CN1020606C - Production method of azole derivatives - Google Patents

Abstract

Disclosed are azole derivatives represented by the formula (wherein R is¹And R²Each represents ₁-C₅) An alkyl group or a hydrogen atom; x represents a halogen atom, (C)₁-C₅) Alkyl or phenyl; n represents an integer of 0 to 2; a represents a nitrogen atom or CH, with the proviso that when R²R is a chlorine atom¹Not a hydrogen atom), a process for the preparation thereof and agricultural and horticultural compositions containing azole derivatives of the formula (I).

Description

The present invention relates to an azole derivative having plant disease controlling activity and plant growth regulating activity, a method for producing the azole derivative, and an agricultural and horticultural composition containing the azole derivative as an active ingredient things. In more detail, the invention relates to:

1) Azole derivatives represented by formula (I):

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, a (C ₁ -C ₅ ) alkyl or phenyl; n represents a 0-2 integer and A represents a nitrogen atom or CH, with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom,

2) A method for producing azole derivatives represented by formula (I), the method comprising the following steps:

a)(i) reacting an alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide and making the resulting 1-(substituted benzyl)-2-oxocyclopentanecarboxylic acid reacting an alkyl ester with a (C ₁ -C ₅ ) alkyl halide; (ii) reacting an alkyl ester of 3-(C ₁ -C ₅ alkyl)-2-oxocyclopentanecarboxylic acid with a substituted benzyl halide; or (iii) reacting 1-(substituted benzyl)-3-(C ₁ -C ₅ alkyl)-2-oxocyclopentanecarboxylic acid with a (C ₁ -C ₅ ) alkyl halide reaction, so as to obtain the ester derivative of cyclopentanecarboxylic acid represented by formula (Ⅴ):

（Ⅴ）

(V)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; R represents a (C ₁ -C ₅ ) alkyl; X represents a halogen atom, (C ₁ -C ₅ ) alkane radical or phenyl and n is an integer from 0 to 2, with ^the proviso that ^R is not a hydrogen atom when R is a hydrogen atom,

b) hydrolysis and decarboxylation of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by formula (IV)

(Ⅳ)

In the formula, R ¹ , R ² , X and n are defined as above,

(c) Sulfurylides or oxothioylides, while subjecting cyclopentane derivatives thus obtained to oxiranation, or cyclopentane derivatives thus obtained by Wittig reaction The derivative of a kind of methylene cyclopentane obtained by ketone derivative carries out epoxidation reaction (the derivative of said methylene cyclopentane is represented by following formula (Ⅲ):

（Ⅲ）

(Ⅲ)

In the formula, R ¹ , R ² , X and n are respectively as defined above), so that the derivatives of cyclopentanone are converted into oxirane derivatives represented by the following formula (II):

（Ⅱ）

(II)

In the formula, R ¹ , R ² , X and n are defined as above, and then

d) reacting the oxirane derivative thus obtained with 1,2,4-triazole or imidazole represented by the following formula (VI):

(VI)

(In the formula, M represents a hydrogen atom or an alkali metal atom, and A represents a nitrogen atom or -CH=, thereby obtaining the azole derivatives represented by the following formula (I):

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer of 0-2 ; A represents a nitrogen atom or CH, provided that R ¹ is not a hydrogen atom when R ² is a hydrogen atom.

3) Agricultural and horticultural compositions having fungicidal activity and plant growth regulating activity, which contain an effective amount of an azole derivative represented by the formula (I).

The damage to crops due to various plant diseases is enormous, and environmental pollution due to the chemicals applied to control these plant diseases poses a problem, so Therefore, agricultural and horticultural chemicals sold to control plant diseases require low toxicity to humans, animals, birds, and fish, and low toxicity to useful plants, that is, a chemical that is safe for application is required. Agricultural and horticultural chemicals with high toxicity, low environmental impact and excellent control of plant diseases.

In order to fulfill such demands, the following agricultural and horticultural fungicides have hitherto been proposed.

(1) A triazole or imidazole compound represented by the following formula:

In the formula, R ¹ represents a -CH=CH-X, -CH≡CX or -CH ₂ -CH ₂ -X (wherein X is a hydrogen atom, alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl , substituted aryl that may be substituted, aralkyl that may be substituted, aryloxyalkyl that may be substituted or heterocyclic group that may be substituted); R ² represents an alkyl, cycloalkyl or substituted Aryl; Z represents a chlorine atom, cyano or -OR ³ (where R ³ is a hydrogen atom, acetyl, alkyl, alkenyl or aralkyl), Y represents a nitrogen atom or CH, and the Acid addition salts of compounds and metal complexes thereof [see Japanese Laid-open Patent Application No. 57-114577 (1982), equivalent to U.S. Patent No. 4,507,140 and European Patent No. 52424].

(2) A triazole or imidazole compound represented by the following formula:

In the formula, R represents a crosslinking group: -(CH ₂ )n- (wherein n is 0, 1 or 2), -CH=CH-, -O-, -S-, -NH- or -C(=O )-; X represents a nitrogen atom or CH; Y and Z can be the same or different, respectively represent a halogen atom, alkyl, alkoxy, haloalkoxy, haloalkyl, nitro, phenyl or phenoxy, m and p represent 0, 1, 2 or 3, respectively, and the acid of said compound, its metal complexes and its functional derivatives [see Japanese Published Patent Application No. 57-126479 (1982), equivalent to European Patent No. 52425 )

(3) Derivatives of 1-hydroxyethylazoles represented by the following formula:

In the formula, R represents an alkyl group, a cycloalkyl group that may be substituted or a phenyl group that may be substituted, X represents a nitrogen atom or CH; Y represents a -OCH ₂ -, -CH ₂ -CH ₂ - or -CH= CH-; Z represents a halogen atom, alkyl, cycloalkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, haloalkylthio, phenyl that may be substituted, phenoxy that may be substituted or Phenylalkyl which may be substituted or phenylalkoxy which may be substituted (m represents 0, 1, 2 or 3), its acid addition salts and its metal complexes [see Japanese Laid-Open Patent Application 57-16868 (1982), equivalent to US Patent 453241 and European Patent 40345].

(4) Compounds of cycloaliphatic alcohol represented by the following formula:

In the formula, ^R6 represents an unsubstituted phenyl group or a phenyl group substituted by 1 to 5 groups selected from the following groups: halogen atom, amino group, nitro group, cyano group, phenyl group, halogenated phenyl group, (C ₁ - C ₁₀ )alkyl, halo(C ₁ -C ₁₀ )alkyl, (C ₁ -C ₁₀ )alkoxy, halo(C ₁ -C ₁₀ )alkoxy, (C ₁ -C ₁₀ )alkoxy Thio, (C ₁ -C ₁₀ ) alkylenedioxy, (C ₁ -C ₁₀ ) alkylamino and di(C ₁ -C ₁₀ ) alkylamino; X represents a hydrogen atom or methine, ring A is a cyclopentane ring, cyclohexane ring, cycloheptane ring, 1,2-indane ring, tetrahydronaphthalene ring or benzocyclopentane ring, each of which may be unsubstituted or The benzene ring in which is substituted by the above 1-4 substituents [see Japanese Published Patent Application No. 58-189171 (1983), equivalent to US Patent 4503062 and European Patent 94146]

(5) A triazole compound or an imidazole compound represented by the following formula

In the formula, W is a CH or nitrogen atom; Q is a substituted or unsubstituted aryl group, especially a substituted or unsubstituted phenyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted alkyl group; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ may be the same or different, each representing a hydrogen atom, hydroxyl, alkyl, cycloalkyl, substituted or unsubstituted aralkyl , substituted or unsubstituted phenyl, any pair of R ¹ and R ² , R ³ and R ⁴ , R ⁵ and R ⁶ or R ⁷ and R ⁸ together with adjacent ring carbon atoms represent a carbonyl group (C=O ); R ⁹ and R ¹⁰ may be the same or different, each representing a hydrogen atom, an alkyl group, a cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted phenyl group, n is 0 or 1, and the Stereoisomers of the compound and its metal complexes [see Japanese Laid-Open Patent Application No. 60-2150674 (1985), equivalent to European Patent No. 153797].

