JP2680319B2 - Novel azole derivative, production method thereof, and agricultural / horticultural fungicide containing the derivative as an active ingredient - Google Patents

Description

TECHNICAL FIELD The present invention relates to an azole derivative having utility as an active ingredient for controlling plant diseases, a method for producing the same, and an agricultural / horticultural sterilization containing the azole derivative as an active ingredient. Regarding agents.

BACKGROUND ART Conventionally, many azole derivatives as active ingredients of agricultural and horticultural fungicides have been proposed, but azole derivatives having a structure bonded to a cyclopentane having a substituent are disclosed in JP-A-60-215674. It can be done. JP 60-2156
In the azole derivative disclosed in No. 74, the azolylmethyl group and the phenyl group have a geminal position (ge
minal position) is bound.

(In the formula, R ₁ and R ₂ are a hydrogen atom, a hydroxyl group or 1 to
It represents an alkyl group having 6 carbon atoms, and X represents a hydrogen atom or a halogen atom. ) The present inventors, unlike the above-mentioned known azole derivatives,
It was found that a novel compound, which has not been described in the literature, has a bactericidal activity, which has a structure in which an azolylmethyl group and a benzyl group are bonded to adjacent carbon atoms on a cyclopentane ring.

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention The present inventors develop an agricultural / horticultural fungicide that has low toxicity to humans and animals, high safety in handling, and excellent control effect against a wide range of plant diseases. Therefore, as a result of synthesizing a large number of azole derivatives and examining the practicality thereof, it was found that the azole derivative represented by the formula (I) can be effectively applied as an agricultural / horticultural fungicide having the above-mentioned properties. The present invention has been accomplished.

That is, an object of the present invention is to provide an azole derivative having usefulness as an active ingredient of an agricultural and horticultural fungicide, a method for producing the same, and an excellent control effect against a wide range of plant diseases, and low toxicity and handling. Another object of the present invention is to provide an agricultural and horticultural fungicide containing the azole derivative as an active ingredient, which is also excellent in terms of safety.

 Hereinafter, the present invention will be described in detail.

Structure of the Invention The structure of the present invention is characterized by the following general formula (I). (Wherein A represents a nitrogen atom or CH), and the following formula (II) as a method for producing the azole derivative: And an oxirane derivative represented by the following general formula (III) (Wherein, M represents a hydrogen atom or an alkali metal, and A represents a nitrogen atom or CH), 1,2,4-triazole or imidazole represented by the general formula (I) (Wherein A represents a nitrogen atom or CH), and a method for producing an azole derivative having the general formula (I) as an active ingredient.

The physicochemical properties of the azole derivative represented by the general formula (I) (a novel compound not described in the literature) and the oxirane intermediate represented by the formula (II) for producing the azole derivative are shown in Table 1 and It is as shown in Table 2.

Means for Solving the Problems The production method for obtaining the azole derivative represented by the general formula (I) according to the present invention, and the usefulness of the azole derivative, the utilization as a fungicide for agricultural and horticultural use will be described.

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

By reacting the oxirane derivative represented by the above formula (II) with 1,2,4-triazole or imidazole represented by the following formula (III) in the presence of a diluent, the oxirane derivative represented by the above general formula (I) The desired azole derivative is obtained.

(In the formula, M represents a hydrogen atom or an alkali metal, and A represents a nitrogen atom or CH.) The oxirane derivative represented by the formula (II) used as the starting material here is a journal of pharmacological Science (J.Pharm.Sci.) 68 , 1501 (1979)
Can be obtained by reacting the known methylenecyclopentane derivative represented by the following formula (IV) and described in the above literature with an organic peracid in the presence of a diluent by referring to the method described in 1).

Hydrocarbons such as benzene, toluene, xylene, and hexane are used as diluents in a series of reactions in the process for producing the compound represented by the general formula (I) according to the present invention; methylene chloride, chloroform, and tetrahydrochloride. Halogenated hydrocarbons such as carbon chloride; alcohols such as methanol and ethanol: diethyl ether, diisopropyl ether,
Ethers such as tetrahydrofuran; other examples include acetonitrile, acetone, dimethylformamide, dimethylsulfoxide and the like.

