JP2008280274A - Cyclohexane carboxamide derivative and fungicide for agriculture and gardening - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cyclohexane carboxamide derivative and a fungicide for agriculture and gardening showing a preventive effect on various plant disease damages. <P>SOLUTION: This cyclohexane carboxamide derivative is represented by general formula (I), wherein n represents an integer of 0-5, X, Y, and Z represent various substituents, and A represents a sulfur or an oxygen atom. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to novel cyclohexanecarboxamide derivatives and agricultural and horticultural fungicides.

  So far, as the similar compounds of the cyclohexanecarboxamide derivative of the present invention, compounds represented by the following general formulas (II) to (VI) are known (see Patent Documents 1 to 6).

  These compounds are known to have bactericidal activity against various plant diseases, and are particularly useful against rice blast and gray mold of tomato, cucumber and green beans.

  Among various plant diseases, rice blast is one of the important diseases, and many fungicides have been developed so far. However, although there is a control effect by foliage spraying, there are few chemicals that show a sufficient control effect even in soil treatment (box treatment) and water surface application scenes. Some drugs have a reduced control effect due to the emergence of resistant bacteria, and therefore, drugs having a novel chemical structure are strongly desired. Furthermore, in today's situation where the number of farmers is declining and aging, there are hopes for drugs that promote the reduction and labor saving of control work with characteristics such as preventive / therapeutic activity, permeability penetration, and long-term residual effect. It is rare. Furthermore, rice blast control by spraying foliage in Honda with pesticides is not a safe control method because there are concerns about the impact on the surrounding environment and the safety of users due to the scattering of chemicals. Therefore, in order to ensure the safety of the user and the surrounding environment as well as the consumer as well as the consumer, there is a strong demand for a drug that can exert a sufficient control effect in soil treatment (box treatment) and water surface application situations. .

  However, although the compounds described in Patent Documents 1 to 6 described below have a control effect by spraying foliage against rice blast, there is a drawback that the soil treatment (box treatment) effect and the water surface application effect are weak.

（式中、一般式（II）におけるＲ、ＸｍおよびＺｎは特許文献１、２に従って定義され、一般式（III）におけるＡ、Ｗ、Ｘｍ、Ｙｎ、Ｚｐは特許文献３に従って定義され、一般式（IV）におけるＡ、Ｂ、Ｘｍ、Ｙｐ、Ｚは特許文献４に従って定義され、一般式（Ｖ）におけるＡ、Ｒ、Ｘ、Ｙｎは特許文献５に従って定義され、一般式（VI）におけるＡ、Ｗｐ、Ｘｍ、Ｙｎ、Ｚは特許文献６に従って定義される。）
国際公開第０２/８８０８６号パンフレット 特開２００４−１４３０４５号公報 国際公開第０４/５２６１号パンフレット 特開２００４−１１５４３５号公報 国際公開第０４/３９７８３号パンフレット 特開２００５−２０６５１７号公報

(In the formula, R, Xm and Zn in the general formula (II) are defined according to Patent Documents 1 and 2, and A, W, Xm, Yn and Zp in the general formula (III) are defined according to Patent Document 3, A, B, Xm, Yp, and Z in (IV) are defined according to Patent Document 4, A, R, X, and Yn in General Formula (V) are defined according to Patent Document 5, and A in General Formula (VI) Wp, Xm, Yn, and Z are defined according to Patent Document 6.)
International Publication No. 02/88086 Pamphlet JP 2004-143045 A International Publication No. 04/5261 pamphlet JP 2004-115435 A International Publication No. 04/39883 Pamphlet JP 2005-206517 A

    In view of the conventional drawbacks as described above, the present invention provides novel cyclohexanecarboxamide derivatives having a high soil treatment effect and water surface application effect required for rice blast, and these compounds as active ingredients It is intended to provide a fungicide used as a rice blast, especially a rice blast control agent.

  As a result of intensive studies to achieve the above object, the present inventors have found that the following novel cyclohexanecarboxamide derivatives or salts thereof have bactericidal activity against various plant diseases, particularly against rice blast. The present invention was completed by finding that it has excellent soil treatment effect and water surface application effect.

一般式（Ｉ）において、Ｘは、ハロゲン原子、炭素数１〜６のアルキル基、炭素数１〜６のハロアルキル基、炭素数１〜６のアルコキシ基、炭素数１〜６のハロアルコキシ基、炭素数１〜６のアシルオキシ基、シアノ基、水酸基、ニトロ基、１もしくは２のアルキル基を有していてもよいアミノ基またはメルカプト基を示し、ｎは、０〜５の整数を示し、ｎが２以上のときは、それぞれのＸは同一または相異なっていてもよく、Ｙ、Ｚは、それぞれ独立して、水素原子、炭素数１〜６のアルキル基または炭素数１〜６のアルコキシ基を示し、Ａは、硫黄原子または酸素原子を示す。 Accordingly, the first invention of the present application relates to a novel cyclohexanecarboxamide derivative represented by the following general formula (I) or a salt thereof.

In general formula (I), X is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, An acyloxy group having 1 to 6 carbon atoms, a cyano group, a hydroxyl group, a nitro group, an amino group or a mercapto group optionally having 1 or 2 alkyl groups, n represents an integer of 0 to 5, When X is 2 or more, each X may be the same or different, and Y and Z are each independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkoxy group having 1 to 6 carbon atoms. A represents a sulfur atom or an oxygen atom.

  The second invention of the present application relates to an agricultural and horticultural fungicide containing the cyclohexanecarboxamide derivative represented by the above general formula (I) or a salt thereof.

When the cyclohexanecarboxamide derivative of the present invention or a salt thereof is used as an agricultural and horticultural fungicide, the following effects are exhibited.
Firstly, the compound of the present invention exhibits control activity against plant diseases such as cucumber gray mold disease, barley powdery mildew, wheat red rust disease, and rice blast disease, and is useful as an agricultural and horticultural fungicide.
Secondly, the compound of the present invention exhibits osmotic transfer into rice even when subjected to soil treatment and water surface application, and rice blast can be controlled by soil treatment and water surface application.
Thirdly, the compound of the present invention has both a prophylactic effect and a therapeutic effect particularly for blast disease, and the effect exhibits long-term residual effect.
Fourthly, the agricultural and horticultural fungicide according to the present invention can be used safely without causing phytotoxicity to useful crops.
Therefore, the agricultural and horticultural fungicide containing the compound according to the present invention as an active ingredient can be used for various diseases of agricultural and horticultural crops by foliage spraying, soil treatment and water surface application.

  Hereinafter, the novel cyclohexanecarboxamide derivative according to the present invention, the production method thereof, and the agricultural and horticultural fungicide containing this as an active ingredient will be specifically described.

[Cyclohexanecarboxamide derivatives]
The cyclohexanecarboxamide derivative of the present invention is a compound represented by the general formula (I). The cyclohexanecarboxamide derivative of the present invention can be various salts. For example, it can be an inorganic acid salt such as hydrochloride, perchlorate, sulfate or nitrate, or an organic acid salt such as acetate or methanesulfonate.

  Below, each substituent shown by X, Y, Z, and A in the said general formula (I), and n are demonstrated. However, X, Y, Z and A, and n in the general formula (I) are not limited to the examples shown here.

  Specific examples of the halogen atom represented by X in the general formula (I) include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Preferably they are a fluorine atom and a chlorine atom.

  Examples of the alkyl group having 1 to 6 carbon atoms represented by X include linear or branched alkyl groups having 1 to 6 carbon atoms. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, Neopentyl group, n-hexyl group, 4-methylpentyl group, 3-methylpentyl group, 2-methylpentyl group, 3,3-dimethylbutyl group, 1,1-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, 1-ethyl-2-methyl-propyl group, 1-methyl-1-ethylpropyl group, 1-methyl-2-ethylpropyl group, 2-methyl-1- Examples thereof include an ethylpropyl group and a 2-methyl-2-ethylpropyl group. Preferably, it is a methyl group.

