WO2023033180A1

WO2023033180A1 - R-enantiomer of azole derivative, agricultural or horticultural chemical agent, and industrial material protective agent

Info

Publication number: WO2023033180A1
Application number: PCT/JP2022/033347
Authority: WO
Inventors: 隆介萩原; 竜行越山
Original assignee: 株式会社クレハ
Priority date: 2021-09-06
Filing date: 2022-09-06
Publication date: 2023-03-09
Also published as: AR126989A1

Abstract

The present invention provides a plant disease control agent that has low toxicity to human and animals and excellent handling safety, and that exhibits an excellent controlling effect on a wide range of plant diseases and exhibits a high antimicrobial activity against plant disease-causing microbes. The present invention pertains to an R-enantiomer or a mixture of a S-enantiomer and the R-enantiomer of a compound represented by general formula (I), or an agriculturally or industrially acceptable salt thereof.

Description

R-enantiomer of azole derivative, agricultural and horticultural agent and industrial material protection agent

The present invention relates to the R-enantiomer of an azole derivative or a mixture of the R-enantiomer and the S-enantiomer. In addition, an agricultural and horticultural fungicide and an industrial material protective agent containing the azole derivative and an active ingredient other than the azole derivative as active ingredients, and a plant disease control agent containing the azole derivative or the agricultural and horticultural fungicide as an active ingredient. and a plant disease control method using the same, and a plant disease control product containing a plurality of active ingredients separately.

Conventionally, there has been a demand for agricultural and horticultural agents that have low toxicity to humans and animals, are excellent in handling safety, and exhibit high control effects against a wide range of plant diseases. Azole-based fungicides are known as agricultural and horticultural agents that exhibit high control effects.

PCT/JP2021/008690

There is a demand for a plant disease control agent that exhibits low toxicity to humans and animals, excellent handling safety, excellent control effect against a wide range of plant diseases, and high antibacterial properties against plant pathogens.

Accordingly, the present invention has been made in view of the above problems, and its object is to provide a compound that meets the above demands.

As a result of intensive studies by the present inventors in order to solve the above problems, the R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative represented by the following general formula (I) exhibits excellent activity. The present inventors have found that the present invention has been completed.

The R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative according to one aspect of the present invention is the R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the compound represented by the following general formula (I): A mixture, or an agriculturally or industrially acceptable salt thereof:

[in the formula (I),
* represents a chiral center;
R ¹ and R ² are each independently hydrogen, a C ₁ -C ₆ -alkyl group, a C ₃ -C ₈ -cycloalkyl group or a C ₃ -C ₈ -cycloalkyl- _{C 1} -C ₄ -alkyl group; ;
R ¹ and R ² may be combined to form a ring;
Z is a phenyl group or a 5- or 6-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from O, N and S;
R ³ is halogen, hydroxy, amino, nitrile, nitro, pentafluorosulfanyl, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy or a C ₁ -C ₄ -haloalkoxy group;
R ³ is bonded to n arbitrary substitution positions of Z;
n is 0, 1, 2, 3, 4 or 5 when at least one of R ¹ and R ² is not hydrogen, n is 1, 2, 3 when both R ¹ and R ² are hydrogen , 4 or 5;
m is 1 or 2; ].

The R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative according to one aspect of the present invention has an excellent bactericidal action against many fungi that cause plant diseases. Therefore, a drug containing as an active ingredient the R-enantiomer of the azole derivative of the present invention or a mixture of the R-enantiomer and the S-enantiomer exhibits a high control effect against a wide range of plant diseases.

FIG. 2 is an ORTEP diagram of the R-enantiomer of azole derivative (I-7) by X-ray crystallography.

A preferred embodiment for carrying out the present invention will be described below. It should be noted that the embodiments described below are examples of representative embodiments of the present invention, and the scope of the present invention should not be construed narrowly.

[1. R-enantiomer of azole derivative or mixture of R-enantiomer and S-enantiomer]
The R-enantiomer of the azole derivative of this embodiment or the mixture of the R-enantiomer and the S-enantiomer is the R-enantiomer or R It is a mixture of the -enantiomer and the S-enantiomer. Further, in the following description, the mixture of the R-enantiomer and S-enantiomer of the azole derivative (I) of this embodiment may be simply referred to as the mixed enantiomer of the azole derivative (I).

In general formula (I), * represents a chiral center.

Since the azole derivative (I) of this embodiment contains a carbon atom serving as a chiral center, it can exist in the form of an optically pure enantiomer or a mixture of the R-enantiomer and the S-enantiomer (mixed enantiomers). is. Mixed enantiomers may contain both the R-enantiomer and the S-enantiomer. The mixing ratio of the R-enantiomer and the S-enantiomer can be appropriately adjusted so that the desired activity can be exhibited. The mixed enantiomers are preferably racemic (ie, the molar ratio of the R-enantiomer to the S-enantiomer in the mixed enantiomers is 1:1) or an R-enantiomer-rich mixture. By R-enantiomer rich is meant that the amount of the R-enantiomer in the mixed enantiomers is greater than the S-enantiomer. For example, when the content of the S-enantiomer in the mixed enantiomer is 1, the content ratio (molar ratio) of the R-enantiomer is greater than 1, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more. , 7 or more, 8 or more, 9 or more, or 10 or more.

R ¹ and R ² are each independently hydrogen, a C ₁ -C ₆ -alkyl group, a C ₃ -C ₈ -cycloalkyl group or a C ₃ -C ₈ -cycloalkyl- _{C 1} -C ₄ -alkyl group .

C ₁ -C ₆ -Alkyl radicals are straight-chain or branched alkyl radicals having 1 to 6 carbon atoms. Linear or branched alkyl groups having 1 to 6 carbon atoms are, for example, methyl group, ethyl group, 1-methylethyl group, 1,1-dimethylethyl group, propyl group and 1-methylpropyl group. , 2-methylpropyl group, 1,1-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group, butyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 3,3 -dimethylbutyl group, 2,2-dimethylbutyl group, 1,1-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, pentyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl and 4-methylpentyl groups.

C ₃ -C ₈ -Cycloalkyl groups are cyclic alkyl groups having 3 to 8 carbon atoms and include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl groups. .

C ₃ -C ₈ -Cycloalkyl-C ₁ -C ₄ -Alkyl radicals are cyclic cycloalkyl radicals having 3 to 8 carbon atoms to linear or branched alkyl radicals having 1 to 4 carbon atoms. Indicates that they are bound. For example, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopropylethyl group, 1-cyclopropylethyl group, 2-cyclohexylethyl group, 3-cyclopropylpropyl group, 2-cyclo Propylpropyl and 4-cyclopropylbutyl groups are included.

R ¹ and R ² may be bonded together to form a ring together with the carbon atom to which R ¹ and R ² are bonded.

Z is a phenyl group or a 5- or 6-membered aromatic heterocyclic ring containing 1, 2, 3 or 4 heteroatoms. Here heteroatoms are atoms selected from O, N and S. When the heteroaromatic ring contains multiple heteroatoms, the multiple heteroatoms may be the same atoms or different atoms. Z is preferably a phenyl group or a 5- or 6-membered aromatic heterocyclic ring containing 1 to 3 heteroatoms selected from N and S, more preferably a phenyl group.

Examples of 5- or 6-membered aromatic heterocyclic groups include furyl, pyrazolyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, and isothiazolyl. oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl and triazinyl groups.

n R ³ are bound to Z at arbitrary positions. where n is 0, 1, 2, 3, 4 or 5. R ³ is halogen, hydroxy, amino, nitrile, nitro, pentafluorosulfanyl, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy or It is a C ₁ -C ₄ -haloalkoxy group. When n is 2 or more, ^R3 may be the same or different.

C ₁ -C ₄ -Alkyl radicals are straight-chain or branched alkyl radicals _having 1 to ₄ carbon atoms; mentioned.

A C ₁ -C ₄ -haloalkyl group is a group in which one or more halogen atoms are substituted at the substitutable positions of the aforementioned C ₁ -C ₄ -alkyl groups. When two or more halogen groups are substituted, the halogen groups may be the same or different. Halogen groups include chlorine, bromine, iodine or fluorine groups. C ₁ -C ₄ -Haloalkyl groups include, for example, chloromethyl, 2-chloroethyl, 2,3-dichloropropyl, bromomethyl, chlorodifluoromethyl, trifluoromethyl and 3,3,3-tri A fluoropropyl group is mentioned.

C ₁ -C ₄ -Alkoxy is a straight-chain or branched alkoxy group having 1 to 4 carbon atoms, for example methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy and 1,1-dimethylethoxy groups are included.

A C ₁ -C ₄ -haloalkoxy group is a group in which the aforementioned C ₁ -C ₄ -alkoxy group is substituted with one or more halogen groups at substitutable positions. When two or more halogen groups are substituted, the halogen groups may be the same or different.

The bonding position of R ³ is not limited, but is preferably 2-, 3- or 4-position relative to the ether bond of general formula (I), more preferably 4-position.

n is 0, 1, 2, 3, 4 or 5 when at least one of R ¹ and R ² is not hydrogen, n is 1, 2, 3 when both R ¹ and R ² are hydrogen , 4 or 5.

m is 1 or 2. That is, when m=1, the R-enantiomer or mixed enantiomer of the azole derivative (I) has an indane skeleton, and when m=2, it has a tetralin skeleton. Preferably m=1.

In a preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I), R ¹ and R ² are each independently hydrogen, a C ₁ -C ₆ -alkyl group, a C ₃ -C ₈ -cycloalkyl group, C ₃ -C ₈ -cycloalkyl-C ₁ -C ₄ -alkyl groups or R-enantiomers or mixtures of azole derivatives (I) in which R ¹ and R ² are joined to form a cycloalkyl group enantiomers. A further preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I) includes the R-enantiomer or mixed enantiomer of azole derivative (I) in which m is 1. A further preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I) includes the R-enantiomer or mixed enantiomer of azole derivative (I) wherein Z is a phenyl group.

In a further preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I), R ¹ and R ² are each independently hydrogen or a C ₁ -C ₆ -alkyl group, or R ¹ and R ² are combined to form a cycloalkyl group, the R-enantiomer or mixed enantiomers of the azole derivative (I). In a further preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I), R ¹ and R ² are each independently hydrogen or a C ₁ -C ₆ -alkyl group, or R ¹ and R ² are combined to form a cycloalkyl group, and the R-enantiomer or mixed enantiomers of the azole derivative (I) in which m is 1 can be mentioned. In a further preferred embodiment of the R-enantiomer or mixed enantiomer of azole derivative (I), R ¹ and R ² are each independently hydrogen or a C ₁ -C ₆ -alkyl group, or R ¹ and R ² is bonded to form a cycloalkyl group, m is 1, and R ³ is a halogen, a C ₁ -C ₄ -haloalkyl group or a C ₁ -C ₄ -haloalkoxy group. R-enantiomers or mixed enantiomers are included.

As a particularly preferred embodiment of the R-enantiomer or mixed enantiomer of the azole derivative (I), the carbon atom marked with * is chiral from the viewpoint of superior antibacterial activity against fungi that cause plant disease compared to the racemate. Centered R-enantiomers are included.

Particularly preferred azole derivatives (I) are listed in Table 1 below. R ¹ , R ² and m in Table 1 below correspond to R ¹ , R ² and m in Formula (I) above, respectively, and Z—(R ³ ) _n in Table 1 is Z in Formula (I) above. and (R ³ ) _n . The azole derivatives in Table 1 below may be R-enantiomers or mixtures of R-enantiomers and S-enantiomers.

The compound represented by number I-17 forms a cyclopropane ring with R ¹ , R ² and the carbon atoms to which R ¹ and R ² are bonded.

Agriculturally or industrially acceptable salts of the R-enantiomer or mixed enantiomers of the azole derivative (I) are, in particular, those of cations and anions that do not adversely affect the action of the R-enantiomer or mixed enantiomers of the azole derivative (I). It includes salts or acid addition salts of these acids. Suitable cations are in particular ions of alkali metals (preferably sodium and potassium), alkaline earth metals (preferably calcium, magnesium and barium), transition metals (preferably manganese, copper, zinc and iron). Suitable cations _are also ammonium ions ( _preferably diisopropylammonium , tetramethylammonium, tetrabutylammonium, trimethylbenzylammonium), and also phosphonium ions, sulfonium ions (preferably tri(C ₁ -C ₄ -alkyl)sulfonium) and sulfoxonium ions (preferably tri(C ₁ —C ₄ -alkyl)sulfoxonium).

Anions of useful acid addition salts are mainly chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, bicarbonate ions, carbonate, sulfonate, aromatic sulfonate, hexafluorosilicate, hexafluorophosphate, benzoate and anions of C ₁ -C ₄ -alkanoic acids. Anions of useful acid addition salts are preferably formate, acetate, propionate and butyrate. These are obtained by reacting the R-enantiomer or mixed enantiomers of the azole derivative (I) with an acid of the corresponding anion (preferably hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid or p-toluenesulfonic acid). can be formed.

