KR900003269B1 - A zole derivatives,process for production thereof and a gricultural and horticultural chemical composition - Google Patents

Abstract

The method for preparing azole derivatives (I) R1 and R2 =(C1-C5) alkyl or hydrogen; X=halogen atom, (C1-C5) alkyl or phenyl group; n=0-2; A=nitrogen atom or (H) having plant blight inhibition and growth control comprises: (a) adding 44.8g of methyl 1-(4- chlorobenzyl)-3,3-dimethyl-2-oxycyclopentane carboxylate to 120ml of bromic acid and agitating at 100≰C for 12 hrs.; (b) cooling the reaction mixtures and extracting with ethylacetate to obtain organic layer; (c) washing organic layer with sodium bicarbonate solution and drying.

Description

Azole derivatives, their preparation and agricultural and horticultural chemical compositions containing them

1 to 76 are infrared absorption spectral diagrams of the azole derivatives according to the present invention obtained in Table 1.

The present invention relates to an azole derivative having a plant disease prevention action and a plant growth regulating effect, a method for producing the azole derivative, and an agricultural and horticultural composition containing the azole derivative as an active ingredient.

In more detail, 1) The present invention relates to an azole derivative represented by the following general formula (I).

(Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer of 0 to 2; and A is nitrogen Represents an atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.)

2) The present invention relates to a reaction of (a) (iii) alkyl ester of 2-oxocyclopentanecarboxylic acid with substituted benzyl halide and thus obtained alkyl of 1- (substituted benzyl) -2-oxocyclopentanecarboxylic acid. Reacting the 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 (C ₁ -C ₅ ) alkyl halide and represented by the following general formula (V) To obtain an ester derivative of cyclopentane carboxylic acid,

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group or n Represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom; (b) hydrolysis and decarboxylation of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by the following general formula (IV),

Wherein R ¹ , R ² , X and n are the same as defined above, respectively; (c) the cyclopentanone derivative thus obtained is subjected to an oxirane reaction using sulfonium lide or oxosulfonium lide or the cyclopentanone derivative thus obtained is obtained by Wittig reaction. The methylene cyclopentane derivative represented by the following general formula (III) is epoxidized to convert the cyclopentanone derivative into an oxirane derivative represented by the following general formula (II),

(Wherein R ¹ , R ² , X and n are the same as defined above); (d) Then, the oxirane derivative thus obtained is reacted with 1,2,4-triazole or imidazole of the following general formula (VI) to obtain an azole derivative represented by the following general formula (I). It relates to a method for producing an azole derivative represented by the general formula (I) consisting of.

(Wherein M represents a hydrogen atom or an alkali metal atom, and A represents a nitrogen atom or -CH =).

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer from 0 to 2; or A is nitrogen Represents an atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.)

3) The present invention relates to agricultural and horticultural compositions containing an effective amount of an azole derivative represented by the general formula (I) and having fungicidal activity and plant growth control activity.

Crop damage due to various plant diseases is serious, and environmental pollution problems caused by chemicals for controlling these plant diseases are occurring.

Thus, agricultural and horticultural chemicals having a control effect on plant diseases, low toxicity in humans, livestock, birds and fishes, and low phytotoxicity in useful crops, ie high handling stability, There is a need for the emergence of agricultural and horticultural chemicals that have a low impact on the environment and are superior to a wide range of plant diseases.

To meet this need, the following agricultural and horticultural fungicides have been proposed so far.

(1) Triazole or imidazole compounds represented by the following general formula, acid addition salts and metal complexes thereof (see Japanese Patent Application Publication No. 57-114577 (1982) corresponding to US Pat. Nos. 4,507,140 and 52,424)). To do).

Wherein R ¹ is —CH═CH—X, —C≡CX or —CH ₂ —CH ₂ —X, wherein X is a hydrogen atom, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, a cycloalkyl group, which may be substituted An aryl group, an optionally substituted aralkyl group, an optionally substituted aryloxyalkyl group or an optionally substituted heterocyclic group, and R ² is an alkyl group, a cycloalkyl group or an optionally substituted aryl group; Z is a chlorine atom, cyano group or -OR ³ , wherein R ³ is a hydrogen atom, an acetyl group, an alkyl group, an alkenyl group or an aralkyl group; And Y is nitrogen atom or CH.

(2) Triazoles or imidazole compounds represented by the following general formula, acid addition salts, metal complexes and functional derivatives thereof (see Japanese Patent Publication No. 57-126479 (1982) corresponding to European Patent No. 52425).

Wherein R is a crosslinking group-(CH ₂ ) _n -where n is 0,1 or 2, and a crosslinking group -CH = CH-, -O-, -S-, -NH- or -C (= O )-; X is nitrogen atom or CH; Y and Z are the same or different halogen atom, alkyl group, alkoxy group, haloalkoxy group, haloalkyl group, nitro group, phenyl group or phenoxy group; M and p represent 0, 1, 2 or 3, respectively.

(3) Derivatives of 1-hydroxyethylazole represented by the following general formula, acid addition salts and metal complexes thereof (Japanese Patent Publication No. 57-16868 (1982 corresponding to US Patent No. 4532341 and European Patent No. 40345) See)

In the formula, R is an alkyl group, a cycloalkyl group which may be substituted, or a phenyl group which may be substituted; X is nitrogen atom or CH; Y is -OCH _2- , -CH ₂ -CH _2- , or -CH = CH-; Z is a halogen atom, an alkyl group, a cycloalkyl group, an alkoxy group, an alkylthio group, a halogenoalkyl group, a halogenoalkoxy group, a halogenoalkylthio group, a substituted phenyl group, a substituted phenoxy group or a substituted phenyl An alkyl group or a phenylalkoxy group which may be substituted; And m represents 0, 1, 2 or 3.

(4) Cycloaliphatic alcohol compounds represented by the following general formula (refer to Japanese Patent Publication No. 58-189171 (1983) corresponding to US Patent No. 4503062 and European Patent No. 94146)

Wherein R ⁶ is an unsubstituted phenyl group or halogen atom, amino group, nitro group, cyano group, phenyl group, halogenophenyl group, (C ₁ -C ₁₀ ) alkyl group, halogeno (C ₁ -C ₁₀ ) alkyl group, (C ₁ -C ₁₀₎ alkoxy group, a halogeno (C ₁ -C ₁₀₎ alkoxy, (C ₁ -C ₁₀₎ alkylthio, (C ₁ -C ₁₀₎ alkylenedioxy group, (C ₁ -C ₁₀₎ A phenyl group substituted by 1 to 5 groups selected from the group consisting of an alkylamino group and a di (C ₁ -C ₁₀ ) alkylamino group; X is nitrogen atom or methyl group; Ring A represents a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, an indan ring, a tetrahydronaphthalene ring or a benzocyclopeptane ring, each of which is unsubstituted or in the benzene ring described above. Substituted with a substituent.

(5) Triazole compounds or imidazole compounds represented by the following general formula, stereoisomers, acid addition salts and metal complexes thereof (see Japanese Patent Publication No. 60-215674 (1985) corresponding to US Patent No. 153797). To do)

Wherein W is CH or a nitrogen atom; Q represents a substituted or unsubstituted aryl group, especially a substituted or unsubstituted phenyl group, a substituted or unsubstituted aralkyl 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 from each other and each hydrogen atom, hydroxy group, alkyl group, cycloalkyl group, substituted or unsubstituted An aralkyl group, a substituted or unsubstituted phenyl group, or a ^{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 the adjacent ring carbon atom each represent a carbonyl group (C = 0); R ⁹ and R ¹⁰ may be the same or different from each other and each represent a hydrogen atom, an alkyl group, a cycloalkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted phenyl group; And n is 0 or 1.

Some of the inventors have conducted research to provide agricultural and horticultural fungicides with high handling stability, low environmental impact and excellent control against a wide range of plant diseases. An azole derivative represented by the formula was found (see Japanese Patent Publication No. 62-149667 (1987) corresponding to US Pat. No. 2180236A).

