 1 mol of the compound represented by the formula (10).

 The reaction temperature of the reaction is usually in the range of 0 to 150, and the reaction time is usually in the range of 0.1 to 24 hours.

After the reaction is completed, acidic water (hydrochloric acid or the like) is added to the reaction mixture, and the mixture is extracted with an organic solvent, and the organic layer is dried and concentrated to perform a post-treatment operation, thereby obtaining the compound represented by the formula (11). Can be isolated. The isolated compound represented by the formula (11) is It can be further purified by chromatography, recrystallization, etc., but can be used as it is in the reaction of the next step. Process ((1)-6)

 The compound represented by the formula (12) can be produced by reacting the compound represented by the formula (11) with a chlorinating agent.

 The reaction is performed in the presence or absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and tert-butyl methyl ether; aliphatic hydrocarbons such as hexane, heptane and octane; toluene; Examples include aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as benzene, and mixtures thereof.

 Examples of the chlorinating agent used in the reaction include thionyl chloride, oxalyl chloride and phosphorus oxychloride.

 The amount of the reagent used in the reaction is such that the chlorinating agent is usually used in a proportion of 1 to 100 mol per 1 mol of the compound represented by the formula (11).

 The reaction temperature of the reaction is usually in the range of 30 to 150 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

 After completion of the reaction, the compound represented by the formula (12) can be isolated by performing an operation such as concentration of the reaction mixture as it is. The isolated compound represented by the formula (12) is used as it is in the reaction of the next step. Process ((1) -7)

 The compound represented by the formula (2-1) can be produced by reacting the compound represented by the formula (12) with the compound represented by the formula (13).

 The reaction is usually performed in the presence of a solvent and in the presence of a base.

Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether; and aliphatic hydrocarbons such as hexane, heptane, and octane. , Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as benzene benzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butylonitrile, N, N— Acid amides such as dimethylformamide, dimethyls Sulfoxides such as rufoxide and mixtures thereof.

 Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] pendec-7-ene, 1,5 —Diazabicyclo [4.3.0] non— Tertiary amines such as 5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.

 The amount of the reagent used in the reaction is usually 1 to 10 mol of the base to 1 mol of the compound represented by the formula (12), and 1 to 5 mol of the compound represented by the formula (13) usually. It is.

 The reaction temperature of the reaction is usually in the range of 20 to 100 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

 After the completion of the reaction, (i) the reaction mixture is poured into water and extracted with an organic solvent. After washing, drying and concentration, or (ii) a post-treatment operation such as adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration, yields the formula (2) — The compound of 1) can be isolated. The isolated compound represented by the formula (2-1) can be further purified by a technique such as chromatography and recrystallization. Process ((1) i 8)

 The compound represented by the formula (2-1) can also be produced by reacting the compound represented by the formula (11) with the compound represented by the formula (13) in the presence of a dehydrating agent. it can.

 The reaction is usually performed in the presence of a solvent.

 Examples of the solvent used in the reaction include acid amides such as N, N-dimethylformamide, sulfoxides such as dimethylsulfoxide, nitrogen-containing aromatic compounds such as pyridine and quinoline, and mixtures thereof.

 Examples of the dehydrating agent used in the reaction include carbodiimides such as 1-ethyl-3- (3-dimethylaminopropyl) carbopimide hydrochloride (hereinafter, referred to as WSC) and 1,3-dicyclohexyl carbopimide.

The amount of the reagent used in the reaction is such that the compound represented by the formula (13) is usually in a ratio of 1 to 3 mol per 1 mol of the compound represented by the formula (11), and the dehydrating agent is usually used. The ratio is 1 to 5 mol.

 The reaction temperature of the reaction is usually in the range of 0 to 140 ° C., and the reaction time is usually 0.:! ~ 24 hours range.

 After completion of the reaction, (i) the reaction mixture is poured into water and extracted with an organic solvent. After washing, drying and concentration, or (ii) a post-treatment operation such as adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration, the formula (2) — The compound represented by 1) can be isolated. The isolated compound represented by the formula (2-1) can be further purified by a technique such as chromatography and recrystallization. Process ((1) -1 9)

 The compound represented by the formula (2-2) is composed of a compound represented by the formula (2-1) and 2,4-bis (4-methoxyphenyl) -11,3-dithia1-2,4-diphosphethane-12,4 —It can be produced by reacting with disulfide (hereinafter, referred to as Lawson's reagent).

 The reaction is usually performed in the presence of a solvent.

 Examples of the solvent used in the reaction include 1,4-dioxane, tetrahydrofuran, ethers such as ethylene glycol dimethyl ether and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane; Aromatic hydrocarbons such as benzene and xylene; halogenated hydrocarbons such as chlorobenzene; nitriles such as acetonitrile and ptyronitrile; sulfoxides such as dimethylsulfoxide; and mixtures thereof.

 The amount of the Lawson reagent used in the reaction is usually 1 to 10 mol per 1 mol of the compound represented by the formula (2-1).

 The reaction temperature of the reaction is usually in the range of 50 to 150 ° C, and the reaction time is usually in the range of 0.5 to 24 hours.

After completion of the reaction, the compound represented by the formula (2-2) is isolated by performing post-treatment operations such as pouring water into the reaction mixture, extracting with an organic solvent, and drying and concentrating the organic layer. can do. The isolated compound represented by the formula (2-2) can be further purified by an operation such as chromatography and recrystallization. The compound represented by the formula (2-3) can also be produced according to the following scheme.

 (2-3)

[Wherein, R ¹ , R ² , R ⁴ and R ⁵ represent the same meaning as described above. ] Process ((2) -1)

 'Is the compound represented by the formula (15) a compound described in, for example, Tetrahedron Letters, vol. 25, No. 41, p. 4583-4586, 1984, or US Pat. Alternatively, it can be produced according to the methods described in these documents. The compound represented by the formula (15) can be used for the reaction of the next step after isolation, but can also be used for the reaction of the next step without isolation. In addition, the compound isolated in the form of a hydrochloride of the compound represented by the formula (15) can be used in the reaction of the next step. Process ((2) — 2)

The compound represented by the formula (2-3) can be produced by reacting the compound represented by the formula (11) with the compound represented by the formula (15) in the presence of a dehydrating agent. The reaction is usually performed in the presence of a solvent.

 Examples of the solvent used in the reaction include acid amides such as N, N-dimethylformamide, sulfoxides such as dimethylsulfoxide, nitrogen-containing aromatic compounds such as pyridine and quinoline, and mixtures thereof.

 Examples of the dehydrating agent used in the reaction include WSC, carbodiimides such as 1,3-dicyclohexyl carbodiimide.

 The amount of the reagent used in the reaction is such that the compound represented by the formula (15) is usually in a ratio of 1 to 3 mol per 1 mol of the compound represented by the formula (11), and the dehydrating agent is usually used; ! To 5 moles.

 The reaction temperature of the reaction is usually in the range of 0 to 140 ° C., and the reaction time is usually in the range of 0.1 to 24 hours.

 After the completion of the reaction, (i) the reaction mixture is poured into water and extracted with an organic solvent. If necessary, the organic layer is diluted with acidic water (dilute hydrochloric acid or the like) and / or basic water (sodium hydrogen carbonate aqueous solution or the like). After washing, drying and concentration, or (ii) a post-treatment operation such as adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration, the formula (2) — The compound of 3) can be isolated. The isolated compound represented by the formula (2-3) can be further purified by operations such as chromatography and recrystallization. Process ((2) — 3)

 The compound represented by the formula (2-3) can also be produced by reacting the compound represented by the formula (15) with the compound represented by the formula (12) in the presence of a base. The reaction is usually performed in the presence of a solvent.

 Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, and aliphatic hydrocarbons such as hexane, heptane, and octane. , Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as benzene benzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, N, N— Acid amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide; and mixtures thereof.

Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diaza Tertiary amines such as bicyclo [5.4.0] pentadec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine Group compounds.

 The amount of the reagent used in the reaction is usually 1 to 10 mol of the base per 1 mol of the compound represented by the formula (12), and 1 to 5 mol of the compound represented by the formula (15) usually. It is.

 The reaction temperature of the reaction is usually in the range of 20 to 100 ° C, and the reaction time is usually in the range of 0.1 to 24 hours.

 After completion of the reaction, (i) the reaction mixture is poured into water and extracted with an organic solvent, and the organic layer is optionally treated with acidic water (dilute hydrochloric acid, etc.) and / or basic water (sodium hydrogen carbonate aqueous solution, etc.) After washing, drying and concentration, or (ii) a post-treatment operation such as adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration, yields the formula (2) — The compound of 3) can be isolated. The isolated compound represented by the formula (2-3) can be further purified by a technique such as chromatography and recrystallization. The compound represented by the formula (13) can be produced, for example, by reacting a compound represented by the formula (16) with a cyanide, an ammonium salt and an ammonium salt.

 (16) (13)

[Wherein, R ¹ and R ² represent the same meaning as described above. ]

 The reaction is usually performed in the presence of a solvent.

 Examples of the solvent used in the reaction include alcohols such as methanol, ethanol, 2-port alcohol, water, and mixtures thereof.

 Examples of the cyanide compound used in the reaction include sodium cyanide and potassium cyanide.

Examples of the ammonium salt used in the reaction include ammonium chloride and ammonium bromide. The amount of the reagent used in the reaction is usually 1 to 5 mol of the cyanide, 1 to 5 mol of the ammonium salt usually, and ammonia is usually 1 mol of the compound of the formula (16). The ratio is from 1 mol to a large excess.

