WO2012165498A1 - Triazole compound and use thereof - Google Patents

Abstract

In order to provide a compound exhibiting a high controlling effect with respect to a plant disease, this triazole compound is the less polar diastereomer of the two diastereomers of the triazole compound indicated in formula (I), and is the (-)-enantiomer of the enantiomers of the diastereomer that is less polar.

Description

Triazole compounds and use thereof

The present invention relates to an enantiomer of a triazole compound, a plant disease control agent containing the same, a plant disease control method using the plant disease control agent, and use thereof.

Conventionally, as an active ingredient of a plant disease control agent, it is a hydroxyethylazole derivative which is a hetero 5-membered ring containing one or more nitrogen atoms in the ring, and a cycloalkyl group or a part of the carbon atom to which the hydroxy group is bonded Many derivatives have been proposed in which an alkyl group in which a hydrogen atom is substituted with a cycloalkyl group is bonded (see, for example, Patent Documents 1 to 13).

European Patent Application No. 0015756 European Patent Application Publication No. 0052424 European Patent Application Publication No. 0061835 European Patent Application No. 0297345 European Patent Application Publication No. 0047594 European Patent Application No. 0212605 Japanese Patent Gazette “JP-A-56-97276” Japanese Patent Gazette "Japanese Patent Laid-Open No. 61-126049" Japanese Patent Gazette “JP-A 2-286664” Japanese Patent Gazette “JP 59-98061 A” Japanese Patent Gazette "Japanese Patent Laid-Open No. 61-271276" European Patent Application No. 0229642 Japanese Patent Gazette “JP-A-4-230270”

Conventionally, there has been a demand for a plant disease control agent that is low in toxicity to human livestock, has excellent handling safety, and exhibits a high control effect on a wide range of plant diseases.

Therefore, the present invention has been made in view of the above-mentioned problems, and an object thereof is to provide a compound that meets the above-mentioned demand.

In order to solve the above problems, the present inventors have studied in detail the chemical structure and physiological activity of many azole derivatives. As a result, the triazole derivative represented by the following formula (I) was found to have excellent activity, and one of the isomers was found to have particularly excellent activity, thereby completing the present invention. It came. This invention is made | formed based on the novel knowledge which concerns, and includes the following inventions.

The triazole compound according to the present invention has the formula (I)

(In the formula ^{(I), X 1 ~ X} 4 represents a hydrogen atom or a halogen atom, ^{X 5} represents a halogen atom, a plurality of ^{X 2} are the same atom together, ^{X 1} and At least one of X ² is a halogen atom, a plurality of X ⁴ are the same atom, a plurality of X ⁵ are the same atom, X ⁴ and X ⁵ are different atoms, m and n Represents 0 to 3. * represents an asymmetric carbon atom.)
Among the two diastereomers in the triazole compound represented by the formula, is a triazole compound that is a lower polar diastereomer, and is a (−)-enantiomer among the enantiomers in the lower polar diastereomer. .

The plant disease control agent according to the present invention is a plant disease control agent containing the above triazole compound as an active ingredient.

The plant disease control method according to the present invention is a method for controlling plant diseases, which comprises a step of performing a foliage treatment or a non-foliage treatment using the above-mentioned plant disease control agent.

The seed according to the present invention is a seed treated with the above plant disease control agent.

The triazole compound according to the present invention has an excellent bactericidal action against many bacteria that cause plant diseases. Therefore, the chemical | medical agent which contains the triazole compound which concerns on this invention as an active ingredient has an effect which can exhibit the high control effect with respect to a wide range of plant diseases.

Hereinafter, an embodiment of a triazole compound, a plant disease control agent, and a plant disease control method according to the present invention will be described.

[Triazole compound]
The triazole compound in the present embodiment has the formula (I)

(In the formula ^{(I), X 1 ~ X} 4 represents a hydrogen atom or a halogen atom, ^{X 5} represents a halogen atom, a plurality of ^{X 2} are the same atom together, ^{X 1} and At least one of X ² is a halogen atom, a plurality of X ⁴ are the same atom, a plurality of X ⁵ are the same atom, X ⁴ and X ⁵ are different atoms, m and n Represents 0 to 3. * represents an asymmetric carbon atom.)
Among the two diastereomers in the triazole compound represented by the formula, is a triazole compound that is a lower polar diastereomer, and is a (−)-enantiomer among the enantiomers in the lower polar diastereomer. .

X ¹ to X ⁴ each independently represents a hydrogen atom or a halogen atom, and X ⁵ represents a halogen atom. Examples of the halogen atom in X ¹ to X ⁴ and X ⁵ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom and a bromine atom are preferable.

A plurality (four) of X ² are the same atom, and at least one of X ¹ and X ² is a halogen atom. Of these, X ¹ is a halogen atom, it is preferred that X ² is a hydrogen atom.

As described above, X ³ is a hydrogen atom or a halogen atom, and preferably a hydrogen atom.

Plural (two) X ⁴ are the same atom, and similarly plural (two) X ⁵ are the same atom. X ⁴ and X ⁵ are atoms different from each other. For example, when two X ⁴ are both hydrogen atoms and two X ⁵ are both chlorine atoms, or two X ⁴ are both hydrogen atoms and two X ⁵ are Examples of these include, but are not limited to, a bromine atom. For example, X ⁴ and X ⁵ may be different halogen atoms.

M and n each independently represents an integer of 0 to 3. Among these, m is preferably 0 or 1, and 0 is particularly preferable. On the other hand, n is preferably from 0 to 2, particularly preferably 1 or 2.

As a preferred specific example, among the two diastereomers in the triazole compound represented by the above formula (I), X ¹ is a halogen atom, X ² is a hydrogen atom, and m is 0, Among the enantiomers in the diastereomers having a low polarity, the triazole compounds which are (−)-enantiomers among the enantiomers in the diastereomers having a lower polarity.

Further, as a preferred embodiment, X ³ and X ⁴ triazole compounds mentioned above are hydrogen atom.

Further specific examples of the compound represented by the above formula (I) (hereinafter referred to as “compound (I)”) include, for example, a compound represented by the following formula (I-1).

(In the formula ^{(I-1), X 1a} and ^{X 5a} are each independently represents a chlorine atom or a bromine atom, ^{n a} represents 0, 1 or 2. * Is an asymmetric carbon atom Is shown.)
In compound (I), there are two asymmetric carbon atoms (the carbon atom indicated by * in formula (I)). Therefore, two diastereomers exist in compound (I). In the present specification, the “diastereomer” refers to a stereoisomer generated by the presence of a plurality of asymmetric carbon atoms in a molecule and not having a mirror image relationship.

The triazole compound in the present embodiment is a diastereomer having a lower polarity among the two diastereomers. Hereinafter, of the two diastereomers in the compound represented by the formula (I), a diastereomer having a lower polarity is referred to as “compound (Ia)”.

As used herein, the term “lower polar diastereomer” means that when the Rf values of normal phase thin layer chromatography under the same conditions (for example, using ethyl acetate / hexane as a solvent) are compared, The larger diastereomer is intended.

Each diastereomer has a pair of enantiomers, but the compound in the present embodiment is the (−)-enantiomer of the pair of enantiomers in the less polar diastereomer. In this specification, “(−)-enantiomer” refers to an enantiomer that rotates the vibration plane of linearly polarized light of the sodium D line to the left. Hereinafter, of the pair of enantiomers in the compound (Ia), the (−)-enantiomer (that is, the compound according to the present embodiment) is referred to as “compound (Ia (−))”.
[Method for producing triazole compound]
(1) Separation of diastereomers and enantiomers Compound (Ia (−)) can be obtained, for example, by separating it from an isomer mixture of compound (I) obtained by the method for producing a triazole compound described later.

As a method for separating each diastereomer from the isomer mixture of compound (I), a known technique for separating using a difference in polarity such as normal phase column chromatography, reverse phase column chromatography, and recrystallization is used. Can be mentioned.

As the stationary phase in column chromatography, silica gel, a highly polar stationary phase such as alumina, and a low polarity stationary phase such as alkyl group-bonded silica gel such as octadecylsilyl silica gel can be used. As the eluent, organic solvents such as hexane, ethyl acetate, chloroform, alcohols and acetonitrile, water, and a mixture thereof can be used, and can be appropriately determined according to the type of stationary phase.

