WO2013069481A1

WO2013069481A1 - Method for producing triazole compound and intermediate of triazole compound

Info

Publication number: WO2013069481A1
Application number: PCT/JP2012/077762
Authority: WO
Inventors: 須藤　敬一; 大河正野
Original assignee: 株式会社クレハ
Priority date: 2011-11-09
Filing date: 2012-10-26
Publication date: 2013-05-16

Abstract

In this method for producing a triazole compound, a diol compound is produced from an oxirane compound, a first oxirane diastereomer is produced from the diol compound, and a triazole compound is produced using the first oxirane diastereomer. The first oxirane diastereomer is a diastereomer from which a diastereomer of the aimed triazole compound is derived. Consequently, a triazole compound is efficiently produced at low cost.

Description

Method for producing triazole compound, and intermediate of triazole compound

The present invention relates to a method for producing a triazole compound.

Patent Document 1 discloses, as an active ingredient of a plant disease control agent, a hydroxyethylazole derivative which is a hetero 5-membered ring containing 2 or more nitrogen atoms in the ring, and further has a cycloalkyl group on the carbon atom to which the hydroxy group is bonded. Or a derivative in which an alkyl group in which some hydrogen atoms are substituted with a cycloalkyl group is bonded.

International Publication Pamphlet “WO2011 / 070742 (Released on June 16, 2011)”

Since the compound described in Patent Document 1 has excellent activity as a plant disease control agent, a method for producing such a compound efficiently and at low cost is required. In addition, such a compound has a plurality of diastereomers, but there is a demand for a production method that minimizes the possibility of unnecessary diastereomers being mixed into the finally obtained compound. Yes.

Therefore, the present invention has been made in view of the above problems, and an object of the present invention is to provide a production method for efficiently and inexpensively producing a compound that meets the above-mentioned demand.

In order to solve the above-described problems, a method for producing a triazole compound according to the present invention includes a diol production step of producing a diol compound represented by the following general formula (Ia) from an oxirane compound represented by the following general formula (III): ,

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are different from each other, and n represents 0 to 3. R ² represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are different from each other, and n represents 0 to 3. R ² represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
A first oxirane diastereomer producing step for producing a first oxirane diastereomer of the oxirane compound represented by the general formula (III) from the diol compound produced in the diol producing step; Using the first oxirane diastereomer produced in the diastereomer production step, a triazole compound production step for producing a triazole compound represented by the following general 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.)
Including
The first oxirane diastereomer is derived from a diastereomer of a target triazole compound in the triazole compound represented by the general formula (I).

The intermediate compound according to the present invention is an intermediate compound of the above triazole compound, and is characterized by being represented by the following general formula (Ia).

The intermediate compound according to the present invention is an intermediate compound of the above-described triazole compound triazole compound, and is characterized by being represented by the following general formula (Ib).

The intermediate compound according to the present invention is the above-described triazole compound intermediate compound, and is characterized by being represented by the following general formula (Ic).

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R ² represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)

According to the method for producing a triazole compound according to the present invention, a triazole compound having an excellent bactericidal action against many bacteria causing disease to plants can be produced efficiently and at low cost. Therefore, according to the present invention, a plant disease control agent comprising the triazole compound produced according to the present invention as an active ingredient and exhibiting a high control effect against a wide range of plant diseases can be produced easily and at low cost. .

Hereinafter, the method for producing the triazole compound according to the present invention will be described.

The method for producing a triazole compound according to the present invention includes a diol production step for producing a diol compound represented by the following general formula (Ia) from an oxirane compound represented by the following general formula (III):

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are different from each other, and n represents 0 to 3. R ² represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
A first oxirane diastereomer producing step for producing a first oxirane diastereomer of the oxirane compound represented by the general formula (III) from the diol compound produced in the diol producing step;
A triazole compound production step for producing a triazole compound represented by the following general formula (I) using the first oxirane diastereomer produced in the first oxirane diastereomer production step;

(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.)
And the first oxirane diastereomer is derived from the diastereomer of the desired triazole compound in the triazole compound represented by the general formula (I).

[1. Triazole compound)
The triazole compound produced by the method for producing a triazole compound in the present embodiment is represented by the following general 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.)
It is a triazole compound shown by these.

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.

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).

(Formula (I-1) ^{in, X 1a} and ^{X 5a} are each independently a chlorine atom or a bromine atom, ^{n a} represents 0, 1 or 2.)

Compound (I) has two asymmetric carbon atoms. Accordingly, compound (I) has a plurality of diastereomers. 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. In the present embodiment, the triazole compound is a more active diastereomer among a plurality of diastereomers. In the present embodiment, all diastereomers other than the higher activity diastereomers among the plurality of diastereomers are referred to as lower activity diastereomers.

As used herein, the term “higher activity diastereomer” intends a diastereomer having an excellent control effect against plant diseases than other diastereomers. Further, the “lower activity diastereomer” intends a diastereomer having a control effect which is inferior to the above-mentioned “higher activity diastereomer” against plant diseases.

In the present embodiment, the case where two asymmetric carbon atoms are present in compound (I) will be described as an example, as shown by the following formula (I-2).

(In Formula (I-2), X ¹ to X ⁴ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, and a plurality of X ² are the same atom, ^At least one of ¹ and 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 atoms different from each other, m And n represents 0 to 3. * represents an asymmetric carbon atom.)

Of the two diastereomers in the compound represented by the formula (I-2), the more active diastereomer is referred to as “compound (IA)”. Of the two diastereomers in the compound represented by the formula (I-2), the less active diastereomer is referred to as “compound (IB)”.

[2: Triazole compound production process]
First, an embodiment of a method 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 ¹ 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 used 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 relative 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 ¹ is zinc-Q2 (Q2 is a halogen atom), it is preferable to carry out the reaction while generating compound (IX) 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, cerium chloride and the like.

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 to give 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))

The amount of the base used for compound (V) is, for example, 0.5 to 20 times mol, preferably 0.8 to 5 times mol. Bases used include alkali metal or alkaline earth metal hydroxide salts such as sodium hydroxide, potassium hydroxide and calcium hydroxide, and alkali metal carbonates or hydrogen carbonates such as sodium carbonate and potassium carbonate. However, it is not limited to these.

The solvent to be used 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 -Amides such as methyl-2-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 solution of a base 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. It is also possible to carry out the reaction 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 formula (III) (hereinafter referred to as “compound (III)” by the reaction of trihalomethane with a base such as sodium hydroxide. ) ”)). 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 relative to the compound (IV) is, for example, 0.001 to 5 times mol, preferably 0.01 to 2 times mol.