 The reaction temperature of the reaction is usually in the range of 110 to 100 ° C, and the reaction time is usually in the range of 1 to 50 hours.

 After completion of the reaction, the compound represented by the formula (13) can be isolated by performing an operation such as adding an organic solvent to the reaction mixture, extracting the mixture, and concentrating the organic layer. The hydrochloride of the compound represented by the formula (13) can be isolated by collecting crystals formed by adding an organic solvent and hydrochloric acid to the compound represented by the formula (13) by filtration. Hereinafter, the production of the compound (I) used in the composition of the present invention will be described in more detail. Production Example 1 [Production Example of Compound (I-1)]

 3- (4-Hydroxy-3-methoxyphenyl) 50 g of acrylylic acid, 0.5 g of 5% palladium carbon, about 0.05 g of 36% hydrochloric acid, 250 ml of ethanol and 100 ml of tetrahydrofuran are mixed and mixed under a hydrogen atmosphere. Stirred. After the absorption of hydrogen gas ceased, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain 52 g of 3- (4-hydroxy-3-methoxyphenyl) propionic acid.

 3- (4-hydroxy-3-methoxy, phenyl) propionic acid

Ή-NMR (CDC1 _3! TMS) Delta (ppm): 6.83 (1H, dd, J = 7.3Hz, 0.8Hz), 6.70-6.81 (2Η, m), 3.86 (3Η, s), 2.88 (2Η, t) , J = 7.6Hz), 2.65 (2H, t, J = 7.6Hz)

A mixture of 50 g of 3- (4-hydroxy-13-methoxyphenyl) propionic acid, 50 ml of pargyi bromide, 88 g of potassium carbonate and 500 ml of acetonitrile was stirred at 80 for 3 hours. Thereafter, the reaction mixture was allowed to cool to around room temperature, ethyl acetate was added, and the mixture was filtered. The filtrate was concentrated under reduced pressure to obtain 67 g of 2-propynyl 3- {3-methoxy-4- (2-propynyloxy) phenyl} propionate.

 3- {3-methoxy-41- (2-propieroxy) phenyl} 2-propynyl propionate

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 6.96 (1H, d, J = 7.8Hz), 6.68-6.75 (2H, m), 4.73 (2H, d, J = 2.2Hz), 4.68 (2H, d, J = 2.2Hz), 3.87 (3H, s), 2.93 (2H, t, J = 7.3Hz), 2.67 (2H, , T, J = 7.3Hz), 2.47-2.50 (2H, m)

3- {3-methoxy-41- (2-propynyloxy) phenyl} 67 g of 2-propynyl propionate, 8.08 g of lithium hydroxide, 400 ml of tetrahydrofuran and 20 Oral of water are mixed at 65 ° C. Stir for 3 hours. Thereafter, the reaction mixture was allowed to cool to around room temperature, water was added, and the mixture was concentrated under reduced pressure. To the residue was added 5% hydrochloric acid, and extracted three times with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to obtain 51 g of 3- {3-methoxy-1- (2-propynyloxy) phenyl} propionic acid.

3 - {3- methoxy 4 one (2-propynyl O carboxymethyl) Hue sulfonyl} propionic acid _{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 6.96 (1H, d, J = 8.2Hz), 6.73- 6.75 (2Η, m), 4.73 (2Η, d, J = 2.4Hz), 3.85 (3H, s), 2.91 (2H, t, J = 8Hz), 2.67 (2H, t, J = 8Hz), 2.49 ( (1H, t, J = 2.4Hz)

3- {3-methoxy-41- (2-propynyloxy) phenyl} 12.7 g of propionic acid, 4.3 ml of thionyl chloride, 10 Oml of toluene and about 0.05 g of N, N-dimethylformamide Then, the mixture was stirred at 80 ° C for 30 minutes. Thereafter, the reaction mixture cooled to near room temperature was concentrated under reduced pressure to obtain 14.6 g of 3- {3-methoxy-41- (2-propynyloxy) phenyl} propionate chloride.

 3-{3-Methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride

_{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 6.97 (1H, d, J = 8.8Hz), 6.72-6.74 (2Η, m), 4.73 (2H, d, J = 2.4Hz), 3.87 ( 3H, s), 3.19 (2H, t, J = 7.2Hz), 2.99 (2H, t, J = 7.2Hz), 2.49 (1H, t, J = 2.4Hz)

3- {3-Methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride 200 mg, 4-methylbenzylamine 99 mg, triethylamine 0.45 ml and tetrahydrofuran 5 ml are mixed and stirred at room temperature for 1 hour. did. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography. Thus, 204 mg of N— (4-methylbenzyl) -3- (3-methoxy-14- (2-propieroxy) phenyl} propanamide was obtained.

lH-賺(CDC1 _3, TMS) delta (ριη): 7.11 (2H, d, J = 8.0 Hz), 7.05 (2H, d, J = 8.0 Hz), 6.94 (1H, d, J = 8.0 Hz), 6.71-6.75 (2H, m), 5.53 (1H, br.s), 4.73 (2H, d, J = 2.4 Hz), 4.36 (2H, d, J = 5.5 Hz), 3.82 (3H, s), 2.94 (2H, t, J = 7.5 Hz), 2.46-2.50 (3H, m), 2.32 (3H, s) Production example 2 [Production example of compound (1-2)]

 3- {3-Methoxy-41- (2-propynyloxy) phenyl} Propionic acid chloride 632 mg, 3,4-dimethylpentylamine 338 mg, triethylamine 379 mg and tetrahydrofuran 7 ml are mixed, and mixed at room temperature. Stirred for hours. Thereafter, water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane to give 83 mg of N- (3,4-dimethylbenzyl) -13- {3-methoxy-41- (2-propynyloxy) phenyl} propanamide.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.06 (1H, d, J = 7.5 Hz), 6.88-7.00 (3H, ffl), 6.75 (1H, d, J = 1.9Hz), 6.73 (1H , dd, J = 8.0 Hz, 1.9 Hz), 5.51 (1H, br.s), 4.73 (2H, d, J = 2.4 Hz), 4.34 (2H, d, J = 5.3 Hz), 3.82 (3H, s ), 2.94 (2H, t, J = 7.3 Hz), 2.44-2.51 (3H, m), 2.23 (6H, s) Production example 3 [Production example of compound (I-13)]

 N- (4-Methylbenzyl) -3- 3- {3-methoxy-41- (2-propynyloxy) phenyl} Propanamide 0.40 g, Mouth-Single's reagent 0.53 g and tetrahydrofuran 1 Oml And stirred at 65 C for 3 hours. Thereafter, the reaction mixture was cooled and concentrated under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed sequentially with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was purified by a silica gel column to give 0.38 g of N- (4-methylbenzyl) -13- {3-methoxy-4- (2-propynyloxy) phenyl} propanethioamide.

_{^{! H-NMR (CDCI 3,}} TMS) delta (ppm): 7.12 (2H, d, J = 7.8 Hz), 6.91-7.02 (3H, m), 6.92 (1H, d, J = 8.2 Hz), 6.75 (1H, d, J = 1.9 Hz), 6.72 (1H, dd, J = 8.2 Hz, 1.9 Hz), 4.72 (2H, d, J = 2 Hz), 4.66 (2H, d, J = 4.8 Hz), 3.82 (3H, s),

3.08 (2H, t, J = 7.2 Hz), 2.97 (2H, t, J = 7.2 Hz), 2.48 (1H, t, J = 2 Hz), 2.33

(3H, s) Production Example 4 [Production Example of Compound (I-14)]

 N- (3,4-dimethylpentyl) 1-3- {3-methoxy-141- (2-propynyloxy) phenyl} Propanamide 0.43 g and Lawson's reagent 0.36 g from Production Example 3 In a similar manner, 34.5 mg of N- (3,4-dimethylpentyl) -13- {3-methoxy-14- (2-propieroxy) phenyl} propanethioamide) was obtained.

 Ή-NMR (CDC, TMS) Delta (ppm): 7.08 (1H, d, J = 7.8Hz), 7.01 (1H, br.s), 6.84-6.96 (3H, m), 6.76 (1H, d, J = 1.9 Hz), 6.72 (1H, dd, J = 8.1 Hz, 1.9 Hz), 4.72 (2H, d, J = 2.2 Hz), 4.63 (2H, d, J = 4.8 Hz), 3.82 (3H, s) , 3.08 (2H, t, J = 7.3 Hz), 2.91 (2H, t, J = 7.3 Hz), 2.47 (1H, t, J = 2.4 Hz), 2.43 (3H, s), 2.23 (3H, s) Production Example 5 [Production Example of Compound (I-I-5)]

 0.33 g of 2-amino-2-phenylacetonitrile hydrochloride, 0.88 ml of diisopropylethylamine and 1 Oml of tetrahydrofuran are mixed, and the mixture is mixed at 0 to 5 ° C with 3- {3-methoxy-4- (2-propynyloxy). A mixture of 0.50 g of phenyl} propion chloride and 3 ml of tetrahydrofuran was added, followed by stirring at room temperature for 1 hour. Thereafter, the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by a silica gel column to obtain 0.39 g of N- (1-phenyl-1-cyanomethyl) -3- (3-methoxy-4- (2-propynyloxy) phenyl} propanamide. Was.