As a result of the inventor's research, a fungicide for agriculture and gardening is provided, which has high application safety, little impact on the environment and excellent control effect on a wide range of plant diseases. The inventor has found the following formula Representative azole derivatives:

In the formula, X represents a halogen atom, alkyl, haloalkyl, phenyl, cyano or nitro; n represents an integer from 0 to 5, and A represents a nitrogen atom or CH, provided that n is 1 to 5 X may be the same or different [see Japanese Published Patent Application 62-1429667 (1987), equivalent to UK Patent 2180236 A].

In order to obtain agricultural and horticultural fungicides with low toxicity to humans and animals, high application safety, and excellent control effects on a wide range of plant diseases, the present inventors have further studied the synthesis of many azole derivatives and Its practicability was measured, and it was found that: the azole derivatives represented by the following formula (I) not only have the above-mentioned specific characteristics, but also can be effectively used as plant growth regulators, and it is based on this discovery that the present invention has been completed .

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer of 0-2 , A represents a nitrogen atom or CH, provided that R ¹ is not a hydrogen atom when R ² is a hydrogen atom.

That is to say, the object of the present invention is to provide an azole derivative which is effective as an active ingredient in an agricultural and horticultural composition, and which has plant disease control activity and plant growth regulation activity; the present invention Also provided are methods for producing the azole derivatives and agricultural and horticultural compositions containing the azole derivatives as active ingredients, and at the same time, the latter exhibit excellent control effects on plant diseases over a wide range and exhibit plant growth regulating effects and low Toxicity and excellent application safety.

One aspect of the present invention provides azole derivatives represented by the following formula (I):

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer of 0-2 and A represents a nitrogen atom or CH, with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom.

The second aspect of the present invention provides an azole derivative represented by formula (I):

(I)

In the formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer from 0 to 2 and A represents a nitrogen atom or CH, with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom. The method comprises the steps of:

a) (i) reacting an alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide and reacting the resulting 1-(substituted benzyl)-2-oxocyclopentane Reaction of an alkyl ester of formic acid with a (C ₁ -C ₅ ) alkyl halide; (ii) making an alkyl ester of 3-(C ₁ -C ₅ alkyl)-2-oxocyclopentanecarboxylic acid with a substituted benzyl halide; or (iii) reacting 1-(substituted benzyl)-3-(C ₁ -C ₅ alkyl)-2-oxocyclopentanecarboxylic acid with a (C ₁ -C ₅ ) alkyl halide reaction, thereby obtaining the ester derivative of cyclopentanecarboxylic acid represented by formula (Ⅴ):

（Ⅴ）

(V)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; R represents a (C ₁ -C ₅ ) alkyl; X represents a halogen atom, (C ₁ -C ₅ ) alkane radical or phenyl and n is an integer from 0 to 2, with ^the proviso that ^R is not a hydrogen atom when R is a hydrogen atom,

b) hydrolysis and decarboxylation of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by formula (IV)

(Ⅳ)

In the formula, R ¹ , R ² , R ³ , X and n are defined as above,

(c) Using sulfonium ylides or oxothioylides, subjecting cyclopentane derivatives thus obtained to oxirane reactions, or reacting cyclopentane derivatives obtained therefrom by Wittig reactions A derivative of methylene cyclopentane obtained from a cyclopentanone derivative is subjected to an epoxidation reaction (the derivative of methylene cyclopentane is represented by the following formula (Ⅲ):

（Ⅲ）

(Ⅲ)

In the formula, R ¹ , R ² , X and n are respectively as defined above), so that the derivatives of cyclopentanone are converted into oxirane derivatives represented by the following formula (II):

（Ⅱ）

(II)

In the formula, R ¹ , R ² , X and n are respectively defined as above, and then

d) reacting the ethylene oxide derivative thus obtained with 1,2,4-triazole or imidazole represented by the following formula (VI):

（Ⅵ）

(VI)

In the formula, M represents a hydrogen atom or an alkali metal atom, and A represents a nitrogen atom or CH.

The third aspect of the present invention provides an agricultural and horticultural composition having fungicidal activity and plant growth regulating activity, which contains an azole derivative represented by the following formula (I) as an active ingredient:

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer of 0-2 and A represents a nitrogen atom or CH, with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom.

The fourth aspect of the present invention provides an oxirane derivative for use in the production of an azole derivative represented by the formula (I), which is represented by the following formula (II):

（Ⅱ）

(Ⅱ)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl; n represents an integer of 0-2 , with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom.

A fifth aspect of the present invention provides a methylenecyclopentane derivative for use in the production of an azole derivative represented by the formula (I), which is represented by the following formula (III):

(Ⅲ)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl and n represents an integer of 0-2 , with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom.

The sixth aspect of the present invention provides a cyclopentanone derivative for use in the production of an azole derivative represented by formula (I), which is represented by the following formula (IV):

（Ⅳ）

(Ⅳ)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl and n represents an integer of 0-2 , with the proviso that ^R1 is not a hydrogen atom when ^R2 is a hydrogen atom.

The seventh aspect of the present invention provides an ester derivative of cyclopentanecarboxylic acid for the production of azole derivatives represented by formula (I), the acid represented by the following formula (V):

（Ⅴ）

(V)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; R represents a (C ₁ -C ₅ ) alkyl; X represents a halogen atom, (C ₁ -C ₅ ) alkane radical or phenyl and n represents an integer of 0-2, with the proviso that R ¹ is not a hydrogen atom when R ² is a hydrogen atom.

In the accompanying drawings, Figures 1 to 76 show the azole derivatives shown in Table 1 according to the present invention infrared absorption spectrum. That is to say, Fig. 1 has shown the infrared absorption spectrum of No. 1 compound in Table 1; Fig. 2 has shown the infrared absorption spectrum of No. 2 compound in Table 1; Fig. 3 has shown the infrared absorption spectrum of No. 3 compound in Table 1; Fig. 4 to 76 show the infrared absorption spectra of compounds No. 4 to No. 76 in Table 1, respectively.

The core of the present invention lies in the novel azole derivatives represented by formula (I):

（Ⅰ）

(I)

In the formula, R ¹ and R ² represent a (C ₁ -C ₅ ) alkyl or hydrogen atom; X represents a halogen atom, (C ₁ -C ₅ ) alkyl or phenyl, n represents an integer of 0-2 and A represents a nitrogen atom or CH, provided that R is ^not a hydrogen atom when ^R is a hydrogen atom; the method for producing azole derivatives represented by formula (I), and each compound used as an intermediate, That is, derivatives of oxirane represented by formula (II), derivatives of methylene cyclopentane represented by formula (III), derivatives of cyclopentanone represented by formula (IV) and derivatives of cyclopentanone represented by formula (V) Derivatives of esters of cyclopentanecarboxylic acid, and agricultural and horticultural compositions containing azole derivatives represented by the formula (I) and having fungicidal activity and plant growth regulating activity.

The physical and chemical properties of the azole derivatives represented by the formula (I) and each intermediate used for the production of the above azole derivatives are shown in Tables 1-5.

In addition, each of these intermediates is a novel compound.

The nuclear magnetic resonance spectra of the compounds in Tables 1-5 are measured by using deuterium nuclear magnetic resonance as an internal standard. The meanings of the symbols are as follows:

s-singlet, d-doublet, t-triplet, q-quartet, m-multiplet, b-broad, j-coupling constant (unit, Hertz).

The infrared absorption spectra of each azole derivative listed in Table 1 are shown in Figures 1-16 respectively.

Based on the consideration of plant disease control ^activity and plant growth regulation activity, R in the preferred azole derivatives represented by formula (I) is a hydrogen atom or (C ₁ -C ₄ ) alkyl; R ² is a hydrogen atom or ( C ₁ -C ₃ ) alkyl (both R ¹ and R ² cannot be hydrogen atoms at the same time); X is a halogen atom at the 4-position of a substituted benzene ring; n=1, and A is a nitrogen atom or CH, in addition, as Especially preferred azole derivatives, wherein R ¹ and R ² each represent a hydrogen atom or (C ₁ -C ₃ ) alkyl (R ¹ and R ² cannot be hydrogen atoms at the same time); X represents a substituted benzene ring 4- Halogen atom at position; n=1, and A represents nitrogen atom.

Among the compounds listed in Table 1, preferred azole derivatives are compounds 1-3, 5, 9-11, 16, 18, 29-32, 37, 38, 42-45, 50, 59, 62, 63, 65 and 69.

The azole derivatives of the present invention can be prepared by the following methods.