  The haloalkyl group having 1 to 6 carbon atoms represented by X means a linear or branched haloalkyl group in which at least a part of hydrogen atoms in the alkyl group is substituted with a halogen atom. Is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. Specifically, trifluoromethyl group, chloromethyl group, bromomethyl group, dichloromethyl group, difluoromethyl group, trichloromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 1,1-difluoro Examples thereof include an ethyl group, 2,2,2-trifluoroethyl group, 3-chloropropyl group, and 3-iodopropyl group. Preferably, it is a trifluoromethyl group.

  Specific examples of the alkoxy group having 1 to 6 carbon atoms represented by X include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, t-butoxy group, Examples thereof include an n-pentyloxy group, 2-methylbutoxy group, 2,2-dimethylpropoxy group, 3-methylbutoxy group, n-hexyloxy group, 2-methylpentyloxy group, and 3-ethylbutoxy group. . Preferably, it is a methoxy group.

  The haloalkoxy group having 1 to 6 carbon atoms represented by X means a linear or branched haloalkoxy group in which at least a part of hydrogen atoms in the alkoxy group is substituted with a halogen atom. Examples thereof include a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a pentafluoroethoxy group, a pentafluoropropoxy group, a pentafluorobutoxy group, and a pentafluoropentoxy group. Preferably, it is a trifluoromethoxy group.

  Specific examples of the acyloxy group having 1 to 6 carbon atoms represented by X include formyloxy group, acetoxy group, propionyloxy group, butyryloxy group, isobutyryloxy group, valeryloxy group, isovaleryloxy group or pivaloyl Examples include groups. An acetoxy group is preferable.

  The amino group represented by X may be an unsubstituted amino group or a substituted amino group such as a monoalkylamino group or a dialkylamino group.

  Examples of the monoalkylamino group represented by X include an alkylamino group in which the alkyl moiety is a linear or branched alkyl having 1 to 6 carbon atoms. Specifically, methylamino group, ethylamino group, n-propylamino group, isopropylamino group, n-butylamino group, isobutylamino group, s-butylamino group, t-butylamino group, n-pentylamino group, etc. Can be mentioned. Of these, a methylamino group is preferable.

  Examples of the dialkylamino group represented by X include dialkylamino groups in which each alkyl moiety is a linear or branched alkyl having 1 to 6 carbon atoms. Specific examples include a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamino group, a di-n-butylamino group, an ethylmethylamino group, and an n-propylmethylamino group. Of these, a dimethylamino group is preferable.

  In the general formula (I), n, which represents the number of substitutions of the substituent X, represents an integer of 0 to 5, preferably 0 or 1. Needless to say, a hydrogen atom is bonded to the benzene ring carbon to which the substituent X is not bonded.

  In the general formula (I), examples of the alkyl group having 1 to 6 carbon atoms represented by Y and Z include a linear or branched alkyl group. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, Neopentyl group, n-hexyl group, 4-methylpentyl group, 3-methylpentyl group, 2-methylpentyl group, 3,3-dimethylbutyl group, 1,1-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group, 1-ethyl-2-methyl-propyl group, 1-methyl-1-ethylpropyl group, 1-methyl-2-ethylpropyl group, 2-methyl-1- Examples thereof include an ethylpropyl group and a 2-methyl-2-ethylpropyl group. Preferably, it is a methyl group.

  In the general formula (I), examples of the alkoxy group having 1 to 6 carbon atoms represented by Y and Z include linear or branched alkoxy groups. Specifically, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, t-butoxy group, n-pentyloxy group, 2-methylbutoxy group, 2,2 -A dimethylpropoxy group, 3-methylbutoxy group, n-hexyloxy group, 2-methylpentyloxy group, 3-ethylbutoxy group, etc. can be mentioned. Preferably, it is a methoxy group.

  In general formula (I), Y and Z each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms. Among these, Y, Z is a hydrogen atom or Y is an alkoxy group having 1 to 6 carbon atoms, and Z is a hydrogen atom.

  In general formula (I), A is a sulfur atom or an oxygen atom.

Next, specific examples of the compound represented by formula (I) are shown in Table 1-1 to Table 1-10, but the compound of the present invention is not limited to the compounds exemplified herein.
In Table 1, “Me” represents a methyl group, “Et” represents an ethyl group, “Pr” represents a propyl group, and “Bu” represents a butyl group.
The compound numbers in Table 1 are also referred to in the following Table 2, Examples, Formulation Examples and Test Examples.

Next, proton NMR data of some cyclohexanecarboxamide derivatives of the present invention are shown in Tables 2-1 to 2-2.
The ¹ H-NMR spectrum data of each compound was measured with a JNM-LA300 type nuclear magnetic resonance apparatus manufactured by JEOL Datum Co., Ltd. using tetramethylsilane (TMS) as a standard substance and deuterated chloroform (CDCl ₃ ) as a solvent. It was measured.

[Method for producing compound of the present invention]
The compound represented by the general formula (I) according to the present invention can be synthesized by any method, and particularly preferred general production methods are shown in the following production scheme 1 and production scheme 2.
In the compound represented by the following general formula (IX), the compound in which A is a sulfur atom is a known compound in the literature, and is described in, for example, J. Org. Chem., Vol. 34, No. 347 (1969). To obtain thieno [2,3-b] pyridine, then Journal of Heterocyclic Chemistry
(IX) can be synthesized and used according to the method described in Vol. 7, No. 81, (1970), but is not limited to these methods.
In the general formula (IX), the compound in which A is an oxygen atom is a known compound in the literature, for example, by the method described in Journal of Heterocyclic Chemistry Vol. 3, Item 202 (1966), and 5-nitro-furo [ 2,3-b] pyridine-2-carboxylic acid can be obtained, and then (IX) can be synthesized and used according to the method described in Journal of Heterocyclic Chemistry Vol. 8, No. 5, 735 (1971). It is not limited to this method.

（式中、Ｘｎ、Ｙ、ＺおよびＡは、それぞれ前記と同様であり、Ｈａｌはハロゲン原子を表す。）

(Wherein, Xn, Y, Z and A are the same as defined above, and Hal represents a halogen atom.)

  In the production scheme 1, an acid halide represented by the general formula (VIII) obtained by halogenating a cyclohexanecarboxylic acid derivative represented by the general formula (VII) is condensed with an amine represented by the general formula (IX). This is a method for producing the invention compound (I).

(Step 1-1)
The acid halide represented by the general formula (VIII) can be produced by halogenating the cyclohexanecarboxylic acid derivative represented by the general formula (VII) with a halogenating agent.
This reaction is preferably carried out in a solvent. Examples of the solvent used include aliphatic halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chloroform, and hydrocarbons such as benzene, toluene and xylene. It is done. Examples of the halogenating agent include oxalyl chloride, thionyl chloride, phosphorus trichloride, phosphorus pentachloride and the like. Preferable examples include oxalyl chloride.
In this reaction, the halogenating agent is generally used in an amount of 1 to 2 mol, preferably 1 to 1.5 mol, per 1 mol of cyclohexanecarboxylic acid derivative (VII). This reaction is usually performed in a temperature range of 0 to 100 ° C, preferably 20 to 80 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 1 to 6 hours.