Wherein X is a halogen atom, an alkyl group, a haloalkyl group, a phenyl group, a cyano group or a nitro group, respectively; n is an integer of 0 to 5; In addition, A represents a nitrogen atom or CH, provided that when n is 1 to 5, X may be the same or different from each other.

The inventors have synthesized many azole derivatives and tested their usefulness in order to obtain agricultural and horticultural fungicides with low toxicity in humans and livestock, high handling stability, and excellent control against a wide range of plant diseases. As a result, he discovered that the azole derivatives represented by the following general formula (I) not only have the above-mentioned special effects but also can be effectively used as plant growth regulators. This invention was completed.

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

That is, an object of the present invention is an azole derivative having utility as an active ingredient of agricultural and horticultural compositions having plant disease control activity and plant growth control activity, a method for preparing the azole derivative and excellent control against a wide range of plant diseases as an active ingredient. The present invention provides an agricultural and horticultural composition containing an azole derivative which exhibits an effect and exhibits plant growth regulating effects, and which has low toxicity and excellent handling stability.

A first feature of the present invention is to provide an azole derivative represented by the following general formula (I).

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

A second feature of the invention is the reaction of (a) (iii) with an alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide and of the 1- (substituted benzyl) -2-oxocyclopentanecarboxylic acid thus obtained Reacting the 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 (C ₁ -C ₅ ) alkyl halide and represented by the following general formula (V) To obtain an ester derivative of cyclopentane carboxylic acid,

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group or n Represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom; (b) hydrolysis and decarboxylation reaction of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by the following general formula (IV),

Wherein R ¹ , R ² , X and n are the same as defined above, respectively; (c) the cyclopentanone derivative thus obtained is subjected to an oxirane reaction using sulfonium lide or oxosulfonium lide or the cyclopentanone derivative thus obtained is obtained by Wittig reaction. The methylene cyclopentane derivative represented by the following general formula (III) is epoxidized to convert the cyclopentanone derivative into an oxirane derivative represented by the following general formula (II),

(Wherein R ¹ , R ² , X and n are the same as defined above); (d) Then, the oxirane derivative thus obtained is reacted with 1,2,4-triazole or imidazole of the following general formula (VI) to prepare an azole derivative represented by the following general formula (I). To provide.

(Wherein M represents a hydrogen atom or an alkali metal atom, and A represents a nitrogen atom or -CH =).

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer from 0 to 2; or A is nitrogen Represents an atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.)

A third aspect of the present invention is to provide an agricultural and horticultural composition containing an azole derivative represented by the following general formula (I) as an active ingredient and having fungicidal activity and plant growth control activity.

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

A fourth feature of the present invention is to provide an oxirane derivative for preparing azole derivatives of general formula (I) represented by the following general formula (II).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; N represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.

A fifth feature of the present invention is to provide a methylenecyclopentane derivative for preparing an azole derivative of general formula (I) represented by the following general formula (III).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; N represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.

A sixth feature of the present invention is to provide a cyclopentanone derivative for preparing azole derivatives of general formula (I) represented by the following general formula (IV).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; N represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.

A seventh feature of the present invention is to provide an ester derivative of cyclopentanecarboxylic acid for preparing the azole derivative of general formula (I) represented by the following general formula (V).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; N represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.

1 to 76 are attached to the infrared absorption spectrum of the azole derivative according to the present invention shown in Table 1. That is, FIG. 1 shows the infrared absorption spectrum of compound number 1 of Table 1, FIG. 2 shows the infrared absorption spectrum of compound number 2 of Table 1, and FIG. 3 shows the infrared absorption spectrum of compound number 3 of Table 1 Spectra are shown, and FIGS. 4 to 76 show infrared absorption spectra of the respective compounds of Compound Nos. 4 to 76 in Table 1, respectively.

The core of this invention is the novel azole derivative represented by the following general formula (I); The manufacturing method of the azole derivative represented by following General formula (I); Individual compounds used as intermediates, that is, oxirane derivatives represented by formula (II), methylenecyclopentane derivatives represented by formula (III), cyclopentanone derivatives represented by formula (IV), and general formula (V Ester derivatives of cyclopentane carboxylic acid represented by; It can be said to be in agricultural and horticultural compositions containing azole derivatives of general formula (I) as active ingredients and having fungicidal activity and plant growth regulating activity.

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

Each of the azole derivatives represented by Formula (I) and the aforementioned intermediates for preparing azole derivatives is listed in Tables 1 to 5 below. All of these intermediates are each new compounds.

TABLE 1a azole derivatives

TABLE 1b

TABLE 1c

TABLE 1d

TABLE 1e

TABLE 1f

Table 1g

TABLE 2a Oxylan Derivatives

TABLE 2b

TABLE 2c

TABLE 3 (Methylenecyclopentane Derivative)

TABLE 4a (cyclopentanone derivatives)

TABLE 4b

TABLE 4c

Table 5a (Ester Derivatives of Cyclopentanecarboxylic Acid)

TABLE 5b

NMR spectra of the compounds in Tables 1 to 5 were measured using TMS as an internal standard. The nomenclature is as follows:

s: single line, d: double line, t: triplet, q: quartet, m: multiplet, b: broad line, j: coupling constant (unit, Hz)

Infrared absorption spectra of each of the azole derivatives shown in Table 1 are shown in FIGS. 1 to 76, respectively.

From the viewpoint of plant disease control activity and plant growth regulation activity, R ¹ represents a hydrogen atom or (C ₁ -C ₄ ) alkyl in the azole derivative represented by the general formula (I); R ² is a hydrogen atom or (C ₁ -C ₃ ) alkyl (R ¹ and R ² do not represent a hydrogen atom at the same time); A halogen atom where X is substituted at the 4 position of the benzene ring; Preferred are azole derivatives wherein n is 1 and A represents a nitrogen atom or CH, and furthermore, R ¹ and R ² each represent a hydrogen atom or a (C ₁ -C ₅ ) alkyl group (R ¹ and R ² simultaneously represent a hydrogen atom). Not); A halogen atom where X is substituted at the 4 position of the benzene ring; Particular preference is given to azole derivatives where n represents 1 or A represents a nitrogen atom.

Among the compounds exemplified in Table 1, the azole derivatives of Compound Nos. 1 to 3, 5, 9 to 11, 16, 18, 29 to 32, 37, 38, 42 to 45, 50, 59, 62, 63, 65 and 69 desirable.

The azole derivative according to the present invention is produced by the following preparation method.

The target azole derivative represented by the general formula (I) is reacted with an oxirane derivative represented by the general formula (II) in the presence of a diluent with 1,2,4-triazole or imidazole represented by the following general formula (IV). Can be prepared.

Wherein M represents a hydrogen atom or an alkali metal atom and A represents a nitrogen atom or CH. The oxirane derivative represented by the general formula (II) used as a starting material can be prepared by the following method.

Namely, the sulfoniumlides of cyclopentanone represented by the general formula (IV) according to the methods described in Org. Syn. 49, 78 (1968) and J. Amer. Chem. Soc., (1965) 1353 in the presence of a diluent Or an oxirane derivative represented by the general formula (II) by reacting with oxosulfonium illide, for example, dimethyloxosulfonium methylide or dimethylsulfonium methylide (this method is called A-producing method).

In addition, as another manufacturing method (referred to as B-producing method), a cyclopentanone represented by the general formula (IV) is reacted by Wittich to prepare a methylenecyclopentane represented by the general formula (III), and [Org.Syn.40, 66 (1966) and J. Org. Chem. 28, 1128 (1963)] [Org. Syn. Coll] for preparing an oxirane derivative represented by formula (II) by epoxidation of the compound thus prepared. Vol., 4, 552 (1963), 49, 62 (1962)].