The base to be used is not particularly limited, and examples thereof include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and are often used as an aqueous solution. The amount of the base used relative to compound (IV) is, for example, 0.1 to 100 times mol, preferably 0.8 to 50 times mol. 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, the compound (III) is reacted with a 1,2,4-triazole compound represented by the following general formula (II) (hereinafter referred to as “compound (II)”) to thereby convert the compound (I). (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) can be obtained.

(Process A4-1)
In addition, when compound (I) is obtained from compound (III) as described above, the obtained compound (I) is a diastereomeric mixture including two kinds of diastereomers. Therefore, when obtaining the compound (IA) which is a higher activity diastereomer, the lower activity diastereomer (IB) remaining separated from the diastereomer mixture of the compound (I) is discarded. Become.

According to the method for producing a triazole compound according to the present invention, the compound (IA) can be efficiently produced without requiring a separation step of the compound (I) from the diastereomer mixture. In addition, according to the present invention, an intermediate which is separated and no longer necessary in the production process of compound (IA) can be reused and used for the production of compound (IA). Thus, according to the present invention, compound (IA) can be produced efficiently and at low cost. The following compounds (Ia), (Ib) and (Ic), which are intermediate compounds of the triazole compound used in the method for producing a triazole compound according to the present invention, are also included in the category of the present invention. .

In this embodiment, compound (IA) can be produced from compound (III) obtained by a known technique as shown in Scheme 2 below.

(Scheme 2)

Hereinafter, each process will be described.

Note that X ¹ to X ⁵ , R ² , m, and n in the above-mentioned scheme 2 and the following reaction formulas are synonymous with the above-described X ¹ to X ⁵ , R ² , m, and n unless otherwise specified.

<Process B1>
First, the compound (III) is hydrolyzed in a solvent containing an acid catalyst to obtain a diol compound represented by the following formula (Ia) (hereinafter referred to as “compound (Ia)”) (see the following reaction formula (5)). ).

(Reaction formula (5))

The amount of the acid catalyst used relative to compound (III) is, for example, 0.001 to 2 times mol, preferably 0.01 to 1 times mol. Examples of the acid catalyst used include sulfuric acid, hydrochloric acid, hydrobromic acid and perchloric acid.

The reaction temperature and reaction time can be appropriately set depending on the type of solvent and acid catalyst. The reaction temperature is preferably 0 to 200 ° C, more preferably 80 to 150 ° C. The reaction time is preferably 0.1 to 12 hours, more preferably 0.5 to 2 hours.

<Process B1-1>
In addition, compound (Ia) acetonides compound (III) in a solvent containing a Lewis acid catalyst to obtain a dioxolane compound represented by the following formula (Ib) (hereinafter referred to as “compound (Ib)”). It can also be obtained by deprotecting compound (Ib) in a solvent containing a catalyst (the following reaction formula (6)).

(Reaction formula (6))

The amount of the Lewis acid catalyst used relative to compound (III) is, for example, 0.001 to 2 times mol, preferably 0.01 to 0.1 times mol. Examples of the Lewis acid catalyst used include tin (II) chloride, tin (IV) chloride, boron trifluoride, copper sulfate, copper (II) trifluoromethanesulfonate, and titanium (IV) chloride.

The reaction temperature and each reaction time can be appropriately set depending on the type of solvent and acid catalyst. The reaction temperature is preferably −20 to 50 ° C., more preferably −10 to 30 ° C. The reaction time is preferably 0.1 to 12 hours, more preferably 0.5 to 3 hours.

The amount of the acid catalyst used relative to compound (Ib) is, for example, 0.01 to 20 times mol, preferably 0.1 to 2 times mol. Examples of the acid catalyst used include hydrochloric acid, sulfuric acid, acetic acid, methanesulfonic acid, and p-toluenesulfonic acid.

The reaction temperature and each reaction time can be appropriately set depending on the type of solvent and acid catalyst. The reaction temperature is preferably −20 to 150 ° C., more preferably 20 to 100 ° C. The reaction time is preferably 0.5 to 24 hours, and more preferably 1 to 12 hours.

<Process C1>
Compound (Ia) is produced from a compound represented by the following formula (Ia-1) obtained by a known technique (hereinafter referred to as “compound (Ia-1)”) as shown in Scheme 3 below. You can also

(Scheme 3)

First, compound (Ia-1) is hydrolyzed in a solvent containing an acid catalyst to obtain a diol compound represented by the above formula (Ia-2) (hereinafter referred to as “compound (Ia-2)”). Next, the compound (Ia-2) is acetonated in acetone containing an acid catalyst to obtain a dioxolane compound represented by the above formula (Ia-3) (hereinafter referred to as “compound (Ia-3)”). At this time, 2,2-dimethoxypropane may be allowed to coexist in acetone. Then, compound (Ib) is synthesized from compound (Ia-3) by reaction of trihalomethane with a base. Compound (Ia) is obtained by deprotecting the obtained compound (Ib) in a solvent containing an acid catalyst.

A diastereomer (hereinafter referred to as “compound (IbA)”) finally derived from compound (IA) is separated from the obtained diastereomeric mixture of compound (Ib), and compound (IbA) is used. To obtain compound (Ia). Thus obtained compound (Ia) is a diastereomer finally derived from compound (IA). Hereinafter, of the diastereomers of compound (Ia), the diastereomer derived from compound (IA) is referred to as “compound (IaA)” or “first diol diastereomer”.

Since the compound (IaA) thus obtained may contain other diastereomers, it is possible to further purify the compound by further separating other diastereomers from the obtained compound (IaA). High compound (IaA) is obtained.

The amount of the acid catalyst used relative to compound (Ia-1) is, for example, 0.001 to 2 times mol, preferably 0.01 to 1 times mol. Examples of the acid catalyst used include sulfuric acid, hydrochloric acid, hydrobromic acid and perchloric acid.

The amount of the acid catalyst used relative to compound (Ia-2) is, for example, 0.001 to 2 moles, preferably 0.01 to 1 moles. Examples of the acid catalyst used include hydrochloric acid, sulfuric acid, p-toluenesulfonic acid and the like. In addition, 2,2-dimethoxypropane can be added to the solvent, and the amount used is, for example, 0.1 to 10 times mol, preferably 1 to 5 times mol.

The reaction temperature and reaction time can be appropriately set depending on the type of solvent and acid catalyst. The reaction temperature is preferably 0 to 150 ° C., more preferably 20 to 80 ° C. The reaction time is preferably 1 to 24 hours, and more preferably 2 to 10 hours.

