JP2012219020A - 5-methyl-3(2h)-isoxazolone derivative, and agricultural and horticultural chemical containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a 5-methyl-3(2H)-isoxazolone derivative showing high controlling effect to pathogenic bacteria causing a disease of stems and leaves including wheat Septoria tritici bacteria.SOLUTION: This 5-methyl-3(2H)-isoxazolone derivative is represented by general formula (I). (In the formula, R represents R, COR, COORor CONHR. R-Reach representing a prescribed substituent).

Description

  The present invention relates to 5-methyl-3 (2H) -isoxazolone derivatives. More specifically, the present invention relates to a 5-methyl-3 (2H) -isoxazolone derivative that exhibits excellent activity as an active ingredient for agricultural and horticultural agents.

  Hydroxyisoxazole (chemical name: 3-hydroxy-5-methylisoxazole, product name: Tatigalen) has been used as an agricultural and horticultural agent for controlling soil diseases such as rice seedling blight.

  Patent Documents 1 to 4 and Non-Patent Document 1 disclose certain isoxazole derivatives as active ingredients of fungicides.

JP 2010-077090 A JP 2002-114784 A Special table 2008-525353 gazette Japanese Patent Publication No. 50-11388

"Studies on Isoxazole Compounds. VI. Acylation of 3-Hydroxyisoxazoles." Ann. Rep. Sankyo Res. Lab. 29, 99-106 (1977)

  In the fungicides used in the agricultural field, bacteria that have acquired drug resistance have emerged as a result of continuing to use specific drugs. In particular, in wheat leaf blight, which is an important disease of wheat, fungi that are resistant to many drugs are widespread, and its control is a major issue. In addition, the currently used bactericides are limited in the number of pathogenic bacteria that can exert their effects, and the creation of drugs having activity against a wider range of pathogenic bacteria is required.

  Conventionally, it has been known that hydroxyisoxazole and derivatives thereof have a controlling effect only on some foliage diseases such as soil diseases and rice blast caused by Psium and Fusarium (see Patent Document 1). ). However, there is no known hydroxyisoxazole and its derivatives that exert a wide range of effects on pathogenic bacteria that cause foliage diseases including wheat leaf blight.

  Therefore, the main object of the present invention is to provide a 5-methyl-3 (2H) -isoxazolone derivative that exhibits a high control effect on pathogenic bacteria that cause stem and leaf diseases including wheat leaf blight.

In order to solve the above problems, the present inventors synthesized a number of derivatives from hydroxyisoxazole, and studied their chemical structures and activities. As a result, the inventors have found that a 5-methyl-3 (2H) -isoxazolone derivative represented by the following general formula (I) has excellent activity, and completed the present invention.
That is, the present invention provides a 5-methyl-3 (2H) -isoxazolone derivative represented by the following general formula (I).

（式中、Ｒは、Ｒ_１、ＣＯＲ_２、ＣＯＯＲ_３、あるいはＣＯＮＨＲ_４を表す。
ＲがＲ_１である場合、Ｒ_１は、フェニル基で置換されていてもよいＣ１−Ｃ３アルキル基、ｐ−トルエンスルホニル基、あるいは１，２−ベンゾイソチアゾール１，１ジオキシド基を示す。
ＲがＣＯＲ_２である場合、Ｒ_２は、ハロゲン原子、メチル基およびフェニル基から選択される同一または異なる一以上の置換基により置換されていてもよい直鎖、分岐鎖または環状のＣ１−Ｃ６アルキル基、あるいは該環状アルキル基とベンゼン環との縮合環を表す。前記Ｃ１−Ｃ６アルキル基は、鎖中にエーテル基を有してもよい。
また、Ｒ_２は、ハロゲン原子およびメチル基、メトキシフェニル基から選択される同一または異なる一以上の置換基により置換されていてもよいフェニル基または環中に窒素原子を含む不飽和の６員環を表す。
さらに、Ｒ_２は、エテニル基またはエチニル基を表す。前記エテニル基およびエチニル基は、ハロゲン原子で一以上置換されていてもよいフェニル基または環中に酸素原子または硫黄原子を含む不飽和の５員環により置換されていてもよい。
また、Ｒ_２は、Ｃ３アルキルスルフィド基、あるいはノルボルネン基を表す。
ＲがＣＯＯＲ_３の場合、Ｒ_３は、Ｃ３−Ｃ４の直鎖または分岐鎖アルキル基、フェニル基、ニトロフェニル基、あるいはメチルイソオキサゾール基を表す。
ＲがＣＯＮＨＲ_４である場合、Ｒ_４は、プロピル基、イソプロピル基、シクロヘキシル基、フェニル基、あるいはクロロアセチル基を表す。）

(In the formula, R represents R ₁ , COR ₂ , COOR ₃ , or CONHR ₄ .
When R is R ₁ , R ₁ represents a C1-C3 alkyl group which may be substituted with a phenyl group, a p-toluenesulfonyl group, or a 1,2-benzisothiazole 1,1 dioxide group.
When R is COR ₂ , R ₂ is linear, branched or cyclic C1-C6 optionally substituted by one or more substituents selected from the same or different halogen atom, methyl group and phenyl group An alkyl group or a condensed ring of the cyclic alkyl group and a benzene ring is represented. The C1-C6 alkyl group may have an ether group in the chain.
R ₂ represents a phenyl group optionally substituted by one or more substituents selected from a halogen atom, a methyl group, and a methoxyphenyl group, or an unsaturated 6-membered ring containing a nitrogen atom in the ring Represents.
R ₂ represents an ethenyl group or an ethynyl group. The ethenyl group and ethynyl group may be substituted with a phenyl group which may be substituted with one or more halogen atoms, or an unsaturated 5-membered ring containing an oxygen atom or a sulfur atom in the ring.
R ₂ represents a C3 alkyl sulfide group or a norbornene group.
When R is COOR ₃ , R ₃ represents a C3-C4 linear or branched alkyl group, a phenyl group, a nitrophenyl group, or a methylisoxazole group.
When R is CONHR ₄ , R ₄ represents a propyl group, an isopropyl group, a cyclohexyl group, a phenyl group, or a chloroacetyl group. )

In the formula (I), when R is R ₁ , R ₁ is a 1,2-benzoisothiazole 1,1 dioxide group, or when R is COR ₂ , R ₂ is cyclic A condensed ring of a C1-C6 alkyl group and benzene (particularly, a condensed ring of a C6 cyclic alkyl group and a benzene ring), an ethenyl group substituted by a phenyl group, an ethynyl group substituted by a phenyl group or a thiophenyl group, or In the case where it is a norbornene group or R is COOR ₃ , R ₃ is a C3-C4 linear alkyl group, or a nitrophenyl group, or when R is CONHR ₄ , R ₄ is a cyclohexyl group. It is particularly preferable from the viewpoint of antibacterial activity.