The reaction schemes according to the aforementioned A- and B-methods are shown below.

Method for preparing oxirane derivative represented by general formula (II):

In addition, the cyclopentanone derivative represented by the general formula (IV) may be prepared by the following method: that is, when R ¹ and R ² in the general formula (IV) are both the same (C ₁ -C ₅ ) alkyl group In the following, the cyclopentanone compound represented by the following general formula (VIII) is dealkylated to be converted to an ester derivative of cyclopentanecarboxylic acid represented by the following general formula (V), and the ester represented by this general formula (V) When the derivative is partially decarboxylated and decarboxylated, and one of R ¹ and R ² is a (C ₁ -C ₅ ) alkyl group and the other is a hydrogen atom, alkylcyclopentane represented by the following general formula (i) The benzyl group required in the carboxylate derivative is introduced to obtain an ester derivative of cyclopentanecarboxylic acid represented by the following general formula (V), and the ester derivative thus obtained is subjected to hydrolysis and decarburization. It reacted clothing Shihwa. By doing in this way, the cyclopentanone derivative represented by general formula (IV) can be obtained.

In addition, when R ¹ and R ² of the general formula (IV) are different from each other (C ₁ -C ₅ ) alkyl group, either one of R ¹ or R ² is a (C ₁ -C ₅ ) alkyl group and the other After introducing a different (C ₁ -C ₅ ) alkyl group into an ester derivative of cyclopentanecarboxylic acid of formula (V) wherein (residual group) is a hydrogen atom, the ester derivative thus obtained is subjected to hydrolysis and decarboxylation reaction. The required derivative represented by general formula (IV) can be obtained.

The reaction form of the aforementioned cyclopentanone is shown next.

Synthetic route of cyclopentanone of general formula (IV)

On the other hand, the compounds represented by the formula (i) and (i) are 2-oxo by the method described in Org. Syn. 45, 7 (1965) and J. Org. Chem. 29, 2781 (1964) as known compounds. It can be prepared from alkyl esters of cyclopentanecarboxylic acid.

As a diluent used for reaction in the manufacturing method of the azole derivative of general formula (I) which concerns on this invention, Hydrocarbons, such as benzene, toluene, xylene, etc .; Halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; Alcohols such as methanol and ethanol; Acetone nitrile, acetone, dimethylformamide, dimethyl sulfoxide, etc. can be illustrated as ethers and other substances, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, etc.

In addition, in the method for preparing an azole derivative according to the present invention, the reaction proceeds in the presence of a base or an acid in addition to the diluent described above. Bases used in the present specification include alkali metal carbonates such as sodium carbonate and potassium carbonate; Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Alkali metal alcoholates, such as sodium methylate, sodium ethylate, and potassium tert-butylate, Alkali metal hydrides, such as sodium hydride and potassium hydride; Triethylamine and pyridine can be illustrated as alkyl compounds of alkali metals such as n-butyllithium and the like and other substances.

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

In order to carry out the process for producing the azole derivative according to the present invention, for example, when preparing an ester derivative of cyclopentanecarboxylic acid represented by the general formula (V), a halogenated alkyl or a substituted benzyl halide is dissolved in a diluent. It is preferable to make it react in the presence of a base with the compound represented by a formula (VII) or a general formula (S) in some cases. The reaction temperature can be arbitrarily selected in the range of the solidification temperature or boiling point of the diluent as the solvent, preferably in the range of 0 to 100 ° C.

The derivative represented by the general formula (IV) is decarboxylated, preferably stirring the ester derivative of the cyclopentanecarboxylic acid represented by the general formula (V) for 2 to 24 hours with an inorganic acid or an organic acid at a temperature of 80 to 150 ° C. Can be obtained by reacting.

When the A-method is used to prepare the derivative represented by the general formula (II), a solution prepared by dissolving the ketone represented by the general formula (IV) in a diluent (particularly, dimethyl sulfoxide is preferred) To a dimethyloxosulfonium methylide or dimethylsulfonium methylide prepared by mixing an equal amount of a base (for example sodium hydride) with trimethyloxosulfonium iodide or trimethylsulfonium iodide, Preference is given to reacting the dog compounds.

In this case, the reaction amount of dimethyloxosulfonium methylide or dimethylsulfonium methylide is preferably in an amount of 1.0 to 2.0 equivalents of the cyclopentanone derivative represented by the general formula (IV). This reaction is preferably carried out for 1 to 40 hours in the temperature range of 25 to 100 ℃.

On the other hand, in the case of producing by the B-producing method, a cyclopentanone derivative represented by the general formula (IV) is preferably a base (for example, sodium hydride) and methyltriphenylphosphonium halide as a diluent (particularly, dimethyl sulfoxide). To triphenylphosphine methylide (Bitchhis reagent) prepared by mixing in equal amounts, and the two compounds were reacted at a temperature of 0 to 100 ° C. for 2 to 10 hours. The methylenecyclopentanone derivative represented by the general formula (III) thus prepared is separated, dissolved in a diluent, and hydrogen peroxide or peracetic acid, at -10 ° C to the boiling point of the diluent, preferably -10 to 80 ° C. The reaction is carried out after the addition of organic peracids such as benzoic acid, m-chloro and benzoic acid.

The oxirane compound (II) obtained from the cyclopentanone derivative represented by the general formula (IV) by the A-preparation method or the B-preparation method is 1-oxaspiro (2, 4) The arrangement of the benzyl group substituted at the oxirane group and the 7 position at the 3 position in heptane has the following stereoisomer structure.

Separation of these stereoisomers represented by the general formulas (II-A) and (II-B) can be carried out, for example, as chromatography (thin layer chromatography, column chromatography, high performance liquid chromatography). The structural properties of these stereoisomers can be found, for example, in the NMR spectrum.

In order to obtain the azole derivative represented by the general formula (I), a base prepared in a solution prepared by dissolving the oxirane compound represented by the general formula (II) in a diluent may dissolve the azole compound represented by the general formula (VI). The two compounds are reacted by addition in the presence or vice versa by adding an alkali metal salt of the azole compound to a solution prepared by dissolving the oxirane compound in a diluent. The reaction temperature may be arbitrarily selected within the coagulation temperature to boiling temperature range of the diluent, but in practice, it is preferable to proceed with stirring for 1 to 10 hours at a temperature of 0 to 120 ° C, more preferably at 60 to 120 ° C.

After the reaction is completed, the reaction mixture thus obtained is cooled and extracted with an organic solvent such as ethyl acetate, chloroform, methylene chloride, benzene and the like in ice water. The organic layer was separated, the organic layer was washed with water and the washed layer was dried, and then the solvent was distilled off under reduced pressure from the organic layer. The desired compound can be obtained by purifying the residue thus obtained. This purification treatment can be carried out by recrystallization of the residue, silica gel chromatography, and the like.

In the oxirane compound which is a starting material of the azole derivative represented by the general formula (I), two isomers represented by the general formulas (II-A) and (II-B) exist, and thus oxy represented by the general formula (II) The following stereoisomer exists in the target azole derivative of general formula (I) obtained by reacting a lan compound with 1,2,4-triazole or imidazole represented by general formula (VI).

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The separation of the isomers represented by the general formulas (I-A) and (I-B) can of course be carried out, for example, by chromatography.

The usefulness of the azole derivative (azolylcyclopentanol derivative) of the general formula (I) according to the present invention as an active ingredient in agricultural and horticultural compositions will be described.