In order to produce the oxirane derivative represented by the above formula (II), the methylenecyclopentane derivative represented by the above formula (IV) is dissolved in the above-mentioned diluent, and hydrogen peroxide, peracetic acid, or perbenzoic acid is added thereto. , 1.0-3.0 equivalents of an organic peracid such as meta-chloroperbenzoic acid may be added and reacted. The reaction temperature at this time is obtained by applying any temperature from the freezing point to the boiling point of the above diluent as a solvent, but in practice, it is 0 to 80.
It is preferable to carry out the reaction at a temperature in the range of ° C. The reaction time is in the range of 0.5 to 6.0 hours, and it is preferable to carry out the reaction with stirring.

After completion of the above reaction, the reaction mixture obtained by the reaction was poured into water, ethyl acetate, chloroform, benzene,
Separate the organic layer by extracting with an organic solvent such as hexane,
Then, the organic layer is washed with water and dried, the solvent is distilled off under reduced pressure, and the resulting residue is subjected to purification treatment to obtain the desired oxirane compound. The purification treatment can be carried out by subjecting it to silica gel column chromatography or the like.

The oxirane compound (II) obtained from the methylenecyclopentane derivative (IV) is 1-oxaspiro [2.
4] An oxirane group at the 3rd and 4th positions of the heptane ring and 4
In the configuration with the -chlorobenzyl group, it has the following stereoisomeric structure.

The document Journal of Pharma Gerhard ticarcillin Science (J.Pharm.Sci.) 68, 1501 but oxirane derivative in (1979) (II) are described as a mixture, the present inventors have two stereoisomers Body (II-A) and (II-B)
However, they have found that they can be easily separated by, for example, chromatography (thin layer, column, liquid high pressure chromatography, etc.). The features of the two structures are, for example, NM
It can be given according to the R spectrum.

To obtain the azole derivative represented by the general formula (I),
For example, the azoles represented by the general formula (III) are dissolved in the above-mentioned diluent and, if necessary, in the presence of a base, the oxiranes represented by the formula (II) are added in an amount of 0.5 to 1.0.
It is advisable to add an equivalent amount or, conversely, to the one obtained by dissolving the oxirane in a diluent, and adding the alkali metal salt of the azole to the reaction.

Examples of the base used here include carbonates of alkali metals such as sodium carbonate and potassium carbonate; sodium hydroxide,
Alkali metal hydroxides such as potassium hydroxide; Alkali metal alcoholates such as sodium methylate, sodium ethylate and potassium tertiary butyrate; Alkali metal hydrides such as sodium hydroxide and potassium hydride; n-butyllithium Examples thereof include alkyl compounds of alkali metals such as, and toluethylamine, pyridine, and the like.

As the reaction temperature at this time, any temperature from the freezing point to the boiling point of the diluent as a solvent can be applied.
It is preferable to carry out the reaction at a temperature in the range of to 150 ° C.
The reaction time is in the range of 5 to 50 hours, and it is preferable to carry out the reaction with stirring.

After the completion of the above reaction, the reaction mixture obtained by the reaction was poured into water, extracted with an organic solvent such as ethyl acetate, chloroform, benzene and the like to separate an organic layer, and then the organic layer was washed with water. After drying, the solvent is distilled off under reduced pressure, and the resulting residue is subjected to purification treatment to obtain the desired azole derivative. The purification treatment can be carried out by subjecting it to recrystallization, silica gel column chromatography or the like.

In addition, the azole derivative represented by the general formula (I) is different from the oxirane derivative (II) due to the presence of isomers of (II-A) and (II-B) in the oxirane derivative which is the starting material compound. The target azo derivative (I) obtained by reacting with 1,2,4-triazole or imidazole has the following two stereoisomers.

Of course, the separation of these two isomers (IA) and (IB) can be carried out, for example, by column chromatography.

Next, the usefulness of the azole derivative (azolylcyclopentanol derivative) represented by the general formula (I) according to the present invention as an active ingredient of an agricultural and horticultural fungicide will be described.

The azole derivative according to the present invention exhibits a controlling effect against a wide range of plant diseases shown below.