Further, a plurality of separation methods may be combined, for example, after separation by column chromatography, separation and purification by recrystallization may be further performed.

Compound (Ia) separated by the above technique is a racemate which is an equivalent mixture of the (−)-enantiomer and (+)-enantiomer of Compound (Ia).

Examples of the separation method of each enantiomer from the racemic compound (Ia) include a method of separation by chiral chromatography. Specifically, amylose tris (3,5-dimethylphenyl carbamate), cellulose tris (3,5-dimethylphenyl carbamate), cellulose tris (3,5-dichlorophenyl carbamate), amylose tris [(S) -α-methyl Benzyl carbamate], cellulose tris (4-methylbenzoate), amylose tris (5-chloro-2-methylphenyl carbamate) or cellulose tris (3-chloro-4-methylphenyl carbamate) immobilized on a silica gel carrier To separate from compound (Ia) using hexane / ethanol (100/0 to 0/100), hexane / isopropanol (100/0 to 0/100), ethanol, methanol or acetonitrile as the mobile phase. By Compound (Ia (-)) to be prepared.

The optical rotation of each separated enantiomer may be determined according to a conventionally known method.

(2) Process for Producing Triazole Compound Next, an embodiment of a process for producing compound (I) will be described.

As shown in the following scheme 1, compound (I) is a compound represented by the following formula (VII) obtained by a known technique (hereinafter referred to as “compound (VII)”), and a compound represented by the following known technique. It can be produced from a compound represented by the formula (VI) (hereinafter referred to as “compound (VI)”).
(Scheme 1)

Hereinafter, each process will be described.

(Process A1)
First, compound (VII) is reacted with compound (VII) in a solvent, and a carbon-carbon bond is generated by a nucleophilic addition reaction of compound (VII) to the carbonyl carbon atom with an organometallic compound. Thereby, a halohydrin compound represented by the following formula (V) (hereinafter referred to as “compound (V)”) is obtained (see the following reaction formula (1)).
(Reaction Formula (1))

Here, X ³ , X ⁴ and n are synonymous with the above-mentioned X ³ , X ⁴ and n.

X ⁶ represents a halogen atom.

L represents alkali metal, alkaline earth metal-Q1 (Q1 is a halogen atom), 1/2 (Cu alkali metal), or zinc-Q2 (Q2 is a halogen atom). Examples of the alkali metal include lithium, sodium, and potassium, and lithium is particularly preferable. Moreover, magnesium etc. are mentioned as an alkaline-earth metal.

R ² represents a functional group represented by the following formula (XIV).

In the formula (XIV), X ¹ , X ² and m have the same meanings as X ¹ , X ² and m described above.

The solvent is not particularly limited as long as it is an inert solvent, and examples thereof include ethers such as diethyl ether, tetrahydrofuran and dioxane, and aromatic hydrocarbons such as benzene, toluene and xylene. These solvents can also be used as a mixture. In addition, when water is used for the reaction, it can be used by mixing with an organic solvent. When used with a hydrophobic organic solvent, a tetrabutylammonium salt, trimethylbenzylammonium salt is added to the reaction mixture as necessary. It is also possible to carry out the reaction by adding a phase transfer catalyst such as a salt and a quaternary ammonium salt such as triethylbenzylammonium salt, and crown ether and the like.

The amount of compound (VI) to be used with respect to compound (VII) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol. Compound (VI) is preferably prepared just before the reaction. Moreover, it may be possible to carry out the reaction while generating the compound (VI) in the reaction system. In particular, when L is zinc-Q2 (Q2 is a halogen atom), it is preferable to carry out the reaction while generating compound (VI) in the reaction system.

Further, a Lewis acid may be added if desired. In this case, the amount of the Lewis acid used relative to compound (VI) is, for example, 0 to 5 times mol (excluding 0), preferably 0.1 to 2 times mol. Examples of the Lewis acid include aluminum chloride, zinc chloride and cerium chloride.

The reaction temperature and reaction time can be appropriately set depending on the type of the solvent, compound (VI), compound (VI) and the like. The reaction temperature is preferably −100 ° C. to 200 ° C., more preferably −70 ° C. to 100 ° C. The reaction time is preferably 0.1 to 12 hours, and more preferably 0.5 to 6 hours.

As the compound (VI), a commercially available compound or a compound that can be produced by an existing synthesis technique such as conversion of a halogenated alkenyl compound into an organometallic reagent can be used. Similarly, as compound (VII), a commercially available compound or a compound that can be produced by existing techniques can be used.

(Process A2)
Next, the compound (V) is reacted in a solvent in the presence of a base, and an oxirane compound having a double bond in the molecule represented by the following formula (IV) (hereinafter referred to as “compound (IV)”). (See the following reaction formula (2)).
(Reaction Formula (2))

Bases used in the reaction include alkali metal or alkaline earth metal hydroxide salts such as sodium hydroxide, potassium hydroxide and calcium hydroxide, and alkali metal carbonates or carbonates such as sodium carbonate and potassium carbonate. Although hydrogen salt etc. can be used conveniently, it is not limited to these.

The amount of the base is, for example, 0.5 to 20 times mol, preferably 0.8 to 5 times mol for the compound (V).

The solvent is not particularly limited. For example, alcohols such as methanol, ethanol and isopropanol; ethers such as diethyl ether, tetrahydrofuran and dioxane; N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2 Amides such as pyrrolidinone; hydrocarbons such as n-hexane, methylcyclohexane, benzene, toluene and xylene; halogenated hydrocarbons such as dichloroethane and chloroform; and mixed solvents thereof. When an aqueous base solution is used with a hydrophobic solvent, the reaction mixture contains quaternary ammonium salts such as tetrabutylammonium salt, trimethylbenzylammonium salt and triethylbenzylammonium salt, and interphases such as crown ether and the like. The reaction can also be carried out by adding a transfer catalyst.

The reaction temperature and reaction time can be appropriately set depending on the solvent, the type of compound (V), and the like. The reaction temperature is preferably −20 ° C. to 150 ° C., and more preferably 0 ° C. to 100 ° C. The reaction time is preferably 0.1 to 24 hours, and more preferably 0.5 to 12 hours.

(Process A3)
Next, from the compound (IV), a compound having a gem-dihalocyclopropane structure in the molecule represented by the following formula (III) (hereinafter referred to as “compound (hereinafter referred to as“ compound ”)” by the reaction of trihalomethane with a base such as sodium hydroxide. III) ”). Alternatively, compound (III) is synthesized from compound (IV) by addition reaction of halocarbenes generated by thermal decomposition of trihaloacetate. These reactions are shown in the following reaction formula (3).
(Reaction Formula (3))

In the formula (III), ^{X 5} has the same meaning as ^{X 5} above.

Hereinafter, as a suitable method for synthesizing compound (III), a method for synthesizing by reaction of trihalomethane and a base such as sodium hydroxide will be described.

Examples of the trihalomethane used include chloroform, bromoform, chlorodifluoromethane, dichlorofluoromethane, and dibromofluoromethane. The amount of trihalomethane used with respect to compound (IV) is not particularly limited, and is, for example, 0.5 to 1000 times mol, preferably 0.8 to 100 times mol.

As the solvent, trihalomethane itself or other solvents such as dichloromethane and toluene inert to the reaction can be used.

When adding a base, when using an aqueous solution such as an aqueous sodium hydroxide solution, it is preferable to use a phase transfer catalyst. The phase transfer catalyst is not particularly limited, and includes quaternary ammonium salts such as tetramethylammonium chloride, tetrabutylammonium bromide, cetyltrimethylammonium bromide, benzyltriethylammonium chloride and benzyltrimethylammonium chloride, and three such as triethylamine and tripropylamine. Secondary amines can be used. The amount of the phase transfer catalyst used is, for example, 0.001 to 5 times mol, preferably 0.01 to 2 times mol, of the compound (IV).