  The present invention also provides a 5-methyl-3 (2H) -isoxazolone derivative represented by the following formula (Ig) or (Ih).

  Furthermore, the present invention provides a fungicide containing the above 5-methyl-3 (2H) -isoxazolone derivative as an active ingredient.

  In addition, the R moiety represented by the formula (I) is effectively one or more compounds selected from 5-methyl-3 (2H) -isoxazolone derivatives represented by any one of the following formulas (Ia) to (If) Also provided is a fungicide for foliar diseases contained as an ingredient.

  The present invention also includes a step of reacting 3-hydroxy-5-methylisoxazole with a compound selected from compounds represented by the following formulas (III) to (VII) in the presence of a base or under heating. There is also provided a method for producing a 5-methyl-3 (2H) -isoxazolone derivative containing

（式（ＩＩＩ）〜（ＶＩＩ）中、Ｒ_１〜Ｒ_４の定義内容は、上記と同様である。）

(In formulas (III) to (VII), the definitions of R _{1 to} R ₄ are the same as described above.)

In the present specification, the symbols defining the same substituent, functional group or atom in each general formula are assigned the same symbol, and details such as substitution indicated by the symbol are not redundantly described. For example, the R ₁ represented in the general formula (I), R ₁ shown in the general formula (III) represents the same substituent, functional group or atom.

  The 5-methyl-3 (2H) -isoxazolone derivative according to the present invention exhibits a high control effect against pathogenic bacteria that cause foliage diseases including wheat leaf blight.

  Hereinafter, preferred embodiments for carrying out the present invention will be described. In addition, embodiment described below shows an example of typical embodiment of this invention, and, thereby, the range of this invention is not interpreted narrowly. The description will be given in the following order.

In the present embodiment, the same terms are used in the same meaning unless otherwise specified. The same applies to symbols indicating substituents, functional groups or atoms, or symbols indicating the number thereof in the general formula.

1.5-methyl-3 (2H) -isoxazolone derivative (1) When R is R ₁ (first compound group)
(2) When R is COR ₂ (second compound group)
(3) When R is COOR ₃ (third compound group)
(4) When R is CONHR ₄ (fourth compound group)
(5) Fifth compound group 2.5-methyl-3 (2H) -isoxazolone derivative production method (1) solvent (2) base / acid (3) first production method of compound (I) (4) compound ( 2. Second production method of I) (5) Third production method of compound (I) (6) Fourth production method of compound (I) Agricultural and horticultural chemicals (1) Plant disease control effect (2) Formulation

1.5-methyl-3 (2H) -isoxazolone derivative The 5-methyl-3 (2H) -isoxazolone derivative (hereinafter referred to as compound (I)) represented by the following general formula (I) according to the present invention will be described. .

Hereinafter, the definition content of R of the compound (I) and specific examples of the compound (I) will be described. Since R may be R ₁ , COR ₂ , COOR ₃ , or CONHR ₄ , each will be described in the following order.

(1) When R is R ₁ (first compound group)
Among the compounds (I), R (R ₁ ) in the first compound group is a C1-C3 alkyl group optionally substituted with a phenyl group, a p-toluenesulfonyl group, or 1,2-benzisothiazole 1 , 1 dioxide group. R ₁ is preferably a C1-C3 alkyl group or a 1,2-benzisothiazole 1,1 dioxide group.

  Examples of the C1-C3 alkyl group include a methyl group, an ethyl group, and a propyl group.

  Examples of the compound (I) belonging to the first compound group include the following specific compounds. In addition, the following structural formula is R part shown by Formula (I). Among these compounds, compound (I-4) exhibits particularly excellent antibacterial activity as described later in Examples.

(2) When R is COR ₂ (second compound group)
Among the compounds (I), R in the _second group of compounds is COR ₂ and R ₂ may be substituted with one or more substituents selected from a halogen atom, a methyl group and a phenyl group. A good linear, branched or cyclic C1-C6 alkyl group, or a condensed ring of the cyclic alkyl group and a benzene ring. The C1-C6 alkyl group may have an ether group in the chain. Of these substituents, a condensed ring of a cyclic C1-C6 alkyl group and benzene is preferable.

  Examples of the halogen atom include a chlorine atom and a fluorine atom.

  The following are illustrated as specific compounds. In addition, the following structural formula is R part shown by Formula (I). Among these compounds, compound (I-7) exhibits particularly excellent antibacterial activity as described later in Examples.

R ₂ represents a phenyl group optionally substituted by one or more substituents selected from a halogen atom, a methyl group, and a methoxyphenyl group, or an unsaturated 6-membered ring containing a nitrogen atom in the ring It may be.

  Examples of the halogen atom include a fluorine atom, an iodine atom, and a chlorine atom.

  The following are illustrated as specific compounds. In addition, the following structural formula is R part shown by Formula (I).

Furthermore, R ₂ may be an ethenyl group or an ethynyl group. The ethenyl group or ethynyl group may be substituted with a phenyl group which may be substituted one or more with a halogen atom, or an unsaturated 5-membered ring containing an oxygen atom or a sulfur atom in the ring. Of these substituents, an ethenyl group substituted by a phenyl group, an ethynyl group substituted by a phenyl group or a thiophenyl group is preferred.

  As a halogen atom, a chlorine atom is mentioned, for example.

  The following are illustrated as specific compounds. In addition, the following structural formula is R part shown by Formula (I). Among these compounds, Compound (I-25), Compound (I-26), and Compound (I-27) exhibit particularly excellent antibacterial activity as described later in Examples.