The azole derivatives shown in the formula (I) can be reacted in a diluent by the oxirane derivatives shown in the formula (II) and 1,2,4-triazole or imidazole shown in the following formula (VI) And made:

(VI)

In the formula, M represents a hydrogen atom or an alkali metal atom and A represents a nitrogen atom or CH.

The ethylene oxide derivative represented by the formula (II) used as a starting material can be prepared by the following method.

That is, reacting cyclopentanone (IV) with a sulfur ylide or an oxysulfide ylide such as dimethyloxythiomethyl ylide or dimethylthiomethyl ylide in the presence of a diluent, The method described in "Organic Synthesis" 49,78 (1968) and "Journal of American Chemical Society" (1965) 1353 (this method is regarded as A-method) can obtain the oxirane shown in formula (II) derivative.

In addition, as a different method (called B-method), the Witting reaction [see "Organic Synthesis" 40 66 (1966) and "Journal of Organic Chemistry" 28 1128 (1963)] by the formula (IV) The shown cyclopentanone obtains the methylene cyclopentane shown in formula (Ⅲ), and by epoxidation [referring to "Organic Synthesis" volume 4, 552 (1963), 49, 62 (1969) ] The oxirane derivative represented by the formula (II) is obtained from the obtained compound.

The reaction formulas of the above-mentioned A-method and B-method are shown below.

The method for preparing formula (II) formula oxirane derivative:

（Ⅲ）

(Ⅲ)

In addition, cyclopentanone derivatives represented by formula (IV) can be prepared by the following method:

That is, in the case where both R ¹ and R ² in formula (IV) are the same (C ₁ -C ₅ )alkyl group, the cyclopentanone compound shown in formula (VII) is subjected to dialkyl Reaction is converted into the ester derivative of cyclopentanecarboxylic acid shown in formula (Ⅴ), and this ester derivative is through hydrolysis and decarboxylation reaction again, and in R ¹ and R ² one of them is a hydrogen atom and the other is ( In the case of C ₁ -C ₅ ) alkyl group, the desired benzyl group can be introduced into the alkyl cyclopentane carboxylate derivative shown in formula (Ⅷ) to obtain cyclopentane shown in formula (Ⅴ) An ester derivative of formic acid, which undergoes hydrolysis and decarboxylation. Thus, a cyclopentanone derivative represented by formula (IV) can be obtained.

In addition, if R ¹ and R ² in formula (IV) are different (C ₁ -C ₅ ) alkyl groups, then when introducing a different (C ₁ -C ₅ ) alkyl group into formula (V) Ester derivatives of cyclopentanecarboxylic acid, wherein one of ^R1 and ^R2 is a ( _C1 - _C5 ) alkyl group and the other is a hydrogen atom, after which the obtained ester derivatives are subjected to hydrolysis and decarboxylation reactions , the desired derivative represented by formula (IV) can be obtained.

The reaction formula of above-mentioned cyclopentanone is as follows

The synthetic route of formula (Ⅳ) cyclopentanone

Incidentally, compounds of the formulas (VII) and (VIII) are known compounds which can be prepared from alkyl esters of 2-oxocyclopentanecarboxylic acid by the method described in Organic Chemistry 29, 2781 (1964).

As the diluent used to prepare the azole derivatives shown in the formula (I) of the present invention, the following can be enumerated, hydrocarbons such as benzene, toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, Tetrahydrocarbon, etc.; alcohols such as methanol, ethanol, etc.; ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, etc.; and other types such as acetonitrile, acetone, dimethylformamide, dimethyl sulfoxide, etc.

In addition, in the method for preparing the azole derivatives of the present invention, the reaction is carried out under the condition that the above-mentioned diluent coexists with a base or an acid. As the base used here, the following can be listed: alkali metal carbonates such as sodium carbonate, carbonic acid Potassium, etc.; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, etc.; alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.; alkali metal hydrides such as sodium hydride, potassium hydride, etc.; alkali metal Alkyl compounds such as n-butyl lithium, etc., other types such as triethylamine, pyridine.

Examples of the acid include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, and the like, and organic acids such as formic acid, acetic acid, butyric acid, p-toluenesulfonic acid, and the like.

In order to implement the method for preparing azole derivatives of the present invention, for example, in the case of preparing ester derivatives of cyclopentanecarboxylic acid represented by formula (V), the preferred way is to make haloalkyl halide or substituted benzyl The halogen is reacted with a compound represented by formula (VII) or (VIII) in a diluent, if necessary, in the presence of a base. The reaction temperature can be selected according to need within the range from the solidification temperature of the diluent (used as a solvent) to its boiling point, preferably 0-100°C.

The compound shown in formula (Ⅳ) can be prepared by making the ester derivative of cyclopentanecarboxylic acid shown in formula (Ⅴ) carry out decarboxylation reaction with inorganic acid or organic acid at 80-150°C for 2-24 hours. Good for stirring.

In order to produce the oxirane derivatives represented by the formula (II), in the case of applying the A-method, it is preferable to dissolve the ketone represented by the formula (IV) in a diluent (especially dimethyl sulfoxide) preferably) to the solution prepared by adding an equal amount of base (such as sodium hydride) and iodide Trimethylsulfonium sulfonium or trimethylsulfonium iodide are mixed in the dimethylsulfoxymethyl ylide or dimethylthiomethyl ylide, and the two compounds are reacted.

In this case, the dimethylthiomethyl ylide or dimethylthiomethyl ylide is preferably 1.0-2.0 equivalents to the cyclopentanone derivative represented by the formula (IV). The reaction is preferably carried out in the range of 25-100°C for 1-40 hours.

In addition, if the above-mentioned preparation process is carried out by B-method, the cyclopentanone derivative shown in formula (IV) must be added to the diluent by diluting an equal amount of alkali (such as sodium hydride) and methyl triphenylphosphonium halide. In the triphenylphosphinemethyl ylide prepared by mixing with a solvent (especially dimethyl sulfoxide), the two compounds are reacted at a temperature of 0-100°C for 2-10 hours. After isolating the methylene cyclopentanone derivative shown in the formula (III) thus generated, it is dissolved in a diluent, and hydrogen peroxide or organic peracids such as peracetic acid, perbenzoic acid, m-chloroperbenzoic acid are added After waiting, make it react at -10°C - the boiling point of the diluent, preferably at -10-80°C.

The oxirane compound (II) obtained from the cyclopentanone derivative shown in formula (II) by A-method or B-method, its stereoisomer structure presents the oxirane compound shown in formula (II) The conformation of the substituted benzyl group at the 7-position and the oxirane group at the 3-position in 1-oxaspiro[2,4]heptane:

For example, separation of these stereoisomers represented by formula (II-A) and formula (II-B) can be accomplished by chromatography (thin layer chromatography, column chromatography, high performance liquid chromatography, etc.). The structural properties of these stereoisomers can be determined by, for example, nuclear magnetic resonance spectroscopy and the like.

In order to obtain azole derivatives represented by formula (I), the oxirane compound represented by formula (II) can be added to the azole compound represented by formula (VI) in the presence of a base (if necessary). in a solution prepared by dissolving an oxirane compound in a diluent, or on the contrary, an alkali metal salt of an azole compound is added to a solution prepared by dissolving an oxirane compound in a diluent, and the two Compounds react. The reaction temperature can be selected from the solidification point of the diluent to its boiling point as required, but it is particularly preferred that the reaction is carried out at a temperature of 0-120°C, more preferably at 60-120°C with stirring. -10 hours.

After completion of the reaction, the obtained reaction mixture was cooled in ice and extracted with an organic solvent such as ethyl acetate, chloroform, dichloromethane, benzene and the like. After the organic layer was separated, washed with water and dried, the solvent of the organic layer was distilled off under reduced pressure. The residue thus obtained can be purified to obtain the desired compound. Purification can be carried out by the residue Line recrystallization, silica gel chromatography, etc. to complete.

Since there are two isomers shown in formula (II-A) and (II-B) in the oxirane compound as the raw material of azole derivatives shown in formula (I), therefore in formula (I) The following stereoisomers exist in the indicated azole derivatives, which are prepared by reacting oxirane compounds shown in formula (II) with 1,2,4-triazoles or imidazoles of formula (VI) have to:

＝于纸面背后，

= behind the paper,

- = on paper,

＝于纸面之前。

= before the paper.