Some examples of agriculturally or industrially acceptable salts of azole derivative (I) are shown in Table 2 below. R ¹ , R ² and m in Table 2 below correspond to R ¹ , R ² and m in Formula (I) above, respectively, and Z—(R ³ ) _n in Table 2 is Z in Formula (I) above. and (R ³ ) _n . The agriculturally or industrially acceptable salt of the azole derivative (I) in Table 2 below may also be an agriculturally or industrially acceptable salt of the R-enantiomer. It can also be an agriculturally or industrially acceptable salt of a mixture of

[2. Method for producing an azole derivative]
Azole derivative (I) can be produced by any of the following methods. Note that the azole derivative produced by each production method described below is a racemate.

R ¹ , R ² , R ³ , Z, m and n in the scheme below correspond to R ¹ , R ² , R ³ , Z, m and n in the general formula (I) above, respectively. A compound represented by formula (x) (where x is a number) is simply referred to as compound (x). In the reaction of the step using a known reaction mechanism, reagents, bases, solvents, etc., and various conditions such as temperature to be subjected to the reaction are within the range that can be appropriately set by those skilled in the art based on common general technical knowledge. is.

(1) Azole derivative production method 1
When R ¹ and R ² are the same group other than hydrogen, the azole derivative (I) can be produced from compounds obtained by known techniques according to Synthesis Scheme 1 below.

(Step 1) Compound (2) is obtained by alkylating the ketone α-position of compound (1). Alkylation may be carried out by a reaction using an alkylating reagent such as alkyl iodide. One example is a method of using an alkyl iodide as an alkylating reagent, sodium hydride as a base, and N,N-dimethylformamide as a solvent, and carrying out the reaction at room temperature, but is not limited thereto.

(Step 2) Compound (3) is obtained by replacing halogen X of compound (2) with a phenol substituted or unsubstituted with one or more R ³ or an aromatic heterocycle having a hydroxy group. Substitution with an aromatic heterocyclic ring having a phenol or hydroxy group may react differently depending on the type of X. For example, when X is F or Cl, substitution in S _N Ar reactions is possible. One example is a method in which X is F, potassium carbonate is used as a base, N,N-dimethylformamide is used as a solvent, and the reaction is carried out at 120° C., but the method is not limited thereto. Alternatively, when X is Cl, Br or I, substitution is possible in a copper-catalyzed Ullmann condensation reaction. The Ullmann condensation reaction is not limited to a reaction at a high temperature (eg, 195° C.), and a ligand may be used and the reaction may be performed under a relatively low temperature (eg, 135° C.) heating condition. One example is a method in which X is Br, copper (I) iodide is used as a copper catalyst, cesium carbonate is used as a base, and N-methylpyrrolidone is used as a solvent, and the reaction is carried out at 195° C. in a microwave reactor. is not limited to As another example, copper (I) iodide as a copper catalyst, tris(2,4-pentanedionato)iron (III) as a ligand, potassium carbonate as a base, and N,N-dimethyl as a solvent are added. For example, formamide is used and the reaction is performed under heating conditions of 135° C. in an oil bath.

(Step 3) Compound (3) is converted to oxirane by Corey-Chaykovsky reaction, followed by azole conversion to obtain azole derivative (I). Oxiration and azole formation may be carried out stepwise as separate reactions, but in the present embodiment they are carried out in one pot. By carrying out the oxiration and azole-forming reactions in one pot, the number of steps can be reduced. When the reaction is carried out in one pot, the target azole derivative (I) is obtained by reacting compound (3) in the presence of 1,2,4-triazole or its alkali metal salt and sulfur ylide in a solvent. Specifically, compound (3) and 1,2,4-triazole or an alkali metal salt thereof are mixed in a solvent. Thereafter, by intermittently adding an ylide reagent and a base, the intermediate oxirane produced in the reaction system is sequentially azoleized to obtain the desired azole derivative (I).

Examples of solvents include polar solvents having an amide bond such as N-methylpyrrolidone, N,N-dimethylacetamide and N,N-dimethylformamide, mixed solvents of the polar solvents and alcohol, or dimethylsulfoxide. Moreover, tert-butanol can be mentioned as the alcohol in the mixed solvent.

Examples of sulfur ylides include sulfonium methylides such as dimethylsulfonium methylide and sulfoxonium methylides such as dimethylsulfoxonium methylide. The sulfonium methylides or sulfoxonium methylides used are sulfonium salts (e.g., trimethylsulfonium iodide and trimethylsulfonium bromide) or sulfoxonium salts (e.g., trimethylsulfoxonium iodide and trimethylsulfoxonium iodide) in solvents. It can be produced by reacting a ylide reagent such as nium bromide (TMSOB) with a base. Examples of bases that can be used include metal hydrides such as sodium hydride, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide. Alkali metal salts of 1,2,4-triazoles may also be used.

As an example of a reaction in which the oxiration and azole formation reactions are carried out in one pot, compound (3) and 1,2,4-triazole sodium salt are mixed in N-methylpyrrolidone at 80° C., and A method in which TMSOB and sodium tert-butoxide as a base are added in portions may be mentioned, but is not limited thereto.

On the other hand, as an example of a reaction method in which oxiration and azole formation are performed stepwise, in the oxiration, trimethylsulfonium iodide (TMSI) is used as the ylide reagent, sodium hydride as the base, and dimethylsulfoxide as the solvent. A method of reacting with Further, in the subsequent azolization, a method of reacting at 80° C. using 1,2,4-triazole, diazabicycloundecene (DBU) as a base, and dimethylsulfoxide as a solvent can be mentioned.

(1′) Method 1′ for producing an azole derivative
When X is Cl, I or Br, instead of steps 2 and 3, the azole derivative (I) can be obtained as shown in Synthetic Scheme 1' below. Specifically, the azole derivative (I) can be obtained by introducing an azole into the compound (2) to obtain the compound (4), and then synthesizing an ether skeleton by Ullmann condensation reaction after the introduction of the azole. .

(Step 2') Compound (4) is obtained by introducing an azole into compound (2). Azolation of compound (2) may be carried out in the same manner as in step 3 above. One example is the one-pot reaction method described in step 3 above.

(Step 3′) Synthesizing an ether skeleton from compound (4) by Ullmann condensation reaction using an aromatic heterocycle having a phenol or hydroxy group substituted with one or more R ³ or unsubstituted, Azole derivative (I) is obtained. The Ullmann condensation reaction here is not limited to a reaction at a high temperature (eg, 195° C.), and a ligand may be used to react at a relatively low temperature (eg, 135° C.). For example, copper (I) iodide as a copper catalyst, tris(2,4-pentanedionato)iron (III) as a ligand, potassium carbonate as a base, and N,N-dimethylformamide as a solvent are used. and a method of reacting at 135° C. in an oil bath, but not limited thereto.

(2) Azole derivative production method 2
When either R ¹ or R ² is H, the azole derivative (I) can be prepared according to the synthesis scheme 2 below from compounds obtained by known techniques. Synthetic schemes 2 and 2′ below are exemplified as R ¹ =H. Moreover, when R ¹ and R ² are alkyl groups and are different from each other, the azole derivative (I) can be produced from the compound (8) obtained by the synthesis scheme 2 below.

(Step 1) by Ullmann reaction or S _N Ar reaction, the halogen X of compound (1) is substituted with a substituted or unsubstituted phenol or an aromatic heterocyclic ring having a hydroxy group, thereby converting compound (1) to compound (5). ). When hydrogen is present at the α-position of the ketone as in compound (1), side reactions starting from the α-position of the ketone may take precedence under basic high-temperature conditions. Therefore, in such a case, the S _N Ar reaction under relatively mild conditions is suitable. One example is a method in which X is F, potassium carbonate is used as a base, N,N-dimethylformamide is used as a solvent, and the reaction is carried out at 120° C., but the method is not limited thereto.

(Step 2) Compound (6) is obtained by carbonizing compound (5) in the form of β-ketoester. This protects one of the substitution positions and also activates the methylene for nucleophilic substitution reactions. Examples of the method for increasing carbon include a method of reacting a dialkyl carbonate represented by ROCOOR (R is an alkyl group, and two Rs may be the same or different) as a reaction reagent and solvent by heating under reflux. In addition, if the compound (5) is directly alkylated, a disubstituted compound may also be produced, making it difficult to selectively synthesize a monosubstituted compound. One example is a method of using dimethyl carbonate as a reaction reagent and solvent, sodium hydride as a base, adding a small amount of methanol, and reacting by heating under reflux, but the method is not limited to this.

(Step 3) Compound (7) is obtained by alkylating the active methine of compound (6). Alkylation may be carried out by a reaction using an alkylating reagent such as alkyl iodide. One example is a method of using isopropyl iodide as an alkylating reagent, sodium hydride as a base, and N,N-dimethylformamide as a solvent, and performing the reaction at 80° C., but is not limited thereto.

(Step 4) Compound (8) is obtained by hydrolyzing and decarboxylating the ester of compound (7). An example is a method of using a 30% aqueous sodium hydroxide solution as a base and tetrahydrofuran as a solvent, and the reaction is carried out by heating under reflux, but the method is not limited to this.

(Step 5) An olefin compound (9) is obtained from a ketone compound (8) by Wittig reaction. When both R ¹ and R ² are H, steps 2, 3 and 4 may be omitted and compound (5) may be directly olefinized. Methyltriphenylphosphonium bromide etc. are mentioned as an ylide reagent used as phosphorus ylide. A more specific example is a method of using methyltriphenylphosphonium bromide as the ylide reagent, potassium tert-butoxide as the base, and tetrahydrofuran as the solvent, and carrying out the reaction at room temperature, but is not limited thereto.

(Step 6) The compound (9) is oxidized in the presence of a catalytic amount of osmium tetroxide and a reoxidant to synthesize the vic-diol compound (10). One example is a method of using a catalytic amount of osmium tetroxide, using N-methylmorpholine oxide as a reoxidizing agent, and a mixture of water and acetone as a solvent, and carrying out the reaction at room temperature, but is limited to this. isn't it. Azole derivative (I) may be obtained by oxiranating compound (9).

(Step 7) A compound (11) is obtained by introducing a sulfonyl group as a leaving group into the primary hydroxy group of the compound (10). A substituted sulfonyl chloride represented by R ⁴ SO ₂ Cl is used to introduce a leaving group. Here, R ⁴ represents an alkyl group having 1 to 3 carbon atoms which may be substituted with a hydrogen atom, a phenyl group or a naphthyl group. R ⁴ is preferably a 4-methylphenyl group. One example is a method of using p-toluenesulfonyl chloride as a leaving group-introducing reagent, pyridine as a base, and chloroform as a solvent, and carrying out the reaction at 0° C., but is not limited thereto.

(Step 8) Azole derivative (I) is obtained by azoleizing compound (11) using an alkali metal salt of 1,2,4-triazole. One example is a method of using 1,2,4-triazole sodium salt as an azole-forming reagent and N-methylpyrrolidone as a solvent, and reacting at 120° C., but the method is not limited to this.

When R ¹ and R ² are alkyl groups and are different from each other, the ketone α-position of compound (8) may be alkylated to introduce R ¹ different from R ² . Alkylation may be carried out by a reaction using an alkylating reagent such as alkyl iodide. One example is a method of using an alkyl iodide as an alkylating reagent, sodium hydride as a base, and N,N-dimethylformamide as a solvent, and carrying out the reaction at room temperature, but is not limited thereto. By performing step 5 to step 8 after alkylation, it is possible to obtain azole derivative (I) which is different from each other in which R ¹ and R ² are alkyl groups.

(2′) Method 2′ for producing an azole derivative
When X is Cl, I or Br, instead of step 1, azole derivative (I) can be obtained as shown in Synthesis Scheme 2' below. Specifically, the azole derivative (I) can be obtained by finally substituting the halogen X of the compound (24) with a substituted or unsubstituted phenol or an aromatic heterocycle having a hydroxy group by Ullmann condensation reaction. can. (Synthetic scheme 2')

(3) Azole derivative production method 3
When R ¹ and R ² are bonded to form a cyclopropane ring together with the carbon atoms to which R ¹ and R ² are bonded, azole derivatives ( I) can be produced.

(Step 1) Compound (12) is obtained by introducing methylene into the ketone α-position of compound (1). The method for introducing methylene can be carried out, for example, by referring to the method described in Non-Patent Document: Org. Syn. Coll., vol.7 (1990) p332. One example is, but not limited to, a method of reacting paraformaldehyde and N-methylanilinium trifluoroacetate in tetrahydrofuran by heating under reflux.

(Step 2) The exomethylene at the ketone α-position of compound (12) is reacted with a sulfur ylide in the Corey-Chaycovsky reaction to introduce a cyclopropane ring to obtain compound (13). It is generally believed that Michael addition occurs when a sulfoxonium ylide is used, but oxiration occurs when a sulfonium ylide is used. Therefore, it is preferable to use a sulfoxonium salt as the ylide reagent. One example is a method of using trimethylsulfoxonium iodide as the ylide reagent, using sodium hydride as the base and dimethylsulfoxide as the solvent, and performing the reaction at room temperature, but is not limited thereto.

