JPS6341476A - Novel tricyclic azole derivative, production thereof and agricultural and horticultural fungicide containing said derivative as active ingredient - Google Patents

Abstract

NEW MATERIAL:A tricyclic azole derivative shown by formula I (X is halogen; A is N or CH). EXAMPLE:8-Fluoro-1,2,3,3a,9,9a-hexahydro-3a-( 1H-1,2,4-triazol-1-ylmethyl )cyclo penta(b)(1)-benzopyrane. USE:An active ingredient for agricultural and horticultural fungicide showing improved controlling effects on brown rust and powdery mildew of wheat, blast, helminthosporium leaf spot and sheath blight of rice plant, powdery mildew and scab of apple, powdery mildew of cucumber, gray mold damaging various crops, etc. PREPARATION:An oxirane derivative shown by formula II is reacted with a 1,2,4-triazole or imidazole shown by formula III (M is H or alkali metal) in a diluent such as anhydrous dimethylformamide, etc., in the presence of a base such as NaH, etc., at 0-100 deg.C for 1-3hr to give a compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a tri-attribute azole derivative useful as an active ingredient for controlling plant diseases caused by various diseased seedlings, a method for producing the same, and a compound containing the derivative as an active ingredient. Regarding agricultural and horticultural fungicides.

PRIOR ART As biologically active compounds in which triazole or imidazole is bonded to a bicyclic compound, compounds represented by the following format are known (Japanese Unexamined Patent Application Publication No. 1983-1999).
126=Refer to Publication No. 179).

N.
．． 1 or 2) also represents a bridging group -CIl=CII- or -〇-, -3-', -NH- or -C~; X represents -N- or =C11-; Y and Z may be the same or different, and each represents halogen, alkyl, alkoxy, haloalkoxy, haloalkyl, or nitro.

Represents phenyl or phenoxy group; m and p are 0.1
．． 2 or 3].

■ Problems to be Solved The present inventors synthesized a number of azole derivatives for the purpose of developing agricultural and horticultural fungicides that exhibit excellent control effects against a wide range of plant diseases, and examined their practicality. As a result, it was discovered that a novel tri-attribute azole derivative can be effectively used as an active ingredient of the above-mentioned fungicide, and the present invention was completed. Therefore, the present invention provides novel pentacyclic azole derivatives useful as active ingredients in agricultural and horticultural fungicides, methods for producing the same, and excellent control effects against a wide range of plant diseases containing the azole derivatives as active ingredients. Our goal is to provide fungicides for agriculture and horticulture.

The present invention will be explained in detail below.

Structure of the Invention The features of the structure of the present invention are as follows: (1) A three-attribute azole derivative represented by the following format (1) (wherein, X represents a halogen atom and A represents a nitrogen atom or CH); A method for producing a trivalent azole derivative represented by the above-mentioned form (1) by reacting an oxirane derivative represented by the form (I[) with 1,2,4-1-lyazole or imidazole (wherein, X (represents a halogen), and (1) - An agricultural and horticultural fungicide containing a three-attribute azole derivative represented by the above-mentioned format (1) as an active ingredient.

The tri-attribute azole derivative according to the present invention is a novel compound that has not been published in any literature, and examples thereof are shown in Table 1, but the invention is not limited thereto.

Table 1 (Note) - The position of X in type (I) is indicated as follows.

In addition, the H'-NMR spectrum of each compound illustrated in Table 1 is shown in the attached figure.

The challenge? The pentacyclic azole derivative represented by the above general formula (1) according to the present invention is produced by the following method.

When the oxirane derivative represented by the above-format (n) is reacted with the following formula (1,2,4-) riazole or imidazole represented by the following formula (I [[)] in the presence of a diluent, the following - The desired pentacyclic azole derivative is obtained through an intermediate consisting of a compound represented by the formula (TV).

(n) (I[I) (■)(
In each of the above formulas, X and A have the same meanings as above, and the gate represents a hydrogen atom or an alkali metal).

That is, by reacting the compound represented by the above formula (IV) with a base in the presence of a diluent, or by prolonging the reaction time without isolating the compound from the reaction system, -m formula ( A pentacyclic azole derivative represented by r) can be obtained.