Of course, separation of the isomers represented by formulas (I-A) and (I-B) can be accomplished, for example, by chromatography.

The use of the azole derivatives (azole-based cyclopentanol derivatives) of the present invention represented by the formula (I) as agricultural and horticultural active ingredients is explained below.

(1) Fungicidal effect on plant disease fungi:

The azole derivatives of the present invention exhibit the efficacy of controlling the following plant diseases in a wide range.

Pyricularia Oryzae on rice,

Cyclosporium miyabei on rice,

Xanthomonas Oryzae on rice,

Rhizoctonia solani on rice,

Helminthospora on rice,

Fujikura on rice,

Monocystis spp. on apples,

Apple nigella on apples,

Sclerotinia on apples,

Alternaria apples on apples,

Apple black rot skin shell on apples,

Alternaria kikuchi on pears,

pear shells on pears,

pear gum rust on pears,

Nashicola on pears,

Grape husks on grapes,

Phakopsora ampelopsidis on grapes,

husks on grapes,

Erysiphe graminis on barley,

Ryecoria on barley,

Puccinia graminearum on barley,

Puccinia triformis on barley,

Puccinia recondita on wheat,

Septoria tritici on wheat,

Puccinia triformis on wheat,

Powdery mildew graminis f.sp.tritci on wheat,

Monofilament shells on melons,

Cucurbitaceae spinosa on melon,

Fusarium oxysporum on watermelon,

Fusarium oxysporum cucumerinum on cucumber,

Fusarium oxysporum raphani on Japanese radish,

Powdery mildew dispora on tomato,

Alternaria solani on tomato,

Powdery mildew dispora on eggplant,

Sephaerotheca humuli on grass mold,

Powdery mildew dispora on tobacco,

Alternaria longhandle on tobacco,

Buckwheat Cercospora on sugar beets,

Alternaria solani on potatoes,

Septoria sojae on soybean,

Cercoides kikuchi on soybean,

Sclerotinia cinerea on a stone fruit tree,

Botrytis cinerea on various crops,

Sclerotinia etc.

In addition, the azole derivatives of the present invention have not only preventive control but also therapeutic effects on some plant diseases.

(2) Regulatory effect on plant growth:

Along with the elucidation of the mechanism of regulating plant growth by phytohormones, in recent years, drugs called plant growth regulators have come to be used in the production fields of agriculture and horticulture.

For example, the use of gibberellin to produce seedless grapes can promote rooting of cuttings with the help of α-naphthylacetic acid, and 2-chloroethyltrimethylammonium chloride (trade name (CCC) can be used as a growth inhibitor of wheat, which Has been well known.

In addition, the application of the technology of regulating the growth cycle of plants by using plant growth regulators has been expanded not only to crops such as cereals, vegetables, fruit trees, etc., but also to horticultural plants such as flowers, etc., and then to plants-trees in a broad sense, The functions of plant growth additives include promoting rooting, controlling flowering, fruiting, increasing fruit size, promoting growth, controlling growth and controlling metabolism.

Therefore, in recent years, there has been a growing trend in the types and amounts of plant growth additives used, however, in fact, the practical application of plant growth additives has not reached the desired level.

The azole derivatives (azole-based cyclopentanol derivatives) of the present invention can exhibit various plant growth regulating activities on a wide range of plants, and this characteristic of the substance can be listed as As follows.

i) inhibition of vegetative growth of plants, especially tree height growth of plants,

ii) activity to increase the content of useful components in plants,

iii) Controlling activities during the maturation and flowering stages of plants.

As an example of utilizing the growth inhibitory activity of i), the azole derivatives of the present invention can inhibit the growth of weeds (showing their herbicidal efficacy) and turf; can prevent lodging of plants prone to lodging such as rice, barley, wheat, etc.; Mechanized harvesting of soybeans and cotton can be realized by inhibiting the growth of its tree height; the growth of tobacco leaves can be promoted by inhibiting the germination of associated buds; the pruning operation can be avoided by inhibiting the growth of hedgerows; the commercial value of ornamental plants can be increased by inhibiting the growth of ornamental plants, etc. wait.

For ii) the activity of increasing the content of useful components in plants, examples include increasing the sugar content of sugar beet, sugar cane and citrus; increasing the protein content of grains and soybeans, etc., and furthermore, for iii) Activities that control plant maturity and flowering, examples include those that can be used to ship fresh fruit and flowers while keeping them in season.

In order to use the azole derivatives represented by formula (I) as fungicides and plant growth regulators, the derivatives themselves or the mixture of derivatives and carriers (diluents) can be processed into powders, wettable powders, Granules, emulsifiable concentrates, liquid preparations, etc., and the preparations thus prepared are conveniently used.

In addition, other auxiliaries such as spreading agents, emulsifiers, wetting agents, adhesives can of course be added in addition to the carrier, if necessary.

Incidentally, since the azole derivatives shown in formula (I) contain 1,2,4-triazole ring or imidazole ring, the azole derivatives can be used in the form of acid addition salts with inorganic or organic acids , or in the form of metal complexes.

In addition, in the azole derivatives of the present invention represented by formula (I), the 1-position, 2-position and 5-position on the cyclopentane ring respectively have azole-based methyl, (C-C)alkyl And substituted benzyl, there may exist stereoisomers such as cis and trans geometric isomers, so the present invention includes individual isomers and isomer mixtures mixed in any proportion.

Accordingly, the agricultural and horticultural compositions of the present invention include those containing one isomer or a mixture of isomers as an active ingredient.

The azole derivatives of the present invention represented by formula (I) have good plant disease control activity and plant regulation activity, and can be used as active ingredients in agricultural and horticultural compositions.

The usefulness of the present invention can be illustrated by these specific examples showing the use of the azole derivatives of the present invention as active ingredients of agricultural and horticultural compositions, however, the following examples are not intended to limit the essential characteristics of the present invention.

[1] Production examples of azole derivatives represented by formula (I) and their intermediates.

Example 1

Preparation of methyl 1-(4-chlorobenzyl)-3,3-dimethyl-2-oxocyclopentanecarboxylate (intermediate compound 156 in Table 5)

Add 5.0 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) to 150 ml of anhydrous benzene while stirring under a nitrogen atmosphere, and then add 50 g of 1-(4-chlorobenzyl) -Methyl 2-oxocyclopentanecarboxylate, and the whole mixture was stirred at 80°C for 40 minutes. After cooling to room temperature, 29.4 g of iodomethane were added dropwise to the reaction mixture and the resulting mixture was stirred at 80° C. for 2 hours. After cooling it to room temperature, 5.0 g of sodium hydride (1 equivalent) was added, and it was stirred at 80° C. for 30 minutes. cool to room After warming, 29.4 g of iodomethane (one equivalent) was added to the reaction mixture, which was stirred at 80°C for 8 hours.

After the reaction mixture thus obtained was cooled, it was poured into a mixture of acetic acid and ice water, and the whole mixture was extracted with ethyl acetate to give an organic layer, which was washed with aqueous sodium bicarbonate and then with brine, and The washed organic layer was dried over anhydrous sodium sulfate, and then the solvent in the organic layer was distilled off under reduced pressure.

By distilling and purifying the residue thus obtained under reduced pressure, 44.8 g of the objective compound [boiling point: 142-143°C (0.7 mm Hg)] was obtained.

Example 2

5-(4-Chlorobenzyl)2,2-dimethyl-1-cyclopentanone (intermediate compound 133 in Table 4)

Add 44.8 grams of 1-(4-chlorobenzyl)-3,3-dimethyl-2-oxocyclopentanecarboxylic acid methyl ester (compound 156 in Table 5) to 120 ml of 47% hydrobromic acid, The mixture thus formed was stirred at 100°C for 12 hours.

After the above reaction mixture was cooled, it was poured into ice water and extracted with ethyl acetate to obtain an organic layer, which was washed with aqueous sodium bicarbonate solution and then brine, and dried over anhydrous sodium sulfate. The residue obtained after distilling off the solvent in the organic layer under reduced pressure was distilled and purified under reduced pressure to obtain 31 g of the objective compound [boiling point: 124°C (1 mmHg)].