In addition, R ₂ may be a C3 alkyl sulfide group or a norbornene group. Of these substituents, a norbornene group is preferred.

  Examples of the C3 alkyl sulfide group include a methylthiopropionyl group.

  The following are illustrated as specific compounds. In addition, the following structural formula is R part shown by Formula (I). Of these compounds, compound (I-33) exhibits particularly excellent antibacterial activity, as will be described later in Examples.

(3) When R is COOR ₃ (third compound group)
Among the compounds (I), R in the _third group of compounds is COOR ₃ and R ₃ is a C3-C4 linear or branched alkyl group, phenyl group, nitrophenyl group, or methylisoxazole group. . R ₃ is preferably a C3-C4 linear alkyl group or a nitrophenyl group.

  Examples of the compound (I) belonging to the third compound group include the following specific compounds. In addition, the following structural formula is R part shown by Formula (I). Among these compounds, Compound (I-34), Compound (I-37), and Compound (I-39) exhibit particularly excellent antibacterial activity as described later in Examples.

(4) When R is CONHR ₄ (fourth compound group)
Among the compounds (I), R in the fourth group of compounds is CONHR ₄ and R ₄ is a propyl group, an isopropyl group, a cyclohexyl group, a phenyl group, or a chloroacetyl group.

  Examples of the compound (I) belonging to the fourth compound group include the following specific compounds. In addition, the following structural formula is R part shown by Formula (I). Among these compounds, compound (I-42) exhibits particularly excellent antibacterial activity, as will be described later in Examples.

(5) Fifth Compound Group The present invention also provides the following compounds which are related compounds of the compound (I) and are effective components of the bactericide described later. In addition, the following structural formula is R part shown by Formula (I). These compounds are particularly preferably used as active ingredients of fungicides for controlling foliage diseases.

  In addition, each compound mentioned above exhibits the outstanding control effect with respect to the pathogenic microbe which causes a stem and leaf disease including a wheat leaf blight fungus. Moreover, about the compound except I-3, 19, 22, 24, the control effect with respect to the pathogenic microbe which causes a soil disease is exhibited together. In addition, many compounds exhibit excellent control effects not only on wheat leaf blight fungi but also on a wide range of pathogenic fungi.

2. Manufacturing method of 2.5-methyl-3 (2H) -isoxazolone derivative Next, the manufacturing method of compound (I) is demonstrated. Unless otherwise stated, the following can be used as the solvent, base, acid and the like used in each step of the production method.

(1) Solvent The solvent to be used is not particularly limited. For example, halogenated hydrocarbons such as dichloromethane, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; petroleum ether, hexane and methylcyclohexane Aliphatic hydrocarbons such as N; N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone and the like amides; ethers such as diethyl ether, tetrahydrofuran and dioxane; methanol, ethanol and the like Alcohols and the like. In addition, examples of the solvent include water, carbon disulfide, acetonitrile, ethyl acetate, pyridine, dimethyl sulfoxide and the like. These solvents can be used as a mixture of two or more.

  Moreover, the solvent composition which consists of a solvent which does not form a uniform layer mutually as a solvent is mentioned. For example, the reaction can be carried out by adding a phase transfer catalyst such as a quaternary ammonium salt, a crown ether, or an analog of crown ether to the reaction mixture. In this case, the solvent is not particularly limited, but benzene, chloroform, dichloromethane, hexane, toluene, tetrahydrofuran and the like can be used as the oil phase. As the quaternary ammonium salt, tetrabutylammonium salt, trimethylbenzylammonium salt, triethylbenzylammonium salt and the like are used.

(2) Base A base may be added to the solvent.

  The base is not particularly limited, and examples thereof include alkali metal carbonates such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate, and potassium hydrogen carbonate; alkaline earth metal carbonates such as calcium carbonate and barium carbonate; sodium hydroxide, Alkali metal hydroxides such as potassium hydroxide; alkali metals such as lithium, sodium and potassium; alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide; sodium hydride, potassium hydride and hydrogen Alkali metal hydrides such as lithium iodide; organometallic compounds of alkali metals such as n-butyllithium and methylmagnesium bromide; sodium; alkali metals such as potassium and lithium; alkali metal amides such as lithium diisopropylamide; Emissions, pyridine, 4-dimethylaminopyridine, N, N-dimethylaniline, 1,8-diazabicyclo-7 [5.4.0] and organic amines such as undecene and the like.

(3) First production method of compound (I) Compound (IA) includes 3-hydroxy-5-methylisoxazole represented by the following chemical formula (II), a compound represented by the following chemical formula (III), Can be produced by the reaction in the presence of a base or under heating (see reaction formula (1)). Hereinafter, 3-hydroxy-5-methylisoxazole represented by the chemical formula (II) is referred to as “compound (II)”, and the compound represented by the chemical formula (III) is referred to as “compound (III)”.

Reaction formula (1)

The definition content of R ₁ of the compound (III) is the same as the definition content of R ₁ of the compound (I) described above. X in compound (III) represents a halogen atom, specifically a chlorine, bromine or iodine atom.

  A 1-fold mole of Compound (I) is produced by a reaction of 1-fold mole of Compound (II) with 1-fold mole of Compound (III).

  It is preferable that the addition amount of compound (III) is 1-2 times mole with respect to 1 time mole of compound (II).

The base is not particularly limited, but is preferably an alkali metal hydride such as sodium hydride (NaH); carbonates such as potassium carbonate (K ₂ CO ₃ ) and sodium carbonate (Na ₂ CO ₃ ); potassium hydroxide ( Alkali metal hydroxides such as KOH) and sodium hydroxide (NaOH); tertiary amines such as triethylamine [(C ₂ H ₅ ) ₃ N] and the like can be used.

  In this production process, it is desirable to use a solvent. For example, amides such as dimethylformamide (DMF) and dimethylacetamide; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); diethyl ether, tetrahydrofuran (THF) and the like Ethers such as benzene, xylene and toluene; alcohols such as ethanol and propanol; ketones such as acetone and methyl ethyl ketone; aliphatic hydrocarbons such as hexane, heptane and octane; dichloromethane, chloroform, Halogenated hydrocarbons such as chlorobenzene and dichlorobenzene; one or two or more of solvents such as water can be used in appropriate combination. The reaction can also be carried out by adding a phase transfer catalyst to the reaction mixture.

