JP2006199637A - Insecticidal or acaricidal agent containing pyrazole derivative as active component and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an insecticidal or acaricidal agent having extremely excellent controlling effect on harmful insects and acarids in agricultural and horticultural fields. <P>SOLUTION: The insecticidal or acaricidal agent contains a pyrazole derivative expressed by general formula (1) as an active component. In the formula, R<SP>1</SP>is a (substituted)1-12C alkyl; R<SP>2</SP>is a (substituted)1-6C alkyl or a (substituted)phenyl; R<SP>3</SP>and R<SP>4</SP>are each independently hydrogen atom, a (substituted)1-12C alkyl or a (substituted)3-8C cycloalkyl or together with carbon atom bonding with R<SP>3</SP>and F<SP>4</SP>form a 3-8C cycloalkyl; n is an integer of 0-5; and R<SP>5</SP>is hydrogen atom, a 1-6C alkyl or a halogen atom. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an insecticide / acaricide containing a pyrazole derivative as an active ingredient and a method for producing them.

Conventionally, in the field of agriculture and horticulture, insecticides and acaricides for the purpose of controlling various pests have been developed and put into practical use. However, conventionally used insecticides and acaricides are not necessarily satisfactory in terms of effects, spectrum, residual effects, and the like. Moreover, it cannot be said that the social request, such as the number of times of application and the amount of applied medicine, is sufficiently satisfied.
In addition, the appearance of pests that have acquired resistance to insecticides and acaricides that have been widely used in the past is also a problem. For example, in the cultivation of vegetables, fruit trees, flower buds, tea, wheat and rice, various strains of insecticides and acaricides, such as organic phosphorus agents (fenitrothion, malathion, prothiophos, DDVP, etc.), pyrethroids (permethrin, Cypermeline, fenvalerate, cyhalothrin, etc.), benzoyl urea series (diflubenzuron, teflubenzuron, chlorfluazuron, etc.), nereistoxin series (cartap, bensultap, etc.) It has become difficult.
In addition, insecticides and acaricides for which pests have not yet acquired resistance (for example, organic halogenated pesticides such as DDT and BHC, chlorinated cyclic diene pesticides such as aldrin, dieldrin, endrin, heptachlor, benzoepin, etc.) However, it is not preferable from the viewpoint of toxicity and environmental pollution. Therefore, it shows a sufficient control effect at low doses against various pests that have acquired resistance to conventional general agricultural and horticultural insecticides and acaricides, and is highly safe for useful organisms, and is environmentally friendly. The development of new insecticides and acaricides with few adverse effects is eagerly desired.
It has already been reported that the pyrazole derivative relating to the present invention is useful as a herbicide (see Patent Document 1). However, the above publication does not describe any physiological activities other than the action of these compounds as herbicides, for example, insecticidal and acaricidal activities.
International Publication No. 01/23358 Pamphlet

  The problem of the present invention is that it exhibits a high control effect against various pests that are resistant to conventional agricultural and horticultural insecticides and acaricides, and is highly safe against useful organisms, and has an adverse effect on the environment. The aim is to provide a few new insecticides and acaricides.

As a result of intensive studies to solve the above problems, the present inventors have found that the pyrazole derivative represented by the general formula (1) is a compound that can solve the above problems, and have completed the present invention. .
That is, the present invention provides a general formula (1)

Wherein R ¹ represents an optionally substituted C _{1 to} C ₁₂ alkyl group, and R ² represents an optionally substituted C _{1 to} C ₆ alkyl group or an optionally substituted phenyl group. R ³ and R ⁴ are the same or different and each represents a hydrogen atom, an optionally substituted C ₁ -C ₁₂ alkyl group or an optionally substituted C ₃ -C ₈ cycloalkyl group. Alternatively, the carbon atom to which R ³ and R ⁴ are bonded together may form a C _{3 to} C ₈ cycloalkyl group, n represents an integer of 0 to ^5. R ⁵ represents hydrogen. atom, it relates to insecticidal and acaricidal agent containing the pyrazole derivatives as active ingredient represented by the representative.) the alkyl group or a halogen atom C ₁ -C _6.
The pyrazole derivative represented by the general formula (1) of the present invention has the general formula (2)

(Wherein R ¹ and R ⁵ represent the same meaning as described above, and R ⁶ represents a C _{1 to} C ₆ alkyl group, benzyl group or allyl group), and a general formula (3)

(Wherein R ³ , R ⁴ and n have the same meaning as described above), in some cases, in the presence of a base,

(Wherein R ¹ , R ³ , R ⁴ , R ⁵ and n represent the same meaning as described above), a 3-hydroxypyrazole-4-carboxamide derivative represented by the following, optionally isolated and purified, This and the general formula (5)

(Wherein R ² represents the same meaning as described above, and X represents a leaving group) and can be produced by reacting in the presence of a base. Hereinafter, the present invention will be described in detail.

  The insecticide / acaricide containing the pyrazole derivative of the present invention as an active ingredient has an extremely excellent control effect against harmful insects and mites in agricultural and horticultural cultivation situations, and is useful as an insecticide / acaricide for agricultural and horticultural use It is.