Example 3

Preparation of 5-(4-chlorobenzyl)-2,2-dimethyl-1-methylenecyclopentane (intermediate compound 122 in Table 3)

Add 3.6g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) into 150ml of anhydrous dimethyl sulfoxide in a helium atmosphere, stir the mixture for 30 minutes at 70°C, and dissolve with ice water After it was cooled, 53.6 g of methyltriphenylphosphine bromide were added, and the mixture was stirred for 30 minutes under ice-cooling, and the cooled mixture was further stirred for 10 minutes at room temperature. Thereafter, 23.6 g of 5-(4-chlorobenzyl)-2,2-dimethyl-1-cyclopentanone (compound 133 in Table 4) were added, which was stirred at room temperature for 1 hour and then at 70°C 30 minutes to complete the entire reaction process.

After the above reaction mixture was cooled, it was poured into ice water and extracted with ethyl acetate to obtain an organic layer, which was washed with brine solution and dried over anhydrous sodium sulfate, and then distilled off the organic layer under reduced pressure. solvent.

The thus obtained oil and the oil in the solid mixture were extracted with n-hexane, and the n-hexane extract was purified by silica gel column chromatography to obtain 22.1 g of the intended compound.

Example 4

Preparation of 7-(4-chlorobenzyl)-4-dimethyl-1-oxospiro[2,4]hexane (intermediate compounds 77 and 78 prepared by A-method in Table 2

3g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) was added to 70ml of anhydrous dimethyl sulfoxide while stirring in a helium atmosphere, and then 27.5g of trimethylsulfoxonium iodide was added. After stirring at room temperature for 30 minutes, add 23.6g of 5-(4-chlorobenzyl)-2,2-dimethyl-1-cyclopentanone (the compound number is 133, shown in Table 4) within 30 minutes ) and 20 ml of anhydrous dimethyl sulfoxide, and the mixture was stirred at 90°C for 2 hours.

After the above reaction mixture was cooled, it was poured into ice water and extracted with ethyl acetate to obtain An organic layer was obtained, which was washed with saline solution and dried over anhydrous sodium sulfate. The solvent in the organic layer was evaporated under reduced pressure, and the resulting residue was separated by silica gel column chromatography to obtain 13.95 g of target compounds 77 and 1.05 Gram object compound 78.

Example 5

Preparation of 7-(4-fluorobenzyl)-4,4-dimethyl-1-oxyspiro[2,4]heptane (intermediate compounds 81 and 82 prepared by B-method in Table 2

17 g of 5-(4-fluorobenzyl)-2,2-dimethyl-1-methylenecyclopentane (compound 124 in Table 3, dissolved in 170 ml of chloroform, and then 27.1 g of methylene Chloroperbenzoic acid, and the mixture was stirred at room temperature for 2 hours. Next, 25.4 g of calcium hydroxide was added to the mixture over 10 minutes, and the mixture was stirred at room temperature for 30 minutes.

After filtering off the solid matter, the chloroform layer in the filtrate was concentrated to obtain a colorless oil, which was purified by silica gel column chromatography to obtain 4.5 g of the target compound 81 and 86 g of the target compound 82.

Example 6

Preparation of C-5-(2,4-dichlorobenzyl)-2,2-dimethyl-1-(1H-imidazol-1-ylmethyl)-γ-1-cyclopentanol (in Table 1 Compound 15)

996 mg of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) was added to 18 ml of anhydrous dimethylformamide with stirring under a helium atmosphere. Next, 2.83 g of 1H-imidazole was added and the mixture was stirred at room temperature until bubbling ceased. Dissolve 5.93g of 7-(2,4-dichlorobenzyl)-4,4-dimethyl-1-oxaspiro[2,4]heptane (compound 83 in Table 2) in 10ml of anhydrous dimethyl The solution formed by methyl formamide was added dropwise to the above The resulting solution was stirred at 80 °C for 2 hours.

After the reaction mixture was cooled, it was poured into ice water and extracted with ethyl acetate to obtain an organic layer.

After washing the organic layer with water, the organic layer was dried over anhydrous sodium sulfate, and the solvent in the organic layer was distilled off under reduced pressure.

The resulting residue was separated and purified by silica gel column chromatography and then recrystallized from a mixture of hexane and ethyl acetate to obtain 2.7 g of the intended compound.

Example 7

Preparation of t-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-γ-1-cyclopentanol ( Compound No.2 in Table 1)

5.0 g of 7-(4-chlorobenzyl)-4,4-dimethyl-1-oxaspiro[2,4]heptane (compound 78 in Table 2) was added to 30 ml without stirring under a helium atmosphere. In water dimethylformamide, and make it dissolve, then slowly add the sodium salt of 2.2g 1H-1,2,4-triazole (purity: 90%, produced and sold by Aldrich Company), at 70 ℃ The mixture was stirred for 2 hours.

After the reaction mixture was cooled, it was poured into ice water and extracted with ethyl acetate to obtain an organic layer. After washing the organic layer with water, it was dried with anhydrous sodium sulfate, and then evaporated under reduced pressure. solvent.

The resulting residue was separated and purified by silica gel column chromatography to obtain 3.1 g of the intended compound.

Example 8

Preparation of 2-(4-chlorobenzyl)-5-methyl-1-cyclopentanone (intermediate compound 137 in Table 4)

Add 3.04 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) to 126 ml of anhydrous benzene, then add 18 g of methyl 3-methyl-2-oxocyclopentanecarboxylate, at room temperature After stirring for 1 hour, 21.5 g of 4-chlorobenzyl chloride were added and the mixture was refluxed in an oil bath at 90°C for 6 hours.

After the reaction mixture was cooled, it was extracted with benzene, and the benzene layer was washed with brine solution. After drying the benzene layer with anhydrous sodium sulfate, the solvent in the benzene layer was evaporated under reduced pressure to obtain 33.6 g of brown oily 1-(4-chlorobenzyl)-3-methyl-2-oxocyclopentanecarboxylic acid Methyl ester (intermediate compound 160 in Table 5).

After adding 100ml of 47% hydrobromic acid to the unpurified above ester, stir vigorously at 110°C for 18 hours. After it was cooled, it was extracted with dichloromethane, and the organic layer was washed successively with aqueous sodium carbonate solution and brine solution. The washed organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.

The resulting residue was purified by distillation under reduced pressure to obtain 17.4 g of the intended compound.

Example 9

Preparation of methyl 1-(4-chlorobenzyl)-3-ethyl-3-methyl-2-oxocyclopentanecarboxylate (intermediate compound 178 in Table 5)

Add 1.7g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) into 80ml of anhydrous tetrahydrofuran while stirring in a helium atmosphere, and then add 18.2g of 1-(4-chlorobenzyl)-3 -Methyl-2-oxocyclopentanecarboxylate, the mixture was stirred at room temperature for 2 hours hour.

Next, while maintaining the temperature of the mixture at 20˜30° C., 11.1 g of iodoethane was added dropwise, which was then stirred at a temperature of 20˜30° C. for 1 hour, followed by stirring at 60° C. for 1 hour.

After the above reaction mixture was cooled, it was poured into a mixture of ice water and acetic acid and extracted with ethyl acetate to obtain an organic layer, which was washed with sodium bicarbonate, then with brine solution, and washed with anhydrous sodium sulfate The organic layer was dried and the solvent in the organic layer was distilled off under reduced pressure.

The resulting residue was purified by distillation under reduced pressure to obtain 15 g of the objective compound.

Example 10

Preparation of 4-(4-chlorobenzyl)-7-methyl-1-oxaspiro[2,4]heptane (intermediate compound 85 in Table 2)

Add 1.44g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) into 37ml of anhydrous dimethyl sulfoxide while stirring in a helium atmosphere, then add 13.2g of trimethylsulfoxonium iodide, The mixture was then stirred at room temperature for 30 minutes. Next, a solution formed from 12.2 g of 2-(4-chlorobenzyl)-5-methyl-1-cyclopentanone (compound 137 in Table 4) in 12 ml of anhydrous dimethylsulfoxide was dissolved within 10 minutes This was added to the mixture and the whole was stirred at room temperature for 4 hours.

The reaction solution thus prepared was poured into ice water, and the mixture was extracted with dichloromethane to obtain an organic layer, which was washed with brine solution and dried over anhydrous sodium sulfate, and finally the solvent in the organic layer was distilled off under reduced pressure. .

The residue thus obtained can be purified by silica gel column chromatography to obtain 6.67 g of the target compound thing.

In addition, three other isomers of the target compound were also isolated.

That is, 0.15 g of intermediate compound 86 in Table 2; 0.16 g of intermediate compound 87 and 0.16 g of intermediate compound 88.