The amount of trihalomethane used in the synthesis using compound (Ia-3) is, for example, 0.5 to 1000 times mol, preferably 0.8 to 100 times mol. Examples of the trihalomethane used include chloroform, bromoform, chlorodifluoromethane, dichlorofluoromethane, and dibromofluoromethane. The amount of base used in the synthesis using compound (Ia-3) is, for example, 0.1 to 100 times mol, preferably 0.8 to 50 times mol. 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). As the base used, 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 amount of the acid catalyst used relative to compound (Ib) is, for example, 0.01 to 20 times mol, preferably 0.1 to 2 times mol. Examples of the acid catalyst used include hydrochloric acid, sulfuric acid, acetic acid, methanesulfonic acid and p-toluenesulfonic acid.

<Process B2>
A halohydrin compound represented by the following formula (Ic) (L represents a halogen atom) from the compound (Ia) obtained in Step B1, Step B1-1, or Step C1 by reaction with a halogenating agent, Alternatively, a sulfonyl compound represented by the following formula (Ic) (L represents a sulfonyloxy group) is obtained by reaction with a sulfonyl halide (see the following reaction formula (7)). Hereinafter, these compounds are referred to as “compound (Ic)”.

(Reaction formula (7))

In order to obtain a halohydrin compound (Ic, L = halogen atom), the amount of the halogenating agent used relative to compound (Ia) is, for example, 0.5 to 10 times mol, preferably 0.8 to 2 times mol. . Examples of the halogenating agent used include phosphorus pentachloride, phosphorus pentabromide, sulfuryl chloride, thionyl chloride and the like.

The reaction temperature and reaction time for obtaining the halohydrin compound can be appropriately set depending on the type of the solvent and the halogenating agent. The reaction temperature is preferably −20 to 100 ° C., more preferably 0 to 50 ° C. The reaction time is preferably 0.5 to 24 hours, and more preferably 1 to 12 hours.

In order to obtain the sulfonyl compound (Ic, L = sulfonyloxy group), the amount of the sulfonyl halide used relative to the compound (Ia) is, for example, 0.5 to 10 times mol, preferably 0.8 to 2 times mol. . Examples of the sulfonyl halide used include mesyl chloride and tosyl chloride.

The reaction temperature and reaction time for obtaining the sulfonyl compound can be appropriately set depending on the solvent, the type of sulfonyl halide, and the like. The reaction temperature is preferably −20 to 100 ° C., more preferably 0 to 50 ° C. The reaction time is preferably 0.5 to 24 hours, and more preferably 1 to 12 hours.

As compound (Ia), a diastereomer mixture of compound (Ia) may be used, compound (IaA) separated from diastereomer mixture of compound (Ia), or compound obtained from compound (IbA) (IaA) may be used. Compound (Ic) obtained using compound (IaA) is a diastereomer finally derived from compound (IA). Hereinafter, among the diastereomers of compound (Ic), the diastereomer derived from compound (IA) is referred to as “compound (IcA)” or “first halohydrin or sulfonyl diastereomer”.

Since the obtained compound (IcA) may contain other diastereomers, the compound (IcA) having higher purity can be obtained by further separating other diastereomers from the obtained compound (IcA). ) Is obtained.

<Process B3>
Compound (III) is obtained from compound (Ic) obtained in step B2 by reaction with a base (see the following reaction formula (8)).

(Reaction formula (8))

The amount of the base used relative to compound (Ic) is, for example, 0.5 to 20 times mol, preferably 0.8 to 5 times mol. Examples of the base used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like.

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

As compound (Ic), it is preferable to use (IcA) separated from the diastereomeric mixture of compound (Ic) or compound (IcA) obtained from compound (IaA). Compound (III) obtained using compound (IcA) is a diastereomer finally derived from compound (IA). Hereinafter, of the diastereomers of compound (III), the diastereomer derived from compound (IA) is referred to as “compound (IIIA)” or “first oxirane diastereomer”.

Since it is difficult to separate the compound (IIIA) from the diastereomeric mixture of the compound (III), the compound (IIIA) can be easily obtained by using the compound (IcA). As a result, compound (IA) can be easily obtained from compound (IIIA).

Even when compound (IcA) is used, other diastereomers may be included in the obtained compound (IIIA). By separation, compound (IIIA) with higher purity can be obtained.

Compound (IA) can be produced by reacting compound (IIIA) obtained in this step according to the above step A4. Thus, the diastereomer derived from the diastereomer of the target compound (I) (compound (IA)) is separated from the intermediate diastereomer mixture obtained in the production process of the compound (I). Used for the production of compound (IA). Thereby, the process of isolate | separating the target diastereomer from the diastereomeric mixture of the compound (I) which is a final product is unnecessary, and a compound (IA) can be manufactured efficiently.

<Process B4>
Compound (IaA) is obtained from the diastereomeric mixture of compound (Ia) obtained in the above-described step, Compound (IbA) is obtained from the diastereomeric mixture of compound (Ib), and Compound is obtained from the diastereomeric mixture of compound (Ic). Compound (Ia) is obtained from diastereomer remaining after separation of (IcA), and is reused in the production of compound (IA) (see the following reaction formula (9)).

(Reaction formula (9))

Here, the diastereomer remaining after separating the compound (IaA) from the diastereomeric mixture of the compound (Ia) is referred to as “compound (IaB)” or “second diol diastereomer”. The diastereomer remaining after separation of compound (IbA) from the diastereomeric mixture of compound (Ib) is referred to as “compound IbB”. Further, the diastereomer remaining after separation of the compound (IcA) from the diastereomeric mixture of the compound (Ic) is referred to as “compound (IcB)” or “second halohydrin or sulfonyl diastereomer”. Of the diastereomeric mixture of compound (III), diastereomers other than compound (IIIA) are referred to as “compound (IIIB)” or “second oxirane diastereomer”.

In reaction formula (9), compound (IbB) to compound (IaB), compound (IaB) to compound (IcB), compound (IcB) to compound (IIIB), compound (IIIB) to compound (Ia) As a method for obtaining, the above-described method can be employed. Moreover, the method mentioned above is employable also about the method of obtaining compound (IA) from compound (Ia). The catalyst and solvent to be used, the amount used, the reaction temperature, the reaction time, etc. are appropriately selected.

Compound (IaB), Compound (IbB), Compound (IcB) and Compound (IIIB) are each derived from Compound (IB). Here, compound (IA) and each intermediate derived from compound (IA) are sometimes referred to as “diastereomers (A)” in comparison with other diastereomers, respectively. Further, compound (IB) and each intermediate derived from compound (IB) may be referred to as “diastereomer (B)” in comparison with other diastereomers, respectively.

Compound (IaB), Compound (IbB), Compound (IcB) and Compound (IIIB) are not required in the production of Compound (IA). In the present invention, compound (Ia) is obtained from compound (IaB), compound (IbB), compound (IcB) and compound (IIIB), and is reused in the production of compound (IA). In addition, compound (IA) can be produced at low cost without wasting diastereomers.

