WO2005068416A1

WO2005068416A1 - Amide compound and method for controlling plant disease using same

Info

Publication number: WO2005068416A1
Application number: PCT/JP2004/017316
Authority: WO
Inventors: Hiroshi Sakaguchi
Original assignee: Sumitomo Chemical Company, Limited
Priority date: 2003-12-12
Filing date: 2004-11-15
Publication date: 2005-07-28

Abstract

An amide compound represented by the formula (1) below has excellent control activity against plant diseases. [In the formula, R1 represents a hydrogen atom, halogen atom, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C1-C4 haloalkyl group, C1-C4 alkoxy group, phenyl group or phenoxy group; R2 represents a hydrogen atom, halogen atom, C1-C3 alkyl group, C1-C3 haloalkyl group or phenoxy group, or alternatively R1 and R2 may combine together to form a C3-C5 alkylene or CH=CH-CH=CH; R4 represents a C1-C4 alkyl group; R5 represents a C3-C4 alkynyl group; and X represents an oxygen atom or sulfur atom.]

Description

Specification

Amide compounds and methods for controlling plant diseases using the same

The present invention relates to an amide compound and a method for controlling plant diseases by applying the amide compound to plants or soil where plants grow. Background art

Drugs for controlling plant diseases have been developed, and many compounds having plant disease controlling effects have been found.However, the effects may not be sufficient, and the search for new compounds is eagerly pursued. Is being done. Disclosure of the invention

The present inventors have conducted intensive studies to find a compound having an excellent plant disease controlling effect, and as a result, have found that the amide compound represented by the following formula (1) has an excellent plant disease controlling effect, and completed the present invention.

That is, the present invention relates to formula (1)

[Wherein R ¹ is a hydrogen atom, a halogen atom, a CI-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C1-C4 alkoxy group, a phenyl group or Represents a phenoxy group, and R ² represents a hydrogen atom, a halogen atom, a CI-C3 alkyl group, a C1-C3 haloalkyl group or a phenoxy group, or R ³ and R ² together form C 3 — Represents C 5 alkylene or CH = CH_CH = CH; R ⁴ represents a 1-C 4 alkyl group; R ⁵ represents a C 3 -C 4 alkynyl group; X represents an oxygen atom or a sulfur atom. ]

And a plant disease control composition containing the compound of the present invention and a carrier, and a plant to which an effective amount of the compound of the present invention is applied to a plant or soil where the plant grows. A method for controlling a disease is provided. Specific examples of the substituents represented by RR ² , R ⁴ and R ⁵ in the formula (1) include the following groups.

Examples of the halogen atom represented by R ¹ 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, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group and a t-tert-butyl group,

Examples of the C 2 -C 4 alkenyl group represented by R ¹ include a vinyl group, a 1-methylvinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methyl-2-propenyl group, 2-methyl-2-propenyl, 2-butenyl and 3-butenyl groups,

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-butyl group.

Examples of the C 1 -C 4 haloalkyl group represented by R ¹ include a fluoromethyl group, a difluoromethyl group and a trifluoromethyl group,

Examples of the C 1 -C 4 alkoxy group represented by R ¹ include a methoxy group, an ethoxy group, a popoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group and a tert-butoxy group;

Examples of the halogen atom represented by R ² include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom,

The C 1 one C 3 alkyl group represented by R ^2, a methyl group, Echiru group, a propyl group and Isopuropiru group,

Examples of the C 1 -C 3 haloalkyl group represented by R ² include a fluoromethyl group, a difluoromethyl group and a trifluoromethyl group;

C 3 -C 5 alkylene in which R ¹ and R ² are taken together includes trimethylene, tetramethylene and pentamethylene.

The C 1 one C 4 alkyl group represented by R ^4, a methyl group, Echiru group, propyl group, isopropyl group, butyl group, isobutyl group, and a sec- butyl group and tert one butyl group.

As the C 3 -C 4 alkynyl group represented by R ⁵ , there are a 2-propynyl group, Examples include a tyl-2-propynyl group, a 2-butynyl group and a 3-butynyl group. The compounds of the present invention include, for example, compounds of the following embodiments.

An amide compound represented by the formula (1), wherein R ¹ is a hydrogen atom;

An amide compound represented by the formula (1), wherein R 'is a halogen atom, a C1-C4 alkyl group, a C1-C4 alkyl group or a C1-C4 alkoxy group;

An amide compound represented by the formula (1), wherein R ¹ is a halogen atom;

An amide compound represented by the formula (1), wherein R ¹ is a C 1 -C 4 alkyl group or a C 1 _C 4 haloalkyl group;

In the formula (1), an amide compound in which R ¹ is a C 1 -C 4 alkoxy group; an amide compound in which R ¹ is a phenyl group or a phenoxy group; in the formula (1), R ′ is chlorine An amide compound that is an atom;

An amide compound represented by the formula (1), wherein R ² is a hydrogen atom;

An amide compound represented by the formula (1), wherein R ² is a C 1 -C 3 alkyl group or a C 1 -C 3 haloalkyl group;

An amide compound represented by the formula (1), wherein R ² is a halogen atom;

In the formula (1), an amide compound wherein R ² is a phenoxy group;

An amide compound represented by the formula (1), wherein R ² is a chlorine atom;

In the formula (1), an amide compound in which R ¹ is a halogen atom and R ² is a hydrogen atom;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkyl group and R ² is a hydrogen atom;

An amide compound represented by the formula (1), wherein R ¹ is a C 2 -C 4 alkenyl group, and R ² is a hydrogen atom;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 haloalkyl group and R ² is a hydrogen atom;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkoxy group and R ² is a hydrogen atom;

In the formula (1), an amide compound in which R ¹ and R ² are the same or different halogen atoms;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkyl group and R ² is a halogen atom; An amide compound represented by the formula (1), wherein R ¹ is a C 1 -C 4 haloalkyl group, and R ² is a halogen atom;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkoxy group and R ² is a halogen atom;

An amide compound represented by the formula (1), wherein R ′ is a halogen atom and R ² is a C 1 -C 4 alkyl group;

In the formula (1), an amide compound wherein R ¹ and R ² are the same or different C 1 -C 4 alkyl groups;

An amide compound represented by the formula (1), wherein R ¹ is a C 1 -C 4 haloalkyl group, and R ² is a C 1 -C 4 alkyl group;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkoxy group and R ² is a CI—C 4 alkyl group;

In the formula (1), an amide compound in which R ¹ is a phenyl group and R ² is a hydrogen atom; In the formula (1), an amide compound in which R ¹ is a phenyl group and R ² is a halogen atom;

In the formula (1), an amide compound wherein R ¹ is a phenyl group and R ² is a C 1 -C 4 alkyl group;

In the formula (1), an amide compound in which R ¹ is a hydrogen atom and R ² is a phenoxy group;

An amide compound represented by the formula (1), wherein R ¹ is a halogen atom and R ² is a phenoxy group;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 haloalkyl group and R ² is a phenoxy group;

In the formula (1), an amide compound wherein R ′ is a C 1 -C 4 alkoxy group and R ² is a phenoxy group;

In the formula (1), an amide compound wherein R ¹ is a C 1 -C 4 alkyl group and R ² is a phenoxy group;

In the formula (1), an amide compound in which R ¹ is a phenoxy group and R ² is a hydrogen atom;

In the formula (1), an amide compound wherein R ¹ is a phenoxy group and R ² is a halogen atom;

In the formula (1), R ′ is a phenoxy group, and R ² is a C 1 -C 4 alkyl group. Amide compound;

An amide compound represented by the formula (1), wherein R ¹ and R ² are combined to form C 3 —C 5 alkylene or CH = CH—CH = CH;

In the formula (1), an amide compound in which R ¹ is a phenyl group and R ² is a hydrogen atom; an amide compound in which R ⁴ is a methyl group or an ethyl group in the formula (1); ^An amide compound in which ⁵ is a 2-propynyl group, a 1-methyl-2-propyl group or a 2-butynyl group;

An amide compound represented by the formula (1), wherein R ⁵ is a 2-propynyl group;

An amide compound represented by the formula (1), wherein X is an oxygen atom;

In the formula (1), an amide compound in which R ¹ is a halogen atom, a CI-C4 alkyl group, a CI-C4 haloalkyl group or a C 1 _C 4 alkoxy group, and R ² is a hydrogen atom;

In the formula (1), R ¹ is a halogen atom, a CI—C4 alkyl group, a C 1—C4A alkyl group or a C 1—C4 alkoxy group, and R ² is a halogen atom, a C 1—C 3 alkyl group, An amide compound which is a 1 _C 3 haloalkyl group;

In the formula (1), an amide compound wherein R ¹ is a hydrogen atom and R ² is a halogen atom or a phenoxy group;

In the formula (1), R ¹ is a halogen atom, a CI—C4 alkyl group, a C 1—C4 haloalkyl group or a C 1—C4 alkoxy group, and R ² is a halogen atom, a C 1—C3 alkyl group. Or an amide compound which is a C 1 -C 3 haloalkyl group;

In the formula (1), R ¹ is a halogen atom, a CI—C4 alkyl group, a C 1—C4 haloalkyl group or a C 1—C4 alkoxy group, R ² is a hydrogen atom, and X is an oxygen atom. An amide compound;

In the formula (1), R ¹ is a halogen atom, a CI—C4 alkyl group, a C 1—C4 haloalkyl group or a C 1—C4 alkoxy group, and R ² is a halogen atom, a C 1—C3 alkyl group. Or an amide compound which is a C 1 -C 3 haloalkyl group and X is an oxygen atom;

In the formula (1), R ⁴ is a methyl group or Echiru group, R ⁵ is 2-propynyl group, amide compound is 1-methyl-2 one-propynyl group or a 2-heptynyl group; in the formula (1), R ⁴ Is a methyl group or an ethyl group, and R ⁵ is a 2-propynyl group. Next, a method for producing the compound of the present invention will be described. The compound of the present invention can be produced, for example, by the following (Production method A;), (Production method B) or (Production method C). (Production method A)

Among the compounds of the present invention, the compound represented by the formula (1-1), wherein X in the formula (1) is an oxygen atom, comprises a compound represented by the formula (2) and a compound represented by the formula (3): It can be produced by reacting in the presence of a base.