(Step 3) Compound (14) is obtained by substituting halogen X of compound (13) with a substituted or unsubstituted phenol or an aromatic heterocycle having a hydroxy group. Specifically, it is the same as the method for synthesizing compound (3) in step 2 of Synthesis Scheme 1 described above.

(Step 4) Compound (14) is converted to oxirane by Corey-Chaykovsky reaction, followed by azole conversion to obtain azole derivative (I). Specifically, it is the same as the method for synthesizing the azole derivative (I) in step 3 of Synthesis Scheme 1 described above.

(4) Azole derivative production method 4
When Z is an aromatic heterocycle, the azole derivative (I) can be produced from compounds obtained by known techniques according to Synthetic Scheme 4 below.

(Step 1) Compound (2) is obtained by alkylating the ketone α-position of compound (1). Specifically, it is the same as the method for synthesizing compound (2) in step 1 of Synthetic Scheme 1 described above.

(Step 2) Compound (15) is synthesized by S _N Ar reaction between compound (2) and benzyl alcohol having a substituent R. In this case, X is preferably F, which has high reactivity. An example is, but not limited to, a method in which X is F, potassium tert-butoxide is used as a base, and N,N-dimethylformamide is used as a solvent, and the reaction is carried out at room temperature. In addition, R includes, but is not limited to, hydrogen, halogen and methoxy group.

(Step 3) Compound (16) is synthesized by converting compound (15) into oxirane by the Corey-Chaykovsky reaction, followed by azole conversion. Specifically, it is the same as the method for synthesizing the azole derivative (I) in step 3 of Synthesis Scheme 1 described above.

(Step 4) Compound (17) is synthesized by catalytically reducing compound (16) in a hydrogen atmosphere using a palladium-based catalyst. One example is a method of using palladium carbon as a catalyst and ethanol as a solvent in a hydrogen atmosphere at room temperature, but the method is not limited to this.

(Step 5) Azole derivative (I) is synthesized by reacting compound (17) as a nucleophilic agent with a halogen-containing heterocycle. Preferably the S _N Ar reaction is used. When using the S _N Ar reaction, the halogen of the heterocycle is preferably F or Cl, more preferably F. One example is a method of reacting at 60° C. using pyridine in which at least one hydrogen atom is substituted with a fluorine atom as the halogen-containing heterocyclic ring, cesium carbonate as the base, and N,N-dimethylformamide as the solvent. , but not limited to.

[3. Method for Producing Enantiomers of Azole Derivatives]
The R-enantiomer and S-enantiomer of azole derivative (I) can be produced by fractionating the racemate of azole derivative (I) using any of the methods shown below. The fractionation methods described below are known, and reagents, bases, solvents, etc., and various conditions such as temperature used for fractionation are within the range that can be appropriately set by those skilled in the art based on common general technical knowledge. be.

As a fractionation method, for example, [2. Azole derivative production method]] was subjected to high-performance liquid chromatography ( HPLC) to obtain each enantiomer, but is not limited thereto.

A mixture of the R-enantiomer and S-enantiomer of azole derivative (I) can be produced by mixing the R-enantiomer and S-enantiomer fractionated by the above method at any mixing ratio. The mixing ratio of the R-enantiomer and the S-enantiomer can be appropriately adjusted so that the desired activity can be exhibited. An example of the mixing ratio conforms to the above explanation, so the explanation will not be repeated.

[4. Agricultural and horticultural fungicide]
Since the R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative (I) of this embodiment has an imidazolyl group or a 1,2,4-triazolyl group, acid addition salts of inorganic acids and organic acids, Or form a metal complex. Therefore, it can be used as an active ingredient of agricultural and horticultural fungicides together with other active ingredients as part of acid addition salts and metal complexes.

(1) Plant disease control effect The agricultural and horticultural fungicide in the present embodiment exhibits a control effect against a wide range of plant diseases.

Examples of applicable diseases include the following. The parentheses after each disease indicate the main pathogen causing the disease. Soybean rust (Phakopsora pachyrhizi, Phakopsora meibomiae), soybean brown spot (Zymoseptoria glycines), soybean purpura (Cercoora kikuchii), soybean brown spot (Alternaria sp.), soybean anthracnose (Collectotrichum truncatum, Colletotrichum glysines), soybean Cercocpora sojina, Rhizoctonia solani, Rhizoctonia solani, Diaporthe phaseolorum, Phytophthora sojae, Fusarium avenaceum , Fusarium oxysporum), soybean wilt (Verticillium dahliae), soybean powdery mildew (Erysiphe glycines), soybean brown spot (Corynespora cassiicola), soybean brown spot (Mycosphaerella sojae), soybean black root rot (Calonectria ilicicola), Macrophomina phaseolina, Thielaviopsis sp., Ascochyta phaseolorum, Elsinoe glycines, Acute soybean blight (Fusarium sp. such as Fusarium virguliforme), Kidney bean anthracnose (Colletotrichum lindemuthianum), Phoma stem canker/stem canker in oilseed rape (Leptosphaeria maculans, Leptosphaeria biglobosa), Light leaf spot (Pyrenopeziza brassicae) in oilseed rape, clubroot of oilseed rape (Plasmodiophora brassicae), Verticillium wilt in oilseed rape (Verticillium longisporum), Blackspot of oilseed rape (Alternaria spp.), rice blast (Pyricularia oryzae), rice leaf blight (Co chliobolus miyabeanus), rice bacterial leaf blight (Xanthomonas oryzae pv. Pythium spp.), rice wilt (Gaeumannomyces graminis), barley powdery mildew (Erysiphe graminis f. sp. hordei), Puccinia graminis, Puccinia striiformis, Puccinia hordei, Pyrenophora graminea, Rhynchosporium secalis, Barley bare smut Ustilago nuda, Pyrenophora teres, Fusarium graminearum, Microdochium nivale, Erysiphe graminis f. sp.tritici, Puccinia recondita, wheat Yellow rust (Puccinia striiformis), wheat eye spot (Oculimacula yallundae), wheat head blight (Fusarium graminearum, Microdochium nivale), wheat blight (Phaeosphaeria nodorum), wheat leaf blight (Zymoseptoria tritici), wheat scarlet Rot (Microdochium nivale), wheat brown snow rot (Pythium iwayamai, Pythium paddicum and Pythium spp.), wheat wilt (Gaeumannomyces graminis), wheat black spot (Epicoccum spp.), wheat yellow spot (Pyrenophora tritici-repentis) ), snow rot of wheat (Typhula incarnata), snow rot of wheat (Typhula ishikariensis), snow rot of wheat (Sclerotinia borealis), wheat rot (Ramularia collo-cygni) ), Sclerotinia homoeocarpa, Rhizoctonia solani, Rhizoctonia solani, Colletotrichum graminicola, Gray leaf spot (Pyricularia grisea), Necrotic tickling spot disease ( Ophiosphaerella korrae), Sheba Red thread (Laetisaria fuciformis), Sheba Rust (Puccinia zoysiae), Sheba Summer Patch (Magnaporthe poae), Sheba Takeall Patch (Gaeumannomyces graminis), Sheba Brown Ring Patch (Waitea circinata) , Agaricus spp. , Calvatia cyathiformis, Chlorophyllum molybdites, Clitocybe spp. , Lepiota spp. , Lepista subnuda, Lycoperdon spp. , Marasmius oreades, Scleroderma spp. , Tricholoma spp. etc.), turfgrass pink snow rot (Microdochium nivale), turfgrass snow rot brown sclerotia (Typhula incarnata), turfgrass snow rot black sclerotia (Typhula ishikariensis), turfgrass curvularia leaf blight (Curvularia sp.) , Binucleate Rhizoctonia, Gaeumannomyces sp., Phialophora sp., Ustilago maydis, Colletotrichum graminicola, Kabatiella zeae, Maize Gray Spot (Cercospora zeae-maydis), Corn Sooty Spot (Setosphaeria turcica), Maize Northern Spot (Bipolaris zeicola), Maize Spot (Physoderma maydis), Maize Rust (Puccinia spp.), Corn Leaf Blight Bipolaris maydis, Phyllosticta maydis, Fusarium asiaticum, Fusarium fujikuroi, Fusarium proliferatum, Fusarium concentricum Fusarium graminearum, Fusarium verticillioides, Phaeosphaeria leaf spot of maize (Phaeosphaeria maydis), Corn Diplodia ear rot (Stenocarpella maydis, Stenocarpella macrospora), sugar cane rust (Puccinia spp.), Cucurbit powdery mildew (Podosphaera xanthii), Cucurbit anthracnose (Colletotrichum orbiculare, Glomerella cingurata), Cucurbit brown spot ( Corynespora cassiicola), gourd downy mildew (Pseudoperonospora cubensis), cucumber gray plague (Phytophthora capsici), cucumber wilt (Fusarium oxysporum f. sp. cucumerinum), Fusarium oxysporum f. sp. niveum, Podosphaera leucotricha, Venturia inaequalis, Monilinia mali, Leaf spot disease Alternaria alternata apple pathotype, Valsa ceratosperma, Alternaria alternata Japanese pear pathotype, Phyllactinia pyri, Gymnosporangium asiaticum, Venturia nasicola ), Podosphaera aphanis, Monilinia fructicola of stone fruit trees, Penicillium italicum, Penicillium digitatum, Uncinula necator, Grape powdery mildew Downy mildew (Plasmopara viticola), Grape late rot (Glomerella cingulata, Colletotoricum acutatum), Grape rust (Phakopsora ampelopsidis), Grape black rot (Elsinoe ampelina), Banana black sigatoka (Mycosphaerella fijiensis), Banana yellow sigatoka Mycosphaerella musicola, Erysiphe cichoracearum, Alternaria solani, Passalora fulva, Pseudocercospora fuligena, Septoria lycopersici, Tomato anthracnose (Colletotrichum coccodes), eggplant powdery mildew (Erysiphe cichoracearum), potato summer blight (Alternaria solani), potato anthracnose (Colletotrichum) coccodes), Erysiphe cichoracearum, Leveillula taurica, Phytophthora infestans, Erysiphe cichoracearum, Alternaria longipes, Cercospora beticola, Sugar beet udon Erysiphe betae, Rhizoctonia solani, Thanatephorus cucumeris, Aphanomyces cochlioides, Fusarium oxysporum f. sp. Discula theae-sinensis, Exobasidium vexans, Pseudocercospora ocellata, Cercospora chaae, Pestalotiopsis longiseta, Pestalotiopsis theae, Exobasidium reticulatum, cotton black Alternaria spp., Glomerella spp., Ascochyta gossypii, Puccinia spp., Phakopsora gossypii, Cercospora blight and leaf spot of cotton (Cercospora spp.) , Cotton Diplopia boll rot (Diplopia spp.), Cotton Hardlock (Fusarium spp.), Cotton Phoma blight (Phoma spp.), Cotton Stemphyllium leaf spot (Stemphyllium spp.), Peanut black stain (Cercosporidium personatum) ), Cercospora arachidicola, Sclerotium rolfsii, Puccinia arachidis, Botrytis cine that affects various crops rea), Pythium spp., Verticillium sp., Sclerotinia sclerotiorum, and the like. Aspergillus, Cochliobolus, Corticium, Diplodia, Penicillium, Fusarium, Gibberella, Mucor, Phoma, Phomopsis, Pyrenophora, Pythium, Rhizoctonia, Rhizopus, Thielaviopsis, Tilletia, Seed-borne diseases or early growth diseases of various plants caused by pathogens such as Trichoderma and Ustilago.

By applying the agricultural and horticultural fungicide according to this embodiment to target plants, it is possible to protect the target plants from damage caused by the plant diseases described above.

The agricultural and horticultural fungicide according to the present embodiment can also be suitably applied to diseases caused by pathogenic bacteria that are less sensitive to existing sterol biosynthesis inhibitors than wild-type. In the present specification, the term "sterol biosynthesis inhibitor" is classified as "cell membrane sterol biosynthesis (G)" in the mechanism of action classification of fungicides (2021 edition) by FRAC (Fungicide Resistance Action Committee). It means a substance that has bactericidal activity by inhibiting sterol biosynthesis in the cell membrane of pathogenic filamentous fungi. In the present specification, the term "existing sterol biosynthesis inhibitors" means known sterol biosynthesis inhibitors for which the presence of drug-resistant bacteria has been confirmed at the time of filing of the present application.

Such existing sterol biosynthesis inhibitors are preferably DMI fungicides (FRAC code: 3) which are inhibitors of demethylase (CYP51) at the C14 position in sterol biosynthesis, Δ ¹⁴ in sterol biosynthesis Amines (FRAC code: 5) that are inhibitors of reductase and Δ ⁸ →Δ ⁷ -isomerase, and KRI fungicides that are inhibitors of 3-keto reductase in C4 demethylation of sterol biosynthesis. (FRAC code: 17), more preferably a DMI fungicide for which the development of resistant bacteria has been confirmed in a plurality of pathogenic bacteria. Specific examples of existing sterol biosynthesis inhibitors are described below.

