JP6566217B2 - Suspension composition containing a crystalline polymorph of an isoxazoline-substituted benzamide compound - Google Patents

Description

  The present invention relates to (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2. -It relates to a suspension composition containing a crystalline polymorph of methylbenzoic acid amide (hereinafter referred to as Compound A).

  The solid state of a chemical compound can be amorphous (ie, there is no long range order at the position of the atoms) or crystalline (ie, the atoms are arranged in an ordered repeating pattern). Only a single crystal form is known for the solid state of many compounds, but polymorphs have been found for some compounds. The term “polymorph” refers to a specific crystal form of a chemical compound (ie, the structure of a crystal lattice) that can exist in two or more crystal forms in the solid state.

  On the other hand, it is already known that Compound A included in the present invention is useful as a pest control agent (for example, see Patent Document 1). The pest control agent in the present invention refers to the field of agriculture and horticulture or the field of animal husbandry / hygiene (controlling agent for mammals or birds as domestic animals or pets, or external parasite control agents, hygiene pests and unpleasant pests for household and commercial use. It means a pest control agent for harmful arthropods such as (control agent).

International Publication No. 2007/026965

It is still impossible to predict physical properties such as the melting point and water solubility of crystals of chemical compounds. Furthermore, it is not possible to predict whether the solid state of a compound can exist in more than one crystalline form, ie crystalline polymorph.
It is an object of the present invention to provide a suspension composition with improved storage stability containing a novel crystalline polymorph of Compound A.

As a result of intensive studies, the present inventors have found a novel crystalline polymorph of Compound A. It was also found that when a suspension composition was prepared using Compound A containing these crystalline polymorphs in a specific weight ratio, the storage stability of the suspension composition was significantly improved.
Specifically, (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2 -Methylbenzoic acid amide produces crystals with a unique crystal form by a crystallization operation. Due to the difference in crystal form, it has now been confirmed that there are an I-type crystal and an II-type crystal described below. In addition, (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoate Acid amides may contain geometrical isomers of E form relative to Z form. In the present invention, pure A compound (Z form) and the substance in the coexistence state (Z form + E form) are combined with compound A. Collectively. In addition, the storage stability of the suspension composition containing the crystal of the compound A and the dispersion medium is remarkable when the proportion (content) of the I-form crystal in the crystal of the compound A is 50 to 100% by weight. It has been found by the present inventor.

That is, the present invention particularly relates to the following [1] to [3].
[1]
(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid A suspension composition containing an amide crystal and a dispersion medium, wherein a diffraction angle 2θ = (7.45 ± 0.2, 11.05) in powder X-ray diffraction by Cu-Kα ray of the crystal. ± 0.2, 12.79 ± 0.2, 15.30 ± 0.2, 20.90 ± 0.2, 21.89 ± 0.2 and 24.32 ± 0.2) A suspension composition in which the content of Form I crystals is 50 to 100% by weight.
[2]
The dispersion medium is water or an organic liquid selected from alcohols, ethers, ketones, esters, acid amides, aromatic hydrocarbons, aliphatic hydrocarbons, mixtures of aromatic hydrocarbons and aliphatic hydrocarbons, or oils and fats. The suspension composition according to [1].
[3]
The suspension composition according to [1] or [2], further comprising a surfactant and the dispersion medium is water.
The present specification also discloses inventions related to the following [1] to [17].
[1]
In powder X-ray diffraction by Cu—Kα ray, diffraction angles 2θ = (7.45 ± 0.2, 11.05 ± 0.2, 12.79 ± 0.2, 15.30 ± 0.2, 20. (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl- having peaks at 90 ± 0.2, 21.89 ± 0.2 and 24.32 ± 0.2) A crystalline polymorph designated as Form I crystal of 4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide.
[2]
A crystalline polymorph designated as Form I crystal according to [1], which shows a diffraction curve substantially the same as FIG. 1 of the present application in powder X-ray diffraction by Cu-Kα rays.
[3]
In powder X-ray diffraction by Cu—Kα ray, diffraction angles 2θ = (5.00 ± 0.2, 9.24 ± 0.2, 13.39 ± 0.2, 16.45 ± 0.2, 19. (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4 having peaks at 35 ± 0.2, 23.17 ± 0.2 and 26.21 ± 0.2) , 5-Dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide, a crystalline polymorph designated as Form II crystals.
[4]
A crystalline polymorph designated as type II crystal according to [3], which shows substantially the same diffraction curve as FIG. 2 of the drawings of the present application in powder X-ray diffraction by Cu—Kα ray.
[5]
(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxa, wherein the content of the I-form crystal described in [1] is 50 to 100% by weight Zol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide crystalline polymorph.
[6]
(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydro, which contains 99.5 to 100% by weight of the type II crystal described in [3] above Crystalline polymorph of isoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide.
[7]
(A) (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2- Prepare a solution of methylbenzoic acid amide in a solvent,
(B) A method for producing a crystalline polymorph designated as type I crystal according to the above [1], wherein the solution is cooled and crystallized.
[8]
(A) (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2- Prepare a solution of methylbenzoic acid amide in a solvent,
(B) A method for producing a crystalline polymorph designated as type II crystal according to the above [3], wherein the solution is crystallized by dropping into a cooled solvent.
[9]
Crystallinity named as Form I crystal according to [1] above, wherein Form II crystal according to [3] is suspended in a dispersion medium, and the obtained suspension solution is allowed to stand or stir. Polymorph manufacturing method.
[10]
A suspension composition containing the I-form crystal of [1] and a dispersion medium.
[11]
An aqueous suspension composition containing water as a I-form crystal, a surfactant and a dispersion medium as described in [1] above.
[12]
A suspension composition containing the type II crystal and the dispersion medium as described in [3] above.
[13]
An aqueous suspension composition containing water as a type II crystal, a surfactant and a dispersion medium as described in [3] above.
[14]
(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxa, wherein the content of the I-form crystal described in [1] is 50 to 100% by weight Zol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide and a suspension composition containing a dispersion medium.
[15]
The suspended composition according to [14], further containing a surfactant and the dispersion medium being water.
[16]
(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydro, which contains 99.5 to 100% by weight of the type II crystal described in [3] above A suspension composition comprising isoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid amide and a dispersion medium.
[17]
The suspended composition according to the above [16], further comprising a surfactant and the dispersion medium being water.

  According to the present invention, the crystalline polymorph of compound A can be controlled. In addition, the suspension composition containing the compound A of the present invention has good storage stability, and the suspension particles of the compound A are prevented from growing over time. The problem of a decrease in pest control activity due to the growth of the plant does not occur.