(1-1)

(Wherein, RRR ⁴ and R ⁵ 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 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; Aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, and acid amides such as N, N-dimethylformamide And sulphoxides such as dimethylsulphoxide 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, Tertiary amines such as 5-diazabicyclo [4.3.0] non-5-ene; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. In the reaction, 1 to 10 mol of a base and usually 1 to 5 mol of a compound represented by the formula (2) are used per 1 mol of the compound represented by the formula (3).

The reaction temperature of the reaction is usually in the range of 20 to 100, 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 washed with acidic water (dilute hydrochloric acid, etc.) and basic water (sodium hydrogen carbonate aqueous solution, etc.) as necessary. , Drying, concentrating, or (ii) adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration to obtain a compound represented by the formula (1-1). The indicated compound can be isolated. The isolated compound represented by the formula (111) may be further purified by an operation such as chromatography and recrystallization.

(Production method B)

Among the compounds of the present invention, the compound represented by the formula (11) wherein X in the formula (1) is an oxygen atom is represented by the compound represented by the formula (2) or a hydrochloride thereof and the formula (4) It can also be produced by reacting a compound with a compound in the presence of a dehydrating condensing agent.

(1-1)

[Wherein, RR ² , R ⁴ and R ⁵ represent the same meaning as described above. ]

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

Solvents used in the reaction include, for example, amides such as N, N-dimethylformamide, sulfoxides such as dimethylsulfoxide, pyridine, quinoline and the like. Nitrogen aromatic compounds and mixtures thereof. Examples of the dehydrating condensing agent used in the reaction include carethylimides such as 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter, referred to as WSC) and 1,3-dicyclohexylcarbodiimide. Is raised.

In the reaction, usually 1 to 3 mol of the compound represented by the formula (2) and usually 1 to 5 mol of the dehydration condensing agent are used per 1 mol of the compound represented by the formula (4).

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 reaction is completed, (i) the reaction mixture is poured into water and extracted with an organic solvent, and the organic layer is washed with acidic water (dilute hydrochloric acid or the like) and basic water (sodium hydrogen carbonate aqueous solution or the like) as necessary. , Drying, and concentrating, or (ii) adding a small amount of water to the reaction mixture, concentrating under reduced pressure, and collecting the obtained solid by filtration to obtain a compound represented by the formula (1-1). The indicated compound can be isolated. The isolated compound represented by the formula (1-1) may be further purified by a technique such as chromatography and recrystallization.

(Production method C)

Among the compounds of the present invention, a compound represented by the formula (1-2) in which X in the formula (1) is a sulfur atom is, for example, a compound represented by the formula (1-1) and 2,4-bis (4- (Methoxy phenyl) can be produced by reacting with 1,3-dithia-2,4-diphosphethane-2,4_disulphide (hereinafter referred to as Lawesson's reagent).

(1-2)

(Wherein, RR ² , R ⁴ and R ⁵ 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 ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and tert-butyl methyl ether; aliphatic hydrocarbons such as hexane, heptane and octane; And aromatic hydrocarbons such as xylene and xylene; halogenated hydrocarbons such as chlorobenzene; nitriles such as acetonitrile and ptyronitrile; sulfoxides such as dimethylsulfoxide; and mixtures thereof.

In this reaction, usually 1 to 10 mol of Lawesson's reagent is used per 1 mol of the compound represented by the formula (111).

The reaction temperature of the reaction is usually in the range of 50 to 150, 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 (1-2) 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 be. The isolated compound represented by the formula (1_2) can be further purified by an operation such as chromatography, recrystallization and the like. Next, a method for producing the intermediate of the present invention will be described.

The compound represented by the formula (3) and the compound represented by the formula (4) can be produced, for example, according to the following scheme.

(In the formula, Ri ^G 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 chlorine atom, a bromine atom, a methanesulfonyloxy group or a trifluoromethanesulfonyl group. Represents a oxy group, and R ⁴ and R ⁵ have the same meanings as described above. ]

Process (II-1)

The compound represented by the formula (8) can be produced by reacting the compound represented by the formula (6) and the compound represented by the formula (7) in the presence of a base. The reaction can be performed in the presence of a solvent.

Examples of the solvent used in the reaction include 1,4-dioxane and tetrahydrofuran. Ethers such as orchid, ethylene glycol dimethyl ether and tert-butyl methyl ether; aliphatic hydrocarbons such as hexane, heptane and octane; aromatic hydrocarbons such as toluene and xylene; halogenated carbons such as benzene Examples include hydrogens, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, acid amides such as N, N-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, alkali metal hydrides such as sodium hydride and potassium hydride, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5. 4. 0] INDEC-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 Group compounds.

In the reaction, 1 to 10 mol of the base and usually 1 to 5 mol of the compound represented by the formula (7) are used per 1 mol of the compound represented by the formula (6).

The reaction temperature of the reaction is usually in the range of 0 to 100, 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 (8) can be isolated by performing post-treatment operations such as pouring the reaction mixture into water, extracting the organic solvent, and drying and concentrating the organic layer. it can. The isolated compound represented by the formula (8) can be further purified by operations such as chromatography and recrystallization.

Process (II-2)

The compound represented by the formula (10) can be produced by reacting the compound represented by the formula (8) with the compound represented by the formula (9) 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, 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 chlorobenzene, acid amides such as N, N-dimethylformamide, sulfoxides such as dimethyl sulfoxide, water, 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, sodium methoxide, and sodium ethoxide. And metal alkoxides such as oxide and potassium tertiary butoxide. In the reaction, usually 1 to 10 mol of a base and 1 to 5 mol of a compound represented by the formula (9) are used per 1 mol of the compound represented by the formula (8).

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 :! to 24 hours.

After completion of the reaction, the compound represented by the formula (10) can be isolated by performing post-treatment operations such as pouring the reaction mixture into water and extracting the organic solvent, and drying and concentrating the organic layer. . The isolated compound represented by the formula (10) can be further purified by operations such as chromatography and recrystallization.

Process (II-3)

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

The reaction is usually performed in the presence of a solvent. Further, the reaction can be performed in the presence of an acid. Examples of the solvent used in the reaction include alcohols such as methanol, ethanol, and propanol; esters such as ethyl acetate and butyl acetate; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof. Can be Examples of the hydrogenation catalyst used for the reaction include transition metal compounds such as palladium carbon, palladium hydroxide, Raney nickel, and platinum oxide. Acids used in the reaction include hydrochloric acid and acetic acid.

In the reaction, usually 0.001 to 0.5 mol of the hydrogenation catalyst is used per 1 mol of the compound represented by the formula (10).

The reaction is usually performed under a hydrogen atmosphere at 1 to 100 atm. The reaction temperature of the reaction is usually in the range of 120 to 10, and the reaction time is usually in the range of 0.1 to 24 hours.

After completion of the reaction, the reaction mixture was filtered, the filtrate was extracted with an organic solvent, and the obtained organic layer was subjected to post-treatment operations such as drying and concentration, whereby the compound represented by the formula (11) was obtained. Can be released. The isolated compound represented by the formula (11) can be further purified by a procedure such as chromatography and recrystallization.

Process (II-4)

The compound represented by the formula (13) can be produced by reacting the compound represented by the formula (11) and the compound represented by the formula (12) in the presence of a base. The reaction can be 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, and tert-butyl methyl ether; aliphatic hydrocarbons such as hexane, heptane, and octane; toluene; Aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, and acid amides such as N, N-dimethylformamide And sulphoxides such as dimethylsulphoxide and mixtures thereof. Examples of the base used for the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] indene-7-ene, And tertiary amines such as 5,5-diazabicyclo [4.3.0] non-1-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.