In pyrazole derivatives of the present invention, examples of the alkyl group substituted by C ₁ optionally -C ₁₂ represented by R ^1, may be straight chain or branched, a methyl group, an ethyl group Propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, 2-pentyl group, 3-pentyl group, neopentyl group, tert-pentyl group, hexyl group, 2-hexyl Examples thereof include a group, 3-hexyl group, octyl group, decyl group, undecyl group, dodecyl group and the like. Further, these alkyl groups halogen atom, a cycloalkyl group of C ₃ -C _8, alkylthio group of C ₁ -C _6, it may be substituted one or more alkoxy groups of C ₁ -C ₆ or the like, more specifically Specifically, 2-chloroethyl group, 3-chloropropyl group, difluoromethyl group, 3-fluoropropyl group, cyclopropylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylthioethyl group, methoxymethyl group, ethoxymethyl group And a 2-methoxyethyl group, and the like. Among them, a C ₁ -C ₄ lower alkyl group is preferable in that it provides high activity.

The alkyl group of R C ₁ may be substituted represented by ² -C _6, it may be straight chain or branched, a methyl group, an ethyl group, a propyl group, an isopropyl group, Butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, 2-pentyl group, 3-pentyl group, neopentyl group, tert-pentyl group, hexyl group, 2-hexyl group, 3-hexyl group, A fluoromethyl group, a difluoromethyl group, a trifluoromethyl group and the like can be exemplified, and among them, a C _{1 to} C ₄ lower alkyl group is preferable in terms of providing high activity.

Examples of the optionally substituted phenyl group represented by R ² include phenyl group, p-tolyl group, 4-tert-butylphenyl group, 4-methoxyphenyl group, 2,4,6-trimethylphenyl group, 4 -Acetylphenyl group, 4-trifluoromethyloxyphenyl group, 3-trifluoromethylphenyl group, 2-trifluoromethylphenyl group, 4-chlorophenyl group, 4-chloro-3-nitrophenyl group, 4-fluorophenyl group 2-bromophenyl group, pentafluorophenyl group, 4-bromophenyl group, 4-acetylaminophenyl group, 2,4,6-triisopropylphenyl group, 2,5-dichlorophenyl group, 3,4-dichlorophenyl group, 2-nitrophenyl group, 4-nitrophenyl group, 3-nitrophenyl group, 2-nitro-4-trifluoromethylphenyl group, 3,5-bistrifluoromethyl group, 3,4-dimethoxyphenyl group, 4-biphenyl It can be exemplified Le group.

The alkyl group of R ³ and may be substituted represented by R ⁴ C ₁ ~C _12, it may be straight chain, branched or cyclic, methyl, ethyl, propyl Group, isopropyl group, cyclopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, pentyl group, isoamyl group, neopentyl group, 2-pentyl group, 3-pentyl group, 2-methylbutyl Group, tert-pentyl group, cyclopentyl group, hexyl group, isohexyl group, 2-ethylbutyl group, 4-methylpentyl group, cyclohexyl group, heptyl group, 2-heptyl group, octyl group, cyclooctyl group, decyl group, undecyl group And dodecyl group. Further, these alkyl groups halogen atom, C ₃ -C cycloalkyl group _8, an alkylthio group of C ₁ ~C _6, C ₁ ~C alkylsulfinyl group _6, an alkylsulfonyl group having C ₁ -C _6, C One or more alkoxy groups of _{1 to} C ₆ , aryloxy groups and the like may be substituted, and more specifically, 2-chloroethyl group, 3-chloropropyl group, difluoromethyl group, 3-fluoropropyl group, cyclopropyl Methyl group, cyclopentylmethyl group, cyclohexylmethyl group, methylthiomethyl group, 2-methylthioethyl group, methylsulfinylmethyl group, 2-methylsulfinylethyl group, methylsulfonylmethyl group, 2-methylsulfonylethyl group, methoxymethyl group, ethoxy Methyl group, 2-methoxyethyl group, 2-chloroethoxymethyl group, phenoxymethyl group, 2-chlorophenoxyme Group, 2-bromophenoxymethyl group, 2-trifluoromethylphenoxymethyl group, 3-fluorophenoxymethyl group, 3-methylthiophenoxymethyl group, 3-trifluoromethylphenoxymethyl group, 4-chlorophenoxymethyl group, 4 -Bromophenoxymethyl group, 4-trifluoromethylphenoxymethyl group and the like can be exemplified.

Examples of the optionally substituted C _{3 to} C ₈ cycloalkyl group represented by R ³ and R ⁴ include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclooctyl group. . These cycloalkyl groups alkyl group halogen atoms or C ₁ -C _4, may be substituted by an alkoxy group C ₁ -C ₄ etc., and more specifically, 1-methylcyclopropyl group, Examples include 2,2-dimethylcyclopropyl group, 2-chlorocyclopropyl group, 2,2-dichlorocyclopropyl group, 2-methoxycyclopropyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, and the like. .