2 shows a powder X-ray diffraction chart of type I crystal. 2 shows a powder X-ray diffraction chart of type II crystal. In Example 4, the powder X-ray-diffraction chart of the dried compound A taken out from the aqueous suspension agricultural chemical composition immediately after manufacture is shown. In Example 17, the powder X-ray-diffraction chart of the dried compound A taken out from the aqueous suspension agricultural chemical composition immediately after manufacture is shown.

Compound A is (Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2 -Methylbenzoic acid amide.
The molecular structure of Compound A can exist as two different stereoisomers (ie enantiomers). However, the present invention relates to a racemic mixture of Compound A comprising equal amounts of these two possible enantiomers.

  In addition, Compound A may contain an E geometric isomer derived from an iminomethyl structure. The ratio of geometric isomers (Z-form: E-form) = 80: 20 to 100: 0, preferably (Z-form: E-form) = 90: 10 to 100: 0, more preferably (Z-form: E-form) ) = 95: 5 to 99.5: 0.5, more preferably (Z form: E form) = 96: 4 to 99.5: 0.5, most preferably (Z form: E form) = 97: 3 to 99.5: 0.5.

なお、第１表に記載したI形結晶のピーク値は、以下の実施例に記載の方法に準じて得られた７つのロットのI形結晶のピーク値の平均値である。
また、第１表に記載したII形結晶のピーク値は、I形結晶と同様に、６つのロットのII形結晶のピーク値の平均値である。 Table 1 shows the powder X-ray diffraction peaks as the characteristics of Compound I Form I and Form II crystals.

In addition, the peak value of the I-form crystal described in Table 1 is an average value of the peak values of the 7 lot I-form crystals obtained according to the method described in the following examples.
Moreover, the peak value of the II type crystal described in Table 1 is the average value of the peak values of the six lots of the II type crystal as in the case of the I type crystal.

  Further, the error of the powder X-ray diffraction peak can be usually ± 0.2, and in some cases ± 0.1, so that the peak value of the I-type crystal considering the error is usually 2θ = 7.45 ± 0.2. 11.05 ± 0.2, 12.79 ± 0.2, 15.30 ± 0.2, 20.90 ± 0.2, 21.89 ± 0.2, 24.32 ± 0.2 2θ = 7.45 ± 0.1, 11.05 ± 0.1, 12.79 ± 0.1, 15.30 ± 0.1, 20.90 ± 0.1, 21.89 ± 0 .1, 24.32 ± 0.1.

  In addition, the peak values of type II crystals in consideration of errors are usually 2θ = 5.00 ± 0.2, 9.24 ± 0.2, 13.39 ± 0.2, 16.45 ± 0.2, 19.35. ± 0.2, 23.17 ± 0.2, 26.21 ± 0.2, and in some cases 2θ = 5.00 ± 0.1, 9.24 ± 0.1, 13.39 ± 0.1 16.45 ± 0.1, 19.35 ± 0.1, 23.17 ± 0.1, 26.21 ± 0.1.

[Powder X-ray diffraction]
Model name: X'PERT-PRO MPD (Spectris Co., Ltd.)
Measurement method: Transmission method X-ray: Cu-Kα Voltage: 45 kV
Current: 40 mA
Sampling interval: 0.026 deg
Data range: 2θ = 2 to 40 deg

  The Form I crystal of Compound A can be produced by the following method. Compound A is dissolved in a solvent by heating and the resulting solution is gradually cooled and crystallized, or by distilling off the solvent from the resulting solution and crystallizing. Crystals are obtained. The solvent to be used may be any solvent inert to the compound A. For example, diethyl ether, methyl t-butyl ether, tetrahydrofuran, dimethoxymethane, diethoxymethane, ethylene glycol dimethyl ether, ethylene Ether systems such as glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether, 1,4-dioxane, etc. Solvent, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, 2-methyl-2-propanol, methyl cellosolve , Ethyl cellosolve, i-propyl cellosol , Alcohol solvents such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, cyclohexanol, benzyl alcohol, pentane, hexane, cyclohexane, methylcyclohexane, heptane, octane, decane Aliphatic hydrocarbon solvents such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, nitrobenzene, tetrahydronaphthalene, etc., acetonitrile, propionitrile Nitrile solvents such as methyl acetate, ethyl acetate, butyl acetate and ethyl propionate, methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1 Halogenated hydrocarbon solvents such as 2-trichloroethane, amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethylimidazolidinone, N, N, N Urea solvents such as', N'-tetramethylurea, sulfur-containing polar solvents such as dimethyl sulfoxide and sulfolane, pyridine such as pyridine, 2-picoline, 3-picoline, 4-picoline and 5-ethyl-2-picoline A system solvent etc. can be used and these solvents can be used individually or in mixture of 2 or more types. Among these solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents or nitrile solvents are preferable, and heptane, xylene, toluene or acetonitrile is more preferable.

  The amount of the solvent to be used is usually 0.5 to 50 parts by weight, preferably 1 to 30 parts by weight with respect to 1 part by weight of Compound A.

  The temperature at which compound A is dissolved in the solvent is usually 30 to 150 ° C., preferably 30 to 100 ° C.

  The cooling rate is usually 0.1 to 40 ° C./hour, preferably 1 to 30 ° C./hour, and can be changed to any cooling rate within the above range as needed.

  The temperature of the solution when taking out the precipitated crystals is usually −30 to 50 ° C., preferably −20 to 30 ° C.

  The time required for crystallization is usually 0.1 to 100 hours, preferably 1 to 50 hours.

  Moreover, when distilling a solvent off, it can distill off by heating to the boiling point or more of a solvent under atmospheric pressure. Moreover, the solvent can be distilled off at an arbitrary temperature up to the boiling point of the solvent under reduced pressure by adjusting the degree of vacuum in the container.

  Form II crystals of Compound A can be produced by the following method. A method in which compound A is heated and dissolved in a solvent, and the resulting solution is rapidly cooled to crystallize. A compound A is heated and dissolved in a solvent, and the resulting solution of compound A is dissolved in a low-temperature solvent. Form II of crystals of compound A is obtained by a method in which the solution is dropped and crystallized, or a method in which compound A is heated and dissolved in a solvent and a low-temperature solvent is dropped therein. The solvent that can be used in preparing the solution of Compound A may be any solvent that is inert with respect to Compound A. For example, diethyl ether, methyl t-butyl ether, tetrahydrofuran, dimethoxymethane, Diethoxymethane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether Ether solvents such as 1,4-dioxane, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, 2-methyl-2-propanol, methyl cellosolve Alcohol solvents such as ethyl cellosolve, i-propyl cellosolve, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, cyclohexanol, benzyl alcohol, pentane, hexane, cyclohexane, methyl Aliphatic hydrocarbon solvents such as cyclohexane, heptane, octane and decane, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, nitrobenzene, tetrahydronaphthalene Solvents, nitrile solvents such as acetonitrile and propionitrile, ester solvents such as methyl acetate, ethyl acetate, butyl acetate, and ethyl propionate, methylene chloride, chloroform, Halogenated hydrocarbon solvents such as carbonized carbon, 1,2-dichloroethane, 1,1,2-trichloroethane, amide solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, 1 , 3-dimethylimidazolidinone, urea solvents such as N, N, N ′, N′-tetramethylurea, sulfur-containing polar solvents such as dimethylsulfoxide and sulfolane, pyridine, 2-picoline, 3-picoline, 4 Pyridine solvents such as -picoline and 5-ethyl-2-picoline can be used, and these solvents can be used alone or in admixture of two or more. Among these solvents, aromatic hydrocarbon solvents, nitrile solvents or ester solvents are preferable, and xylene, toluene, acetonitrile, ethyl acetate or butyl acetate is more preferable.