In this reaction, usually 1 to 10 mol of the base and usually 1 to 5 mol of the compound represented by the formula (12) are used per 1 mol of the compound represented by the formula (11). The reaction temperature of the reaction is usually in the range of 0 to 100 t, 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 (13) 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 (13) can be further purified by an operation such as distillation, chromatography, and recrystallization.

Process (I-5)

The compound represented by the formula (4) can be produced by reacting the compound represented by the formula (13) with water in the presence of a base.

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

Examples of the solvent used for 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, and halogens such as benzene. Hydrocarbons, 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 lithium metal hydroxide such as lithium hydroxide, sodium hydroxide, and hydroxylated water. In this reaction, usually 1 to 10 mol of a base and usually 1 to 100 mol of water are used per 1 mol of the compound represented by the formula (13).

The reaction temperature of the reaction is usually in the range of 0 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 (4) is isolated by performing post-treatment operations such as adding acidic water (hydrochloric acid, etc.) to the reaction mixture, extracting the organic solvent, and drying and concentrating the organic layer. be able to. The isolated compound represented by the formula (4) can be further purified by chromatography, recrystallization or the like, but can be used as it is in the next step.

Process (II_6)

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

The reaction can be 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 and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane and heptane, toluene, xylene and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as benzene and the like, and mixtures thereof. Examples of the chlorinating agent used in the reaction include, for example, thionyl chloride, oxalyl chloride and phosphorus oxychloride.

In the reaction, usually 1 to 10 mol of a chlorinating agent is used per 1 mol of the compound represented by the formula (4).

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 (3) can be isolated by performing post-treatment operations such as concentration of the reaction mixture as it is. The isolated compound represented by the formula (3) is usually used for the reaction in the next step without purification, but can be purified by distillation or the like, if necessary. The compound represented by the formula (2) can be produced, for example, by reacting the compound represented by the formula (14) with a reducing agent.

(1 4) (2)

[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 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 and mixtures thereof. Examples of the reducing agent used in the reaction include metal hydrides such as lithium aluminum hydride and diisobutyl dimethyl hydride.

In the reaction, a reducing agent is usually used in an amount of 0.5 to 5 mol per 1 mol of the compound represented by the formula (14).

After the reaction is completed, the reaction mixture is poured into water, extracted with an organic solvent, and the organic layer is washed with basic water (aqueous sodium hydroxide solution or the like) as necessary, followed by drying, concentration, and other post-treatment operations. By performing the above, the compound represented by the formula (2) can be isolated. The isolated compound represented by the formula (2) can be further purified by an operation such as distillation or chromatography. The compound represented by the formula (2) can also be produced according to the following scheme.

[In the formula, R i and R ² represent the same meaning as described above, and L ³ represents a chlorine atom, a bromine atom or a mainsulfonyloxy group. ]

Process (I I I— 1)

The compound represented by the formula (16) can be produced by reacting the compound represented by the formula (15) with potassium phthalimide.

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

Solvents 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, and toluene. , Aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as benzene and the like, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butylonitrile, and acids such as N, N-dimethylformamide Examples thereof include amides, sulfoxides such as dimethyl sulfoxide, and mixtures thereof.

In this reaction, usually 1 to 3 mol of fluoroimide potassium is used per 1 mol of the compound represented by the formula (15).

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 (16) can be isolated by performing post-treatment operations such as pouring the reaction mixture into water, extracting with an organic solvent, and drying and concentrating the organic layer. it can. The isolated compound represented by the formula (16) can be further purified by operations such as chromatography and recrystallization. Process (III_2)

The compound represented by the formula (2) can be produced by reacting the compound represented by the formula (16) with hydrazine.

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, and propanol, water, and mixtures thereof. In the reaction, hydrazine itself or hydrate of hydrazine is used as hydrazine.

In the reaction, 1 to 10 mol of hydrazine is usually used per 1 mol of the compound represented by the formula (16).

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 completion of the reaction, the reaction mixture is filtered, water is added to the filtrate, the mixture is extracted with an organic solvent, and the compound represented by the formula (2) is subjected to post-treatment operations such as drying and concentration of the organic layer. Can be released. The isolated compound represented by the formula (2) can be further purified by an operation such as distillation, and mouth chromatography. The compound represented by the formula (2) can also be produced according to the following scheme.

(2)

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

Process (V1)

The compound represented by the formula (18) is the same as the compound represented by the formula (17) It can be produced by reacting with a min or a salt thereof (for example, hydrochloride).

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

Solvents 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 and xylene Aromatic hydrocarbons such as benzene, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and ptyronitrile, and acid amides such as N, N-dimethylformamide And sulfoxides such as dimethyl sulfoxide, alcohols such as methanol, ethanol, propanol and isopropanol, water, and mixtures thereof.

In the reaction, 1 to 5 mol of hydroxylamine or a salt thereof is usually used per 1 mol of the compound represented by the formula (17).

After completion of the reaction, the compound represented by the formula (18) can be isolated by performing post-treatment operations such as pouring the reaction mixture into water, extracting with an organic solvent, and drying and concentrating the organic layer. it can. The isolated compound represented by the formula (18) can be further purified by an operation such as chromatography, recrystallization and the like.

Process (VI-2)

The compound represented by the formula (2) can be produced by reacting the compound represented by the formula (18) with hydrogen in the presence of a hydrogenation catalyst.

The reaction is usually performed in the presence of a solvent. It can also be carried out in the presence of an acid.

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

In the reaction, a hydrogenation catalyst is usually used in an amount of 0.000 :! to 0.5 mol per 1 mol of the compound represented by the formula (18). The reaction is usually performed under a hydrogen atmosphere at 1 to 100 atm. The reaction temperature of the reaction is usually in the range of 120 to 100, 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 (2) can be isolated by performing post-treatment operations such as filtering the reaction mixture and concentrating the filtrate. The isolated compound represented by the formula (2) can be further purified by a procedure such as chromatography and recrystallization. Examples of the plant disease having the controlling effect of the compound of the present invention include plant diseases caused by algae, and specific examples include the following diseases.

Vegetables, downy mildew of radish (Peronospora brassicae), downy mildew of spinach (Peronospora spinaciae, downy mildew of perensis (Peronospora tabacina), downy mildew of cucumber (Pseudoperonospora cubensis), downy mildew Disease (Plas Sir ara vi t icola), apple, strawberry, ginseng plague (Phytophthora cactorum), tomato, gray plague of cucumber (Phytophora capsici), pineapple plague (Phytophthora cinnamomi), potato, infestation of tomato phytothora > Phytophthora nicotianae var. Pythium rot (Pythium abariderumatum, P. debaryanum, P. irregulare, P. myriotylum, P. ultimum) of tobacco seedling blight (Pythium debaryanum). According to the above, plant disease can be controlled, but usually, a composition containing the compound of the present invention and a carrier, that is, a form of a composition for controlling a plant disease in which the compound of the present invention is supported on an appropriate carrier The compound for controlling plant diseases of the present invention is obtained by mixing the compound of the present invention with a solid carrier, a liquid carrier, a surfactant and other auxiliaries for preparation, and preparing an emulsion, a water-dispersible powder, a water-dispersible granule, and a flowable powder. It is formulated into powders, granules, etc. These formulations usually contain 0.1 to 90% by weight of the compound of the present invention.

Examples of the solid carrier used in the formulation include kaolin clay, Atsuya pulgite clay, bentonite, montmorillonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite and other minerals, corn cob powder, walnut shell powder etc Fine powders or granules of synthetic organic substances such as natural organic substances, synthetic organic substances such as urea, salts such as calcium carbonate and ammonium sulfate, and synthetic inorganic substances such as synthetic hydrous silicon oxide. Aromatic hydrocarbons such as alkylbenzene and methylnaphthylene, alcohols such as 2-propanol, ethylene glycol, propylene glycol, and cellosolve; ketones such as acetone, cyclohexanone, and isophorone; and vegetable oils such as soybean oil and cottonseed oil , Aliphatic hydrocarbons, esters, dimethylsulfoxide, acetonitrile and water.

Examples of the surfactant include alkyl sulfates, alkyl aryl sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkyl aryl ether phosphates, lignin sulfonates, and naphthyl sulfonate formaldehyde polycondensates. And anionic surfactants such as polyoxyethylene alkylaryl ether, polyoxyethylene alkylpolyoxypropylene block copolymer, and sorbitan fatty acid ester.

Other pharmaceutical auxiliaries include, for example, water-soluble polymers such as polyvinyl alcohol and polyvinyl pyrrolidone, gum arabic, alginic acid and salts thereof, polysaccharides such as CMC (potassium oxymethylcellulose), xanthan gum, aluminum magnesium silicate, and the like. And inorganic substances such as alumina sol, preservatives, coloring agents, stabilizers such as PAP (isopropyl isopropyl phosphate) and BHT.

The plant disease controlling agent of the present invention is used, for example, for protecting plants from plant diseases by foliar treatment of plants, and for treating plants that grow on the soil by treating the soil with plants. Used to protect against disease.