As used herein, "a pathogen that is less sensitive to existing sterol biosynthesis inhibitors compared to wild-type" refers to at least one existing sterol biosynthesis inhibitor compared to wild-type pathogens It refers to pathogens with low susceptibility. Such pathogenic bacteria are at least selected from the group consisting of mutations in genes encoding target proteins that serve as sites of action of sterol biosynthesis inhibitors, overexpression of the target proteins, and development of drug efflux pumps in cell membranes. One factor is pathogens that have acquired low sensitivity to existing inhibitors of sterol biosynthesis.

Diseases to which the agricultural and horticultural fungicide according to this embodiment is applied, and diseases caused by pathogenic bacteria that are less sensitive to existing sterol biosynthesis inhibitors than wild type, specifically, this embodiment is the same as the plant disease that exhibits a control effect by the agricultural and horticultural fungicide in , so the description thereof will not be repeated.

The agricultural and horticultural fungicide in this embodiment can be used for all plants, and examples of applicable plants include the following: rice, wheat, barley, rye, oat, triticale (triticale), corn. , sorghum (sorghum), sugarcane, turfgrass, bentgrass, bermudagrass, fescue and ryegrass, etc., legumes such as soybean, peanut, kidney bean, pea, adzuki bean and alfalfa, convolvulaceae such as sweet potato, hot pepper, Solanaceae such as bell peppers, tomatoes, eggplants, potatoes and tobacco; Polygonaceae such as buckwheat; Asteraceae such as sunflowers; Araliaceae such as ginseng; , Chenopodiaceae such as sugar beet, Malvaceae such as cotton, Rubiaceae such as coffee, Rubiaceae such as cacao, Theaceae such as tea, Cucurbitaceae such as watermelon, melon, cucumber and pumpkin, Liliaceae such as onions, leeks and garlic; Rosaceae such as strawberries, apples, almonds, apricots, plums, cherry blossoms, plums, peaches and pears; Apiaceae such as carrots; Araceae such as taro; Anacardiaceae, pineapples and other pineapples, papayas and other papayae, persimmons and other persimmons, blueberries and other ericaceae, pecans and other walnuts, bananas and other musaceae, olives and other Oleaceae, Palms such as coconut palms and dates, Rutaceae such as tangerines, oranges, grapefruits and lemons, Grapes such as grapes, Flowers and ornamental plants, trees other than fruit trees, and other ornamental plants plant. Examples of applicable plants also include wild plants, plant cultivars, plants and plant cultivars obtained by conventional biological breeding such as crossbreeding or protoplasmic fusion, and transgenic plants and plant cultivars obtained by genetic engineering. be able to. Genetically modified plants and plant cultivars include, for example, herbicide-tolerant crops, pest-resistant crops incorporating an insecticidal protein-producing gene, disease-tolerant crops incorporating a disease-resistance inducer-producing gene, taste-enhancing crops, and yield-enhancing crops. Crops, storability-improved crops, yield-improved crops, and the like can be mentioned. Genetically modified plant cultivars that have been approved in each country include those accumulated in the database of the International Agri-Bio Agency (ISAAA). Specifically, AgriSure, AgriSure 3000GT, AgriSure 3122 E-Z Refuge, AgriSure 3122 Refuge Renew, AgriSure Artesian 3030A, AgriSure Artesian 3011A, AgriSure Duracade, AgriSure Duracade 5222 E-Z Refuge, AgriSure GT, AgriSure SCB/LL, AgriSure GT AgriSure Viptera 3110, AgriSure Viptera 3111, AgriSure Viptera 3220 E-Z Refuge, AgriSure Viptera 3220 Refuge Renew, BiteGard, Bollgard, Bollgard II, Bollgard II/Roundup Ready, Bollgard 3 XtendFlex Cotton, Bollgard Bound. . t/BXN Cotton, B.t. Maize, BtXtra, BXN, BXN Canola, BXN Cotton, Clearfield, DroughtGard, Enlist, Enlist Cotton, Enlist WideStrike 3 Cotton, Genuity, Genuity Bollgard II XtendFlex, Genuity Intacta RR2 Pro, Genuity SmartStax, Genuity SmartStax RIB Complete, Genuity VT Double Pro, Genuity VT Double Pro RIB Complete, Genuity VT Triple Pro, Genuity VT Triple Pro RIB Complete, GlyTol, GlyTol Cotton, Herculex, Herculex 1, Herculex RW, Herculex XTRA, IMI, IMI Canola, InVigor, KnockOut, Liberty Link, Liberty Link Conola, Liberty Link cotton, NatureGard, Newleaf, N ucotn, Optimum, Optimum AcreMax, Optimum AcreMax I, Optimum AcreMax-R, Optimum AcreMax RW, Optimum AcreMax RW-R, Optimum AcreMax Xtra-R, Optimum AcreMax Xtreme-R, Optimum AcreMax Xtreme, Optimum Intrasect, Optimum Intrasect Xtra, Optimum Intrasect Xtreme, Optimum Leptra, Optimum TRIsect, Poast Compatible, Powercore, Powercore Corn, Powercore Corn Refuge Advanced, Protecta, Roundup Ready, Roundup Ready 2, Roundup Ready Conola, Roundup Ready Cotton, Roundup Ready/YieldGard, RR Flex/Bollgard II, SCS, SmartStax, SmartStax Refuge Advanced, StarLink, Twinlink, VipCot, VipCot Cotton, WideStrike, WideStrike 3, Xtend, YieldGard, YieldGard Corn Borner, YieldGard Rootworm, YieldGard Plus and YieldGard VT Triple, to name a few. can.

(2) Formulation The agricultural and horticultural fungicide in the present embodiment may contain, as active ingredients, the R-enantiomer or mixed enantiomer of the azole derivative (I) and other active ingredients. Therefore, examples of agricultural and horticultural fungicides include (a) those prepared by including the R-enantiomer or mixed enantiomer of azole derivative (I) and other active ingredients, and (b) azole derivative (I) A first preparative agent containing the R-enantiomer or mixed enantiomers of and, independently of this, a second preparative agent containing other active ingredients are mixed just before use. . Hereinafter, the form (a) will be referred to as a "formulation-incorporating agricultural and horticultural fungicide", and the form (b) will be referred to as a "tank mix type agricultural and horticultural fungicide". Thus, the agricultural and horticultural fungicide in this embodiment contains the R-enantiomer or mixed enantiomer of the azole derivative (I) and other active ingredients as active ingredients. Therefore, the objective is to provide an agricultural and horticultural fungicide capable of obtaining a synergistic effect between the azole derivative and other active ingredients, exhibiting a high control effect and reducing the dosage as compared with the case where each is used alone. can be done.

In addition, according to such a configuration, it is possible to reduce the toxicity to non-target organisms and the load on the environment by reducing the dosage of the fungicide for farms. Therefore, the agricultural and horticultural fungicide in this embodiment can contribute to Goal 2 "Sustainable agriculture" and Goal 15 "Protect greenery" of the Sustainable Development Goals (SDGs) led by the United Nations. It becomes possible. Moreover, according to the agricultural and horticultural fungicide of the present embodiment, it is possible to contribute to efficiency improvement of agriculture and to turn agriculture into a growth industry. Therefore, it will be possible to contribute to Goal 8 of the Sustainable Development Goals (SDGs), "industrial development and job creation." Moreover, according to the agricultural and horticultural fungicide of the present embodiment, the risk of mycotoxins in agricultural products can be reduced. Therefore, it is possible to contribute to Goal 3 of the Sustainable Development Goals (SDGs), "Good Health for All."

(2-1) Formulation-incorporating agricultural and horticultural fungicide The content of the R-enantiomer or mixed enantiomer of the azole derivative (I) in the formulation-incorporating agricultural and horticultural fungicide is, for example, 0.1 to 95% by weight, It is preferably 0.5 to 90% by weight, more preferably 2 to 80% by weight. The content of the R-enantiomer or the mixed enantiomer of the azole derivative (I) in the spray liquid when actually sprayed is not particularly limited as long as the desired activity can be exhibited.

The R-enantiomer or mixed enantiomer of the azole derivative (I) contained as an active ingredient in the formulation-incorporated agricultural and horticultural fungicide may be a single compound, or two or more compounds may be mixed. good. In addition, in the R-enantiomer or mixed enantiomer of one or more types of azole derivative (I) contained as an active ingredient in the formulation-incorporated agricultural and horticultural fungicide, all types of azole derivative (I) contained are R-enantiomers There may be a mixture of the R-enantiomer and the S-enantiomer depending on the type of the azole derivative (I). The ratio between the R-enantiomer and the S-enantiomer finally contained in the formulation-incorporating agricultural and horticultural fungicide can be appropriately set. Since the mixing ratio conforms to the explanation so far, the explanation thereof will not be repeated.

As a preferred embodiment of the formulation-incorporating agricultural and horticultural fungicide, a mixture of the R-enantiomer of the azole derivative (I) and other active ingredients and the S-enantiomer of the azole derivative (I) are incorporated into the formulation. type agricultural and horticultural fungicides. Such formulation-incorporating agricultural and horticultural fungicides are compared to a mixture of the R-enantiomer of the azole derivative (I) and other active ingredients, or the S-enantiomer of the azole derivative (I) alone. A high control effect can be obtained.

The content of other active ingredients in the formulation-incorporated agricultural and horticultural fungicide is, for example, 0.1 to 95% by weight, preferably 0.5 to 90% by weight, and 2 to 80% by weight. is more preferred. The content of other active ingredients in the spray liquid when actually sprayed is not particularly limited as long as the desired effect can be obtained. Formulation-incorporating agricultural and horticultural fungicides include, in addition to the R-enantiomer or mixed enantiomer of azole derivative (I) and other active ingredients, solid carriers, liquid carriers (diluents), surfactants, or other Formulation auxiliaries may be included.

(2-2) Tank mix type agricultural and horticultural fungicide The content of the R-enantiomer or mixed enantiomer of the azole derivative (I) and the content of other active ingredients in the tank mix type agricultural and horticultural fungicide are It may be the same as each content in the built-in agricultural and horticultural fungicide. The first preparation agent containing the R-enantiomer or the mixed enantiomer of the azole derivative (I) for preparing the tank-mix agricultural and horticultural fungicide is the formulation except that it does not contain other active ingredients. It can be in the same aspect as the built-in agricultural and horticultural fungicide. In addition, the second preparation agent containing other active ingredients, which is used for preparing the tank-mix type agricultural and horticultural fungicide, does not contain the R-enantiomer or mixed enantiomers of the azole derivative (I). Except for this, it can be the same aspect as the formulation-integrated agricultural and horticultural fungicide. The content of the R-enantiomer or mixed enantiomer of the azole derivative (I) in the first pharmaceutical preparation and the content of other active ingredients in the second pharmaceutical preparation are finally determined by the tank mix type agricultural and horticultural It is sufficient that the content of the R-enantiomer or mixed enantiomer of the azole derivative (I) and the content of other active ingredients in the fungicide can be achieved.

The tank-mix type agricultural and horticultural fungicide contains, in addition to the R-enantiomer or mixed enantiomer of the azole derivative (I) and other active ingredients, a solid carrier, a liquid carrier (diluent), a surfactant, or other Formulation auxiliaries may be included.

The mixing ratio of the first preparation agent and the second preparation agent in the tank mix type agricultural and horticultural fungicide can be appropriately determined according to the composition and purpose of each preparation agent.

In addition, in the tank-mix type agricultural and horticultural agent, a first agent for preparation containing the R-enantiomer or mixed enantiomer of the azole derivative (I) and a second agent for preparation containing other active ingredients are prepared separately. and mixing them to prepare agricultural and horticultural fungicides. Therefore, plant disease control products containing separately the R-enantiomer or mixed enantiomers of azole derivative (I) and other active ingredients as combination preparations for mixed use in plant disease control are also of the present invention. included in the category.

(2-3) Formulation Auxiliary Agricultural and horticultural agents are prepared by mixing the R-enantiomer or mixed enantiomer of the active ingredient azole derivative (I) and other active ingredients with carriers, surfactants and other formulation auxiliaries. Various powders, granules, powder granules, wettable powders, water solutions, emulsions, liquids, oils, aerosols, microcapsules, pastes, coating agents, fumigants, fumigants, and microspray agents. It is formulated into a form and used.

Carriers used as formulation adjuvants include solid carriers and liquid carriers. Solid carriers are used as powder carriers, granular carriers, and the like. Examples of solid carriers include clay, talc, diatomaceous earth, zeolite (zeolite), montmorillonite, bentonite, kaolinite, kaolin, pyrophyllite, pyrophyllite, acid clay, activated clay, attapulgite, attapulgus clay, limestone, calcite. , minerals such as marble, vermiculite, perlite, pumice, silica, silica sand, sericite and porcelain stone; synthetic organic substances such as urea; calcium carbonate, sodium carbonate, magnesium carbonate, sodium sulfate, ammonium sulfate, potassium chloride, slaked lime and salts such as baking soda; amorphous silica (white carbon, fumed silica, etc.) and synthetic inorganic substances such as titanium dioxide; , sawdust, wheat bran, soybean flour, powdered cellulose, starch, dextrin and sugars (lactose, sucrose, etc.); Gels (agar, etc.), various polymer carriers such as chlorinated polyethylene, chlorinated polypropylene, polyvinyl acetate, polyvinyl chloride, ethylene/vinyl acetate copolymers and urea/aldevide resins can be used.

