JP2012180339A - Isoxazoline compound and harmful organism-controlling agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a compound capable of being industrially advantageously synthesized, having a reliable effect, and capable of especially being safely used to bring the compound to be stably formulated, and a harmful organism-controlling agent containing the compound as an active ingredient.SOLUTION: There is provided a crystal composed of a single diastereomer of an isoxazoline compound represented by formula (I). [In the formula, X represents a halogen atom or the like; n represents the number of substituent(s) of X; X' represents a halogen atom or the like; m represents the number of substituent(s) of X'; Rrepresents a 1-6C haloalkyl group; Rrepresents H or the like; Rrepresents H, a substituted or non-substituted 1-6C alkyl group or the like; p represents a repeating number of the methylene group in the parenthesis and is an integer of 1 or 2].

Description

  The present invention relates to a crystal composed of a single diastereomer of an isoxazoline compound, an optically active isoxazoline compound, and a pest control agent.

  Many pesticides, acaricides, and other pesticides are used in the fields of agriculture, horticulture, livestock, etc., but their use is insufficient or due to drug resistance problems. It is restricted, causes phytotoxicity and pollution to plants, or is highly toxic to human and livestock fish. Therefore, there is a demand for development of a drug that can be safely used with few such drawbacks.

  In relation to the present invention, Patent Document 1 describes a compound having the same skeleton as the compound of the present invention.

WO2009 / 022746

  The present invention provides a single diazol of an isoxazoline compound that can be advantageously synthesized industrially, has a certain effect, can be an active ingredient of a pest control agent that can be used particularly safely, and can be stably formulated. It is an object of the present invention to provide a stereomer crystal, an optically active isoxazoline compound or a salt thereof, and a pest control agent containing these compounds as active ingredients.

  In order to solve the above-mentioned problems, the present inventors have conducted an extensive search. And the present inventors paid attention to the isoxazoline compound or its salt known in Patent Document 1 as an active ingredient of a drug for assisting the growth of agricultural crops, and repeated studies. As a result, it was found that the specific optically active isoxazoline compound or salt thereof obtained by optical resolution of the isoxazoline compound or salt thereof described in Patent Document 1 can achieve both efficacy and safety. Moreover, the crystal | crystallization of the isoxazoline compound which consists of a single diastereomer which can be stabilized, and its manufacturing method were discovered. The present invention has been completed based on these findings.

That is, the present invention includes the following.
[1] A crystal comprising a single diastereomer of an isoxazoline compound represented by the formula (I).

（式（I）中、Ｘは、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｎは、Ｘの置換数を示し且つ０〜５のいずれかの整数である。ｎが２以上のとき、Ｘ同士は互いに同一でも異なっていてもよい。
Ｘ’は、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｍは、Ｘ’の置換数を示し且つ０〜６のいずれかの整数である。ｍが２以上のとき、Ｘ’同士は互いに同一でも異なっていてもよい。
Ｒ¹は、Ｃ１〜６ハロアルキル基を示す。
Ｒ²は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ１〜７アシル基、または無置換のもしくは置換基を有するＣ１〜６アルコキシカルボニル基を示す。
Ｒ³は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ２〜６アルケニル基、無置換のもしくは置換基を有するＣ２〜６アルキニル基、無置換のもしくは置換基を有するＣ３〜８シクロアルキル基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、無置換のもしくは置換基を有するＣ２〜６アルケニルオキシ基、無置換の若しくは置換基を有するＣ２〜６アルキニルオキシ基、無置換のもしくは置換基を有するＣ６〜１０アリール基、または無置換のもしくは置換基を有するヘテロ環基を示す。
ｐは、括弧内のメチレン基の繰返し数を示し且つ１または２のいずれかの整数である。）

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. )

[2] A crystal comprising a combination of an isoxazoline compound represented by formula (I-1) and an isoxazoline compound represented by formula (I-2).

（式（I-1）中、Ｘ、ｎ、Ｘ’、ｍ、Ｒ¹、Ｒ²、Ｒ³、およびｐは、前記式（I）におけるものと同じ意味を示す。）

(In formula (I-1), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in formula (I).)

（式（I-2）中、Ｘ、ｎ、Ｘ’、ｍ、Ｒ¹、Ｒ²、Ｒ³、およびｐは、前記式（I）におけるものと同じ意味を示す。）

(In the formula (I-2), X, n, X ′, m, R ¹ , R ² , R ³ and p have the same meaning as in the formula (I).)

[3] An optically active isoxazoline compound represented by the formula (II) or a salt thereof.

（式（II）中、Ｘは、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｎは、Ｘの置換数を示し且つ０〜５のいずれかの整数である。ｎが２以上のとき、Ｘ同士は互いに同一でも異なっていてもよい。
Ｘ’は、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｍは、Ｘ’の置換数を示し且つ０〜６のいずれかの整数である。ｍが２以上のとき、Ｘ’同士は互いに同一でも異なっていてもよい。
Ｒ¹は、Ｃ１〜６ハロアルキル基を示す。
Ｒ²は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ１〜７アシル基、または無置換のもしくは置換基を有するＣ１〜６アルコキシカルボニル基を示す。
Ｒ³は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ２〜６アルケニル基、無置換のもしくは置換基を有するＣ２〜６アルキニル基、無置換のもしくは置換基を有するＣ３〜８シクロアルキル基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、無置換のもしくは置換基を有するＣ２〜６アルケニルオキシ基、無置換の若しくは置換基を有するＣ２〜６アルキニルオキシ基、無置換のもしくは置換基を有するＣ６〜１０アリール基、または無置換のもしくは置換基を有するヘテロ環基を示す。
ｐは、括弧内のメチレン基の繰返し数を示し且つ１または２のいずれかの整数である。
* および**は、光学活性な炭素原子を示す。）

(In Formula (II), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2.
* And ** represent optically active carbon atoms. )

[4] An optically active isoxazoline compound represented by the formula (II-1) or a salt thereof.

（式（II-1）中、Ｘ、ｎ、Ｘ’、ｍ、Ｒ¹、Ｒ²、Ｒ³、およびｐは、前記式（II）におけるものと同じ意味を示す。）

(In formula (II-1), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in formula (II).)

[5] A pest control agent comprising the crystal according to [1] or [2] or the optically active isoxazoline compound or salt thereof according to [3] or [4] as an active ingredient.
[6] An insecticide containing, as an active ingredient, the crystal according to [1] or [2], or the optically active isoxazoline compound or salt thereof according to [3] or [4].
[7] An acaricide containing the crystal according to [1] or [2], or the optically active isoxazoline compound or salt thereof according to [3] or [4] as an active ingredient.
[8] An animal ectoparasite control agent comprising the crystal according to [1] or [2], or the optically active isoxazoline compound according to [3] or [4] or a salt thereof as an active ingredient.

[9] A mixture of diastereomers of the isoxazoline compound represented by the formula (I) is mixed with any two or more of an ether solvent, an ester solvent, a halogen solvent, or a hydrocarbon solvent. The method for producing a crystal according to [1], comprising dissolving and then crystallizing.

（式（I）中、Ｘは、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｎは、Ｘの置換数を示し且つ０〜５のいずれかの整数である。ｎが２以上のとき、Ｘ同士は互いに同一でも異なっていてもよい。
Ｘ’は、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｍは、Ｘ’の置換数を示し且つ０〜６のいずれかの整数である。ｍが２以上のとき、Ｘ’同士は互いに同一でも異なっていてもよい。
Ｒ¹は、Ｃ１〜６ハロアルキル基を示す。
Ｒ²は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ１〜７アシル基、または無置換のもしくは置換基を有するＣ１〜６アルコキシカルボニル基を示す。
Ｒ³は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ２〜６アルケニル基、無置換のもしくは置換基を有するＣ２〜６アルキニル基、無置換のもしくは置換基を有するＣ３〜８シクロアルキル基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、無置換のもしくは置換基を有するＣ２〜６アルケニルオキシ基、無置換の若しくは置換基を有するＣ２〜６アルキニルオキシ基、無置換のもしくは置換基を有するＣ６〜１０アリール基、または無置換のもしくは置換基を有するヘテロ環基を示す。
ｐは、括弧内のメチレン基の繰返し数を示し且つ１または２のいずれかの整数である。）

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. )

[10] A mixture of diastereomers of the isoxazoline compound represented by the formula (I) is mixed with any two or more of an ether solvent, an ester solvent, a halogen solvent, or a hydrocarbon solvent. The method for producing a crystal according to [2], comprising dissolving and then crystallizing.

（式（I）中、Ｘは、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｎは、Ｘの置換数を示し且つ０〜５のいずれかの整数である。ｎが２以上のとき、Ｘ同士は互いに同一でも異なっていてもよい。
Ｘ’は、ハロゲン原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、水酸基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、ニトロ基、またはシアノ基を示す。
ｍは、Ｘ’の置換数を示し且つ０〜６のいずれかの整数である。ｍが２以上のとき、Ｘ’同士は互いに同一でも異なっていてもよい。
Ｒ¹は、Ｃ１〜６ハロアルキル基を示す。
Ｒ²は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ１〜７アシル基、または無置換のもしくは置換基を有するＣ１〜６アルコキシカルボニル基を示す。
Ｒ³は、水素原子、無置換のもしくは置換基を有するＣ１〜６アルキル基、無置換のもしくは置換基を有するＣ２〜６アルケニル基、無置換のもしくは置換基を有するＣ２〜６アルキニル基、無置換のもしくは置換基を有するＣ３〜８シクロアルキル基、無置換のもしくは置換基を有するＣ１〜６アルコキシ基、無置換のもしくは置換基を有するＣ２〜６アルケニルオキシ基、無置換の若しくは置換基を有するＣ２〜６アルキニルオキシ基、無置換のもしくは置換基を有するＣ６〜１０アリール基、または無置換のもしくは置換基を有するヘテロ環基を示す。
ｐは、括弧内のメチレン基の繰返し数を示し且つ１または２のいずれかの整数である。）

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. )

According to the present invention, there is provided an optically active isoxazoline compound or a salt thereof that can be advantageously synthesized industrially, has a certain effect, and can be an active ingredient of a pest control agent that can be used particularly safely. In addition, a crystal composed of a single diastereomer of an isoxazoline compound, which can be stably formulated, and a method for producing the same are provided.
These isoxazoline compounds or salts thereof are effective as insecticides, acaricides, sanitary pest control agents, animal ectoparasite control agents, and the like.

It is a figure which shows the HPLC chart of the mixture of the diastereomer used in manufacture example 3 (1). It is a figure which shows the HPLC chart of the crystal | crystallization obtained by manufacture example 3 (1). It is a figure which shows the HPLC chart of the mixture of the diastereomer used in manufacture example 3 (2). It is a figure which shows the HPLC chart of the crystal | crystallization obtained by manufacture example 3 (2). It is a figure which shows the HPLC chart of the mixture of the diastereomer used in manufacture example 3 (3). It is a figure which shows the HPLC chart of the crystal | crystallization obtained by manufacture Example 3 (3).

[Crystal consisting of a single diastereomer of an isoxazoline compound]
The crystal composed of a single diastereomer of the isoxazoline compound represented by the formula (I) according to the present invention has a relatively high melting point and a narrow temperature range between the starting point and the ending point of the melting, and is stable as a substance. And has the advantage of excellent stability during formulation and in formulation. Here, the “single diastereomer” is a combination of any one of a plurality of isomers in a diastereomeric relationship.

  In general, a mixture of diastereomers is often amorphous and has a low melting point. Even if a mixture of diastereomers is obtained as crystals, the reproducibility of the crystallization is poor. Furthermore, it contains a lot of impurities and is not suitable for actual formulation. On the other hand, the compound according to the present invention has excellent characteristics as compared with general diastereomeric mixtures.