(Step 1-2)
The compound of the present invention represented by the general formula (I) can be produced by reacting an acid halide represented by the general formula (VIII) with an amine represented by the general formula (IX) in the presence of a base.
This reaction is preferably carried out in a solvent. Solvents used include aliphatic halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chloroform, ethers such as tetrahydrofuran and dioxane, benzene, toluene and xylene. In some cases, it can be used as a mixed solvent of these organic solvents and water.
Examples of the base to be used include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, and organic bases such as pyridine, triethylamine, tri n-propylamine and N, N-diisopropylethylamine.
The amount of the acid halide (VIII) to be used is generally 1-2 mol, preferably 1.05 mol, per 1 mol of amine (IX). The base is usually used in an amount of 1 to 5 mol, preferably 1 to 2 mol. This reaction is usually performed in a temperature range of 0 to 80 ° C, preferably 0 to 40 ° C. The reaction time of this reaction may be any time at which the reaction ends. The completion of the reaction means, for example, that one or both of the raw materials in the solvent are consumed, and can be confirmed by, for example, thin layer chromatography. Generally, it is in the range of 1 hour to 24 hours.
After completion of the reaction, the compound (I) of the present invention is extracted, for example, by adding water and an organic solvent to the reaction solution containing the compound (I) of the present invention, and further washed with water and saturated brine, and the solvent is distilled off. It is obtained by leaving.
If necessary, the obtained target product can be further purified by operations such as column chromatography or recrystallization.

（式中、Ｘｎ、Ｙ、ＺおよびＡは、それぞれ前記と同様である。）

(In the formula, Xn, Y, Z and A are the same as defined above.)

In the production scheme 2, a cyclohexanecarboxylic acid derivative represented by the general formula (VII) and an amine represented by the general formula (IX) are subjected to dehydration condensation with a condensing agent in the presence of a base to produce the compound (I) of the present invention. Is the method.
This reaction is preferably carried out in a solvent. Examples of the solvent used include aliphatic halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chloroform, nitriles such as acetonitrile, and amides such as dimethylformamide. Can be mentioned.
Examples of the condensing agent include 1,3-dicyclohexylcarbodiimide, 1-ethyl-3- (3′-dimethylaminopropyl) carbodiimide, 2-methyl-6-nitrobenzoic acid anhydride, and the like.
Examples of the base used include pyridine, triethylamine, tri-n-propylamine, N, N-diisopropylethylamine, 4-dimethylaminopyridine and the like.
The usage-amount of cyclohexanecarboxylic acid derivative (VII) is 1-2 mol with respect to 1 mol of amine (IX), Preferably, it is 1.05 mol.
The amount of the condensing agent to be used is usually 1 to 2 mol, preferably 1 to 1.1 mol, and the base is usually 1 to 4 mol, preferably 1 to 2 with respect to 1 mol of cyclohexanecarboxylic acid derivative (VII). Used in molar amounts. This reaction is usually performed in a temperature range of 0 to 80 ° C, preferably 0 to 40 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 1 to 24 hours. After completion of the reaction, the compound (I) of the present invention is extracted by adding water and an organic solvent to the reaction solution containing the compound (I) of the present invention, and further washed with water and saturated brine, and the solvent is distilled off. Can be obtained. The obtained object (I) can be further purified by operations such as column chromatography or recrystallization, if necessary.

  Next, a typical production method of the cyclohexanecarboxylic acid derivative represented by the general formula (VII) which is a production intermediate of the compound of the present invention is shown in the following production scheme 3.

（式中、Ｘｎ、Ｙ、ＺおよびＨａｌは、前記と同様である。Ｐは、炭素数１〜６のアルキル基を表し、具体的にはメチル基、エチル基などが挙げられる。Ｑは、炭素数１〜６のアルキル基を表し、具体的にはメチル基、エチル基、イソプロピル基などが挙げられる。Ｒは、水素原子または炭素数１〜６のアルキル基を表し、具体的にはメチル基などが挙げられる。）

(In the formula, Xn, Y, Z and Hal are the same as described above. P represents an alkyl group having 1 to 6 carbon atoms, and specifically includes a methyl group, an ethyl group, etc. Q is Represents an alkyl group having 1 to 6 carbon atoms, specifically, a methyl group, an ethyl group, an isopropyl group, etc. R represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, specifically, methyl Group, etc.)

(Step 3-1)
A compound represented by the general formula (XII) when Y is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms and Z is a hydrogen atom (for example, (Y, Z) = (H, H), (Me, H), (Et, H), (iPr, H), etc.) is a reaction of cyclohexanecarboxylic acid ester represented by general formula (X) and benzyl halide represented by general formula (XI) in the presence of a base. Can be manufactured.
This reaction is preferably performed in a solvent, and examples of the solvent used include ethers such as diethyl ether, tetrahydrofuran and ethylene glycol dimethyl ether, and hydrocarbons such as hexane and toluene.
Examples of the base used include alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal alkoxides such as potassium t-butoxide and sodium methoxide, organic compounds such as butyl lithium, lithium diisopropylamide, and lithium hexamethyldisilazane. Metals are mentioned.
The usage-amount of benzyl halide (XI) is 1-1.5 mol with respect to 1 mol of cyclohexanecarboxylic acid ester (X), Preferably it is 1-1.2 mol. The amount of the base used is 1 to 10 mol, preferably 1.1 to 5 mol.
This reaction is usually performed in a temperature range of −70 to 80 ° C., preferably −70 to 40 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 10 minutes to 24 hours. After completion of the reaction, the compound (XII) is obtained by adding water and an organic solvent to the reaction solution containing the compound (XII), followed by extraction, further washing with water and saturated brine, and distilling off the solvent. . If necessary, the obtained target product (XII) can be further purified by operations such as column chromatography or recrystallization.
Compound (X) used in this step is a known compound.
Compound (XI) used in this step is a known compound or a known method such as J. Am. Chem.
Soc., 110, 8153 Mitsugu (1988), J. Org. Chem., 58, 964 Mitsugu (1993).

(Steps 3-2 and 3-3)
A compound represented by the general formula (XII) when Y is an alkoxy group having 1 to 6 carbon atoms and Z is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms (for example, (Y, Z) = (OMe, H), (OMe, Me), (OEt, H), (OMe, Me), (OiPr, H), (OiPr, Me) and the like.) Is a cyclohexanecarboxylic acid represented by the general formula (X) It can be produced by reacting a compound represented by the general formula (XIII) obtained by silylenolizing an ester with an acetal represented by the general formula (XIV) in the presence of a Lewis acid. Hereinafter, Step 3-2 and Step 3-3 are specifically shown.

(Step 3-2)
The compound represented by the general formula (XIII) can be produced by reacting the cyclohexanecarboxylic acid ester represented by the general formula (X) with trimethylsilyl chloride in the presence of a base.
This reaction is preferably performed in a solvent, and examples of the solvent used include ethers such as diethyl ether, tetrahydrofuran and ethylene glycol dimethyl ether, and hydrocarbons such as hexane and toluene.
Examples of the base used include alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal alkoxides such as potassium t-butoxide and sodium methoxide, organic compounds such as butyl lithium, lithium diisopropylamide, and lithium hexamethyldisilazane. Metals are mentioned.
The amount of trimethylsilyl chloride (TMSCl) to be used is 1 to 2.0 mol, preferably 2.0 mol, per 1 mol of cyclohexanecarboxylic acid ester (X). The amount of the base used is 1 to 10 mol, preferably 1.1 to 5 mol.
This reaction is usually performed in a temperature range of −70 to 80 ° C., preferably −70 to 40 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 10 minutes to 24 hours. After completion of the reaction, the compound (XIII) is obtained by adding water and an organic solvent to the reaction solution containing the compound (XIII), followed by extraction, further washing with water and saturated brine, and distilling off the solvent. . The obtained target product (XIII) can be used for the next step without purification.