When the plant disease controlling agent of the present invention is used by applying foliar treatment to plants or by applying it to soil, the amount of treatment depends on the type of crop, etc., which is the plant to be controlled, the type of disease to be controlled, It can be varied depending on the occurrence of the disease to be controlled, the form of preparation, the treatment time, the weather conditions, etc., but usually 1 to 500 g, preferably 5 to 1 as the compound of the present invention per 1000 m ^2. 0 g.

Emulsions, wettable powders, flowables, etc. are usually processed by diluting with water and spraying. In this case, the compound of the present invention is usually diluted to a concentration in the range of 0.001 to 3% by weight, preferably 0.0005 to 1% by weight. Dusts, granules, etc. are usually processed without dilution.

Further, the plant disease controlling agent of the present invention can be used in a treatment method such as seed disinfection. Examples of the seed disinfection method include a method of immersing a plant seed in the plant disease controlling agent of the present invention prepared so that the concentration of the compound of the present invention is 1 to 100 ppm, and a method of dissolving the present invention in a plant seed. A method of spraying or smearing the plant disease controlling agent of the present invention having a compound concentration of 1 to 100 ppm, and a method of dressing a plant seed with the plant disease controlling agent of the present invention formulated in a dust. Is raised.

The method for controlling plant diseases of the present invention generally comprises treating an effective amount of the agent for controlling plant diseases of the present invention on a plant in which the occurrence of a disease is predicted or a soil in which the plant is grown, and / or confirming the occurrence of the disease. It is carried out by treating the soil where the plant or its animal grows.

The plant disease controlling agent of the present invention is generally used as a plant disease controlling agent for agricultural and horticultural use, i.e., a plant disease controlling agent for controlling plant diseases such as fields, paddy fields, orchards, tea fields, pastures, and lawns. Can be

The plant disease controlling agent of the present invention can be used together with other plant disease controlling agents, insecticides, acaricides, nematicides, herbicides, plant growth regulators and / or fertilizers. Examples of the active ingredients of such plant disease controlling agents include closanilonil, fluazinam, diclofluanid, Josetyl-A-cyclic imide derivatives (such as capbutane, captaphor, and phorpet), and dithiocarbamate derivatives (manneb, mancozeb, Thiram, Ziram, Zineb, Propineb, etc.), inorganic or organic copper derivatives (basic copper sulfate, basic copper chloride, copper hydroxide, oxine copper, etc.), and acylylanine derivatives (metalaxyl, furalaxyl, offrace, ciprofran, benalaxil) And oxadixyl), stoline viruline compounds (cresoxime methyl, azoxystrobin, trifloxystrobin, picoxystrobin, pyraclostrobin, dimoxystrobin, etc.), anilinopyrimidine derivatives (cyprodinii) , Pyrimethanil, mepanipyrim, etc.), phenylhydrol derivatives (fenpiclonil, fludioxonil, etc.), imide derivatives (procimidone, iprodione, vinclozolin, etc.), benzimidazoyl derivatives (carbendazim, benomyl, thiabendazole, thiophanate methyl) ), Amine derivatives (fenpropimorph, toridemorph, fenprovidin, spiroxamine, etc.), azoyl derivatives (propiconazole, triazimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromuconazole, epoxyconazole , Diphenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, microbutanol, fenbuconazole , Hexaconazole, Flukincona Zol, triticonazole, vitelenol, imazalil, furtriahole, etc.), simoxanil, dimethomorph, famoxadone, phenamidone, iprovacarb, benciavaricalp, cyazofamide, zoxamide, ethaboxam, boscalid, fenhexamide, quinoxyfen Prokinazit, dietophene carb, benzobenzoral S-methyl, guazatine, and penthiovirad. Specific examples of the compound of the present invention include the following compounds <

Amide compounds represented by formulas (i) to (xi i)

(xi) (xii) In the formulas (i) to (xii), Z represents any of the following groups.

3-fluorophenyl group, 3-chlorophenyl group, 3-bromophenyl group, 3-iodophenyl group, 3-methylphenyl group, 3-ethylphenyl group, 3-propylphenyl group, 3-isopropylphenyl group Group, 3-butylphenyl group, 3_ (sec-butyl) phenyl group, 3-isobutylphenyl group, 3- (tert-butyl) phenyl group, 3-vinylphenyl group, 3- (1-methylvinyl) phenyl group , 3- (1-Propenyl) phenyl, 3-ethynylphenyl, 3- (fluoromethyl) phenyl, 3- (difluoromethyl) phenyl, 3- (trifluoromethyl) phenyl, 3-methoxyphenyl , 3-ethoxyphenyl group, 2,3-difluorophenyl group, 3-chloro-2 fluorophenyl group, 3-bromo-1-fluorophenyl group, 2-fluoro Rho 3 —Methylphenyl, 2-Fluoro 3 — (Trifluoromethyl) phenyl, 2 —Fluoro-3-methoxyphenyl, 3 —Fluoro-2-chlorophenyl, 2,3-Dichlorophenyl, 3 —Bromo _ 2 _ chloro phenyl group, 2 _ chloro mouth — 3 _ methylphenyl group, 2 _ chloro mouth — 3 _ (trifluoromethyl) phenyl group, 2 — chloro _ 3-methoxyphenyl group, 3 _Fluoro-2-methylphenyl group, 3-chloro-2_methylphenyl group, 3_bromo-2-methylphenyl group, 2,3-dimethylphenyl group, 2-methyl-3- (trifluoromethyl) phenyl group , 3-methoxy-2-methylphenyl, 3-phenylphenyl, 2-fluoro-3-phenylphenyl, 2-chloro-3-phenylphenyl, 2-methyl-3-phenylphenyl, 2 —Phenoxyphenyl group, 3-fluoro-2 —Phenoxyphenyl group, 3-chloro-1- 2 —Phenoxyphenyl group, 3 _bromo — 2 _Phenoxyphenyl group, 3-(trifluoromethyl 1) 2-phenoxyphenyl group, 3-methoxy-12-phenyloxyphenyl group, 3 _methyl-2 phenoxyphenyl group, 3-phenoxyphenyl group, 2-fluoro-3-phenoxyphenyl group, 2 _________________________________________ 3-phenoxyphenyl group, 2-methyl-3-phenoxyphenyl group, indane-4-yl group, 5, 6, 7, 8-tetrahydronaphthylene _ 1 -yl group, 6 , 7,8,9-Tetrahydro-5H_benzocycloheptene-11-yl and 1-naphthyl groups. Hereinafter, the present invention will be described in more detail with reference to Production Examples, Formulation Examples, Test Examples, and the like, but the present invention is not limited to these Examples.

First, Production Examples of the compound of the present invention will be described. Production Example 1

3- {3-methoxy-4- (2-propynyloxy) phenyl} propionic acid chloride 0.20 g, benzylamine 0.085 g, triethylamine 0.17m

1 and 5 ml of tetrahydrofuran were mixed and stirred at room temperature for 30 minutes. Water was added to the reaction mixture, and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane and N-benzyl-3- {3-methoxy-4-

(2-propieroxy) phenyl} propionamide (hereinafter, referred to as the present compound 1) 0.19 g was obtained.

Compound of the present invention 1

¹ H-NMR (CDC 13, TMS) 6 (p pm): 7.27 to 7.32 (3H, m), 7.14 to 7.16 (2H, m), 6.94 (1H, d, J = 8.0Hz), 6.72 to 6.75 (2H, m), 5.57 (1H, br.s), 4.73 (2H, d, J = 2.4Hz), 4.41 (2H, d, J = 5.5Hz), 3.82 (3H, s), 2.95 (2H, t, J = 7.5Hz), 2.48 to 2.51 (3H, m) Example 2

3-{3-Methoxy-4- (2-propynyloxy) phenyl} propionic acid Chloride Same as Preparation Example 1 using 0.20 g of chloride and 0.1 g of 3-chlorobenzylamine To obtain 0.24 g of N- (3-chlorobenzyl) _3_ {3-methoxy-4- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as the present compound 2). Obtained.

Compound 2 of the present invention

CH

Ή-NMR (CDC 13, TMS) 6 (p pm): 7.18-7.29 (3H, m), 6.93 to 6.95 (1H, m), 6.94 (1H, d) , J = 8.0 Hz), 6.71 to 6.75 (2H, m), 5.62 (1H, br.s), 4.73 (2H, d, J = 2.4Hz), 4.38 (2H, d, J = 5.8Hz), 3.83 (3H, s), 2.95 (2H, t, J = 7.5Hz), 2.48 ~ 2. 54 (3H, m) Production example 3

3- {3-methoxy-41- (2-propynyloxy) phenyl} propionic acid chloride 0.21 g and 2-chlorobenzylamine 0.11 g, the same as in Production Example 1 The operation was performed to obtain 0.13 g of N— (2-chlorobenzyl) -3-({3-methoxy-41- (2-propynyloxy) phenyl) propionamide (hereinafter, referred to as the present compound 3). Obtained.