Examples of liquid carriers include aliphatic solvents such as paraffins (normal paraffin, isoparaffin, naphthene); aromatic solvents such as xylene, alkylbenzene, alkylnaphthalene and solvent naphtha; mixed solvents such as kerosene; machine oils such as aliphatic hydrocarbons; alcohols such as methanol, ethanol, isopropanol, butanol and cyclohexanol; polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, hexylene glycol, polyethylene glycol and polypropylene glycol Polyhydric alcohol derivatives such as propylene glycol ether; Ketones such as acetone, acetophenone, cyclohexanone, methylcyclohexanone and γ-butyrolactone; Fatty acid methyl ester (coconut fatty acid methyl ester), ethylhexyl lactate, propylene carbonate and dibasic esters such as acid methyl esters (dimethyl succinate, dimethyl glutamic acid, dimethyl adipate); nitrogen-containing solvents such as N-alkylpyrrolidones and acetonitrile; sulfur-containing solvents such as dimethyl sulfoxide; coconut oil, soybean oil and Fats and oils such as rapeseed oil; dimethylformamide, N,N-dimethyloctanamide, N,N-dimethyldecanamide, 5-(dimethylamino)-2-methyl-5-oxo-valeric acid methyl ester and N-acylmorpholine Amide-based solvents such as solvents (CAS No. 887947-29-7, etc.);

Surfactants used as formulation aids include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, silicone surfactants, fluorosurfactants and biosurfactants. etc. Examples of nonionic surfactants include sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, sucrose fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene resin acid esters, polyoxyethylene fatty acid diesters, polyoxyethylene alkyl Ether, polyoxyethylene alkylphenyl ether, polyoxyethylene dialkylphenyl ether, polyoxyethylene alkylphenyl ether formalin condensate, polyoxyethylene/polyoxypropylene block polymer, alkylpolyoxyethylene/polyoxypropylene block polymer ether, alkylphenyl Polyoxyethylene/polyoxypropylene block polymer ether, polyoxyethylene alkylamine, polyoxyethylene fatty acid amide, polyoxyethylene fatty acid bisphenyl ether, polyoxyethylene benzylphenyl (or phenylphenyl) ether, polyoxyethylene styrylphenyl (or phenylphenyl) ether, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil and alkyl glycosides.

Examples of anionic surfactants include alkyl sulfates, polyoxyethylene alkyl ether sulfates, polyoxyethylene alkylphenyl ether sulfates, polyoxyethylene benzyl (or styryl) phenyl (or phenylphenyl) ether sulfates and polyoxyethylene/poly Sulfates such as oxypropylene block polymer sulfate; paraffin (alkane) sulfonate, α-olefin sulfonate, dialkyl sulfosuccinate, alkylbenzene sulfonate, mono- or dialkylnaphthalene sulfonate, naphthalene sulfonate/formalin condensate, alkyldiphenyl ether disulfonate, lignin sulfonate, sulfonates such as polyoxyethylene alkylphenyl ether sulfonates and polyoxyethylene alkyl ether sulfosuccinic acid half esters; Laths; polyoxyethylene alkyl ether phosphate, polyoxyethylene mono- or dialkylphenyl ether phosphate, polyoxyethylene benzyl (or styryl) phenyl (or phenylphenyl) ether phosphate, polyoxyethylene/polyoxypropylene block polymer phosphate and alkyl phosphate and phosphates such as

Examples of cationic surfactants include salts of amines such as alkylamines and alkylpentamethylpropylenediamine; salts of ammoniums such as nium and benzethonium (octylphenoxyethoxyethyldimethylbenzylammonium);

Examples of amphoteric surfactants include dialkyldiaminoethyl betaine, alkyldimethylbenzyl betaine, and lecithin (phosphatidylcholine, phosphatidylethanolamine, etc.).

Examples of silicone-based surfactants include trisiloxane ethoxylate.

Examples of fluorine surfactants include perfluoroalkylcarboxylates, perfluoroalkylsulfonates, and perfluoroalkyltrimethylammonium salts.

Examples of biosurfactants include sophorolipids, rhamnolipids, trehalose lipids, mannosylalditol lipids, cellobiose lipids, glucose lipids, oligosaccharide fatty acid esters, spiculesporic acid, corynomycolic acid, agaritic acid, surfactin, cerauethin, viscosine, licensin, Arthrofactin, Emulzan and Arasan and the like can be mentioned.

Other formulation adjuvants include inorganic salts (sodium, potassium, etc.) used as pH adjusters; water-soluble salts such as common salt; Vinyl polymers, acrylic polymers, polyvinyl alcohol, starch derivatives, water-soluble polymers (polysaccharides, etc.), alginic acid and salts thereof, etc.; metal stearates used as disintegrating dispersants, sodium tripolyphosphate, sodium hexametaphosphate, etc.; preservatives Benzoic acid and its salts, sorbic acid and its salts, propionic acid and its salts, p-hydroxybenzoic acid, methyl p-hydroxybenzoate, 1,2-benzthiazolin-3-one, etc. used as agents; Sodium polyphosphate, sodium polyacrylate, sodium ligninsulfonate, sodium citrate, gluconic acid/sodium glucoheptanoate, ethylenediaminetetraacetic acid and its disodium salt or ammonium salt, etc.; pigments and dyes used as coloring agents etc.; fluorine-based defoaming agents, silicone-based defoaming agents, ethylene oxide/propylene oxide copolymers, etc. used as anti-foaming agents; phenol-based antioxidants, amine-based antioxidants, sulfur-based antioxidants used as antioxidants Inhibitors, phosphoric acid-based antioxidants, etc.; salicylic acid-based UV absorbers, benzophenone-based UV absorbers, etc. used as UV absorbers; quicklime, magnesium oxide, etc. used as drying agents; agents and the like.

Some formulations are used as they are, and some are diluted with a diluent such as water to a predetermined concentration. When used after dilution, the concentration of the total amount of active ingredients, which is the sum of the R-enantiomer or mixed enantiomer of azole derivative (I) and other active ingredients, is desirably in the range of 0.001 to 1.0%.

In addition, the total usage amount of the active ingredient, which is a combination of the R-enantiomer or mixed enantiomer of azole derivative (I) and other active ingredients, is 20 to 5000 g per 1 ha of agricultural and horticultural land such as fields, rice fields, orchards and greenhouses. , more preferably 50 to 2000 g. Since the concentrations and amounts used vary depending on the dosage form, time of use, method of use, place of use, target crops, etc., it is possible to increase or decrease without adhering to the above ranges.

(3) Other Active Ingredients Other active ingredients contained together with the R-enantiomer or mixed enantiomer of the azole derivative (I) include fungicides, insecticides, acaricides, nematicides, and plant growth regulators. The known active ingredients included can be mentioned. Among these, known active ingredients contained in fungicides, insecticides, and plant growth regulators are preferred.

(3-1) Active Ingredients for Bactericidal Use Active ingredients suitable for bactericidal use include, for example, nucleic acid synthesis and metabolism inhibitors, bactericidal agents acting on the cytoskeleton and motor proteins, respiratory inhibitors, amino acid/protein synthesis inhibitor, signaling inhibitor, lipid biosynthesis or transport/cell membrane structure or function inhibitor, cell membrane sterol biosynthesis inhibitor, cell wall biosynthesis inhibitor, melanin biosynthesis inhibitor, host plant resistance inducer , multi-site fungicides and biopesticides/pesticides of biological origin with multiple mechanisms of action.

Nucleic acid synthesis and metabolism inhibitors include benalaxyl, benalaxyl M or chiralaxyl, furalaxyl, metalaxyl, metalaxyl M or mefenoxam, ofrace, oxadixyl, bupirimate, dimethylmol, ethylimol, hydroxyisoxazole, octylinone and oxolinic acid. The nucleic acid synthesis metabolism inhibitor can be at least one selected from these.

Bactericides that act on the cytoskeleton and motor proteins include benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, ethaboxam, pencycuron, zoxamide, fluopicolide, fluopimomide, fenamacril, metrafenone, and pyriophenone. The bactericidal agent that acts on the cytoskeleton and motor proteins can be at least one selected from these.

Respiratory inhibitors include diflumetrim, fenazaquin, tolfenpyrad, benodanil, benzovindiflupyr, bixafen, boscalid, carboxin, fenfuran, fluveneteram, fluindapyr, fluopyram, flutolanil, fluxapyroxad, furametpyr, impylfluxam, isofetamide , isoflucipram, isopyrazam, mepronil, oxycarboxin, penflufen, penthiopyrad, pydiflumetofen, pyrapropoin, pyraziflumide, sedaxane, thifluzamide, azoxystrobin, cumoxystrobin, dimoxystrobin, enestrobin, enoxastrobin , famoxadone, fenamidone, phenaminestrobin, fluphenoxystrobin, fluoxastrobin, cresoxime methyl, mandestrobin, metminostrobin, methyltetraprole, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyra Oxystrobin, pyribencarb, triclopiricarb, trifloxystrobin, amisulbrom, cyazofamid, fenpicoxamide, florylpicoxamide, binapacryl, dinocap, fluazinam, meptyldinocap, triphenyltin acetate, triphenyltin chloride , triphenyltin hydroxide, silthiofam and amethoctrazine. The respiratory inhibitor can be at least one selected from these.

Amino acid and protein biosynthesis inhibitors include cyprodinil, mepanipyrim, pyrimethanil, blasticidin S, kasugamycin, streptomycin, oxytetracycline, and the like, and can be at least one selected from these.

Signal transduction inhibitors include proquinazid, quinoxifene, fludioxonil, clozolinate, dimethaclone, fenpicronil, iprodione, procymidone, vinclozoline, and the like, and may be at least one selected from these.

Lipid biosynthesis or transport/cell membrane structure or function inhibitors include edifenphos (EDDP), iprobenfos (IBP), isoprothiolane, pyrazophos, biphenyl, chloroneb, dichlorane (CNA), etridiazole, quintozene (PCNB), technazene (TCNB) , tolclofos-methyl, iodocarb, propamocarb, prothiocarb, extract of Gosseikajeupte (tea tree), vegetable oil mixture (eugenol, geraniol, thymol), natamycin (pimaricin), fluoxapiproline and oxathiapiproline. The lipid biosynthesis or transport/cell membrane structure or function inhibitor may be at least one selected from these.

Cell membrane sterol biosynthesis inhibitors include azaconazole, bitertanol, bromconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, etaconazole, fenbuconazole, fluoxythioconazole, fluquinconazole, flusilazole, flutria hall, hexaconazole, imazalil, imibenconazole, ipconazole, ipfentrifluconazole, mefentrifluconazole, metconazole, microbutanil, oxpoconazole, pefurazoate, penconazole, prochloraz, propiconazole, prothioconazole, simeconazole, tebuconazole , tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole, fenarimol, nuarimol, pyrifenox, pyrisoxazole, trifoline, methyl(2RS)-2-[2-chloro-4-(4-chlorophenoxy ) phenyl]-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propanoate, 1-((1H-1,2,4-triazol-1-yl)methyl)-5- (4-chlorobenzyl)-2-(chloromethyl)-2-methylcyclopentan-1-ol, methyl 2-((1H-1,2,4-triazol-1-yl)methyl)-3-(4 -chlorobenzyl)-2-hydroxy-1-methylcyclopentane-1-carboxylate, aldimorph, dodemorph, fenpropimorph, tridemorph, fenpropidine, piperaline, spiroxamine, phenhexamide, fenpyrazamine, pirbuticarb, naftifine and terbinafine, etc. is mentioned. The cell membrane sterol biosynthesis inhibitor can be at least one selected from these.

Cell wall biosynthesis inhibitors include polyoxin, bentiavalicarb (bentiavalicarb isopropyl), dimethomorph, flumorph, iprovalicarb, mandipropamide, pirimorph, and valifenalate. The cell wall biosynthesis inhibitor can be at least one selected from these.

Melanin biosynthesis inhibitors include fthalide, pyroquilone, tricyclazole, carpropamide, diclocimet, fenoxanyl and tolprocarb. The melanin biosynthesis inhibitor can be at least one selected from these.

Examples of host plant resistance inducers include acibenzolar-S-methyl, probenazole, thiazinyl, isotianil, laminarin, Oitadori extract, Bacillus mycoides isolate J, cell wall of Saccharomyces cerevisiae strain LAS117, fosetyl (fosetyl-aluminum, fosetyl potassium, fosetyl sodium), phosphoric acid, phosphates and diclobentiazox. The host plant resistance inducer may be at least one selected from these.