(Step 3-3)
When Y is an alkoxy group having 1 to 6 carbon atoms and Z is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, the compound represented by the general formula (XII) is a silyl enol represented by the general formula (XIII). It can be produced by reacting ether with an acetal represented by the general formula (XIV) in the presence of a Lewis acid.
This reaction is preferably carried out in a solvent. Examples of the solvent used include hydrocarbons such as hexane and toluene, aliphatic halogenated hydrocarbons such as dichloromethane and chloroform, and ethers such as tetrahydrofuran. Includes dichloromethane.
Examples of the Lewis acid used include zinc chloride, titanium tetrachloride, aluminum chloride, tetrafluoroboric acid, and preferably zinc chloride is used.
The amount of acetal (XIV) used is 1.0 to 2.0 mol, preferably 1.0 to 1.5 mol, per 1 mol of silyl enol ether (XIII). The amount of Lewis acid used is 0.01 to 0.2 mol, preferably 0.01 to 0.1 mol.
This reaction is usually performed in the temperature range of -20 to 150 ° C, preferably -10 to 40 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 10 minutes to 24 hours. After completion of the reaction, compound (XIV) is obtained by adding water and an organic solvent to the reaction solution containing compound (XIV), followed by extraction, further washing with water and saturated brine, and distilling off the solvent. . If necessary, the obtained target product (XIV) can be further purified by operations such as column chromatography or recrystallization.
The compound (XIV) used in this step is a known compound, or a known method such as Synth. Commun., Vol. 7 409 (1977), J. Org. Chem., 60, 7334 ( (1995).

(Step 3-4)
The cyclohexanecarboxylic acid derivative (VII) can be easily obtained by hydrolyzing the cyclohexanecarboxylic acid ester derivative represented by the general formula (XII) in the presence of a base.
This reaction is preferably carried out in a solvent, and examples of the solvent to be used include a solvent mixture of water and methanol, ethanol, isopropanol, dimethyl sulfoxide and the like.
Examples of the base used include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and alkali metal alkoxides such as potassium t-butoxide.
The amount of the base used is 1 to 3 mol, preferably 1 to 2 mol, per 1 mol of the cyclohexanecarboxylic acid ester derivative. The reaction is usually performed in a temperature range of 10 to 100 ° C, preferably 20 to 60 ° C. The reaction time varies depending on the reaction substrate and reaction temperature, but is usually completed in 1 to 6 hours.
After completion of the reaction, the cyclohexanecarboxylic acid derivative (VII) is made acidic by adding water to the reaction solution containing the compound (VII) and then adding hydrochloric acid, sulfuric acid, etc., and an extraction solvent such as diethyl ether, toluene, ethyl acetate, etc. After extraction with, it is obtained by washing with water and saturated saline and distilling off the solvent.
The compound represented by the general formula (VII) is analyzed and confirmed by melting point, infrared absorption spectrum, ¹ H-NMR spectrum, ¹³ C-NMR spectrum, mass spectrometry, X-ray structural analysis, etc., if necessary. can do.

  More specific production examples of the compound represented by formula (I) according to the present invention are shown in Examples 1 to 4 described later.

[Agricultural / horticultural fungicide of the present invention]
The compounds represented by the general formula (I) according to the present invention include a wide variety of filamentous fungi, such as, for example, Plasmodiophoromycetes, algae (Oomycetes), Ascomycetes, incomplete It can be controlled at low doses against bacteria belonging to fungi (Deuteromycetes) and basidiomycetes, and is useful, for example, as a bactericidal composition for agriculture and horticulture.

Specific examples of plant diseases that can be controlled according to the present invention include rice blast (Pyricularia grisea), sesame leaf blight (Cochliobolus).
miyabeanus), blight (Thanatephorus cucumeris), stupid seedling (Gibberella fujikuroi), seedling blight (Fusarium, Rhizopus, Pythium, Trichoderma)
viride), rice mildew (Claviceps virens), wheat fungus (Gibberella zeae, Fusarium avenaceum, Fusarium culmorum, Monographella nivale), snow rot (Pythium, Typhula, Monographella)
nivalis, Myriosclerotinia borealis), naked smut (Ustilago nuda), lintel scab (Tilletia)
controversa), eyespot (Pseudocercosporella herpotrichoides), leaf blight (Septoria tritici), blight (Phaeosphaeria)
nodorum), citrus sunspot (Diaporthe citri), small sunspot (Diaporthe medusa, Alternaria citri), scab (Elsinoe)
fawcettii), brown rot (Phytophthora citrophthra), green mold (Penicillium digitatum), blue mold (Penicillium)
italicum), apple Monilinia mali, black star disease (Venturia inaequalis), spotted leaf disease (Alternaria mali), black spot disease (Mycosphaerella pomi), soot spot (Gloeodes)
pomigena), soot spot disease (Zygophiala jamaicensis), ring rot disease (Botryosphaeria berengeriana), brown spot disease (Diplocarpon)
mali), red scab (Gymnosporangium yamadae), rot (Valsa ceratosperma), pear scab (Venturia)
nashicola), red scab (Gymnosporangium asiaticum), ring rot (Botryosphaeria berengeriana), blight (Phomopsis)
fukushii), peach streak (Taphrina deformans), ash scab (Monilinia fructicola, Monilinia fructigena), black scab (Cladosporium carpophilum), homopsis rot (Phomopsis), sweet scab (Monilinia fructicola, Monilinia fructigena) , Larvae (Monilinia kusanoi), ume black scab (Cladosporium)
carpophilum), grape black rot (Elsinoe ampelina), late rot (Colletotrichum acutatum, Glomerella)
cingulata), brown spot disease (Pseudocercospora vitis), vine split disease (Phomopsis viticola) oyster spot leaf spot disease (Cercospora)
kaki), lobster leaf disease (Mycosphaerella nawae), ringworm disease of chia (Pestalotiopsis longiseta, Pestalotiopsis)
theae), brown circle rot (Pseudocercospora ocellata, Cercospora chaae), blast (Exobasidium vexans), net blast (Exobasidium reticulatum), cucumber vine blight (Mycosphaerella
melonis), vine split disease (Fusarium oxysporum), black spot disease (Cladosporium cucumerinum), brown spot disease (Corynespora)
cassiicola), tomato leaf mold (Fulvia fulva), ring rot (Alternaria solani), eggplant brown mold (Phomopsis vexans), scab (Mycovellosiella nattrassii), cruciferous vegetable white rust (Albugo)
macrospora), vitiligo disease (Cercosporella brassicae, Pseudocercosporella capsellae), onion gray rot (Botrytis)
allii), strawberry potato disease (Mycosphaerella fragariae), potato summer plague (Alternaria solani), soybean stem rot (Phytophthora)
sojae), purpura (Cercospora kikuchii), azuki bean plague (Phytophthora vignae), peanut brown (Mycosphaerella)
arachidis), sugar beet brown spot (Cercospora beticola), leaf rot (Thanatephorus cucumeris), buckwheat curbularia leaf blight (Curvularia), dollar spot disease (Sclerotinia homoeocarpa), hermintosporum leaf blight (Cochliobolus) ), Rose scab (Diplocarpon rosae), chrysanthemum rust (Puccinia)
horiana), and mildew of various crops (Peronospora, Pseudoperonospora, Plasmopara, Bremia), plague (Phytophthora), powdery mildew (Erysiphe, Blumeria, Sphaerotheca, Podosphaerea, Phyllactinia, Uncinula Fungus, Oidiopsis), rust (Puccinia, Uromyces, Physopella), anthrax (Glomerella, Colletotrichum, Gloeosporium), black spot (Alternaria), gray mold (Botrytis cinerea), sclerotia Disease (Sclerotinia sclerotiorum), white coat (Rosellinia)
necatrix), purple herb disease (Helicobasidium mompa), white silkworm disease (Sclerotium rolfsii), various other soil diseases (Fusarium, Rhizoctonia, Pythium, Aphanomyces, Phoma, Verticillium, Plasmodiophora brassicae, etc.)
And other diseases.