The base used for the reaction is not particularly limited, but alkali metal hydroxides such as sodium hydroxide and potassium hydroxide are preferably used, and in many cases, used as an aqueous solution. The amount of the base to be used is, for example, 0.1 to 100 times mol, preferably 0.8 to 50 times mol with respect to compound (IV). Further, the concentration of the aqueous solution of alkali metal hydroxide at this time is, for example, 10% to a saturated aqueous solution, and preferably 30% to a saturated aqueous solution.

The reaction temperature is, for example, 0 ° C. to 200 ° C., preferably 10 ° C. to 150 ° C. The reaction time is, for example, 0.1 hour to several days, preferably 0.2 hour to 2 days.

(Process A4)
Next, compound (I) is obtained by reacting compound (III) with a 1,2,4-triazole compound represented by the following formula (II) (hereinafter referred to as “compound (II)”). (See the following reaction formula (4)).
(Reaction Formula (4))

In formula (II), M represents a hydrogen atom or an alkali metal.

In this step, a carbon atom in the oxirane ring of compound (III) is reacted with compound (II), and a carbon atom is present between the carbon atom in the oxirane ring of compound (III) and the nitrogen atom of compound (II). -Generate nitrogen bonds.

In this case, the solvent to be used is not particularly limited, and examples thereof include amides such as N-methylpyrrolidone and N, N-dimethylformamide.

The amount of the compound (II) used relative to the compound (III) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol. Moreover, you may add a base if desired. In this case, the amount of the base used relative to the compound (II) is, for example, 0 to 10 times mol (excluding 0), preferably 0.5 to 5 times mol.

The reaction temperature and reaction time can be appropriately set depending on the solvent, base and the like. The reaction temperature is preferably 0 ° C. to 250 ° C., more preferably 10 ° C. to 150 ° C. The reaction time is preferably 0.1 hour to several days, more preferably 0.5 hour to 2 days.

Thus, compound (I) according to the present embodiment can be obtained.

Of the compounds (IV), an oxirane compound represented by the following formula (IVa) wherein n is 1 or 2 (hereinafter referred to as “compound (IVa)”) is synthesized by the above steps A1 to A2. In addition to the method, it can be obtained by the following suitable synthesis method (see the following Scheme 2).
(Scheme 2)

Hereinafter, each step for obtaining the compound (IVa) will be described.

(Process B1)
First, with respect to a methyl ketone compound represented by the following formula (XIII) (hereinafter referred to as “compound (XIII)”), a dialkyl carbonate compound represented by the following formula (XII) (hereinafter referred to as “compound (XII)” in the presence of a base. And a keto ester compound represented by the following formula (XI) (hereinafter referred to as “compound (XI)”) (see the following reaction formula (5)).
(Reaction Formula (5))

Here, R ² has the same meaning as R ² described above.

R ¹ represents an alkyl group having 1 to 4 carbon atoms.

This reaction can be carried out in a solvent or using compound (XII) as a solvent.

The amount of compound (XII) used relative to compound (XIII) is, for example, 0.5 to 20 times mol, preferably 0.8 to 10 times mol.

Examples of the base include, but are not limited to, alkali metal hydrogen compounds such as sodium hydride, and alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium t-butoxide. The amount of the base to be used with respect to compound (XIII) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol.

The reaction temperature is, for example, 0 ° C. to 250 ° C., preferably room temperature to 150 ° C. The reaction time is, for example, 0.1 hour to several days, preferably 0.5 hour to 24 hours.

Compound (XIII) and compound (XII) used here can be synthesized by commercially available products or known methods.

(Process B2)
Next, in the presence of a base, a request for a halogenated alkenyl compound represented by the following formula (X) (hereinafter referred to as “compound (X)”) at the carbon atom to which the alkoxycarbonyl group in compound (XI) is bonded is shown. A carbon-carbon bond is generated by a nuclear substitution reaction to obtain an alkenylated ketoester compound represented by the following formula (IX) (hereinafter referred to as “compound (IX)”) (see the following reaction formula (6)).
(Reaction Formula (6))

Here, X ³ and X ⁴ are synonymous with X ³ and X ⁴ described above.

X ⁷ represents a halogen atom. p represents 1 or 2.

This reaction is usually performed in a solvent in the presence of a base.

The amount of the compound (X) used relative to the compound (XI) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol.

Examples of the base include, but are not limited to, alkali metal hydrogen compounds such as sodium hydride, and alkali metal carbonates such as sodium carbonate and potassium carbonate.

The amount of base used with respect to compound (XI) is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol.

The reaction temperature is, for example, 0 ° C. to 250 ° C., preferably room temperature to 150 ° C. The reaction time is, for example, 0.1 hour to several days, preferably 0.5 hour to 24 hours.

By the way, the acidity of the hydrogen atom of the methylene part between the carbonyl group and the ester group of the compound (XI) produced in the reaction in the above-mentioned step B1 is more than the acidity of the hydrogen atom of the acetyl group in the compound (XIII). Since it is high, an alkali metal salt of compound (XI) is formed in the course of the reaction in step B1. Therefore, the reaction liquid in Step B1 can be used as it is for the reaction in this step (Step B2) without isolating compound (XI). In that case, it is also possible to react without adding a new base.

(Process B3)
Next, the compound (IX) is hydrolyzed and decarboxylated to obtain a carbonyl compound represented by the following formula (VIII) (hereinafter referred to as “compound (VIII)”) (see the following reaction formula (7)).
(Reaction Formula (7))

This hydrolysis and decarboxylation reaction can be carried out in a solvent under basic conditions or acidic conditions.

When the reaction is performed under basic conditions, an alkali metal base such as sodium hydroxide or potassium hydroxide is used as the base. As the solvent, for example, water or water to which alcohols are added is used.

Further, when the reaction is carried out under acidic conditions, the acid catalyst is preferably an inorganic acid such as hydrochloric acid, hydrobromic acid and sulfuric acid, or an organic acid such as acetic acid. As the solvent, for example, water or water to which an organic acid such as acetic acid is added is used.

The reaction temperature is, for example, from 0 ° C. to the reflux point, and preferably from 10 ° C. to the reflux point. The reaction time is, for example, 0.1 hour to several days, preferably 0.5 hour to 24 hours.

As another method, (i) a method in which hydrolysis is first performed under basic conditions, followed by decarboxylation under acidic conditions, or (ii) a β-ketocarboxylic acid obtained by hydrolysis is organically treated. A method of decarboxylation by heating in a solvent can also be employed. In that case, the above-mentioned thing is mentioned as a base, an acid, etc. which are used.

(Process B4)
Finally, compound (VIII) is oxiraneated to obtain compound (IVa) (see the following reaction formula (8)).
(Reaction Formula (8))

As this reaction, a method of reacting compound (VIII) with a sulfur ylide such as sulfonium methylides such as dimethylsulfonium methylide and sulfoxonium methylides such as dimethylsulfoxonium methylide in a solvent can be employed. .

The amount of the sulfonium methylides and the sulfoxonium methylides is, for example, 0.5 to 10 times mol, preferably 0.8 to 5 times mol for the compound (XI).

The solvent is not particularly limited. For example, aromatic hydrocarbons such as toluene and xylene, amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidinone, diethyl ether, tetrahydrofuran And ethers such as dioxane, and dimethyl sulfoxide. These solvents can be used as a mixture of two or more.

In addition, when water is used for the reaction, it can be used by mixing with an organic solvent. When used with a hydrophobic organic solvent, a tetrabutylammonium salt, trimethylbenzylammonium salt is added to the reaction mixture as necessary. It is also possible to carry out the reaction by adding a phase transfer catalyst such as a salt and a quaternary ammonium salt such as triethylbenzylammonium salt, and crown ether and the like.

In addition, when an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide is used in an organic solvent such as toluene, it may be preferable to add an alcohol such as diethylene glycol.

The amount of alcohol used at this time is, for example, 0.001 to 10 times mol, preferably 0.005 to 5 times mol, of the compound (VIII).

The reaction temperature and reaction time can be appropriately set depending on the type of solvent, compound (VIII), sulfonium salt or sulfoxonium salt. The reaction temperature is preferably −100 ° C. to 200 ° C., more preferably −50 ° C. to 150 ° C. The reaction time is preferably 0.1 hour to several days, more preferably 0.5 hour to 2 days.