Compound 3 of the present invention

_{1 H-NMR (CDC 1 3} , TMS) 6 (p pm): 7. 20~ 7. 34 (4H, m), 6. 92 (1H, d, J = 8. 0Hz) 6. 70~6. 72 (2H, m), 5.76 (1H, br.s), 4.73 (2H, d, J = 2.4 Hz), 4.49 (2 H, d, J = 5.8 Hz), 3 80 (3H, s), 2.93 (2H, t, J = 7.2 Hz), 2.48 to 2.52 (3H, m)

Production Example 4

3- {3-methoxy-4- (2-propynyloxy) phenyl} propionic acid 0.50 g, 3_trifluoromethylbenzylamine 0.41 g, WSC 0.45 g and N, N— 10 ml of dimethylformamide was mixed and stirred at room temperature for 4 hours. Water was added to the reaction mixture, which 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 washed with hexane and N_ (3_trifluoromethylbenzyl) —3- {3-methoxy-4-1 (2-propieroxy) phenyl} propionamide (hereinafter referred to as the present compound 4). 0.50 g was obtained.

Compound 4 of the present invention

_{1 H-NMR (CDC 1 3} , TMS) δ (p pm): 7. 32~ 7. 53 (3H, m), 7.31 (1H, d, J = 7.6Hz), 6.94 (1H, d, J = 8.0Hz), 6.72 to 6.77 (2H, m), 5.71 (1H , Br. S), 4.73 (2H, d, J = 2.4 Hz), 4.46 (2H, d, J = 6.0 Hz), 3.82 (3H, s), 2.96 (2H , T, J = 7.6 Hz), 2.53 (2H, t, J = 7.6 Hz), 2.48 (2H, t, 1 = 2.4 Hz)

Production Example 5

3-{3-Methoxy-4_ (2-propynyloxy) phenyl} The same operation as in Production Example 4 was performed using 0.50 g of propionic acid and 0.32 g of 3-methoxybenzylamine. 0.39 g of N— (3-methoxybenzyl) _3— {3-methoxy—4- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as the present compound 5) was obtained.

Compound 5 of the present invention

Ή-NMR (CDC 13, TMS) δ (p pm): 7.22 (1 H, t, J = 8.0 Hz), 6.93 (1 H, d, J = 7.9 Hz), 6.71 ~ 6.81 (5H, m), 5.59 (1H, br.s), 4.73 (2H, d, J = 2.4Hz), 4.38 (2H, d, J = 5.5Hz) ), 3.83 (3H, s), 3.78 (3H, s), 2.95 (2H, t, J = 7.lHz), 2.48 to 2.52 (3H, m) Production Example 6

3-{3-Methoxy-41- (2-propynyloxy) phenyl} The same operation as in Production Example 4 was performed using 0.50 g of propionic acid and 0.29 g of 3-methylbenzylamine. Then, 0.34 g of N- (3-methylbenzyl) _3_ {3-methoxy-14- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as the present compound 6) was obtained.

Compound 6 of the present invention

_{1 H-NMR (CDC 1 3} , TMS) δ (p pm): 7. 19 (1H, t, J = 7 5Hz), 7.07 (1H, d, J = 7.5Hz), 6.92 to 7.00 (3H, m), 6.71 to 6.75 (2H, m), 5.60 (1H , br. s)> 4.72 (2 H, d, J = 2.5 Hz), 4.36 (2 H, d, J = 5.5 Hz), 3.82 (3 H, s), 2.95 (2H, t, J = 7.5 Hz), 2.44 to 2.51 (3H, m), 2.32 (3H, s)

Production Example 7

3-{3-Methoxy-4- (2-propynyloxy) phenyl} 702 mg of propionic acid, 589 mg of (1-naphthalene) methylamine hydrochloride, 0.63 g of WSC and 10 ml of pyridine are mixed, and the mixture is mixed at room temperature for 4 hours. Stirred. Water was added to the reaction mixture, which 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 washed with hexane to obtain N—K naphthylene-1-yl) methyl} —3— {3_methoxy—4 -— (2-propynyloxy) phenyl} propionamide (hereinafter referred to as “the book”). Inventive compound 7) 800 mg was obtained.

Compound 7 of the present invention

Ή-NMR (CDC 13, TMS) δ (p pm): 7.76 (3H, m), 7.47 to 7.56 (2H, m), 7.29 to 7.43 (2H, m) , 6.89 (1H, d, J = 7.9 Hz), 6.73 (1H, d, J = 1.9 Hz), 6.69 (1H, dd, J = 8.1 Hz, 2 0 Hz), 5.55 (1 H, b r.s), 4.86 (2 H, d, J = 5.3 Hz), 4.70 (2H, d, J = 2.4 Hz), 3. 80 (3 H, s), 2.94 (2H, t, J = 7.5 Hz), 2.44 to 2.51 (3H, m)

Production Example 8

N — {(Naphthalene-1-yl) methyl} —3— {3-Methoxy-4- (2-provinyloxy) phenyl} Propionamide (500 mg), Lawson's reagent (390 mg) and tetrahydrofuran (10 ml) are mixed, and mixed with 65 Stir for 4 hours. It was allowed to cool to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel column purification, and N-{(naphthalene-11-yl) methyl} —3 -— {3-methoxy-4_ (2-propynyloxy) B) 80 mg of thiopropionamide (hereinafter referred to as compound 8 of the present invention).

Compound 8 of the present invention

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):.. 7. 80~ 7. 90 (2H, m), 7. 68~7 75 (1H, m), 7. 48~7 55 ( 2H, m), 7.30 to 7.44 (2H, m), 7.11 (1H, br.s), 6.84 (1H, d, J = 7.9Hz), 6 73 (1 H, d, J = 1.9 Hz), 6.66 (1 H, dd, J = 8.1 Hz, 2.0 Hz), 5.1 1 (2H, d, J = 4.8 Hz) ), 4.68 (2H, d, J = 2.2Hz), 3.78 (3H, s), 3.07 (2H, t, J = 7.2Hz), 2.89 (2H, t, J = 7.2 Hz), 2.46 (1 H, t, J = 2.4 Hz)

Production Example 9

3- {3-methoxy-4- (2-propynyloxy) phenyl} propionic acid 1.17 g, 3-phenylbenzylamine 917 mg, WSC 1.05 g and N, N-dimethylformamide 2 Om were mixed and stirred at room temperature for 4 hours. 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 hydrogencarbonate and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is washed with hexane to give N- (3-phenylbenzyl) -3- {3-methoxy-4- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as compound 9 of the present invention). .) 1. 48 g were obtained.

Compound 9 of the present invention

¹ H-NMR (CDC 1 J, TMS) δ (p pm): 7.30 7.60 (8H, m), 7.10 to 7.15 (1H, m), 6.89 (1H , d, = 8.2 Hz), 6.69-6.75 (2H, m), 5.80 (1 H, b r.s), 4.68 (2H, d, J = 2.4 Hz), 4.46 (2H, d, J = 5.7Hz), 3.80 (3H, s), 2.94 (2H, t, J = 7.55HHzz)), 22.50 (2H, J = 7.6Hz), 2.46 (1H, t, J = 24Hz)

Production Example 10

3- {3-methoxy-4- (2-propynyloxy) phenyl} propionic acid 1.17 g, 3-phenoxybenzylamine 1.00 g, WSC l. 06 g and N, N— 10 ml of dimethylformamide was mixed and stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is washed with hexane to give N- (3-phenoxybenzyl) _3- {3-methoxy-41- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as compound 10 of the present invention). .) 1. Obtained 50 g

The present compound 10

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):.. 7. 23~ 7. 36 (3H, m), 7. 10~7 15 (1H, m), 6. 84~7 02 ( 6H, m), 6.75 (1 H, d, J = 2. OHz), 6.72 (1 H, dd, J = 8. OHz, 2. OHz), 5.65 (1H, br.s) ), 4.71 (2H, d, J = 2.4 Hz), 4.38 (2H, d, J = 5.6 Hz), 3.82 (3H, s), 2.93 (2H, t, J = 7.6 Hz), 2.47 to 2.52 (3H, m)

Production Example 11

N- (3-phenylpentyl) 1-3- {3-methoxy-41- (2-propynyloxy) phenyl} propionamide (799 mg), Lawson's reagent (58 Omg) and tetrahydrofuran (1 Om1) were mixed and mixed at 65 ° C. Stir for 4 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was subjected to silica gel column purification to give N- (3-phenylbenzyl) 13- {3-methoxy-4- (2-propynyloxy) phenyl} thiopropionamide (hereinafter referred to as Compound 11 of the present invention). 405 mg was obtained. Compound of the present invention 11

H-NMR (CDC 13 TMS) δ (p pm): 7.52 to 7.57 (3H, m),

7.34 to 7.48 (5H, m), 7.14 (1H, br.s), 7.10 (1H, d, J-7.5Hz), 6.90 (1H, d, J = 8.2Hz), 6.76 (1H, d, J = 1.9Hz), 6.72 (1H, dd, J = 8.0Hz, 1.9Hz),