In addition, the oxirane derivative having the general formula (n) used as a starting material here can be prepared by combining a ketone represented by the following formula (V) with, for example, dimethyloxosulfonium methylide or dimethylsulfonium methylide in the presence of a diluent. Obtained by reacting with

(wherein, , “Organic Synthesis
) 45.7 (1965) and Journal of the Chemical Society (J, Chem, Soc,) +
(1950), 325, and can also be obtained from the enamine of cyclopentanone and the corresponding substituted benzyl halide [Journal of Pharmaceutical Sciences
J. Pharm. 5ci), 68.1501 (1979
)reference〕.

Diluents used in the above production method according to the present invention include hydrocarbons such as benzene, toluene, xylene, and hexane; halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride; alcohols such as methanol and ethanol; Ethers such as didiethyl ether, diisopropyl ether, and tetrahydrofuran; other examples include acetonitrile, acetone, dimethylformamide, and dimethyl sulfoxide.

In addition, in the production method according to the present invention, as described above, in order to promote the reaction of the compound of formula (IV) produced as an intermediate by the reaction to the target pentacyclic azole derivative,
The reaction may be carried out in the presence of a base in addition to the above diluent. Bases used here include alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; sodium methylate, sodium ethylate, potassium tert-butylade, etc. alkali metal alcolade,
Examples include alkali metal hydrides such as sodium hydride and potassium hydride, as well as triethylamine and pyridine.

In order to carry out the production method according to the present invention, for example, in a solution of the azole represented by the above-mentioned formula (I[l) in the above-mentioned diluent, if necessary, in the presence of the above-mentioned base, The oxirane represented by the above-format (II) is added in an amount of 0.5 to 1.
It is preferable to add 0 equivalent, or conversely, add the alkali metal salt of the azole to a solution of the oxirane in a diluent and react.

The reaction temperature at this time may be any temperature from the freezing point to the boiling point of the diluent as a solvent, but in practice it is preferable to carry out the reaction at a temperature in the range of 0 to 100°C. Moreover, the reaction time is in the range of 1 to 3 hours, and it is preferable to carry out the reaction while stirring.

After the completion of the above reaction, the reaction mixture obtained by the reaction was cooled, and then ethyl acetate, chloroform,
Is there benzene, etc.? The target compound is obtained by extracting with 8 reagents to separate the organic layer, then washing the organic layer with water and drying, distilling off the solvent under reduced pressure, and purifying the resulting residue. . Note that the purification treatment can be performed by subjecting to recrystallization, silica gel column chromatography, or the like.

Next, the usefulness of the pentacyclic azole derivative having the above-mentioned format (1) as an active ingredient of the agricultural and horticultural fungicide according to the present invention will be explained.

The above-mentioned pentacyclic azole derivatives exhibit excellent control effects against a wide range of plant diseases shown below.

Rice blast disease (Pyricularia oryza)
e) Sesame leaf blight of rice (Cochliobolus
mlyabeanus) s Rice bacterial leaf blight (Xant
homonas oryzae), rice sheath blight (R
hizoctonia 5olani), Hel-minthosporium sigm of rice
oideum), Gi-bberel disease of rice
la fujikuroi), powdery mildew of apples (
P〇-dosphala 1eucotricha)
, apple scab (Vcnt-uria 1naequ)
alis), apple molinia disease (Sclero-ti
nia mali), apple leaf fall disease (Altern
aria mali), apple rot disease (Valsa
mali), pear black spot (A!-ternaria)
kikuchiana), pear powdery mildew (Phyl
-1 actinia pyri), pear red star disease (Gy
mnosporangium haraeonum), pear scab (Venturia nashicola)
, powdery mildew of grapes (Unccinula neca
tor), grape rust (Phakospora a
mpelopsidis), powdery mildew of barley (E.
rysiphe graminis r,sp hor
de+), barley cloud disease (Rhynchospor
ium 5ecalis), barley black rust (Pu
ccinia graminis), barley yellow rust (Puccinia triformis), wheat rust (Puccinia recondita)
, wheat leaf blight (Septoria trtiti)
ci), wheat yellow rust (Pucci-nia tr
itomis), wheat powdery mildew (Erysip
hegraminis l sp, tritici)
, powdery mildew of cucurbits (Sphaerotheca
fuliginea), watermelon vine splitting disease (Fusar)
ium oxsporum) ,) Powdery mildew (
Er-ysiphe cichoracearum)
,) Alte-rnaria 5ola
ni), powdery mildew of eggplant (Erys iphecic)
horacearum), strawberry powdery mildew (Sep.
haero-theca humuli), tobacco powdery mildew (Erysiphecishoracear)
um), Tobacco Akaboshi (Alternarialon)
gipes), sugar beet brown spot (Csrcospo
ra 1)et-4cola), summer blight of potatoes (
Alternaria 5ola-ni), Septoria glycines, Cercospora kikuchi
i) Sclerotinia of stone fruit trees
cinerea), botrytis blight (B
otrytis cinerea), Scle
It has activity against rotinia sclerotirum and others.