Example 11

Preparation of 4-(4-chlorobenzyl)-7-ethyl-1-oxaspiro[2,4]heptane (intermediate compounds 93, 94, 95 and 96 in Table 2)

Dissolve 8.0 g of 2-(4-chlorobenzyl)-5-ethyl-1-methylenecyclopentane (compound 129 in Table 3) in 100 ml of chloroform, add 11.6 g of m-chloroperbenzoic acid, and dissolve in Stir at room temperature for 2 hours. Next, 11 g of calcium hydroxide was added to the mixture under ice-water cooling, and the mixture was stirred at room temperature for 30 minutes.

The solid matter was filtered off, and the chloroform layer of the filtrate was concentrated to obtain a colorless oil, which was purified by silica gel column chromatography to obtain 0.7 g of compound 93, 2.4 g of compound 94, 2.2 g of compound 95 and 2.6 g of compound 96.

Example 12

Preparation of C-2-(4-chlorobenzyl)-5-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)-γ-1-cyclopentanol (Table 1 compound 16)

Add 630mg of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) to 10ml of anhydrous dimethylformamide, then add 1.8g of 1H-1,2,4-triazole, then at room temperature The mixture was stirred until bubbling ceased.

Added by 3.1g 4-(4-chlorobenzyl)-7-methyl-1-oxyspiro[2,4]heptane (Table 2 Compound 85) was dissolved in 6.2 ml of anhydrous dimethylformamide, and the mixture was stirred at 80°C for 1 hour.

After it was cooled, the reaction solution was poured into ice water, and the mixture was extracted with dichloromethane to obtain an organic layer.

After washing with saline solution, the organic layer was dried over anhydrous sodium sulfate and the solvent in the organic layer was distilled off under reduced pressure.

The resulting residue was purified by silica gel column chromatography, and 2.83 g of the intended compound were obtained after recrystallization from a n-hexane/ethyl acetate mixture.

Example 13

Preparation of C-2(4-chlorobenzyl)-5-methyl-1-(1H-imidazol-1-ylmethyl)-γ-1-cyclopentanol (compound 17 of Table 1)

Add 670 mg of sodium hydride (prepared by washing 60% oily sodium hydride) to 10 ml of anhydrous dimethylformamide, add 1.9 g of 1H-imidazole, and stir the mixture at room temperature until bubbling ceases.

Next, add the mixture formed by 3.3g 4-(4-chlorobenzyl)-7-methyl-1-oxospiro[2,4]heptane (Table 2 compound 85) and 6.6ml anhydrous dimethylformamide solution, and the mixture was stirred at 80°C for 1 hour.

After the reaction solution was cooled, it was poured into ice water and extracted with dichloromethane to obtain an organic layer.

The organic layer was washed with saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.

The obtained residue was purified by silica gel column chromatography from n-hexane/ethyl acetate After recrystallization, 3.16 g of the target compound were obtained.

[II] Examples of preparation of agricultural and horticultural fungicidal compositions.

Example 14: Dust (powder) agent

3 parts by weight of the azole derivative (compound 3) of the present invention, 40 parts by weight of pottery clay and 57 parts by weight of talc were mixed together and ground to prepare a dusty agricultural and horticultural fungicidal composition.

A method of making a spread of the composition.

Example 15: Wettable powder

Mix 50 parts by weight of the azole derivatives (compound 1) of the present invention, 5 parts by weight of lignin sulfonate, 3 parts by weight of alkylsulfonate and 42 parts by weight of diatomaceous earth, and grind them to produce Wet powder.

The composition thus obtained is used as a wettable powder after dilution with water.

Example 16: Granules

Mix 5 parts by weight of the azole derivatives of the present invention (compound 16), 43 parts by weight of bentonite, 45 parts by weight of pottery clay and 7 parts by weight of lignosulfonate, then add water, knead them together, and press After being processed into granules by a granulator, the granulated composition is obtained by drying.

Example 17: Emulsifiable Concentrates

20 parts by weight of the azole derivatives of the present invention (compound 13) and 10 parts by weight of polyoxyethylene Alkenyl aryl ether, 3 parts by weight of polyoxyethylene sorbitan monolaurate and 67 parts by weight of xylene were uniformly mixed to prepare an emulsifiable concentrate-like composition.

[III] Examples of treatment of plant diseases using the agricultural and horticultural fungicidal composition of the present invention.

Example 18

Control of Erysiphe graminis f.sp.tritici on wheat｜Efficacy test

The suspension of the wettable powder (diluted to predetermined concentration with water) that every pot implements 5ml example 15 to make is applied on the two-leaf stage wheat seedling (kind. seedlings) These seedlings were grown in unglazed pots with a diameter of 10 cm. After the dilution was air-dried, the sporozoite suspension of Erysiphe grarainis f.sp.tritici collected from the infected wheat leaves was sprayed on the seedlings in the pots, and these pots were placed at 20-24°C and high humidity for 24 hours. hours, and then put it in the greenhouse. After 9 to 11 days, the disease degree (disease degree) of the seedlings is detected according to the following detection standards, and the control value of the fungicidal composition is calculated according to the following formula.

(measurement standard)

Disease degree Disease scope

0 no harm

0.5 The disease spot area rate is less than 10%

1 The area rate of diseased spots is not less than 10%,

less than 20%

2 The area rate of diseased spots is not higher than 20%,

less than 40%

3 The area rate of diseased spots is not less than 40%,

less than 60%

4 The area rate of diseased spots is not less than 60%,

less than 80%

5 The area rate of diseased spots is not less than 80%,

Control value = (1- (disease degree in treatment area)/(disease degree in control area)) × 100 (%)

The test results are shown in Table 6.

Table 6

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

1 125 100

2 125 100

3 125 95

4 125 100

5 125 100

6 125 100

7 125 95

8 125 95

9 125 100

10 125 100

11 125 100

12 125 90

13 125 100

14 125 100

15 125 95

16 125 100

17 125 95

18 125 100

19 125 100

Table 6 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

20 125 50

21 125 100

22 125 100

23 125 100

24 125 100

25 125 100

26 125 100

27 125 100

28 125 100

29 125 100

30 125 100

31 125 100

32 125 100

33 125 100

34 125 100

35 125 100

36 125 100

37 125 100

38 125 100

Table 6 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

39 125 100

40 125 100

41 125 100

42 125 100

43 125 95

44 125 100

45 125 100

46 125 95

47 125 100

48 125 100

49 125 100

50 125 100

51 125 100

52 125 100

53 125 75

54 125 100

55 125 100

56 125 100

57 125 100

Table 6 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

58 125 100

59 125 100

60 125 100

61 125 100

62 125 100

63 125 100

64 125 100

65 125 100

66 125 100

67 125 100

68 125 100

69 125 100

70 125 100

71 125 100

Table 6 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

72 125 100

73 125 100

74 125 100

75 125 100

76 125 100

Commodity Triadim- 125 100

ephon ^*

Control (untreated) 0

Note ^* ): Commercial Triadimephon has a compound represented by the following formula as an active ingredient.

Example 19

Cucumber Sphaerotheca fuliginea control effect test

Take 3 unglazed flowerpots with a diameter of 10cm, each plant a two-leaf stage cucumber (variety: SAGAMI HAMPAKU), apply 5ml of emulsifiable concentrate as diluted in Example 15 (diluted to a predetermined concentration with water) for each pot . After the sprayed leaves are dried in the air, the spores are brushed off the sick cucumber leaves with a brush to inoculate the cucumbers, so that the cucumbers in the greenhouse are susceptible to the disease.

9 to 11 days after the inoculation, the disease degree of the cucumber plants was measured according to the following measurement standards. The control value of the fungicidal composition is calculated with the following formula:

(measurement standard)

Disease degree Disease scope

0 no harm

0.5 The disease spot area rate is less than 10%

1 The area rate of diseased spots is not less than 10%,

less than 20%

2 The area rate of diseased spots is not higher than 20%,

less than 40%

3 The area rate of diseased spots is not less than 40%,

less than 60%

4 The area rate of diseased spots is not less than 60%,

less than 80%

5 The area rate of diseased spots is not less than 80%,

Control value = (1- (disease degree in treatment area)/(disease degree in control area)) × 100 (%)

The test results are shown in Table 7.