_{lH-NMR (CDC1 3, TMS} ) delta (ppm): 7.38-7.41 (3H, m), 7.31-7.34 (2H, m), 6.95 (1H, d, J = 8.2 Hz), 6.70-6.73 (2H, m), 6.10 (1H, d, J = 8.5 Hz), 5.80 (1H, br.d), 4.73 (2H, d, J = 2.4 Hz), 3.83 (3H, s), 2.96 (2H, t, J = 7.3 Hz), 2.48-2.62 (3H, m) Production Example 6 [Production Example of Compound (I-I-6)]

 2.2 g of 2-amino 2- (4-methylphenyl) acetonitrile hydrochloride was obtained from 5.0 g of 4-methylbenzaldehyde in the same manner as in Production Example 16.

Ή-NR (CD ₃ S0CD ₃ , TMS) Delta (ppm): 9.51 (3H, br.s), 7.54 (2H, d, J = 8.2 Hz), 7.35 (2H, d, J = 8.2 Hz), 5.90 (1H, s), 2.35 (3H, s)

Reaction of 0.40 g of 2-amino-1- (4-methylphenyl) acetonitrile hydrochloride with 0.50 g of 3- {3-methoxy-4- (2-propynyloxy) phenyl} propion chloride This yielded 0.54 g of N- {111- (4-methylphenyl) 1-11-cyanomethyl} -13- {3-methoxy-41- (2-propieroxy) phenyl} propanamide.

_{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 7.19-7.23 (4H, m), 6.94 (1H, d, J = 7.8 Hz), 6.70-6.72 (2H,), 6.04 (1H, d, J = 8.2 Hz), 5.75 (1H, br.d, J = 8.2 Hz), 4.73 (2H, d, J = 2.2 Hz), 3.83 (3H, s), 2.95 (2H, t, J = 7.5 Hz) , 2.46-2.60 (3H, m), 2.36 (3H, s) Production Example 7 [Production Example of Compound (I-17)]

 0.27 g of 2-amino-2- (4-methylphenyl) acetonitrile hydrochloride, 0.30 g of 3- (3-methoxy-4-ethoxyethoxy) propionic acid and 5.8 ml of pyridine were mixed. 244 mg of WSC was added to the mixture, and the mixture was stirred at room temperature for 1.5 hours. Thereafter, water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water and saturated saline, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.24 g of N— {1- (4-methylphenyl) -11-cyanomethyl} -3- (3-methoxy-4-ethoxyethoxyphenyl) propanamide.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.17-7.22 (4H, m), 6.77 (1H, d, J = 7.9 Hz), 6.67-6.70 (2H, m), 6.04 (1H, d, J = 7.9 Hz), 5.75 (1H, br.d, J = 7.9 Hz), 4.06 (2H, q, J = 7.1 Hz), 3.83 (3H, s), 2.94 (2H, t, J = 7.1 Hz) , 2.46-2.59 (2H, m), 2.36 (3H, s), 1.45 (3H, t, J = 7.1 Hz) Production Example 8 [Production Example of Compound (I-18)] 3- {3-Methoxy-4- (2-prodenyloxy) phenyl} Propionic acid 30 g of chloride and 0.16 g of 4-ethylbenzylamine are reacted in the same manner as in Production Example 2. As a result, 0.40 g of N- (4-ethylbenzyl) -3- (3-methoxy-41- (2-propynyloxy) phenyl} propanamide was obtained. _{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.08-7.15 (4H, m), 6.94 (1H, d, J = 8.1 Hz), 6.72-6.75 (2H, m), 5.55 (1H, br. s), 4.73 (2H, d, J = 2.2 Hz), 4.37 (2H, d, J = 5.6 Hz), 3.82 (3H, s), 2.95 (2H, t, J = 7.3 Hz), 2.63 (2H, q, J = 7 Hz), 2.47-2.50 (3H, m), 1.22 (3H, t, J = 7 Hz) Production Example 9 [Production Example of Compound (I-19)]

 (4) 0.53 g of monoethylbenzaldehyde, 0.55 ml of trimethylsilyl cyanide and 0.03 g of zinc iodide were mixed, and the mixture was stirred at room temperature for 15 minutes.After that, 10 ml of a 10% ammonia methanol solution was added thereto. And stirred at 40 C for 2 hours. The reaction mixture cooled to room temperature was concentrated under reduced pressure, and 0.68 ml of diisopropylethylamine and 10 ml of tetrahydrofuran were added to the obtained residue, and 3- {3-methoxy-4- (2-propynyloxy) was added thereto. A mixed solution of 0.50 g of [phenyl] propion chloride and 3 ml of tetrahydrofuran was added at 0 to 5 ° C, and the mixture was stirred at room temperature for 1 hour. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give N- {1- (4-ethylphenyl) 1-11-cyanomethyl} -3-{3-methoxy-41- (2-propynyloxy) phenyl} propanamide 0 73 g were obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.20-7.25 (4H, m), 6.94 (1H, d, J = 7.8 Hz), 6.70-6.72 (2H, m), 6.04 (1H, d, J = 8.3 Hz), 5.83 (1H, br.d), 4.73 (2H, d, J = 2.4 Hz), 3.82 (3H, s), 2.96 (2H, t, J = 7.6 Hz), 2.66 (2H, q, J = 7.6 Hz), 2.46-2.58 (3H, m), 1.23 (3H, t, J = 7.6 Hz) Production Example 10 (Production example of compound (I-I-10)).

3- {3-methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride 200 mg, 4-cyclobenzyl benzylamine 112 mg, triethylamine 0.17 ml and tetrahydrofuran 5 ml were mixed and stirred at room temperature for 30 minutes. . That Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane to obtain 212 mg of N- (4-chlorobenzyl) 13- {3-methoxy-4- (2-propynyloxy) phenyl} propanamide.

_{^{! H-NMR (CDC1 3,}} TMS) Del evening (ppm): 7.25-7.27 (2H, m), 7.05 (2H, d, J = 8.2

Hz), 6.94 (1H, d, J = 8.0 Hz), 6.71-6.74 (2H, m), 5.59 (1H, br.s), 4.73 (2H, d, J = 2.5 Hz), 4.36 (2H, d , J = 5.9 Hz), 3.82 (3H, s), 2.94 (2H, t, J = 7.5 Hz), 2.45-2.52 (3H, m) Production example 1 1 [Production example of compound (I-11)]

 3- {3-methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride 30 Omg and 3,4-dichlorobenzamine 209 mg were reacted in the same manner as in Production Example 10 to give N — (3,4-dichlorobenzyl) —3- {3-methoxy-41- (2-propynyloxy) phenyl} propanamide 43 Omg was obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.35 (1H, d, J-8.2 Hz), 7.28 (1H, d, J = 1.9 Hz), 6.93-6.99 (2H, m), 6.71-6.74 (2H, m), 5.64 (1H, br.s), 4.73 (2H, d, J = 2.4 Hz), 4.34 (2H, d, J = 6.1 Hz), 3.83 (3H, s), 2.95 (2H, t, J = 7.5 Hz), 2.48-2.54 (3H, in) Production Example 12 [Production Example of Compound (I-I-12)]

3- {3-ethoxy-4-1- (2-propieroxy) phenyl} propionic acid chloride 81 g, 4-cyclohexylbenzylamine 0.46 g, triethylamine 0.64 ml, and tetrahydrofuran 1 Oml are mixed, and room temperature is mixed. For 20 minutes. Thereafter, water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography. Thus, 0.79 g of N- (4-cyclobenzyl) -3- (3-ethoxy-14- (2-propieroxy) phenyl} propanamide was obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.24-7.26 (2H, m), 7.04-7.06 (2H, m), 6.95 (1H, d, J = 8.0 Hz), 6.70-6.74 (2H, m), 5.60 (1H, br.s), 4.74 (2H, d, J = 2.4 Hz), 4.35 (2H, d, J = 5.8 Hz), 4.02 (2H, q, J = 7 Hz), 2.92 ( 2H, t, J = 7.5 Hz), 2.27-2.51 (3H, m), 1.42 (3H, t, J = 7 Hz) Production Example 13 [Production Example of Compound (I-13)]

 N- (4-cyclobenzyl) 1-3- {3-methoxy-14- (2-propynyloxy) phenyl} propanamide 0.59 g, Lawson's reagent 0.67 g and tetrahydrofuran 1 Oml And stirred at 65 ° C. for 3 hours. Thereafter, the reaction mixture was cooled and concentrated under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed sequentially with 3% aqueous sodium hydroxide, 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel gel chromatography to give N— (4-chlorobenzyl) —3- {3-methoxy-41- (2-propynyloxy) phenyl} propanethioamide. .59 g were obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.26-7.29 (2H, m), 6.99-7.06 (3H, m), 6.92 (1H, d, J = 8.0 Hz), 6.70-6.75 (2H, m), 4.73 (2H, d, J = 2 Hz), 4.70 (2H, d, J = 5.3 Hz), 3.82 (3H, s), 3.09 (2H, t, J = 7.2 Hz), 2.97 (2H, t, J = 7.2 Hz), 2.49 (1H, t, J = 2 Hz) Production Example 14 [Production Example of Compound (I-I-14)]

N- (3,4-dichloro mouth benzyl) 1-3- {3-methoxy-4- (2-propynyloxy) phenyl} propanamide 0.40 g, Lawesson's reagent 0.45 g and tetrahydrofuran 15 ml The mixture was stirred at 65 ° C. for 3 hours. Thereafter, the reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed sequentially with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 0.42 g of N- (3,4-dichlorobenzyl) -13- {3-methoxy-4- (2-propynyloxy) phenyl} propanethioamide. Obtained. _{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.34 (1H, d, J = 8.2 Hz), 7.28 (1H, d, J = 2.2 Hz), 7.12 (1H, br.s), 6.89-6.99 (2H, m), 6.71-6.75 (2H, m) 4.70- • 4.73 (4H, m), 3.82 (3H, s), 3.09 ( 2H, t, J = 7.5 Hz), 2.96 (2H, t, J = 7.5 Hz), 2.49 (1H, t, J = 2.1 Hz) Production Example 15 [Production Example of Compound (Il5)]

 By reacting 425 mg of N— (4-cyclohexylbenzyl) —3- {3-ethoxy-4- (2-propynyloxy) phenyl} propanamide with 33 Omg of Lawesson's reagent in the same manner as in Preparation Example 13 There were obtained 360 mg of N- (4-cyclobenzyl) -3- (3-ethoxy-41- (2-propynyloxy) phenyl} propanethioamide.