Rice blast (fungus name: Pyricularia oryzae, the same applies below), rice sesame blight (Cochliobolus miyabeanus),
White leaf blight of rice (Xanthomonasoryzae), leaf blight of rice (Rhizoctonia solani), small black rot of rice (Helminth)
osporium sigmoideum), an idiotic fungal disease (Gibberell) of rice
afujikuroi), powdery mildew of apple (Podosphaeraleuco
tricha), apple scab (Venturiainaequalis), apple monilia (Moniliniamali), apple leaf spot (Alternaria mali) apple rot (Valsa mal)
i), Pear black spot (Alternaria kikuchiana), Pear powdery mildew (Phyllactinia pyri), Pear scab (Ven)
turia nashicola), powdery mildew of grape (Uncinula ne
cator), grape rust (Phakopsora ampelopsidi)
s), powdery mildew of barley (Erysiphe grminis f.sp.h
ordei), a cloud disease of barley (Rhynchosporium secalis
f.sp.hordei), barley black rust (Puccinia gramin)
is), and barley stripe rust (Puccinia striiformis),
Wheat leaf rust (Puccinia recondita), wheat leaf rot (Septoria tritici), wheat rust (Puccin)
ia striiformis, wheat powdery mildew (Erysiphe gra)
minis f.sp.tritici), powdery mildew of cucumber (Sphaerot)
heca fuliginea), Fusarium oxysp
orum f.sp.niveum), powdery mildew of tomato (Erysipheci
choracearum), tomato rot (Alternariasolan)
i), eggplant powdery mildew (Erysiphe cichoracearum),
Powdery mildew of strawberry (Sephaerotheca humuli), powdery mildew of tobacco (Erysiphe cichoracearum), red scab of tobacco (Alternaria longipes), leaf spot of sugar beet (Cer)
cospora beticola), the potato epidemic (Alternaria)
solani), soybean scab (Septoria glycines), soybean purpura (Cercospora kikuchii), drupe (Monilinia fructicola) of drupe fruit trees, gray mold (Botrytis cinerea), sclerotial disease of crops of various species. (Sclerotini
a sclerotiorum), etc.

The azole derivative according to the present invention has not only a preventive control effect but also a therapeutic effect against some of the above-listed plant diseases.

To apply the compound of the azole derivative represented by the general formula (I) as a fungicide for agricultural and horticultural use, the compound as it is or mixed with a carrier (diluent) is powder, wettable powder, granule, emulsion. It can also be used advantageously as a liquid formulation. Further, it is of course possible to further secure the effect by adding an auxiliary agent such as a spreading agent, an emulsifying agent, a wetting agent, and a fixing agent in addition to the above carrier, if necessary.

By the way, since the present compound contains a 1,2,4-triazole ring or an imidazole ring, it can be used in the form of an inorganic acid salt, an organic acid salt, a metal complex salt or the like.

In addition, since the present compound contains an azolylmethyl group, a 4-chlorobenzyl group and a methyl group at the 1-position and 2-position of the cyclopentane ring, respectively, geometric isomers of cis- and trans-forms and optical isomers, etc. However, the present invention includes all single isomers as well as a mixture of each isomer in any ratio. Therefore, the agricultural and horticultural fungicide according to the present invention contains these stereoisomers. It is to be understood to include those containing the isomers, alone or as a mixture, as the active ingredient.

EXAMPLES AND EFFECTS OF THE INVENTION Hereinafter, specific examples of the azole derivative according to the present invention and a specific method for producing an oxirane derivative as an intermediate and a specific example of an agricultural and horticultural fungicide using the derivative as an active ingredient The effect of the invention will be described.

Example of Process for Producing Azole Derivative Represented by General Formula (I) and Oxirane Intermediate Represented by Formula (II) for Producing the Same: Example 1 c-2- (4-chlorobenzyl) -2,5,5 -Trimethyl-1- (1H-1,2,4-triazol-1-ylmethyl)
Preparation of -r-1-cyclopentanol (compound of No. 1 shown in Table 1) To 3 ml of anhydrous dimethylformamide, 230 mg of sodium hydride (60% oily sodium hydride washed with anhydrous hexane) was added, Then, 390 mg of 1H-1,2,4-triazole was added, and the mixture was stirred at room temperature until foaming stopped. 4- (4-chlorobenzyl) -4,7, was added to the resulting solution.
A solution of 7 g of 7-trimethyl-1-oxaspiro [2.4] heptane (compound of No. 1 shown in Table 2) (1.0 g) in anhydrous dimethylformamide was added, and the mixture was stirred at 120 ° C. for 24 hours.