  The cyclohexanecarboxamide derivative represented by the general formula (I) according to the present invention exhibits bactericidal activity. Therefore, the composition containing the compound represented by general formula (I) can be used as a bactericidal agent. In particular, a composition containing the compound represented by formula (I) as an active ingredient can be used as an agricultural and horticultural fungicide.

  The composition of the agricultural and horticultural fungicide containing the compound represented by the general formula (I) according to the present invention as an active ingredient is ordinary agricultural and horticultural except that the active ingredient contains the compound represented by the general formula (I). It is good also as a composition of an antibacterial agent. The normal composition is described in, for example, an agrochemical formulation guide (1997 edit: Japan Agricultural Chemical Society application method study group, issue: Japan Plant Protection Association). That is, a compound represented by the general formula (I), an appropriate carrier, an auxiliary agent, a surfactant, a binder, a stabilizer, and the like may be blended.

  The composition of the agricultural and horticultural fungicide containing the compound represented by the general formula (I) according to the present invention can be formulated into any dosage form generally used as an agrochemical dosage form. For example, powder, coarse powder, DL (driftless type) powder, flow dust, fine granules, fine granules, granules, wettable powder, wettable powder, liquid, sol (flowable), emulsion, and Although it can be formulated into an oil or the like, it is not limited to these.

The content of the compound represented by the general formula (I) according to the present invention can be appropriately selected depending on the dosage form of the preparation and the method of use. In general, the preferable content is in the range of 0.1 to 90% by weight based on the total amount of the preparation.

  The active compound of the formula (I) according to the present invention is a fungicide (fungicides, bactericides, antiviral agents, plant resistance inducers) at the time of formulation or spraying as necessary when used as an agrochemical. , Insecticides, acaricides, nematocides, herbicides, avian repellents, growth regulators, fertilizers and / or soil conditioners, etc. may be mixed and applied.

Representative examples that can be used by mixing and mixing with the compound of the formula (I) of the present invention are shown below, but are not necessarily limited thereto.
Fungicide:
Probenazole, acibenzolar, tiadinil, carpropamid, diclocymet, fenoxanil, phthalide, pyroquilon, tricyclazole, azoxyst Robin (azoxystrobin), mettominostrobin, oryzastrobin, blasticidin-S (blasticidin-S), kasugamycin, ferimzone, isoprothiolane, iprobenfos, Benomyl, thiophanate-methyl, pefurzoate, ipconazole, prochloraz, triflumizole, fludioxonil Thiram (thiram),
Flutolanil, mepronil, thifluzamide, furametpyr, penencycuron, diclomedine, validamycin, metalaxyl, hymexazol, hymexazol

Insecticide:
Fipronil, dinotefuran, imidacloprid, clothianidin, thiaclopid, thiamethoxam, nitenpyram, carb, carb, bet, carb ), Silafluofen, spinosad, cartap fenthion, fenitrothion, buprofezin, etofenprox, fenobucarb, fenobucarb, tebfenide, tebfenide bensultap), acephate, ethiprole, pymetrozine and the like.

  The agricultural and horticultural fungicide containing the compound represented by the general formula (I) according to the present invention as an active ingredient can be used in the same manner as a method in which a general agricultural and horticultural fungicide is used. Specifically, in the case of wettable powders, liquids, emulsions, sols (flowables), granular wettable powders, or oils, the active ingredient is generally diluted 1 to 50 times with water, It is prepared to be a liquid with a concentration of 10,000 ppm, and this diluted liquid varies depending on the form of crops such as paddy rice and fruit trees, but it is in the range of 50 to 1,000 liters, usually 100 to 600 liters per 10 ares of farmland. It can be sprayed on the foliage at the plant disease occurrence site.

  Moreover, in the case of a liquid agent, an emulsion, or a sol (flowable agent), it is not diluted with water or diluted within 50 times, and a quantity of 5 to 5000 mL per 10 are as a microdispersant is mainly used. It can be sprayed in the air. Air spraying is performed using a helicopter.

  In addition, in the case of powder, coarse granule, DL powder, flow dust, fine granule, fine granule, or granule, 0.3 to 5 kg of agent per 10 ares (active ingredient content is about 5 to 500 g) May be applied to the foliage, the soil surface, the soil, or the water surface at the plant disease occurrence site.

  Further, in seedling box cultivation such as paddy rice, 10-100 g per grain seedling box (standard size: 30 cm × 60 cm × 5 cm), or flowable or the like without dilution, or diluted 30 to 1, 000 ml can be applied to the soil surface during the seedling stage before or after sowing.

  Specific examples of the method for formulating the compound represented by formula (I) according to the present invention as an agricultural and horticultural fungicide are shown in Examples 5 to 9 described later.

  Moreover, the usefulness of the agricultural and horticultural fungicide containing the compound represented by the general formula (I) according to the present invention, that is, the fungicidal activity, is specifically shown by Test Examples 1 to 6 described later.

  EXAMPLES Hereinafter, although an Example and a test example demonstrate this invention concretely, the scope of the present invention is not limited by these.

Preparation of 1- (4-fluorobenzyl) -N- (5- [2,3-b] thienopyridyl) -cyclohexanecarboxamide (Compound No. 6)

[Production Scheme 3]
(Step 3-1)
Synthesis of methyl 1- (4-fluorobenzyl) -1-cyclohexanecarboxylate In a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer, 0.392 g of diisopropylamine dissolved in 20 ml of tetrahydrofuran (3. 87 mmol) was added, and after cooling to -70 ° C., 2.42 ml (3.87 mmol) of a 1.60 mol / l n-butyllithium / hexane solution was added and stirred for 1 hour. To this was added 0.500 g (3.52 mmol) of methylcyclohexanecarboxylate, and after stirring for 1 hour, 0.509 g (3.52 mmol) of (4-fluorobenzyl) chloride was added, and the mixture was stirred at −60 ° C. for 1 hour.
After completion of the reaction, 20 ml of water and 40 ml of ethyl acetate were added for extraction treatment. The obtained organic layer was washed with 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (silica gel; Silica gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 65: 1 (volume ratio)) to give 0.775 g of the title compound. (Oil, yield 88%).

(Step 3-4)
Synthesis of 1- (4-fluorobenzyl) -1-cyclohexanecarboxylic acid 1- (4-fluorobenzyl) dissolved in 20 ml of dimethyl sulfoxide in a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer Methyl -1-cyclohexanecarboxylate (0.775 g, 3.10 mmol), water (2 ml) and potassium hydroxide (0.522 g, 9.30 mmol) were added, and the mixture was stirred at 90 ° C. for 2 hours.
After completion of the reaction, the reaction mixture was washed with 20 ml of water and 20 ml of diethyl ether, acidified with 1N aqueous hydrochloric acid, and extracted with 40 ml of ethyl acetate. The obtained ethyl acetate layer was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 0.689 g of the crude title compound (colorless solid, crude yield 94). %). This was used in the next step without purification.