The meanings of symbols, terms and the like used in formula (I) are shown below.
First, the term “unsubstituted” means that the group is only a parent nucleus. When there is no description of “having a substituent” and only the name of the group serving as a mother nucleus is used, it means “unsubstituted” unless otherwise specified.
On the other hand, the term “having a substituent” means that any hydrogen atom of a group serving as a mother nucleus is substituted with a group having the same or different structure from the mother nucleus. Accordingly, the “substituent” is another group bonded to a group serving as a mother nucleus. The number of substituents may be one, or two or more. Two or more substituents may be the same or different.
Terms such as “C1-6” indicate that the number of carbon atoms of the group serving as the mother nucleus is 1-6. This number of carbon atoms does not include the number of carbon atoms present in the substituent. For example, a butyl group having an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group.

The “substituent” is not particularly limited as long as it is chemically acceptable and has the effects of the present invention.
Examples of groups that can be “substituents” include halogen atoms such as fluorine atom, chlorine atom, bromine atom, iodine atom; methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl C1-6 alkyl group such as a group, i-butyl group, t-butyl group, n-pentyl group, n-hexyl group; C3-8 such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group A cycloalkyl group; a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-2-butenyl group, 2-methyl-2-butenyl group, 1-hetenyl group C2-6 alkenyl groups such as xenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group; 2-cyclopropenyl group, 2-cyclopentenyl group, 3-cyclohexenyl group, 4- C3-8 cycloalkenyl groups such as cyclooctenyl group; ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2- Methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentynyl group, 1-hexynyl group, A C2-6 alkynyl group such as a 1,1-dimethyl-2-butynyl group;

  C1-6 alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, s-butoxy group, i-butoxy group, t-butoxy group; vinyloxy group, allyloxy group, propenyl C2-6 alkenyloxy groups such as oxy group and butenyloxy group; C2-6 alkynyloxy groups such as ethynyloxy group and propargyloxy group; C6-10 aryl groups such as phenyl group and naphthyl group; phenoxy group and 1-naphthoxy group A C7-10 aralkyl group such as a benzyl group or a phenethyl group; a C7-11 aralkyloxy group such as a benzyloxy group or a phenethyloxy group; a formyl group, an acetyl group, a propionyl group, a benzoyl group, C1- such as a cyclohexylcarbonyl group Acyl group; C1-7 acyloxy group such as formyloxy group, acetyloxy group, propionyloxy group, benzoyloxy group, cyclohexylcarbonyloxy group; methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group A C1-6 alkoxycarbonyl group such as n-butoxycarbonyl group and t-butoxycarbonyl group; carboxyl group;

  Hydroxyl group; oxo group; C1-6 haloalkyl such as chloromethyl group, chloroethyl group, trifluoromethyl group, 1,2-dichloro-n-propyl group, 1-fluoro-n-butyl group, perfluoro-n-pentyl group Group; C2-6 haloalkenyl group such as 2-chloro-1-propenyl group and 2-fluoro-1-butenyl group; 4,4-dichloro-1-butynyl group, 4-fluoro-1-pentynyl group, 5- C2-6 haloalkynyl group such as bromo-2-pentynyl group; C1-6 haloalkoxy group such as 2-chloro-n-propoxy group and 2,3-dichlorobutoxy group; 2-chloropropenyloxy group, 3-bromo C2-6 haloalkenyloxy groups such as butenyloxy group; 4-chlorophenyl group, 4-fluorophenyl group, 2,4-dichlorophen C6-10 haloaryl group such as 4-fluorophenyloxy group, C6-10 haloaryloxy group such as 4-fluorophenyloxy group, 4-chloro-1-naphthoxy group; chloroacetyl group, trifluoroacetyl group, trichloroacetyl group, 4- Halogen-substituted C1-7 acyl groups such as chlorobenzoyl groups;

  Cyano group; isocyano group; nitro group; isocyanato group; cyanato group; amino group; C1-6 alkylamino group such as methylamino group, dimethylamino group and diethylamino group; C6-10 arylamino group such as anilino group and naphthylamino group Group: C7-11 aralkylamino group such as benzylamino group, phenylethylamino group; C1-7 such as formylamino group, acetylamino group, propanoylamino group, butyrylamino group, i-propylcarbonylamino group, benzoylamino group Acylamino group; C1-6 alkoxycarbonylamino group such as methoxycarbonylamino group, ethoxycarbonylamino group, n-propoxycarbonylamino group, i-propoxycarbonylamino group; aminocarbonyl group, dimethylaminocarbonyl An unsubstituted or substituted aminocarbonyl group such as phenylaminocarbonyl group, N-phenyl-N-methylaminocarbonyl group; iminomethyl group, (1-imino) ethyl group, (1-imino) -n-propyl A C1-6 alkyl group substituted with an imino group such as a group; hydroxyiminomethyl group, (1-hydroxyimino) ethyl group, (1-hydroxyimino) propyl group, methoxyiminomethyl group, (1-methoxyimino) ethyl A C1-6 alkyl group substituted with a hydroxyimino group or an alkoxyimino group such as a group;

  Mercapto group; C1-6 alkylthio group such as methylthio group, ethylthio group, n-propylthio group, i-propylthio group, n-butylthio group, i-butylthio group, s-butylthio group, t-butylthio group; vinylthio group, allylthio C2-6 alkenylthio groups such as groups; C2-6 alkynylthio groups such as ethynylthio groups and propargylthio groups; C6-10 arylthio groups such as phenylthio groups and naphthylthio groups; heteroarylthio groups such as thiazolylthio groups and pyridylthio groups;

  C1-6 alkylsulfinyl groups such as methylsulfinyl group, ethylsulfinyl group, t-butylsulfinyl group; C2-6 alkenylsulfinyl groups such as allylsulfinyl group; C2-6 alkynylsulfinyl groups such as propargylsulfinyl group; phenylsulfinyl group and the like A heteroarylsulfinyl group such as thiazolylsulfinyl group and pyridylsulfinyl group; a C7-11 aralkylsulfinyl group such as benzylsulfinyl group and phenethylsulfinyl group; a methylsulfonyl group, an ethylsulfonyl group, t- C1-6 alkylsulfonyl group such as butylsulfonyl group; C2-6 alkenylsulfonyl group such as allylsulfonyl group; C2 such as propargylsulfonyl group A C6-10 arylsulfonyl group such as a phenylsulfonyl group; a heteroarylsulfonyl group such as a thiazolylsulfonyl group or a pyridylsulfonyl group; a C7-11 aralkylsulfonyl group such as a benzylsulfonyl group or a phenethylsulfonyl group;

  5-membered heteroaryl groups such as pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl; pyridyl, pyrazinyl Groups, 6-membered heteroaryl groups such as pyrimidinyl groups, pyridinidyl groups, triazinyl groups; saturated heterocyclyl groups such as aziridinyl groups, epoxy groups, pyrrolidinyl groups, tetrahydrofuranyl groups, piperidyl groups, piperazinyl groups, morpholinyl groups; trimethylsilyl groups, triethylsilyl groups A tri-C1-6 alkyl-substituted silyl group such as a t-butyldimethylsilyl group; a triphenylsilyl group;

  These “substituents” may be those in which any hydrogen atom in the group is further substituted with another “substituent”.

(X)
X in the formula (I) represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. . n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.

  The “C1-6 alkyl group” in X may be a straight chain or a branched chain. As the alkyl group, methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, n-hexyl group, i-propyl group, i-butyl group, s-butyl group, t-butyl group I-pentyl group, neopentyl group, 2-methylbutyl group, 2,2-dimethylpropyl group, i-hexyl group and the like.

  The “C 1-6 alkyl group having a substituent” in X is a C 3-8 cyclo group such as cyclopropylmethyl group, 2-cyclopropylethyl group, cyclopentylmethyl group, 2-cyclohexylethyl group, 2-cyclooctylethyl group, etc. Alkyl C1-6 alkyl group; fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, trifluoromethyl group, trichloromethyl group, tribromomethyl group, 2,2,2- Trifluoroethyl group, 2,2,2-trichloroethyl group, pentafluoroethyl group, 4-fluorobutyl group, 4-chlorobutyl group, 3,3,3-trifluoropropyl group, 2,2,2-trifluoro -1-trifluoromethylethyl group, perfluorohexyl group, perchlorohexene A C1-6 haloalkyl group such as a xyl group or a 2,4,6-trichlorohexyl group;

  Hydroxy C1-6 alkyl groups such as hydroxymethyl group and 2-hydroxyethyl group; methoxymethyl group, ethoxymethyl group, methoxyethyl group, ethoxyethyl group, methoxy-n-propyl group, n-propoxymethyl group, i-propoxy group C1-6 alkoxy C1-6 alkyl groups such as ethyl group, s-butoxymethyl group, t-butoxyethyl group; methoxymethoxymethyl group, 1-methoxyethoxymethyl group, 2-methoxyethoxymethyl group, 2- (1- C1-6 alkoxy C1-6 alkoxy C1-6 alkyl groups such as methoxyethoxy) ethyl group, 2- (2-methoxyethoxy) ethyl group; dimethoxymethyl group, diethoxymethyl group, 2,2-dimethoxyethyl group, 1 , 2-dimethoxyethyl group, 3,3-dimethoxy n-propyl group, Di-C1-6 alkoxy C1-6 alkyl group such as 2-diethoxyethyl group; C1-7 acyloxy such as formyloxymethyl group, acetoxymethyl group, 2-acetoxyethyl group, propionyloxymethyl group, propionyloxyethyl group A C1-6 alkyl group; a C1-6 alkyl group substituted with an imino group such as an iminomethyl group, a (1-imino) ethyl group, or a (1-imino) propyl group; a hydroxyiminomethyl group, (1-hydroxyimino) ethyl A C1-6 alkyl group substituted with a hydroxyimino group or an alkoxyimino group such as a group, (1-hydroxyimino) -n-propyl group, methoxyiminomethyl group, (1-methoxyimino) ethyl group; Substituted benzyl group, unsubstituted or substituted phen And an unsubstituted or substituted C7-11 aralkyl group such as a netyl group;

As the “C 1-6 alkoxy group” in X, a methoxy group, an ethoxy group, an i-propoxy group, an n-butoxy group, an i-butoxy group, an s-butoxy group, a t-butoxy group, an n-pentyloxy group, i -A pentyloxy group, n-hexyloxy group, etc. can be mentioned.
Examples of the “C1-6 alkoxy group having a substituent” in X include a fluoromethoxy group, a chloromethoxy group, a bromomethoxy group, a difluoromethoxy group, a dichloromethoxy group, a dibromomethoxy group, a trifluoromethoxy group, a trichloromethoxy group, Bromomethoxy group, 2,2,2-trifluoroethoxy group, 2,2,2-trichloroethoxy group, pentafluoroethoxy group, 4-fluorobutoxy group, 3,3,3-trifluoropropoxy group, 2,2 , 2-trifluoro-1-trifluoromethylethoxy group, perfluorohexyloxy group and other C1-6 haloalkoxy groups; methoxymethoxy group, 1-methoxyethoxy group, 2-methoxyethoxy group, ethoxymethoxy group, 1- Ethoxyethoxy group, 2-ethoxyethoxy group, 1-methyl A C1-6 alkoxy C1-6 alkoxy group such as a xy-n-propoxy group, a 2-methoxy-n-propoxy group, a 3-methoxy-n-propoxy group; a cyclopropylmethoxy group, a cyclobutylmethoxy group, a cyclopentylmethoxy group, C3-8 cycloalkyl C1-6 alkoxy groups such as cyclohexylmethoxy group, 2-methylcyclopropylmethoxy group, 2,3-dimethylcyclopropylmethoxy group, 2-cyclopropylethoxy group; benzyloxy group, phenethyloxy group, etc. C7-11 aralkyloxy group; and the like.

  Among these, X is preferably a halogen atom or a C1-6 haloalkyl group.

(X ')
X ′ in formula (I) represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show. m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.

  Examples of the “C1-6 alkyl group” and “C1-6 alkoxy group” in X ′ include the same groups as those described above for X.