Multi-point fungicides include farbum, mancozeb, maneb, metiram, propineb, thiuram, thiazole zinc, zineb, ziram, ambam, anilazine, dithianone, diclofluanide, tolylfluanide, guazatine, iminoctadine acetate, iminoctadine albecil copper or various copper salts (e.g. basic copper chloride, cupric hydroxide, basic copper sulfate, copper sulfate, organic copper (oxine copper), copper nonylphenol sulfonate, DBEDC, etc.), sulfur, captan, captafol, folpet, TPN (chlorothalonyl), quinoxaline (quinomethionate), fluorimide and metasulfocarb, and the like. The multi-site disinfectant can be at least one selected from these.

Biological pesticides/organism-derived pesticides having multiple mechanisms of action include Bacillus subtilis AFS032321 strain, Bacillus amyloliquefaciens strain QST713, Bacillus amyloliquefaciens strain FZB24, Bacillus amyloliquefaciens strain MBI600, Bacillus amyloliquefaciens strain MBI600, Amyloliquefaciens D747 strain, Bacillus amyloliquefaciens F727 strain, Chronostakis rosea CR-7 strain, Gliocladium catenaratum J1446 strain, Pseudomonas chlorophaphis AFS009 strain, Streptomyces griseovirides K61 strain, Strept Mrs. ridicus WYEC108 strain, Trichoderma atroviride I-1237 strain, Trichoderma atroviride LU132 strain, Trichoderma atroviride SC1 strain, Trichoderma aspererum strain T34, extracts from Swaingrea glutinosa, extracts from cotyledons of lupine seedlings, etc. is mentioned. The biopesticide/pesticide of biological origin with multiple mechanisms of action can be at least one selected from these.

Other fungicidal compounds include chloroinconazide, cyflufenamide, cymoxanil, diclomedine, dipimethitrone, dodine, fenitropane, ferimzone, fursulfamide, flutianil, harpine, inorganic salts (bicarbonates (sodium bicarbonate, potassium bicarbonate), potassium carbonate), ipflufenoquine, quinoprole, natural origin, machine oil, organic oil, picarbutrazox, pyridacromethyl, quinofumeline, tebufuroquine, teclofthalam (bactericide), triazoxide, validamycin, aminopyrifene and shiitake mushroom A mycelium extract etc. are mentioned. Other antiseptic compounds may be at least one selected from these.

(3-2) Active Ingredients for Use as Insecticides, Acaricides and Nematicides Active ingredients suitable for use as insecticides, acaricides and nematicides include, for example, acetylcholinesterase (AChE) inhibitors , GABAergic chloride ion channel blockers, sodium channel modulators, nicotinic acetylcholine receptor (nAChR) competitive modulators, nicotinic acetylcholine receptor (nAChR) allosteric modulators, glutamatergic chloride channel (GluCl) allosteric modulators, larvae Juvenile hormone analogues, other non-specific (multisite) inhibitors, chordotonal TRPV channel modulators, mite growth inhibitors acting on CHS1, microbial-derived insect midgut lining disrupters, mitochondrial ATP synthase inhibitors, Oxidative phosphorylation uncoupler that disrupts the proton gradient, nicotinic acetylcholine receptor (nAChR) channel blocker, chitin biosynthesis inhibitor acting on CHS1, chitin biosynthesis inhibitor (type 1), molting inhibitor (Diptera) insect), molting hormone (ecdysone) receptor agonist, octopamine receptor agonist, mitochondrial electron transport complex III inhibitor, mitochondrial electron transport complex I inhibitor (METI), voltage-dependent sodium channel blocker, acetyl-CoA carboxylase inhibitors, mitochondrial electron transport system complex IV inhibitors, mitochondrial electron transport system complex II inhibitors, ryanodine receptor modulators, chordotonal organ modulators, GABAergic chloride ion channel allosteric modulators, baculovirus and the like.

Acetylcholinesterase (AChE) inhibitors include alanicarb, aldicarb, bendiocarb, benfuracarb, butocaboxime, butoxycarboxime, NAC (carbaryl), carbofuran, carbosulfan, ethiofencarb, BPMC (phenocarb), phenothiocarb, formetanate, Furatiocarb, MIPC (isoprocarb), methiocarb, methomyl, MTMC (metolcarb), oxamyl, pirimicarb, PHC (propoxur), thiodicarb, thiophanox, triazamate, trimetacarb, XMC, MPMC (xylylcarb), acephate, azamethifos, azinphosethyl, azinphosmethyl, Cadusaphos, chloretoxyphos, CVP (chlorfenvinphos), chlormephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, CYAP (cyanophos), dimethone-S-methyl, diazinon, DDVP (dichlorvos), dicrotophos, dimethoate, dimethylvinphos, ethylthiomethone (disulfotone) ), EPN, Ethion, Ethoprophos, Fanfur, Fenamiphos, MEP (Fenitrothion), MPP (Fenthion), Hostiazate, Heptenophos, Imisiaphos, Isofenphos, Isopropyl O-(methoxyaminothiophosphoryl) salicylate, Isoxathion, Marathon (malathion), Mecarbam , methamidophos, DMTP (methidathion), mevinphos, monocrotophos, BRP (naled), omethoate, oxydimethone methyl, parathion, methyl parathion (parathion methyl), PAP (phenthoate), folate, fosarone, PMP (phosmet), phosphamidone, phoxime, pyrimiphos-methyl, propenophos, propetamphos, prothiophos, pyraclophos, pyridafenthion, quinalphos, sulfotep, tebpilimphos, temefos, terbufos, CVMP (tetrachlorbinphos), thiometone, triazophos, DEP (trichlorfon) and vamidothione.

GABAergic chloride ion channel blockers include chlordane, benzoepine (endosulfan), dienochlor, ethiprole, fipronil, pyriprole and nicoflurrole.

Sodium channel modulators include acrinathrin, allethrin (allethrin, d-cis-trans-, d-trans-isomer), bifenthrin, bioallethrin (biorethrin, S-cyclopentenyl-isomer), bioresmethrin, chloroprathrin, Chlorphenthone, cycloprothrin, cyfluthrin (cyfluthrin, β-isomer), cyhalothrin (cyhalothrin, λ-, γ-isomer), cypermethrin (cypermethrin, α-, β-, θ-, ζ-isomer ), cyphenothrin [(1R)-trans isomer], deltamethrin, dimefluthrin, empenthrin [(EZ)-(1R)-isomer], esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flubrocitrin flucythrin, flumethrin, fluvalinate (τ-fluvalinate), halfenprox, imiprothrin, cadethrin, metofruthrin, monfluorothrin, epsilon metofluthrin, epsilon monfluorothrin, permethrin, phenothrin [(1R)-trans isomer], prallethrin, profluthrin, pyrethrin, resmethrin, silafluofen, tefluthrin, phthalthrin (tetramethrin), tetramethrin [(1R)-isomer], tralomethrin, transfluthrin, DDT, methoxychlor, aldrin, dieldrin and lindane (lindane), etc. is mentioned.

Nicotinic acetylcholine receptor (nAChR) competitive modulators include acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, nicotine sulfate (nicotine), sulfoxaflor, flupyradifron, dichloromesothiaz and triflumezopyrim. .

Nicotinic acetylcholine receptor (nAChR) allosteric modulators include spinetoram, spinosad, flupyrimine and GS-omega/kappa HXTX-Hv1a peptide.

Glutamatergic chloride channel (GluCl) allosteric modulators include abamectin, emamectin benzoate, lepimectin and milbemectin.

Juvenile hormone mimics include hydroprene, kinoprene, methoprene, fenoxycarb and pyriproxyfen.

Other non-specific (multi-site) inhibitors include methyl bromide (methyl bromide), other alkyl halides, chloropicrin, sodium aluminum fluoride, sulfuryl fluoride, borax, boric acid, disodium octaborate salts, metaborate sodium salt, tartar emetic, dazomet, carbam (metam ammonium salt), metam sodium salt (carbam sodium salt), methyl isothiocyanate (methyl isothiocyanate), and the like.

String tone organ TRPV channel modulators include pymetrozine, pyrifluquinazone and aphidopyropene.

Mite growth inhibitors that act on CHS1 include clofentezine, diflovidazine, hexythiazox and etoxazole.

As a microorganism-derived insect midgut lining-disrupting agent, Bacillus thuringiensis subsp. israelensis, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. Kurstaki, Bacillus thuringiensis subsp. tenebrionis, proteins contained in B.t. crops (Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Bb, Cry34Ab1/Cry35Ab1) and Bacillus sphaericus.

Mitochondrial ATP synthase inhibitors include diafenthiuron, azocyclotin, tricyclohexyltin hydroxide (cyhexatin), fenbutatin oxide, BPPS (propargite) and tetradifon.

Oxidative phosphorylation uncouplers that disrupt the proton gradient include chlorfenapyr, DNOC and sulfluramide.

Nicotinic acetylcholine receptor (nAChR) channel blockers include bensultap, cartap hydrochloride, thiocyclam, thiosultap sodium salt and monosultap.

Chitin biosynthesis inhibitors that act on CHS1 include bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron.

Buprofezin and the like are examples of chitin biosynthesis inhibitors (type 1).

Moulting inhibitors (Diptera insects) include cyromazine and the like.

Moulting hormone (ecdysone) receptor agonists include chromafenozide, halofenozide, methoxyfenozide and tebufenozide.

Examples of octopamine receptor agonists include amitraz.

Mitochondrial electron transport chain complex III inhibitors include hydramethylnon, acequinosyl, fluacrypyrim and bifenazate.

Mitochondrial electron transport chain complex I inhibitors (METI) include fenazaquin, fenpyroximate, pyridaben, pyrimidifen, tebufenpyrad, tolfenpyrad and delis (rotenone).

Voltage-gated sodium channel blockers include indoxacarb and metaflumizone.

Acetyl-CoA carboxylase inhibitors include spirodiclofen, spiromesifen, spiropidione and spirotetramat.

Mitochondrial electron transport system complex IV inhibitors include aluminum phosphide, calcium phosphide, hydrogen phosphide, zinc phosphide, hydrocyanic acid (calcium cyanide/sodium cyanide) and potassium cyanide.

Mitochondrial electron transport chain complex II inhibitors include cyenopyrafen, cietopirafen, cyflumetofen, piflubumide and cyclobutrifluram.

Ryanodine receptor modulators include chlorantraniliprole, cyantraniliprole, cyclaniliprole, flubendiamide, tetraniliprole, tetrachlorantraniliprole, cyhalodiamide and ciprofuranilide.

String tone organ modulators include flonicamid and the like.

GABAergic chloride ion channel allosteric modulators include brofuranilide, fluxametamide and isocycloseram.

Baculoviruses include codling moth Cydia pomonella GV, codling moth Thaumatotibia leucotreta GV, velvet bean beetle Anticarsis gemmatalis MNPV and Helicoverpa armigera NPV.

Other insecticides, acaricides and nematicides include azadirachtins, benzomates (benzoximates), phenisobromorates (bromopropylates), quinoxalines (quinomethionates), quercene (dicofol), lime-sulfur mixtures. , mancozeb, pyridalyl, sulfur, acinonapyr, amidoflumet, benzpyrimoxane, fluazaindolizine, fluenesulfone, fluhexafone, flupentiophenox, flometoquine, metaldehyde, cyclopyrazofurol, zinpropyridaz, Burkholderia sp., Wolbachia Pipientis (Zap), Aritasou extract, fatty acid monoester with glycerin or propanediol, neem oil, machine oil, rapeseed oil, formulated oil, starch, reduced starch saccharate, sodium oleate, ferric phosphate, Nemadectin, Beauveria bassiana strain, Metarhidium anisopria strain (F52), Pecilomyces fumosoroseus apopka strain (97), diatomaceous earth, DCIP (dichlorodiisopropyl ether), DD (1,3 dichloropropene), levamisole hydrochloride, morantel tartrate and thioxazaphene.

(3-3) Active Ingredients for Plant Growth Regulator Applications Suitable active ingredients for plant growth regulator applications include, for example, aminoethoxyvinylglycine, chlormecort, chlorpropham, cyclanilide, dikeglac, daminozit, ethephon, flurprimidol, flumetralin, forchlorfenurone, gibberellin, maleic acid hydrazide salt, mepiquat chloride, methylcyclopropene, benzylaminopurine, paclobutrazole, prohexadione, thidiazuron, tributylphosphorotrithioate, trinexapac-ethyl, Uniconazole, sodium 1-naphthaleneacetate, 1-naphthylacetamide, 1-methylcyclopropene, 4-CPA (4-chlorophenoxyacetic acid), MCPB (ethyl 2-methyl-4-chlorophenoxybutyrate), isoprothiolane, itaconic acid, indole butyric acid, eticlozate, calcium formate, chlormequat, choline, cyanamide, dichlorprop, gibberellin, daminozide, decyl alcohol, sorbitan trioleate, nicosulfuron, pyraflufenethyl, butruarin, prohydrojasmon and pendimethalin, etc. .