Table 7

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

1 125 100

2 125 100

3 125 100

4 125 100

5 125 100

6 125 100

7 125 100

8 125 100

9 125 100

10 125 100

11 125 100

12 125 100

13 125 100

14 125 100

15 125 100

16 125 100

17 125 100

Commodity Triadim- 125 100

ephon ^*

Control (untreated) 0

Example 20

Experiment on Control Effect of Wheat Puccina recondita

Get 3 unglazed flowerpots with a diameter of 10cm, plant 2-leaf stage wheat seedlings (variety: NOR IN No. 64, 16 plants per pot), and spray 5ml of the wettable powder suspension prepared in Example 15 for each pot (with diluted with water to a predetermined concentration).

After the dilute suspension was air-dried, the suspension of summer spores of Puccina recondita (collected from shrunken wheat leaves) was sprayed on the wheat seedlings in the pots, and the pots were kept at 20-23°C under high humidity. After 24 hours, put the pots in the greenhouse. After 3-10 days of inoculation, measure the range of disease of 10 seedlings according to the following measurement standards, then calculate the control value of the fungicidal composition according to the average degree of disease of each leaf with the following formula:

(measurement standard)

Disease degree Disease scope

0 no harm

0.5 The disease spot area rate is less than 10%

1 The disease spot area rate is higher than 10%,

less than 20%

2 The area rate of diseased spots is not less than 20%,

less than 40%

3 The area rate of diseased spots is not less than 40%,

less than 60%

4 The area rate of diseased spots is not less than 60%,

less than 80%

5 The area rate of diseased spots is not less than 80%,

Control value = (1- (disease degree in treatment area)/(disease degree in control area)) × 100 (%)

The test results are shown in Table 8

Table 8

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

1 125 100

2 125 95

3 125 100

4 125 95

5 125 100

6 125 100

7 125 100

8 125 95

9 125 100

10 125 100

11 125 100

12 125 95

13 125 100

14 125 100

15 125 100

16 125 100

17 125 95

18 125 100

19 125 100

Table 8 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

21 125 100

22 125 100

23 125 100

24 125 70

25 125 100

26 125 95

27 125 100

28 125 100

29 125 100

30 125 100

31 125 100

32 125 100

33 125 100

34 125 100

35 125 100

36 125 100

37 125 100

38 125 100

39 125 100

40 125 100

Table 8 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

41 125 100

42 125 100

43 125 100

44 125 100

45 125 100

46 125 100

47 125 100

48 125 100

49 125 90

50 125 100

51 125 100

52 125 100

53 125 95

54 125 100

55 125 100

56 125 100

57 125 100

58 125 90

59 125 100

60 125 90

Table 8 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

61 125 90

62 125 100

63 125 100

64 125 100

65 125 100

66 125 100

67 125 100

68 125 100

69 125 100

70 125 100

71 125 100

72 125 100

73 125 100

74 125 100

75 125 90

76 125 90

Commodity Triadim- 125 95

ephon ^*

Control (untreated) 0

Example 21

Experiment on Controlling Effect of Botrytis spp.

Be that the unglazed flowerpot of 10cm in diameter is planted bean, when its first true leaf stage, spray the suspension (diluted to predetermined concentration with water) of the wettable powder that example 15 makes, every pot 5ml.

After the leaves were air-dried, 4 mm diameter agar discs containing Botrytis anophora (fungus pre-incubated in sugared agar medium containing potato broth for 3 days at 20°C) were adhered directly to the middle of the bean leaves , Bean plants are kept at 20-22°C under high humidity conditions. On the 3rd day after the inoculation, the area of disease spots in the treatment area was compared with the area of disease spots in the control area according to the following measurement standards, to measure the degree of disease, and then calculate the control value of the fungicide composition according to the following formula:

(measurement standard)

Disease degree Disease scope

0 not violated

0.5 Only on agar-containing inoculated fungi

The lower and surrounding parts are affected

1 The area rate of diseased spots is less than 20%,

2 The area rate of diseased spots is not less than 20%,

less than 40%

3 The area rate of diseased spots is not less than 40%,

less than 60%

4 The area rate of diseased spots is not less than 60%,

less than 80%

5 The area rate of diseased spots is not less than 80%,

Control value = (1- (disease degree in treatment area)/(disease degree in control area)) × 100 (%)

The test results are shown in Table 9

Table 9

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

1 500 100

2 500 100

3 500 90

4 500 80

5 500 100

6 500 100

7 500 70

8 500 70

9 500 100

10 500 100

11 500 85

12 500 80

13 500 100

14 500 100

15 500 90

16 500 100

17 500 80

18 500 100

19 500 100

Table 9 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

21 500 100

22 500 65

23 500 100

24 500 90

25 500 85

27 500 100

28 500 90

29 500 100

30 500 100

31 500 60

32 500 100

33 500 85

37 500 100

38 500 100

39 500 75

41 500 100

42 500 100

44 500 100

45 500 100

Table 9 (continued)

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

46 500 70

47 500 60

48 500 100

49 500 100

50 500 100

54 500 100

55 500 100

56 500 95

57 500 70

58 500 70

59 500 80

60 500 80

61 500 85

62 500 100

63 500 100

64 500 80

65 500 100

66 500 60

67 500 100

Table 9 (continued)

Test compound Spray concentration limit value

(No. in Table 1) (ppm) (%)

68 500 60

69 500 100

70 500 65

71 500 100

72 500 100

73 500 80

74 500 60

75 500 85

76 500 60

Commodity Rovral ^＊ 500 100

Note ^＊ ): Commodity Rovral

A compound represented by the following formula is contained as an active ingredient.

Example 22

Experiment on the control effect of Helicosporum miyabei in rice

Get an unglazed flowerpot with a diameter of 10cm, sow 16 rice (variety: SASANIS-HIK I) seeds in each pot, and when the rice seedlings grow to the 4-5 leaf stage, the diluted emulsifiable concentrate in Example 15 ( Diluted with water to a predetermined concentration) and sprayed on the seedlings.

After the treated leaves were dried in the air, each pot was sprayed with 5ml of the suspension of the spores of the spores of the spores of the spores of the spores of the spores of the spores of the spores of the spores (the spores of the spores of the spores of the spores of the spores were pre-cultured). Fifteen fungal spores were visible in the suspension under a microscope at 150X.

After the inoculation, the treated flower pots were placed in an inoculation room with saturated humidity at 25° C. After 2 days, the flower pots were moved into the greenhouse to infect the rice. On the 5th day after inoculation, count the number of diseased spots on 10 leaves per pot, and calculate the control value of the fungicidal composition according to the following formula.

Control value = (1- (number of diseased spots in the treatment area)/(number of diseased spots in the control area (untreated))) × 100 (%)

The test results are shown in Table 10.

Table 10

Test compound Spray concentration Control value

(No. in Table 1) (ppm) (%)

1 125 100

2 125 100

3 125 100

4 125 100

5 125 100

6 125 100

7 125 100

8 125 100

9 125 100

10 125 100

11 125 100

12 125 100

13 125 100

14 125 95

15 125 90

16 125 100

17 125 100

Commodity Rovral 125 85

Control (untreated) 0

Example 23

Antibacterial test of several pathogenic fungi

This example shows the antifungal properties of azole derivatives according to the present invention to various plant pathogenic fungi

experiment method:

The compound of the present invention was dissolved in dimethyl sulfoxide to a predetermined concentration, and 0.6 ml of the prepared solution was thoroughly mixed with 60° C. PAS culture medium in a 100 ml capacity Erlenmeyer flask. The mixture was poured into a glass petri dish and solidified to become a flat culture medium containing the compound of the present invention.

Separately, the test fungus (preliminarily cultured in a flat culture medium) was made into small pieces using a 4 mm diameter punch, and the culture medium small pieces containing the test fungus were inoculated on the flat culture medium containing the compound of the present invention. After inoculation, the prepared medium containing the compound and the fungus is incubated at a suitable temperature for 1-3 days to allow the fungus to grow. Fungal growth was measured by the method for measuring the diameter of fungal colonies. The growth of fungi in the culture medium prepared in this way is compared with that of the untreated area (the culture medium does not contain compounds), and the inhibition rate of fungal mycelium growth can be obtained according to the following formula:

R = (dc-dt) 100 (%)

In the formula, R is the inhibition rate of mycelium growth, dc is the diameter of the fungal colony on the flat medium without the compound; dt is the diameter of the fungal colony on the flat medium containing the compound.