  The amount of the solvent used for dissolving Compound A is usually 0.5 to 50 parts by weight, preferably 1 to 30 parts by weight with respect to 1 part by weight of Compound A.

The low-temperature solvent may be any solvent that is inert with respect to Compound A. For example, diethyl ether, methyl t-butyl ether, tetrahydrofuran, dimethoxymethane, diethoxymethane, ethylene glycol dimethyl ether Ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, triethylene glycol dimethyl ether, 1,4-dioxane, etc. -Tel solvents, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, 2-methyl-2-propanol , Methyl cellosolve, ethyl cellosolve, i-propyl cell Alcohol solvents such as sorb, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, cyclohexanol, benzyl alcohol, pentane, hexane, cyclohexane, methylcyclohexane, heptane, octane, Aliphatic hydrocarbon solvents such as decane, aromatic hydrocarbon solvents such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, nitrobenzene, tetrahydronaphthalene, acetonitrile, propio Nitrile solvents such as nitrile, ester solvents such as methyl acetate, ethyl acetate, butyl acetate, ethyl propionate, methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, , 1,2-trichloroethane and other halogenated hydrocarbon solvents, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and other amide solvents, 1,3-dimethylimidazolidinone, N, Urea solvents such as N, N ′, N′-tetramethylurea, sulfur-containing polar solvents such as dimethyl sulfoxide, sulfolane, pyridine, 2-picoline, 3-picoline, 4-picoline, 5-ethyl-2-picoline A pyridine-based solvent such as these can be used, and these solvents can be used alone or in admixture of two or more. Among these solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents or nitrile solvents are preferable, and heptane, xylene, toluene or acetonitrile is more preferable. The low-temperature solvent may be the same as or different from the solvent that dissolves the compound.

  The amount used in the case of using a low-temperature solvent is usually 1 to 100 parts by weight, preferably 5 to 50 parts by weight with respect to 1 part by weight of Compound A.

  The rate at which the solution containing Compound A is rapidly cooled is usually 40 ° C./hour or more.

  The temperature of the low temperature solvent is usually −30 to 50 ° C., preferably −20 to 30 ° C.

  The temperature of the solution when taking out the precipitated crystals is usually −30 to 50 ° C., preferably −20 to 30 ° C.

  Further, the Form I crystal of Compound A can be obtained by converting the Form II crystal of Compound A according to the method described below.

(1) Suspension method:
A solid form of compound A containing Form II crystals is charged into a dispersion medium, and the resulting suspension is allowed to stand or stir for a certain period of time to obtain Form I crystals of Compound A. As the dispersion medium, the solvent used in the production of the above-mentioned type I crystal can be used. Among these dispersion media, aromatic hydrocarbons or nitriles are preferable, and xylene, toluene, or acetonitrile is particularly preferable. The temperature of the suspension during standing or stirring is usually -20 to 100 ° C. In order to obtain high-purity type I crystals, the standing or stirring time is preferably as long as possible. Usually, the standing or stirring is performed for 1 hour or longer.
(2) Crystallization method + suspension method:
In the above crystallization method, when a mixture of Form I and Form II crystals of Compound A is obtained, the resulting suspension is converted to Form I crystals by standing or stirring for a certain period of time. Can do.
(3) Heating method:
By heating Compound A in solid state containing Form II crystals, it can be converted to Form I crystals. Examples of the heating method include a method by contact with a high-temperature inert gas, and a method of mixing with a mixer equipped with a heating device. It can also be converted to Form I crystals by heating a suspension of Compound A Form II crystals or a mixture of Form II crystals and Form I crystals.
(4) Wet grinding method:
A solid suspension containing Compound A Form II crystals can be converted to Form I crystals by wet milling. As the wet pulverizer, an in-line mill or a bead mill can be used.
(5) Dry grinding method:
A solid containing Compound II Form II crystals can be converted to Form I crystals by dry milling. As the dry pulverizer, a hammer mill, a pin mill, a jet mill, a ball mill, a roll mill, or the like can be used.
Each of the Form I crystals and Form II crystals of Compound A has technical characteristics such as not only improvement in formulation stability but also improvement in activity and ease of handling.

  Next, a suspension composition containing Form I or Form II crystals of Compound A of the present invention (hereinafter referred to as the present composition) will be described in detail.

  In the composition of the present invention, an organic liquid in which water or compound A is hardly dissolved can be used as the dispersion medium. Examples of the organic liquid include alcohols such as ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol and isopropanol, ethers such as butyl cellosolve, ketones such as cyclohexanone, esters such as γ-butyrolactone, N-methylpyrrolidone and N-octyl. Acid amides such as pyrrolidone, aromatic hydrocarbons such as xylene, alkylbenzene, phenylxylylethane and alkylnaphthalene, aliphatic hydrocarbons such as machine oil, normal paraffin, isoparaffin and naphthene, aromatic hydrocarbons such as kerosene and aliphatic Fats and oils such as a mixture of hydrocarbons, soybean oil, linseed oil, rapeseed oil, coconut oil, cottonseed oil and castor oil can be mentioned.

  The content of Form I crystals and / or Form II crystals of Compound A is usually 0.1 to 50 parts by weight, more preferably 1 to 30 parts by weight, per 100 parts by weight of the composition of the present invention.

  The suspension composition containing Compound I form I crystals suppresses the growth of Compound A suspension particles over time. In addition, the suspension composition containing Compound A having a content of Form I crystals of 50 to 100% by weight also suppresses the growth of Compound A suspension particles over time.

  In the suspension composition containing Compound A type II crystals, the growth of the suspended particles of Compound A over time is suppressed. In addition, the suspension composition containing Compound A having a content of Form II crystals of 99.9 to 100% by weight also suppresses the growth of suspended particles of Compound A over time.