(R ¹ )
R ¹ in formula (I) represents a C 1-6 haloalkyl group.

As the “C 1-6 haloalkyl group” in R ¹ , a fluoromethyl group, a chloromethyl group, a bromomethyl group, a difluoromethyl group, a dichloromethyl group, a dibromomethyl group, a trifluoromethyl group, a trichloromethyl group, a tribromomethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, pentafluoroethyl group, 4-fluorobutyl group, 4-chlorobutyl group, 3,3,3-trifluoropropyl group, 2, A 2,2-trifluoro-1-trifluoromethylethyl group, a perfluorohexyl group, a perchlorohexyl group, a 2,4,6-trichlorohexyl group, and the like can be given.
Of these, R ¹ is preferably a trifluoromethyl group.

(R ² )
R ² in formula (I) has a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 1-7 acyl group, or an unsubstituted or substituted group A C1-6 alkoxycarbonyl group is shown.

Examples of the “C1-6 alkyl group” for R ² include the same as those described above for X.

Examples of the “C1-7 acyl group” in R ² include a formyl group, an acetyl group, a propionyl group, and a benzoyl group.
Examples of the “C1-7 acyl group having a substituent” in R ² include halogen-substituted C1-7 acyl groups such as a chloroacetyl group, a trifluoroacetyl group, a trichloroacetyl group, and a 4-chlorobenzoyl group.

Examples of the “C1-6 alkoxycarbonyl group” for R ² include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, and an i-propoxycarbonyl group.
Examples of the “substituted C1-6 alkoxycarbonyl group” for R ² include cyclopropylmethoxycarbonyl group, cyclobutylmethoxycarbonyl group, cyclopentylmethoxycarbonyl group, cyclohexylmethoxycarbonyl group, 2-methylcyclopropylmethoxycarbonyl group, 2 , 3-dimethylcyclopropylmethoxycarbonyl group, 2-chlorocyclopropylmethoxycarbonyl group, C3-8 cycloalkyl C1-6 alkoxycarbonyl group such as 2-cyclopropylethoxycarbonyl group; fluoromethoxycarbonyl group, chloromethoxycarbonyl group, Bromomethoxycarbonyl group, difluoromethoxycarbonyl group, dichloromethoxycarbonyl group, dibromomethoxycarbonyl group, trifluoromethoxycarbonyl group, Trichloromethoxycarbonyl group, tribromomethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, pentafluoroethoxycarbonyl group, 4-fluorobutoxycarbonyl group, 3,3 , 3-trifluoropropoxycarbonyl group, 2,1,2-trifluoro-1-trifluoromethylethoxycarbonyl group, C1-6 haloalkoxycarbonyl group such as perfluorohexyloxycarbonyl group; and the like.

(R ³ )
R ³ in formula (I) is a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2 -6 alkynyl group, unsubstituted or substituted C3-8 cycloalkyl group, unsubstituted or substituted C1-6 alkoxy group, unsubstituted or substituted C2-6 alkenyloxy group, none A substituted or substituted C2-6 alkynyloxy group, an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group is shown.

Examples of the “C1-6 alkyl group” and the “C1-6 alkoxy group” in R ³ include the same groups as those described above for X.

As the “C2-6 alkenyl group” in R ³ , a vinyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-2-propenyl group, 2-methyl-2-propenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-2-butenyl group, 2-methyl-2-butenyl group, 1-hexenyl Group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group and the like.
Examples of the “C2-6 alkenyl group having a substituent” for R ³ include C2-6 haloalkenyl groups such as 2-chloro-1-propenyl group and 2-fluoro-1-butenyl group;

Examples of the “C2-6 alkynyl group” in R ³ include ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl-2-propynyl group, 2-methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentynyl group, 1-hexynyl And a 1,1-dimethyl-2-butynyl group.
Examples of the “substituted C2-6 alkynyl group” in R ³ include C2-6 such as 4,4-dichloro-1-butynyl group, 4-fluoro-1-pentynyl group, and 5-bromo-2-pentynyl group. A haloalkynyl group;

Examples of the “C3-8 cycloalkyl group” for R ³ include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group.
Examples of the “cycloalkyl group having a substituent” for R ³ include a chlorocyclohexyl group, a bromocyclohexyl group, a 2-methylcyclopropyl group, and a 2,3-dimethylcyclopropyl group.

Examples of the “C2-6 alkenyloxy group” in R ³ include a vinyloxy group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 1-methyl-2- Propenyloxy group, 2-methyl-2-propenyloxy group, 1-pentenyloxy group, 2-pentenyloxy group, 1-methyl-2-butenyloxy group, 2-methyl-2-butenyloxy group, 1-hexenyloxy group, A 2-hexenyloxy group can be exemplified.
Examples of the “substituted C2-6 alkenyloxy group” for R ³ include C2-6 haloalkenyloxy groups such as 2-chloro-1-propenyloxy group and 2-fluoro-1-butenyloxy group; Can do.

Examples of the “C2-6 alkynyloxy group” in R ³ include ethynyloxy group, 1-propynyloxy group, 2-propynyloxy group, 1-butynyloxy group, 2-butynyloxy group, 3-butynyloxy group, 1-methyl-2 -Propynyloxy group, 2-methyl-3-butynyloxy group, 1-pentynyloxy group, 2-pentynyloxy group, 1-methyl-2-butynyloxy group, 2-methyl-3-pentynyloxy group, 1- A hexynyloxy group etc. can be mentioned.
The “C2-6 alkynyloxy group having a substituent” for R ³ includes a 4,4-dichloro-1-butynyloxy group, a 4-fluoro-1-pentynyloxy group, and a 5-bromo-2-pentynyloxy group. C2-6 haloalkynyloxy groups such as, and the like.

The “C6-10 aryl group” in R ³ may be monocyclic or polycyclic. In the polycyclic aryl group, if at least one ring is an aromatic ring, the remaining ring may be a saturated alicyclic ring, an unsaturated alicyclic ring, or an aromatic ring. Examples of the C6-10 aryl group include a phenyl group, a naphthyl group, an azulenyl group, an indenyl group, an indanyl group, and a tetralinyl group.

The “heterocyclic group” in R ³ includes 1 to 4 heteroatoms selected from a nitrogen atom, oxygen atom and sulfur atom as atoms constituting the ring. The heterocyclic group may be monocyclic or polycyclic.
Examples of the heterocyclic group include a 5-membered heteroaryl group, a 6-membered heteroaryl group, a condensed heteroaryl group, a saturated heterocyclic group, and a partially unsaturated heterocyclic group.

  Examples of the 5-membered heteroaryl group include pyrrolyl groups such as pyrrol-1-yl group, pyrrol-2-yl group and pyrrol-3-yl group; furyl groups such as furan-2-yl group and furan-3-yl group. A thienyl group such as a thiophen-2-yl group and a thiophen-3-yl group; an imidazolyl group such as an imidazol-1-yl group, an imidazol-2-yl group, an imidazol-4-yl group, and an imidazol-5-yl group; A pyrazolyl group such as a pyrazol-1-yl group, a pyrazol-3-yl group, a pyrazol-4-yl group, and a pyrazol-5-yl group; an oxazol-2-yl group, an oxazol-4-yl group, and an oxazole-5 -Oxazolyl groups such as yl groups; isoxazol-3-yl groups, isoxazol-4-yl groups, isoxazol-5-yl groups and the like Isoxazolyl group; thiazolyl group such as thiazol-2-yl group, thiazol-4-yl group, thiazol-5-yl group; isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5-yl 1,2,3-triazol-1-yl group, 1,2,3-triazol-4-yl group, 1,2,3-triazol-5-yl group, 1,2,4 -Triazolyl groups such as triazol-1-yl group, 1,2,4-triazol-3-yl group, 1,2,4-triazol-5-yl group; 1,2,4-oxadiazole-3- Oxadiazolyl group such as yl group, 1,2,4-oxadiazol-5-yl group, 1,3,4-oxadiazol-2-yl group; 1,2,4-thiadiazol-3-yl group, 1, , 4-thiadiazol-5-yl group, 1,3,4-thiadiazol-2-yl group and the like thiadiazolyl group; tetrazol-1-yl group, tetrazol-2-yl group and the like; it can.

  Examples of the 6-membered heteroaryl group include pyridyl groups such as pyridin-2-yl group, pyridin-3-yl group and pyridin-4-yl group; pyrazinyl groups such as pyrazin-2-yl group and pyrazin-3-yl group A pyrimidinyl group such as a pyrimidin-2-yl group, a pyrimidin-4-yl group and a pyrimidin-5-yl group; a pyridazinyl group such as a pyridazin-3-yl group and a pyridazin-4-yl group; a triazinyl group; be able to.

  Other heterocyclic groups include: aziridin-1-yl group, aziridin-2-yl group, epoxy group; pyrrolidin-1-yl group, pyrrolidin-2-yl group, pyrrolidin-3-yl group, tetrahydrofuran-2- Yl group, tetrahydrofuran-3-yl group; piperidin-1-yl group, piperidin-2-yl group, piperidin-3-yl group, piperidin-4-yl group, piperazin-1-yl group, piperazin-2-yl Group, morpholin-2-yl group, morpholin-3-yl group, morpholin-4-yl group; 1,3-benzodioxol-4-yl group, 1,3-benzodioxol-5-yl group 1,4-benzodioxan-5-yl group, 1,4-benzodioxan-6-yl group, 3,4-dihydro-2H-1,5-benzodioxepin-6-yl group, , 4-Dihydro-2H-1,5-benzodioxepin-7-yl group, 2,3-dihydrobenzofuran-4-yl group, 2,3-dihydrobenzofuran-5-yl group, 2,3-dihydro A benzofuran-6-yl group, a 2,3-dihydrobenzofuran-7-yl group;

Among these, R ³ is preferably a C 1-6 alkyl group, a C 1-6 alkoxy C 1-6 alkyl group, or a C 1-6 alkoxy C 1-6 alkoxy C 1-6 alkyl group.

(P)
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. p is preferably 1.
The part of the ring containing p is a cyclopentane ring when p is 1 and a cyclohexane ring when p is 2.
In the formula (I), it is preferable to have an indane ring.

In the isoxazoline compound represented by the formula (I), the carbon attached with * on the isoxazoline and the carbon attached with ** on the saturated ring in the following formula (1) are asymmetric carbons. (Here, in formula (1), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in formula (I).)

  Therefore, the isoxazoline compound represented by the formula (I) has at least four stereoisomers. Among them, a single diastereomer is a crystal having a relatively high melting point and a narrow temperature range at the start and end points of the melting.

In the present invention, a single diastereomer particularly includes an isoxazoline compound represented by the following formula (I-1) (hereinafter sometimes referred to as (S, S) form) and a formula (I- It is preferably a combination with the isoxazoline compound represented by 2) (hereinafter sometimes referred to as (R, R) form). (In the formula, X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in the formula (I).)

As the isoxazoline compound represented by the formula (I), the isoxazoline compound described in WO2009 / 022746 is applicable. A mixture of diastereomers of the isoxazoline compound represented by the formula (I) can be produced by a production method described in WO2009 / 022746.
Then, the obtained mixture of diastereomers of the isoxazoline compound is dissolved in a solvent obtained by mixing any two or more of an ether solvent, an ester solvent, a halogen solvent, or a hydrocarbon solvent, and then crystallized. Crystallization of an isoxazoline compound consisting of a single diastereomer can be produced by analyzing.

Examples of ether solvents that can be used for the production include diethyl ether, tetrahydrofuran, 1,4-dioxane, methyl t-butyl ether, dimethoxyethane, and the like. Examples of the ester solvent include ethyl acetate, n-propyl acetate, and t-butyl acetate. Examples of the halogen solvent include methylene chloride, chloroform, 1,1,1-trichloroethane and the like. Examples of the hydrocarbon solvent include hexane, heptane, cyclohexane, benzene, toluene and the like.
In the present invention, a mixed solvent of an ester solvent and a hydrocarbon solvent is preferable. In this case, the ratio of the solvent can be appropriately selected based on the isoxazoline compound, but is preferably about ester solvent: hydrocarbon solvent = 1: 1 to 1:10.