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

In order to apply the compound of the pentacyclic azole derivative shown in form (1) above as a fungicide for horticulture, the compound can be used as it is or mixed with a carrier (diluent) to form a powder, wettable powder, or granule. It can be advantageously used in the form of tablets, emulsions, liquids, and the like. Furthermore, it goes without saying that the effectiveness can be ensured by adding auxiliary agents such as spreading agents, emulsifiers, wetting agents, and fixing agents in addition to the above-mentioned carriers, if necessary. , due to the fact that
Since the present compound contains a 1,2,4-) lyazole ring or an imidazole ring, it can also be used in the form of an inorganic acid salt, an organic acid salt, or a metal complex salt.

In addition, this compound has asymmetric carbon atoms at the 3a and 9a positions of the bicyclic skeleton, so it may exist in stereoisomers such as cis and trans geometric isomers and optical isomers.
The present invention includes all of these individual isomers as well as mixtures of each isomer in any ratio.

Therefore, it should be understood that the horticultural fungicides according to the present invention include those containing these isomers alone or in mixtures as active ingredients.

Leaving At! i (J!, != j1) Below, we will show a specific method for producing the pentacyclic azole derivative according to the present invention and a specific example of an agricultural and horticultural fungicide using the derivative as an active ingredient, and explain its effects. do.

Example 1 This example shows a production example of a pentacyclic azole derivative represented by the -FIQ formula (1) using the compound No. 5 in Table 1 above.

Add 324 mg of sodium hydride (60% oily sodium hydride washed with anhydrous benzene) to 10 ml of anhydrous dimethylformamide under a helium atmosphere while stirring. Then, IH-1,2,4-) Riazole 930 rI@ was added thereto, and the mixture was stirred at room temperature until foaming stopped. 4-(2,6-cyfluorohendyl)-1-oxaspiro(2,4)hebutane 2,
A solution of 5 g of S in anhydrous dimethylformamide was added dropwise, and the mixture was stirred at 80° C. for 3 hours.

The resulting reaction mixture was allowed to cool, then poured into ice water, extracted with ethyl acetate to obtain an organic layer, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. did.

The obtained residue was purified by silica gel column chromatography to obtain 0.6 g of the title compound.

The results of measuring the physical properties of this compound are as follows. The NMR spectra were measured using TMS as an internal basis and are indicated by the symbols below.

S knee multiple line II: multiple line ■IRCNeat method): Vmax 2950.1
580.1460.1260゜1050, 770cm-
' ■ NMR (C[lCl s , ppm): δ
1.18-2.88 (m, 911).

4.32 (s, 2) 1) 6.50-7.40 (m, 311), 7.97 (s
, 1tl), 8.08 (s, IH) Next, formulation examples of the agricultural and horticultural fungicide according to the present invention (Examples 2 to 5) and plant disease control effects (Examples 6 to 7) will be shown. .

Example 2: Parts by weight of powder Compound of the present invention (Compound No. 1 in Table 1) 3 Clay
40 talc
57 was ground and mixed and used as powder.

Example 3: Parts by weight of wettable powder Compound of the present invention (compound number 2 in Table 1) 50 Lignin sulfonate 5 Alkyl sulfonate 3 Silicon 1; Soil
4゜Culture and mix to make a wettable powder and dilute with water for use.

Compound of the present invention (compound number 3 in Table 1) 5 hentonite
43 clay
45 lignin sulfonate
7 are uniformly mixed, water is added and kneaded, and the mixture is processed and dried into granules using an extrusion type granulator to obtain granules.

Ru.

The compounds of the present invention (compound number 1 in Table 1): 30 polyoquinoenalene alkyl allyl ether 10 polyoquinoethylene sorbitan monolaurate 3 quinolene 57 are uniformly mixed and dissolved to form an emulsion.