(1) fungicidal activity against plant disease fungi

The azole derivatives according to the present invention have a control effect against the following broad plant diseases:

Pyricularia oryzae in rice crops

Cochliobolus miyabeanus in rice crops

Xanthomonas oryzae in rice crops

Rhizoctonia solani in rice crops

Helminthosporium sigmoideum in rice crops

Gibberella fugikuroi in rice crops

Grapes in apples Podosphaera leucotricha

Venturia inaequalis in apples

Sclerotinia mali in apples

Alternaria mail in the apple

Valsa mali in an apple

Alternaria kikuchiana on the ship

Phyllactinia pyri in the embryo

Kimnosporangium haraeonum

Venturia nashicola on the ship

Unccinula necator in grapes

Pakospora ampelopsidis in grapes

Glomerella cingulata in grapes

Erysiphe graminis f.sp Hordei on barley

Rhynchosporium secalis in barley

Puccinia graminis on barley

Puccinia triformis on barley

Puccinia recondita on wheat

Septoria tritici in wheat

Puccinia triformis in wheat

Erysiphe graminis f.sp.Hordei in wheat

Sphaerotheca fuliginea in melon

Colletotricum lagenarium in melon

Fusarium oxysporum in watermelon

Fusarium oxysporum f. Cucumerinum in cucumber

Fusarium oxysposum f. Raphani in Japanese radishes

Erysiphe cichoracearum on the tomato

Alteraria solani on tomato

Erysiphe cichoraceanum on the branch

Sephaerotheca humuli in strawberries

Erysiphe cichoracearum in tobacco

Alternaria longipes in tobacco

Sercospora beticola in sugar beet

Alternaria solani in potatoes

Septoria glycines in soybeans

Sercospora kikuchii in soybeans

Sclerotinia cinerea in Nucleus Trees

Botrytis cinerea, Sclorotinia sclerotiorum, etc. in various crops.

Moreover, the azole derivatives according to the present invention have a therapeutic effect as well as a prophylactic control effect against some of these plant diseases.

(2) plant growth regulation activity

As plant growth regulators by plant hormones become descriptive, chemicals called plant growth regulators have recently been used in agriculture and horticultural production.

For example, the use of 2-chloroethyl-trimethylammonium chloride (trade name CCC) as the production of seedless grapes by Gibberellin, the improvement of the rooting of cherry blossoms by α-naphthaleneacetic acid and growth inhibition on wheat Known.

In addition, the application of techniques for controlling the plant's living 1 using plant growth regulators has been extended not only to cultivated crops such as cereals, vegetables, fruit trees, etc., but also to horticultural plants such as flowers, and to plants as broad-ranging plants. The function of this plant growth regulator is likely to be responsible for rooting improvement, flowering control, fruit bearing, fruit enlargement, growth improvement, growth control, and metabolism control.

Therefore, although the types and usage of plant growth regulators have recently increased, the actual use of plant growth regulators has not been as effective as expected.

The azole derivative (azolylcyclopentanol derivative) according to the present invention has inherent properties showing various plant growth regulating activities for a wide range of plants, which can be illustrated as follows.

(Iv) Inhibiting vegetative growth of plants, in particular, inhibiting plant growth.

(Ii) increasing the useful plant content, and

(Iii) the regulating action of plant attribution and flowering time

Examples of using the growth inhibitory activity of (iii) include growth inhibition of weeds (herbicidal function) and grass; Anti-falling of fallen plants, such as rice crops, barley, and the like; Mechanically multiply these flowers by suppressing the height of soybean and cotton crops; Inhibition of germination of auxillary buds for the growth of tobacco leaves; Reduction of pruning process by growth inhibition of Hedges; Increase in commercial value of ornamental plants by growth inhibition.

Examples of utilizing the useful action of increasing the content of plant components in (ii) include, but are not limited to, quality improvement of beets, sugar cane, and citrus fruits by increased sugar content; The quality improvement of grains and soybeans by increasing protein, etc., and other examples using the control effect of ripening time and flowering time of fruits are raw and naturalized according to the seasons required. The shipment of (生 花) can be mentioned.

In order to use the azole derivatives represented by the general formula (I) as fungicides and plant growth regulators, their derivatives or mixtures thereof and carriers (diluents) are prepared as powders, hydrated ingredients, granules, emulsion concentrates, liquids, etc. And the preparations thus prepared may be advantageously used.

In addition, if necessary, it is also possible to add an adjuvant such as a dispersant, an emulsifier, a humectant, and a caking agent in addition to the carrier, to add an effect.

However, since the azole derivative represented by the general formula (I) contains a 1,2,4-triazole ring or an imidazole ring, the azole derivative can be used in the form of an acid addition salt or a metal complex with an inorganic acid or an organic acid. There is a number.

In addition, the azole derivative represented by the general formula (I) according to the present invention includes an azolylmethyl group, a (C ₁ -C ₅ ) alkyl group and a substituted benzyl group in the 1-position, 2-position and 5-position of the cyclopentane ring, respectively. Because of the inclusion in position, stereoisomers such as the geometric and optical isomers of the cis and trans may exist, and the invention also includes individual isomers and mixtures of these individual isomers in any proportion.

Thus, agricultural and horticultural compositions according to the invention comprise compositions containing a single isomer or a mixture of these isomers as active ingredients.

The azole derivatives represented by the general formula (I) according to the present invention are excellent in plant disease control activity and plant growth control activity, and are useful compounds as active ingredients of agricultural and horticultural compositions.

The effects of the present invention will be described by showing specific examples of agricultural and horticultural compositions using the azole derivatives according to the present invention as active ingredients, but the present invention is not limited to the following examples only, unless the main characteristics thereof are lost. no.

(I) Examples of the preparation of individual intermediates for producing the azole derivative represented by the general formula (I) and the azole derivative represented by the general formula (I);

Example 1

Preparation of Methyl 1- (4-chlorobenzyl) -3,3-dimethyl-3-oxocyclopentanecarboxylate (Intermediate Compound No. 156 listed in Table 5)

Add 5.0 g sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) in 150 ml anhydrous benzene with stirring under helium stream and add 50 g of methyl 1- (4-chlorobenzyl) to the mixture After adding 2-oxocyclopentanecarboxylate, the whole mixture was stirred at 80 ° C. for 40 minutes. After cooling the reaction mixture to room temperature, 29.4 g of methyl iodide was added dropwise to the reaction mixture and the mixture thus prepared was stirred at 80 ° C. for 2 hours. After cooling the reaction mixture to room temperature, 5.0 g of sodium hydride (1 equivalent) was added to the reaction mixture, and the reaction mixture was stirred at 80 ° C for 30 minutes. After the reaction mixture was cooled to room temperature again, 29.4 g of methyl iodide (1 equivalent) was added to the reaction mixture, and the reaction mixture was stirred at 80 ° C for 8 hours.

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

The residue thus obtained was purified by distillation under reduced pressure to obtain 44.8 g of the target compound [boiling point: 142-143 ° C (0.7 mmHg)].

Example 2

Preparation of 5- (4-chlorobenzyl) -2,2-dimethyl-2-cyclopentanone (Intermediate Compound No. 133 listed in Table 4)

To 120 ml of 47% bromic acid, 44.8 g of methyl 1- (4-chlorobenzyl) -3,3-dimethyl-2-oxocyclopentanecarboxylate (Compound No. 156 listed in Table 5) was added and so prepared. The resulting mixture was stirred vigorously at 100 ° C. for 12 hours.

The reaction mixture thus obtained was left to cool and then poured into ice water, and the mixture was extracted with ethyl acetate to obtain an organic layer. The organic layer was washed with an aqueous solution of sodium bicarbonate and then with brine solution and then dried over anhydrous sodium sulfate. The solvent was distilled off from the organic layer under reduced pressure to obtain a residue. The residue thus obtained was purified by distillation under reduced pressure to obtain 31 g of the target compound (boiling point: 124 ° C (1 mmHg)).