_{'H-NMR (CDC1 3,} TMS) delta (ppm): 7.41 (1H, br.s), 7.25 (2H, d, J = 8.4Hz), 7.01 (2H, d, J = 8.2 Hz), 6.91 ( 1H, d, J = 8.2 Hz), 6.73. (1H, d, J = 1.9 Hz), 6.69 (1H, dd, J = 8.0 Hz, 1.9 Hz), 4.67-4.71 (4H, m), 3.99 (2H , q, J = 7.0 Hz), 3.05 (2H, t, J = 7.1 Hz), 2.91 (2H, t, J = 7.1 Hz), 2.48 (1H, t, J = 2.4 Hz), 1.40 (3H, t , J = 6.9 Hz) Production Example 16 [Production Example of Compound (I-I-16)]

 A mixture of 22 g of ammonium chloride, 12 g of sodium cyanide and 30 Oml of a 28% aqueous ammonia solution was gradually added at 0 ° C, and 30 g of 4-cyclobenzaldehyde was gradually added. After the reaction mixture was stirred at 0 ° C. for 1 hour and at room temperature for 8 hours, water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile 30 Om1, and 25 ml of 36% hydrochloric acid was gradually mixed at 0 ° C. The resulting solid was collected by filtration, washed with acetonitrile, tert-butyl methyl ether and hexane, and dried under reduced pressure to obtain 23 g of 2-amino-2- (4-phenylphenyl) acetonitrile hydrochloride. Obtained.

Ή-NMR (CD ₃ SOCD3, TMS) Delta (ppm): 9.54 (3H, br.s), 7.68-7.72 (2H, m), 7.61-7.64 (2H, m), 5.98 (1H, s) 2— Amino-2- (4-chlorophenyl) acetonitrile hydrochloride 8. Og, 17 ml of diisopropylpropyrylamine and 15 Oml of tetrahydrofuran are mixed, and mixed at 0-5 ° C with 3— {3— Methoxy 41 (2-propieroxy) A mixture of 8.3 g of propionate chloride and 30 ml of tetrahydrofuran was added, and the mixture was stirred at room temperature for 1 hour. Thereafter, the reaction mixture was concentrated under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water, a saturated aqueous solution of sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give N— {1- (4-chlorophenyl) 1-11-cyanomethyl} -3--3- {3-methoxy-4-1 (2-propynyloxy) phenyl} propanamide 8.6 g was obtained.

Ή-NMR (CD ₃ S0CD ₃ , TMS) Delta (ppm): 7.35-7.38 (2H, m), 7.22-7.24 (2H, ffl), 6.94 (1H, d, J = 7.8Hz), 6.69—6.72 ( 2H, m), 6.08 (1H, d, J = 8.5Hz), 5.87 (1H, br.d, J = 8.5Hz), 4.73 (2H, d, J = 2.4Hz), 3.82 (3H, s), 2.95 (2H, t, J = 7.3Hz), 2.48-2.63 (3H, m) Production Example 17 (Production Example of Compound (I-17))

 By reacting 406 mg of 2-amino-2- (4-phenylphenyl) acetonitrile hydrochloride with 448 mg of 3- (3-methoxy-4-ethoxyethoxy) propionic acid in the same manner as in Production Example 7, N- {11- (4-chlorophenyl) -111-cyanomethyl} -3- (3-methoxy-4-ethoxyphenyl) propanamide 30 Omg was obtained.

lH-NMR (CDCI3, TMS) Delta (ppm): 7.20-7.37 (4H, m), 6.65-6.78 (3H, m), 6.09 (1H, d, J = 8.3 Hz), 5.83 (1H, br.d ), 4.06 (2H, q, J = 7.0 Hz), 3.83 (3H, s), 2.93 (2H, t, J = 7.1 Hz), 2.45-2.64 (2H, m), 1.45 (3H, t, J = 7.0 Hz) Production Example 18 [Production example of compound (I-18)]

3- {3-methoxy-4- (2-propieroxy) phenyl} propionic acid chloride 20 Omg, 4-bromobenzylamine hydrochloride 176 mg, triethylamine 29 ml and tetrahydrofuran 5 mi, mixed at room temperature for 30 minutes Stirred. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution, and washed with magnesium sulfate. And concentrated under reduced pressure. The residue was washed with hexane to obtain 177 mg of N- (4-bromobenzyl) 13- {3-methoxy-14- (2-propieroxy) phenyl} propanamide.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppni): 7.41 (2H, d, J = 8 Hz), 7.00 (2H, d, J = 8 Hz), 6.94 (1H, d, J = 8.0 Hz), 6,71-6.74 (2H, m), 5.59 (1H, br.s), 4.74 (2H, d, J = 2.4 Hz), 4.34 (2H, d, J = 5.8 Hz), 3.82 (3H, s) , 2.94 (2H, t, J = 7.5 Hz), 2.49-2.52 (3H, m) Production Example 19 [Production Example of Compound (I-19)]

 N— (4-bromobenzyl) —3- {3-methoxy-41- (2-propynyloxy) phenyl} Propanamide 66 Omg and Lawson's reagent 435 5 mg are reacted in the same manner as in Example 13. As a result, 463 mg of N- (4-bromobenzyl) 1- {3-methoxy-4- (2-propynyloxy) phenyl} propane amide was obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.39-7.43 (2H, m), 7.28 (1H, br.s), 6.95 (2H, d, J = 8.4 Hz), 6.90 (1H, d, J = 8.2 Hz), 6.74 (1H, d, J = 1.7 Hz), 6.70 (1H, dd, J = 7.9 Hz, 2.0 Hz), 4.71 (2H, d, J = 2.4 Hz), 4.68 (2H, d , J = 5.3 Hz), 3.79 (3H, s), 3.07 (2H, t, J = 7.1 Hz), 2.93 (2H, t, J = 7.1 Hz), 2.49 (1H, t, J = 2.4 Hz) Example 20 [Production Example of Compound (I-20)]

 1.5 g of 2-amino-2- (4-bromophenyl) acetonitrile hydrochloride was obtained from 5.O g of 4-bromobenzaldehyde.

Ή-NMR (CD ₃ S0CD ₃ , TMS) Delta (ppm): 9.49 (3H, br.s), 7.75-7.77 (2H, m), 7.61-7.64 (2H, m), 5.96 (1H, s)

0.73 g of 2-amino-2- (4-bromophenyl) acetonitrile hydrochloride and 50 g of 3- {3-methoxy-41- (2-propieroxy) phenyl} propion chloride were prepared in the same manner as in Preparation Example 5. 0.67 g of N- {1- (4-bromophenyl) 1-1-cyanomethyl} —3- {3-methoxy-41- (2-propieroxy) phenyl} propanamide .

'H-NMR (CDC1 ₃ , TMS) Derby (ppm): 7.50-7.54 (2H, m), 7.15-7.17 (2H, m), 6.94 (1H, d, J = 8.0 Hz), 6.69-6.71 (2H, m), 6.07 (1H, d, J = 8.2 Hz), 5.92

(1H, br.d), 4.74 (2H, d, J = 2.2 Hz), 3.82 (3H, s), 2.95 (2H, t, J = 7.2 Hz), 2.47-2.62 (3H, m) Production example 21 [Production Example of Compound (I-21)]

 By reacting 0.36 g of 2-amino-2- (4-bromophenyl) acetonitrile hydrochloride with 0.30 g of 3- (3-methoxy-4-ethoxyethoxy) propionic acid in the same manner as in Production Example 7, 0.34 g of N- {1- (4-bromophenyl) -111-cyanomethyl} -3- (3-methoxy-4-ethoxy-phenyl) propanamide was obtained.

lH- Awakening: (CDC1 _3, TMS) delta (ppm): 7.51 (2H, d, J = 8.7 Hz), 7.15 (2H, d, J = 8.7 Hz), 6.75 (1H, d, J = 7.9 Hz), 6.66-- 6.70 (2H, m), 6.07 (1H, d, J = 8.3 Hz), 5.79 (1H, br.d J = 8.3 Hz), 4.06 (2H, q, J = 7.1 Hz), 3.83 (3H, s), 2.94 (2H, t, J = 7.1 Hz), 2.47-2.63 (2H, m), 1.46 (3H, t, J = 7.1 Hz) Production example 22 [Production example of compound (I-22)]

 A mixture of 31 g of aluminum chloride and 15 Oral of methylene chloride was ice-cooled, 30 g of ethyl oxalyl chloride was mixed, and the mixture was stirred under ice-cooling for 30 minutes. The obtained mixture was gradually added to a mixture of 22 g of indane and 200 ml of methylene chloride under ice-cooling, followed by stirring at room temperature for 1 hour.

Thereafter, the reaction mixture was gradually poured into ice water, and the organic layer was separated. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 37 g of a crude product of indane-5-yloxoethyl acetate.