Specific examples of the isooxazoline compound represented by the formula (I) include the following compounds. The combination of these (S, S) isomers and the corresponding (R, R) isomers constitutes the crystals of the isoxazoline compound comprising the single diastereomer of the present invention.
N- (5- (5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5- (dihydroisoxazol-3-yl) -2,3-dihydro-1H-indene -1-yl) propanamide [English: N- (5- (5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro -1H-inden-1-yl) propanamide),
3-methoxy-N- (5- (5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro- 1H-Inden-1-yl) propanamide [English: 3-methoxy-N- (5- (5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl ) -2,3-dihydro-1H-inden-1-yl) propanamide],
N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-indene -1-yl) propanamide [English: N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro- 1H-inden-1-yl) propanamide], 3-methoxy-N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazole -3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide (English: 3-methoxy-N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) ) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide

  Combinations of (S, S) isomers and corresponding (R, R) isomers form crystals with relatively high melting points and narrow starting and ending temperature ranges, and are included in (S, S) isomers. However, since it has the highest activity among the four stereoisomers, this crystal is effective as the main component of the pest control agent.

[Optically active isoxazoline compound]
The optically active isoxazoline compound of the present invention is a compound represented by the formula (II).

In formula (II), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in formula (I).

(*, **)
* And ** indicate that the attached carbon atom is optically active, meaning that the abundance of a specific isomer for that carbon atom is greater than 50%. Preferably, the abundance of the one particular isomer is 90% or more, more preferably 95% or more, and even more preferably 98% or more.

  As the optically active isoxazoline compound, in addition to the (S, S) isomer and (R, R) isomer described above, (S, R) isomer and (R, S) isomer which are diastereomers different from these are used. Can be mentioned.

  The optically active isoxazoline compound represented by the formula (II) corresponds to the optically active form of the isoxazoline compound described in the pamphlet of WO2009 / 022746. The optically active isoxazoline compound represented by the formula (II) can be obtained by obtaining an isoxazoline compound by a production method described in WO2009 / 022746 and dividing it by a known optical resolution method. Further, it can be obtained by synthesis by a known asymmetric synthesis method.

Specific examples of the optically active isoxazoline compound include the following compounds.
N-((R) -5-((S) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5- (dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((R) -5-((S) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl)- 4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
N-((R) -5-((R) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5- (dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((R) -5-((R) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl)- 4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
N-((S) -5-((R) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5- (dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((S) -5-((R) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl)- 4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide], and N-((S) -5-((S) -5- (3,5- (Dichloro-phenyl) -5- (trifluoromethyl) -4,5- (dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide [English: N- ( (S) -5-((S) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden- 1-yl) propanamide

3-methoxy-N-((R) -5-((S) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl ) -2,3-Dihydro-1H-inden-1-yl) propanamide [English: 3-methoxy-N-((R) -5-((S) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
3-methoxy-N-((R) -5-((R) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl ) -2,3-Dihydro-1H-inden-1-yl) propanamide [English: 3-methoxy-N-((R) -5-((R) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
3-methoxy-N-((S) -5-((R) -5- (3,5-dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl ) -2,3-Dihydro-1H-inden-1-yl) propanamide [English: 3-methoxy-N-((S) -5-((R) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide], and 3-methoxy-N-((S) -5- ( (S) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-indene-1- Yl) propanamide [English: 3-methoxy-N-((S) -5-((S) -5- (3,5-Dichloro-phenyl) -5- (trifluoromethyl) -4,5-dihydroisoxazol-3 -yl) -2,3-dihydro-1H-inden-1-yl) propanamide)

N-((R) -5-((S) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((R) -5-((S) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4 , 5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
N-((R) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((R) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4 , 5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
N-((S) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide [English: N-((S) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4 , 5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide], and N-((S) -5-((S) -5- (trifluoromethyl)- 5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide [English: N-(( S) -5-((S) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1- yl) propanamide]

3-methoxy-N-((R) -5-((S) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazole-3- Yl) -2,3-dihydro-1H-inden-1-yl) propanamide (English: 3-methoxy-N-((R) -5-((S) -5- (trifluoromethyl) -5- (3 -(trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
3-methoxy-N-((R) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazole-3- Yl) -2,3-dihydro-1H-inden-1-yl) propanamide (English: 3-methoxy-N-((R) -5-((R) -5- (trifluoromethyl) -5- (3 -(trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide],
3-methoxy-N-((S) -5-((R) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazole-3- Yl) -2,3-dihydro-1H-inden-1-yl) propanamide (English: 3-methoxy-N-((S) -5-((R) -5- (trifluoromethyl) -5- (3 -(trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide], and 3-methoxy-N-((S) -5- ( (S) -5- (Trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-indene-1 -Il) propanamide (English: 3-methoxy-N-((S) -5-((S) -5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3 -yl) -2,3-dihydro-1H-inden-1-yl) propanamide)

  Furthermore, the salt of the compound represented by the formula (II) includes inorganic acid salts such as hydrochloride, nitrate, sulfate and phosphate; organic salts such as acetate, lactate, propionate and benzoate. An acid salt;

[Pesticides]
The pest control agent of the present invention contains the optically active isoxazoline compound of the present invention or a salt thereof as an active ingredient.
Control targets include pests such as pests and ticks on crops, fruit trees, flower buds, or trees.
That is, the pest control agent of the present invention is effective as an insecticide and acaricide that protects the above-mentioned crops and the like.
Examples of target pests and mites are shown below.
(1) Lepidoptera pests such as Spodoptera litura, Mamestra brassicae, Agrotis ypsilon, Autographa nigrisigna, Plutella xylostella, Adeno hon, mai, hon Homona magnanima), peach sigai (Carposina sasakii), pear tiger squirrel (Grapholitha molesta), mandarin moth (Phyllocnistis citrella), chanohosoga (Caloptilia theivora), kinmonhosoga (Phyllonorycter ringoniella), maiparigai (Lymanttis quaga) suppressalis, Cnaphalocrocis medinalis, European corn borer (Ostrinia nubilalis), Hyphantria cunea, Cadra cautella, Heliothis spp., Heliobelpa (. Agrotis spp) (Helioverpa), Agurotisu species, clothes moth (Tinea translucens), codling moth (Cydia pomonella), etc. pink bollworm (Pectinophora gossypiella);

(2) Hemiptera pests, for example, Myzus persicae, Aphis gossypii, Lipaphis erysimi, Rhopalosiphum padi, Riptortus clavatus, Riptortus clavatus Acrosternum hilare, Unaspis yanonensis, Pseudococcus comstocki, Trialeurodes vaporariorum, Bemisia tabaci, Silver leaf white genta Stephanitis nashi, Japanese green planthopper (Nilaparvata lugens), Japanese green planthopper (Laodelphax stratella), Japanese white planthopper (Sogatella furcifera), Nephotettix cincticeps, etc .;

(3) Coleoptera pests, for example, Phyllotreta striolata, Aulacophora indica, Colorado potato beetle (Leptinotarsa decemlineata), rice weevil (Lissorhoptrus oryzophilus), Pond weevil (Sitophilus orbru japonica), Anomala rufocuprea, Diabrotica spp., Tobacco beetle (Lasioderma serricorne), Lyctus brunneus, Monochamus alternatus, Malocasi pl Agriotes spp.), Epilachna vigintioctomaculata, Tenebroides mauritanicus, cotton weevil (Anthonomus grandis), etc .;

(4) Diptera pests, for example, Bactrocera cucurbitae, Bactrocera dorsalis, Delia platura, Hydrellia griseola, Drosophila melanogaster, etc .;
(5) Thripidae pests, for example, Thrips palmi, Scirtothrips dorsalis, etc .;
(6) Hymenoptera, for example, Monomorium pharaonis, Vespa simillima, Athalia rosae, etc .;
(7) Diptera pests, such as Locusta migratoria;

(8) Cockroach (Blattodea) pests such as German cockroach (Blattella germanica), Black cockroach (Periplaneta fuligginosa), Japanese cockroach (Periplaneta japonica), American cockroach (Periplaneta americana), Black cockroach (Periplaneta australasiae);
(9) Termite pests such as termites (Coptotermes formosanus), termites (Reticulitermes speratus),
(10) Plant parasitic nematodes, such as sweet potato nematodes (Meloidogyne incognita), Negusale nematodes, soybean cyst nematodes (Heterodera glycines), rice nesting nematodes (Aphelenchoides besseyi), pine wood nematodes (Bursaphelenchus xylophil; etc.)

Examples of target mites (Acari) are shown below.
(1) Astigmata (Acaridida):
(A) Acaridae mites, for example, Rhizoglyphus echinopus, Rhizoglyphus robini; Rhizoglyphus robini; Tyrophagus spp., Tyrophagus spp. Tyrophagus neiswanderi, Tyrophagus perniciosus, Tyrophagus similis; Others, Acarus siro, Mysticus (Aleuroglyphus cetus)

(2) Prostigmata mites (Actinedida)
(A) mites of the Tetranychidae family, for example of the genus Bryobia spp., Clover spider mite (Bryobia praetiosa), fake clover spider mite (Bryobia rubrioculus); Aid spider mite (Eotetranychus sidani) (Eotetranychus seidu) (Eotetranychus shii) ), White spider mite (Eotetranychus asiaticus), Eotetranychus kankitus; eg Oligonychus mangiferus, Oligonychus perseae, ulosus Spider mite (Oligonychus karamatus), Sugino spider mite (Oligonychus hondoensis), Crimson spider mite (Oligonychus ununguis), Rice spider mite (Oligonychus shinkajii), sugarcane spider mite (Oligonychus or spp. (Panonychus citri), quail spider mite (Panonychus mori), apple spider mite (Panonychus ulmi); (Tetranychus phaselus), Tetranychus cinnabarinus, Kanzawa spider mite (Tetranychus kanzawai), Nite spider mite (Tetranychus urticae); for example, Aponychus spp. For example, the green spider mite (Sasanychus spp.), The green spider mite (Sasanychus akitanus), the Japanese spider mite (Sasanychus pusillus); ), Spider spider mite (Shizotetranychus longus), Spider spider mite (Shizotetranychus schizopus), Shizotetranychus recki;

(B) Tenuipalpidae ticks, for example, Brevipalpus spp., Brevipalpus lewsulus, Brevipalpus russulus, Brevipalpus obovatus, Penis phoeni ); For example, Tenuipalpus pacificus, Tenuipalpus zhizhilashviliae from Tenuipalpus spp .; other, Dolichotetranychus floridanus;
(C) Eriophyidae mites such as Aceria spp., Aceria diospyri, Aceria ficus, Aceria japonica, Aceria kuko, Carnation mite (Aceria paradianthi), black spider mite (Aceria tiyingi), tulip spider mite (Aceria tulipae), Shibahamaki fushi mite (Aceria zoysiea); for example, Eriophyes spp., Eriophyes chibaensis, For example, Aculops spp., Aculops lycopersici, Aculops pelekassi; eg, Aculus fockeui, Aculus schlechtendali, Aculus schlechtendali; In addition, grape ticks (Colomerus vitis), grape rust mites ( Calepitrimerus vitis), Phyllocotruta citri, Paracaracarus podocarpi, Calacarus carinatus, Acaphylla theavagrans, Paraphytoptus kikus;
(D) Mites of the family Transonemidae (eg, Tarsonemus spp.), Tarsonemus bilobatus, Tarsonemus waitei; ;
(E) Penthaleidae mites, for example, Penthaleus spp., Penthaleus erythrocephalus, Penthaleus major;

The pest control agent of the present invention can be further used to control pests such as sanitary pests, storage shell pests, clothing pests, house pests, and parasites. In particular, it has an excellent control effect against ectoparasites that harm humans. The ectoparasites that are subject to control include those that inhabit the back, underarms, lower abdomen, and inner crotch of the host animal and obtain nutrients such as blood and dandruff from the animal, and the back of the host animal. Including those that come to the buttocks and inhabit by obtaining nutrients such as blood and dandruff from animals. Examples of ectoparasites include ticks, lice and fleas.
Examples of host animals in which the control agent of the present invention is effective include dogs, cats, mice, rats, hamsters, guinea pigs, squirrels, rabbits, ferrets; Cattle, horses, pigs, sheep, goats; poultry (eg, ducks, chickens, quails, geese); bees (eg, honey bees, Japanese bees);
That is, the pest control agent of the present invention is effective as an ectoparasite control agent for animals that protects the above animals.