[Production Scheme 1]
Synthesis of 1- (4-fluorobenzyl) -N- (5- [2,3-b] thienopyridyl) -1-cyclohexanecarboxamide In a 50 ml four-necked flask equipped with a reflux condenser, stirrer and thermometer, Add 0.689 g (2.92 mmol) of 1- (4-fluorobenzyl) -1-cyclohexanecarboxylic acid dissolved in 20 ml of dichloromethane, and after cooling to 0 ° C., 0.408 g (3.21 mmol) of oxalyl chloride and a catalytic amount of N, N-dimethylformamide was added and stirred at room temperature. After 1 hour, the reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 5 ml of dichloromethane. Then, this solution was added to a separately prepared solution of thieno [2,3-b] pyridin-5-amine (0.29 g, 1.95 mmol), triethylamine (0.592 g, 5.85 mmol) and dichloromethane (20 ml) at room temperature. For 24 hours.
After completion of the reaction, the resulting reaction mixture was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified. Purification by silica gel column chromatography (silica gel; Silica gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 3: 1 (volume ratio)) gave 0.503 g (colorless solid, yield 70) of the title compound. %, Melting point 123-4 ° C.).

Preparation of 1- (1-phenylethyl) -N- (5- [2,3-b] thienopyridyl) -cyclohexanecarboxamide (Compound No. 58)

[Production Scheme 3]
(Step 3-1)
Synthesis of methyl 1- (1-phenylethyl) -1-cyclohexanecarboxylate In a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer, 0.392 g of diisopropylamine dissolved in 20 ml of tetrahydrofuran (3. 87 mmol) was added, and after cooling to -70 ° C., 2.42 ml (3.87 mmol) of a 1.60 mol / l n-butyllithium / hexane solution was added and stirred for 1 hour. To this, 0.500 g (3.52 mmol) of methylcyclohexanecarboxylate was added and stirred for 1 hour, and then 0.651 g (3.52 mmol) of (1-bromoethyl) benzene was added and stirred at −60 ° C. for 1 hour. The mixture was further stirred at room temperature for 12 hours.
After completion of the reaction, 20 ml of water and 40 ml of ethyl acetate were added for extraction treatment. The obtained organic layer was washed with 20 ml of saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (silica gel; Silica gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 65: 1 (volume ratio)) to give 0.546 g of the title compound. (Oil, yield 63%) was obtained.

(Step 3-4)
Synthesis of 1- (1-phenylethyl) -1-cyclohexanecarboxylic acid In a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer,
0.546 g (2.22 mmol) of methyl 1- (1-phenylethyl) -1-cyclohexanecarboxylate and 0.747 g (6.66 mmol) of potassium t-butoxide dissolved in 20 ml of dimethyl sulfoxide were added, and the mixture was stirred at 50 ° C. for 8 hours. Stir.
After completion of the reaction, the reaction mixture was washed with 20 ml of water and 20 ml of diethyl ether, acidified with 1N aqueous hydrochloric acid, and extracted with 40 ml of ethyl acetate. The obtained ethyl acetate layer was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 0.222 g of crude title compound (oil, crude yield 43 %). This was used in the next step without purification.

[Production Scheme 1]
Synthesis of 1- (1-phenylethyl) -N- (5- [2,3-b] thienopyridyl) -1-cyclohexanecarboxamide In a 50 ml four-necked flask equipped with a reflux condenser, stirrer and thermometer, Add 0.222 g (0.956 mmol) of 1- (1-phenylethyl) -1-cyclohexanecarboxylic acid dissolved in 20 ml of dichloromethane, and after cooling to 0 ° C., 0.133 g (1.05 mmol) of oxalyl chloride and a catalytic amount of N, N-dimethylformamide was added and stirred at room temperature. After 1 hour, the reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 5 ml of dichloromethane. Then, this solution was added to a separately prepared solution of 95.7 mg (0.637 mmol) of thieno [2,3-b] pyridin-5-amine, 0.193 g (1.91 mmol) of triethylamine and 20 ml of dichloromethane. Stir for hours at room temperature.
After completion of the reaction, the reaction mixture was washed with 20 ml of water and 20 ml of saturated aqueous sodium chloride solution, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography. (Silica gel; Silica gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 3: 1 (volume ratio)) to obtain 0.186 g (amorphous, yield 80%) of the title compound. .

Preparation of 1- (1-methoxy-1-phenylethyl) -N- (5- [2,3-b] thienopyridyl) -cyclohexanecarboxamide (Compound No. 110)

[Production Scheme 3]
(Step 3-2)
Synthesis of [methoxy (trimethylsilyloxy) methylene] cyclohexane 0.392 g (3.87 mmol) of diisopropylamine dissolved in 20 ml of tetrahydrofuran was placed in a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer, After cooling to 70 ° C., 1.42 mol / l n-butyllithium / hexane solution 2.42 ml (3.87 mmol) was added, and the mixture was stirred for 1 hour. Next, 0.500 g (3.52 mmol) of methyl cyclohexanecarboxylate was added, and after stirring for 1 hour, 0.764 g (7.04 mmol) of trimethylsilyl chloride was added, and the mixture was stirred at −60 ° C. for 1 hour.
After completion of the reaction, 20 ml of water was added and extracted with 40 ml of hexane. The organic layer was washed with 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 0.753 g of crude title compound (oil, crude yield 100%). This was used in the next step without purification.

(Step 3-3)
Synthesis of methyl 1- (1-methoxy-1-phenylethyl) -1-cyclohexanecarboxylate In a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer, dissolved in 20 ml of dichloromethane [methoxy (trimethylsilyl Oxy) methylene] cyclohexane 0.753 g (3.52 mmol), (1,1-dimethoxyethyl) benzene 0.585 g (3.52 mmol) and zinc chloride 23.9 mg (0.176 mmol) were added and stirred at room temperature for 1 hour. did.
After completion of the reaction, 20 ml of water was added and extracted with 20 ml of chloroform. The organic layer was washed with 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (silica gel; Silica gel 60H (manufactured by Merck). Product name) Developing solvent; hexane: ethyl acetate = 50: 1 (volume ratio)) to give 0.603 g (oil, yield 62%) of the title compound.

(Step 3-4)
Synthesis of 1- (1-methoxy-1-phenylethyl) -1-cyclohexanecarboxylic acid 1- (1 dissolved in 20 ml of dimethyl sulfoxide in a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer. 0.603 g (2.18 mmol) of methyl -methoxy-1-phenylethyl) -1-cyclohexanecarboxylate, 2 ml of water and 0.367 g (6.55 mmol) of potassium hydroxide were added and stirred at 90 ° C. for 8 hours.
After completion of the reaction, 20 ml of water was added, washed with 20 ml of diethyl ether, acidified with 1N aqueous hydrochloric acid, and extracted with 40 ml of ethyl acetate. The ethyl acetate layer was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.526 g of crude title compound (oil, crude yield 92%). Obtained. This was used in the next step without purification.

[Production Scheme 1]
Synthesis of 1- (1-methoxy-1-phenylethyl) -N- (5- [2,3-b] thienopyridyl) -1-cyclohexanecarboxamide Four 50 ml volumes equipped with reflux condenser, stirrer and thermometer 0.526 g (2.01 mmol) of 1- (1-methoxy-1-phenylethyl) -1-cyclohexanecarboxylic acid dissolved in 20 ml of dichloromethane was placed in a neck flask, cooled to 0 ° C., and then 0.281 g of oxalyl chloride ( 2.21 mmol) and a catalytic amount of N, N-dimethylformamide were added and stirred at room temperature. After 1 hour, the residue obtained by concentrating the reaction solution was dissolved in 5 ml of dichloromethane. Next, this solution was added to a solution of 0.201 g (1.34 mmol) of thieno [2,3-b] pyridin-5-amine, 0.407 g (4.02 mmol) of triethylamine and 20 ml of dichloromethane, which was prepared separately. For 24 hours.
After completion of the reaction, the organic layer was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (silica gel; Silica Purified by gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 3: 1 (volume ratio)), 0.270 g of the title compound (colorless solid, yield 51%, melting point 158-160 ° C.) Got.