_{^{1 H-NMR (CDC1 3,}} TMS) delta (ppm): 7.84 (1H, s), 7.78 (1H, d, J = 7,8Hz), 7.34 (1H, d, J = 7.8 Hz), 4.44 (2H , q, 1-7.1 Hz), 2.95-2.99 (4H, m), 2.09-2.17 (2H, m), 1.42 (3H, t, J-7.1 Hz) Indane-1 Crude product of 5-yloxoacetic acid ethyl ester 25 g, sodium borohydride (7.0 g) and ethanol (250 ml) was stirred at room temperature for 1 hour and then at 6 for 2 hours. Water was added to the reaction mixture, and the organic solvent was distilled off under reduced pressure. Thereafter, the pH was adjusted to 2 with 36% hydrochloric acid, and the mixture was extracted with black form. After the organic layer was washed with water and dried over magnesium sulfate, the organic solvent was distilled off under reduced pressure. Residue By washing with hexane, indane-5-ylethane-1,1,2-diol 11 was obtained.

_{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 7.22 (1H, s), 7.20 (1H, d, J = 7.7Hz), 7.11 (1H, d, 1 = 7.7 Hz), 4.78 (1H, dd, J = 8.2 Hz, 3.6 Hz), 3.62-3.75 (2H, m), 2.87-2.91 (4H, m), 2.5 (1H, br.s), 2.3 (1H, br.s), 2.03-2.10 A mixture of 11 g of a crude product of (2H, m) indane-5- ^ T-leutane-1,2-diol, 18 g of periodic acid, 10 Oml of water and 10 Oral of ethanol was stirred at room temperature for 12 hours. Water was added to the reaction mixture, extracted with ethyl acetate, washed twice with water, the organic solvent was distilled off under reduced pressure, and the residue was purified with a silica gel column to give indone-5-propanol. 8. 1 g was obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 9.95 (1H, s), 7.73 (1H, s), 7.65 (1H, dd, J = 7.7 Hz, 1.2 Hz), 7.36 (1H, d, J = 7.7 Hz), 2.97 (4H, t, J-7.5 Hz), 2.08-2.17 (2H, m) Indane-5-carboxaldehyde 8.1 g, hydroxylamine hydrochloride 4.3 g, sodium acetate 5. A mixture of 0 g, 25 ml of water and 10 Om1 of ethanol was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and extracted with tert-butyl methyl ether. After the organic layer was washed with water and saturated saline in this order, the organic solvent was distilled off under reduced pressure. The obtained residue was washed with hexane to obtain 6.3 g of indane-5-potassium lipoaldehyde oxime.

lH - thigh (CDC1 _3, TMS) delta (ppm): 8.11 (1H, s), 7.45 (1H, s), 7.30-7.35 (2H, m), 7.22 (1H, d, J = 7.7 Hz), 2.91 (4H, t, J = 7.5 Hz), 2.05-2.13 (2H, m) Indane-5-force aldehyde aldeoxime 3.0 g, 10% palladium on carbon 0.8 g, 36% hydrochloric acid approx.3.8 m 1 And a mixture of ethanol and 9 Om1 were stirred under a hydrogen atmosphere. After the absorption of hydrogen gas ceased, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain 3.2 g of indane-5-ylmethylamine hydrochloride.

Ή-NMR (CD ₃ S0CD ₃ , TMS) Delta (ppm): 8.37 (3H, br.s), 7.34 (1H, s), 7.21-7.34 (2H, m), 3.94 (2H, s), 2.85 ( 4H, t, J = 7.5 Hz), 1.98-2.05 (2H, m) 3- {3-methoxy-41- (2-propieroxy) phenyl} propionic acid chloride 0.50 g, (indane-5-yl) methylamine hydrochloride 0.36 g, triethylamine 0.8 ml and tetrahydrofuran 2 Oml were mixed and stirred at room temperature for 20 minutes. Thereafter, water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was washed sequentially with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was washed with hexane to give 0.34 g of N — {(indan-5-yl) methyl} —3— {3-methoxy-4- (2-propynyloxy) phenyl} propanamide. Obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 6.71-7.16 (6H, m), 5.54 (1H, br.s), 4.72 (2H, m), 4.36 (2H, d, J = 4.6 Hz) , 3.82 (3H, s), 2.65-2.94 (6H, m), 2.48 (3H, m), 2.04-2.08 (2H, m) Production Example 23 [Production Example of Compound (I-23)]

 N— (indan-5-ylmethyl) —3— {3-methoxy—41- (2-propynyloxy) phenyl} propanamide 50 Omg is reacted with 627 mg of Lawesson's reagent to give N— (indan-5-methyl). —Ylmethyl) -3- (3-Methoxy 41- (2-propynyloxy) phenyl} propanethioamide 35 Omg was obtained.

lH- thigh (CDC1 _3, TMS) delta (ppm): 7.16 (1H, d, J = 7.7 Hz), 6.86-7.10 (4H, m), 6.75 (1H, d, J = 1.9 Hz), 6.72 (1H , dd, J = 8.2 Hz, 1.9 Hz), 4.72 (2H, d, J = 2.4 Hz), 4.65 (2H, d, J = 4.8 Hz), 3.81 (3H, s), 3.08 (2H, t, J = 7.4 Hz), 2.84-2.95 (6H, i), 2.47 (1H, t, J = 2.4 Hz), 2.01-2.11 (2H, m) Production example 24 [Production example of compound (I-24)]

 Reaction of 73 lmg of indane-5-hydroxylaldehyde with 0.7 g of 3- {3-methoxy-4-((2-propynyloxy) phenyl) propionic acid in the same manner as in Production Example 9 This gave 25 Omg of N- {11- (indane-1-yl) -11-cyanomethyl} -3- (3-methoxy-41- (2-propynyloxy) phenyl) propanamide.

_{lH-NMR (CDC1 3, TMS} ) delta (ppm): 7.20-7.25 (2H, m), 7.05-7.10 (1H, m), 6.94 (1H, d, J = 7.9 Hz), 6.68-6.74 (2H, m), 6.01 (1H, d, J = 8.2 Hz), 5.74 (IH, d, J = 7.4 Hz), 4.72 (2H, d, J = 2.4 Hz), 3.82 (3H, s), 2.85-- 2.98 (6H, m), 2.45-2.60 (3H, m), 2.03- 2.14 (2H, m) Production Example 25 [Production Example of Compound (I-25)]

 In a similar manner to Production Example 22, 55 g of a crude product of 5,6,7,8-tetrahydronaphthalene_2-ethyloxoethyl acetate was obtained from 58 g of 1,2,3,4-tetrahydronaphthalene.

_{^{! H-NMR (CDC1 3,}} TMS) delta (ppra): 7.69-7.72 (2H, m), 7.17 (IH, d, J = 7.8Hz), 4.44 (2H, q, J = 7.2 Hz), 2.75- 2.83 (4H, m), 1.17-1.85 (4H, m), 1.42 (3H, t, J = 7.2 Hz)

From 5,6,7,8-tetrahydronaphthalene-12-yloxoacetate crude ester 30 g, 5,6,7,8-tetrahydronaphthylene-2-perethane-1 1,2-diol 17 g Obtained.

_{'H-NMR (CDC1 3,} TMS) delta (ppm): 7.01-7.04 (3H, m), 4.76 (IH, dd, J = 8.1 Hz, 3.7), 3.63-3.77 (2H, m), 2.75-2.76 (4H, m), 2.4 (IH, br.s), 2.0 (IH, br.s), 1.17-1.18 (4H, m)

13 g of 5,6,7,8-tetrahydronaphthylene-2-ene-l-propaldehyde was obtained from 16 g of 5,6,7,8-tetrahydronaphthylene-1-1,2-diol. Was.

lH- thigh (CDC1 _3, TMS) delta (ppm): 9.92 (1H, s), 7.57-7.59 (2H, m), 7.20 (IH, d, J = 7.5 Hz), 2.82-2.85 (4H,), 1.81-1.84 (4H, m) 5,6,7,8-tetrahydronaphthalene-one-l-propanolaldehyde From 2.6 g of 5,6,7,8-tetrahydronaphthylene-l-l-l-l-aldehyde aloxime 1.5 g were obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 8.08 (IH, s), 7.33 (IH, s), 7.26-7.31 (2H, in), 7.07 (IH, d, J = 7.6 Hz), 2.75 -2.79 (4H, 1), 1.78-1.82 (4H, m).

From 5,6,7,8-tetrahydronaphthalene-l-2-propanolaldehydeoxime 2.6 g 5,6,7,8-tetrahydronaphthalene-l- 2-methylmethylamine salt 1.5 g of the acid salt were obtained.

'H-NMR (CD ₃ S0CD ₃ , TMS) Delta (ppm): 8.43 (3H, br.s), 7.17-7.19 (2H, m),

7.06-7.07 (1H, m), 3.89 (12H, d, J = 5.1 Hz), 2.70 (4H, s), 1.72-1.73 (4H, m) 3— {3-Methoxy-4— (2-propieroxy) By reacting 0.30 g of propionic acid chloride with 0.23 g of (5,6,7,8-tetrahydronaphthalene-1-yl) methylamine hydrochloride and 0.42 ml of triethylamine N — {(5,6,7,8-tetrahydronaphthalene-1-yl) methyl} —3 -— {3-methoxy-41- (2-propynyloxy) phenyl} propane amide (0.41 g) was obtained. Was.