<Separation of diastereomers>
As a method for separating each diastereomer from the diastereomer mixture of the compound (Ia), the compound (Ib) and the compound (Ic) obtained in the above-mentioned steps, normal phase column chromatography, reverse phase column chromatography, Alternatively, a known technique of separation utilizing the difference in polarity, solubility, or melting point such as recrystallization 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.

The optical center carbon of each diastereomer separated may be determined according to a conventionally known method.

Note that, in each step of the above-described production method, the solvent, base, acid, and the like used can be as follows unless otherwise specified.

[3: Solvent]
The solvent used is not particularly limited as long as it does not participate in the reaction, but usually ethers such as diethyl ether, tetrahydrofuran and dioxane; alcohols such as methanol, ethanol and isopropanol; aromatics such as benzene, toluene and xylene Hydrocarbons; aliphatic ethers such as petroleum ether, hexane and methylcyclohexane; and amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidinone it can. 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]
You may add a base or an acid 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.

[5. Usefulness of triazole compounds)
The triazole compound according to the present embodiment can be used in a plant disease control agent and a plant disease control method using the same.

Triazole compounds have a controlling effect against a wide range of plant diseases including foliage diseases, seed infectious diseases and soil infectious diseases. In addition, triazole compounds exhibit an effect of increasing the yield by controlling the growth and an effect of improving the quality of a wide variety of crops and horticultural plants.

The plant disease control agent containing a triazole compound can be applied by non-foliage treatment such as seed treatment, irrigation treatment, water surface treatment, etc. 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. Moreover, the plant disease control agent containing a triazole compound can control not only non-foliage diseases but also foliage diseases by non-foliage treatment.

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.

[Example 1]
(Synthesis of 1-1: 2- (1-chlorocyclopropyl) -4-pentene-1,2-diol (compound (Ia-2a)))
5.55 g of 2- (1-chlorocyclopropyl) -4-pentene-1,2-diol-oxirane was suspended in 10.0 ml of water, and several drops of 70% perchloric acid solution were added with stirring. After stirring at 100 ° C. for 1 hour, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 5.95 g of the desired crude product of the compound (Ia-2a) quantitatively.
Purity: 74% (GCarea)
¹ H-NMR (CDCl ₃ ) δ:
0.86 ~ 0.95 (m, 2H), 1.06 ~ 1.18 (m, 2H), 1.80 (dd, 1H, J = 5.1,8.1Hz), 2.29 (s, 1H), 2.50 (dd, 1H, J = 8.8,14.1 Hz), 2.68 (dd, 1H, J = 6.3, 14.1Hz), 3.70 (dd, 1H, J = 8.1, 11.5Hz), 3.88 (dd, 1H, J = 5.1, 11.5Hz), 5.17 to 5.21 (m , 2H), 5.95 to 6.06 (m, 1H).

(1-2: Synthesis of 4- (1-chlorocyclopropyl) -4- (2-propenyl) -2,2-dimethyl-1,3-dioxolane (Compound (Ia-3a)))
Under a nitrogen stream, 5.80 g of compound (Ia-2a) was dissolved in 10.0 ml of acetone, and 8.54 g of 2,2-dimethoxypropane and p-toluenesulfonic acid were added in a catalytic amount. After stirring at room temperature for 3 hours, the reaction solution was poured into ice water and extracted with hexane. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting oil was purified by silica gel column chromatography to obtain 4.18 g of the desired compound (Ia-3a) as a pale yellow oil.
Yield: 58% in two steps from 2- (1-chlorocyclopropyl) -4-pentene-1,2-diol-oxirane of Example (1-1)
¹ H-NMR (CDCl ₃ ) δ:
0.83 ~ 0.91 (m, 1H), 0.95 ~ 1.00 (m, 1H), 1.08 ~ 1.27 (m, 2H), 1.36 (s, 3H), 1.41 (s, 3H), 2.58 (dd, 1H, J = 7.1 , 14.2Hz), 2.78 (dd, 1H, J = 7.4,14.2Hz), 3.94 (d, 1H, J = 8.9Hz), 4.04 (d, 1H, J = 8.9Hz), 5.10-5.18 (m, 2H ), 5.90 to 6.00 (m, 1H).

(1-3: Synthesis of 4- (1-chlorocyclopropyl) -4- (2,2-dibromocyclopropylmethyl) -2,2-dimethyl-1,3-dioxolane (compound (Ib-a)))
4.18 g of compound (Ia-3a) was dissolved in 4.2 ml of dichloromethane, and 4.23 ml of bromoform and 0.18 g of BTMAC (Benzyltrimethylammonium chloride) were added. A solution prepared by dissolving 7.72 g of sodium hydroxide in 7.72 ml of water was added while vigorously stirring the reaction solution at room temperature, and vigorously stirred at 50 ° C. for 10 hours. Furthermore, 4.23 ml of bromoform was added to the reaction solution, and the mixture was stirred at 50 ° C. for 3 hours. According to GC analysis at this time, the ratio of the compound (Ia-3a) used as a raw material was 13% and the target compound (Ib-a) was 87% in the reaction solution.

After cooling, the reaction solution was poured into ice water and extracted with dichloromethane. 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 excess bromoform was distilled off from the resulting crude extract by distillation under reduced pressure. The distillation residue partially solidified and separated into two diastereomers when the solid and oil were separated.

2.20 g of diastereomer (A) was obtained as a white solid. The yield was 29%. 2.94 g of diastereomer (B) was obtained as a yellow oil. The yield was 39%. The remaining oil (compound (Ia-3a)) was contained in the diastereomer (B) oil.

Diastereomer (A);
Melting point: 100-101 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.91 ~ 1.00 (m, 2H), 1.14 ~ 1.21 (m, 2H), 1.39 (s, 3H), 1.47 (s, 3H), 1.48 ~ 1.52 (m, 1H), 1.80 ~ 1.85 (m, 2H), 2.02 to 2.08 (m, 1H), 2.26 to 2.30 (m, 1H), 4.02 (d, 1H, J = 9.0Hz), 4.12 (d, 1H, J = 9.0Hz).
Diastereomer (B);
¹ H-NMR (CDCl ₃ ) δ:
.91 to 0.98 (m, 1H), 1.07 to 1.14 (m, 1H), 1.17 to 1.25 (m, 2H), 1.35 (s, 3H), 1.39 (s, 3H), 1.76 to 1.92 (m, 3H) , 2.58 (d, 1H, J = 4.7Hz), 2.62 (d, 1H, J = 4.5Hz), 3.98 (d, 1H, J = 9.0Hz), 4.12 (d, 1H, J = 9.0Hz).