Preparation of 1- [methoxy (phenyl) methyl)]-N- (5- [2,3-b] furopridyl) -cyclohexanecarboxamide (Compound No. 230)

[Production Scheme 3]
(Step 3-2)
Synthesis of [methoxy (trimethylsilyloxy) methylene] cyclohexane 0.392 g (3.87 mmol) of diisopropylamine dissolved in 20 ml of tetrahydrofuran was placed in a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer, After cooling to 70 ° C., 1.42 mol / l n-butyllithium / hexane solution 2.42 ml (3.87 mmol) was added, and the mixture was stirred for 1 hour. To this solution, 0.500 g (3.52 mmol) of methylcyclohexanecarboxylate was added, and after stirring for 1 hour, 0.764 g (7.04 mmol) of trimethylsilyl chloride was added, and stirred at −60 ° C. for 1 hour.
After completion of the reaction, 20 ml of water was added and extracted with 40 ml of hexane. The organic layer was washed with 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 0.753 g of crude title compound (oil, crude yield 100%). This was used in the next step without purification.

(Step 3-3)
Synthesis of methyl 1- [methoxy (phenyl) methyl)]-1-cyclohexanecarboxylate [Methoxy (trimethylsilyloxy) dissolved in 20 ml of dichloromethane in a 50 ml four-necked flask equipped with a reflux condenser, a stirrer and a thermometer Methylene] cyclohexane 0.753 g (3.52 mmol), benzaldehyde dimethyl acetal 0.535 g (3.52 mmol) and zinc chloride 23.9 mg (0.176 mmol) were added, and the mixture was stirred at room temperature for 1 hour.
After completion of the reaction, 20 ml of water was added and extracted with 20 ml of chloroform. The organic layer was washed with 20 ml of saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (silica gel; Silica gel 60H (Merck's product). Name) Developing solvent; hexane: ethyl acetate = 55: 1 (volume ratio)) to give 0.637 g (oil, yield 69%) of the title compound.

(Step 3-4)
Synthesis of 1- [methoxy (phenyl) methyl)]-1-cyclohexanecarboxylic acid 1- [methoxy (phenyl) dissolved in 20 ml of dimethyl sulfoxide in a 50 ml four-necked flask equipped with a reflux condenser, stirrer and thermometer ) Methyl)]-1-cyclohexanecarboxylate methyl 0.637 g (2.43 mmol), water 2 ml and potassium hydroxide 0.408 g (7.29 mmol) were added and stirred at 90 ° C. for 8 hours.
After completion of the reaction, the reaction mixture was washed with 20 ml of water and 20 ml of diethyl ether, acidified with 1N aqueous hydrochloric acid, and extracted with 40 ml of ethyl acetate. The ethyl acetate layer was washed with 20 ml of water and 20 ml of saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.501 g of crude title compound (oil, crude yield 83%). Obtained. This was used in the next step without purification.

[Production Scheme 1]
Synthesis of 1- [methoxy (phenyl) methyl)]-N- (5- [2,3-b] furopridyl) -1-cyclohexanecarboxamide 50 ml four-necked flask equipped with reflux condenser, stirrer and thermometer Into this, 0.501 g (2.02 mmol) of 1- [methoxy (phenyl) methyl)]-1-cyclohexanecarboxylic acid dissolved in 20 ml of dichloromethane was added. After cooling to 0 ° C., 0.282 g (2.22 mmol) of oxalyl chloride. And a catalytic amount of N, N-dimethylformamide was added and stirred at room temperature. After a long time, the residue obtained by concentrating the reaction solution was dissolved in 5 ml of dichloromethane. Then, this solution was added to a separately prepared solution of furo [2,3-b] pyridin-5-amine (0.181 g, 1.35 mmol), triethylamine (0.410 g, 4.05 mmol) and dichloromethane (20 ml). Stir for hours.
After completion of the reaction, the organic layer was washed with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (silica gel; Silica). Purified by gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; hexane: ethyl acetate = 3: 1 (volume ratio)), 0.236 g of the title compound (oil, yield 48%, n _D ²⁰ 1.5738) )

[Production Scheme 2]
Synthesis of 1- [methoxy (phenyl) methyl)]-N- (5- [2,3-b] furopridyl) -1-cyclohexanecarboxamide 50 ml four-necked flask equipped with reflux condenser, stirrer and thermometer 1- [methoxy (phenyl) methyl)]-1-cyclohexanecarboxylic acid 0.501 g (2.02 mmol) and furo [2,3-b] pyridin-5-amine 0.181 g (1 .35 mmol) and 0.320 g (4.05 mmol) of pyridine, and after cooling to 0 ° C., 0.425 g (2.22 mmol) of 1-ethyl-3- (3′-dimethylaminopropyl) carbodiimide hydrochloride and a catalytic amount 4- (dimethylamino) pyridine was added and stirred at room temperature for 48 hours.
After completion of the reaction, the organic layer was washed with 20 ml of 1N hydrochloric acid aqueous solution and 20 ml of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (silica gel Silica gel 60H (trade name, manufactured by Merck & Co., Inc.) developing solvent; purified by hexane: ethyl acetate = 3: 1 (volume ratio)) to give 0.148 g of the title compound (oil, yield 30%, n _D ²⁰ 1); 5738).

(Powder)
Compound of compound No. 1 (2 parts by weight), PAP (isopropyl phosphate ester, physical property improver) (1 part by weight) and clay (97 parts by weight) were uniformly ground and mixed to obtain the active ingredient. A powder containing 2% by weight can be obtained. Furthermore, each powder agent can be obtained by the same method except using each compound shown in Table 1 instead of Compound No. 1.

(Wettable powder)
Mix uniformly and grind a mixture of Compound No. 6 (20 parts by weight), sodium alkylbenzenesulfonate (3 parts by weight), polyoxyethylene nonylphenyl ether (5 parts by weight) and clay (72 parts by weight). Thus, a wettable powder containing 20% by weight of the active ingredient can be obtained. Furthermore, a wettable powder can be obtained in the same manner except that each compound shown in Table 1 is used instead of the compound of Compound No. 6.

(emulsion)
Compound No. 27 (30 parts by weight), methyl ethyl ketone (40 parts by weight) and polyoxyethylene nonylphenyl ether (30 parts by weight) are mixed and dissolved to obtain an emulsion containing 30% by weight of the active ingredient. it can. Furthermore, emulsions can be obtained in the same manner except that each compound shown in Table 1 is used in place of the compound of Compound No. 27.

Sol agent (flowable agent)
A mixture of Compound No. 230 (25 parts by weight), polyoxyethylene alkyl ether (1 part by weight), sodium alkylnaphthalene sulfonate (1 part by weight), carboxymethyl cellulose (1 part by weight) and water (72 parts by weight). By uniformly mixing, a sol containing 25% by weight of the active ingredient can be obtained. Furthermore, each sol can be obtained by the same method except that each compound shown in Table 1 is used instead of the compound of Compound No. 230.

(Granule)
To a mixture of compound No. 230 (5 parts by weight), sodium lauryl sulfate (1 part by weight), calcium lignin sulfonate (5 parts by weight), bentonite (30 parts by weight), and clay (59 parts by weight), water After adding (15 parts by weight) and kneading with a kneader, the mixture is granulated with a granulator and dried with a fluid dryer to obtain a granule containing 5% by weight of the active ingredient. Further, each granule can be obtained by the same method except that each compound shown in Table 1 is used instead of the compound of Compound No. 230.

The usefulness of agricultural and horticultural fungicides containing the compound (I) of the present invention as an active ingredient is shown in the following Test Examples 1 to 6, but the usefulness of the present invention is limited to these test examples. It is not a thing.
The test compound number represents the same number as the compound shown in Table 1.