Sulfonium methylides and sulfoxonium methylides are prepared in a solvent by sulfonium salts (eg, trimethylsulfonium iodide and trimethylsulfonium bromide) or sulfoxonium salts (eg, trimethylsulfoxonium iodide and trimethylsulfoxonium bromide). Etc.) and a base.

The base used for the production of sulfonium methylides and sulfoxonium methylides is not particularly limited, for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, metal hydrogen compounds such as sodium hydride, In addition, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide and potassium t-butoxide are preferably used.

Thus, compound (IVa) can be obtained.

Note that, in each step of the above-described production method (steps A1 to A4 and steps B1 to B4), the solvents, bases, acids, and the like used can be as follows unless otherwise specified.

(3) Solvent The solvent to be used is not particularly limited as long as it does not participate in the reaction. Usually, ethers such as diethyl ether, tetrahydrofuran and dioxane; alcohols such as methanol, ethanol and isopropanol; benzene, toluene and xylene Aromatic hydrocarbons such as petroleum ether, aliphatic hydrocarbons such as hexane and methylcyclohexane, and amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidinone Can be mentioned. In addition, water, acetonitrile, ethyl acetate, acetic anhydride, acetic acid, pyridine, dimethyl sulfoxide, and the like can be used as the solvent. These solvents may be used as a mixture of two or more.

Also, examples of the solvent include a solvent composition composed of solvents that do not form a uniform layer with each other. In this case, a phase transfer catalyst such as a conventional quaternary ammonium salt or crown ether may be added to the reaction system.

(4) Base / acid A base or an acid may be added to the above-mentioned solvent.

The base used is not particularly limited. Examples of the base include alkali metal carbonates such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate and barium carbonate; sodium hydroxide and potassium hydroxide Alkali metal hydroxides; alkali metals such as lithium, sodium and potassium; alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide; sodium hydride, potassium hydride and lithium hydride, etc. Alkali metal hydrogen compounds; organometallic compounds of alkali metals such as n-butyllithium; alkali metal amides such as lithium diisopropylamide; and triethylamine, pyridine, 4-dimethylaminopyridine, N, N-dimethyla Phosphorus and 1,8-diazabicyclo-7- [5.4.0] Organic amines such as undecene, and the like.

Moreover, the acid used is not particularly limited. Examples of the acid include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid and sulfuric acid; organic acids such as formic acid, acetic acid, butyric acid, trifluoroacetic acid and p-toluenesulfonic acid; and lithium chloride, bromide Mention may be made of Lewis acids such as lithium, rhodium chloride, aluminum chloride and boron trifluoride.

[Plant Disease Control Agent and Plant Disease Control Method]
The usefulness when the triazole compound (compound (Ia (−))) according to the present embodiment is used as a plant disease control agent and a plant disease control method using the same will be described below.

Since the compound (Ia (−)) has a 1,2,4-triazolyl group, it forms an acid addition salt with an inorganic acid or an organic acid, or a metal complex. Compound (Ia (−)) may be used in the form of these acid addition salts and metal complexes.

(1) Plant disease control effect The usefulness of the plant disease control agent which concerns on this Embodiment is demonstrated. Compound (Ia (−)) exerts a controlling effect against a wide range of plant diseases including foliage diseases, seed infectious diseases and soil infectious diseases. Examples of applicable diseases include: soybean rust (Phakopsora pachyrhizi, Phakopsora meibomiae), rice blast (Pyricularia grisea, Pyricularia oryzae), rice sesame leaf blight (Cochliobolus miyabeanus), rice blight (Rhizoctonia solani) , Apple powdery mildew (Podosphaera leucotricha), apple black spot disease (Venturia inaequalis), apple morinia disease (Monilinia mali), apple spotted leaf disease (Alternaria alternata), apple rot disease (Valsa mali), pear black spot disease (Alternaria kikuchiana) Pear powdery mildew (Phyllactinia pyri), pear red star disease (Gymnosporangium asiaticum), pear black spot disease (Venturia nashicola), grape powdery mildew (Uncinula necator), grape downy mildew (Plasmopara viticola), grape late rot (anthrax) Disease) (Glomerella cingulata), barley powdery mildew (Erysiphe graminis f. Sp hordei), barley black rust (Puccinia graminis), barley yellowness Disease (Puccinia striiformis), barley leaf leaf disease (Pyrenophora graminea), barley cloud shape disease (Rhynchosporium secalis), barley naked scab (Ustilago nuda), wheat powdery mildew (Erysiphe graminis f. Sp tritici), wheat red rust recondita), wheat yellow rust (Puccinia striiformis), wheat eyespot (Pseudocercosporella herpotrichoides), wheat red mold (Fusarium graminearum), wheat red snow rot (Microdochium nivale), wheat leaf blight (Gaeumannomyces graminis), wheat Dry blight (Phaeosphaeria nodorum), wheat leaf blight (Septoria tritici), cucumber powdery mildew (Sphaerotheca fuliginea), cucumber anthracnose (Colletotrichum lagenarium), cucumber downy mildew (Pseudoperonospora cubensis), cucumber gray plague ( Phytophthora capsici), tomato powdery mildew (Erysiphe cichoracearum), tomato ringworm (Alternaria solani), eggplant powdery mildew (Erysip he cichoracearum), strawberry powdery mildew (Sphaerotheca humuli), tobacco powdery mildew (Erysiphe cichoracearum), sugar beet brown spot disease (Cercospora beticola), berries of Monasteria fruit tree (Monilinia fructicola), gray molds that can be used in various crops Diseases (Botrytis cinerea), sclerotia (Sclerotinia sclerotiorum), grape rust (Phakopsora ampelopsidis), tobacco star rot (Alternaria longipes), pea moss (Alternaria solani), soybean brown spot (Septoria glycines), Soybean purpura (Cercospora kikuchii), rice leaf blight (Xanthomonas oryzae), rice black fungus nuclear disease (Helminthosporium sigmoideun), rice scab (Gibberella fujikuroi), rice seedling blight (Pythium aphanidermatum, Rhizopus oryz) Corn smut (Ustillaga maydis), watermelon vine split (Fusarium oxysporum f.sp.niveum), cucumber vine split (Fusarim oxysporum f.sp.cucumerinum), mosquito Tight blue mold (Penicillium italicum) and radish yellows disease (Fusarium oxysporum f.sp.raphani) and the like.

Examples of applied plants include wild plants, plant cultivars, plants and plant cultivars obtained by conventional biological breeding such as crossbreeding or protoplast fusion, genetically modified plants and plant cultivars obtained by genetic manipulation. Can be mentioned. Examples of genetically modified plants and plant cultivars include herbicide-tolerant crops, pest-tolerant crops incorporating insecticidal protein production genes, disease-resistant crops incorporating resistance-inducing substance production genes for diseases, improved crops, improved yields Examples include crops, preservative-enhancing crops, and yield-enhancing crops. Specific examples of genetically modified plant cultivars include those containing registered trademarks such as ROUNDUP READY, LIBERTY LINK, CLEARFIELD, YIELDGARD, HERCULEX, BOLLGARD and the like.

(2) Plant Growth Action In addition, compound (Ia (−)) exhibits an effect of increasing the yield or improving the quality of a wide variety of crops and horticultural plants by controlling the growth. Examples of such crops include wheat, barley and buckwheat, rice, rapeseed, sugar cane, corn, maize, soybeans, peas, peanuts, sugar beet, cabbage, garlic, radish, carrots, apples, pears, tangerines, Citrus such as orange and lemon, peach, cherry peach, avocado, mango, papaya, pepper, cucumber, melon, strawberry, tobacco, tomato, eggplant, turf, chrysanthemum, azalea, and other ornamental plants.

(3) Formulation A plant disease control agent containing the compound (Ia (-)) as an active ingredient is usually mixed with a solid carrier, liquid carrier, surfactant or other formulation adjuvant, and powder, wettable powder, granule It is formulated and used in various forms such as agents and emulsions.