Example 3

5- (4-chlorobenzyl) -2,2-dimethyl-1-methylenecyclopentane (Intermediate Compound No. 122 listed in Table 3)

3.6 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) in 50 ml anhydrous dimethyl sulfoxide under helium airflow were added, and the resulting mixture was stirred at 70 ° C. for 30 minutes. . After cooling the reaction mixture with ice water, 53.6 g of methyltriphenyl phosphonium bromide was added to the reaction mixture, and the thus formed mixture was stirred for 30 minutes while cooling with ice water, and the thus cooled mixture was stirred at room temperature for 10 minutes. Stirred. 23.6 g of 5- (4-chlorobenzyl) -2,2-dimethyl-1-cyclopentanone (Compound No. 133 listed in Table 4) were then added to the mixture, and the entire mixture was allowed to stand at room temperature for 1 hour. The reaction was completed by stirring at 70 ° C. for 30 min.

After the reaction mixture was left to cool, the reaction mixture was poured into iced water and extracted with ethyl acetate to obtain an organic layer. The organic layer thus obtained was washed with a saline solution, and the organic layer thus washed was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure from the dried organic layer obtained.

From the mixture of the oily substance and solid substance thus obtained, the oily substance was extracted with n-hexane, and the obtained n-hexane extract was purified by silica gel column chromatography to obtain 22.1 g of the target compound.

Example 4

Preparation of 7- (4-chlorobenzyl) -4,4-dimethyl-1-oxaspiro [2.4] heptane (intermediate compounds No. 77 and 78 listed in Table 2 according to the A-preparation method)

While stirring dimethyl sulfoxide under a helium stream, 3 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) was added to 70 ml of anhydrous dimethyl sulfoxide, followed by 27.5 to the mixture thus formed. g of trimethyloxosulfonium iodide is added. The whole mixture was stirred at room temperature for 30 minutes and then 23.6 g of 5- (4-chlorobenzyl) -2,2-dimethyl-1-cyclopentanone (Compound No. 133 listed in Table 4) in 20 ml of anhydrous dimethyl sulfoxide. The dissolved solution was added to this mixture within 30 minutes, and the whole mixture was stirred at 90 ° C for 2 hours.

The reaction mixture thus obtained was left to cool, poured into ice water, and the mixture thus obtained was extracted with ethyl acetate to obtain an organic layer. After washing the organic layer with a saline solution, the organic layer is dried over anhydrous sodium sulfate and the solvent is evaporated off from the dried organic layer under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 13.95 g of target compound No. 77 and 1.05 g of target compound No. 78.

Example 5

Preparation of 7- (4-fluorobenzyl) -4,4-dimethyl-1-oxaspiro [2.4] heptane (Intermediate compounds No. 81 and 82 listed in Table 2 according to the B-preparation method)

Dissolve 17 g of 5- (4-fluorobenzyl) -2,2-dimethyl-1-methylenecyclopentane (Compound No. 124 listed in Table 3) in 170 ml chloroform, followed by 27.1 g of m-chloroperbenzoic acid. To the mixture was added within 10 minutes, and the mixture thus obtained was stirred at room temperature for 2 hours. Next, 25.4 g of calcium hydroxide was added to the mixture within 10 minutes, and the mixture was stirred at room temperature for 30 minutes.

The separated solid material was filtered and the chloroform layer of the filtrate was condensed to give a colorless oily material. The residual oily substance was thus purified by silica gel column chromatography to obtain target compound number 81, 4.5 g and target compound number 82, 8.6 g.

Example 6

Preparation of C-5- (2,4-dichlorobenzyl) -2,2-dimethyl-1- (1H-imidazol-1-ylmethyl) -r-1-cyclopentanol (Compound No. listed in Table 1) 15)

To 18 ml of anhydrous dimethylformamide was added 996 mg of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) with stirring under a helium stream. Then, 2.83 g of 1 H-imidazole was added to the thus formed mixture, and the whole mixture was stirred at room temperature until bubbling stopped. To the solution thus obtained, 5.93 g of 7- (2,4-dichlorobenzyl) -4,4-dimethyl-1-oxaspiro [2,4] heptane (compound number listed in Table 2) in 10 ml anhydrous dimethylformamide 83) was added dropwise and the mixture thus obtained was stirred at 80 ° C. for 2 hours.

The reaction mixture thus obtained was left to cool, poured into ice water, and the mixture thus obtained was extracted with ethyl acetate to obtain an organic layer.

After the organic layer was washed with water, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off from the organic layer under reduced pressure. The residue thus obtained was purified by silica gel column chromatography, and further recrystallized as a mixture of n-hexane and ethyl acetate. As a result, 2.7 g of the target compound were obtained.

Example 7

Preparation of t-5- (4-chlorobenzyl) -2,2-dimethyl-1- (1H-1,2,4-triazol-1-ylmethyl) -r-1-cyclopentanol (from Table 1 Compound number 2)

5.0 g of 7- (4-chlorobenzyl) -4,4-dimethyl-1-oxaspiro [2,4] heptane (Compound No. 78 in Table 2) is added to 30 ml of anhydrous dimethylformamide while stirring under a helium stream. To the solution thus formed was added 2.2 g of sodium salt of 1H-1,2,4-triazole (purity: 90%; sold by Aldrich Co.) slowly. The mixture was then stirred at 70 ° C. for 2 hours.

The reaction mixture thus obtained was left to cool, poured into ice water, and the whole mixture was extracted with ethyl acetate to obtain an organic layer. After washing this organic layer with water, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off from this dry organic layer under reduced pressure.

The residue thus obtained was purified by silica gel column chromatography to obtain 3.1 g of the target compound.

Example 8

Preparation of 2- (4-chlorobenzyl) -5-methyl-1-cyclopentanone (Intermediate Compound No. 137 from Table 4)

3.04 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) in 126 ml anhydrous benzene was added and then 18 g of methyl 3-methyl-2-oxocyclopentane was added to the resulting mixture. Carboxylate was added. The whole mixture was stirred at room temperature for 1 hour, after which 21.5 g of 4-chlorobenzylchloride was added, and the mixture thus obtained was heated to reflux for 6 hours in a 90 ° C oil bath.

After the reaction mixture was left to cool, it was extracted with benzene and the benzene layer was washed with brine solution. After drying this benzene layer over anhydrous sodium sulfate, the solvent was distilled off from this dry benzene layer under reduced pressure, and 33.6 g of tan oils of methyl 1- (4-chlorobenzyl) -3-methyl-2-oxocyclopentanecarboxylate were obtained. Obtained. (Intermediate Compound No. 160 in Table 5).

The thus obtained ester was not purified, 100 ml of 47% bromic acid was added to this ester, and the mixture thus obtained was vigorously stirred at 110 ° C. for 18 hours. After the reaction mixture was left to cool, it was extracted with methylene chloride and the organic layer was washed with an aqueous solution of sodium carbonate or brine solution. The organic layer thus washed was dried over inorganic sodium sulfate, and the solvent was distilled off from the organic layer under reduced pressure.

The residue thus obtained was purified by distillation under reduced pressure to obtain 17.4 g of the target compound.

Example 9

Methyl 1- (4-chlorobenzyl) -3-ethyl-3-methyl-2-oxocyclopentanecarboxylate (Intermediate Compound No. 178 listed in Table 5)

To 80 ml of anhydrous tetrahydrofuran, 1.7 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) with stirring under helium stream is added and then 18.2 g of methyl to the resulting mixture. 1- (4-chlorobenzyl) -3-methyl-2-oxocyclopentanecarboxylate (Intermediate Compound No. 160 listed in Table 5) was added and the whole mixture was stirred at room temperature for 2 hours.

Then, 11.1 g of ethyl iodide was added dropwise to the mixture while maintaining the mixture at a temperature of 20 to 30 DEG C, and then the whole mixture was stirred at a temperature of 20 to 30 DEG C for 1 hour, and then 60 Stir at 1 ° C. for 1 hour.

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

The residue thus obtained was distilled off under reduced pressure to yield 15 g of the target compound.