4.80 (2H, d, J = 5.0 Hz), 4.67 (2H, d, J = 2.4 Hz),

3.81 (3H, s), 3.10 (2H, t, J = 7.2 Hz), 2.95 (2H, t, J = 7.2 Hz), 2.45 (1H, s)

Production Example 12

N— (3-phenoxybenzyl) -1-3- {3-II-methoxy-14_ (2-propynyloxy) phenyl} Propionamide 415 mg, Lawson reagent 29 Omg and

Dimension

And 10 ml of tetrahydrofuran, and the mixture was stirred at 65 for 4 hours. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel column purification, and N_ (3-phenoxybenzyl) -3- (3-methoxy-4- (2-propynyloxy) phenyl} thiopropionamide (hereinafter referred to as compound 12 of the present invention). ) 38 Omg was obtained. Compound of the present invention 12

Ή-NMR (CDC 13, TMS) δ (ρ pm): 7.31 to 7.38 (2H, m), 7.23 to 7.29 (1H, m), 7.07 to 7.16 ( 2H, m), 6.97 to 7.02 (2H, m), 6.81 to 6.95 (4H, m), 6.70 to 6.77 (2H, m), 4.70 to 4 72 (4H, m), 3.82 (3H, s), 3.07 (2 H, t, J = 7.3 Hz), 2.93 (2H, t, J = 7.3 Hz), 2. 47 (1 H, t, J = 1.9 Hz)

Production Example 13

3- {3-methoxy-41- (2-propynyloxy) phenyl} 937 mg of propionic acid, 797 mg of 2-phenoxybenzylamine, 842 mg of WSC, and 20 ml of N, N-dimethylformamide are mixed at room temperature. Stir for 4 hours. reaction Water was added to the mixture, which was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane to give N- (2-phenoxybenzyl) -3- (3-methoxy-4- (2-propynyloxy) phenyl} propionamide (hereinafter referred to as Compound 13 of the present invention). 1. 12 g was obtained.

Compound 13 of the present invention

_{Ή NMR (CDC 1 3, TMS} ) δ (p pm):.. 7. 20~ 7. 36 (4H, m), 7. 06~7 14 (2H, m), 6. 84~6 96 (4H , M), to 6.66 6.74 (2H, m), 5.74 (1H, br.s), 4.71 (2H, d, J = 22..4Hz), 4.46 (2H, d, J = 5.8Hz), 379 (3H, s), 2.87 (2H, t, J = 7.6Hz), 2.47 (1H, t, J = 2.4Hz), 2. 39 (2H, t, J = 7.5Hz)

Production Example 14

3- {3-methoxy-4- (2-propynyloxy) phenyl} 0.50 g of propionic acid, 0.52 g of 3-bromobenzylamine hydrochloride, 0.45 g of WSC, 2 ml of pyridine and N , N-dimethylformamide (10 ml) were mixed and stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed three times with 5% hydrochloric acid, once with a saturated aqueous solution of sodium hydrogencarbonate and once with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane, and N_ (3-bromobenzyl) -13- {3-methoxy-4- (2-propynyloxy) phenyl} propionamide (hereinafter, referred to as compound 14 of the present invention) 0 65 g were obtained. Compound of the present invention 14

Ή-NMR (CDC 13, TMS) δ (p pm): 7.15 to 7.40 (3H, m), 7.06 (1H, d, J = 7.5Hz), 6.95 (1H, d, J = 8.3Hz), 6.Ί2 to et al. 75 (2H, m), 5.63 ( S), 4.74 (2H, d, J = 2.4 Hz), 4.38 (2H, d, J = 5.9 Hz), 3.83 (3H, s), 2.95 (2H, t, J = 7.5Hz), 2.52 (2H, t, J = 7.5Hz), 2.49 (1H, t, J = 2.4Hz)

Production Example 15

3- {3-Methoxy-4_ (2_propynyloxy) phenyl} propionic acid 0.50 g, 3_ethylbenzylamine hydrochloride 0.378 and \ ¥ 3〇 0.45 g Then, the same operation as in Production Example 14 was performed, and N— (3_ethylbenzyl) -3- (3-methoxy-4 -_ (2_propieroxy) phenyl} propionamide (hereinafter, referred to as compound 15 of the present invention). 0.48 g was obtained.

Compound 15 of the present invention

Ή-NMR (CDC 13 ₎ TMS) <5 (p pm): 7.22 (1H, t, J = 7.5 Hz), 7.11 (1H, d, J = 75 Hz), 7.04 (1H, s), 6.98 (1 H, d, J = 7.5 Hz), 6.94 (1H, d, J = 7.5 Hz), 6.70 to 6.76 (2H, m) , 5.58 (1H, br.s), 4.73 (2H, d, 1 = 2.4 Hz), 4.39 (2H, d, J-5.5 Hz), 3.83 (3H, s) , 2.95 (2H, t, J = 7.5 Hz) 2.62 (2H, q, 1 = 7.5 Hz), 2.48 to 2.52 (3H, m), 1.22 (3H, t , J = 7.5 Hz) Next, the production of the intermediate of the present invention will be described as a reference example.

Reference example 1

100 g of 4-benzyloxy-3-methoxybenzaldehyde, 120 g of ethylphosphonoethyl acetate, 570 g of potassium carbonate and 570 ml of water were mixed and stirred under reflux for 20 hours. After allowing the reaction mixture to cool to room temperature, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was recrystallized from ethanol to give 58.6 g of 3- {3-methoxy_4_ (benzyloxy) phenyl} ethyl acrylate. Obtained,

B) Phenyl} ethyl acrylate

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):. 7. 60 (1H, d, J = 15 Hz), 7. 29~7 44 (5H, m), 7. 06 (1 H, d, J = 1.9Hz), 7.02 (1H, dd, J = 8.2Hz, 1.9Hz), 6.86 (1H, d, J = 8.2Hz), 6.29 (1H, d, J = 15Hz), 5.18 (2H, s), 4.25 (2H, q, J = 7.3Hz), 3.91 (3H, s), 1.33 (3H, t, J = (7.3 Hz)

Reference example 2

3-{3-Methoxy-4- (benzyloxy) phenyl} Ethyl acrylate 33 g, 5% palladium on carbon 0.3 g, 36% hydrochloric acid approx. 0.05 g and ethanol 200 ml are mixed and hydrogen atmosphere The mixture was stirred until the absorption of hydrogen gas stopped. The reaction 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, about 5 g of activated carbon and about 5 g of activated clay were added, and the mixture was filtered. The filtrate was concentrated under reduced pressure. The residue was washed with hexane to obtain 23 g of ethyl 3- (4-hydroxy-13-methoxyphenyl) propionate. 3- (4-hydroxy-3-methoxyphenyl) ethyl propionate

^{_{1 H-NMR (CDC 1 3}} , TMS) 6 (p pm):. 6. 82 (1 H, d J = 7. 7Hz), 6. 67~6 70 (2H, m), 5. 47 (1 H, s), 4.19 (2 H, q, J = 7.2 Hz), 3.87 (3H, s), 2.88 (2H, t, J = 7.5 Hz), 2.58 (2H , t, J = 7.5Hz), 1.24 (3H, t, J = 7.2Hz)

Reference example 3

3- (4-hydroxy-1-methoxyphenyl) ethyl propionate (23.8 g), propargyl bromide (11.4 ml), potassium carbonate (20.5 g) and acetonitrile 250 ml was mixed and stirred at 80 ° C. for 2 hours. The reaction mixture was cooled to room temperature, added ethyl acetate and filtered. The filtrate was concentrated under reduced pressure to obtain 28.9 g of 3_ {3-methoxy-4 -_ (2-propynyloxy) phenyl} ethyl propionate. 3-{3-Methoxy-4-1- (2-propynyloxy) phenyl} ethyl propionate

Ή-NMR (CDC 13, TMS) δ (p pm): 6.95 (1 H, d, J = 7.7 Hz), 6.72 to 6.75 (2H, m), 4.73 (2H, d, J = 2.4 Hz, 4.13 (2H, q, J = 7.2 Hz), 3.86 (3H, s), 2.90 (2 H, t, J = 7.5 Hz), 2.60 (2H, t, J = 7.5Hz), 2.49 (1H, t, J = 2.4Hz), 1.24 (3H, t, J = 7.OHz)

Reference example 4

3— {3-Methoxy—4- (2-propynyloxy) phenyl} 28.9 g of ethyl propionate, 4.O g of lithium hydroxide, 300 ml of tetrahydrofuran and 10 Oml of water are mixed, and 65: Stir for 3 hours. Water was added to the reaction mixture, which was concentrated under reduced pressure. 5% Hydrochloric acid was added to the residue, and the mixture was 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 22.7 g of 3- {3-methoxy-4- (2-propynyloxy) phenyl} propionic acid.