The obtained reaction solution was allowed to cool, then poured into ice water and extracted with methylene chloride to obtain an organic layer. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Distilled off.

The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate), and recrystallized from n-hexane-ethyl acetate to give 1.06 g of the title compound.

Example 2 c-2- (4-chlorobenzyl) -2,5,5-trimethyl-1- (imidazol-1-ylmethyl) -r-1-cyclopentanol (Compound No. 3 shown in Table 1) 290 mg of sodium hydride (60% oily sodium hydride washed with anhydrous hexane) was added to 3 ml of anhydrous dimethylformamide, and then 1H-imidazole 500 mg
Was added, and the mixture was stirred at room temperature until foaming stopped. To the resulting solution was added 980 mg of 4- (4-chlorobenzyl) -4,7,7-trimethyl-1-oxaspiro [2.4] heptane (compound No. 1 shown in Table 2) of anhydrous dimethylformamide 2
The ml solution was added, and the mixture was stirred at 120 ° C. for 22 hours.

The obtained reaction solution was allowed to cool, then poured into ice water and extracted with methylene chloride to obtain an organic layer. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. Distilled off.

The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate), and recrystallized from n-hexane-ethyl acetate to give 0.87 g of the title compound.

Example 3 4- (4-chlorobenzyl) -4,7,7-trimethyl-1
-Oxaspiro [2.4] heptane (No. 1 shown in Table 2
And an intermediate compound of No. 2) 2- (4-chlorobenzyl) -2,5,5-trimethyl-
6.1 g of 1-methylenecyclopentane (a compound represented by the formula (IV)) was dissolved in 60 ml of chloroform, 8.5 g of m-chloroperbenzoic acid was added, and the mixture was stirred for 5 hours under ice cooling. Next, 4.0 g of calcium hydroxide was added and stirred for 30 minutes at room temperature.

The precipitated solid was separated, and chloroform was distilled off from the liquid chloroform layer under reduced pressure to obtain a colorless oily substance.

The obtained oily substance was purified by subjecting it to silica gel column chromatography (eluent: n-hexane-methylene chloride, 6: 1) to obtain 2.0 g of the title compound No. 1 and 4.0 g of the number 2 compound. It was

Next, the formulation of a fungicide for agricultural and horticultural use containing the azole derivative as an active ingredient and a pathogen control test will be shown.

In the present invention, these compounds are advantageously used as an agricultural / horticultural fungicide in the form of powder, wettable powder, granules, emulsion or liquid, etc., as they are or as a mixture with a carrier (diluent).

If necessary, a spreading agent for the agricultural and horticultural control agent of the present invention,
Of course, it is good to ensure the effect by adding an auxiliary agent such as an emulsifier, a wetting agent, and a fixing agent.

Next, some examples will be shown in order to prove the effectiveness of the compound of the present invention, but the carrier (diluent) and auxiliary agent, the mixing ratio thereof and the active ingredient can be varied within a wide range.

Prescription example: Example 4: Dust Part by weight Compound of the present invention (Compound No. 1) 3 Clay 40 Talc 57 is ground and mixed and used as a dusting powder.

Example 5: Wettable powder Part by weight Compound of the present invention (Compound No. 2) 50 Lignin sulfonate 5 Alkyl sulfonate 3 Diatomaceous earth 42 is ground and mixed to obtain a wettable powder, which is diluted with water and used.

Example 6: Granule parts by weight Compound of the present invention (Compound No. 3) 5 Bentonite 43 Clay 45 Lignin sulfonate 7 is uniformly mixed, further water is added and kneaded, and the mixture is processed into granules by an extrusion granulator and dried. Use as granules.

Example 7: Emulsion parts by weight Compound of the present invention (Compound No. 4) 20 Polyoxyethylene alkyl allyl ether 10 Polyoxyethylene sorbitan monolaurate 3 Xylene 67 is uniformly mixed and dissolved to prepare an emulsion.