Example 10

Preparation of 4- (4-chlorobenzyl) -7-methyl-1-oxaspiro [2.4] heptane (Intermediate Compound No. 85 in Table 2)

To 37 ml anhydrous dimethyl sulfoxide was added 1.44 g of sodium hydride (prepared by washing 60% oily sodium hydride with anhydrous benzene) with stirring under helium stream, followed by 13.2 g of trimethyloxo in the resulting mixture. Sulfonium iodide was added and the whole mixture was stirred for 30 minutes at room temperature. Then to this mixture was added a solution in which 12.2 g of 2- (4-chlorobenzyl) -5-methyl-1-cyclopentanone (Compound No. 137 in Table 4) was dissolved in 12 ml anhydrous dimethyl sulfoxide within 10 minutes. And the whole mixture was stirred at room temperature for 4 hours.

The reaction solution thus obtained was poured into ice water, and the mixture thus formed was extracted with methylene chloride to obtain an organic layer. The organic layer is washed with a saline solution, and then the organic layer is dried over anhydrous sodium sulfate, and the solvent is distilled off from the organic layer under reduced pressure.

The residue thus obtained was purified by silica gel column chromatography, obtaining 6.67 g of the target compound.

In addition, the target compound, another compound, and three isomers of the target compound were separated. That is, intermediate compound No. 86 of the Table 2, 0.15g; 0.16 g of intermediate compound No. 87 and 0.16 g of intermediate compound No. 88 were obtained.

Example 11

Preparation of 4- (4-chlorobenzyl) -7-ethyl-1-oxaspiro [2.4] heptane (Intermediate Compound Nos. 93, 94, 95, and 96 of Table 2)

In 100 ml chloroform, 8.0 g of 2- (4-chlorobenzyl) -5-ethyl-1-methylenecyclopentane (Compound No. 129 as listed in Table 3) are dissolved and then 11.6 g of m- to the mixture thus formed. Chloroperbenzoic acid was added within 5 minutes and the whole mixture was stirred at room temperature for 2 hours. Then, 11 g of calcium hydroxide was added to the mixture while cooling with ice water, and the whole mixture was stirred at room temperature for 30 minutes.

The solid material thus separated was filtered off and the chloroform layer was concentrated with filtrate to give a colorless oily material. This oily substance was purified by silica gel column chromatography, and 0.7 g of the compound number 93 as the title compound; 2.4 g of compound number 94; 2.2 g of compound number 95; And 2.6 g of Compound No. 96 were obtained.

Example 12

Preparation of C-2- (4-chlorobenzyl) -5-methyl-1- (1H-1,2,4-triazol-1-ylmethyl) -r-1-cyclopentanol (Compound No. in Table 1) 16)

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

In the reaction mixture thus obtained, a solution in which 3.1 g of 4- (4-chlorobenzyl) -7-methyl-1-oxaspiro [2.4] heptane (Compound No. 85 in Table 2) was dissolved in 6.2 ml anhydrous dimethylformamide. Was added and the mixture thus formed was stirred at 80 ° C. for 1 hour.

The reaction solution thus obtained was left to cool, poured into ice water, and the mixture thus obtained was extracted with chloride to obtain an organic layer.

The organic layer is washed with brine solution, dried over anhydrous sodium sulfate, and the solvent is distilled off from the organic layer under reduced pressure. The residue thus obtained was purified by silica gel column chromatography and then recrystallized in a mixture of N-hexane and ethyl acetate to give 2.83 g of the target compound.

Example 13

Preparation of C-2- (4-chlorobenzyl) -5-methyl-1- (1H-imidazol-1-ylmethyl) -r-1-cyclopentanol (Compound No. 17 in Table 1)

670 mg of sodium hydride (prepared by washing 60% oily sodium hydride) in 10 ml anhydrous dimethylformamide was added and 1.9 g of 1H-imidazole was added to the resulting mixture followed by bubbling the entire mixture. It stirred at room temperature until it stopped.

Then to this mixture was added a solution of 3.3 g of 4- (4-chlorobenzyl) -7-methyl-1-oxaspiro [2.4] heptane in 6.6 ml anhydrous dimethylformamide and the whole mixture was heated to 80 deg. Stirred for 1 h.

The reaction solution thus obtained was left to cool, poured into ice water, and the mixture thus formed was extracted as methylene chloride to obtain an organic layer. After the organic layer was washed with a saline solution, the organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off from the organic layer under reduced pressure.

The residue thus obtained was purified by silica gel column chromatography, and then recrystallized in a mixture of n-hexane and ethyl acetate to obtain 3.16 g of the target compound.

[II] Production of agricultural and horticultural fungicide compositions:

Example 14

Spraying agent (powdering agent)

3 parts by weight of the azole derivative (compound No. 3), 40 parts by weight of clay and 57 parts by weight of talc were mixed and ground to prepare an agricultural and horticultural fungicide composition in the form of a spraying agent.

The composition thus prepared was used by spraying.

Example 15

Wettable Powder

50 parts by weight of the azole derivative (compound number 1) according to the present invention, 5 parts by weight of lignin sulfonate; 3 parts by weight of alkyl sulfonate and 42 parts by weight of diatomaceous earth were mixed and ground to prepare a wettable powder.

The composition thus prepared was diluted with water as a wettable powder.

Example 16

Granulation

5 parts by weight of an azole derivative (compound No. 16) according to the present invention, 43 parts by weight of bentonite, 45 parts by weight of clay and 7 parts by weight of lignin sulfonate were uniformly mixed, and the mixture was kneaded together after adding water to the mixture. The granulated granules were formed into granules using a granule and then dried to obtain a granular composition.

Example 17

Emulsion concentrate

20 parts by weight of an azole derivative (compound No. 13) according to the present invention, 10 parts by weight of polyoxyethylene alkyl aryl ether, 3 parts by weight of polyoxyethylene sorbitan monolaurate and 67 parts by weight of xylene were mixed together to prepare a composition in the form of an emulsion concentrate. Prepared.

[III] Application Example of Agricultural and Horticultural Fungicide Compositions According to the Present Invention for Plant Disease

Example 18

Control Effect Test on Erysiphe graminis f.sp.

In Example 15 per port for two-leaf wheat crop seedlings (cultivar: NORIN No. 64, three seedlings per treatment group using 16 seedlings per pot) grown using a 10 cm diameter unglazed pot. Diluted emulsion concentrate (diluted to a predetermined concentration as water) was added at a rate of 5 ml. After air dilution of the dilution, E.ci. gramminis f.sp. Tritici summer seed suspension was sprayed on the seedlings in the pot, and the pot was stored for 24 hours at a temperature of 20 to 24 ° C. under high humidity and then the pot was stored in a room with a window. Nine to 11 days after the inoculation, the degree of disease in seedlings was examined according to the following inspection criteria, and the control value of the fungicidal composition was calculated according to the following equation.

〈Inspection Criteria〉

Sickness

0 not infringed

0.5 area spot of disease spot is less than 10%

1 Area of disease spots is more than 10% and less than 20%

2 area spot of disease spot is more than 20% and less than 40%

3 Area rate of disease spot is more than 40% and less than 60%

4 Area rate of disease spot is more than 60% and less than 80%

5 area spot of disease spot is more than 80%

The test results are listed in Table 6 below.

TABLE 6a

TABLE 6b

TABLE 6c

^*) : Commercially available triadimefon is an active ingredient and has a compound represented by the following general formula.

Example 19

Control Effect Test on Sphaerotheca fuliginea in Cucumber

Dilution of two-stage cucumber crops (variety: SAGAMI HAMPAKU) grown using a 10 cm diameter unglazed pot, 1 pot per pot, using 3 pots per treatment group as in Example 15 per pot 5 ml of emulsion concentrate (diluted to a defined concentration as water) was added. After air drying the applied leaves, the seeds of spaerotheca polyginia were taken from the diseased leaves of cucumber crops using a brush and inoculated into these cucumber crops, and these crops were stored in a room with windows to cause disease. .

Nine to eleven days after the inoculation, the diseases of the cucumber crops were examined according to the following test criteria, and the control value of the fungicidal composition was calculated according to the following equation.