(1-4: Synthesis of 2- (1-chlorocyclopropyl) -3- (2,2-dibromocyclopropyl) propane-1,2-diol (compound (Ia-a)))
0.54 g of diastereomer (A) of compound (Ib-a) was dissolved in 5.0 ml of methanol, and 0.7 ml of 2N HCl solution was added. The reaction solution was heated to reflux for 2 hours, and most of methanol was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.45 g of a crude product of the diastereomer (A) of the target compound (Ia-a) as a pale yellow oil which was later solidified at room temperature as a pale yellow solid. . The yield was 93%.

The diastereomer (B) of the compound (Ib-a) reacted in the same manner to obtain 0.49 g of a crude product containing the diastereomer (B) of the target compound (Ia-a). The olefin compound derived from the compound (Ia-3a) and other impurities, which are impurities contained in the diastereomer (B) of the compound (Ia-a), are distilled away by washing with hexane, and the target compound (Ia-a) 0.31 g of diastereomer (B) was obtained as a white solid. The yield was 64%.

Diastereomer (A);
Melting point: 79-80 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.89 to 1.00 (m, 2H), 1.17 to 1.29 (m, 2H), 1.38 to 1.42 (m, 1H), 1.81 to 1.94 (m, 3H), 1.96 to 2.09 (m, 2H), 2.72 (s, 1H ), 3.76 (dd, 1H, J = 7.6, 11.3Hz), 4.07 (dd, 1H, J = 4.7, 11.5Hz).
Diastereomer (B);
Melting point: 103-105 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.94 ~ 1.01 (m, 2H), 1.20 ~ 1.23 (m, 2H), 1.33 (t, 1H, J = 7.4Hz), 1.71 (dd, 1H, J = 8.2,14.6Hz), 1.77 ~ 1.85 (m, 2H), 1.88 to 1.94 (m, 1H), 2.32 (dd, 1H, J-4.9, 14.6Hz), 2.56 (s, 1H), 3.70 (dd, 1H, J = 7.8, 11.3Hz), 4.03 (dd , 1H, J = 4.8,11.3Hz).

(1-5: Synthesis of 2- (1-chlorocyclopropyl) -3- (2,2-dibromocyclopropyl) -2-hydroxypropylmethanesulfonic acid ester (compound (Ic-a)))
0.43 g of the diastereomer (A) of compound (Ia-a) was dissolved in 5.0 ml of toluene, and 0.26 ml of triethylamine and 0.14 ml of mesyl chloride were added. After stirring at room temperature for 3 hours, the reaction solution was poured into ice water and extracted with toluene. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.51 g of the diastereomer (A) of the target compound (Ic-a) as a yellow oil. The yield was 96%.

The diastereomer (B) of the compound (Ic-a) reacted in the same manner to obtain 0.36 g of the diastereomer (B) of the target compound (Ic-a) as a white solid. The yield was 99%. In addition, ethyl acetate was used instead of toluene as an extraction solvent after the reaction.

Diastereomer (A);
Melting point: 69-70 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.95 to 1.04 (m, 2H), 1.22 to 1.27 (m, 1H), 1.32 to 1.37 (m, 1H), 1.38 to 1.47 (m, 1H), 1.84 to 1.97 (m, 2H), 2.06 to 2.16 (m , 2H), 2.69 (bs, 1H), 3.13 (s, 3H), 4.51 (d, 1H, J = 10.9Hz), 4.58 (d, 1H, J = 10.9Hz).
Diastereomer (B);
Melting point: 138-139 ° C
¹ H-NMR (CDCl ₃ ) δ:
1.02 to 1.06 (m, 2H), 1.21 to 1.27 (m, 2H), 1.33 to 1.37 (m, 1H), 1.73 to 1.79 (m, 1H), 1.83 to 1.94 (m, 2H), 2.41 (dd, 1H , J = 4.6,9.9Hz), 2.51 (s, 1H), 3.12 (s, 3H), 4.47 (d, 1H, J = 10.9Hz), 4.53 (d, 1H, J = 10.9Hz).

(Synthesis of 1-6: 2- (1-chlorocyclopropyl) -2- (2,2-dibromocyclopropylmethyl) oxirane (compound (III-a)))
0.51 g of the diastereomer (A) of compound (Ic-a) was dissolved in 5.0 ml of methanol, and 1.5 ml of 2N sodium hydroxide solution was added. After stirring at room temperature for 1 hour, 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 0.36 g of a crude product of the diastereomer (A) of the target compound (III-a) as a pale yellow oil. The yield was 91%.

The diastereomer (B) of the compound (Ic-a) reacted in the same manner to obtain 0.25 g of the diastereomer (B) of the target compound (III-a) as a colorless oil. The yield was 92%.

Diastereomer (A);
¹ H-NMR (CDCl ₃ ) δ:
0.83 to 0.89 (m, 1H), 0.93 to 0.99 (m, 1H), 1.02 to 1.12 (m, 2H), 1.36 to 1.40 (m, 1H), 1.58 to 1.66 (m, 1H), 1.79 to 1.84 (m , 1H), 2.17 (dd, 1H, J = 8.0,15.4Hz), 2.34 (dd, 1H, J = 5.9,15.4Hz) 2.83 (d, 1H, J = 4.7Hz), 2.97 (d, 1H, J = 4.7Hz).
Diastereomer (B);
¹ H-NMR (CDCl ₃ ) δ:
0.84 to 0.90 (m, 1H), 0.93 to 0.99 (m, 1H), 1.06 to 1.15 (m, 2H), 1.32 to 1.36 (m, 1H), 1.73 to 1.82 (m, 2H), 1.86 to 1.92 (m , 1H), 2.53 to 2.58 (m, 1H), 2.77 (d, 1H, J = 4.8Hz), 2.85 (d, 1H, J = 4.8Hz).

[Example 2]
(2-1: Synthesis of 2- (1-chlorocyclopropyl) -5-hexene-1,2-diol (Compound (Ia-2b)))
8.60 g of 2- (1-chlorocyclopropyl) -5-hexene-oxirane was suspended in 40.0 ml of water, and 0.2 ml of 70% perchloric acid solution was added with stirring. After stirring at 100 ° C. for 1 hour, the mixture was extracted with dichloromethane. 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 quantitatively obtain 9.85 g of a crude product of the target compound (Ia-2b).
Purity: 88% (GCarea)
¹ H-NMR (CDCl ₃ ) δ:
0.88 to 0.95 (m, 2H), 1.07 to 1.19 (m, 2H), 1.73 to 1.80 (m, 2H), 1.88 to 1.95 (m, 1H), 2.17 to 2.37 (m, 2H), 2.39 (s, 1H ), 3.62 (dd, 1H, J = 7.7, 11.1Hz), 3.95 (dd, 1H, J = 4.8, 11.3Hz), 4.97 to 5.11 (m, 2H), 5.82 to 5.92 (m, 1H).