  In addition to Compound A, the composition of the present invention may also contain one or more other known agricultural chemicals such as herbicides, insecticides, acaricides, nematicides, antiviral agents, plant growth regulators, fungicides, A synergist, an attractant, a repellent, and the like may be contained, and in this case, a more excellent control effect may be exhibited. Particularly preferred as known agrochemicals are fungicides, bactericides, nematicides, acaricides and insecticides. Specific examples of common names are as follows, but the general names are not necessarily limited thereto.

Bactericides: acibenzolar-S-methyl, acylaminobenzamide, acypetacs, aldimorph, ametoctradin, amisulbrom, amobam, ampropyl Phos (ampropyfos), anilazine, azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M (benalaxyl-M), benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiazole, benzamacril, benzamorf, bethoxazine, benaxal, (Binapacryl), Biphenyl, bitertanol, blasticidin-S, bixafen, bordeaux mixture, boscalid, bromoconazole, bupirimate, buthiobate (Buthiobate), calcium polysulfide, calcium polysulfide, captafol, captan, carpropamid, carbamorph, carbendazim, carboxin ( carboxin, carvone, cheshunt mixture, chinomethionat, clobenthiazone, chloraniformethane, chloranil, chlorfenazol, chloronebu (Chl oroneb), chloropicrin, chlorothalonil, chlorquinox, chlozolinate, climbazole, clotrimazole, copper acetate, basic copper carbonate (copper carbonate, basic), cupric hydroxide, copper naphthenate, copper oleite, copper oxychloride, copper sulfate, basic copper sulfate sulfate, basic), copperzincchromate, cufraneb, cuprobam, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cymoxanil Cypendazole, cyproconaz ol), cyprodinil, cyprofuram, dazomet, debacarb, decaentin, dehydroacetic acid, dichlofluanid, dichlone, Dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomedine, dicloran, etc.

Bactericides (continued): diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole-M, diniconazole-M, diniconazole-M M), dinobuton, dinocap, dinocap-4, dinocap-6, dinoton, dinosulfon, dinoterbon, diphenylamine ), Dipyrithione, ditalimfos, dithianon, dodemorph, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, etaconazole Xham (ethaboxam), etem, etirimol, ethoxyquin, etridianol, famoxadone, fenarimol, febuconazole, fenamidone, phenaminosulf ), Fenapanil, fendazosulam, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpyrazamine (fenpyrazamine), fenpropimorph, fentin, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, full Fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, fluthianyl (fluoxanil) flutianil), flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminium, fuberidazole, fluralaxyl, flametopyr ( furametpyr), furcarbanil, furconazole, fluconazole-cis, furmecyclox, furphanate, furyonate, glyodin, griseofulvin, guazachi (Guazatine), halacrinate, hexachlorobenzene, hexaconazole, hexylthiofos, hydroxyquinoline sulfate, hymexazol, imazalil, Imibenconazole, iminoctadine, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isovaledione, etc.

  Fungicide (continued): kasugamycin, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid , Mepanipyrim, mepronil, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, metasulfocarb, metoxasulfocarb, metoxafloxam ), Methyl isothiocyanate, metiram, metinominostrobin, metrafenone, metsulfovax, milneb, microbutanil, microzoline (myclozo) lin), nabam, natamycin, nickel bis (dimethyldithiocarbamate), nitrostyrene, nitrothal-isopropyl, nuarimol, OH (OCH), octhilinone, offurace, orysastrobin, oxadixyl, oxine copper, oxycarboxin, oxpoconazole fumarate , Pefurzoate, penconazole, penflufen, penencycuron, penthiopyrad, o-phenylphenol, phosdiphen, phthalide, picoxis Robin (picoxystrobin), piperalin (piperalin), polycarbamate (polycarbamate), polyoxins (polyoxins), polyoxorim (polyoxorim), potassium azide (potassium hydrogen carbonate) (potassium hydrogencarbonate), proquinazid (proquinazid) (proquinazid) , Prochloraz, procymidone, propamocarbhydrochloride, propiconazole, propineb, prothiocarb, prothioconazole, pyracarbolid, pyraclostrobin (Pyraclostrobin), pyrazophos, pyridiinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon (pyroquil) on), pyroxychlor, pyroxyfur, quinomethionate, quinoxyfen, quintozene, quinacetol-sulfate, quinazamid, quinazamid, quinconazole, quinconazole rabenzazole).

Bactericides (continued): sodium azide, sodium hydrogen carbonate, sodium hypopochlorite, sulfur, spiroxamine, salicylanilide, silthiofam ( silthiofam), simeconazole, tebuconazole, tecnazene, tecoram, tetraconazole
, Thiabendazole, thiadifluor, thicyofen, thifluzamide, thiochlorfenphim, thiophanate, thiophanate-methyl, thioquinox, Thiram, thiadinil, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol , Triazoxide, triazbutil, tributyltin oxide, trichlamide, tricyclazole, triridemorph, trifloxys Trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, vinclozolin, zarilamide, zinc sulfate (zinc) sulfate, zineb, ziram, zoxamide and shiitake mycelium extract.

  Bactericides: benzalkonium chloride, bithionol, bronopol, cresol, formaldehyde, nitrapyrin, oxolinic acid, oxyterracycline , Streptomycin and tecloftalam.

  Nematicides: aldoxycarb, cadusafos, DCP, DBCH, dichlofenthion, DSP (DSP), etoprophos, fenamiphos, fensulfothion, fluene Sulfone (fluensulfone), fosthiazate (fosthiazate), fosthietan (fosthietan), imisiafos (imicyafos), isamidofos (isamidofos), isazofos (isazofos), oxamyl (oxamyl) and thionazin (thionazin) and the like.

  Acaricide: acequinocyl, acrinathrin, amitraz, BCI-033 (test name), bifenazate, bromopropylate, chinomethionat, chlorobezilate , Clofentezine, cyenopyrafen, cyflumetofen, cyhexatine, dicofol, dienochlor, denochlor (DNOC), etoxazole, quinazaquin (fenaza) Fenbutatin oxide, fenothiocarb, fenpropathrin, fenpyroximate, fluacrypyrim, halfenprox (halfenpro) x), hexythiazox, milbemectin, propargite, pyridaben, pyrimidifen, S-1870 (test name), spirodiclofen, spiromesifen ( spyromesifen), NNI-0711 (test name), CL900187 (test name) and tebufenpyrad.