Inspection standard

Sickness

0 not infringed

0.5 area spot of disease spot is less than 10%

1 Area of disease spots is more than 10% and less than 20%

2 area spot of disease spot is more than 20% and less than 40%

3 Area rate of disease spot is more than 40% and less than 60%

4 Area rate of disease spot is more than 60% and less than 80%

5 area spot of disease spot is more than 80%

The test results are listed in Table 7.

TABLE 7

Example 20

Control Effect Test on Puccinia recondita in Wheat

In Example 15 per port for two-leaf crop seedlings (cultivar: NORIN No. 64, three seedlings per treatment group with 16 seedlings per pot) grown using a 10 cm diameter unglazed pot. Diluted emulsion concentrate (diluted to a predetermined concentration as water) was spray applied at a rate of 5 ml.

After spraying the application dilution, spray the seedlings of Puccinia recondita, harvested from the leaves of infected crops, in the pots and spray these pots for 24 hours at 20-23 ° C under high humidity conditions These ports were left in this room. Seven to 10 days after the inoculation, the degree of disease in seedlings was examined according to the following inspection criteria, and the control value of the fungicidal composition was calculated according to the following equation from the average disease degree in leaves.

Inspection standard

Sickness

0 not infringed

0.5 area spot of disease spot is less than 10%

1 Area of disease spots is more than 10% and less than 20%

2 area spot of disease spot is more than 20% and less than 40%

3 Area rate of disease spot is more than 40% and less than 60%

4 Area rate of disease spot is more than 60% and less than 80%

5 area spot of disease spot is more than 80%

Test results are listed in Table 8.

TABLE 8a

TABLE 8b

TABLE 8c

Example 21

Control Effect Test of Botrytis cinerea in Gangnam Beans

5 ml of dilute emulsified concentrate (diluted to a defined concentration as water), as in Example 15, per pot on the leaves of the first soybean-grown crop (kind: HONKINTOKI) grown using a 10 cm diameter unglazed pot. Spray application at a rate.

After these coated leaves were air-dried, a 4 mm diameter round agar cut containing Botrytis cinerea fungi was pre-cultured for 3 days at 20 ° C. using potato agar medium containing sugar-added agar medium. Directly attached to the center part, these crops were maintained at 20-22 ° C. under high humidity conditions. On the third day of inoculation, the area of the disease spots of the treated group was compared with the area of the disease spots of the control group (untreated group), and the diseases according to the following inspection criteria were investigated, and the control value of the fungicide composition was calculated according to the following equation.

Inspection standard

Degree of attack

0 not infringed

Only the bottom or periphery of 0.5 inoculated fungal agar is invaded

1 Area of disease spots is more than 10% and less than 20%

2 area spot of disease spot is more than 20% and less than 40%

3 Area rate of disease spot is more than 40% and less than 60%

4 Area rate of disease spot is more than 60% and less than 80%

5 area spot of disease spot is more than 80%

The test results are listed in Table 9 below.

Table 9a

TABLE 9b

TABLE 9c

Note *): Commercially available substance (lobral) is an active ingredient and contains a compound represented by the following general formula.

Example 22

Control Effect Test on Cochliobolus miyabeanus in Rice Crops

Dilute emulsified concentrate as in Example 15 (specified as water) was sprinkled with 16 seeds of rice crop (variety: SASANISHIKI) on each of the 10 cm diameter unglazed pots. Diluted to a concentration) was sown on the seedlings.

After the leaves thus treated were air dried, a pre-cultivated Cochribolius miyabeanus spore suspension was sprayed onto the treated seedlings at 5 ml per pot. Fifteen fungal spores in suspension were found in the package under a microscope of 150x magnification.

Immediately after the end of the inoculation, the pots thus treated were placed in the incubation chamber at 25 ° C. and saturated water and stored in the pot for 2 days, and then these ports were transferred to a greenhouse with a glass window to facilitate invasion. Five days after the inoculation, the disease spot score was counted at 10 leaves per pot, and the control value of the fungicide composition was calculated according to the following equation.

The test results are listed in Table 10 below.

TABLE 10

Example 23

Antifungal test for several types of pathogenic fungi

This example obtains the results of the antifungal properties of the azole derivatives according to the invention against various plant pathogenic fungi.

Test Methods

The compound according to the present invention was dissolved in dimethyl sulfoxide to obtain a solution of a predetermined concentration, and 0.6 ml of the solution thus prepared was mixed well with 60 ml of PAS medium at about 60 ° C. in a 100 ml conical beaker. The mixture thus formed was poured into a glass dish and solidified to obtain a planar medium containing the compound.

On the other hand, test fungi pre-cultivated in this planar medium were punched out with a cork hole 4 mm in diameter, and the test fungus-containing medium pieces thus inoculated on a planar medium containing the compound. After inoculation, the compound-containing medium and fungi thus prepared were incubated at a suitable temperature for 1 to 3 days to grow the individual fungi, and the growth of the fungi was measured by the diameter of the fungal colony. The mycelial growth inhibition rate of the fungi was obtained according to the following formula in comparison with the growth in the untreated group (medium containing no compound) in the medium thus prepared.

R = (dc-dt) 100 / dc

In the formula, R is mycelial growth inhibition rate; dt is the diameter of the fungus on a flat medium containing no compound and dt is the diameter of the fungal on a flat medium containing the compound.

The test results were evaluated in five steps according to the following criteria and listed in Table 11.

Mycelial growth inhibition rate:

5: growth inhibition rate is 90-100%

4: Growth inhibition rate is 70% or more but less than 90%

3: Growth inhibition rate is 40% or more but less than 70%

2: Growth inhibition rate is 20% or more but less than 40%

1: growth inhibition rate is less than 20%

TABLE 11a

Table 11b

TABLE 11c

The abbreviations in Table 11 each mean the following fungi.

P.o. : Pilicularia Orizae in Rice Crop

C.m. : Cocliobolus Miyabeanus in Rice Crop

G.f. : Gibeberella fujikuroi in rice crops

H.s: Helmintosporium sigmideum in rice crops

R.s: Ligitonia sorani in rice crops

Bo.c: Botrytis Cinerea

S.s: Sclerotinia sclerotium

F.n. : Fusarium oxysporium in watermelon f. Niveum

F.c. : Fusarium oxysporium f, Cucumerium on cucumber

F.r. : Fusarium oxysporium in Japanese radish f. Raffani

C.l. : Colletotricum Lagenaria in Melon

C.b. : Sercospora Beticola in Beet

S.c. : Sclerotinia Cinerea in Peach

V.m. : Launch Mali from an Apple

A.m. : Alternaria Mali in Apples

A.k. : Alternaria Alternata (Kiguchiana) on the ship

G.c: glomerella singulata in grapes

(IV) Examples of agricultural and horticultural plant growth regulators containing the azole derivatives according to the present invention as active ingredients

Example 24

Wettable Powder Form

50 parts by weight of the azole derivative (compound No. 3 in Table 1) according to the present invention, 5 parts by weight of lignin sulfonate, 3 parts by weight of alkyl sulfonate and 42 parts by weight of diatomaceous earth were mixed and ground to obtain a composition in the form of a wet powder. This composition was used after dilution with water.

Example 25

Emulsion Concentrate Form

25 parts by weight of the azole derivative (compound No. 20 of Table 1) according to the present invention, 65 parts by weight of xylene and 10 parts by weight of polyoxyethylene alkylaryl ether were uniformly mixed together to obtain a composition in the form of an emulsion concentrate. This composition was used after dilution with water.

Example 26

Spraying agent (powdering) form

8 parts by weight of the azole derivative (compound No. 11 in Table 1) according to the present invention, 40 parts by weight of bentonite, 45 parts by weight of clay and 7 parts by weight of lignin sulfonate were mixed uniformly, and the mixture was formed and then added with water. The mixture was kneaded together and granulated in an extrusion granulator and dried to form a composition in the form of a spray.