3-{3-Methoxy-4- (2-propieroxy) phenyl} propionic acid

^{_{1 H-NMR (CDC 1 3}} , TMS) δ (ppm):. 6. 96 (1H, d, J = 8. 2Hz), 6. 73~6 75 (2H, m), 4. 73 (2H, d, J = 2.4H z), 3.85 (3H, s), 2.91 (2H, t, J = 8Hz), 2.67 (2H, t, J = 8Hz), 2.49 (1 (H, t, J = 2.4 Hz)

Reference Example 5

3- {3-methoxy-4 _ (2-propynyloxy) phenyl} propionic acid The mixture was mixed with 12.7 g, Shii-Dai-Thionyl 4.3 m 1, toluene 100 m 1 and about 0.05 g of N, N-dimethylformamide and stirred at 8 Ot: for 30 minutes. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure to obtain 14.6 g of 3- {3-methoxy-4- (2-propynyloxy) phenyl} propionate chloride.

3- {3-methoxy-4-1- (2-propynyloxy) phenyl} propionate chloride

Ή-NMR (CDC 13, TMS) 6 (p pm): 6.97 (1H, d, J = 8.8 Hz), 6.72 to 6.74 (2H, 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 (1 H, t, J = 2.4 Hz)

Reference example 6

Naphthalene-1-carbaldehyde 7.81 g, hydroxylamine hydrochloride 6.

94 g, 5.93 g of pyridine and 90 ml of ethanol were mixed and stirred at 80 for 4 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The organic layer was washed sequentially with 5% hydrochloric acid and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with hexane to obtain 7.43 g of naphthalene-one-potency lipaldehyde oxime.

Naph Yu-Len—One-strength Lupoaldehyde Oxime

Ή-NMR (CDC 13, TMS) δ (p pm) 8.79 (1H, s), 8.49 (1Η, d, J = 8.3Hz), 7.84 to 793 (2H, m), 7.73 to 7.79 (1 H, m), 7.44 to 7.6 1 (3H m), 7.64 (1 H, br.s)

Reference Example 7

A mixture of 7.43 g of naphthalene-1-carbaldehyde oxime, 0.8 g of 10% palladium on carbon, about 9.4 ml of 36% hydrochloric acid and 200 ml of ethanol is mixed with hydrogen. The mixture was stirred under an atmosphere until absorption of hydrogen gas stopped. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain 7.52 g of (1-naphthalene) methylamine hydrochloride.

(1 naphthylene) Methylamine hydrochloride

¹ H-NMR (DMS O-d 6, TMS) δ (p pm): 8.45 (3H, br.s), 8.13 (1H, d, J = 8.5 Hz), 7.94 Up to 8.00 (2H, m), 7.52 to 7.68 (4H, m), 4.46 to 4.56 (2H, m)

Reference Example 8

3.73 g of 3-bromocyanobenzene, 2.0 g of phenylproponic acid, 9.55 g of tripotassium phosphate hydrate, {1,1'-bis (diphenylphosphino) phenoctene } Dichloropalladium (II) 367 mg of methylene chloride complex and 40 ml of ethylene glycol dimethyl ether were mixed and stirred at 80 for 4 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column purification to obtain 2.60 g of biphenyl-2-carbonitrile.

Biphenyl — 2-potassium

Ή-NMR (CDC 1 J, TMS) δ (p pm): 7.84 to 7.88 (1H, m), 7.78 to 7.83 (1H, m), 7.61 to 7.65 (1H, m), 7.5 1 to 7.58 (3H, m), 7.39 to 7.50 (3H, m)

Reference Example 9

A solution of 2.6 g of biphenyl-3-butanol was added dropwise to a mixture of 825 mg of lithium aluminum hydride and 15 ml of tetrahydrofuran, followed by stirring at room temperature for 3 hours. The reaction mixture was cooled to 0-5: and a 25% aqueous sodium hydroxide solution was added dropwise to the reaction mixture. The mixture was filtered and the filtrate was concentrated under reduced pressure. To the residue was added form-form and water, and the layers were separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain 2.62 g of 3-phenylpentylamine.

_{Ή-NMR (CDC 1 3,} TMS) <5 (p pm):. 7. 57~ 7. 62 (2H, m), 7. 53 (lH, s), 7. 27~7 50 (6H, m ), 3.93 (2H, s), 1.47 (2H, br.s)

Reference example 10

4.71 g of methanesulfonyl chloride is added dropwise at 0 to a mixture of 7.5 g of (3-phenoxyphenyl) methanol, 5.67 g of triethylamine and 100 ml of tetrahydrofuran at 0 ° C. for 30 minutes and then at room temperature. For 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. Ethyl acetate and water were added to the residue, and the layers were separated. The organic layer was washed successively with 5% hydrochloric acid and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 9.8 g of 3-phenoxybenzyl methanesulfonate. Methanesulfonic acid = 3 _ phenoxybenzyl

Ή-NMR (CDC 13, TMS) δ (ρ pm): 7.31 to 7.39 (3H, m), 7.11 to 7.17 (2Η, m), 6.98 to 705 (4H, m), 5.19 (2Η, s), 2.94 (3Η, s)

Reference example 1 1

6.52 g of potassium phthalimide, 9.80 g of methanesulfonic acid = 3-phenoxybenzyl and 20 Om1 of N, N-dimethylformaldehyde were mixed and stirred at 50 for 4 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was washed with hexane to obtain 6.91 g of N- (3-phenoxybenzyl) phenylimide.

N- (3-phenoxybenzyl) phthalimide

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):.. 7. 83~ 7. 88 (2H, m), 7. 69~7 74 (2H, m), 7. 22~7 36 ( 3H, m), 7.06 to 7.16 (3H, m), 6.96 to 7.01 (2H, m), 6.85 to 6.89 (1H, m), 4.82 (2H , S)

Reference Example 12

Hydrazine monohydrate (1.24 g) was added dropwise to a mixture of 6.91 g of N- (3-phenoxybenzyl) phthalimide and 100 ml of methanol, and the mixture was stirred at 65 for 4 hours. The reaction mixture was allowed to cool to room temperature, water was added, and the mixture was concentrated under reduced pressure. 1 M ZL hydrochloric acid was added to the residue, and the mixture was filtered. Black-mouthed form was added to the filtrate. A 25% aqueous sodium hydroxide solution was added until the aqueous layer of the mixture became alkaline, and the mixture was separated. The obtained organic layer was washed successively with a saturated saline solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 3-fe.

3-phenoxybenzylamine

Ή-NMR (CDC 13, TMS) δ (p pm): 4 to 7.36 (3H, m), 6.95 to 7.13 (5H, m), 6.85 to 6 (1 H, m) , 3.84 (2H, s), 1.42 (2H, br.s)

Reference Example 13

A solution of 10.7 g of 2-phenoxybenzoic acid in tetrahydrofuran was added dropwise to a mixture of 2.85 g of lithium aluminum hydride and 50 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was cooled to 0-5 "C and water was added dropwise. The mixture was filtered and the filtrate was concentrated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was separated. It was dried and concentrated under reduced pressure to give 8.5 g of (2-phenoxyphenyl) methanol.

(2-phenoxyphenyl) methanol

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):.. 7. 43~ 7. 48 (lH, m), 7. 30~7 36 (2H, m), 7. 21~7 28 ( 1H, m), 7.07 to 7.17 (2H, m), 6.95 to 7.02 (2H, m), 6.84 to 6.90 (1H, m), 4.75 ( 2H, d, J = 6.2Hz), 2.07 (1H, t, J = 6.2Hz)

Reference Example 14

2.52 g of methanesulfonyl chloride were added dropwise at 0 to a mixture of 4.0 g of (2-phenoxyphenyl) methanol, 3.03 g of triethylamine and 80 ml of tetrahydrofuran, 0 at 30 minutes, and Stirred at room temperature for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. Ethyl acetate and water were added to the residue, and the layers were separated. The obtained organic layer was washed sequentially with 5% hydrochloric acid and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 5.45 g of 2-phenoxybenzyl methanesulfonate. Methanesulfonic acid = 2-phenoxybenzyl

Ή-NMR (CDC 13 _> TMS) 6 (p pm): 7.47 to 7.53 (1H, m), 7.31 to 7.39 (3H, m), 7.10 to 7.10 ( 2H, m), 6.96 to 7.01 (2H, m), 6.87 to 6.92 (1H, m), 5.33 (2H, s), 2.90 (3H, s)

Reference Example 15

3.331 g of potassium phthalimide, 2.018 methanesulfonic acid = 2_phenoxybenzyl 5.018 and N-dimethylformaldehyde 8 Om1 were mixed and stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was washed with hexane to obtain 5.3 g of N_ (2-phenoxybenzyl) phthalimide.

N- (2-phenoxybenzyl) phthalimide

Ή-NMR (CDC 13, TMS) d (p pm): 7.78 to 7.82 (2H, m), 7.66 to 7.72 (2H, m), 7.05 to 7.36 (4H , m), 6.86-7.12 (5H, m), 4.96 (2H, s)

Reference Example 16

0.91 g of hydrazine monohydrate was added dropwise to a mixture of 5.0 g of N- (2-phenoxybenzyl) phthalimide and 50 ml of methanol, and the mixture was stirred at 65 for 2 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was concentrated under reduced pressure. 1 mol L hydrochloric acid was added to the residue, and the mixture was filtered. To the resulting filtrate was added form. A 25% aqueous sodium hydroxide solution was added until the aqueous layer of the mixture became alkaline, and the mixture was separated. The obtained organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 2-lg of 2-phenoxybenzylamine.