Insecticides: abamectin, acephate, acetamipirid, alanamicarb, aldicarb, allethrin, azamethiphos, azinphos-methyl, bacillus tubulin Bacillus thuringiensis, bendiocarb, benfluthrin, benfuracarb, bensultap, bifenthrin, bioallethrin, bioresmethrin, bistrifluron, tris Buprofezin (bupro
fezin, butocarboxim, carbaryl, carbofuran, carbofuran, carbosulfan, cartap, chlorantraniliprole, chlorethoxyfos, chlorfenapyr ( chlorfenapyr), chlorfenvinphos, chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyanantani Cyantraniliprole, cycloprothrin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhthrin alothrin), cypermethrin, alpha-cypermethrin, beta-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diacloden (Diacloden), diafenthiuron, diazinon, dichlorvos, diflubenzuron, dimethylvinphos, dinotefuran, diofenolan, disulfoton, dimethoate (Dimethoate), emamectin-benzoate, empenthrin, endosulfan, endo-sulfan, alpha-endosulfan, EPN, esfenvalera te), etiofencarb, ethiprole, etofenprox, etrimfos, fenitrothion, fenobucarb, phenoxycarb, fenpropathrin, fenpropathrin fenthion, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenerim, flufenoxuron, flufenprox , Flumethrin, fluvalinate, tau-fluvalinate, fonophos, formetanate, formothion, furthiocarol (Furathiocarb), full-Fi Prowl (flufiprole), Furupirajifuron (flupyradifurone), such as Furometokin (flometoquin).

Insecticides (continued): halofenozide, hexaflumuron, hydramethylnon, imidacloprid, isofenphos, indoxacarb, isoprocarb, isoxathion ), Lepimectin, lufenuron, malathion, meperfluthrin, metaflumizone, metalaldehyde, methamidophos, methidathion, methidathion, methacrifos (methacrifos) ), Metalcarb, methomyl, metoprene, methoxychlor, methoxyfenozide, methyl bromide , Monocrotophos, muscalure, nitenpyram, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydemeton-methyl (oxydemeton-methyl) oxydeprofos, parathion, parathion-methyl, pentachlorophenol (PCP), permethrin, phenothrin, phenthoate, phoxim, phorate ), Phosalone, phosmet, phosphamidon, pirimicarb, pirimiphos-methyl, profenofos, prothiofos, propaphos, prototri Protrifenbute, pyrometrozine, pyraclofos, pyrethrins, pyridalalyl, pyrifluquinazon, pyriprole, pyrafluprole, proxy, pyrifiprofen, py Resmethrin, rotenone, SI-0405 (study name), sulprofos, silafluofen, spinetram, spinosad, spirotetramat, sulfoxaflor ), Sulfotep, SYJ-159 (test name), tebfenozide, teflubenzuron, tefluthorin, terbufos, tetrachlorvinphos, tetrame Trimethrin, dT-80-phthalthrin, d-tetramethrin, tetramethylfluthrin, thiacloprid, thiocyclam, thiodicarb, thiamethoxam, thiophanox ( thiofanox, thiometon, tolfenpyrad, tralomethrin, trichlorfon, triazuron, triflumuron, vamidomion and ME-5343 (test name).

  In the composition of the present invention, a surfactant can be added as necessary. Examples of these surfactants include the following (A), (B), (C), (D), and (E).

(A) Nonionic surfactant:
(A-1) Polyethylene glycol type surfactant: For example, polyoxyethylene alkyl (for example, C _8-18 ) ether, ethylene oxide adduct of alkyl naphthol, polyoxyethylene (mono or di) alkyl (for example, C _8-12 ) ) Phenyl ether, polyoxyethylene (mono or di) alkyl (eg C _8-12 ) phenyl ether formalin condensate, polyoxyethylene (mono, di or tri) phenyl phenyl ether, polyoxyethylene (mono, di or tri) ) Benzyl phenyl ether, polyoxypropylene (mono, di or tri) benzyl phenyl ether, polyoxyethylene (mono, di or tri) styryl phenyl ether, polyoxypropylene (mono, di or tri) styryl phenyl ether, polyoxy Ethylene (mono-, di- or tri-) styryl phenyl ether polymer, polyoxyethylene polyoxypropylene (mono-, di- or tri-) styryl phenyl ether, polyoxyethylene polyoxypropylene block polymers, alkyl (e.g., C _{8 to 18)} polyoxy Ethylene polyoxypropylene block polymer ether, alkyl (e.g. _C8-12 ) phenyl polyoxyethylene polyoxypropylene block polymer ether, polyoxyethylene bisphenyl ether, polyoxyethylene resin acid ester, polyoxyethylene fatty acid (e.g. _{C8- 18)} monoesters, polyoxyethylene fatty acid (e.g. _{C 8 to 18)} diesters, polyoxyethylene sorbitan (mono-, di- or tri) fatty acid (e.g. _{C 8 to 18)} Ester, glycerol fatty acid ester ethylene oxide adduct, castor oil ethylene oxide adduct, hydrogenated castor oil ethylene oxide adduct, alkyl (e.g., C _{8 to 18)} amine ethylene oxide adduct and a fatty acid (e.g. C _{8 to 18)} amide ethylene oxide Additives etc.

(A-2) Polyhydric alcohol type surfactant: For example, glycerol fatty acid ester, polyglycerin fatty acid ester, pentaerythritol fatty acid ester, sorbitol fatty acid (eg C _8-18 ) ester, sorbitan (mono, di or tri) fatty acid ( For example, _C8-18 ) ester, sucrose fatty acid ester, polyhydric alcohol alkyl ether, alkyl glycoside, alkyl polyglycoside, fatty acid alkanolamide and the like.

(A-3) Acetylene-based surfactant: for example, acetylene glycol, acetylene alcohol, ethylene oxide adduct of acetylene glycol, ethylene oxide adduct of acetylene alcohol, and the like.

(B) Anionic surfactant:
(B-1) Carboxylic acid type surfactant: For example, polyacrylic acid, polymethacrylic acid, polymaleic acid, polymaleic anhydride, maleic acid or maleic anhydride and an olefin (for example, isobutylene and diisobutylene) Polymer, Copolymer of acrylic acid and itaconic acid, Copolymer of methacrylic acid and itaconic acid, Copolymer of maleic acid or maleic anhydride and styrene, Copolymer of acrylic acid and methacrylic acid, Acrylic acid Copolymer of acrylic acid and methyl acrylate, copolymer of acrylic acid and vinyl acetate, copolymer of acrylic acid and maleic acid or maleic anhydride, polyoxyethylene alkyl (e.g. _C8-18 ) ether acetic acid, methyl N-- fatty acids (e.g., _{C 8 to 18)} sarcosinates, resin acids and fatty acids (e.g., _{C 8 to 18),} such as Carboxylic acid, and salts thereof carboxylic acid.

(B-2) Sulfate ester type surfactant: For example, alkyl (for example, C _8-18 ) sulfate ester, polyoxyethylene alkyl (for example, C _8-18 ) ether sulfate ester, polyoxyethylene (mono or di) alkyl ( For example, C _8-12 ) phenyl ether sulfate, polyoxyethylene (mono or di) alkyl (eg C _8-12 ) phenyl ether polymer sulfate, polyoxyethylene (mono, di or tri) phenyl phenyl ether sulfate , Polyoxyethylene (mono, di or tri) benzyl phenyl ether sulfate, polyoxyethylene (mono, di or tri) styryl phenyl ether sulfate, polyoxyethylene (mono, di or tri) styryl phenyl ether polymer sulfuric acid ester Sulfate esters of polyoxyethylene polyoxypropylene block polymers, sulfated oils, fatty acid ester sulfuric, sulfate ester such as sulfated fatty acids and sulfated olefins, and salts thereof sulfate.