[5. Plant disease control agent]
The plant disease control agent in this embodiment is the R-enantiomer or mixed enantiomer of the azole derivative (I) of this embodiment, or an agriculturally or industrially acceptable salt thereof, or the agricultural and horticultural fungicide of this embodiment. A foliage treatment or non-foliage treatment plant disease control agent contained as a component. Since the R-enantiomer or mixed enantiomer of the azole derivative (I) of this embodiment, or its agriculturally or industrially acceptable salt conforms to the previous explanation, the explanation thereof will not be repeated. Since the agricultural and horticultural fungicide of this aspect also conforms to the above explanation, the explanation thereof will not be repeated.

The plant disease control agent in this aspect is for foliage treatment or non-foliage treatment. The foliage treatment includes foliage spraying. Non-foliage treatments include seed treatments, irrigation treatments, and water surface treatments, including treatments for bulbs and tubers.

The plant disease control agent of this embodiment may contain a component other than the R-enantiomer or mixed enantiomer of the azole derivative (I), or an agriculturally or industrially acceptable salt thereof, or an agricultural or horticultural fungicide. good. Such components include formulation aids. Since the formulation adjuvant is as described above, the description thereof will not be repeated. In addition, the content of the R-enantiomer or mixed enantiomer of the azole derivative (I) contained in the plant disease control agent, or an agriculturally or industrially acceptable salt thereof, or the content of the agricultural and horticultural fungicide may be adjusted depending on the purpose. It can be determined as appropriate.

[6. Plant disease control method]
The agricultural and horticultural agent in this embodiment can be used, for example, in agricultural or non-agricultural lands such as fields, paddy fields, lawns and orchards. In addition, the agricultural and horticultural chemical in the present embodiment can be applied not only by foliage treatment such as foliage spraying, but also by non-foliage treatment such as seed treatment, irrigation treatment and water surface treatment, including treatment of bulbs and tubers. Therefore, the method for controlling plant diseases in the present embodiment is a method including a procedure of foliage treatment or non-foliage treatment using the agricultural and horticultural agent described above. By applying the agricultural and horticultural fungicide according to this embodiment to target plants, it is also possible to protect the target plants from damage caused by the plant diseases described above. Therefore, it can be said that the method for controlling plant diseases in this embodiment is a method for protecting target plants from damage caused by the plant diseases described above. In addition, when performing non-foliage processing, labor can be reduced compared with the case where foliage processing is performed.

In the application by seed treatment, the drug is attached to the seeds by mixing and stirring the wettable powder, powder, etc. with the seeds, or by immersing the seeds in a diluted wettable powder, etc. Also included are seed coating treatments. The amount of the active ingredient used for seed treatment is, for example, 0.01 to 10000 g, preferably 0.1 to 1000 g, per 100 kg of seed. Seeds treated with agricultural and horticultural chemicals may be used in the same manner as ordinary seeds.

Application by irrigation is carried out by applying granules, etc. to the planting hole or its surroundings when transplanting seedlings, or applying granules, wettable powders, etc. to the soil around seeds or plants. . The amount of the active ingredient used in irrigation treatment is, for example, 0.01 to 10,000 g, preferably 0.1 to 1,000 g per 1 m ² of agricultural land.

Application by water surface treatment is performed by treating paddy field water with granules, etc. The amount of the active ingredient used for water surface treatment is, for example, 0.1 to 10000 g, preferably 1 to 1000 g, per paddy field 10a.

The amount of the active ingredient used for foliar application is, for example, 20 to 5000 g, more preferably 50 to 2000 g, per 1 ha of agricultural and horticultural land such as fields, rice fields, orchards and greenhouses.

In addition, since the concentration and amount used vary depending on the dosage form, timing of use, method of use, place of use, target crops, etc., it is possible to increase or decrease without sticking to the above range.

[7. Industrial material protective agent]
(1) Effect of Protecting Industrial Materials The R-enantiomer or mixed enantiomers of azole derivative (I) or industrially acceptable salts thereof exhibit an excellent effect of protecting industrial materials from a wide range of harmful microorganisms. It can also be used as a protective agent for industrial materials. Examples of such microorganisms include the microorganisms shown below.

Aspergillus sp., Trichoderma sp., Penicillium sp., Geotrichum sp., Chaetomium sp., Cadphora, which are paper and pulp degrading microorganisms (including slime-forming bacteria) (Cadophora sp.), Ceratostomella sp., Cladosporium sp., Corticium sp., Lentinus sp., Lenzites sp., Phoma sp. , Polysticus sp., Pullularia sp., Stereum sp., Trichosporium sp., Aerobacter sp., Bacillus sp., Desulfovibrio (Desulfovibrio sp.), Pseudomonas sp., Flavobacterium sp., Micrococcus sp., Aspergillus sp.), Penicillium sp., Chaetomium ( Chaetomium sp.), Myrothecium sp., Curvularia sp., Gliomastix sp., Memnoniella sp., Sarcopodium sp., Stschybotrys sp. ), Stemphylium sp., Zygorhynchus sp., Bacillus sp., Staphylococcus sp., etc., wood-altering fungi Tyromyces palustris, Coriolus versicolor ), Aspergillus sp., Penicillium sp., Rhizopus zopus sp.), Aureobasidium sp., Gliocladum sp., Cladosporium sp., Chaetomium sp., Trichoderma sp., leather Aspergillus sp., Penicillium sp., Chaetomium sp., Cladosporium sp., Mucor sp., Paecilomyces p., Pilobus sp. ), Pullularia sp., Trichosporon sp., Tricothecium sp., rubber and plastic degrading microorganisms Aspergillus sp., Penicillium sp., Rhizopus sp. ), Trichoderma sp., Chaetomium sp., Myrothecium sp., Streptomyces sp., Pseudomonas sp., Bacillus sp., Micrococcus sp.), Serratia sp., Margarinomyces sp., Monascus sp., Aspergillus sp., Penicillium sp. Cladosporium sp., Aureobasidium sp., Gliocladium sp., Botryodiplodia sp., Macrosporium sp., Monilia sp. ), Phoma sp., Pullularia sp., Sporotrichum sp., Trichoderma (Tric hoderma sp.), bacillus sp., Proteus sp., Pseudomonas sp., Serratia sp.

(2) Formulation An industrial material protecting agent containing the R-enantiomer or mixed enantiomer of azole derivative (I) or an industrially acceptable salt thereof as an active ingredient is the R-enantiomer or mixed enantiomer of azole derivative (I) or Various ingredients may be included in addition to the industrially acceptable salts thereof. The industrial material protective agent containing the R-enantiomer or mixed enantiomer of azole derivative (I) or industrially acceptable salt thereof as an active ingredient is dissolved or dispersed in a suitable liquid carrier, or mixed with a solid carrier. can be used The industrial material protective agent containing the R-enantiomer or mixed enantiomer of the azole derivative (I) or an industrially acceptable salt thereof as an active ingredient may further include an emulsifier, a dispersant, a spreading agent and a penetrating agent, if necessary. , wetting agents or stabilizers. In addition, as the dosage form of the industrial material protective agent containing the R-enantiomer or mixed enantiomer of the azole derivative (I) or industrially acceptable salt thereof as an active ingredient, wettable powders, powders, granules, tablets, Pastes, suspensions, sprays and the like can be mentioned. The industrial material protective agent containing the R-enantiomer or mixed enantiomer of the azole derivative (I) or an industrially acceptable salt thereof as an active ingredient may contain other fungicides, insecticides or antidegradants. good.

The liquid carrier is not particularly limited as long as it does not react with the active ingredient. Examples of liquid carriers include water, alcohols (e.g., methyl alcohol, ethyl alcohol, ethylene glycol, cellosolve, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., dimethyl ether, diethyl ether, dioxane, tetrahydrofuran). etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnaphthalene, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, kerosene, machine oil, fuel oil, etc.), acid amides (e.g., dimethylformamide , N-methylpyrrolidone, etc.), halogenated hydrocarbons (e.g., chloroform, carbon tetrachloride, etc.), esters (e.g., ethyl acetate, fatty acid glycerol esters, etc.), nitriles (e.g., acetonitrile, etc.) and dimethyl sulfoxide etc. can be mentioned.

As solid carriers, fine powders or granules such as kaolin clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, urea and ammonium sulfate can be used.

Examples of emulsifiers and dispersants include soaps, surfactants such as alkylsulfonic acids, alkylarylsulfonic acids, dialkylsulfosuccinic acids, quaternary ammonium salts, oxyalkylamines, fatty acid esters, polyalkylene oxides and anhydrosorbitols. can be used.

When the R-enantiomer or mixed enantiomer of azole derivative (I) or an industrially acceptable salt thereof is contained as an active ingredient in a formulation, the content ratio varies depending on the dosage form and purpose of use, but the total amount of the formulation 0.1 to 99.9% by weight with respect to In actual use, the treatment concentration is usually 0.005 to 5% by weight, preferably 0.01 to 1% by weight. preferably.

The R-enantiomer or mixed enantiomers of azole derivative (I) or industrially acceptable salts thereof exhibit excellent effects of protecting industrial materials from a wide range of harmful microorganisms that attack them. That is, the industrial material protective agent containing the R-enantiomer or mixed enantiomer of the azole derivative (I) or an industrially acceptable salt thereof as an active ingredient has low toxicity to humans and animals, is excellent in handling safety, and does not attack industrial materials. It can show excellent effect of protecting materials from a wide range of harmful microorganisms. Therefore, the industrial material protective agent in this embodiment can contribute to Goal 12 of the Sustainable Development Goals (SDGs), "responsible consumption and production".

〔summary〕
As described above, the R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative according to one embodiment of the present invention is the R-enantiomer or the R-enantiomer of the compound represented by the following general formula (I) and S - mixtures with enantiomers, or agriculturally or industrially acceptable salts thereof.

[in the formula (I),
* represents a chiral center;
R ¹ and R ² are each independently hydrogen, a C ₁ -C ₆ -alkyl group, a C ₃ -C ₈ -cycloalkyl group or a C ₃ -C ₈ -cycloalkyl- _{C 1} -C ₄ -alkyl group; ;
R ¹ and R ² may be combined to form a ring;
Z is a phenyl group or a 5- or 6-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from O, N and S;
R ³ is halogen, hydroxy, amino, nitrile, nitro, pentafluorosulfanyl, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy or a C ₁ -C ₄ -haloalkoxy group;
R ³ is bonded to n arbitrary substitution positions of Z;
n is 0, 1, 2, 3, 4 or 5 when at least one of R ¹ and R ² is not hydrogen, n is 1, 2, 3 when both R ¹ and R ² are hydrogen , 4 or 5;
m is 1 or 2; ]

Further, the agricultural and horticultural fungicide or the industrial material protective agent according to the present invention includes the R-enantiomer of the azole derivative of claim 1 as one of the active ingredients, or a mixture of the R-enantiomer and the S-enantiomer, or an agricultural chemical thereof. It is characterized by containing a commercially or industrially acceptable salt and further containing other active ingredients.

In addition, in the agricultural and horticultural fungicide or industrial material protection agent according to the present invention, the other active ingredients include (i) a nucleic acid synthesis and metabolism inhibitor, a fungicide acting on the cytoskeleton and motor protein, a respiratory inhibitor, Amino acid/protein biosynthesis inhibitors, signal transduction inhibitors, lipid biosynthesis or transport/cell membrane structure or function inhibitors, cell membrane sterol biosynthesis inhibitors, cell wall biosynthesis inhibitors, melanin biosynthesis inhibitors, host plant an active ingredient of a fungicide selected from resistance inducers and multisite fungicides, (ii) nicotinic acetylcholine receptor antagonistic modulators, sodium channel modulators, ryanodine receptor modulators, acetylcholinesterase inhibitors, oxidative phosphorylation It preferably contains at least one selected from an active ingredient of an insecticide selected from an uncoupler and a mitochondrial electron transport chain complex I inhibitor, and (iii) an active ingredient of a plant growth regulator.

In addition, the plant disease control agent according to the present invention is the R-enantiomer of the above-mentioned azole derivative, or a mixture of the R-enantiomer and the S-enantiomer, or an agriculturally or industrially acceptable salt thereof, or the above-mentioned agricultural and horticultural A plant disease control agent for foliage treatment or non-foliage treatment, containing a fungicide for foliage as an active ingredient.

In addition, the plant disease control method according to the present invention has a configuration including a step of performing foliage treatment or non-foliage treatment using the plant disease control agent described above.

Further, the plant disease control product according to the present invention is a plant disease control product for preparing the above agricultural and horticultural fungicide, which is a combination preparation for mixing and using, the above azole derivative or a mixture of the R-enantiomer and the S-enantiomer, or an agriculturally or industrially acceptable salt thereof, and the above-described other active ingredients separately.

Examples are shown below to describe the embodiments of the present invention in more detail. Of course, the present invention is not limited to the following examples, and it goes without saying that various aspects are possible for the details. Furthermore, the present invention is not limited to the above-described embodiments, and can be modified in various ways within the scope of the claims. It is included in the technical scope of the invention. In addition, all documents described in this specification are incorporated by reference.