Example 27

Inhibitory Effect of Crop Height on Rice Crops

Each glass dish having a diameter of 8.5 cm was placed in 10 ml of a solution containing 10 ppm of the compound according to the present invention, and 10 seed crops (variety: SASANISHIKI) were seeded on the glass dish. These dishes were stored indoors at 27 ° C. for 7 days to germinate seeds, and then the heights of the seedlings were measured to obtain the data listed in Table 12.

As shown in Table 12, all the test azole derivatives according to the present invention showed a growth inhibitory effect, but no phytotoxicity.

TABLE 12

Claims (17)

Azole derivatives represented by the following general formula (I):

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer of 0 to 2; A represents a nitrogen atom or CH, provided that R ¹ is not a hydrogen atom when R ² is a hydrogen atom. The compound of claim 1, wherein R ¹ is a hydrogen atom or (C ₁ -C ₄ ) alkyl; R ² is a hydrogen atom or (C ₁ -C ₃ ) alkyl; A halogen atom where X is substituted at the 4-position of the benzene ring; n is 1 and A represents a nitrogen atom or CH, provided that R ¹ is not a hydrogen atom when R ² is a hydrogen atom. 3. A compound according to claim 2, wherein R ¹ and R ² are each hydrogen atom or a (C ₁ -C ₃ ) alkyl group; A halogen atom where X is substituted at the 4-position of the benzene ring; An azole derivative which is not a hydrogen atom, which is R ¹ when n represents 1 and A represents a nitrogen atom, and R ² represents a hydrogen atom. An azole represented by the following general formula (I) consisting of reacting an oxirane derivative represented by the following general formula (II) with 1,2,4-triazole or imidazole represented by the following general formula (VI): Process for the preparation of derivatives.

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer of 0 to 2; A represents a nitrogen atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom, and M represents a hydrogen atom or an alkali metal atom. The oxirane derivative represented by the general formula (II) is reacted with (a) (i) an alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide, and thus 1- ( Reacting the alkyl ester of substituted benzyl) -2-oxocyclopentanecarboxylic acid 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) 1- (substituted benzyl) -3- (C ₁ -C ₅ alkyl) -2-oxocyclopentanecarboxylic acid is reacted with (C ₁ -C ₅ ) alkyl halide to obtain an ester derivative of cyclopentane carboxylic acid represented by the following general formula (V),

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group or n Represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom; (b) hydrolysis and decarboxylation reaction of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by the following general formula (IV),

Wherein R ¹ , R ² , X and n are the same as defined above, respectively; (c) the cyclopentanone derivative thus obtained is subjected to oxirane reaction using sulfonium lide or oxosulfonium lide or the cyclopentanone derivative thus obtained is obtained by Wittig reaction. A method for producing an azole derivative, which is prepared by converting a cyclopentanone derivative to an oxirane derivative represented by the following general formula (II) by epoxidizing a methylene cyclopentane derivative represented by the following general formula (III).

(Where R ¹ , R ² , X and n are the same as the previous definitions) The process according to claim 4, wherein the process is carried out by reacting (a) (i) an alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide and obtaining 1- (substituted benzyl) -2-oxocyclo Reacting an alkyl ester of pentanecarboxylic acid 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) 1- (substituted benzyl) -3- (C ₁ -C ₅ alkyl) -2-oxocyclopentanecarboxylic acid is reacted with (C ₁ -C ₅ ) alkyl halide to obtain an ester derivative of cyclopentane carboxylic acid represented by the following general formula (V),

Wherein R ¹ and R ² are each a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group or n Represents an integer of 0 to 2, provided that R ² is not a hydrogen atom when R ¹ is a hydrogen atom; (b) hydrolysis and decarboxylation of the ester derivative of cyclopentanecarboxylic acid thus obtained to obtain a cyclopentanone derivative represented by the following general formula (IV),

Wherein R ¹ , R ² , X and n are the same as defined above, respectively; (c) the cyclopentanes thus obtained are obtained by oxirane reaction of the derivatives with sulfonium lide or oxosulfonium lide or by Wittig reaction with the cyclopentanone derivatives thus obtained. The methylene cyclopentane derivative represented by the following general formula (III) is epoxidized to convert the cyclopentanone derivative into an oxirane derivative represented by the following general formula (II),

(Wherein R ¹ , R ² , X and n are the same as defined above); (d) Then, a method for producing an azole derivative comprising the step of reacting the oxirane derivative thus obtained with 1,2,4-triazole or imidazole of the following general formula (VI).

(Where n is a hydrogen atom or an alkali metal atom and A is a nitrogen atom or CH) An oxirane derivative for preparing an azole derivative of the general formula (I) represented by the following general formula (II):

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n represents an integer of 0 to 2; Provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. (1) an oxirane reaction of a cyclopentanone derivative represented by the following general formula (IV) using sulfonium lide or oxosulfonium lide, or (2) from the cyclopentanone derivative by a Wittich reaction. And a step of converting the cyclopentanone derivative to the oxirane derivative represented by the following general formula (II) by epoxidation of the methylenecyclopentane derivative prepared and represented by the following general formula (III). Method for producing an oxirane derivative represented by).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n represents an integer of 0 to 2; Provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. Methylene cyclopentane derivatives for the preparation of azole derivatives of general formula (I) represented by the following general formula (III):

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. A method for producing a methylenecyclopentane derivative represented by the following general formula (III) by reacting the cyclopentanone derivative represented by the following general formula (IV) with Wittig.

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. Cyclopentanone derivatives for the production of azole derivatives of the general formula (I) represented by the following general formula (IV).

Wherein R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. A method for producing a cyclopentanone derivative represented by the following general formula (IV) by subjecting the ester derivative of cyclopentanecarboxylic acid represented by the following general formula (V) to hydrolysis decarboxylation reaction.

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. An ester derivative of cyclopentanecarboxylic acid for preparing the azole derivative of general formula (I) represented by the following general formula (V).

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. (i) reacting the alkyl ester of 2-oxocyclopentanecarboxylic acid with a substituted benzyl halide, and thus obtaining the alkyl ester of 1- (substituted benzyl) -2-oxocyclopentanecarboxylic acid (C ₁ -C _5). ) With an alkyl halide; (ii) reacting an alkyl ester of 3- (C ₁ -C ₅ ) -2-oxocyclopentanecarboxylic acid with a substituted benzyl halide; Or (iii) reacting 1- (substituted benzyl) -3- (C ₁ -C ₅ alkyl) -2-oxocyclopentanecarboxylic acid with (C ₁ -C ₅ ) alkyl halide, represented by the following general formula (V) A process for preparing an ester derivative of cyclopentanecarboxylic acid, which is used.

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; R is a (C ₁ -C ₅ ) alkyl group; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; And n represents an integer of 0 to 2, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. An agricultural horticulture and composition containing an azole derivative represented by the following general formula (I) as an active ingredient and having fungicidal activity and plant growth regulating activity.

In the above formula, R ¹ and R ² each represent a (C ₁ -C ₅ ) alkyl group or a hydrogen atom; X is a halogen atom, a (C ₁ -C ₅ ) alkyl group or a phenyl group; n is an integer of 0 to 2; A represents a nitrogen atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom. The compound of claim 15, wherein R ¹ is a hydrogen atom or (C ₁ -C ₄ ) alkyl; R ² is a hydrogen atom or (C ₁ -C ₃ ) alkyl; A halogen atom where X is substituted at the 4-position of the benzene ring; wherein n represents 1 and A represents a nitrogen atom or CH, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom; The compound of claim 16, wherein R ¹ and R ² each represent a hydrogen atom or a (C ₁ -C ₃ ) alkyl group; A halogen atom where X is substituted at the 4-position of the benzene ring; n represents 1 and A represents a nitrogen atom, provided that when R ² is a hydrogen atom, R ¹ is not a hydrogen atom.

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