  The reaction temperature is preferably −10 to 120 ° C. When the reaction temperature is less than −10 ° C., the reaction rate is slow, and when the reaction temperature is higher than 120 ° C., the side reaction tends to proceed. The reaction time can be appropriately determined in consideration of temperature conditions, pressure conditions, etc., but is preferably in the range of 1 to 24 hours.

(4) Second production method of compound (I) Compound (IB) is composed of 3-hydroxy-5-methylisoxazole represented by the following chemical formula (II) and a compound represented by the following chemical formula (IV) or It can be produced by reacting the compound represented by the chemical formula (V) with the presence of a base or under heating (see reaction formulas (2) and (3)). Hereinafter, the compound represented by the chemical formula (IV) is referred to as “compound (IV)”, and the compound represented by the chemical formula (V) is referred to as “compound (V)”.

Reaction formula (2)

Reaction formula (3)

The definition content of R _{2 in} compound (IV) and compound (V) is the same as the definition content of R _{2 in} compound (I) described above. X in compound (IV) represents a halogen atom, specifically a chlorine, bromine or iodine atom.

  A 1-fold mole of Compound (I) is produced by a reaction of 1-fold mole of Compound (II) with 1-fold mole of Compound (IV). Moreover, 1 time mole of compound (I) will be produced | generated when 1 time mole of compound (II) and 1 time mole of compound (V) react.

  It is preferable that the addition amount of compound (IV) is 1-3 times mole with respect to 1 time mole of compound (II). Moreover, it is preferable that the addition amount of a compound (V) is 1-3 times mole with respect to 1 time mole of compound (II).

The base is not particularly limited, but is preferably an alkali metal hydride such as sodium hydride (NaH); carbonates such as potassium carbonate (K ₂ CO ₃ ) and sodium carbonate (Na ₂ CO ₃ ); potassium hydroxide ( Alkali metal hydroxides such as KOH) and sodium hydroxide (NaOH); tertiary amines such as triethylamine [(C ₂ H ₅ ) ₃ N] and the like can be used. In addition, this reaction can also be performed in absence of a base.

  In this production process, it is desirable to use a solvent. For example, amides such as dimethylformamide (DMF) and dimethylacetamide; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); diethyl ether, tetrahydrofuran (THF) and the like Ethers; aromatic hydrocarbons such as benzene, xylene and toluene; ketones such as acetone and methyl ethyl ketone; aliphatic hydrocarbons such as hexane, heptane and octane; halogenation such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons: One or two or more of solvents such as water can be used in appropriate combination. The reaction can also be carried out by adding a phase transfer catalyst to the reaction mixture. In addition, this reaction can also be performed without a solvent.

  The reaction temperature is preferably −10 to 120 ° C. When the reaction temperature is less than −10 ° C., the reaction rate is slow, and when the reaction temperature is higher than 120 ° C., the side reaction tends to proceed. The reaction time can be appropriately determined in consideration of temperature conditions, pressure conditions, etc., but is preferably in the range of 10 minutes to 24 hours.

(5) Third production method of compound (I) Compound (IC) is obtained by reacting compound (II) with a compound represented by the following chemical formula (VI) in the presence of a base or under heating. Can also be produced (see reaction formula (4)). Hereinafter, the compound represented by the chemical formula (VI) is referred to as “compound (VI)”.

Reaction formula (4)

The definition content of R ₃ of the compound (VI) is the same as the definition content of R ₃ of the compound (I) described above. X in the compound (VI) represents a halogen atom, specifically a chlorine, bromine or iodine atom.

  A 1-fold mole of Compound (I) is produced by a reaction between 1-fold mole of Compound (II) and 1-fold mole of Compound (VI).

  It is preferable that the addition amount of compound (VI) is 1-3 times mole with respect to 1 time mole of compound (II).

The base is not particularly limited, but is preferably an alkali metal hydride such as sodium hydride (NaH); carbonates such as potassium carbonate (K ₂ CO ₃ ) and sodium carbonate (Na ₂ CO ₃ ); potassium hydroxide ( Alkali metal hydroxides such as KOH) and sodium hydroxide (NaOH); tertiary amines such as triethylamine [(C ₂ H ₅ ) ₃ N] and the like can be used. In addition, this reaction can also be performed in absence of a base.

  In this production process, it is desirable to use a solvent. For example, amides such as dimethylformamide (DMF) and dimethylacetamide; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); diethyl ether, tetrahydrofuran (THF) and the like Ethers; aromatic hydrocarbons such as benzene, xylene and toluene; ketones such as acetone and methyl ethyl ketone; aliphatic hydrocarbons such as hexane, heptane and octane; halogenation such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene Hydrocarbons: One or two or more of solvents such as water can be used in appropriate combination. The reaction can also be carried out by adding a phase transfer catalyst to the reaction mixture. In addition, this reaction can also be performed without a solvent.

  The reaction temperature is preferably −10 to 120 ° C. When the reaction temperature is less than −10 ° C., the reaction rate is slow, and when the reaction temperature is higher than 120 ° C., the side reaction tends to proceed. The reaction time can be appropriately determined in consideration of temperature conditions, pressure conditions, etc., but is preferably in the range of 10 minutes to 24 hours.

(6) Fourth Production Method for Compound (I) Compound (ID) is obtained by reacting compound (II) with a compound represented by the following chemical formula (VII) in the presence of a base or under heating. Can also be produced (see reaction formula (4)). Hereinafter, the compound represented by the chemical formula (VII) is referred to as “compound (VII)”.

Reaction formula (5)

The definition content of R ₄ of compound (VII) is the same as the definition content of R ₄ of compound (I) described above.

  A 1-fold mole of compound (II) and a 1-fold mole of compound (VII) react to produce 1-fold mole of compound (I).

  It is preferable that the addition amount of compound (VII) is 1-2 times mole with respect to 1 time mole of compound (II).