(2-2: Synthesis of 4- (3-butenyl) -4- (1-chlorocyclopropyl) -2,2-dimethyl-1,3-dioxolane (Compound (Ia-3b)))
Under a nitrogen stream, 9.50 g of compound (Ia-2b) was dissolved in 20.0 ml of acetone, and 13.0 ml of 2,2-dimethoxypropane and p-toluenesulfonic acid were added in a catalytic amount. After stirring at room temperature for 3.5 hours, the reaction solution was poured into ice water and extracted with ether. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 10.44 g of a crude product of the target compound (Ia-3b).
Yield: 90% in two steps from 2- (1-chlorocyclopropyl) -5-hexene-oxirane of Example (2-1)
Purity: 94% (GCarea)
¹ H-NMR (CDCl ₃ ) δ:
0.84 to 0.91 (m, 2H), 0.98 to 1.02 (m, 1H), 1.10 to 1.17 (m, 2H), 1.35 (s, 3H), 1.38 (s, 3H), 2.12 to 2.22 (m, 1H), 2.24 ~ 2.31 (m, 2H), 3.91 (d, 1H, J = 8.8Hz), 4.08 (d, 1H, J = 8.8Hz), 4.95 ~ 5.08 (m, 2H), 5.81 ~ 5.90 (m, 1H)

(2-3: 4- [2- (2,2-dichlorocyclopropyl) ethyl] -4- (1-chlorocyclopropyl) -2,2-dimethyl-1,3-dioxolane (compound (Ib-b) )
Compound (Ia-3b) 10.90g was melt | dissolved in chloroform 40.0ml, BTEAC 0.54g was added. A solution prepared by dissolving 18.92 g of sodium hydroxide in 19.0 ml of water was added little by little while stirring the reaction solution vigorously at room temperature. During the addition of the solution, the reaction solution temperature rose to about 50 ° C., and after adding the entire amount of sodium hydroxide solution, the mixture was vigorously stirred at 50 ° C. After stirring for 2 hours, the temperature of the reaction solution became 50 ° C. or less, and according to GC analysis at this point, the ratio in the reaction solution was 1.5% of the compound (Ia-3b) used as a raw material and the target compound (Ib -B) was 97%.

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 resulting oil was purified by silica gel column chromatography. 12.25 g of the target compound (Ib-b) was obtained as a yellow oily diastereomer mixture. The yield was 82%.
¹ H-NMR (CDCl ₃ ) δ:
0.85 to 0.88 (m, 2H), 0.98 to 1.06 (m, 1H), 1.10 to 1.13 (m, 2H), 1.33, 1.34 (s x 2, 3H), 1.39, 1.40 (s x 2, 3H), 1.56 ~ 1.62 (m, 2H), 1.70 ~ 1.95 (m, 2H), 1.85 ~ 1.88,1.97 ~ 2.04 (m × 2,1H), 2.20 ~ 2.26,2.33 ~ 2.40 (m × 2,1H), 3.93,3.94 (d × 2,1H, J = 8.8Hz), 4.11,4.12 (d × 2,1H, J = 8.8Hz).

(2-4: Synthesis of 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) butane-1,2-diol (compound (Ia-b)))
12.25 g of compound (Ib-b) was dissolved in 200 ml of methanol, and 20.0 ml of 2N HCl solution was added. The reaction solution was heated under reflux for 6 hours, and most of methanol was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting oil was purified by silica gel column chromatography. 10.09 g of the target compound (Ia-b) was obtained as a yellow solid diastereomeric mixture. The yield was 94%.

As a result of ¹ H-NMR measurement, the production ratio of the two diastereomers, diastereomer (A) and diastereomer (B) contained in the obtained diastereomer mixture was approximately A / B = 1/1. It was estimated. This solid is washed with hexane, separated into a filtrate and an insoluble solid, a yellow oil (diastereomer (A)) (partially solidified at room temperature) from the filtrate, and a white crystal (diastereoisomer) from the insoluble solid. (B)). The respective diastereomeric ratios are as follows. From the result of ¹ H-NMR measurement, the oily substance (diastereomer (A)) is A / B = about 70/30, and the white crystal (diastereomer (B)) is A / B. = Estimated to be about 30/70.

Diastereomer (A);
¹ H-NMR (CDCl ₃ ) δ:
0.86 ~ 0.95 (m, 2H), 1.10 ~ 1.16 (m, 3H), 1.56 ~ 1.97 (m, 6H), 2.39 (s, 3H), 3.63 (dd, 1H, J = 7.6,11.2Hz), 3.98 ( dd, 1H, J = 4.8,11.2Hz).
Diastereomer (B);
¹ H-NMR (CDCl ₃ ) δ:
0.90 to 0.95 (m, 2H), 1.06 to 1.19 (m, 2H), 1.57 to 1.65 (m, 2H), 1.68 to 1.87 (m, 3H), 2.05 to 2.11 (m, 1H), 2.42 (s, 1H ), 3.62 (d, 1H, J = 7.5, 11.2 Hz), 3.99 (dd, 1H, J = 4.9, 11.2 Hz).

(2-5: Synthesis of 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) -2-hydroxybutylmethanesulfonic acid ester (compound (Ic-b)))
0.27 g of diastereomer (A) of compound (Ia-b) and 0.20 ml of triethylamine were dissolved in 5.0 ml of toluene, and 0.11 ml of mesyl chloride was added. After stirring at room temperature for 3.5 hours, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 0.37 g of the target compound (Ic-b) was quantitatively obtained as a diastereomeric mixture of yellow oil.

As a result of ¹ H-NMR measurement, it was estimated that the diastereomer ratio in the obtained diastereomer mixture was hardly changed from the ratio in the starting compound (Ia-b).

The diastereomer (B) of the compound (Ia-b) was subjected to the same reaction as described above to obtain 0.32 g of the target compound (Ic-b) as a white crystal diastereomer mixture. The yield was 94%.

Similarly, from the ¹ H-NMR measurement results, the diastereomer ratio in the obtained diastereomer mixture is almost different from the ratio in the diastereomer (B) of the starting compound (Ia-b). Not estimated.

Each diastereomer mixture was recrystallized with hexane / ethyl acetate = 10/1 to isolate the diastereomer (A) and the diastereomer (B).

Diastereomer (A);
White crystalline melting point: 86-87 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.92 to 1.00 (m, 2H), 1.11 to 1.18 (m, 2H), 1.21 to 1.27 (m, 1H), 1.56 to 1.71 (m, 3H), 1.82 to 1.88 (m, 1H), 1.90 to 2.08 (m , 2H), 2.28 (s, 1H), 3.10 (s, 3H), 4.41 (d, 1H, J = 10.8Hz), 4.48 (d, 1H, J = 10.8Hz).
Diastereomer (B);
White crystalline melting point: 78-79 ° C
¹ H-NMR (CDCl ₃ ) δ:
0.92 to 1.00 (m, 2H), 1.09 to 1.18 (m, 2H), 1.21 to 1.25 (m, 1H), 1.55 to 1.75 (m, 3H), 1.79 to 2.05 (m, 2H), 2.15 to 2.20 (m , 1H), 2.29 (s, 1H), 3.10 (s, 3H), 4.40 (d, 1H, J = 10.7Hz), 4.49 (d, 1H, J = 10.7Hz).