These preparations may contain 0.1 to 95% by weight, preferably 0.5 to 90% by weight, more preferably 2 to 80% by weight, of the compound (Ia (−)) as an active ingredient. .

Examples of carriers, diluents and surfactants used as formulation adjuvants include the following. First, examples of the solid carrier include talc, kaolin, bennite, diatomaceous earth, white carbon, and clay. Examples of the liquid diluent include water, xylene, toluene, chlorobenzene, cyclohexane, cyclohexanone, dimethyl sulfoxide, dimethylformamide and alcohol. It is preferable to use different surfactants depending on their effects. As the emulsifier, it is preferable to use polyoxyethylene alkylaryl ether, polyoxyethylene sorbitan monolaurate, or the like. In addition, lignin sulfonate and dibutyl naphthalene sulfonate are preferably used as the dispersant, and alkyl sulfonate and alkylphenyl sulfonate are preferably used as the wetting agent.

Preparations include those that are used as they are and those that are diluted to a predetermined concentration with a diluent such as water. When diluted and used, the concentration of the compound (Ia (−)) contained in the spray liquid is desirably in the range of 0.001 to 1.0%.

(4) Plant Disease Control Method The plant disease control agent containing the compound (Ia (−)) can be applied by non-foliage treatment such as seed treatment, irrigation treatment and water surface treatment in addition to foliage treatment such as foliage spraying. In addition, when performing a non-foliage process, a labor can be reduced compared with the case where a foliage process is performed. In addition, the plant disease control agent containing the compound (Ia (-)) can control not only non-foliage diseases but also foliage diseases by non-foliage treatment.

In application by seed treatment, a wettable powder or powder is mixed with the seed and stirred, or the seed is immersed in a diluted wettable powder to attach the drug to the seed. The amount of compound (Ia (−)) used in the seed treatment is 0.01 to 10000 g, preferably 0.1 to 1000 g, per 100 kg of seeds.

Application by irrigation treatment is performed by treating granules or the like around the planting hole at the time of transplanting seedlings, or treating the soil around the seeds or plants with granules or wettable powder. . The amount of compound (Ia (−)) used in the irrigation treatment is 0.01 to 10000 g, preferably 0.1 to 1000 g, per 1 m ^{2 of} agricultural and horticultural land.

Application by water surface treatment is performed by treating the surface of paddy fields with granules. In the case of water surface treatment, the amount of compound (Ia (−)) used is 0.1 to 10000 g, preferably 1 to 1000 g, per 10 a paddy field.

The concentration and amount used vary depending on the dosage form, time of use, method of use, place of use and target crop, and can be increased or decreased without sticking to the above range.

The amount of compound (Ia (−)) used for foliage spraying is 20 to 5000 g, more preferably 50 to 2000 g, per ha of horticultural lands such as fields, rice fields, orchards and greenhouses.

Further, the compound (Ia (−)) should be used in combination with other active ingredients such as fungicides, insecticides, acaricides or herbicides as exemplified below to enhance performance as plant disease control agents. You can also.
<Antimicrobial substances>
Acibenzolar S methyl, 2-phenylphenol (OPP), azaconazole, azoxystrobin, amisulbrom, bixaphene, benalaxyl, benomyl, bench avaricarb-isopropyl, bicarbonate, biphenyl, viteltanol, blasticidin-S, borax, bordeaux, boscalid, Bromuconazole, bronopol, bupirimate, secbutyramine, calcium polysulfide, captafor, captan, carbendazim, carboxin, carpropamide, quinomethionate, chloronebu, chloropicrin, chlorothalonil, clozolinate, cyazofamide, cyflufenamide, simoxanil, cyproconil, cyprodiazole Dazomet, debacarb, diclofuranide, diclocimet, dichrome Gin, Dichlorane, Dietofencarb, Difenoconazole, Diflumethrin, Dimethomorph, Dimethoxystrobin, Diniconazole, Dinocup, Diphenylamine, Dithianon, Dodemorph, Dodine, Edifenfoss, Epoxyconazole, Etapoxam, Ethoxyquin, Etridiodone, Enestropheline, Namidon Fenarimol, fenbuconazole, fenflam, fenhexamide, phenoxanyl, fenpicuronyl, fenpropidin, fenpropimorph, fentin, felvam, ferrimzone, fluazinam, fludioxonil, flumorph, fluoromide, floxastrobin, fluquinconazole, flusilazole, flusulfamide , Flutolanil, furtriafor, fu Rupet, Focetyl-aluminum, Fuberidazole, Furaxil, Furatopir, Fluopicolide, Fluopyram, Guazatine, Hexachlorobenzene, Hexaconazole, Himexazole, Imazalil, Imibenconazole, Iminotazine, Ipconazole, Iprobenfos, Iprodione, Iprovalithiol , Kasugamycin, copper preparations (eg copper hydroxide, copper naphthenate, copper oxychloride, copper sulfate, copper oxide, oxine-copper), crezooxime methyl, mancocapper, mancozeb, maneb, mandipropamide, mepanipyrim, mepronil, metalaxyl , Metconazole, methylam, metminosoutrobin, myrdiomycin, microbutanyl, nitrotal-isopropyl, Limol, off-race, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxyl, oxytetracycline, pefrazoate, orisatrobin, penconazole, pencyclon, penthiopyrad, pyribencarb, fusalide, picoxystrobin, piperaline, polyoxin, probenazole, prochloraz, procymidone , Propamocarb, propiconazole, propinebole, proquinazide, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroxylone, quinoxyphene, quintozen, silthiofam, cimeconazole, spiroxamine, sulfur and sulfur preparation, tebuconazole, teclophthalam, , Tetraconazole, thiabendazole, tifluzamide, Thiophanate-methyl, thyram, thiazinyl, tolcrophos-methyl, tolylfluanid, triadimethone, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, trifolin, triticonazole, validamycin, vinclozoline, Zineb, ziram, zoxamide, amisulbrom, sedaxane, flutianil, varifenal, amethoctrazine, dimoxystrobin, metolaphenone, hydroxyisoxazole, metasulfocarb and the like.
<Insecticide / acaricide / nematicide>
Abamectin, Acephate, Acrinathrin, Alanicarb, Aldicarb, Alletrin, Amitraz, Avermectin, Azadirachtin, Azamethifos, Azinphos-ethyl, Azinphos-methyl, Azocycline, Bacillus filmus, Bacillus subtilis, Bacillus thuringibulbbenthulbenbencarb , Benzoxymate, Bifenazite, Bifenthrin, Bioarethrin, Bioresmethrin, Bistriflurone, Buprofezin, Butocaboxin, Butoxycarboxyne, Kazusafos, Carbaryl, Carbofuran, Carbosulfan, Cartap, CGA50439, Chlordein, Chloretifol, Chlorfenapir Fenbinfoss, Chlorfluazuron Chlormefos, Chlorpyrifos, Chlorpyrifosmethyl, Chromaphenozide, Clofentedine, Clothianidin, Chloranthraliniprol, Counpafos, Cryolite, Cyanophos, Cycloproton, Cyfluthrin, Cyhalothrin, Cihexatin, Cipermethrin, Cifenotrin, Cyromazine, Ciazapyr, Sienopyrafen, DCIP, DDT, Deltamethrin, Demeton-S-methyl, Diafenthiuron, Diazinone, Dichlorophene, Dichloropropene, Dichlorvos, Dicofor, Dicrotophos, Dicyclanil, Diflubenzuron, Dimethoate, Dimethylvinphos, Franbutone, Dinobutone , Emamectin, endosulfan, EPN, esfenvalerate, etiophencarb, ethion, Tiprol, etofenprox, etoprofos, etoxazole, famflu, fenamifos, phenazaquin, fenbutatin oxide, fenitrothion, fenocarb, phenothiocarb, phenoxycarb, fenpropatrine, fenpyroximate, fenthionate, fenvalerate, fipronil, flunipyamide Ron, flucitrinate, fluphenoxuron, flumethrin, fulvalinate, flubendiamide, formethanate, fostiazate, halfenprox, furthiocarb, halohenozide, gamma-HCH, heptenofos, hexaflumuron, hexithiazox, hydramethylnon , Imidacloprid, imiprothrin, indoxacarb, isoprocar Bu, isoxathion, lufenuron, malathion, mecarbam, metham, methamidophos, methidathione, metiocarb, methomyl, methoprene, methosrine, methoxyphenozide, metorcarb, milbemectin, monocrotofos, nared, nicotine, nitenpyram, novalflumetron, oxyflumetron Tonmethyl, parathion, permethrin, phentoate, folate, fosaron, phosmet, phosfamidone, foxim, pirimicarb, pirimiphos methyl, profenofos, propoxur, prothiophos, pymetrozine, pyracrofos, pyrethrin, pyridaben, pyridalyl, pyrimidifene, pyriproxy Fen, Pyrifluquinazone, Pyriprole, Quinarfos, Shirafu Ofen, Spinosad, Spirodiclofen, Spiromethifene, Spirotetramat, Sulframide, Sulfotep, SZI-121, Tebufenozide, Tebufenpyrad, Tebupyrimfos, Teflubenzuron, Tefluthrin, Temefos, Terbufos, Tetrachlorbinfos, Thiacloprio, Thiamethioxam Fanox, thiometone, tolfenpyrad, tralomethrin, tralopyril, triazamate, triazophos, trichlorphone, triflumuron, bamidithione, varifenal, XMC, xylylcarb, imisiaphos, and lepimectin.
<Plant growth regulator>
Ansimidol, 6-benzylaminopurine, paclobutrazole, diclobutrazole, uniconazole, methylcyclopropene, mepiquat chloride, ethephone, chlormequat chloride, inabenfide, prohexadione and salts thereof, and trinexa Pack ethyl etc. In addition, as plant hormones, jasmonic acid, brassinosteroid, gibberellin and the like.