The following pests are listed as target mites (Acari).
(1) Mesostigmata mites (mite)
(A) Dermanyssidae mites, for example, Dermanyssus gallinae from the genus Dermanyssus spp .;
(B) mites of the family Mronyssidae, for example, Ornithonyssus spp., Ornithonyssus sylviarum, Ornithonyssus bursa, Ornithonyssus bacoti;
(C) Mites from the family Laelapidae, for example, Laelaps echidninus, Laelaps jettmari; Tropilaelaps clarae
(D) Varroidae ticks, such as Varroa spp., Varroa destructor, Varroa jacobsoni, Varroa underwoodi;

(2) Metastigmata tick (tick)
(A) mites of the family Argasidae, for example Argas spsi., Argas persicus, Argas reflexus; for example Ornithodoros spp. Ornithodoros moubata;
(B) Ixodidae ticks, such as Haemaphysalis concinna, Haemaphysalis punctata, Haemaphysalis puncta, Haemaphysalis cinnaina, Haemaphysalis cinnaina Haemaphysalis otophila), Haemaphysalis leachi, Haemaphysalis longicornis, ali flis (Haemaphysalis mageshimaensis), physalis tick (Haemaphysalis yeni), tuna swordfish ), Haemaphysalis megaspinosa, Haemaphysalis japonica, Haemaphysalis douglasi; for example, Amblyomma spp. Amblyomma americanum, Amblyomma variegatum, Amblyomma maculatum, Amblyomma hebraeum, Amblyomma ticken test Tick species (Ixodes spp.), Tick (Ixodes ricinus), Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus, Ixodes rubicundus, Ixodes rubicundus Ixodes scapularis, Ixodes holocyclus, Ixodes ovatus, Ixodes persulcatus, Ixodes nipponensis; Of the subgenus (Boophilus spp.), The tick (Rhipicephalus (Boophilus) microplus), Lipicephalus (Boophilus) decoloratus (Rhipicephalus (Boophilus) decoloratus), Lipicephalus (Boophilus) Annuratus (Rhipicephalus (Boophilus) annulatus) (Bhipophilus) Calcerata (Rhipicephalus (Boophilus) calceratus), for example, Rhipicephalus spp. ), Rhipicephalus evertsi, Rhipicephalus sanguineus, Rhipicephalus bursa, Rhipicephalus appendiculatus, Rhipicephalus appendiculatus, Rhipicephalus appendiculatus Rhipicephalus turanicus, Rhipicephalus zambeziensis; for example Dermacentor marginatus, Dermacentor marginatus, Dermacentor reticulatica (Dermacentor pictus), Dermacentor albipictus, Dermacentor andersoni, Dermacentor Barrier Squirrel (Dermacentor variabilis);

(3) Astigmata (Acaridida)
(A) Mites of the family Psoroptidae (Psoroptidae), for example Psoroptidae spp., Psoroptes ovis, rabbits Psoroptes cuniculi, Psoroptes equi; Psoroptes equi Chorioptes spp., Chorioptes bovis; Otodectes spp., Otodectes cynotis;
(B) Scaroptidae mites, for example, Sarcoptes spabi., Sarcoptes canis, Sarcoptes bovis, Sarcoptes spis. ovis), Sarcoptes rupicaprae, Sarcoptes equi, Sarcoptes suis; for example, Notoedres spp., Notoedres cati;
(C) Mites of the family Knemidokoptidae, for example, Knemidokoptes mutans of the genus Knemidokoptes spp .;

(4) Prostigmata mites (Actinedida)
(A) Acaridaceae (Demodixidae) mites, for example, Demodex spp., Demodex canis, Demodex bovis, Demodex ovis, Demodex ovis, Demodex caprae, Demodex catid, Demodex caballi, Demodex suis, Caterpillar (Demodex cati);
(B) Trombiculidae ticks, for example, Troombicula spp., Trombicula alfreddugesi, Trombicula akamushi;

Examples of lice (Phthiraptera) include the following pests.
(1) Louse of Anoplura
(A) lice of the family Haematopinidae, such as the Haematopinus asini, the Haematopinus eurysternus, the Haematopinus suis of the Haematopinus spp .;
(B) Linognathidae lice, for example, Linognathus setosus, Linognathus vituli, Linognathus ovillus, Linognathus ovillus, Linognathus ovillus Linognathus pedalis, Linognathus stenopsis; for example, Solenopotes capillatus from the Solenopotes spp.

(2) Amblycera subs (biting louse)
(A) Mennoponidae larvae, for example, Menacanthus stramineus, Menacanthus cornutus, Menacanthus cornutus, Menacanthus cornutus, Menacanthus corp. From the genus Species (Menopon spp.);

(3) Ischnocera subs (biting louse)
(A) Philopteridae lice, for example, Columbicola spp., Columbicola columbae; for example, Cuclotogaster spp., Cuclotogaster spp. heterographus); eg, Goniodes spp., Goniodes dissimilis, Goniodes gigas, Goniodes gallinae; eg, Lipeurus spp. caponis);
(B) Trichodectidae, such as Bovicola spp., Bovicola bovis, Bovicola ovis, Bovicola limbata, Bovicola e, Bovicola capra Bovicola equi; for example, Trichodectes spis., Trichodectes canis; for example, Felicola spp., Felicola subrostrata;

The fleas (Siphonaptera) include the following pests.
(A) fleas from the family Tungidae, for example from the genus Tunga spp., Tunga penetrans;
(B) Pulicidae fleas, for example, Ctenocephalides canis, Fleas of Ctenocephalides felis; for example, Hedgehog ); For example, Xenopsylla spp., For example, Xenopsylla cheopis; for example, for Pulex irritans; Flea (Echidnophaga gallinacea);
(C) fleas of the family Ceratophyllidae, for example Ceratophyllus gallinae, Ceratophyllus anisus, for example Ceratophyllus anisus; for example, Nosopsyllus spp. (Nosopsyllus fasciatus),
(D) fleas of the family Leptopsyllidae, for example, Leptopsylla segnis of the genus Leptopsylla spp .;

  In addition, the target ectoparasites include stink bugs.

Examples of the insects of the order of the Hemiptera include the following pests.
(A) insects of the family Cimicidae, for example Cimex lectularius, of the species of Simex spp .;
(B) Insects of Reduviidae, and also of Triatominae, for example Panstrongylus spp .; for example, Rhodnius spp., Rhodnius prolixus For example, Triatoma infestans of the genus Triatoma spp .;

  In addition, it is also effective against Diptera pests, which are biting insects (chewable flies, adult sucking flies, migratory dipterous larvae, parasitic fly maggots).

The following pests can be mentioned as pests of flies (Diptera).
(1) Nematocera
(A) Culicidae mosquitoes, for example, Culex spp., Culex quinquefasciatus, Culex pipiens pallens, Culex tarsalis, Culex pipiens molestus , Culex pipiens fatigans, Culex tritaeniorhynchus summorosus; eg, Armigeres subalbatus; eg, Anopheles spp. Ele, g. Anopheles maculipennis, Anopheles sinensis, Anopheles lesteri; for example, Aedes aegypti, Aedes aegypti, tus (Aedes taeniorhynchus), Ugouyabuka (Aedes togoi), Kin'iroyabuka (Aedes vexans nipponii);
(B) Simuliidae, for example, Simulium spp., Simulium reptans, Simulium ornatum, Simulium venustum, Simulium salopiense For example Prosimulium spp, Prosimulium yezoense;
(C) Ceratopogonidae, such as the Culiodes spp., Culicoides arakawae, Culicoides pictimargo, Culicoides kibunensis, musul, C oxystoma), Nipponukaka (Culicoides nipponensis), Hoshinukaka (Culicoides punctatus), Miyamanukaka (Culicoides maculatus), Matsuzawawanakaka (Culicoides matsuzawai)

(2) Short horns (a) Abs of the Tabidae family, for example, Tabanus bromius, Tabanus spodopterus, Tabanus atratus (Tabanus spp.) atratus), Tabanus sudeticus, Tabusus trigonus, Tabanus chrysurus, Tabanus trigeminus, Tabanus fulvimedioides, Tabbanus iyoens sp. Of Chrysops caecutiens, Chrysops relictus, Chrysops suavis, Chrysops japonicus;
(B) Muscidae flies such as Muscina spp., Musca domestica, Musca bezzii, Musca hervei, Musca conducens, Musca conducens Musca stabulans); for example, Stomoxys spp., For Stomoxys calcitrans; Haematobia stimulans; Fannia spp., Fannia canisularis;
(C) Glossina spp. From the family Glossinidae;
(D) flies of the family Hippoboscidae, for example, Melophagus ovinus of the genus Melofagus spp .;
(E) Calliphoridae flies, eg, Calliphora, Calliphora lata; eg, Lucilia spp., Lucilia (Phaenicia) cuprina, Lucilia (Lucilia) Phaenicia) sericata), Lucilia illustris; for example, Chrysomya hominivorax, Chrysomya chloropyga, Chrysom bezia (Chrysom bez)
(F) Oestridae flies, such as the Cuterebrinae Rabbit genus Cuterebra spp .; for example the Hypodermatinae, and also the Hypoderma spp. (Hypoderma bovis), Hypoderma lineatum; for example, Gasterophilus spp., Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gastrophilus Gasterophilus inermis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum; eg from the Oestrinae family, and also from the genus Oestrus spp. Oestrus ovis);

  The pest control agent of the present invention may be used in combination with or in combination with other active ingredients such as fungicides, other insecticides / miticides, nematicides, soil insecticides, and plant regulators. Typical examples of fungicides, other insecticides / acaricides, nematicides, soil insecticides, and plant growth regulators that can be used in combination with the pest control agent of the present invention are shown below.