The base is not particularly limited, but is preferably an alkali metal hydride such as sodium hydride (NaH); carbonates such as potassium carbonate (K ₂ CO ₃ ) and sodium carbonate (Na ₂ CO ₃ ); potassium hydroxide ( Alkali metal hydroxides such as KOH) and sodium hydroxide (NaOH); tertiary amines such as triethylamine [(C ₂ H ₅ ) ₃ N] and the like can be used.

  In this production process, it is desirable to use a solvent. For example, amides such as dimethylformamide (DMF) and dimethylacetamide; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); diethyl ether, tetrahydrofuran (THF) and the like Ethers; aromatic hydrocarbons such as benzene, xylene and toluene; ketones such as acetone and methyl ethyl ketone; aliphatic hydrocarbons such as hexane, heptane and octane; halogenation such as dichloromethane, chloroform, chlorobenzene and dichlorobenzene One or two or more kinds of solvents such as hydrocarbons can be used in appropriate combination. The reaction can also be carried out by adding a phase transfer catalyst to the reaction mixture.

  The reaction temperature is preferably 20 to 120 ° C. When the reaction temperature is less than 20 ° C, the reaction rate is slow, and when the reaction temperature is higher than 120 ° C, the side reaction is likely to proceed. The reaction time can be appropriately determined in consideration of temperature conditions, pressure conditions, etc., but is preferably in the range of 1 to 24 hours.

3. Agricultural and Horticultural Agents The usefulness of the 5-methyl-3 (2H) -isoxazolone derivative (compound (I)) according to the present invention as an agricultural and horticultural agent will be described.

(1) Plant Disease Control Effect Compound (I) exhibits a control effect on a wide range of plant diseases, and is a conventional hydroxyisoxazole (chemical name: 3-hydroxy-5-methylisoxazole, product name: tatigalene). In contrast to soil diseases, it is effective not only for soil diseases but also for stem and leaf diseases including wheat leaf blight.

  Further, the above-mentioned formula (Ia), formula (Ib), formula (Ic), formula (Id), formula (Ie), formula (If), formula (Ig), formula (Ih) which are related compounds of compound (I) The effect of the 5-methyl-3 (2H) -isoxazolone derivative represented by) has been confirmed not only on soil diseases but also on foliage diseases including wheat leaf blight.

  Examples of applicable diseases include the following diseases.

  Wheat leaf blight (Septoria tritici), soybean rust (Phakopsora pachyrhizi, Phakopsora meibomiae), rice blast (Pyricularia grisea), rice sesame leaf blight (Cochliobolus miyabeanus), rice blight (Xanthomonas oryzae), rice crest Disease (Rhizoctonia solani), rice small black mold sclerosis (Helminthosporium sigmoideun), rice blast seedling disease (Gibberella fujikuroi), rice seedling blight (Pythium aphanidermatum), apple powdery mildew (Podosphaera leucotricha), apple black star disease (Ventia qualia) ), Apple morinia disease (Monilinia mali), apple spotted leaf disease (Alternaria alternata), apple rot disease (Valsa mali), pear black spot disease (Alternaria kikuchiana), pear powdery mildew (Phyllactinia pyri), pear red leaf disease (Gymnosporangium asiaticum) ), Pear scab (Venturia nashicola), grape powdery mildew (Uncinula necator), grape downy mildew (Plasmopara viticola), grape late rot (Glomerella cingulata), barley powdery mildew (Erysiphe gramin) is f. sp hordei), barley black rust (Puccinia graminis), barley yellow rust (Puccinia striiformis), barley leaf (Pyrenophora graminea), barley cloud (Rhynchosporium secalis), wheat powdery mildew (Erysiphe graminis) sp tritici), wheat red rust (Puccinia recondita), wheat yellow rust (Puccinia striiformis), wheat eyespot (Pseudocercosporella herpotrichoides), wheat red mold (Fusarium graminearum, Microdochium nivale), wheat blight (Phaeosphaeria no ), Cucumber powdery mildew (Sphaerotheca fuliginea), cucumber anthracnose (Colletotrichum lagenarium), cucumber downy mildew (Pseudoperonospora cubensis), cucumber gray plague (Phytophthora capsici), tomato powdery mildew (Erysiphe cichoracearum) Disease (Alternaria solani), eggplant powdery mildew (Erysiphe cichoracearum), strawberry powdery mildew (Sphaerotheca humuli), tobacco powdery mildew (Erysiphe cichoracearum), sugar beet brown Spot disease (Cercospora beticola), corn smut (Ustillaga maydis), ash fruit disease of fruit fruits (Monilinia fructicola), gray mold disease (Botrytis cinerea), and sclerotia disease (Sclerotinia sclerotiorum).

  Grape rust (Phakopsora ampelopsidis), watermelon vine split (Fusarium oxysporum f.sp.niveum), cucumber vine split (Fusarim oxysporum f.sp.cucumerinum), radish yellow (Fusarium oxysporum f.sp.raphani), tobacco Red Star Disease (Alternaria longipes), Potato Summer Pest (Alternaria solani), Soybean Brown Ripe Disease (Septoria glycines), Soybean Purpura (Cercospora kikuchii), Wheat Red Snow Rot Fungus (Microdochium nivale), Wheat Blight Fungus (Gaeumannomyces graminis) .

Examples of applied plants include wild plants, plant cultivars, plants and plant cultivars obtained by conventional biological breeding such as crossbreeding or protoplast fusion, genetically modified plants and plant cultivars obtained by genetic manipulation. Can be mentioned. Examples of genetically modified plants and plant cultivars include herbicide-tolerant crops, pest-tolerant crops incorporating insecticidal protein production genes, disease-resistant crops incorporating resistance-inducing substance production genes against diseases, food-enhancing crops, and yield improvement Examples include crops, crops with improved shelf life, and crops with improved yield. Specifically, genetically modified plant cultivars include ROUNDUP READY, LIBERTY LINK, CLEARFIELD, YIE
Examples include those containing registered trademarks such as LDGARD, HERCULEX, and BOLLGARD.

(2) Formulation Compound (I) can be formulated in various forms such as powders, wettable powders, granules, emulsions, etc. alone or mixed with formulation adjuvants such as solid carriers, liquid carriers, and surfactants. Used.