[Synthesis of Racemic Form of Azole Derivative]
A racemate of the following azole derivative (I) was synthesized according to the method described in Patent Document 1.
Azole derivative I-7: 1-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenoxy)-2,2-dimethyl-2,3-dihydro-1H- Indene-1-olazole derivative I-11: 1-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-fluorophenoxy)-2,2-dimethyl-2,3 -dihydro-1H-indene-1-olazole derivative I-13: 1-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-trifluoromethoxyphenoxy)-2, 2-dimethyl-2,3-dihydro-1H-inden-1-ol

[Fractionation of Enantiomers of Azole Derivatives]
The racemate of the azole derivative I-7 prepared above was subjected to high performance liquid chromatography (HPLC) connected to a preparative column in which amylose tris(3,5-dimethylphenylcarbamate) was immobilized on a silica gel carrier. A preparative separation of the enantiomers was carried out. Specific conditions are as follows.

(Fraction conditions)
Preparative column: product name “CHIRALPAK IA”, manufactured by Daicel Chemical Industries, Ltd. Mobile phase: 100% acetonitrile Column temperature: 40°C
Detection wavelength: 230 nm
Flow rate: 2mL/min
Amount applied: 10 μL

When separated under the above conditions, two peaks with different elution times were detected. For these two peaks, the specific rotations of the compounds derived from the peaks were measured. The specific optical rotation was measured using P-1020 (manufactured by JASCO Corporation, Na lamp: 589 nm).

As a result of measuring the specific optical rotation, the compounds eluted later showed levorotatory properties. The measurement results of the specific rotation of the (−)-enantiomer were as follows:
Specific rotation: [α] ²⁰ D=−72.5° (2.4 mg sample in 1.5 mL chloroform).

[Determination of configuration of (−)-enantiomer of azole derivative]
(Sample preparation method)
A 1 mg solid sample of the (−)-enantiomer fractionated above was dissolved in 1 mL of ethyl acetate. After standing, the recrystallized sample was subjected to single crystal X-ray structural analysis to determine the configuration of the (−)-enantiomer.

(Measurement condition)
Equipment: R-AXIS RAPID II diffractometer (manufactured by Rigaku Corporation)
X-ray source: Cu-Kα
Measurement temperature: 93K
Solve: SHELXT
Refinement: SHELXL

The (-)-enantiomer of the azole derivative I-7 was the R-configuration. Crystallographic data for a single crystal of the R-(-)-enantiomer of azole derivative I-7 are shown in Table 3. FIG. 1 shows the results of X-ray crystal structure analysis. FIG. 1 is an ORTEP diagram showing the molecular structure of the R-(−)-enantiomer of the azole derivative I-7 by X-ray crystallography.

<Formulation example>
Using the synthesized azole derivative racemate and each enantiomer, wettable powders and emulsions were formulated as follows.
Formulation example 1 (wettable powder)
Azole derivative racemate or each enantiomer 20.0 parts Sodium lauryl sulfate 2 parts Sodium salt of alkylnaphthalenesulfonic acid formalin condensate 5 parts Zinc stearate 0.2 parts White carbon 3 parts Clay 69.8 parts were pulverized and mixed. used as a hydrating agent.
Formulation Example 2 (Emulsion)
Azole derivative racemate or each enantiomer 4.0 parts polyoxyalkylene allyl phenyl ether metal alkylbenzene sulfonate xylene mixture 10.0 parts 1-butyl-2-pyrrolidone 30.1 parts N,N-dimethyloctanamide 30.1 parts of N,N-dimethyldecanamide mixture and 25.8 parts of solvent naphtha were uniformly mixed and dissolved to prepare an emulsion.

<Wheat leaf blight fungus with low sensitivity to existing sterol biosynthesis inhibitors compared to wild type>
Strains A to G of wheat leaf blight fungi were prepared as pathogens that are less sensitive to existing sterol biosynthesis inhibitors than wild type. These strains have mutations at specific amino acid positions in the wild-type CYP51 protein, making them less sensitive to existing sterol biosynthesis inhibitors compared to the wild-type. The position and type of mutation for each strain are shown in Table 4 below. In the table, "Del" means deletion mutation. In addition, the amino acid sequence of the wild-type CYP51 protein is easily obtained from public databases such as the M. graminicola genome sequencing project (https://mycocosm.jgi.doe.gov/Mycgr1/Mycgr1.home.html) and GenBank. For example, disclosed at: https://mycocosm.jgi.doe.gov/cgi-bin/getDbSeq?db=Mycgr1&searchTabList=protein,proteinHitDesc&hitSeqList=97669.

<Control compound>
The following compounds were prepared as control compounds.
Mefentrifluconazole (compound described in WO2020/078942): 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1,2,4- Triazol-1-yl)propan-2-ol Metconazole: (1RS,5RS; 1RS,5SR)-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H-1,2,4- triazol-1-ylmethyl)cyclopentanol

<Antibacterial activity test against plant pathogens>
The antibacterial activity of the synthesized azole derivative racemate or each enantiomer against various phytopathogenic filamentous fungi was tested by a petri dish test.

After autoclave sterilization, in PDA medium (potato-dextrose-agar medium) cooled to around 60° C., the test compound was dissolved in dimethyl sulfoxide to a predetermined drug concentration, and 1% (V/V) was added to the PDA medium. added. The PDA medium was thoroughly mixed so that the drug concentration in the medium was uniform, and the medium was poured into a petri dish to prepare a plate medium containing various test compounds.

On the other hand, the fungal flora of various plant pathogenic bacteria previously cultured on PDA medium was punched out with a cork borer with a diameter of 4 mm, and inoculated onto the above-mentioned drug-containing plate medium. After culturing at a temperature for a given period of time according to Table 5, the diameter of the bacterial colony on the drug-treated plate was measured. The mycelial elongation inhibition rate (%) was calculated by the following formula in comparison with the bacterial lawn diameter on an untreated plate containing no test compound.

R=100(dc−dt)/dc
(In the formula, R = hyphal elongation inhibition rate (%), dc = diameter of bacterial lawn on non-treated plate, dt = diameter of bacterial lawn on drug-treated plate, respectively.)

When two types of compounds are mixed and used, then Colby's formula (the following formula)
Inhibition rate when mixed (theoretical value) = α + ((100-α) × β) / 100
The synergistic effect of the two compounds was determined by the method using . In the above formula, α and β indicate the inhibitory rate when each compound is used alone.

(Test Example 1: Antibacterial activity test when using a single agent)
The racemate of the azole derivative I-7 or the R-(-)-enantiomer of the azole derivative I-7 (hereinafter simply "the R-enantiomer of the azole derivative I-7") is treated against various plant pathogenic fungi by the method described above. An antibacterial activity test was performed.

Table 6 shows the results. The rate of inhibition of mycelial growth when the R-enantiomer of the azole derivative I-7 was used against various plant pathogenic fungi was higher than the rate of inhibition of mycelial growth when the racemate of the azole derivative I-7 was used. These results indicated that the R-enantiomer of the azole derivative I-7 was superior in antibacterial properties to the racemate of the azole derivative I-7.

(Test Example 2: Antibacterial activity test when using a mixture of two agents)
The racemate of azole derivative I-7, I-11 or I-13 or the R-enantiomer of I-7 together with another active ingredient (prothioconazole, isoflurcipram, trifloxystrobin or fluoxythioconazole) ) was tested for antibacterial activity against various plant pathogens by the method described above.

The results are shown in Tables 7-71. Suppression of mycelial elongation when using a two-drug mixture prepared by mixing the racemate of azole derivative I-7, I-11 or I-13 or the R-enantiomer of I-7 with another active ingredient The rate was higher than the theoretical value calculated from the mycelial elongation inhibition rate when each was used alone. These results reveal that the racemate of azole derivative I-7, I-11 or I-13 or the R-enantiomer of I-7 and other active ingredients exhibit a synergistic effect. .

(Test Example 3: Antibacterial activity test when using a mixture of three agents)
The antibacterial activity against various plant pathogenic fungi is obtained by the method described above for a three-drug mixture obtained by mixing the R-enantiomer of the azole derivative I-7 and other active ingredients with the S-enantiomer of the azole derivative I-7. did the test. In each table, mixed enantiomer indicates the total amount of R-enantiomer and S-enantiomer of azole derivative I-7 contained in the triple mixture. The molar ratio of R-enantiomer to S-enantiomer in the mixed enantiomers is 1:1.

The results are shown in Tables 72-95. A ternary mixture prepared by further mixing (a) the R-enantiomer of the azole derivative I-7 and another active ingredient with the (b) S-enantiomer of the azole derivative I-7 was used. The rate of inhibition of mycelial elongation in this case was higher than the theoretical value calculated from the rate of inhibition of mycelial elongation when (a) or (b) was used alone. From these results, (a) a two-drug mixture of the R-enantiomer of the azole derivative I-7 and another active ingredient and (b) the S-enantiomer of the azole derivative I-7 exhibit a synergistic effect. It became clear.

(Test Example 4: Antibacterial activity test against sterol biosynthesis inhibitor low-susceptibility strains A to G of wheat leaf blight fungus)
The racemate of the azole derivative I-7, the R-enantiomer, or the control compound were tested for antibacterial activity against wheat leaf blight strains AG by the method described above.

The results are shown in Tables 96-98. The racemate and R-enantiomer of the azole derivative I-7 exhibited a higher mycelial elongation inhibition rate against strains A to G than any of the control compounds (mefentrifluconazole and fluquinconazole), and had excellent antibacterial activity. was

(Test Example 5: Antibacterial activity test when using a mixture of two agents)
A mixture of the racemic azole derivative I-7 and another active ingredient (fluopyram or spiroxamine) was tested for antibacterial activity against various plant pathogens by the method described above.

The results are shown in Tables 99-111. The rate of inhibition of mycelial growth when using a two-drug mixture prepared by mixing the racemate of azole derivative I-7 and other active ingredients is calculated from the rate of inhibition of mycelial growth when each is used alone. higher than the theoretical value given.

The R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative according to one aspect of the present invention, or an agriculturally or industrially acceptable salt thereof, is used as an agricultural or horticultural fungicide or industrial material protection agent. It can be suitably used as an active ingredient of a drug.

Claims

The R-enantiomer of an azole derivative represented by the following general formula (I), or a mixture of the R-enantiomer and the S-enantiomer, or an agriculturally or industrially acceptable salt thereof.

[in the formula (I),
* represents a chiral center;
R 1 and R 2 are each independently hydrogen, a C 1 -C 6 -alkyl group, a C 3 -C 8 -cycloalkyl group or a C 3 -C 8 -cycloalkyl- C 1 -C 4 -alkyl group; ;
R 1 and R 2 may be combined to form a ring;
Z is a phenyl group or a 5- or 6-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from O, N and S;
R 3 is halogen, hydroxy, amino, nitrile, nitro, pentafluorosulfanyl, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy or a C 1 -C 4 -haloalkoxy group;
R 3 is bonded to n arbitrary substitution positions of Z;
n is 0, 1, 2, 3, 4 or 5 when at least one of R 1 and R 2 is not hydrogen, n is 1, 2, 3 when both R 1 and R 2 are hydrogen , 4 or 5;
m is 1 or 2; ]
It contains the R-enantiomer of the azole derivative of claim 1 as one of the active ingredients, or a mixture of the R-enantiomer and the S-enantiomer, or an agriculturally or industrially acceptable salt thereof, and further contains other active ingredients. An agricultural or horticultural fungicide or an industrial material protective agent characterized by:
Other active ingredients include (i) nucleic acid synthesis and metabolism inhibitors, bactericidal agents that act on the cytoskeleton and motor proteins, respiratory inhibitors, amino acid/protein biosynthesis inhibitors, signal transduction inhibitors, lipid biosynthesis or transport/ Efficacy of a fungicide selected from cell membrane structure or function inhibitors, cell membrane sterol biosynthesis inhibitors, cell wall biosynthesis inhibitors, melanin biosynthesis inhibitors, host plant resistance inducers, and multi-site fungicides component, (ii) an insecticide selected from nicotinic acetylcholine receptor antagonist modulators, sodium channel modulators, ryanodine receptor modulators, acetylcholinesterase inhibitors, oxidative phosphorylation uncouplers, and mitochondrial electron transport chain complex I inhibitors. and (iii) an active ingredient of a plant growth regulator.
The R-enantiomer or the mixture of the R-enantiomer and the S-enantiomer of the azole derivative according to claim 1, or an agriculturally or industrially acceptable salt thereof, or the agricultural and horticultural fungicide according to claim 2 or 3. A plant disease control agent for foliage treatment or non-foliage treatment, containing the agent as an active ingredient.
A method for controlling plant diseases, comprising the step of performing foliage treatment or non-foliage treatment using the plant disease control agent according to claim 4.
A plant disease control product for preparing the agricultural and horticultural fungicide according to claim 2 or 3,
As a combination preparation for mixed use, the R-enantiomer of the above azole derivative or a mixture of the R-enantiomer and the S-enantiomer, or an agriculturally or industrially acceptable salt thereof, and the above other active ingredients. A product for controlling plant diseases, characterized in that it contains and separately.