_{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 6.89-7.02 (4H, m), 6.71-6.76 (2H, m), 5.52 (1H, br.s), 4.73 (2H, d, J = 2.5 Hz), 4.33 (2H, d, J = 5.4 Hz), 3.83 (3H, s), 2.92 (2H, t, J = 7.8 Hz), 2.49-2.72 (4H, m), 2.45-2.49 (3H, m), 1.76 -1.79 (4H, m) Production Example 26 [Production Example of Compound (I-26)]

 N- (5,6,7,8-tetrahydronaphthalene-l-2-ylmethyl) -13- {3-methoxy-41- (2-propynyloxy) phenyl} propanamide 637mg, mouth reagent 769mg and tetrahydrofuran 1 Om1 was mixed and stirred at 65 ° C. for 3 hours. Thereafter, the reaction mixture was cooled and concentrated under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layer was sequentially washed with 5% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give N- (5,6,7,8-tetrahydronaphthalene-1-ylmethyl) -13- {3-methoxy-14- (2-propynyloxy) phenyl } 394 mg of propanethioamide were obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 6.91-7.03 (3H, m), 6.85 (2H, d, J = 7.5 Hz), 6.76 (1H, d, J = 2.0 Hz), 6.72 (1H , dd, J = 8.1 Hz, 2.0 Hz), 4.72 (2H, d, J = 2.2 Hz), 4.62 (2H, d, J = 4.6 Hz), 3.82 (3H, s), 3.08 (2H, t, J = 7.3 Hz), 2.91 (2H, t, J = 7.3 Hz), 2.69-2.77 (4H, m), 2.48 (1H, t, J = 2.4 Hz), 1.75-1.81 (4H, m) Production Example 27 [Production Example of Compound (1-27)]

 0.65 g of 5,6,7,8-tetrahydronaphthalene-l- 2-propanol and 0.50 g of 3- {3-methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride By reacting in the same manner as in Production Example 9, N- {1-1 (5,6,7,8-tetrahydronaphthalene-1-yl) -1-cyanomethyl} 13- {3-methoxy-4-1 ( 0.27 g of 2-propynyloxy) propaneamide was obtained.

_{^{! H-NMR (CDC1 3,}} TMS) Del evening (ρριη): 7.07-7.09 (2H, m), 7.02 (1H, dd, J = 8.0 Hz, 2.2 Hz), 6.95 (1H, d, J = 7.8 Hz ), 6.70-6.72 (2H, m), 5.89 (1H, d, J = 8.3 Hz), 5.76 (1H, br.d, J = 8.2 Hz), 4.73 (2H, d, J = 2.4 Hz), 3.83 (3H, s), 2.94 (2H, t, J = 7.5 Hz), 2.50-2.80 (4H, m), 2.49-2.58 (2H, m), 2.48 (1H, t, J = 2.5 Hz), 1.77- 1.80 (4H, m) Production Example 28 [Production Example of Compound (1-28)]

 7.58 g of lithium aluminum hydride and 100 ml of tetrahydrofuran were mixed, and a solution of 15.3 g of 2-naphthonitrile in tetrahydrofuran was added dropwise little by little, followed by stirring at room temperature for 3 hours. Thereafter, the reaction mixture was cooled to 0 to 5 ° C., and sodium hydroxide solution was added dropwise little by little. After the addition, the mixture was filtered, and the filtrate was concentrated under reduced pressure. Ethyl acetate and water were added to the residue, and the mixture was separated.

The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to obtain 12.5 g of 2- (aminomethyl) naphthalene.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.80-7.83 (3H, m), 7.74 (1H, s), 7.41-7.49 (3H, m), 4.03 (2H, s), 1.62 (2H, br. s) 3- {3-methoxy-41- (2-propieroxy) phenyl} propionic acid chloride 0.30 g, 2- (aminomethyl) naphthalene 0.19 g and triethylamine 0.5 ml By the reaction, 0.25 g of N — {(naphthalene-1-yl) methyl} —3- {3-methoxy-41- (2-propieroxy) phenyl} propanamide was obtained.

_{Ή-NMR (CDC1 3, TMS} ) delta (ppm): 7.76-7.82 (3H, m), 7.60 (1H, s), 7.44 -7.49 (2H, m), 7.29-7.29 (1H, m), 6.89- 6.90 (1H, m), 6.71-6.95 (2H, m), 5.74 (1H, br.s), 4.69 (2H, d, J = 2.2 Hz), 4.55 (2H, d, J = 5.9 Hz), 3.78 (3H, s), 2.96 (2H, t, J = 7.6 Hz), 2.46-2.54 (3H, m) Production Example 29 [Production Example of Compound (I-29)]

 N-{(naphthalene-2-yl) methyl} -3- {3-methoxy-41- (2-provinyloxy) phenyl} propanamide ◦. 61 g and Lawson reagent 745 mg as in Production Example 26 0.38 g of N-{(naphthalene-121-yl) methyl} -13- {3-methoxy-41- (2-propynyloxy) phenyl} propane amide Was.

_{Ή-NMR (CDC1 3, TMS} ) Del evening (ppm): 8.7-8.9 (3H, m), 7.60 (1H, s), 7.4- 7.6 (2H, m), 7.20 (1H, dd, J = 8.5 Hz , 1.7 Hz), 7.15 (1H, br), 6.88 (1H, d, J = 8.0 Hz), 6.77 (1H, d, J = 1.9 Hz), 6.72 (1H, dd, J = 8.2 Hz, 1.8 Hz) , 4.88 (2H, d, J = 5.1 Hz), 4.67 (2H, d, J = 2.4 Hz), 3.80 (3H, s), 3.10 (2H, t, J = 7.2 Hz), 2.96 (2H, i, (J = 7.2 Hz), 2.44 (1H, t, J = 2.4 Hz) Next, compound (II) will be described. In the composition of the present invention, the ethylenebisdithiocarbamate compound means a salt of ethylenebisdithiocarbamate. The ethylenebisdithiocarbamate compounds include zineb (generic name) [chemical name: zinc ethylenebis (di thiocarbamete) (polymeric)], maneb (generic name) [chemical name: manganese ethylenebis (dithiocarb teba polymeric)] and mansef (Generic name) [manganese ethylenebis (di thiocarbamete; (polymeric) complex with zinc salt]).

 Among the ethylenebisdithiocarbamate compounds, zineb is described in The Pesticide Manual, Thirteenth Edition edited by Clive Tomlin, ublished by The British Crop Protection Council. And The Royal Society of Chemistry, 2003), p. Maneb is described on page 608 of the same document. Manzeb is described on page 606 of the same document. Embodiments of the composition of the present invention include, for example, the following.

 (i) A fungicidal composition containing an amide compound represented by the formula (1) and an ethylenebisdithiocarbamate compound as active ingredients.

(ii) In the formula (1), X is an oxygen atom or a sulfur atom, R ¹ is a halogen atom or a C 1 -C 2 alkyl group, and R ² is a hydrogen atom, a halogen atom or a C A force that is a 1-C 2 alkyl group, or R ¹ and R ² together form a C 3 -C 4 polyethylene group or a 1,3-butadiene 1,4-diyl group, and R ³ is hydrogen The germicidal composition according to (i), wherein R ⁴ is a C 1 -C 2 alkyl group, and R ⁵ is a C 3 alkynyl group.

(iii) In the formula (1), X is an oxygen atom, R ¹ is a hydrogen atom, a halogen atom or a C 1 -C 2 alkyl group, and R ² is a hydrogen atom or a halogen atom, or R ¹ and R ² are joined together to form a C3-C4 polymethylene group or 1,3-butadiene-1,4-diyl group, R ³ is a cyano group, and R ⁴ is a C 1 -C 2 alkyl group. The bactericidal composition according to (i) or (ii), wherein R ⁵ is a C 1 -C 2 alkyl group, a C 3 alkenyl group or a C 3 alkynyl group.

 (iv) The amide compound represented by the formula (1) is N— (4-cyclobenzyl) 13- {3-methoxy-41- (2-propynyloxy) phenyl} propanamide (i) Or the bactericidal composition of (ii).

 (V) When the amide compound represented by the formula (1) is N- {1- (4-chlorophenyl) 1-11-cyanomethyl} -3--3- {3-methoxy-4- (2-propynyloxy) phenyl } The fungicidal composition according to (i) or (ii), which is propanamide.

 (V i) The fungicidal composition according to any one of (i) to (V), wherein the ethylenebisdithiocarbamate compound is zineb, maneb or manzeb.