The stabilization results are classified into 5 grades according to the following criteria, and are shown in Table 11. Mycelium Growth Inhibition Rate:

5: The growth arrest rate is not less than 90 to 100%

4: The growth arrest rate is not less than 70%, less than 90%

3: The growth arrest rate is not less than 40%, less than 70%

2: Growth inhibition rate is not less than 20%, less than 40%

1: The growth arrest rate is less than 20%

The abbreviations of each fungus in Table 11 are as follows:

P.o. Rice Pyricularia Oryzae

C.m. Oryzae Miyabe

G.f. Bakanae oryzae

H.s. Helminthospora oryzae

R.s. Rhizoctonia solani

Bo.c. Botrytis analis

S.s. Sclerotinia sclerotirum

F.n. Watermelon Fusarium Oxysporum f.niveum

F.c. Cucumber Fusarium Oxysporum f.cucumerinum

F.r. Japanese Radish Fusarium Oxysporum f.raphani

C.l. Cucurbitaceae spinosa

C.b. Beet Cercospora brassicae

S.c. Peach Sclerotinia cinerea

V.m. apple tree rot

A.m. Apple Alternaria

A.k. Alternaria peach tree

G.c.

[IV] Examples of agricultural or horticultural plant growth regulators using the azole derivatives of the present invention as active ingredients

Example 24

wettable powder form

50 parts (weight) of azole derivatives of the present invention (compound 3 in Table 1), 5 parts (weight) of lignosulfonate, 3 parts (weight) of alkylsulfonate and 42 parts (weight) of silicon Alginate is mixed and ground to prepare a wettable powder composition, which is used after being diluted with water.

Example 25

emulsifiable concentrated form

Mix 25 parts (weight) of azole derivatives of the present invention (compound 20 in Table 1), 65 parts (weight) xylene and 10 parts (weight) polyoxyethylene alkaryl ether to make emulsifiable Concentrate composition for use after dilution with water.

Example 26

powder form

Mix 8 parts (weight) of azole derivatives of the present invention (compound 11 in Table 1), 40 parts of bentonite, 45 parts (weight) of clay and 7 parts (weight) of lignosulfonate, and mix the whole The mixture is kneaded together and processed into granules by an extrusion granulator, and the granules are dried to form a powder composition.

Example 27

Inhibition of Plant Height in Rice

In each glass dish with a diameter of 8.5 cm, 10 ml of a solution containing a different compound of the present invention at a concentration of 10 ppm was added. Sow 10 rice seeds per tray (Pin Species: SASANISHIKI). The trays were placed in a room at 27°C for 7 days to germinate, and then the height of the seedlings was measured. The data are shown in Table 12.

It can be seen from Table 12 that each azole derivative of the present invention exhibits growth inhibitory effect without any phytotoxicity.

Table 12

Compound No. High Inhibition Rate Phytotoxicity

(Number in Table 1) (%)

1 84.2 None

2 63.8 ″

3 71.8 ″

4 70.0 ″

5 70.0 ″

6 74.6 ″

7 85.9 ″

8 72.3 ″

9 75.7 ″

10 79.7 ″

11 76.8 ″

12 67.2 ″

13 87.0 ″

14 76.8 ″

15 77.4 ″

16 84.2 ″

17 76.8 ″

Claims (3)

1, preparation is by formula I

(Ⅰ)

(R in the formula ¹And R ²Each representative-(C ₁-C ₅) alkyl or hydrogen atom; X represents a hydrogen atom, (C ₁-C ₅) alkyl or phenyl; N represents the integer of 0-2; A represents a nitrogen-atoms or CH, but must work as R ²R during for hydrogen atom ¹Be not hydrogen atom) method of azole derivative of representative, this method comprises formula II

(Ⅱ)

(R in the formula ¹, R ², as above defined of X and n) epoxyethane derivative and the formula IV of representative

(Ⅳ)

(M represents hydrogen atom or alkali metal atom in the formula; A represents nitrogen-atoms or CH) representative 1,2,4-triazole or imidazoles react.

2, method according to claim 1, wherein the preparation method of the epoxyethane derivative of formula II representative comprises:

A) (ⅰ) 2-oxo-cyclopentane alkyl formate and substituted benzyl halogen reaction is with the 1-(substituted benzyl that obtains)-2-oxo-cyclopentane alkyl formate and (C ₁-C ₅) the alkylogen reaction; (ⅱ) with 3-(C ₁-C ₅Alkyl)-2-oxo-cyclopentane alkyl formate and the reaction of substituted benzyl halogen; Or (ⅲ) with the 1-(substituted benzyl)-3-(C ₁-C ₅Alkyl)-2-oxo-cyclopentane formic acid and (C ₁-C ₅) the alkylogen reaction, the cyclopentane-carboxylic acid ester derivative that obtains thus is with formula (V)

（Ⅴ）

(R in the formula ¹And R ²Each representative-(C ₁-C ₅) alkyl or hydrogen atom; R ²Representative-(C ₁-C ₅) alkyl; X represents a hydrogen atom, (C ₁-C ₅) alkyl or phenyl; N represents the integer of 0-2; But must work as R ²R during for hydrogen atom ¹Be not hydrogen atom) representative,

B) the cyclopentane-carboxylic acid ester derivative that obtains is hydrolyzed decarboxylation obtains with formula IV

（Ⅳ）

(R in the formula ¹, R ², as above defined of X and n) cyclopentanone derivatives of representative,

(c) cyclopentanone derivatives with above-mentioned gained carries out the oxyethane reaction with sulphur inner salt or oxygen sulphur inner salt, or carries out the oxyethane reaction with the feasible methylene radical cyclopentane derivatives from cyclopentanone derivatives of the uncommon reaction of prestige ladder, and the methylene radical pentamethylene is with formula III

（Ⅲ）

(R in the formula ¹, R ², X and n and above-mentioned person define with) representative, thus cyclopentane derivatives is transformed into epoxyethane derivative, and represents with formula II

（Ⅱ）

(R in the formula ¹, R ², X and n and above-mentioned person define with).

3, method according to claim 1, this method may further comprise the steps:

A) (ⅰ) is with 2-oxo-cyclopentane alkyl formate and the reaction of substituted benzyl halogen, again with the 1-(substituted benzyl that obtains)-2-oxo-cyclopentane alkyl formate and (C ₁-C ₅) the alkylogen reaction; (ⅱ) with 3-(C ₁-C ₅Alkyl)-2-oxo-cyclopentane alkyl formate and the reaction of substituted benzyl halogen; Or (ⅲ) with the 1-(substituted benzyl)-3-(C ₁-C ₅Alkyl)-2-oxo-cyclopentane formic acid and (C ₁-C ₅) the alkylogen reaction, obtain with formula (V)

（Ⅴ）

(R in the formula ¹And R ²Representative-(C respectively ₁-C ₅) alkyl or hydrogen atom; R representative-(C ₁-C ₅) alkyl; X represents a hydrogen atom, (C ₁-C ₅) alkyl or phenyl; N represents the integer of 0-2; But must work as R ²R during for hydrogen atom ¹Be not hydrogen atom) representative the cyclopentane-carboxylic acid ester derivative,

B) resulting cyclopentane-carboxylic acid ester derivative is hydrolyzed decarboxylation obtains with formula IV

（Ⅳ）

(R in the formula ¹, R ², X and n define as mentioned above) cyclopentanone derivatives of representative,

(c) with sulphur inner salt or oxygen sulphur inner salt the cyclopentanone derivatives of gained is carried out the oxyethane reaction, the methylene radical cyclopentane derivatives that maybe will derive from cyclopentanone derivatives carry out oxyethaneization with the uncommon reaction of prestige ladder, and the methylene radical cyclopentane derivatives is with formula III

（Ⅲ）

(R in the formula ¹, R ², X and n such as above-mentioned definition) represent it, be about to cyclopentanone derivatives thus and be transformed into formula II

（Ⅱ）

(R in the formula ¹, R ², X and n such as above-mentioned definition) epoxyethane derivative of representative, then

D) with the epoxyethane derivative of gained and with formula VI

（Ⅵ）

(representative one hydrogen atom or the alkali metal atom of M in the formula; A represents a nitrogen-atoms or CH) representative 1,2, the reaction of 4-triazole or imidazoles.

Images