In addition, the seed treated with the above-mentioned plant disease control agent is also included in the category of the present invention. Since the treatment with the plant disease control agent has been described above, the description thereof is omitted. Seeds treated with a plant disease control agent can be used in the same manner as seeds not treated with seeds.

The plant disease control agent only needs to contain the compound (Ia (−)), and may contain an enantiomer of the compound (Ia (−)), that is, a (+)-enantiomer. . However, in order to enhance the effect of the compound (I) as an active ingredient, the content of the (+)-enantiomer is preferably less than the content of the compound (Ia (−)). The content is more preferably 40% or less, still more preferably 20% or less, and particularly preferably no (+)-enantiomer is contained.

Examples will be shown below, and the embodiments of the present invention will be described 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 in detail. Further, the present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims, and the present invention is also applied to the embodiments obtained by appropriately combining the disclosed technical means. It is included in the technical scope of the invention. Moreover, all the literatures described in this specification are used as reference.

<Production Example 1: 2- (1-chlorocyclopropyl) -1- (2,2-dibromocyclopropyl) -3- (1H-1,2,4-triazol-1-yl) propan-2-ol Synthesis>
According to the above reaction scheme 1, compound (I) was synthesized from compound (VII).

(1) 1-chloro-2- (1-chlorocyclopropyl) -4-penten-2-ol (compound (V): R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H, X Synthesis of ⁶ = Cl, n = 1) Under an argon atmosphere, 2-chloro-1- (1-chlorocyclopropyl) ethanone (compound (VII): R ² = 1-chlorocyclopropyl, X ⁶ = Cl) (0 .0098 mol) was dissolved in diethyl ether (20 ml) and cooled to −50 ° C. Allylmagnesium bromide (compound (VI): X ³ = H, X ⁴ = H, L = MgBr, n = 1) 1M diethyl ether solution (18 ml) was added, and the mixture was stirred at the same temperature for about 20 minutes, then cooled on ice The mixture was further stirred for 1 hour while gradually warming to the bottom. After stirring, ice water and saturated aqueous ammonium chloride solution were added. After extraction with diethyl ether, the organic layer was extracted with saturated aqueous sodium hydrogen carbonate and saturated brine. The extract was dried over anhydrous sodium sulfate and concentrated to obtain a crude product.
Yield: 77%
(2) 2- (1-chlorocyclopropyl) -2- (2,2-dibromocyclopropylmethyl) oxirane (compound (III): R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H , X ⁵ = Br, n = 1) Compound (V) (0.0031 mol) was mixed with bromoform (9.2 mmol), 50% aqueous sodium hydroxide (2 g) and benzyltriethylammonium chloride (0.154 mmol). In addition, the mixture was stirred at room temperature for 1 hour, further stirred at about 60 ° C. for 1 hour, and then further stirred at about 80 ° C. for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. Bromoform (9.2 mmol), 50% aqueous sodium hydroxide solution (2 g) and benzyltriethylammonium chloride (0.30 mol) were added to the obtained crude product, and the mixture was stirred at 80 ° C. for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The product was purified by silica gel column chromatography to obtain a crude product, which was directly used in the next reaction.
Yield: 59%
(3) 2- (1-chlorocyclopropyl) -1- (2,2-dibromocyclopropyl) -3- (1H-1,2,4-triazol-1-yl) propan-2-ol (compound ( I): Synthesis of R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H, X ⁵ = Br, n = 1) and preparation of the low polar isomers Potassium carbonate (2.7 mmol) was added to DMF After suspending in (3 ml), sodium t-butoxide (0.36 mmol) and 1,2,4-triazole (compound (II): M = H) (2.7 mmol) were added thereto. To this was added compound (III) (0.0018 mol) dissolved in DMF (3 ml), and the mixture was stirred at 90 ° C. for 2 hours. Ethyl acetate and water were added thereto and partitioned, and the organic layer was washed with saturated brine. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated. Purification was performed by silica gel column chromatography, and a low-polar isomer (hereinafter referred to as isomer (1a-1)) was isolated from the two isomers.
[Isomer (1a-1)]
Yield: 9%
(4) 2- (1-chlorocyclopropyl) -1- (2,2-dibromocyclopropyl) -3- (1H-1,2,4-triazol-1-yl) propan-2-ol (-) —Preparation of Enantiomers The isomer (1a-1) 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, and each enantiomer was Was separated.

Specific conditions are as follows.
Preparative column: Product name “CHIRALPAK AD-H”, Daicel Chemical Industries mobile phase: 100% methanol Column temperature: 40 ° C.
Detection wavelength: 210 nm
When separated under the above conditions, two peaks with different elution times were detected. As a result of measuring the specific rotation of the compound derived from each peak, the compound eluted first is the dextrorotatory enantiomer ((+)-enantiomer), and the compound eluted later is the levorotatory enantiomer (( -)-Enantiomer). Hereinafter, the (+)-enantiomer is referred to as compound (1a-1 (+)), and the (−)-enantiomer is referred to as compound (1a-1 (−)).

The specific rotation was measured 20 times using P-1020 (manufactured by JASCO Corporation, Na lamp: 589 nm). Specific measurement results are as follows.
Average specific rotation of compound (1a-1 (−)):
[Α] _D ²⁸ = −64.2 ° (100 mg per 10 ml of chloroform)
Average specific rotation of compound (1a-1 (+)):
[Α] _D ²⁷ = + 65.7 ° (100 mg per 10 ml of chloroform)
Moreover, each property is as follows.
Compound (1a-1 (−)): white solid, melting point 86.9 ° C.
Compound (1a-1 (+)): white solid, melting point 88.4 ° C.
<Production Example 2: 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) -1- (1H-1,2,4-triazol-1-yl) butan-2-ol Synthesis>
According to the above reaction scheme 2, compound (IVa) was synthesized from compound (XIII), and according to the above reaction scheme 1, compound (I) was synthesized from compound (IVa).