Test example 1
Pest control effect test (flowable agent) for rice blast
In accordance with Example 8 to 2.5 leaf seedlings of paddy rice (variety: Asahi) grown in a greenhouse using a seedling box (1/10 area size of standard seedling box: 12 cm × 15 cm × height 4 cm) 50 ml of the prepared flowable diluent (5000 ppm) was irrigated. The paddy rice seedlings treated with the chemicals were immediately transplanted at 5 seedlings / pot into a pot (1/10000 are size) filled with paddy soil (brown water). After 4 weeks of cultivation in a greenhouse, inoculate the rice blast fungus (Pyricularia grisea) conidia formed on another rice leaf in advance into the drug-treated rice and leave it in a 24 ° C inoculation box for 24 hours. After that, the disease was promoted in an artificial weather room at 24 ° C. Seven days after the inoculation, the number of rice blast lesions per one rice plant was investigated, the average number of lesions was determined, and the control value (%) was calculated by the following formula 1. And according to following Table 3, the control value was converted into the evaluation value. This evaluation value was applied also in Test Examples 2-6. This test was conducted in a five-column system with one pot and one pot per drug group.

In addition, the degree of chemical damage to paddy rice was investigated according to the following criteria.
Survey index of the degree of phytotoxicity (evaluated in 6 levels)
5: Excitement 4: Acupuncture 3: Many 2: Slight 1: Slight 0: None This investigation index of the degree of chemical damage was also applied to Test Examples 2-6.
These results are shown in Table 4 below.

また、この比較薬剤Ａは、試験例２、３においても、比較薬剤として用いる。 Comparative drug A in Table 4 represents the following compound. Comparative drug A is described in WO 04/55261.

The comparative drug A is also used as a comparative drug in Test Examples 2 and 3.

Test example 2
Pest control effect test (granule) for rice blast
In accordance with Example 9, a 2.5-leaf seedling of paddy rice (variety: Asahi) grown in a greenhouse using a seedling box (1/10 area size of standard nursery box: 12 cm × 15 cm × height 4 cm) The prepared granule 5g was sprayed from the upper part of the seedling box. The paddy rice seedlings treated with the chemicals were immediately transplanted at 5 seedlings / pot into a pot (1/10000 are size) filled with paddy soil (brown water). After 6 weeks of cultivation in a greenhouse, inoculate the rice blast fungus (Pyricularia grisea) conidia formed on another rice leaf in advance into the drug-treated rice and leave it in a 24 ° C inoculation box for 24 hours. After that, the disease was promoted in an artificial weather room at 24 ° C. Seven days after the inoculation, the number of rice blast lesions per rice strain was investigated, the average number of lesions was determined, and the control value (%) was calculated by the following formula 2. This test was conducted in a five-column system with one pot and one pot per drug group.

これらの結果を以下の表５に示す。

These results are shown in Table 5 below.

Test example 3
Control effect test by applying water to rice blast disease (flowable agent)
Example 8 on 5 leaf seedlings (5 seedlings / strain, 1 strain / pot) of paddy rice (variety: Asahi) cultivated in a pot (1/10000 are size) filled with paddy soil (brown water) in a greenhouse 1 ml of a diluted solution (1000 ppm) of a flowable agent prepared according to the above was instilled into Ta surface water. After cultivating in a greenhouse for 1 week, inoculate rice plants treated with chemicals with rice blast fungus (Pyricularia grisea) conidia formed on another rice leaf in advance, and leave them in a 24 ° C inoculation box for 24 hours. After that, the disease was promoted in an artificial weather room at 24 ° C. Seven days after the inoculation, the number of rice blast lesions per one rice plant was investigated, the average number of lesions was determined, and the control value (%) was calculated by the following formula 3. This test was conducted in a five-column system with one pot and one pot per drug group.

これらの結果を以下の表６に示す。

These results are shown in Table 6 below.

Test example 4
Barley powdery mildew control effect test Dilution of wettable powder prepared according to Example 6 to 1.5-leaf seedlings of barley (variety: Nigi Akagi) grown in a plastic pot with a diameter of 6 cm in a greenhouse 10 ml of the liquid (500 ppm) was sprayed per one pot (stem and leaf spraying). The day after the drug treatment, a pot pre-sprayed with a spore suspension of conidia of barley powdery mildew (Erysiphe graminis) formed on another barley leaf (spore concentration 5 × 10 ⁵ cells / ml) On the top, 5 ml per pot was spray-inoculated, and the disease was controlled in an artificial climate room at 20 ° C. Seven days after the inoculation, the lesion area ratio (%) of barley powdery mildew on the first leaf was investigated, and the control value (%) was calculated by the following formula 4. This test was conducted in a triple system of 1 pot per 1 chemical solution concentration. The average evaluation value of the control effect was obtained.

これらの結果を以下の表７に示す。

These results are shown in Table 7 below.

Test Example 5
Wheat red rust control effect test Dilution of wettable powder prepared according to Example 6 on 1.5 leaf seedlings of wheat (variety: Norin 61) grown in a plastic pot with a diameter of 6 cm in a greenhouse 10 ml of liquid (500 ppm) was sprayed per pot (stem and leaf spraying). The day after the drug treatment, per spore suspension (spore concentration 5X10 ⁵ / ml) of wheat spore fungus (Puccinia recondite) formed in advance on a separate wheat leaf per pot. 5 ml of spray was inoculated, and the disease was controlled in an artificial climate room at 20 ° C. Ten days after the inoculation, the number of lesions on the first leaf was examined, and the control value (%) was calculated by the following formula 5. This test was conducted in a triple system of 1 pot per 1 chemical solution concentration. The average evaluation value of the control effect was obtained.

これらの結果を以下の表８に示す。

These results are shown in Table 8 below.

Test Example 6
Cucumber gray mold control effect test A cucumber (variety: Sagamihanjiro) 1.5 leaf stage seedling cultivated in a plastic pot with a diameter of 6 cm in a greenhouse was treated with a wettable powder prepared according to Example 4. 10 ml of diluted solution (100 ppm) was sprayed per pot (stem and leaf spraying). The day after the drug treatment, inoculate the first leaf of the cucumber treated with cucumber gray fungus (Botrytis cinerea) cultivated on the first leaf of the drug-treated cucumber gray mold (Botrytis cinerea). Put it inside. Four days after the inoculation, the lesion diameter (cm) was measured, and the control value (%) was calculated by the following formula 6. This test was conducted in a triple system of 1 pot per 1 chemical solution concentration. The average evaluation value of the control effect was obtained.

これらの結果を以下の表９に示す。

These results are shown in Table 9 below.

Claims (3)

Formula (I)

(In the general formula (I), X is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a haloalkoxy group having 1 to 6 carbon atoms. , An acyloxy group having 1 to 6 carbon atoms, a cyano group, a hydroxyl group, a nitro group, an amino group or a mercapto group optionally having 1 or 2 alkyl groups, and n represents an integer of 0 to 5, When n is 2 or more, each X may be the same or different, and Y and Z are each independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkoxy group having 1 to 6 carbon atoms. A cyclohexanecarboxamide derivative or a salt thereof represented by: A represents a sulfur atom or an oxygen atom;   In the general formula (I), X is a halogen atom, an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or a haloalkoxy group having 1 to 6 carbon atoms. Or a cyano group, n represents an integer of 0 to 5, and when n is 2 or more, each X may be the same or different, and Y represents an alkoxy group having 1 to 6 carbon atoms. The cyclohexanecarboxamide derivative or a salt thereof according to claim 1, wherein Z represents a hydrogen atom, and A represents a sulfur atom or an oxygen atom.   An agricultural and horticultural fungicide comprising the cyclohexanecarboxamide derivative represented by the general formula (I) according to claim 1 or 2 or a salt thereof.