  These preparations are formulated so as to contain 0.1 to 95% by weight, preferably 0.5 to 90% by weight, more preferably 2 to 80% by weight of the compound (I) as an active ingredient.

  As the solid carrier, talc, kaolin, bennite, diatomaceous earth, white carbon, clay and the like can be used. As the liquid diluent, water, xylene, toluene, chlorobenzene, cyclohexane, cyclohexanone, dimethyl sulfoxide, dimethylformamide, alcohol or the like is used. Surfactants should be used properly according to their effects. Polyoxyethylene alkylaryl ether, polyoxyethylene, BR> toluene monolaurate, etc. as emulsifiers, lignin sulfonate, dibutylnaphthalene as dispersants, etc. As the wetting agent, an alkyl sulfonate, an alkyl phenyl sulfonate, or the like can be used.

  Some preparations are used as they are, while others are diluted to a predetermined concentration with a diluent such as water. When diluted and used, the concentration of compound (I) is preferably in the range of 0.001 to 1.0%. Moreover, the usage-amount of compound (I) is 20-5000g per 1ha of agricultural and horticultural lands such as a field, a rice field, an orchard, and a greenhouse, More preferably, it is 50-2000g. The concentration and amount used vary depending on the dosage form, use period, method of use, place of use, target crop, etc., and can be increased or decreased without sticking to the above range.

  Furthermore, the compound (I) can be used in combination with other active ingredients such as fungicides, insecticides, acaricides and herbicides as exemplified below to enhance performance as agricultural and horticultural agents.

<Antimicrobial substances>
Acibenzora S methyl, 2-phenylphenol (OPP), azaconazole, azoxystrobin, amisulbrom, bixaphene, benalaxyl, benomyl, benchavaricarb-isopropyl, bicarbonate, biphenyl, viteltanol, blasticidin-S, borax, bordeaux, boscalid, Bromuconazole, bronopol, bupirimate, secbutyramine, calcium polysulfide, captafor, captan, carbendazim, carboxin, carpropamide, quinomethionate, chloronebu, chloropicrin, chlorothalonil, clozolinate, cyazofamide, cyflufenamide, simoxanil, cyproconil, cyprodiazole Dazomet, debacarb, diclofuranide, diclocimet, dicromedi , Dichlorane, diethofencarb, difenoconazole, diflumethrin, dimethomorph, dimethoxystrobin, diniconazole, dinocup, diphenylamine, dithianone, dodemorph, dozine, edifenfoss, epoxiconazole, etapoxam, ethoxyquin, etridiazole, enestroborone, famidone Fenarimol, fenbuconazole, fenflam, fenhexamide, phenoxanyl, fenpicuronyl, fenpropidin, fenpropimorph, fentin, felvam, ferrimzone, fluazinam, fludioxonil, flumorph, fluoromide, floxastrobin, fluquinconazole, flusilazole, flusulfamide , Flutolanil, furtriafol, pho PET, Focetyl-Aluminum, Fuberidazole, Furaxil, Furatopir, Fluopicolide, Fluopyram, Guazatine, Hexachlorobenzene, Hexaconazole, Himexazole, Imazalil, Imibenconazole, Iminotazine, Ipconazole, Iprobenfos, Iprodione, Iprovalithiol, Isoprolanthiol , Kasugamycin, copper preparations such as copper hydroxide, copper naphthenate, copper oxychloride, copper sulfate, copper oxide, oxine-copper, crezoxime methyl, manco kappa, mancozeb, maneb, mandipropamide, mepanipyrim, mepronil, metalaxyl, metconazole , Methylam, metminosoutrobin, myrdiomycin, microbutanyl, nitrotal-isopropyl, nuarimo , Off-race, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxyl, oxytetracycline, pefrazoate, orisatrobin, penconazole, pencyclon, penthiopyrad, pyribencarb, fusalide, picoxystrobin, piperaline, polyoxin, probenazole, prochloraz, procymidone, Propamocarb, propiconazole, propinebole, proquinazide, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroxylone, quinoxyphene, quintozen, silthiofam, cimeconazole, spiroxamine, sulfur and sulfur preparations, tebuconazole, teclophthalam, technazene, technazene Tetraconazole, thiabendazole, tifluzamide, thiof Phanate-methyl, thyram, thiazinyl, tolcrophos-methyl, tolylfluanid, triadimethone, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, trifolin, triticonazole, validamycin, vinclozoline, Zineb, ziram, zoxamide, amisulbrom, sedaxane, flutianil, varifenal, amethoctrazine, dimoxystrobin, metolaphenone, hydroxyisoxazole, metasulfocarb, etc.