2-phenoxybenzylamine

_{Ή-NMR (CDC 1 3,} TMS) δ (p pm):.. 7. 28~ 7. 40 (3H, m), 7. 18~7 25 (1H, m), 7. 05~7 15 ( 2H, m), 6.93 to 6.99 (2H, m), 6.88 (1H, dd, J = 8.OHz, 1.2Hz), 3.86 (2H, s), 1. 70 (2H, br.s)

Reference Example 17

5.0 g of 3-cyanoacetophenone, 0.65 g of sodium borohydride and 7 Om1 of ethanol were mixed and stirred at room temperature for 1 hour. To the reaction mixture was added a saturated aqueous solution of ammonium chloride, and the mixture was concentrated under reduced pressure. The obtained residue was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 5.O g of crude 3- (1-hydroxyethyl) benzonitrile.

3- (1-hydroxyethyl) benzonitrile

Ή-NMR (CDC 13, TMS) 6 (p pm): 7.68 to 7.69 (lH, m), 7.60 to 7.63 (1H, m), 7.55 to 7.57 (1 H, m), 7.46 (1 H, t, J = 7.7 Hz) 4.92 to 4.97 (1 H, m), 1.97 (1 H, br.s), 1. 51 (3H, d, J = 6.7Hz)

Reference Example 18

3.7 g of methanesulfonyl chloride was added to a mixture of 4.5 g of crude 3- (1-hydroxyethyl) benzonitrile, 3.4 g of triethylamine and 150 ml of tetrahydrofuran under ice-cooling, followed by stirring at room temperature for 30 minutes. did. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain crude methanesulfonic acid = 1- (3-cyanophenyl) ethyl.

A solution of crude methanesulfonic acid = 1- (3-cyanophenyl) ethyl in tetrahydrofuran was added dropwise to a mixture of 1.7 g of lithium aluminum hydride and 100 ml of tetrahydrofuran, and the mixture was stirred under reflux for 1 hour. The reaction mixture was allowed to cool to room temperature, and 3.5 ml of a 20% aqueous sodium hydroxide solution and then 5.2 ml of water were added dropwise. The mixture was stirred at room temperature for 1 hour and filtered. The filtrate was concentrated under reduced pressure. The residue was mixed with acetonitrile, added with 3.6 g of 36% hydrochloric acid, and concentrated under reduced pressure. The obtained residue was sequentially washed with acetonitrile, methyl-tert-butyl ether and hexane to obtain 1.2 g of 3-ethylbenzylamine hydrochloride.

3-ethylpentylamine hydrochloride

¹ H-NMR (DMSO-d 6, TMS) δ (p pm): 8.34 (3H, br.s), 7.22 to 7.34 (4H, m), 3.99 (2 H, br) s), 2.62 (2H, q, J = 7.5Hz), 1.20 (3H, t, J = 7.5Hz) The following shows formulation examples. Parts represent parts by weight.

Formulation Example 1

50 parts of each of the present compounds 1 to 15, 3 parts of calcium ligninsulfonate, Each wettable powder is obtained by well pulverizing and mixing 2 parts of magnesium persulfate and 45 parts of synthetic hydrous silicon oxide.

Formulation Example 2

20 parts of each of the present compounds 1 to 15 and 1.5 parts of sorbitan trioleate were mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and finely pulverized by a wet pulverization method. 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate are added thereto, and 10 parts of propylene glycol are further added and stirred and mixed to obtain each flowable preparation.

Formulation Example 3

Each powder is obtained by thoroughly pulverizing and mixing 2 parts of each of the present compounds 1 to 15, 88 parts of kaolin clay and 10 parts of talc.

Formulation Example 4

Each of the emulsions is obtained by thoroughly mixing 5 parts of each of the compounds 1 to 15 of the present invention, 14 parts of polyoxyethylenestyrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene.

Formulation Example 5

2 parts of each of the compounds 1 to 15 of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are well pulverized and mixed, and water is added and kneaded well. Each granule is obtained by granulation and drying. Formulation Example 6

10 parts of each of the present compounds 1 to 15; 35 parts of white carbon containing 50 parts of a polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts of water were mixed, and finely pulverized by a wet pulverization method. By doing so, each formulation is obtained. Next, Test Examples show that the compounds of the present invention are useful for controlling plant diseases.

The control effect was determined by visually observing the area of the lesion on the plant where the test was conducted at the time of the survey, and comparing the area of the lesion of the plant treated with the compound of the present invention with the area of the lesion of the untreated plant. It was evaluated by:

Test example 1

Plastic pots were filled with sandy loam, and tomatoes (variety: Ponterosa) were sown and grown in a greenhouse for 20 days. Compounds of the present invention 1-2 and 4 to 15 were prepared according to Preparation Example 6, diluted to a predetermined concentration (500 ppm) with water, and the diluted solution was applied to the tomato leaf surface. The foliage was sprayed so as to adhere sufficiently. After drying the diluted solution on the leaf surface, spray inoculation with a suspension of zoospores of tomato blight (containing about 10,000 zoospores per lm of suspension) (about 2 ml per plant) Percentage) After inoculation, they were cultivated for 1 day at 23 ° C and a relative humidity of 90% or more, and then cultivated for 4 days in a greenhouse at 24 ° C during the day and 20 ° C at night. After that, the control effect was investigated.

As a result, the lesion area on plants treated with the present compounds 1-2 and 4-15 was 10% or less of the lesion area of untreated plants.

The following compound represented by the formula (A) described in the Journal of Organic Chemistry, Vol. 38, No. 19, pp. 3390 (1975) was similarly subjected to the test. As a result, the lesion area on the plant treated with the compound represented by the formula (A) was 51% or more of the lesion area of the untreated plant.

Test example 2

Plastic pots were filled with sandy loam, sown with grapes (variety: Berry A), and grown in a greenhouse for 40 days. Each of the present compounds 1 to 4 and 7 to 15 was prepared into a preparation according to Preparation Example 6, diluted with water to a predetermined concentration (200 ppm), and the diluted solution was sprayed on foliage so as to sufficiently adhere to the vine leaves. After drying the diluted solution on the leaf surface, spray inoculation with a suspension of zoosporangium of scabs (containing about 10000 zoospores per lm of suspension) is performed. 2 ml). After inoculation, the plants were cultivated for 1 day under conditions of 23 and relative humidity of 90% or more, and then transferred to a greenhouse at 24 during the day and 20 at night for 6 days. After that, the control effect was investigated.

As a result, the lesion area on plants treated with the present compounds 1 to 4 and 7 to 15 was 10% or less of the lesion area of untreated plants.

Test example 3

Plastic pots were filled with sandy loam, sown with grapes (variety: Veri A), and grown in a greenhouse for 40 days. Compound 11 of the present invention was prepared as a preparation according to Preparation Example 6, diluted with water to a predetermined concentration (50 ppm), and the diluted solution was sprayed on the foliage so as to sufficiently adhere to the vine leaves. After drying the diluted solution on the leaf surface, spray inoculation with a suspension of zoosporangia of grape downy mildew (containing about 10,000 zoospores per m1 of suspension) (one plant Per 2m1). 23t after inoculation: 90% or more relative humidity The plants were cultivated for one day under the conditions, then transferred to a greenhouse at 24 ° C during the day and 20 at night, and cultivated for 6 days. After that, the control effect was investigated.

As a result, the lesion area on the plant treated with the compound 11 of the present invention was 10% or less of the lesion area of the untreated plant. Industrial applicability

By using the compound of the present invention, plant diseases can be controlled.

Claims

The scope of the claims

Equation (1)

[Wherein, R ¹ is a hydrogen atom, a halogen atom, a CI-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C1-C4 alkoxy group, a phenyl R ² represents a hydrogen atom, a halogen atom, a CI-C 3 alkyl group, a C 1-C 3 haloalkyl group or a phenoxy group, or R ¹ and R ² are taken together. Represents C 3 -C 5 alkylene or CH = CH—CH = CH;

R ⁴ represents a C 1 -C 4 alkyl group; R ⁵ represents a C 3 -C 4 alkynyl group; X represents an oxygen atom or a sulfur atom. ]

An amide compound represented by the formula:

2. The amide compound according to claim 1, wherein R ⁴ is a methyl group or an ethyl group, and R ⁵ is a 2-propynyl group, a 1-methyl-2-propynyl group or a 2-butynyl group.

3. A plant disease controlling composition comprising the amide compound according to claim 1 or 2 and a carrier.

4. A method for controlling plant diseases, comprising a step of applying an effective amount of the amide compound according to claim 1 to a plant or soil where the plant grows.

5. Use of the amide compound according to claim 1 or 2 as an active ingredient of a composition for controlling plant diseases.