(B-3) Sulfonic acid type surfactant: For example, paraffin (for example, _C8-22 ) sulfonic acid, alkyl (for example, _C8-12 ) benzenesulfonic acid, alkyl (for example, _C8-12 ) benzenesulfonic acid formalin Condensate, formalin condensate of cresol sulfonic acid, α-olefin (eg C _8-16 ) sulfonic acid, dialkyl (eg C _8-12 ) sulfosuccinic acid, lignin sulfonic acid, polyoxyethylene (mono or di) alkyl (eg _C8-12 ) phenyl ether sulfonic acid, polyoxyethylene alkyl (e.g. _C8-18 ) ether sulfosuccinic acid half ester, naphthalene sulfonic acid, (mono or di) alkyl (e.g. _C1-6 ) naphthalene sulfonic acid, naphthalene sulfone Acid formalin condensate (mono or ) Alkyl (e.g. _{C 1 to 6)} formalin condensates of naphthalenesulfonic acid formalin condensate of creosote oil sulfonic acid, alkyl (e.g., _{C 8 to 12)} ether disulfonic acid, Igepon T (trade name), and polystyrene sulfonic acid Sulfonic acids such as copolymers of styrene sulfonic acid and methacrylic acid, and salts of these sulfonic acids.

(B-4) Phosphate ester type surfactants: For example, alkyl (eg, C _8-12 ) phosphate ester, polyoxyethylene alkyl (eg, C _8-18 ) ether phosphate ester, polyoxyethylene (mono or di) alkyl ( For example, C _8-12 ) phenyl ether phosphate ester, polyoxyethylene (mono, di or tri) alkyl (eg C _8-12 ) phenyl ether polymer phosphate ester, polyoxyethylene (mono, di or tri) phenyl phenyl ether Phosphate ester, polyoxyethylene (mono, di or tri) benzyl phenyl ether phosphate ester, polyoxyethylene (mono, di or tri) styryl phenyl ether phosphate ester, polyoxyethylene (mono, di or tri) styryl phenyl ether polymer The phosphoric acid beauty treatment salon , Phosphoric acid esters of polyoxyethylene polyoxypropylene block polymers, phosphoric acid esters such as phosphatidylcholine, phosphatidylethanolimine and condensed phosphoric acid (such as tripolyphosphoric acid), and salts of these phosphoric acid esters.

  As counter ions of the salts in the above (B-1) to (B-4), alkali metals (lithium, sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), ammonium, and various amines (eg, alkyl) Amine, cycloalkylamine, alkanolamine, etc.).

(C) Cationic surfactant:
For example, alkyl amines, alkyl quaternary ammonium salts, ethylene oxide adducts of alkyl amines and ethylene oxide adducts of alkyl quaternary ammonium salts.

(D) Amphoteric surfactant:
(D-1) Betaine type surfactant: For example, alkyl (eg C _8-18 ) dimethylaminoacetic acid betaine, acyl (eg C _8-18 ) aminopropyldimethylaminoacetic acid betaine, alkyl (eg C _8-18 ) hydroxy And sulfobetaines and 2-alkyl (e.g., _C8-18 ) -N-carboxymethyl-N-hydroxyethylimidazolinium betaines.

(D-2) Amino acid type surfactants: For example, alkyl (eg C _8-18 ) aminopropionic acid, alkyl (eg C _8-18 ) _{aminodipropionic} acid and N-acyl (eg C _8-18 ) -N And '-carboxyethyl-N'-hydroxyethylethylenediamine.

(D-3) Amine oxide type surfactants: Examples include alkyl (eg C _8-18 ) dimethylamine oxide and acyl (eg C _8-18 ) aminopropyldimethylamine oxide.

(E) Other surfactants:
(E-1) Silicone surfactant: for example, polyoxyethylene / methylpolysiloxane copolymer, polyoxypropylene / methylpolysiloxane copolymer and poly (oxyethylene / oxypropylene) / methylpolysiloxane copolymer Etc.

  (E-2) Fluorosurfactant: For example, perfluoroalkenyl benzene sulfonate, perfluoroalkyl sulfonate, perfluoroalkyl carboxylate, perfluoroalkenyl polyoxyethylene ether, perfluoroalkyl polyoxyethylene ether And perfluoroalkyltrimethylammonium salt.

  These surfactants can be used alone or in admixture of two or more, and the ratio in the case of mixing can be freely selected. Although content of this surfactant in this invention composition can be selected suitably, the range of 0.1-20 weight part is preferable with respect to 100 weight part of this invention composition.

  Various adjuvants can be further contained in the composition of the present invention. Examples of auxiliary agents that can be used include thickeners, organic solvents, antifreezing agents, antifoaming agents, antibacterial and antifungal agents, coloring agents, and the like.

The thickener is not particularly limited, and organic, inorganic natural products, synthetic products, and semi-synthetic products can be used. For example, heteropolysaccharides such as xanthan gum (xanthan gum), welan gum and rhamzan gum, polyvinyl alcohol, polyvinyl Water-soluble polymer compounds such as pyrrolidone, polyacrylic acid, sodium polyacrylate and polyacrylamide, cellulose derivatives such as methylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose, montmorillonite,
Examples thereof include smectite clay minerals such as saponite, hectorite, bentonite, laponite, and synthetic smectite. These thickeners may be used alone or in combination of two or more, and the ratio in the case of mixing can be freely selected. These thickeners may be added as they are, or those previously dispersed in water may be added. Moreover, content in this invention composition can also be selected freely.

  Examples of the organic solvent include alcohols such as ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol and isopropanol, ethers such as butyl cellosolve, ketones such as cyclohexanone, esters such as γ-butyrolactone, N-methylpyrrolidone and N-octylpyrrolidone. Aromatic hydrocarbons such as acid amides such as xylene, alkylbenzene, phenylxylylethane and alkylnaphthalene, aliphatic hydrocarbons such as machine oil, normal paraffin, isoparaffin and naphthene, aromatic hydrocarbons such as kerosene and aliphatic carbonization Examples include fats and oils such as a mixture of hydrogen, soybean oil, linseed oil, rapeseed oil, coconut oil, cottonseed oil and castor oil.

  As the antifreezing agent, for example, ethylene glycol, diethylene glycol, propylene glycol, glycerin and the like can be used. Preferred are propylene glycol and glycerin. Moreover, content in this invention composition can also be selected freely.