<Insecticide / acaricide / nematicide>
Abamectin, Acephate, Acrinathrin, Alanicarb, Aldicarb, Alletrin, Amitraz, Avermectin, Azadirachtin, Azamethyphos, Azinphos-ethyl, Azinphos-methyl, Azocycline, Bacillus filmus, Bacillus subtilis, Bacillus thuringibulbbenthulbenbencarben , Benzoxymate, Bifenazite, Bifenthrin, Bioarethrin, Bioresmethrin, Bistriflurone, Buprofezin, Butocaboxin, Butoxycarboxin, Kazusafos, Carbaryl, Carbofuran, Carbosulfan, Cartap, CGA 50439, Chlordein, Chloretifos, Chlorfenapal Chlorfenvin foss, chlorfluazuron , Chlormefos, Chlorpyrifos, Chlorpyrifosmethyl, Chromaphenozide, Chlofenthedin, Clothianidin, Chloranthraliniprol, Counpafos, Cryolite, Cyanophos, Cycloproton, Cyfluthrin, Cyhalothrin, Cihexatin, Cipermethrin, Ciphenothrin , Cyromazine, ciazapyr, sienopyrfen, DCIP, DDT, deltamethrin, demeton-S-methyl, diafenthiuron, diazinon, dichlorophen, dichloropropene, dichlorovos, dicofol, dicrotophos, dicyclanil, diflubenzuron, dimethoate, dimethylvinphos, dinobutone Dinotefuran, emamectin, endosulfan, EPN, esfenvalerate, etiophencarb, ethion, Tiprol, etofenprox, etoprofos, etoxazole, famflu, fenamifos, phenazaquin, fenbutatin oxide, fenitrothion, fenocarb, phenothiocarb, phenoxycarb, fenpropatrine, fenpyroximate, fenthionate, fenvalerate, fipronil, flunipyamide Ron, flucitrinate, flufenoxuron, flumethrin, fulvalinate, flubendiamide, formethanate, fostiazate, halfenprox, furthiocarb, halohenozide, gamma-HCH, heptenofos, hexaflumuron, hexithiazox, hydramethylnon , Imidacloprid, imiprothrin, indoxacarb, isoproca Bu, isoxathion, lufenuron, malathion, mecarbam, metham, methamidophos, methidathione, metiocarb, methomyl, methoprene, methosrine, methoxyphenozide, metorcarb, milbemectin, monocrotofos, nared, nicotine, nitenpyram, novalflumetron, oxyflumetron Tonmethyl, parathion, permethrin, phentoate, folate, fosaron, phosmet, phosfamidone, foxim, pirimicarb, pirimiphos methyl, profenofos, propoxur, prothiophos, pymetrozine, pyracrofos, pyrethrin, pyridaben, pyridalyl, pyrimidifene, pyriproxy Fen, Pyrifluquinazone, Pyriprole, Quinalfos, Shirafu Luofen, Spinosad, Spirodiclofen, Spiromesifene, Spirotetramat, Sulfamide, Sulfotep, SZI-121, Tebufenozide, Tebufenpyrad, Tebupyrimfos, Teflubenzuron, Tefluthrin, Temefos, Terbufos, Tetrachlorbinfos, Thiacloprid, Thiadithiosum Fanox, thiometon, tolfenpyrad, tralomethrin, tralopyril, triazamate, triazophos, trichlorphone, triflumuron, bamidithione, varifenal, XMC, xylylcarb, imisiaphos, lepimectin and the like.

<Plant growth regulator>
Ansimidol, 6-benzylaminopurine, paclobutrazole, diclobutrazole, uniconazole, methylcyclopropene, mepiquat chloride, ethephone, chlormequat chloride, inabenfide, prohexadione and its salts, trinexapac Ethyl etc. Jasmonic acid as a plant hormone, brassinosteroid, gibberellin, etc.

(Additional notes)
The present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims. That is, embodiments obtained by combining technical means appropriately modified within the scope of the claims are also included in the technical scope of the present invention.

  Hereinafter, the present invention will be specifically described with reference to production examples, formulation examples, and test examples. In addition, this invention is not limited to the following manufacture examples, formulation examples, and test examples, unless the summary is exceeded. Commercially available products can be used as appropriate for the compounds used in the following production examples.

1. First production method <Production Example 1>
5-Methyl-2- (4-methylbenzene) sulfonyl-3 (2H) -isoxazolone (compound (I-5))
5-Methyl-3 (2H) -isoxazolone (1) (99 mg, 1.0 mmol) and pyridine (100 mg) were dissolved in toluene (10 ml) and cooled with ice water. While stirring the toluene solution, paratoluenesulfonyl chloride (191 mg, 1.0 mmol) was added to the solution. After 10 minutes, the temperature was returned to room temperature and stirring was continued for another 5 hours. The reaction solution was added to ice water, toluene and 1% hydrochloric acid were added, and the toluene layer was separated. The toluene layer was washed with 1% hydrochloric acid followed by water and dried. Toluene was distilled off under reduced pressure, and the target product was separated from the residue using column chromatography (silica gel, eluent: ethyl acetate / hexane (1: 3)). The physical property values are shown in “Table 1”.

  The physical property values (melting point, IR spectrum and NMR spectrum) of the target compound were measured under the conditions shown in “Table 2” below.

  The compounds shown in “Table 1” were synthesized by the same method.

2. Second production method <Production Example 2>
2- (2,2-Dimethylpropionyl) -5-methyl-3 (2H) -isoxazolone (compound (I-13))
A solution of 5-methyl-3 (2H) -isoxazolone (1) (99 mg, 1.0 mmol) and 2,2-dimethylpropionyl chloride (134 mg, 1.0 mmol) in toluene (10 ml) is heated for 3 hours. Refluxed. Toluene was distilled off under reduced pressure, water was added to the residue, and the solid was collected by filtration. The filtered product was washed with water on a filter paper and dried to obtain the desired product. The physical property values are shown in “Table 3”.

3. Third production method <Production Example 3>
5-Methyl-2- (4,4,4, -trifluoromethylbutanoyl) -3 (2H) -isoxazolone (compound (I-9))
5-Methyl-3 (2H) -isoxazolone (1) (99 mg, 1.0 mmol), 4,4,4-trifluoromethylbutanoyl chloride (144 mg, 1.0 mmol), N- (3-dimethylaminopropyl)- N'-ethylcarbodiimide hydrochlorid (191 mg, 1.0 mmol) and 4,4-dimethylaminopyridine (133 mg, 1.1 mmol) were suspended in 20 ml of dichloromethane and stirred at room temperature for 12 hours. 10 ml of 1% aqueous HCl and 20 ml of dichloromethane were added to the reaction solution, and the dichloromethane phase was separated. The dichloromethane solution was washed with water, 1% aqueous NaOH, water in this order and dried over anhydrous MgSO ₄ . Dichloromethane was distilled off, and the target product was separated from the residue using column chromatography (silica gel, eluent: ethyl acetate / hexane (1: 10-1: 5)). The physical property values are shown in “Table 4”.

  The compounds shown in “Table 4” were synthesized by the same method.

4). Fourth Production Method <Production Example 4>
5-Methyl-2-propylcabamoyl-3 (2H) -isoxazolone (compound (I-40))
To the THF solution (1 ml) in which 5-methyl-3 (2H) -isoxazolone (1) (99 mg, 1.0 mmol) was dissolved, propylisocyanate (85 mg, 1.0 mmol) was added dropwise. After stirring at room temperature for 10 hours, THF was distilled off under reduced pressure. The desired product was recrystallized from ether. The physical property values are shown in “Table 5”.

  The compounds shown in “Table 5” were synthesized by the same method.

  Furthermore, the compounds shown in “Table 6” were synthesized by the same method as in any one of Production Examples 1 to 4.