(1) Synthesis of methyl 3- (1-chlorocyclopropyl) -3-oxopropionate (compound (XI): R ² = 1-chlorocyclopropyl, R ¹ = Me) 60% hydrogenation under a nitrogen stream Sodium (95.0 mmol) was washed with hexane, suspended in dimethyl carbonate (compound (XII): R ¹ = Me) (80 ml), anhydrous methanol (0.5 ml) was added, and the mixture was heated to 80 ° C. To this solution, 1- (1-chlorocyclopropyl) ethanone (compound (XIII): R ² = 1-chlorocyclopropyl) (86.0 mmol) was added to dimethyl carbonate (compound (XII): R ¹ = Me) (6 ml). The solution dissolved in) was added and stirred at 80 ° C. for 3 hours. After allowing to cool, acetic acid (10 ml) was added to the reaction solution, and then poured into ice water to separate the organic layer. The aqueous layer was extracted with diethyl ether, and the organic layers were washed with water and saturated brine, and then dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the desired product was obtained by distillation under reduced pressure.
Yield: 58%
(2) Methyl 2- (2-propenyl) -3- (1-chlorocyclopropyl) -3-oxopropionate (Compound (IX): R ¹ = Me, R ² = 1-chlorocyclopropyl, X ³ = Synthesis of H, X ⁴ = H, p = 1) Under a nitrogen stream, 60% sodium hydride (33.0 mmol) was washed with hexane and then suspended in anhydrous DMF (70 ml). A solution prepared by dissolving compound (XI) (30.0 mmol) in anhydrous DMF (15 ml) was added thereto, followed by stirring at room temperature for 1.5 hours. After stirring, a solution of allyl bromide (compound (X): X ³ = H, X ⁴ = H, X ⁷ = Br, p = 1) (33.0 mmol) dissolved in anhydrous DMF (15 ml) was added at room temperature. Stir for 3 hours. The reaction solution was poured into ice water and extracted with hexane. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the desired product.
Yield: 98%
(3) 1- (1-chlorocyclopropyl) -4-penten-1-one (compound (VIII), R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H, p = 1) Synthesis Compound (IX) (28.5 mmol) was dissolved in isopropanol (10 ml). A solution obtained by dissolving sodium hydroxide (55.0 mmol) in water (11 ml) was added thereto, followed by stirring at 80 ° C. for 4.5 hours. After allowing to cool, the reaction solution was poured into ice water and extracted with hexane. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the desired product.
Yield: 67%
(4) 2- (3-Butenyl) -2- (1-chlorocyclopropyl) oxirane (compound (IVa): R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H, p = 1) In a nitrogen stream, 60% sodium hydride (43.7 mmol) was washed with hexane and then suspended in anhydrous DMSO (70 ml). Trimethylsulfoxonium bromide (43.4 mmol) was added thereto and stirred at room temperature for 1.5 hours. After stirring, a solution of compound (VIII) (31.5 mmol) dissolved in anhydrous DMSO (30 ml) was added, and the mixture was further stirred at room temperature for 3 hours. The reaction solution was poured into ice water and extracted with hexane. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting oil was distilled under reduced pressure to obtain the desired product.
Yield: 31%
(5) 2- (1-chlorocyclopropyl) -2- [2- (2,2-dichlorocyclopropyl) ethyl] oxirane (compound (III): R ² = 1-chlorocyclopropyl, X ³ = H, Synthesis of X ⁴ = H, X ⁵ = Cl, n = 2) Compound (IVa) (110 mmol) and benzyltriethylammonium chloride (2.26 mmol) were dissolved in chloroform (63 ml), and then sodium hydroxide ( 577 mmol) / water (23.5 ml) solution was added, and the mixture was stirred at 60 ° C. for 2 hours. The reaction solution was poured into ice water and extracted with chloroform. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product. The obtained crude product was purified by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the desired product.
Yield: 71%
(6) 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) -1- (1H-1,2,4-triazol-1-yl) butan-2-ol (compound ( I): Synthesis of R ² = 1-chlorocyclopropyl, X ³ = H, X ⁴ = H, X ⁵ = Cl, n = 2) 1H-1,2,4-triazole (compound (II ): M = H) (2.06 mmol), potassium carbonate (1.96 mmol), and potassium t-butoxide (0.13 mmol) were suspended in DMF (2 ml). To this was added a DMF (2 ml) solution of compound (III) (1.54 mmol), and the mixture was stirred at 70 ° C. for 5 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography to obtain a low-polar isomer (hereinafter referred to as isomer (1a-2)) of the two isomers. Purified. The crude product was recrystallized to obtain the isomer (1a-2). Of the two isomers obtained at this time, the highly polar isomer is referred to as “isomer (1b-2)”.
[Isomer (1a-2)]
Yield: 8%
[Isomer (1b-2)]
Yield: 11%
(7) 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) -1- (1H-1,2,4-triazol-1-yl) butan-2-ol (-) —Preparation of Enantiomers The isomer (1a-2) was subjected to high performance liquid chromatography (HPLC) connected to a preparative column in which cellulose tris (3,5-dimethylphenylcarbamate) was immobilized on a silica gel carrier, and each enantiomer was Was separated.

Specific conditions are as follows.
Preparative column: Product name “CHIRALCEL OD-H”, Daicel Chemical Industries mobile phase: hexane / ethanol = 95/5
Column temperature: 40 ° C
Detection wavelength: 205 nm
When separated under the above conditions, two peaks with different elution times were detected. As a result of measuring the specific rotation of the compound derived from each peak, the compound eluted first is the dextrorotatory enantiomer ((+)-enantiomer), and the compound eluted later is the levorotatory enantiomer (( -)-Enantiomer). Hereinafter, the (+)-enantiomer is referred to as compound (1a-2 (+)), and the (−)-enantiomer is referred to as compound (1a-2 (−)).

Specific rotation was measured 14 times (compound (1a-2 (−))) or 26 times (compound (1a-2 (+)) using P-1020 (manufactured by JASCO Corporation, Na lamp: 589 nm). ))went. Specific measurement results are as follows.
Average specific rotation of compound (1a-2 (−)):
[Α] _D ²² = −42.2 ° (20 mg per 2 ml of chloroform)
Average specific rotation of compound (1a-2 (+)):
[Α] _D ²² = + 41.8 ° (20 mg per 2 ml of chloroform)
Moreover, each property is as follows.
Compound (1a-2 (−)): white solid, melting point 116 ° C.
Compound (1a-2 (+)): white solid, melting point 115 ° C.
<Formulation example 1 (wettable powder)>
Compound (1a-1 (-)) 50 parts lignin sulfonate 5 parts alkyl sulfonate 3 parts diatomaceous earth 42 parts were pulverized and mixed to obtain a wettable powder and diluted with water for use.

<Formulation example 2 (powder)>
Compound (1a-1 (-)) 3 parts Clay 40 parts Talc 57 parts were ground and mixed and used as dust.

<Formulation example 3 (granule)>
Compound (1a-1 (-)) 5 parts Bennite 43 parts Clay 45 parts Lignin sulfonate 7 parts are mixed uniformly, kneaded with water, processed into granules with an extrusion granulator, dried and granulated did.

<Formulation example 4 (emulsion)>
Compound (1a-1 (-)) 20 parts polyoxyethylene alkyl aryl ether 10 parts polyoxyethylene sorbitan monolaurate 3 parts xylene 67 parts were mixed and dissolved uniformly to give an emulsion.

<Test Example 1: Cucumber gray mold control effect test by foliar spray treatment>
To a cotyledon cucumber (variety: SHARP1) cultivated using a square plastic pot (6 cm × 6 cm), the compound (1a-1 (−)) or the compound ((1a-2 (−)) as in Preparation Example 1 ) In the form of a wettable powder was diluted with water to a predetermined concentration and sprayed at a rate of 1,000 L / ha, and the sprayed leaves were air-dried and then a paper disc impregnated with a spore solution of gray mold fungus. 8 mm in diameter) and kept under high humidity conditions at 20 ° C. On the fourth day after inoculation, the morbidity of cucumber gray mold disease was investigated according to the survey criteria shown in Table 1, and the control value was calculated by the following formula: did.
Control value (%) = (1− (average morbidity in sprayed area / average illness in non-sprayed area)) × 100

The results are shown in Tables 2 and 3. In this test example and the subsequent test examples, the compound (1a-1 (+)) and the compound (1a) were used instead of the compound (1a-1 (−)) and the compound (1a-2 (−)), respectively. -(+)) Was used for each test. In addition, when the average morbidity in the sprayed area exceeded the average illness in the non-sprayed area, the control value was set to 0%.