(Vii) The fungicidal composition according to any one of (i) to (V), wherein the ethylenebisdithiocarbamate is manzeb. The composition of the present invention includes, for example, rice blast (Pyricularia oryzae), sesame leaf blight (Cochliobolus miyabeanus), crest blight;) hei (Rhizoctonia solani)> barley powdery mildew (Erysiphe graminis, f. Sp. , f. sp.triticu, Fusarium head blight (Gibberella zeae), Rust (Puccinia str i if ormis, P. graminis, P. recondita, P. hordei), Snow rot (Typ ula sp. > Nude smut (Ustilago iritici, U.nuda), stag smut (Tilletia caries), eye spot (PseudocercosporeUa herpotrichoides), bacterial rot (Rhizoctonia cerealis), cloudy disease (Rhynchosporium secalis), leaf blight (Septoria) tritici), Fusarium wilt (Leptosphaeria nodorum), Black spot of citrus fruit (Diaporthe citri), Scab (Elsinoe fawcetti), Fruit rot (Penicilliumdigitatum, P. i tanicum), Monilia disease of apple (Moniliniamali), rot Disease (Valsa mali), powdery mildew (Podosp aera leucotricha), spot leaf spot (Alternaria mali), scab (Venturia inaequalis), pear scab (Venturia nasshicola), black scab (Alternaria kikuchiana) scab (Gymnosporangium haraeanum), peach scab (Monilinia fructicola), scab (Cladosporium carp) ilum), Phomopsis rot (Phomopsis sp.), Grape downy mildew (Plasmopara viticola), Black rot (Elsinoe ampelina) ^ Bcing rot (Glomerella cingulata), Unc inula necator, rust Byko (Phakopora ampelopsidis)> Leaf blight (Gloeosporium kak, deciduous disease (Cercospora kaki, Mycospharerel la nawae), Cucumber downy mildew (Pseudoperonospora cubensi.s), Anthracnose

(Colletotrichum lagenarium ^ Unko Byo (Sphaerotheca ful iginea), vine blight (Mycosphaerella melonis) Tomato ring rot (Alternaria solanli, leaf fungi

(Cladosporium fulvumj plague (Phytophthora infestans))

(Phomopsis vexans), powdery mildew (Erysiphe cichoracearum), black spot of cruciferous field (Alternaria japonica), white spot (Cercosporella brassicae), green onion rust (Puccinia allii), soybean purpura (Cercospora kikuchii) Black scab (Elsinoe glycines), Black spot (Diaporthe phaseolorum var. Saj ae), Inken anthracnose (Colletotrichum lindemthia recitation), Black scab of Mytaria (Mycosphaerella personatum), Leaf spot (Cercospora arachidicola; Bytonko Byton

(Erysiphe pisi), Beto and Behei (Peronospora isu) Powdery mildew

(Sphaerotheca h painting li), Phytophthora nicotianae var.parasitica Net scab (Exobasidium recticulatum)> White scab (Erysiphe leucospila), Red scab (Al ternaria longipes), Etosi (Erysiphe) cichoracearum> Anthracnose (Colletotrichum tabacum, plague (Phytophthora nicotianae var. nicotianae), sugar beet brown spot (Cercospora beticola), rose scab

(Diplocarpon rosae) _¾ powdery mildew (Sphaerotheca pannosa late blight (Phytophthora megasperma), chrysanthemum brown spot disease (Septoria chrysanthemiindici), white rust炳(Puccinia oriana), various crops Botrytis (Botrytis cinerea), Sclerotinia rot (Sclerotinia sclerotiorum), can be used for controlling various plant diseases such as diseases caused by Pythium sp .. The composition of the present invention is excellent in controlling plant diseases caused by algae (mycetes). Has the effect. 1214

38

 In the composition of the present invention, the mixing ratio of the compound (I) and the compound (II) is not particularly limited. 0 parts by weight, preferably in the range of 0.5 to 50 parts by weight. That is, in the composition of the present invention, the mixing ratio of the compound (I) and the compound (II) is usually from 10: 1 to 1: 100, preferably from 2: 1 to L: 50. The composition of the present invention may be a mixture of the compound (I) and the compound (II) itself, but is usually a solid carrier, a liquid carrier, or a gaseous carrier, if necessary, a surfactant, a fixing agent, a dispersant, Formulation into wettable powders, suspensions, granules, dry floor tablets, emulsions, aqueous liquids, oils, smokers, aerosols, microcapsules, etc. .

 The composition of the present invention can be prepared by mixing the formulated compound (I) with the formulated compound (II). Compound (I) and compound (II) can be mixed at the time of application.

These preparations usually contain the active ingredient compound in a total amount of 0.1 to 99% by weight, preferably 0.2 to 90% by weight. '' Solid carriers include clays (kaolin clay, diatomaceous earth, synthetic hydrous silicon oxide, attapulgite clay, bentonite, acid clay, etc.), talcs, and other inorganic minerals (sericite, quartz powder, sulfur powder) , Activated carbon, calcium carbonate, hydrated silica, etc.) and fine powders or granules such as chemical fertilizers (ammonium sulfate, phosphorous ammonium, ammonium nitrate, urea, salt ammonium, etc.). Examples of the liquid carrier include water, alcohols and the like. (Methanol, ethanol, etc.), ketones (acetone, methylethylketone, cyclohexanone, etc.), aromatic hydrocarbons (benzene, toluene, xylene, ethylbenzene, methylnaphthalene, etc.), aliphatic hydrocarbons (Hexane, kerosene, etc.), esters (ethyl acetate, butyl acetate, etc.), nitriles (acetonitrile, isoprene) Thyronitrile, etc.), ethers (dioxane, diisopropyl ether, etc.), acid amides (dimethylformamide, dimethylacetamide, etc.), octogenated hydrocarbons (dichloroethane, trichloroethylene, tetrachloride, etc.). Examples of the gaseous carrier include butane gas, carbon dioxide gas, and fluorocarbon gas. Surfactants include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and their polyoxyethylenates, polyethers. Tylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives and the like. Examples of fixatives and dispersants include casein, gelatin, polysaccharides (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, saccharides, synthetic water-soluble polymers (polyvinyl alcohol, polypinyl pyrrolyl). And stabilizers such as PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), and BHA (2-tert-butyl-4). -Methoxyphenol and a mixture of 3-tert-butyl 4-methoxyphenol), vegetable oils, mineral oils, fatty acids or esters thereof, and the like. The preparation of the composition of the present invention is applied as it is or diluted with water to a plant or a soil where the plant grows. When the formulation is applied to soil, for example, the formulation or its water dilution is sprayed on the soil surface, and the formulation or its water dilution is mixed with the soil. When the composition of the present invention is used by applying it to a plant or soil where the plant grows, the application rate is determined by the type of the active ingredient compound, the mixing ratio, the weather conditions, the formulation, the application time, the application method, the application place, and the control. It can be varied depending on the type of the target disease, the type of the crop to be controlled, etc., but is usually 0.01 to from the total amount of the active ingredient compound per 10 Om ² : L 000 g, preferably 0.1 to : LOO g.

 Emulsions, wettable powders, suspensions, and the like are usually diluted with water so that the active ingredient concentration is 0.0001 to 1% by weight, preferably 0.001 to 0.5% by weight. And powders are usually applied as they are.

The preparation of the composition of the present invention can also be used in treatment methods such as seed treatment and ULV. Examples of the seed treatment method include a seed dressing treatment with the composition of the present invention, a seed immersion treatment in the composition of the present invention, and a seed spraying treatment of the composition of the present invention. The application rate is usually from 0.01 to 50 g, preferably from 0.01 to: LO g, based on the total amount of the active ingredient compound per kg of seed. The composition of the present invention can be used together with other fungicides, insecticides, acaricides, nematicides, herbicides, fertilizers, soil conditioners, and the like. Hereinafter, the present invention will be described in more detail with reference to formulation examples and test examples, but the present invention is not limited to the following examples. Parts represent parts by weight. First, Formulation Examples, Formulation Example 1

 Compound (I) of any one of compounds (1-1) to (1-29) 1 part; zineb, manneb or manzeb 5 parts; synthetic hydrous silicon oxide 1 part; lignin sulfonate calcium 2 parts; bentonite 30 Parts and kaolin clay 61 parts are well ground and mixed, water is added, and the mixture is thoroughly kneaded, and then granulated and dried to obtain granules. Formulation Example 2

 5 parts of compound (I) of any one of compounds (I-11) to (1-29); 5 parts of zineb, maneb or manzeb; 1 part of synthetic hydrous silicon oxide; 2 parts of calcium ligninsulfonate; 30 parts of bentonite And 57 parts of kaolin clay are well ground and mixed, water is added and kneaded well, and the mixture is granulated and dried to obtain granules. Formulation Example 3

 Compound (I) of any of Compounds (I-I) to (I-29) 0.5 part; Zineb, Maneb or Manzeb 2.5 parts; 86 parts of Kaolinkure and 11 parts of talc are thoroughly ground and mixed. Obtain a powder. Formulation Example 4

 5 parts of compound (I) of any one of compounds (1-1) to (1-29); 25 parts of zineb, manneb or manzeb; 3 parts of polyoxyethylene sorbitan monooleate; 3 parts of carboxymethyl cellulose and 64 water Parts and mix by wet milling to a particle size of 5 microns or less to obtain a suspending agent. Formulation Example 5

10 parts of compound (I) of any one of compounds (I-11) to (1-29); 50 parts of zineb, maneb or manzep; 3 parts of calcium ligninsulfonate; 2 parts of sodium lauryl sulfate; The hydration agent is obtained by thoroughly grinding and mixing the parts. Next, test examples show that the composition of the present invention has an excellent effect of controlling plant diseases. You. In general, the expected control effect when two kinds of given active ingredient compounds are mixed and treated is determined by the formula of Co 1 by shown in the following equation.