  Furthermore, you may mix | blend antifoaming agents, such as a silicone type emulsion, antibacterial antifungal agent, and a coloring agent.

  The method for producing the composition of the present invention is not particularly limited, and can be obtained by adding the above-described components to a dispersion medium and mixing them with a stirrer. If necessary, the pesticidal active ingredient, surfactant and other auxiliary agents may be singly or mixed and finely pulverized by a dry type and a wet type pulverizer.

  Dry pulverization can be performed with a hammer mill, a pin mill, a jet mill, a ball mill, a roll mill, or the like. The fine pulverization by wet pulverization can be performed by a wet pulverizer such as an in-line mill or a bead mill.

  The composition of the present invention is diluted by about 50 to 5000 times with, for example, a stock solution or water, and sprayed onto a crop or tree or soil where it grows using a sprayer or the like, using a helicopter from the air, etc. It can be applied by diluting with a stock solution or water about 2 to 100 times and spraying.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. High performance liquid chromatography (HPLC), powder X-ray diffraction and DSC measurement (differential scanning calorimetry) in the examples were performed under the measurement conditions shown below.
[HPLC]
Column: Inertsil ODS-SP, φ4.6 mm, length 150 mm,
Particle size 3μm (manufactured by GL Sciences Inc.)
Flow rate: 1.0 ml / min
Eluent: acetonitrile / water / acetic acid = 600/400/1 (volume ratio)
Detection: UV254nm
[Powder X-ray diffraction]
Model name: X'PERT-PRO MPD (Spectris Co., Ltd.)
Measurement method: Transmission method
X-ray: Cu-Kα
Voltage: 45kV Current: 40mA
Sampling interval: 0.026 deg
Data range: 2θ = 2 to 40 deg
[DSC measurement] (measured in air)
Model name: Shimadzu Corporation suggested scanning calorimeter DSC-60
Comparative substance: Alumina Sample pan: Aluminum Sampling rate: 1 second Heating rate: 5 ° C / min

Example 1 Preparation of a crystalline polymorph of Compound A, designated as Form I 4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazole-3 -Il] -2-methylbenzoic acid amide (2.00 g), orthoethyl triethyl (4.26 g) and methoxyamine hydrochloride (0.60 g) in toluene (10 ml) were stirred at 35 ° C. for 24 hours. After stirring, 10 ml of toluene was added to the reaction solution. After completion of the addition, the reaction solution was heated to 60 to 65 ° C. and washed with water (4 ml × 3 times). The toluene solution obtained after washing with water was analyzed by HPLC. As a result, after removing the area corresponding to toluene, the relative area percentage of the peak derived from the main product was 90.4%. The relative area percentage of the derived peak was 3.4%.

  From the toluene solution, 10 ml of toluene was distilled off under reduced pressure. After the distillation, the toluene solution was cooled from about 70 ° C. at a rate of about 20 ° C./hour. After crystals were formed in the toluene solution, the solution was stirred at 0 to 5 ° C. for 3 hours. After the stirring, the precipitated crystals were taken out by filtration under reduced pressure, and the obtained crystals were dried under reduced pressure to obtain 1.92 g of white crystals.

  As a result of analyzing the obtained white crystals by HPLC, the relative area percentage of the peak derived from the main product was 93.0%, and the relative area percentage of the peak derived from the by-product was 3.3%. It was.

The addition obtained crystals, liquid chromatography mass spectrometry (LC-MS) was analyzed by the main product and by-product organisms were both the same value as ^{[M + + H] = 473.9} . The LC-MS analysis was performed under the conditions described below.
LC-MS system: Waters Alliance HPLC system
2695 Separation Module
2998 Photodiode Array Detector
Analysis conditions
Column: SunFire C18, 2.5μm, 2.1 x 50mm (Waters)
Column temperature: 40 ° C
Detection: UV254nm
Eluent: A = acetonitrile, B = 0.1% by volume formic acid aqueous solution
0 to 5 minutes; A: B = 50: 50 → 95: 5 (volume ratio)
5 to 8 minutes; A: B = 95: 5 (volume ratio)
Flow rate: 0.3 ml / min
Mass spectrometer: 3100 Mass Detector
Ionization method: electrospray (positive)

Furthermore, nuclear magnetic resonance (NMR) measurement was performed on the obtained crystal under the conditions described below.
Equipment: AVANCE III 600 (Bruker BioSpin Corporation)
Resonance frequency: 600 MHz Measurement solvent: Deuterated chloroform (CDCl ₃ )
Reference substance: Tetramethylsilane [S _i (CH ₃ ) ₄ ]
As a result of proton nuclear magnetic resonance ( ¹ H-NMR) measurement, the chemical shift values described below were obtained.
¹ H-NMR δ (ppm) 8.49 (d, J = 9.6Hz, 1H), 7.77 (d, J = 9.6Hz, 1H), 7.58 (d, J = 8.6Hz, 1H),
7.57 (s, 1H), 7.54 (d, J = 8.6Hz, 1H), 7.51 (d, J = 1.9Hz, 2H), 7.44 (dd, J = 1.9Hz, 1H), 4.09 (d, J = 17.2 Hz, 1H), 3.90 (s, 3H), 3.71 (d, J = 17.2Hz, 1H), 2.53 (s, 3H).
In addition, the symbol in < ¹ > H-NMR chemical shift value represents the following meaning.
s: singlet, d: doublet, J: coupling constant, aH: a hydrogen atoms calculated from the integral value.

Furthermore, as a result of HSQC (Hetero-nuclear Single Quantum Coherence) measurement, which is a kind of two-dimensional NMR, using the sample used for ¹ H-NMR measurement, the peak derived from 7.77 ppm hydrogen atom is located at the carbon atom. Although a correlation was observed with the peak derived from, a peak derived from 8.49 ppm of hydrogen atoms was not correlated with a peak derived from carbon atoms. From this result, the peak derived from 8.49 ppm of hydrogen atoms was assigned to be a hydrogen atom on the nitrogen atom of the amide structure. Organic Letters 2011, Vol. 13, p. 5160 and Supporting Information include a chemical shift value of a peak derived from a hydrogen atom on a nitrogen atom of an amide structure in a compound similar to the structure of Compound A (hereinafter referred to as amide). And a chemical shift value of a peak derived from a hydrogen atom on a carbon atom of an iminomethyl structure (hereinafter, referred to as a chemical shift value of iminomethyl). According to the description, in the case of a compound whose geometric isomerism is Z, the chemical shift value of amide is shifted to a lower magnetic field side as compared with the chemical shift value of iminomethyl. On the other hand, in the case of a compound whose geometric isomerism is E, the chemical shift value of amide shifts to the high magnetic field side as compared with the chemical shift value of iminomethyl.