<Test Example 2: Wheat red rust control effect test by foliar spray treatment>
Compound (1a-1 (−)) or compound (1a-2) as in Preparation Example 1 was added to the second leaf wheat (cultivar: Norin 61) grown using a square plastic pot (6 cm × 6 cm). (-)) In the form of a wettable powder was diluted and suspended in water to a predetermined concentration and sprayed at a rate of 1,000 L / ha. The sprayed leaves were air-dried and then spray-inoculated with spores of wheat red rust fungus (adjusted to 200 cells / field of view, added with Grameen S to 60 ppm), and kept at 25 ° C. and high humidity for 48 hours. After that, it was managed in the greenhouse. On the 11th day after the inoculation, the morbidity of wheat rust was investigated according to the survey criteria shown in Table 4, and the control value was calculated by the following formula.
Control value (%) = (1− (average morbidity in sprayed area / average illness in non-sprayed area)) × 100

The results are shown in Tables 5 and 6.

<Test Example 3: Wheat powdery mildew control effect test by foliar spray treatment>
Compound (1a-1 (−)) or compound (1a-2) as in Preparation Example 1 was added to the second leaf wheat (cultivar: Norin 61) grown using a square plastic pot (6 cm × 6 cm). (-)) In the form of a wettable powder was diluted and suspended in water to a predetermined concentration and sprayed at a rate of 1,000 L / ha. After airing the sprayed leaves, wheat seedlings infected with wheat powdery mildew were sprinkled with powdery mildew fungus. On the 11th day after inoculation, the morbidity of wheat powdery mildew was examined according to the survey criteria shown in Table 4 above, and the control value was calculated in the same manner as in Test Example 2. The results are shown in Tables 7 and 8.

<Test Example 4: Wheat red mold control effect test by foliar spray treatment>
In a wheat head at the flowering stage (variety: Norin 61), a compound (1a-1 (−)) or a compound (1a-2 (−)) in the form of a wettable powder as in Formulation Example 1 was added to water. The suspension was diluted to a predetermined concentration and sprayed at a rate of 1,000 L / ha. After the head was air-dried, it was spray-inoculated with spores of wheat red mold fungus (adjusted to 2 × 10 ⁵ cells / ml, containing Gramine S having a final concentration of 60 ppm), and kept at 20 ° C. under high humidity conditions. On the 5th day after inoculation, the morbidity of wheat red mold was investigated according to the survey criteria shown in Table 9, and the control value was calculated by the following formula.
Control value (%) = (1− (average morbidity in sprayed area / average illness in non-sprayed area)) × 100

Results are shown in Tables 10 and 11.

<Test Example 5: Effect of controlling wheat red rust by seed treatment>
By pot test, the control effect of wheat red rust caused by seed treatment was evaluated. The compound (1a-1 (−)) dissolved in DMSO so that the treatment amount is 20 g ai / 100 kg seeds or 5 g ai / 100 kg seeds was smeared on the wheat seeds in a vial, and then 8 wheat seeds were 80 cm. ² pots were seeded. The lower water supply was controlled in a greenhouse, and 27 days after sowing, wheat red rust fungus was inoculated and stored in a wet box for 2 days. Thereafter, the lower water supply was managed again in the greenhouse, and the diseased area ratio was investigated 8 days after the inoculation, and the control value was calculated by the following formula.
Control value (%) = (1− (Affected area ratio of treated area / Affected area ratio of untreated area)) × 100
The results are shown in Table 12.

<Test Example 6: Controlling effect of rice seedling disease by seed treatment>
The pot test was used to evaluate the control effect of rice seedling disease by seed treatment. Processing amount is 5g
A compound (1-1a) dissolved in DMSO so as to be ai / 100 kg seeds was smeared on rice seeds infected with scab seedlings in a vial, and then 32 rice seeds were sown in 50 cm ² pots. The lower water supply was managed in the greenhouse, and the diseased seedling rate was investigated 21 days after sowing, and the control value was calculated in the same manner as in Test Example 5.

The results are shown in Table 13.

<Test Example 7: Antibacterial test against pathogenic bacteria>
In this test example, antibacterial properties against various phytopathogenic fungi were tested.

Compound (1a-1 (−)) or compound (1a-2 (−)) was dissolved in dimethyl sulfoxide and added to PDA medium (potato-dextrose-aggar medium) at around 60 ° C. After mixing well in an Erlenmeyer flask, it was poured into a petri dish and solidified to prepare a plate medium containing the compound (1a-1 (−)) or compound (1a-2 (−)) at a predetermined concentration.

On the other hand, a test bacterium previously cultured on a plate medium was punched out with a cork borer having a diameter of 4 mm and inoculated on the drug-containing plate medium. After inoculation, each fungus was cultured for 1 to 14 days at a suitable temperature for growth of the fungus (see, for example, LIST OF CULTURES 1996 microorganisms 10th edition, literature from the Institute for Fermentation, etc.), and the growth of the fungus was measured by the fungus diameter. The growth degree of the bacteria obtained on the drug-containing plate medium was compared with the growth degree of the bacteria in the drug-free group, and the mycelial elongation suppression rate was determined by the following formula. In the following formula, R represents the hyphal elongation inhibition rate (%), dc represents the diameter of the fungus on the untreated plate, and dt represents the diameter of the fungus on the drug-treated plate.
R = 100 (dc−dt) / dc
The obtained results were evaluated in five stages according to the criteria shown in Table 14. The larger the antibacterial index, the better the antibacterial property.

Results are shown in Tables 15 and 16.

In addition, the abbreviation of the microbial species in Table 15 or 16 represents the following microbial species, respectively.
Pn: wheat blight (Phaeosphaeria nodorum)
Ph: Wheat eye spot disease fungus (Pseudocercoporella herpotrichoides)
Mn: Wheat red snow rot fungus (Microdochium nivale)
Gg: Wheat Blight Fungus (Gaeumannomyces graminis)
Pg ： Pyrenophora graminea
Fg: Fusarium graminearum
Un: Barley Bare Smut Fungus (Ustilago nuda)
Po: Rice blast fungus (Pyricularia oryzae)
Rs ： Rhizoctonia solani
Gf ： Gibberella fujikuroi
Ro: Rice seedling blight (Rhizopus oryzae)
Am: Apple spotted leaf disease (Alternaria alternata)
Ss: Sclerotinia sclerotiorum
Bc: Botrytis cinerea
Gc: Glomerella cingurata
Fc: Cucumber vine (Fusarim oxysporum f.sp.cucumerinum)
Pi: Citrus blue mold (Penicillium italicum)
Cb: sugar beet brown spot (Cercospora beticola)
R.sec: Rhynchosporium secalis
St: Wheat leaf blight fungus (Septoria tritici)

The present invention can be suitably used as an active ingredient of a control agent capable of controlling plant diseases by foliage treatment and non-foliage treatment.

Claims (7)

1. Formula (I)
   

   

   (In the formula ^{(I), X 1 ~ X} 4 represents a hydrogen atom or a halogen atom, ^{X 5} represents a halogen atom, a plurality of ^{X 2} are the same atom together, ^{X 1} and At least one of X ² is a halogen atom, a plurality of X ⁴ are the same atom, a plurality of X ⁵ are the same atom, X ⁴ and X ⁵ are different atoms, m and n Represents 0 to 3. * represents an asymmetric carbon atom.)
   Of the two diastereomers in the triazole compound represented by the formula:
   Of the enantiomers in the diastereomers having a lower polarity, a triazole compound which is a (−)-enantiomer.
2. The triazole compound according to claim 1, wherein in the formula (I), X ¹ is a halogen atom, X ² is a hydrogen atom, and m is 0.
3. The triazole compound according to claim 1 or 2, wherein n is 0 to 2 in the formula (I).
4. The triazole compound according to any one of claims 1 to 3, wherein in the formula (I), X ³ and X ⁴ are hydrogen atoms.
5. A plant disease control agent comprising the triazole compound according to any one of claims 1 to 4 as an active ingredient.
6. A plant disease control method comprising a step of performing a foliage treatment or a non-foliage treatment using the plant disease control agent according to claim 5.
7. Seeds treated with the plant disease control agent according to claim 5.