(2-6: Synthesis of 2- (1-chlorocyclopropyl) -2- [2- (2,2-dichlorocyclopropyl) ethyl] oxirane (Compound (III-b)))
A solution of 0.32 g of the diastereomer (B) of compound (Ic-b) in 2.0 ml of methanol and a solution of 0.40 g of sodium hydroxide in 1.0 ml of water were added. After stirring at room temperature for 1 hour, 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 0.21 g of the objective compound (III-b) as a diastereomeric mixture of pale yellow oil. The yield was 91%. As a result of ¹ H-NMR measurement, the diastereomer ratio of diastereomer (A) and diastereomer (B) was estimated to be A / B = 34/66, and the compound (Ic-b) used as the starting material It was speculated that there was no change from the diastereomer ratio (A / B = 3/7) in the diastereomer (B).

Further, 0.10 g of diastereomer (B) of compound (Ic-b) was dissolved in 1.5 ml of methanol, and 1.5 ml of 2N sodium hydroxide solution was added thereto. After stirring at room temperature for 1 hour, 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 56 mg of the objective compound (III-b) as a colorless oil. The yield was 77%. As a result of ¹ H-NMR measurement, it was confirmed that the obtained compound (III-b) contained only the diastereomer (B).

(2-7: Synthesis of 2- (1-chlorocyclopropyl) -2- [2- (2,2-dichlorocyclopropyl) ethyl] oxirane (compound (III-b)))
0.27 g of the diastereomer (B) of compound (Ia-b) was added in small portions to 2.0 ml (ca. 5.2 mmol) of 30% HBr acetic acid solution. After stirring at room temperature for 1.5 hours, the reaction solution was poured into ice water and extracted with ether. 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 quantitatively obtain 0.32 g of a crude extract of the target intermediate acetoxy bromide as a yellow oil.

This crude extract was dissolved in 2.0 ml of methanol, and a solution in which 0.40 g of sodium hydroxide was dissolved in 1.0 ml of water was added. After stirring at room temperature for 1 hour, 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 purified by silica gel column chromatography. 0.13 g of the target compound (III-b) was obtained as a diastereomeric mixture of pale yellow oil. The yield was 53%. As a result of ¹ H-NMR measurement, the production ratio of diastereomer (A) and diastereomer (B) was estimated to be approximately A / B = 47/53. This changed from the diastereomer content ratio 3/7 of the diastereomer (B) of the compound (Ia-b) used as a raw material, and it was speculated that racemization proceeded.

(2-8: Synthesis of acetoxy-2-bromo-2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) butane (compound (III-c)))
1.01 g of diastereomer (B) of compound (Ia-b) was added to 2.17 ml of a saturated HBr acetic acid solution while stirring little by little, and then stirred at room temperature for 1 hour. The reaction solution was poured into ice water, neutralized with sodium carbonate, and extracted with ether. 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 1.25 g of the obtained oil was purified by silica gel column chromatography. 0.39 g of the objective compound (III-c) was obtained as a colorless oil. The yield was 28%. As a result of ¹ H-NMR measurement, the production ratio of diastereomer (A) and diastereomer (B) was estimated to be approximately A / B = 1/1.
¹ H-NMR (CDCl ₃ ) δ:
1.06 to 1.17 (m, 3H), 1.36 to 1.48 (m, 2H), 1.57 to 1.64 (m, 2H), 1.74 to 1.86 (m, 1H), 1.90 to 2.00 (m, 1H), 2.10 to 2.43 (m , 2H), 2.13, 2.14 (s × 2,3H), 4.48 to 4.55 (m, 2H)

(2-9: Synthesis of 2- (1-chlorocyclopropyl) -4- (2,2-dichlorocyclopropyl) butane-1,2-diol (compound (Ia-b)))
0.51 g of compound (III-b) was dissolved in a mixed solution of 15.0 ml of water and 5.0 ml of t-butanol, and 1 drop of concentrated sulfuric acid was added. After 5 hours of stirring at room temperature, the reaction was not progressing, so the mixture was further stirred at 100 ° C for 1 hour. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting oil was purified by silica gel column chromatography. 0.44 g of the target compound (Ia-b) was obtained as a diastereomeric mixture of pale yellow oil. The yield was 81%. As a result of ¹ H-NMR measurement, the production ratio of diastereomer (A) and diastereomer (B) was estimated to be approximately A / B = 1/1.

Further, 0.21 g of diastereomer (B) of compound (III-b) was dissolved in a mixed solution of 4.5 ml of water and 1.5 ml of t-butanol, and 1 drop of concentrated sulfuric acid was added. After stirring at 100 ° C. for 2 hours, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 0.24 g of the target compound (Ia-b) was quantitatively obtained as a diastereomeric mixture of pale yellow oil. As a result of ¹ H-NMR measurement, the production ratio of diastereomer (A) and diastereomer (B) was estimated to be approximately A / B = 33/67.

The present invention can also be expressed as follows.

The method for producing a triazole compound according to the present invention includes a second oxirane diastereomer that produces a second oxirane diastereomer of the oxirane compound represented by the general formula (III) from the diol compound produced in the diol production step. Preferably, the method further includes a stereomer production step and a diol regeneration step of producing the diol compound using the second oxirane diastereomer produced in the second oxirane diastereomer production step.

Furthermore, in the method for producing a triazole compound according to the present invention, it is preferable that in the diol production step, the oxirane compound is hydrolyzed to produce a diol compound.

Further, in the method for producing a triazole compound according to the present invention, in the diol production step, the oxirane compound is acetonated to produce a dioxolane compound represented by the following general formula (Ib):

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are different from each other, and n represents 0 to 3. R ² represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
It is preferable to hydrolyze the dioxolane compound to produce a diol compound.

In the method for producing a triazole compound according to the present invention, in the diol production step, a first dioxolane diastereomer is separated from the dioxolane compound, and the first dioxolane diastereomer is hydrolyzed to obtain a diol compound. It is preferable to produce.

Furthermore, in the method for producing a triazole compound according to the present invention, a halohydrin or sulfonyl compound represented by the following general formula (Ic) is obtained from the diol compound produced in the diol production step in the first oxirane diastereomer production step. Generate

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R ² represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
It is preferred to separate the first halohydrin or sulfonyl diastereomer from the halohydrin or sulfonyl compound to produce the first oxirane diastereomer from the first halohydrin or sulfonyl diastereomer.