In the case of Compound A obtained in this example, the chemical shift value of amide is 8.49 ppm, and the chemical shift value of iminomethyl is 7.77 ppm.
Therefore, the main product was identified as Compound A (geometric isomerism Z), and the byproduct was identified as Compound A geometric isomerism E (hereinafter referred to as E-form of Compound A).

As a result of measuring the powder X-ray diffraction of the obtained white crystal, the diffraction pattern of FIG. 1 was shown, which was designated as type I crystal.
Moreover, as a result of performing DSC measurement of the obtained crystal, the peak top showed an endothermic peak of 171.2 ° C., and no endothermic peak was observed at other temperatures.

[Example 2] Production of crystalline polymorphs designated as Form II crystals 0.5 g of Compound A crystals obtained according to the method of Example 1 (percent HPLC relative area Compound A: E of Compound A) Body = 97.0: 2.6), 15 ml of toluene was added to prepare a toluene suspension of compound A. The suspension solution was heated and stirred at 85 ° C. to completely dissolve the crystals of Compound A to prepare a toluene solution of Compound A.
To 15 ml of ice-cooled n-hexane, the toluene solution of Compound A was added dropwise over 10 minutes so that the temperature of n-hexane did not exceed 5 ° C. After completion of the dropwise addition, the solution was stirred for 5 minutes under ice cooling. After completion of the stirring, the crystals precipitated in the solution were taken out by filtration under reduced pressure, and the obtained crystals were dried under reduced pressure to obtain 0.45 g of white crystals.

  As a result of analyzing the obtained crystals by HPLC, the relative area percentage of compound A was 97.3%, and the relative area percentage of E-form of compound A was 2.4%.

Further, as a result of measuring powder X-ray diffraction of the obtained crystal, it was found that a crystal completely different from the crystal obtained in Example 1 was obtained, showing the diffraction pattern of FIG. Named.
Further, when DSC measurement was performed on the obtained crystal, the peak top showed an endothermic peak of 164.3 ° C., and no endothermic peak was shown at other temperatures.

Example 3 Production of Form I Crystals by Stirring a Suspension of Form II Crystals 0.19 g of Form A crystals of Compound A obtained according to the method of Example 2 (HPLC relative area percentage Compound A: A suspension of Compound A in E form = 96.8: 2.8) and 0.77 g of toluene was stirred at 60 ° C. for 4 hours. After completion of the stirring, the suspension was filtered under reduced pressure, and the resulting crystals were dried under reduced pressure to obtain 0.12 g of white crystals.

When the obtained crystal was analyzed by HPLC, the relative area percentage of compound A was 97.3%, and the relative area percentage of E-form of compound A was 2.5%.
Further, as a result of measuring the powder X-ray diffraction of the obtained crystal, it was found that it was an I-type crystal showing substantially the same pattern as FIG.

[Examples 4 to 17]
In the following, “parts” means all parts by weight.
1. Preparation of pulverized slurry In 56.86 parts of water, 3 parts of a mixture of polyoxyethylene styrylphenyl ether and polyoxyalkylene glycol (trade name: Solpol 3353, manufactured by Toho Chemical Industry Co., Ltd.), silicone antifoam 0.1 part of an agent (trade name: KM-73, manufactured by Shin-Etsu Chemical Co., Ltd.), 10 parts of propylene glycol, and a total of 10.04 parts of Compound I and Form I crystals were dispersed in an amount of 0.04 parts. Using 200 g of 8-1.2 mmφ glass beads, wet grinding was performed with a sand grinder (manufactured by IMEX Co., Ltd.) to obtain 80 parts of a pulverized slurry.
As shown in Table 2, the weight ratio of Form I crystals to Form II crystals contained in Compound A was arbitrarily changed.

2. Preparation of dispersion medium In 19.55 parts of water, 0.05 part of 1,2-benzisothiazolin-3-one (trade name: PROXEL GXL, manufactured by Avisia), xanthan gum (trade name: KELZAN ASX, manufactured by CP Kelco) ) 0.1 part and 0.3 part of smectite clay (trade name: VEEGUM R, manufactured by RT Vanderbilt) were dispersed in this order to obtain 20 parts of a dispersion medium.

3. Preparation of aqueous suspension pesticide composition 80 parts of the pulverized slurry and 20 parts of dispersion medium were mixed to obtain 100 parts of a uniform aqueous suspension pesticide composition.

  About 5 g of the aqueous suspension pesticide composition obtained immediately after production obtained in Example 4 (content ratio Form I crystal: Form II crystal = 100: 0) was collected and centrifuged to remove the supernatant. The obtained sediment was spread on a filter paper and dried in a desiccator. As a result of measuring the powder X-ray diffraction of the obtained dried product, the diffraction pattern of FIG. 3 was shown, which was substantially the same as that of FIG. That is, no transition of Form I crystals was observed during the preparation of the aqueous suspension pesticide composition.

  Further, about 5 g of the aqueous suspension pesticide composition obtained immediately after production obtained in Example 17 (content rate form I crystal: form II crystal = 0: 100) was collected and centrifuged to remove the supernatant. The obtained sediment was spread on a filter paper and dried in a desiccator. As a result of measuring the powder X-ray diffraction of the obtained dried product, the diffraction pattern of FIG. 4 was shown and the diffraction pattern substantially the same as FIG. 2 was shown. That is, no transition of Form II crystals was observed at the stage of preparation of the aqueous suspension pesticide composition.

Immediately after the production of the obtained aqueous suspension pesticide composition, and after placing them in an 8 ml vial, the particle diameter was measured after storage in a thermostatic bath at 54 ° C. for 14 days. The average particle size was measured under the following measurement conditions.
(Average particle size measurement)
Model name: Particle size distribution measuring machine LS-13320 manufactured by Beckman Coulter
Measurement method: Laser diffraction scattering method The results are shown in Table 2. However, “%” means% by weight.

  According to the present invention, it is possible to produce two types of crystal forms of Compound A. In addition, the suspension composition containing the crystal form has good storage stability and is useful as a pest control agent.

Claims (2)

(Z) -4- [5- (3,5-dichlorophenyl) -5-trifluoromethyl-4,5-dihydroisoxazol-3-yl] -N- (methoxyiminomethyl) -2-methylbenzoic acid A suspension composition containing an amide crystal and a dispersion medium, wherein a diffraction angle 2θ = (7.45 ± 0.2, 11.05) in powder X-ray diffraction by Cu-Kα ray of the crystal. ± 0.2, 12.79 ± 0.2, 15.30 ± 0.2, 20.90 ± 0.2, 21.89 ± 0.2 and 24.32 ± 0.2) the content of form I crystal of the form is, Ri 50 to 100 wt% der,
The dispersion medium is Ru Ah with water, suspension composition. Further comprises a surfactant, suspension composition of claim 1 Symbol placement.

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