 X: Control value when the active ingredient compound A is treated at mppm ()

Y: Control value (%) when the active ingredient compound B is treated with nppm

 E: Expected control value (%) when active compound A is treated with mppm and active compound B is treated with nppm (hereinafter referred to as expected control value)

In general, it can be said that there is a mixing effect unless the control value () obtained by actually mixing and treating two active ingredient compounds is smaller than the expected control value (%). Test example 1

A plastic pot was filled with sandy loam and sown with grapes (variety: Berry A). The plant was grown in a greenhouse for 40 days. A test agent prepared as a wettable powder according to Formulation Example 5 was diluted to a predetermined concentration with water, and sprayed with foliage so as to adhere sufficiently to the leaf surface of a grape seedling having three true leaves developed. Next, a suspension of zoosporangia of the grape downy mildew was spray-inoculated to the foliage of the seedling of the grape. After inoculation, the grape seedlings were allowed to stand overnight at 23 T and high humidity, and then grown in a greenhouse for 7 days. The affected area (%) of grape downy mildew in the foliage of the grape seedlings obtained in this manner was investigated, and the actual control value (%) was obtained from the results of the control using the following formula. Affected area of untreated plant (%) Affected area of single-treated plant (%) Control value (%) = X100 Affected area of untreated plant (%) The results are shown in Tables 2 and 3. Table 2

Test compound Active ingredient treatment concentration Actual control value (tt Control value expected value (»

 (ppm

 (I-I 1 Manse-p 50 + 250 100 100

 (1-2) + Mance 'F' 50 + 250 100 100

 (I-3 mump 50 + 250 100 100

 (I-one 4> + Mance 'F' 50 + 250 100 100

 (1-5) + Mance '* 50 + 250 100 100

 (I-1 6) + Mance '50 + 250 100 100

 (1-7) + Mance 'F' 50 + 250 100 100

 (I-1 8) + mump 50 + 250 100 100

 (1-9) + Mance * F'50 + 250 100 100

 (I-1 10) + Mance 'F' 50 + 250 100 100

 (I-11) + Mance 'F' 50 + 250 100 100

 (I-12) + Mance 'F' 50 + 250 100 100

 (I- 13 Mance 'F' 50 + 250 100 100

 (I-1 14) + Mance 'F' 50 + 250 100 100

 (I-I 15) + Manze 50 + 250 100 100

 (1-16) + Mance 'F' 50 + 250 100 100

 (I-17 Mancep 50 + 250 100 100

 (1-18) + Mance 'r 50 + 250 100 100

 (I-19) + Mance's 50 + 250 100 100

 (I-20) + Mance 'F' 50 + 250 100 100

 (G21) + Manse'p 50 + 250 100 100

 (1-22) + Mance 'F' 50 + 250 100 100

 (1-23) + Mance 'F' 50 + 250 100 100

 (I-24) + Mance 'F' 50 + 250 100 100

 (1-25) + Mance'r 50 + 250 100 100

 (I-26) + Mance 'F' 50 + 250 100 100

 -27) + Man '50' 250 100 100 100

 (I-28) + Man f '50 + 250 100 100

(1-29) + Mance 'H' 50 + 250 100 100 Table 3

Test compound Active ingredient treatment concentration Actual control value «) Expected control value (

 (ppm)

 (1-1) 50 100 ―

 (1-2) 50 100 ―

 (1-3) 50 100 ―

 (1-4) 50 100 ―

 (1-5) 50 100 ―

 (1-6) 50 100 ―

 (1-7) 50 100 ―

 (1-8) 50 100 one

 (1-9) 50 100 ―

 (1-10) 50 100 ―

 (1-11) 50 100 ―

 (1-12) 50 100 ―

 (1-13) 50 100 ―

 (1-14) 50 100 ―

 (I-15) 50 100 ―

 (1-16) 50 100 ―

 (1-17) 50 100 ―

 (1-18) 50 100 ―

 (1-19) 50 100 ―

 (1-20) 50 100 ―

 (1-21) 50 100 ―

 (1-22) 50 100 one

 (1-23) 50 100 ―

 (1-24) 50 100 ―

 (1-25) 50 100 ―

 (1-26) 50 100 ―

 (1-27) 50 100 ―

 (1-28) 50 100 ―

 (1-29) 50 100 ―

Mance '250 100 ― Industrial applicability

 INDUSTRIAL APPLICABILITY The composition of the present invention has an excellent effect in controlling plant diseases, and particularly exhibits an excellent effect in controlling plant diseases caused by alga (egg fungi) such as downy mildew and plague.

Claims

The scope of the claims (I) Equation (1)

 [In the formula, x represents an oxygen atom or a sulfur atom, R ¹ is a hydrogen atom, a halogen atom, a CI-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a CI-C4 alkoxy group, a C1-C4 halo Represents an alkoxy group or a cyano group, R ² represents a hydrogen atom, a genogen atom, a CI-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group or a C2-C4 alkynyl group, or R ¹ and R ² are Together represent a C3-C5 polymethylene group or a 1,3-butene-1,4-diyl group; R ³ represents a hydrogen atom, a C 1 -C 3 alkyl group or a cyano group, R ⁴ ¾C 1—C 3 represents an alkyl group, R ⁵ represents a C 1 _ C 4 alkyl group, C 3- C 4 alkenyl group or a C 3- C 4 alkynyl group. ] A germicidal composition comprising, as active ingredients, an amide compound represented by the formula: and (II) an ethylenebisdithiocarbamate compound. 2. The mixing ratio of the amide compound represented by the formula (1) and the ethylenebisdithiocarbamate compound is 0. The disinfecting composition according to claim 1, wherein the amount is 1 to 100 parts by weight. 3. In equation (1),  X is an oxygen atom or a sulfur atom, R ¹ is a halogen atom or a C 1 -C 2 alkyl group, R ² is a hydrogen atom, a halogen atom or a C 1 -C 2 alkyl group, Or R ¹ and R ² are joined together to form a C 3 -C 4 polymethylene group or a 1,3-butene gen-1,4-diyl group, R ³ is a hydrogen atom, Shaku ⁴ is a 1-C 2 alkyl group, R ⁵ is a C 3 alkynyl group 3. The bactericidal composition according to claim 1 or 2. 4. In equation (1), X is an oxygen atom, R ¹ is a hydrogen atom, a halogen atom or a C 1 -C 2 alkyl group, R ² is a hydrogen atom or a Hagen atom, Or R ¹ and R ² together form a C 3—C 4 polymethylene group or a 1,3-butadiene 1,4-diyl group, R ³ is a cyano group, R ⁴ is a C 1 -C 2 alkyl group, Scale ⁵ Gazi 1 one C 2 alkyl group, claim 1 or claim 2 fungicidal composition wherein the C 3 alkenyl or C 3 alkynyl group. 5. The amide compound represented by the formula (1) is N- (4-cyclobenzyl) 13- {3-methoxy-4_ (2-propynyloxy) phenyl} propanamide. 3. The germicidal composition according to claim 2. 6. When the amide compound represented by the formula (1) is N- {1— (4-chlorophenyl) —1-cyanomethyl} 13— {3-methoxy-4- (2-propynyloxy) phenyl 3. The fungicidal composition according to claim 1, which is propanamide. 7. Equation (I) (1) R ³ X (1) [In the formula, X represents an oxygen atom or a sulfur atom, R ¹ is a hydrogen atom, a halogen atom, C 1 one C4 alkyl group, CI- C4 haloalkyl group, C 2-C 4 alkenyl group, C 2-C 4 alkynyl group, C 1 one C4 alkoxy group, C 1-C4 halo Represents an alkoxy group or a cyano group, R ² represents a hydrogen atom, a halogen atom, a CI-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group or a C2-C4 alkynyl group, or R ¹ and R ² together Stands for C 3 — C 5 polymethylene group or 1,3-butadiene — 1,4-diyl group, R ³ represents a hydrogen atom, a C 1 -C 3 alkyl group or a cyano group, R ⁴ represents a C 1 -C 3 alkyl group, R ⁵ represents a C 1 one C 4 alkyl group, C 3- C 4 alkenyl group or a C 3- C 4 alkynyl group. ] A method for controlling plant diseases, comprising applying an effective amount of an amide compound represented by the formula (II) and (II) an ethylenebisdithiocarbamate compound to a plant or soil where the plant grows. 8. The mixing ratio of the amide compound represented by the formula (1) and the ethylenebisdithiocarbamate compound is 1 part by weight of the amide compound represented by the formula (1) with respect to 1 part by weight of the ethylenebisdithiocarbamate compound. 8. The method for controlling plant diseases according to claim 7, wherein the amount is 0.1 to 100 parts by weight. 9. In equation (1),  X is an oxygen atom or a sulfur atom, R ¹ is a halogen atom or a C 1 -C 2 alkyl group, R ² is a hydrogen atom, a halogen atom or a C 1 -C 2 alkyl group, or R ¹ and R ² are taken together to form a C 3 -C 4 polymethylene group or 1,3-butene A diyl group, R ³ is a hydrogen atom,  4 is a 01-C 2 alkyl group, R ⁵ is a C 3 alkynyl group 9. The method for controlling plant diseases according to claim 7 or 8. 10. In equation (1), X is an oxygen atom, R ¹ is a hydrogen atom, a halogen atom or a C 1 -C 2 alkyl group, R ² is a hydrogen atom or a halogen atom, Or R ¹ and R ² are joined together to form a C 3 -C 4 polymethylene group or a 1,3-butene gen-1,1,4-diyl group, R ³ is a cyano group,  4 is a 〇 1 C 2 alkyl group, 9. The method for controlling plant diseases according to claim 7, wherein R ⁵ is a C 1 -C 2 alkyl group, a C 3 alkenyl group or a C 3 alkynyl group. 11. The amide compound represented by the formula (1) is N- (4-cyclobenzyl) 13- {3-methoxy-41- (2-propynyloxy) phenyl} propanamide, or 9. The method for controlling plant diseases according to claim 8. 12. When the amide compound represented by the formula (1) is N- {1- (4-chlorophenyl) 1-11-cyanomethyl} 13- {3-methoxy-4- (2-propynyloxy) phenyl} 9. The method for controlling plant diseases according to claim 7, which is propanamide. 13. A method for controlling plant diseases, comprising applying an effective amount of the composition according to any one of claims 1 to 6 to a plant or soil in which the plant grows. 14. Use of the composition according to any one of claims 1 to 6 for controlling plant diseases.