Further, the method for producing a triazole compound according to the present invention includes separating the first diol diastereomer from the diol compound produced in the diol production step in the first oxirane diastereomer production step. From the diol diastereomer, a first halohydrin or sulfonyl diastereomer of a halohydrin or sulfonyl compound represented by the following general formula (Ic) is produced:

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R ² represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
Preferably, the first oxirane diastereomer is generated from the first halohydrin or sulfonyl diastereomer.

Furthermore, in the method for producing a triazole compound according to the present invention, a halohydrin or sulfonyl compound represented by the following general formula (Ic) is obtained from the diol compound produced in the diol production step in the second oxirane diastereomer production step. Generate

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R ² represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
It is preferred that the second halohydrin or sulfonyl diastereomer is separated from the halohydrin or sulfonyl compound to produce the second oxirane diastereomer from the second halohydrin or sulfonyl diastereomer.

In the method for producing a triazole compound according to the present invention, in the second oxirane diastereomer production step, the second diol diastereomer is separated from the diol compound produced in the diol production step. From the diol diastereomer, a second halohydrin or sulfonyl diastereomer of the halohydrin or sulfonyl compound represented by the following general formula (Ic) is produced:

(X ³ to X ⁵ represent a hydrogen atom or a halogen atom, X ⁵ represents a halogen atom, a plurality of X ⁴ are the same atom, and a plurality of X ⁵ are the same atom. X ⁴ and X ⁵ are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R ² represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
Preferably, the second oxirane diastereomer is produced from the second halohydrin or sulfonyl diastereomer.

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

Claims

A diol production step of producing a diol compound represented by the following general formula (Ia) from an oxirane compound represented by the following general formula (III):

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are different from each other, and n represents 0 to 3. R 2 represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are different from each other, and n represents 0 to 3. R 2 represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
A first oxirane diastereomer producing step for producing a first oxirane diastereomer of the oxirane compound represented by the general formula (III) from the diol compound produced in the diol producing step;
A triazole compound production step for producing a triazole compound represented by the following general formula (I) using the first oxirane diastereomer produced in the first oxirane diastereomer production step;

(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.)
Including
The method for producing a triazole compound, wherein the first oxirane diastereomer is derived from a target diastereomer in the triazole compound represented by the general formula (I).
A second oxirane diastereomer producing step for producing a second oxirane diastereomer of the oxirane compound represented by the general formula (III) from the diol compound produced in the diol producing step;
The triazole according to claim 1, further comprising a diol regenerating step of generating the diol compound using the second oxirane diastereomer generated in the second oxirane diastereomer generating step. Compound production method.
The method for producing a triazole compound according to claim 1, wherein, in the diol production step, the oxirane compound is hydrolyzed to produce a diol compound.
In the diol production step,
The oxirane compound is acetonated to produce a dioxolane compound represented by the following general formula (Ib):

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are different from each other, and n represents 0 to 3. R 2 represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
The method for producing a triazole compound according to claim 1, wherein the dioxolane compound is hydrolyzed to produce a diol compound.
5. The diol production step according to claim 4, wherein in the diol production step, a first dioxolane diastereomer is separated from the dioxolane compound, and the first dioxolane diastereomer is hydrolyzed to produce a diol compound. A method for producing a triazole compound.
In the first oxirane diastereomer production step,
A halohydrin or sulfonyl compound represented by the following general formula (Ic) is produced from the diol compound produced in the diol production step,

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R 2 represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
The first halohydrin or sulfonyl diastereomer is separated from the halohydrin or sulfonyl compound to produce the first oxirane diastereomer from the first halohydrin or sulfonyl diastereomer. The manufacturing method of the triazole compound of description.
In the first oxirane diastereomer production step,
A first diol diastereomer is separated from the diol compound produced in the diol production step, and from the first diol diastereomer, a halohydrin represented by the following general formula (Ic) or a first halohydrin of a sulfonyl compound or Producing sulfonyl diastereomers,

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R 2 represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
The method for producing a triazole compound according to claim 1, wherein the first oxirane diastereomer is produced from the first halohydrin or sulfonyl diastereomer.
In the second oxirane diastereomer production step,
A halohydrin or sulfonyl compound represented by the following general formula (Ic) is produced from the diol compound produced in the diol production step,

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R 2 represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
3. The second halohydrin or sulfonyl diastereomer is separated from the halohydrin or sulfonyl compound to produce the second oxirane diastereomer from the second halohydrin or sulfonyl diastereomer. The manufacturing method of the triazole compound of description.
In the second oxirane diastereomer production step,
A second diol diastereomer is separated from the diol compound produced in the diol production step, and from the second diol diastereomer, a halohydrin represented by the following general formula (Ic) or a second halohydrin of a sulfonyl compound or Producing sulfonyl diastereomers,

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R 2 represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
The method for producing a triazole compound according to claim 2, wherein the second oxirane diastereomer is produced from the second halohydrin or sulfonyl diastereomer.
An intermediate compound obtained by the method for producing a triazole compound according to claim 1, which is represented by the following general formula (Ia).

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are different from each other, and n represents 0 to 3. R 2 represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
An intermediate compound obtained by the method for producing a triazole compound according to claim 1, wherein the intermediate compound is represented by the following general formula (Ib).

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are different from each other, and n represents 0 to 3. R 2 represents a C3 to C6 cycloalkyl group or a C1 to C4 substituted with the cycloalkyl group The cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, an aryl group, or an arylalkyl group (alkyl The aromatic ring of the aryl group and the arylalkyl group may be a halogen atom, a C1-C4 alkyl group, Haloalkyl group 1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)
An intermediate compound obtained by the method for producing a triazole compound according to claim 1, wherein the intermediate compound is represented by the following general formula (Ic).

(X 3 to X 5 represent a hydrogen atom or a halogen atom, X 5 represents a halogen atom, a plurality of X 4 are the same atom, and a plurality of X 5 are the same atom. X 4 and X 5 are mutually different atoms, n represents 0 to 3, L represents a halogen atom or a sulfonyloxy group, R 2 represents a C3 to C6 cycloalkyl group, Or a C1-C4 alkyl group substituted with the cycloalkyl group, wherein the cycloalkyl group and the alkyl group are a halogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C6 The aryl group and the arylalkyl may be substituted with a cycloalkyl group, an aryl group, or an arylalkyl group (carbon chain C1 to C3 of the alkyl moiety). The aromatic ring, a halogen atom, an alkyl group of C1 ~ C4, haloalkyl group of C1 ~ C4, alkoxy group of C1 ~ C4, or may be substituted with a haloalkoxy group having C1 ~ C4.)