  Next, formulation examples and test examples are shown. The carrier (diluent) and auxiliary agent, and the mixing ratio thereof can be changed within a wide range. “Parts” in each formulation example represents parts by weight.

<Formulation example 1 (wettable powder)>
Compound (I-5) 50 parts lignin sulfonate 5 parts alkyl sulfonate 3 parts diatomaceous earth 42 parts were pulverized and mixed to obtain a wettable powder and diluted with water for use.

<Formulation example 2 (powder)>
Compound (I-13) 3 parts Clay 40 parts Talc 57 parts were ground and mixed and used as dust.

<Formulation example 3 (granule)>
Compound (I-9) 5 parts Bennite 43 parts Clay 45 parts Lignin sulfonate 7 parts were mixed uniformly, kneaded with water, processed into granules by an extrusion granulator and dried to give granules.

<Formulation example 4 (emulsion)>
Compound (I-40) 20 parts polyoxyethylene alkyl aryl ether 10 parts polyoxyethylene sorbitan monolaurate 3 parts xylene 67 parts were mixed and dissolved uniformly to prepare an emulsion.

<Test Example 1: Antibacterial test against pathogenic bacteria and harmful microorganisms>
In this test example, antibacterial properties against various phytopathogenic fungi and industrial material harmful microorganisms were tested.

A compound solution dissolved in dimethyl sulfoxide was added to a PDA medium (potato-dextrose-aggar medium) at around 60 ° C., mixed well, poured into a petri dish, and solidified to prepare a plate medium containing a compound of a predetermined concentration.
A test bacterium previously cultured on a plate medium was punched out with a cork borer having a diameter of 4 mm and inoculated on the compound-containing plate medium.
After inoculation, each bacterium was cultured for 1 to 14 days at a suitable temperature for growth (see Table 7).
The growth degree of the bacteria obtained on the compound-containing plate medium was compared with the growth degree of the bacteria in the compound-free group, and the hyphal elongation inhibition rate was determined by the following formula.
R = 100 (dc−dt) / dc
(In the formula, R is the hyphal elongation inhibition rate (%), dc is the diameter of the fungus on the untreated plate, and dt is the diameter of the fungus on the compound-treated plate)

Antibacterial properties were evaluated according to the following criteria. The results are shown in “Table 8” and “Table 9”.
5: Mycelium elongation inhibition rate is 50% or more 4: Mycelium elongation inhibition rate is less than 50% and 40% or more 3: Mycelium elongation inhibition rate is less than 40% and 30% or more 2: Mycelium elongation inhibition rate is 30 Less than 20% or more: 1 Mycelium elongation inhibition rate is less than 20% 10% or more 0: Mycelial elongation inhibition rate is less than 10%

  The 5-methyl-3 (2H) -isoxazolone derivative according to the present invention is useful as an active ingredient of an agricultural and horticultural medicine for controlling pathogenic bacteria that cause foliage diseases.

Claims (7)

5-methyl-3 (2H) -isoxazolone derivatives represented by the following general formula (I).

(In the formula, R represents R ₁ , COR ₂ , COOR ₃ , or CONHR ₄ .
When R is R ₁ , R ₁ represents a C1-C3 alkyl group which may be substituted with a phenyl group, a p-toluenesulfonyl group, or a 1,2-benzisothiazole 1,1 dioxide group.
When R is COR ₂ , R ₂ is linear, branched or cyclic C1-C6 optionally substituted by one or more substituents selected from the same or different halogen atom, methyl group and phenyl group An alkyl group or a condensed ring of the cyclic alkyl group and a benzene ring is represented. The C1-C6 alkyl group may have an ether group in the chain.
R ₂ represents a phenyl group optionally substituted by one or more substituents selected from a halogen atom, a methyl group, and a methoxyphenyl group, or an unsaturated 6-membered ring containing a nitrogen atom in the ring Represents.
R ₂ represents an ethenyl group or an ethynyl group. The ethenyl group and ethynyl group may be substituted with a phenyl group which may be substituted with one or more halogen atoms, or an unsaturated 5-membered ring containing an oxygen atom or a sulfur atom in the ring.
R ₂ represents a C3 alkyl sulfide group or a norbornene group.
When R is COOR ₃ , R ₃ represents a C3-C4 linear or branched alkyl group, a phenyl group, a nitrophenyl group, or a methylisoxazole group.
When R is CONHR ₄ , R ₄ represents a propyl group, an isopropyl group, a cyclohexyl group, a phenyl group, or a chloroacetyl group. ) In the formula (I), when R is R ₁ , R ₁ is a 1,2-benzoisothiazole 1,1 dioxide group, or
In the case where R is COR ₂ , R ₂ is a condensed ring of a cyclic C1-C6 alkyl group and benzene, an ethenyl group substituted by a phenyl group, an ethynyl group substituted by a phenyl group or a thiophenyl group, or a norbornene group Or
When R is COOR ₃ , R ₃ is a C3-C4 linear alkyl group, or a nitrophenyl group, or
The 5-methyl-3 (2H) -isoxazolone derivative according to claim 1, wherein when R is CONHR ₄ , R ₄ is a cyclohexyl group. The 5-methyl-3 (2H) -isoxazolone derivative according to claim 2, wherein, in the formula (I), when R is COR ₂ , R ₂ is a condensed ring of a C6 cyclic alkyl group and a benzene ring. A 5-methyl-3 (2H) -isoxazolone derivative represented by the following formula (Ig) or (Ih).

  A bactericide containing the 5-methyl-3 (2H) -isoxazolone derivative according to any one of claims 1 to 4 as an active ingredient. A fungicide for foliage disease containing one or more compounds selected from 5-methyl-3 (2H) -isoxazolone derivatives represented by any one of the following formulas (Ia) to (If) as an active ingredient.

5-methyl-3 comprising a step of reacting 3-hydroxy-5-methylisoxazole with a compound selected from the compounds represented by the following formulas (III) to (VII) in the presence of a base or under heating. A method for producing a (2H) -isoxazolone derivative.

(In formulas (III) to (VII), the definitions of R _{1 to} R ₄ are the same as in claim 1).