Insecticides, acaricides, nematicides, soil insecticides:
(1) Organic (thio) phosphates: acephate, azamethiphos, azinephos methyl, azinephos ethyl, bromophos ethyl, bromfenbinphos, BRP, chlorpyrifos, chlorpyrifos methyl, chlorpyrifos ethyl, chlorfenvinphos, kazusafos, Carbophenothione, chloroethoxyphos, chlormefos, coumaphos, cyanophenphos, cyanophos, CYAP, diazinon, dichlorvos, dicrotophos, dimethoate, disulfotone, dimeton-S-methyl, dimethylvinphos, dimeton-S-methylsulfone, diariphos, diazinon , Diclofenthion, dioxabenzophos, disulfoton, ethion, etoprophos, etrimphos, EPN, fenamifos, fenitrothion, fenthion, phensulfothio , Flupyrazophos, phonophos, formothione, phosmethylan, heptenophos, isazophos, iodofenphos, isofenphos, isoxathione, iprobenphos, malathion, mevinphos, methamidophos, methidathion, monocrotophos, mecarbam, methalyphos, nared, ometoate, oxydimethone parathione , Parathion methyl, phentoate, hosalon, phosmet, phosphamidone, folate, phoxime, pyrimifos methyl, pyrimifos ethyl, propenophos, prothiophos, phosthiazate, phosphocarb, propaphos, propetamphos, protoate, pyridafenthion, pyracrophos, quinalphos, sulthiote, sulfophos , Tetrachlorbinphos, ter Host, triazophos, trichlorfon, tebupirimfos, temephos, thiometon, vamidothion;

(2) Carbamate series: alanic carb, aldicarb, bendiocarb, benfuracarb, carbaryl, carbofuran, carbosulfan, phenoxycarb, phenothiocarb, methiocarb, mesomil, oxamyl, pirimicurve, propoxyl, thiodicarb, triazamate, etiofencarb, MPPC, MPC , MTMC, pyridafenthion, furiothiocarb, XMC, aldoxicarb, arixicarb, aminocarb, bendiocarb, bufencarb, butacarb, butcarboxyme, butoxycarboxyme, cloetocarb, dimethylane, formethanate, isoprocarb, metam sodium, metolcarb, promecarb Fanox, Trimetacarb, Xylylcarb;
(3) Pyrethroids: alletrin, bifenthrin, cyfluthrin, beta cyfluthrin, cyhalothrin, lambda cyhalothrin, ciphenothrin, cypermethrin, alpha cypermethrin, beta cypermethrin, zeta cypermethrin, deltamethrin, esfenvalerate, eth Fenprox, fenpropatoline, fenvalerate, imiprothrin, permethrin, praretrin, pyrethrin, pyrethrin I, pyrethrin II, resmethrin, silafluophene, fulvalinate, tefluthrin, tetramethrin, tralomethrin, transfluthrin, profluthrin, cyclomethrin, promethrin , Halfenprox, flucitrinate, bioareslin, bioethanomethrin, bio Rumetorin, Bioresmethrin, trans permethrin, empenthrin, fenfluthrin Trinh, Fen pyridinium Trinh, full Bro shea tri sulphonate, full Fen flufenprox, flumethrin, metofluthrin, phenothrin, protrifenbute, pyresmethrin, terallethrin;

(4) Growth regulator:
(a) Chitin synthesis inhibitor: chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, nobarulone, teflubenzuron, triflumuron, bistrifluron, nobiflumuron, buprofezin, hexithiazox, etoxazole, clofente Gin, fluazuron, penfluron;
(b) ecdysone antagonists: halofenozide, methoxyphenozide, tebufenozide, chromafenozide, azadirachtin;
(c) juvenile hormone-like substances: pyriproxyfen, metoprene, geophenolan, epofenanane, hydroprene, quinoprene, triprene;
(d) Lipid biosynthesis inhibitors: spirodiclofen, spiromesifen, spirotetramat, flonicamid;

(5) Nicotine receptor agonist / antagonist compounds: acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, nithiazine, nicotine, bensultap, cartap;
(6) GABA antagonist compound:
(a) acetoprole, ethiprole, fipronil, vaniliprole, pyrafluprole, pyriprole;
(b) Organochlorine; camfechlor, chlordane, endosulfan, HCH, γ-HCH, heptachlor, methoxychlor (7) macrocyclic lactone insecticide: abamectin, emamectin benzoate, milbemectin, lepimectin, spinosad, ivermectin, selamectin, doramectin, Epinomectin, moxidectin,
(8) METI I compounds: phenazaquin, pyridaben, tebufenpyrad, tolfenpyrad, flufenerim, hydramethylnon, fenpyroximate, pyrimidifen, dicophor;
(9) METI II and III compounds: acequinosyl, fluacrylpyrim, rotenone;
(10) Uncoupler compound: chlorfenapyr, binapacryl, dinobutone, dinocup, DNOC;

(11) Oxidative phosphorylation inhibitor compounds: cyhexatin, diafenthiuron, phenbutatin oxide, propargite, azocyclotin;
(12) molting disruptor: cyromazine;
(13) Mixed function oxidase inhibitor compound: piperonyl butoxide;
(14) Sodium channel blocker compounds: indoxacarb, metaflumizone;
(15) Microbial pesticides: BT agent, entomopathogenic virus agent, entomopathogenic fungus agent, nematode pathogenic fungus agent; Bacillus spp. Lilium species;
(16) Latrophilin receptor agonist: depsipeptide, cyclic depsipeptide, 24-membered cyclic depsipeptide, emodepside;
(17) Octopaminergic agent: Amitraz;
(18) Ryanodine derivative agonist: fulvendiamide, chlorantraniliprole, cyantraliniprol (19) Inhibitor of magnesium-stimulated ATPase: thiocyclam, thiosultap, nereistoxin;
(20) Antifeedant: Pymetrozine;
(21) Tick growth inhibitor: clofentezin, etoxazole;
(22) Others: Benclothiaz, Bifenazate, Pyridalyl, Sulfur, Sienopyraphene, Ciflumethofene, Amidoflumet, Tetradiphone, Chlordimeform, 1,3-Dichloropropene, DCIP, Phenisobromolate, Benzomate, Metaaldehyde, Spinetram, Pyrifluquinazone, Benzo Ximate, bromopropyrate, quinomethionate, chlorbenzilate, chloropicrin, clothiazoben, dicyclanyl, phenoxacrime, fentriphanyl, flubenzimine, flufenzine, gossip lure, japonyla, methoxadiazone, petroleum, potassium oleate, sulfluramide, tetrasul, trialacene;

Fungicide:
(1) Benzimidazole series: benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate methyl, etc .;
(2) Dicarboximide type: Clozolinate, iprodione, procymidone, vinclozolin and the like;
(3) DMI-bactericidal system: imazalyl, oxpoconazole, pefazoate, prochloraz, triflumizole, triphorin, pyrifenox, fenarimol, nuarimol, azaconazole, viteltanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, Epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafor, hexaconazole, imibenconazole, ipconazole, metconazole, microbutanyl, penconazole, propiconazole, prothioconazole, cimeconazole, tebuconazole, tetraconazole, triazimephone, Triadimenol, triticonazole, etaconazole, farconazole cis etc .;

(4) Phenylamide: Benalaxyl, furaxyl, metalaxyl, metalaxyl-M, oxadixyl, ophthalse and the like;
(5) Amine type: aldimorph, dodemorph, fenpropimorph, tridemorph, fenpropidin, piperalin, spiroxamine and the like;
(6) phosphorothiolate type: EDDP, iprobenphos, pyrazophos, etc .;
(7) Dithiolane type: isoprothiolane and the like;
(8) Carboxamide: benodanyl, boscalid, carboxin, fenfuran, flutolanyl, furamethopyl, mepronil, oxycarboxin, pentiopyrad, tifluzamide and the like;
(9) Hydroxy- (2-amino) pyrimidine series: bupyrimeto, dimethylolymol, ethylimole, etc .;

(10) AP fungicide (anilinopyrimidine) type: cyprodinil, mepanipyrim, pyrimethanil, etc .;
(11) N-phenyl carbamate type: dietofencarb, etc.
(12) QoI-fungicide (Qo inhibitor) system: azoxystrobin, picoxystrobin, pyraclostrobin, cresoxime-methyl, trifloxystrobin, dimoxystrobin, methinostrobin, orizastrobin, Famoxadone, floxastrobin, phenamidon, metminophen, etc .;
(13) PP fungicide (phenylpyrrole): Fenpiconyl, fludioxonil, etc .;
(14) Quinoline series: quinoxyphene, etc .;

(15) AH fungicide (aromatic hydrocarbon) series: biphenyl, chloronebu, dichlorane, kintozen, technazen, tortofos-methyl, etc .;
(16) MBI-R series: fusaride, pyrokilone, tricyclazole, etc .;
(17) MBI-D system: carpropamide, diclocimet, phenoxanyl, etc .;
(18) SBI agents: fenhexamide, pyributicarb, terbinafine, etc .;
(19) Phenylurea: Pencyclon, etc .;
(20) QiI-bactericides (Qi inhibitors): cyazofamide, etc .;
(21) Benzamide series: Zoxamide and the like;
(22) Enopyranuron series: blastcidin, mildiomycin, etc .;
(23) Hexopyranosyl: Kasugamycin, etc.
(24) Glucopyranosyl: streptomycin, validamycin, etc .;
(25) Cyanoacetamide series: Simoxanyl and the like;
(26) Carbamate series: iodocarb, propamocarb, prothiocarb, polycarbamate, etc .;
(27) Uncouplers: Vinapacryl, Zinocup, Ferimzone, Fluazinam, etc .;
(28) Organotin compounds: triphenyltin acetate, triphenyltin chloride, triphenyltin hydroxide, etc .;

(29) Phosphate ester: phosphorous acid, tolcrofosmethyl, fosetyl and the like;
(30) Phthalamic acid type: Teclophthalam, etc .;
(31) Benzotriazine series: triazoxide and the like;
(32) Benzenesulfonamide series: fullsulfamide and the like;
(33) Pyridazinone: Dichromedin and the like;
(34) CAA disinfectant (carboxylic amide) type: dimethomorph, fullmorph, benchavaricarb, iprovaricarb, mandipropamide, etc .;
(35) Tetracycline: oxytetracycline, etc .;
(36) Thiocarbamate type: metasulfocarb, etc.
(37) Other compounds: etridiazole, polyoxin, oxolinic acid, hydroxyisoxazole, octinoline, silthiofam, diflumetrim, acibenzoral S methyl, probenazole, thiazinyl, ethaboxam, cyflufenamide, proquinazide, metolaphenone, fluopicolide, cupric hydroxide, organic Copper, sulfur, farbum, manzeb, mannebu, manebu, methylam, propineb, thiuram, dineb, diram, captan, captahol, phorpet, chlorothalonil, diclofluuride, tolylfluanid, dodine, guazatine, iminocazine acetate, iminoctadine dodecylbenzenesulfonic acid Salt, anilazine, dithianone, chloropicrin, dazomet, metham sodium salt, quinomethionate, ciprofram, Chiofamu, Agrobacterium, Furuoruimido) and the like;

Plant growth regulator:
Abscisic acid, indole butyric acid, uniconazole, etiquelozate, etephone, cloxiphonac, chlormecote, chlorella extract, calcium peroxide, cyanamide, dichlorprop, gibberellin, daminozide, decyl alcohol, trinexapac ethyl, mepicoat chloride, pack Lobutrazole, paraffin wax, piperonyl butoxide, pyraflufenethyl, flurprimidol, prohydrojasmon, prohexadione calcium salt, benzylaminopurine, pendimethalin, forchlorphenuron, potassium maleate hydrazide, 1-naphthyl Acetamide, 4-CPA, MCPB, choline, oxyquinoline sulfate, ethiclozate, butorarin, 1-methylcyclopropene, abiglycine hydrochloride;

  The pest control agent of the present invention may contain only an active ingredient, but may contain a carrier such as a solid carrier, a liquid carrier or a gaseous carrier. Moreover, the pest control agent of the present invention may be obtained by impregnating a base material such as a porous ceramic plate or a nonwoven fabric with an active ingredient. Furthermore, a surfactant and other auxiliary agents may be added as necessary.

  The pest control agent of the present invention is in a form that can be taken by general agricultural chemicals, that is, wettable powder, granule, powder, emulsion, aqueous solvent, suspension, granular wettable powder, flowable, microcapsule, aerosol, fumes. In the case of an agent, a heat transpiration agent, a smoke agent, and an acaricide, it can be formulated in the form of a bait agent.

  Additives and carriers used in formulation into solid dosage forms include vegetable powders such as soybean flour and wheat flour, mineral fine powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, pyrophyllite and clay And organic and inorganic compounds such as sodium benzoate, urea, and sodium sulfate.

  Solvents used in formulating liquid dosage forms include kerosene, xylene and petroleum aromatic hydrocarbons, cyclohexane, cyclohexanone, dimethylformamide, dimethyl sulfoxide, alcohol, acetone, trichloroethylene, methyl isobutyl ketone, mineral oil , Vegetable oil, water and the like.

  Examples of the gaseous carrier used in formulating a propellant include butane gas, LPG, dimethyl ether, carbon dioxide gas and the like.