Example 6 The water shown in Example 3 was applied to seedling wheat (variety: Norin No. 64, 16 trees/pot) at the second leaf stage grown using the bisque firing method and having a diameter of 10 cm. The mixture was diluted and suspended in water to a predetermined concentration, and applied to 11 pots at a rate of 5 ml/pot. After spraying and air-drying the leaves, the leaves were spray-inoculated with a suspension of summer spores of the wheat rust fungus collected from the rotten leaves and kept at 20-23°C under high humidity conditions for 24 hours.

After that, it was left in a gas greenhouse, and 7 to 10 days after inoculation, the disease severity was investigated on 10 plants according to the following investigation criteria.
The control value was calculated from the average disease severity per leaf using the following formula.

(Survey criteria) Disease severity: 0 No symptoms: 0.5 Lesion area rate: less than 10%l Lesion area rate: 10% or more but less than 20%2: Lesion area rate: 20%
More than 10% 3 Lesion area rate 40% or more 60
4. Lesion area ratio of 60% or more and less than 80%. 5. Lesion area ratio of 80% or more.

Example 7 Powdery Mildew Disease 1 liter of seedlings of wheat (crystal cuttings; Kirin No. 64, 16 trees/pot, 3 pots/ A wettable powder as in Example 3 was diluted and suspended in water at a predetermined 4 degrees, and 5 ml per pot was sprayed on the treated area. Summer spores of wheat powdery mildew collected from diseased leaves after spraying and air-drying the leaves! l!
Spray inoculation with rA solution and incubate at 20-24°C under high humidity conditions for 2 hours.
It was kept for 4 hours and then left in a greenhouse. 9-11 after inoculation
On the following day, investigate the disease severity according to the following investigation criteria, and calculate the control value using the formula below.

(Survey criteria) Disease severity: 0 No symptoms: 0.5 Lesion area rate: less than 10% 1: Lesion area rate: 10% or more but less than 20% 2: Lesion area rate: 20%
40% or more and less than 3 Lesion area ratio 40% or more 60
4 Those with a lesion area ratio of 60% or more but less than 80% 5 Those with a lesion area ratio of 80% or more The disease severity results for the untreated section are shown in Table 3.

Table 3 Example 8 Antibacterial activity test against various pathogenic bacteria This example shows the results of testing the antibacterial activity of the pentacyclic azole derivative compound according to the present invention against various plant pathogenic bacteria.

Test method: The compound of the present invention was added to Dime-t to a predetermined concentration.
Dissolve in hyl 5ulfoxide and add 0.6ml of it.
Then, at around 60'C, add 60ml of PAS medium to 100ml.
The mixture was mixed well in an Erlenmeyer flask, poured into a petri dish, and solidified. On the other hand, a test bacterium cultured in advance on a plate medium was punched out using a cork polar plate with a diameter of 4 squares, and inoculated onto the above-mentioned drug-containing plate medium.
After culturing for ~3 days, the growth of the fungi was measured by the fungal diameter, and compared with the growth of the fungi in the drug-free plot, the inhibition rate of hyphal elongation was determined according to the following formula.

R=(dc-dmu) 100/dc where R=
Inhibition rate of hyphal elongation (%) dc - Diameter of untreated fungus on a plate dt = Diameter of fungus on a drug-treated plate.

The results were evaluated in five stages according to the following criteria and are shown in Table 4.

Growth inhibition degree 5: 100-90% hyphal growth inhibition 4: 89-709 < hyphal growth inhibition 3: 69-40% hyphal growth inhibition 2: 39-20% hyphal growth inhibition Thing 1 Hyphal elongation inhibition rate is 19%
Figures 1 to 6 attached below are the 11'-:JMR absorption spectra of the compounds numbered 1 to 6 shown in Table 1 in the main text. It is.

Claims (1)

[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a halogen atom and A represents a nitrogen atom or CH) Cyclic azole derivative. 2. General formula (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) The oxirane derivative represented by (in the formula, X represents a halogen) and the following general formula (III) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (III) (In the formula, M represents a hydrogen atom or an alkali metal, and A represents a nitrogen atom or CH) is reacted with 1,2,4-triazole or imidazole. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a halogen atom and A represents a nitrogen atom or CH) A method for producing a tricyclic azole derivative . 3. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a halogen atom and A represents a nitrogen atom or CH). An agricultural and horticultural fungicide that contains it as an ingredient.