Example of pathogen control test: Example 8 Wheat powdery mildew control effect test Second leaf stage seedling wheat (cultivar; Norin No. 64, 16 / pot, 3 pots / treatment area use) cultivated in a clay pot with a diameter of 10 cm In (), the wettable powder form as in Example 5 was diluted and suspended in water to a predetermined concentration and sprayed at a rate of 5 ml per pot. After air-drying the leaves,
A suspension of wheat powdery mildew spores collected from scab was spray-inoculated, kept under high humidity conditions at 20 to 24 ° C for 24 hours, and then left in a greenhouse. 9 to 11 days after the inoculation, the lesion area ratio of wheat powdery mildew was investigated, and the control value was calculated by the following formula.

The results are shown in Table 3.

Example 9 Wheat leaf rust control test A seedling wheat (variety: Norin 64, 16 / pot) seedlings at the time of the second true leaf cultivated in a biscuit pot with a diameter of 10 cm was used for the wettable powder form shown in Example 5. 5 ml /
It was sprayed in the proportion of pots. After air-drying the sprayed leaves, spray-inoculate a suspension of wheat rust disease summer spores collected from scab leaves to 20-23
It was kept under high humidity conditions at ℃ for 24 hours. After that, it was allowed to stand in a glass greenhouse, and 7 to 10 days after the contact, the lesion area ratio of wheat red rust was investigated, and the control value was calculated by the following formula.

The results are shown in Table 4.

Example 10 Cucumber powdery mildew control effect test Cucumber at the time of the second true leaf cultivated in a unglazed pot with a diameter of 10 cm (variety: Sagamihanjiro, 1 / pot, 3 pots / treatment group used)
The water-dispersible powder as in Example 5 was diluted and suspended in water to a predetermined concentration and sprayed in an amount of 5 ml per pot. After air-drying the sprayed leaves, spores were sprinkled on the diseased leaves with a brush to inoculate them, and the disease was caused in a glass greenhouse. On the 9th to 11th day after contact, the lesion area ratio of cucumber powdery mildew was investigated, and the control value was calculated by the following formula.

Table 5 shows the results.

Example 11 Antibacterial Test Against Various Pathogenic Bacteria This example shows the results of testing the antibacterial activity of the compound of the azole derivative according to the present invention against various plant pathogenic bacteria.

Test method: The compound of the present invention was dissolved in dimethyl sulfoxide to a predetermined concentration, and 0.6 ml thereof was added to a PSA medium at about 60 ° C.
60 ml was mixed well in a 100 ml Erlenmeyer flask and poured into a petri dish to solidify. On the other hand, the test bacteria previously cultivated on a plate medium were removed with a cork borer having a diameter of 4 mm and contacted with the above drug-containing plate medium. After inoculation, each strain was cultured at an appropriate growth temperature for 1 to 3 days, the growth of the bacteria was measured by the diameter of the bacteria, and the rate of inhibition of hyphal elongation was determined according to the following formula in comparison with the growth of the bacteria in the drug-free group. .

R = (dc-dt) 100 / dc In the formula, R = sterile thread elongation inhibition rate (%) dc = untreated plate diameter on bacterial plate dt = drug treated plate diameter on bacterial plate.

The results are shown in Table 6 according to the following criteria.

Growth inhibition 5 Hyphal elongation inhibition rate of 100% to 90% or more 4 Hyphal elongation inhibition rate of less than 90% to 70% or more 3 Hyphal elongation inhibition rate of less than 70% to 40% or more 2 Hyphal elongation Inhibition rate of less than 40% to 20% or more 1. Hyphal elongation inhibition rate of less than 20%

[Brief description of the drawings]

1 to 4 of the accompanying drawings are infrared absorption spectra of compound numbers 1 to 4 of Table 1 according to the present invention, and FIGS. 5 and 6 are infrared absorption spectra of compound numbers 1 and 2 of Table 2 respectively. Indicates.

Claims (3)

(57) [Claims] 1. The compound of the general formula (I) (In the formula, A represents a nitrogen atom or CH). 2. Formula (II) And an oxirane derivative represented by the following general formula (III) (Wherein, M represents a hydrogen atom or an alkali metal, and A represents a nitrogen atom or CH), 1,2,4-triazole or imidazole represented by the general formula (I) (In the formula, A represents a nitrogen atom or CH). 3. A compound of the general formula (I) (In the formula, A represents a nitrogen atom or CH) A fungicide for agricultural and horticultural use containing an azole derivative represented by the formula as an active ingredient.