  As a base for poison bait, food ingredients such as cereal flour, vegetable oil, sugar and crystalline cellulose, antioxidants such as dibutylhydroxytoluene and nordihydroguaiaretic acid, preservatives such as dehydroacetic acid, children such as pepper Pest-attracting perfumes such as anti-fouling agents for pets, cheese fragrances, and onion fragrances.

  In order to take a uniform and stable form in the preparation, a surfactant can be added as necessary. The surfactant that can be added is not particularly limited. For example, alkyl phenyl ether added with polyoxyethylene, alkyl ether added with polyoxyethylene, higher fatty acid ester added with polyoxyethylene, sorbitan higher fatty acid ester added with polyoxyethylene, tristyryl added with polyoxyethylene Nonionic surfactants such as phenyl ether, sulfates of alkylphenyl ethers added with polyoxyethylene, alkylbenzene sulfonates, sulfates of higher alcohols, alkylnaphthalene sulfonates, polycarboxylates, lignin sulfones Acid salt, formaldehyde condensate of alkyl naphthalene sulfonate, and isobutylene-maleic anhydride copolymer.

  The content of the active ingredient in the preparation is usually preferably 0.01 to 90% by weight, more preferably 0.05 to 85% by weight, based on the whole preparation.

The wettable powder, emulsion, flowable powder, aqueous solvent, and granular wettable powder thus obtained are diluted with water to a predetermined concentration to obtain a solution, suspension or emulsion. Granules can be sprayed on plants or soil as they are.
In addition, when used as an acaricide for prevention of epidemics, preparations supplied in the form of oils, aerosols, fumes, poison baits, mite-proof sheets, etc. can be used as they are.

In addition, when the pest control agent of the present invention is used as an acaricide for controlling mites parasitic on livestock such as cattle and pigs, and pet animals such as dogs and cats, Thus, the active ingredient can be used in an amount of 0.01 to 1000 mg.
The acaricide for control can be applied by a known veterinary technique. For example, for the purpose of systemic control, the animal is treated by tablets, capsules, immersion liquid, feed mixing, suppositories, injection (intramuscular, subcutaneous, intravenous, intraperitoneal, etc.). In cases where non-systemic control is intended, administration by spraying, pour-on, dropping (spot-on), etc. with oily or aqueous solutions And a method of kneading an acaricide in a resin, forming the kneaded product into an appropriate shape such as a collar or an ear tag, and attaching it to an animal.

[Production Example 1]
Isoxazoline compound (3-methoxy-N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl)) of compound No. 1-28 described in WO2009 / 022746 -4,5-dihydroisoxazol-3-yl) -2,3-dihydro-1H-inden-1-yl) propanamide) was synthesized by the production method described in the literature. In this case, a mixture of four stereoisomers was obtained.

Thereafter, optical resolution was performed by a known method using chiral HPLC. The analytical test results of the obtained optically active isoxazoline compounds (optically active compounds AD) and the [α] _D value of each optically active compound are shown below.

Evaluation system Pump: LC-2-AD (manufactured by Shimadzu Corporation)
Detector: SPD-20A (manufactured by Shimadzu Corporation)
Auto sampler: SIL-20A (manufactured by Shimadzu Corporation)

Analysis conditions Column: CHIRALPAK IA
Size: 0.46cm ID x 25cmL
Mobile phase: normal hexane / ethanol = 90/10 (v / v)
Flow rate: 1.0 mL / min.
Temperature: 40 ° C
Wavelength: 263nm

Optically active compound A: tR = 13.956: [α] _D ^22.4 -96.60 ° (c = 1.00, CHCl ₃ )
Optically active compound B: tR = 15.604: [α] _D ^23.6 -45.00 ° (c = 0.22, CHCl ₃ )
Optically active compound C: tR = 24.622: [α] _D ^24.0 + 97.52 ° (c = 1.05, CHCl ₃ )
Optically active compound D: tR = 30.565: [α] _D ^22.8 + 41.60 ° (c = 0.24, CHCl ₃ )

[Production Example 2]
Optically active isoxazoline compound A was produced by the following production method.
(Step 1) Synthesis of (R) -5-bromo-indan-1-ol (hereinafter sometimes referred to as compound [(R) -2]) 200 ml glass-made two necks set with a three-way cock and a bubbler The flask was charged with a fluororesin-coated stir bar, 40 g (190 mmol) of 5-bromo-indan-1-one, 47 ml of N, N-dimethylformamide and 94 ml of formic acid-triethylamine (5: 2 azeotrope), and the inside of the flask was filled with argon. Ultrasonic deaeration was performed while replacing.
While flowing argon, 1.23 g (1.93 mol, 1 mol%) of RuCl [(R, R) -Tsdpen] [p-cymene] as a catalyst was added and then deaerated. Thereafter, the three-way cock was connected to a bubbler and stirred at 40 ° C. for 65 hours. When the reaction solution was analyzed by HPLC, 95.5% conv. 95% ee.
After allowing to cool, 100 ml of water was added and the mixture was extracted with 1.4 L of a 1/1 mixture of n-hexane / ethyl acetate, and then the organic layer was washed 3 times with 500 ml of water. 20 ml of ethylenediamine was added and stirred. Thereafter, the mixture was washed successively with 500 ml of water, 300 ml of 10% hydrochloric acid, 500 ml of water, 300 ml of saturated aqueous sodium hydrogen carbonate solution, and 500 ml of saturated brine. Subsequently, it was dried with anhydrous magnesium sulfate.
Kiriyama funnel was filled with 200 g of celite and diamine silica for heavy metal removal, and the organic layer obtained above was poured into it and suction filtered. The solvent was removed and the resulting residue was dissolved in hot ethyl acetate. This was recrystallized by adding n-hexane. 32.95 g (155 mmol, 81%) of compound [(R) -2] was obtained as white needle crystals. This was analyzed by chiral HPLC and found to be> 99% ee.

The analytical conditions for chiral HPLC are as follows.
The measurement temperature was 20 ° C., DAICEL CHIRALPACK AD-3 (25 cm × φ4.6 mm) was used as the column, hexane: ethanol = 90: 10 mixture was used as the eluent, and a 1 ml / min, UV (220 nm) detector was used.
The retention time of S-form was 8.0 minutes, and the retention time of R-form was 9.9 minutes.

The [α] _D value of the obtained compound, ie, (R) -5-bromo-indan-1-ol, was [α] ³³ _D -13.2 ° (c 0.53, CH ₂ Cl ₂ ).

In addition, (S) -5-bromo-indan-1-ol was obtained by using the same method as in Production Example 2 except that the catalyst was changed to RuCl [(S, S) -Tsdpen] [p-cymene]. Can be synthesized.
In this case, the [α] _D value of the obtained (S) -5-bromo-indan-1-ol was [α] ³¹ _D + 12.6 ° (c 0.53, CH ₂ Cl ₂ ).

(Step 2) Synthesis of (S) -5-bromo-indan-1-ylamine (hereinafter sometimes referred to as compound [(S) -3]) Compound [(R ) -2] To 30 ml of 8.52 g (40 mmol) of toluene solution, 30 ml of toluene solution of 13.2 g (48 mmol) of (PhO) ₂ P (O) N _{3 in} the temperature range of −5 to 0 ° C. and diaza 30 ml of a toluene solution of 7.31 g (48 mmol) of bicycloundecene was added and stirred for 1 hour in the same temperature range. Then it was warmed to room temperature.
Cool to 0 ° C. and add water. It was stirred for 10 minutes at room temperature. Then, it extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. Kiriyama funnel was filled with celite and diamine silica for heavy metal removal, and the organic layer was poured into it and suction filtered. The solvent was distilled off to obtain a crude azide product.
A Kiriyama funnel was filled with silica gel, and the azide crude product was put therein and eluted using a 97/3 mixed solution of n-hexane / ethyl acetate. The eluate was distilled off. ^{By 1} H-NMR analysis, 9.57 g (quant.) Of almost pure azide was obtained as a pale yellow oily substance.
The obtained azide was dissolved in 100 ml of methanol, and 19 g (84 mmol) of SnCl ₂ .2H ₂ O was added thereto at room temperature, followed by stirring for 6 hours. Thereafter, the solvent was distilled off. To this, 190 ml of 2M aqueous sodium hydroxide solution was added and stirred for 2 hours.
The reaction solution was filtered through celite, extracted three times with dichloromethane, and the organic layer was washed with saturated brine. Thereafter, it was dried over anhydrous magnesium sulfate. When the solvent was distilled off, 6.97 g (82%, 2 steps) of compound [(S) -3] was obtained as a pale red oily substance.

(Step 3) Synthesis of (S) -N- (5-bromo-indan-1-yl) -3-methoxy-propionamide (hereinafter sometimes referred to as compound [(S) -4]).

To 60 ml of a dichloromethane solution of 6.97 g (32.9 mmol) of the compound [(S) -3] obtained above and 4.3 g (36.4 mmol) of 3-methoxy-propionic acid at 0 ° C. Ethyl-3- (3-dimethylaminopropyl) carbodiimide (9.5 g, 50 mmol) and N, N-dimethyl-4-aminopyridine (2.0 g, 16.4 mmol) were added, and the mixture was stirred at room temperature for 3 hours. Water was added to this and extracted with dichloromethane. The organic layer was washed successively with saturated brine, 10% hydrochloric acid and saturated brine. It was dried over anhydrous magnesium sulfate and then the solvent was distilled off. A crude product of 9.18 g (98.4% ee) of compound [(S) -4] was obtained. When the crude product was recrystallized from n-hexane / ethyl acetate, 6.68 g of compound [(S) -4] (56% yield from compound [(R) -2], 99.6% ee) Was obtained as white needle crystals.
The HPLC conditions in the analysis of enantiomeric excess are as follows.
Measurement temperature 30 ° C., DAICEL CHIRALPACK AD-3 (25 cm × φ4.6 mm) as column, hexane: ethanol = 90: 10 mixture as eluent, 1.0 ml / min, UV (220 nm) detector was used. .
The retention time of S-form was 16.3 minutes, and the retention time of R-form was 25.5 minutes.

(Step 4) Synthesis of (S) -N-5-acetyl-indan-1-yl) -3-methoxy-propionamide (hereinafter sometimes referred to as compound [(S) -5]) Three-way cock and argon In a 200 ml glass two-necked flask with a balloon set, a fluororesin coating stirrer, 6.68 g (22.4 mmol) of the above compound [(S) -4], 5.6 g (553.9 mmol) of n-butyl vinyl ether, Potassium carbonate (3.72 g, 26.9 mmol), N, N-dimethylformamide (75 ml) and water (19 ml) were added, and the inside of the flask was ultrasonically degassed while purging with argon.
To this, 923 mg (2.24 mmol) of 1,3-bis (diphenyl-phosphino) propane and 251 mg (1.12 mmol) of Pd (OAc) ₂ were added while flowing argon, and further deaeration operation was performed. Thereafter, the three-way cock was connected to an argon balloon and stirred at 80 ° C. for 5 hours.
20 ml of water was added at 0 ° C., and concentrated hydrochloric acid was added dropwise until the pH of the solution reached 2. Then, it stirred at room temperature for 2 hours. Extraction was performed with a 1/1 mixture of n-hexane / ethyl acetate. It was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the resulting residue was purified using silica gel column chromatography eluting with a 5: 1 mixture of n-hexane: ethyl acetate and then with ethyl acetate. 4.8 g (82%) of compound [(S) -5] was obtained as white crystals.

(Step 5) (S) -3-Methoxy-N- (5- (4,4,4-trifluoro-3- (3- (trifluoromethyl) phenyl) but-2-enoyl) -2,3- Synthesis of dihydro-1H-inden-1-yl) propanamide (hereinafter sometimes referred to as compound [(S) -6]) 2,2,2-trifluoro-1- (3-trifluoromethyl -Phenyl) -ethanone 1.82 g (7.5 mmol), the above compound [(S) -5] 1.3 g (5 mmol), potassium carbonate 1.38 g (10 mmol) and tetrabutylammonium bromide in toluene solvent 10 mL The reaction was stirred for 22 hours under reflux. After completion of the reaction, water was added and then extracted with ethyl acetate. Then, it was dried, concentrated, and purified with a 1: 1 mixture of n-hexane: ethyl acetate using column chromatography. 2.3 g (63%) of the compound [(S) -6] was obtained.

(Step 6) 3-methoxy-N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2 , 3-Dihydro-1H-inden-1-yl) propanamide (hereinafter sometimes referred to as compound [(S) -7]) 48.5 mg (0 0.1 mmol), 20 mg (0.3 mmol) of 50% aqueous hydroxylamine and 2 mL of a chloroform solution of N-3,5-trifluoromethylbenzylquinidinium bromide (6.3 mg, 10 mol%) were cooled to 0 ° C. and stirred. While, 0.5 mL of 50% aqueous potassium hydroxide solution was added dropwise. After completion of dropping, the mixture was stirred at 0 ° C. for 15 hours. Then, water was added and extracted with a toluene solvent. Then, it dried, concentrated, and column-purified using the 1: 1 liquid mixture of n-hexane: ethyl acetate. Compound [(S) -7] (86%) was obtained. In addition, the optical purity of the obtained compound was 81.3% ee.
The HPLC conditions for the analysis of enantiomeric excess are shown below.
Measurement temperature 20 ° C., DAICEL CHIRALPAK AD-H (25 cm × φ4.6 mm) as column, hexane: ethanol 90:10 mixture as eluent, 1.0 ml / min, UV (254 nm) detector. .
The main product retention time was 16.4 minutes and the by-product retention time was 21.9 minutes.
The main product obtained by this reaction is optically active compound A, and the absolute configuration is (isoxazoline, indane) = (* R, S). The by-product is the optically active compound B, and the absolute configuration is (isoxazoline, indane) = (* S, S). Note that the absolute configuration of the isoxazoline moiety is estimated.

  Other optically active compounds can be produced by a method similar to the above method.

[Production Example 3]
(1) 3-methoxy-N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2, Preparation of crystals of 3-dihydro-1H-inden-1-yl) propanamide According to the method described in the pamphlet of WO2009 / 022746, a mixture (1) of diastereomers of the isoxazoline compound in which the HPLC chart of FIG. Synthesized.
Crystallization was performed by dissolving 10 g of the diastereomer mixture (1) in a mixed solvent of 30 mL of ethyl acetate and 60 mL of hexane. The precipitated crystals were filtered, and the obtained crystals were further recrystallized with a mixed solvent of ethyl acetate-hexane to obtain crystals consisting of a single diastereomer (1.85 g, 37%). The melting point of the obtained crystal was 129 to 130 ° C. From the HPLC chart of the obtained crystal (see FIG. 2), the crystal is composed of an (S, S) body showing the second retention time and an (R, R) body showing the fourth retention time. I understood.

(2) N- (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3-dihydro- Production of Crystal of 1H-Inden-1-yl) propanamide According to the method described in WO2009 / 022746, a diastereomer mixture (2) of an isoxazoline compound in which the HPLC chart of FIG. 3 was observed was synthesized.
Crystallization was performed by dissolving 4 g of the diastereomer mixture (2) in a mixed solvent of 20 mL of ethyl acetate and 20 mL of hexane. The precipitated crystals were filtered, and the obtained crystals were further recrystallized with a mixed solvent of ethyl acetate-hexane to obtain crystals consisting of a single diastereomer (681 mg, 34%). The melting point of the obtained crystal was 170 to 171 ° C. From the HPLC chart of the obtained crystal (see FIG. 4), the crystal is composed of an (S, S) body showing the second retention time and an (R, R) body showing the fourth retention time. I understood.

(3) Cyclopropanecarboxylic acid (5- (5- (trifluoromethyl) -5- (3- (trifluoromethyl) phenyl) -4,5-dihydroisoxazol-3-yl) -2,3- Preparation of dihydro-1H-inden-1-yl) amide crystals According to the method described in WO2009 / 022746, a mixture (3) of diastereomers of isoxazoline compounds in which the HPLC chart of FIG. 5 is observed was synthesized. .
Crystallization was performed by dissolving 430 mg of the diastereomer mixture (3) in a mixed solvent of 4 mL of ethyl acetate and 12 mL of hexane. The precipitated crystals were filtered, and the obtained crystals were further recrystallized with a mixed solvent of ethyl acetate-hexane to obtain crystals consisting of a single diastereomer (70 mg, 33%). The melting point of the obtained crystal was 208 to 209 ° C. From the HPLC chart of the obtained crystal (see FIG. 6), the crystal consists of an (S, S) body showing the second retention time and an (R, R) body showing the fourth retention time. I understood.

[Formulation Examples]
Although some formulation examples of the pest control agent of the present invention are shown, the additives and addition ratios should not be limited to these examples, and can be varied in a wide range. The part in a formulation example shows a weight part. Examples of formulations for agricultural and horticultural use are shown below.

Formulation Example 1 (wettable powder)
Active ingredient 40 parts Diatomaceous earth 53 parts Higher alcohol sulfate 4 parts Alkyl naphthalene sulfonate 3 parts The above ingredients were uniformly mixed and finely pulverized to obtain a wettable powder containing 40% active ingredient.

Formulation Example 2 (Emulsion)
Active ingredient 30 parts Xylene 33 parts Dimethylformamide 30 parts Polyoxyethylene alkyl allyl ether 7 parts The above components were mixed and dissolved to obtain an emulsion containing 30% active ingredient.

  Examples of formulation for prevention of disease and animals are shown below.

Formulation Example 3 (Granule)
Active ingredient 5 parts Kaolin 94 parts White carbon 1 part The active ingredient is dissolved in an organic solvent, sprayed onto a carrier, and then the solvent is evaporated under reduced pressure. This type of granule can be mixed with animal food.

Formulation Example 4 (Injection)
Active ingredient 0.1-1 part Peanut oil Balance After preparation, filter sterilize with a sterilization filter.

Formulation Example 5 (Pour-on agent)
Active ingredient 5 parts Myristic acid ester 10 parts Isopropanol Balance

Formulation Example 6 (Spot-on agent)
Active ingredient 10-15 parts Palmitic acid ester 10 parts Isopropanol Balance

Formulation Example 7 (Spray-on agent)
Active ingredient 1 part Propylene glycol 10 parts Isopropanol Balance

Test examples of the pest control agent of the present invention obtained as described above are shown below.
[Test Example 1]
Efficacy Confirmation Test for Ayayoto An emulsion was obtained according to the formulation shown in Formulation Example 2. It was diluted with water so that the optically active compound concentration was 0.49 ppm. Corn leaves were immersed in the diluted solution for 30 seconds. Corn leaves were air-dried and then placed in plastic containers with filter paper. It was inoculated with 5 second-instar larvae. The plastic container was covered and placed in a temperature-controlled room at a temperature of 25 ° C. and a humidity of 65%. After 6 days, the life-and-death of Ayayotou was examined, and the insecticidal rate was determined. The test was performed in duplicate. As a result, an insecticidal rate of 100% was shown in corn leaves in which an emulsion using the optically active compound B ((S, S) form) was immersed.

[Test Example 2]
Efficacy confirmation test for diamondback moth An emulsion was obtained according to the formulation shown in Formulation Example 2. It was diluted with water so that the optically active compound concentration was 0.49 ppm. Cabbage leaf pieces were immersed in the diluted solution for 30 seconds. The cabbage leaf pieces were air-dried and then placed in a plastic container with filter paper. It was inoculated with 5 koganaga second instar larvae. The plastic container was covered and placed in a temperature-controlled room at a temperature of 25 ° C. and a humidity of 65%. After 3 days, the life-and-death of the diamondback moth was examined and the insecticidal rate was determined. The test was performed in duplicate. As a result, an insecticidal rate of 100% was exhibited in the cabbage leaf pieces in which the emulsion using the optically active compound B was immersed.

According to the present invention, there is provided an optically active isoxazoline compound or a salt thereof that can be synthesized industrially advantageously, has a certain effect, and can be an active ingredient of a pest control agent that can be used safely. Moreover, the crystal | crystallization of the isoxazoline compound which consists of a single diastereomer which can be stabilized, and its manufacturing method are provided.
These isoxazoline compounds or salts thereof are effective for insecticides, acaricides, sanitary pest control agents, animal ectoparasite control agents, and the like, and the present invention is extremely useful industrially.

Claims (10)

Formula (I)

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. The crystal | crystallization of the isoxazoline compound which consists of a single diastereomer of the isoxazoline compound represented by this. A single diastereomer of the isoxazoline compound represented by the formula (I) is represented by the formula (I-1)

(In the formula (I-1), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in the formula (I)). Oxazoline compounds,
And the formula (I-2)

(In formula (I-2), X, n, X ′, m, R ¹ , R ² , R ³ , and p have the same meaning as in formula (I)). The crystal of an isoxazoline compound according to claim 1, which is a combination of two stereoisomers of the oxazoline compound. Formula (II)

(In Formula (II), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2.
* And ** represent optically active carbon atoms. Or an optically active isoxazoline compound or a salt thereof. The optically active isoxazoline compound represented by the formula (II) is represented by the formula (II-1)

(In formula (II-1), X, n, X ′, m, R ¹ , R ² , R ³ and p have the same meaning as in formula (II)). The isoxazoline compound or a salt thereof according to claim 3.   A pest control agent comprising the crystal according to claim 1 or claim 2 or the optically active isoxazoline compound or salt thereof according to claim 3 or claim 4 as an active ingredient.   An insecticide containing the crystal according to claim 1 or 2, or the optically active isoxazoline compound according to claim 3 or claim 4 or a salt thereof as an active ingredient.   The acaricide which contains the crystal | crystallization of Claim 1 or Claim 2, or the optically active isoxazoline compound of Claim 3 or Claim 4, or its salt as an active ingredient.   An animal ectoparasite control agent comprising the crystal according to claim 1 or claim 2, or the optically active isoxazoline compound or salt thereof according to claim 3 or claim 4 as an active ingredient. Formula (I)

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. The diastereomer mixture of the isoxazoline compound represented by) is dissolved in a solvent obtained by mixing any two or more of an ether solvent, an ester solvent, a halogen solvent, or a hydrocarbon solvent, and then crystallized. The method of producing the crystal | crystallization of the isoxazoline compound which consists of a single diastereomer of Claim 1 by analyzing. Formula (I)

(In the formula (I), X represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group. Show.
n shows the substitution number of X and is an integer in any one of 0-5. When n is 2 or more, Xs may be the same as or different from each other.
X ′ represents a halogen atom, an unsubstituted or substituted C1-6 alkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a nitro group, or a cyano group.
m shows the substitution number of X 'and is an integer in any one of 0-6. When m is 2 or more, X ′ may be the same as or different from each other.
R ¹ represents a C 1-6 haloalkyl group.
R ² represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group, or an unsubstituted or substituted C1-6 alkoxycarbonyl group. Indicates.
R ³ represents a hydrogen atom, an unsubstituted or substituted C 1-6 alkyl group, an unsubstituted or substituted C 2-6 alkenyl group, an unsubstituted or substituted C 2-6 alkynyl group, A substituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted group; A C2-6 alkynyloxy group having an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted heterocyclic group;
p represents the number of repeating methylene groups in parentheses and is an integer of either 1 or 2. The diastereomer mixture of the isoxazoline compound represented by the above formula) is dissolved in a solvent in which any two or more of an ether solvent, an ester solvent, a halogen solvent, or a hydrocarbon solvent are mixed, and then crystallized. And producing a crystal of an isoxazoline compound comprising a combination of two stereoisomers of the isoxazoline compound represented by formula (I-1) and formula (I-2) according to claim 2 .

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