The C _{3 to} C ₈ cycloalkyl group formed integrally with the carbon atom to which R ³ and R ⁴ are bonded includes a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. Examples include groups. These cycloalkyl groups alkyl group halogen atoms or C ₁ -C _4, may be substituted by an alkoxy group C ₁ -C ₄ etc., and more specifically, 1-methylcyclopropyl group, Examples include 2,2-dimethylcyclopropyl group, 2-chlorocyclopropyl group, 2,2-dichlorocyclopropyl group, 2-methoxycyclopropyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, and the like. .

Examples of the C _{1 to} C ₆ alkyl group represented by R ⁵ and R ⁶ include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a pentyl group, and a hexyl group. It can be illustrated.

Examples of the halogen atom represented by R ⁵ include a fluorine atom, a chlorine atom, and a bromine atom.

  Next, the manufacturing method of the pyrazole derivative of this invention is demonstrated in detail. The pyrazole derivative of the present invention can also be produced by the method described in Patent Document 1, but the production method exemplified in the following production method has a short reaction step and is not required to use an expensive reaction reagent as an industrial production method. It is advantageous.

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , n and X represent the same meaning as described above, and R ⁷ represents a methyl group, ethyl group, propyl group, butyl group, isobutyl group refers to lower alkyl groups C ₁ -C ₄ and the like.)

Step-1 is a step of producing a 3-hydroxypyrazole-4-carboxylic acid derivative (7) by hydrolyzing the ester of the 3-hydroxypyrazole-4-carboxylic acid ester derivative (6).
The reaction is carried out in the presence of a base. As the base, an aqueous solution of lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide or the like can be used. The target product can be obtained in a high yield by reacting the base using 0.5 equivalent to a large excess of the substrate. The reaction can also be carried out in the presence of an organic solvent. As the organic solvent, alcohol solvents such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, tert-butyl alcohol, ethylene glycol, propylene glycol, diethyl ether, tetrahydrofuran (THF), dimethoxyethane (DME), 1, Ether solvents such as 4-dioxane, nitrile solvents such as acetonitrile and propionitrile, amide solvents such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide and N-methylpyrrolidone, dimethyl sulfoxide ( DMSO) or a mixed solvent thereof can be used.

Step-2 is a step of producing the pyrazole derivative (2) by reacting the 3-hydroxypyrazole-4-carboxylic acid derivative (7) with the chloroformate (8).
The reaction is carried out in the presence of a base. Bases include triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N, N-dimethylaniline, N, N-diethylaniline, 4-tert-butyl-N, N-dimethylaniline, pyridine, picoline, lutidine, etc. Organic bases, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyl Alkali metal bases such as lithium, tert-butyllithium, lithium diisopropylamide, trimethylsilyllithium, lithium hexamethyldisilazide and the like can be used. Among these bases, alkali metal carbonates such as sodium carbonate and potassium carbonate are preferable in terms of a good yield. By reacting the base with 1 to 5 equivalents based on the substrate, the target product can be obtained in good yield.
This reaction is preferably carried out in a solvent. As the solvent, any solvent that does not harm the reaction can be used, aromatic hydrocarbon solvents such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbon solvents such as pentane, hexane and octane, Ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, THF, DME, 1,4-dioxane, ketones such as acetone, methyl ethyl ketone, cyclohexanone, halogen solvents such as chloroform, dichloromethane, acetonitrile, propionitrile, etc. Nitrile solvents, ester solvents such as ethyl acetate, propyl acetate, butyl acetate, methyl propionate, amide solvents such as DMF, N, N-dimethylacetamide, N-methylpyrrolidone, DMSO, water, or a mixture thereof A solvent can be used. The reaction can be carried out at a temperature appropriately selected from the range from −78 ° C. to the solvent reflux temperature, although it varies depending on the base used and the reaction conditions.

Step-3 is a step of producing a 3-hydroxypyrazole-4-carboxamide derivative (4) by reacting the pyrazole derivative (2) with an amine (3), optionally in the presence of a base. Some of the amines (3) used in Step-3 are commercially available, but Journal of the Chemical Society (Journal of the Chemical Society, Abstracts; 1961, p4372-4379, 1962, p3977-3980) Can be produced by the method described in the above.
This reaction can also be carried out in a solvent. As the solvent, any solvent that does not harm the reaction can be used, aromatic hydrocarbon solvents such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbon solvents such as pentane, hexane and octane, Ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, THF, DME, 1,4-dioxane, ketones such as acetone, methyl ethyl ketone, cyclohexanone, halogen solvents such as chloroform, dichloromethane, acetonitrile, propionitrile, etc. Nitrile solvents, ester solvents such as ethyl acetate, propyl acetate, butyl acetate, methyl propionate, amide solvents such as DMF, N, N-dimethylacetamide, N-methylpyrrolidone, DMSO, water, or a mixture thereof A solvent can be used.
The reaction can also be carried out in the presence of a base. Bases include sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, potassium hydride, sodium amide, butyl Alkali metal bases such as lithium, tert-butyllithium, lithium diisopropylamide, trimethylsilyllithium, lithium hexamethyldisilazide, triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N, N-dimethylaniline, N, N- Organic bases such as diethylaniline, 4-tert-butyl-N, N-dimethylaniline, pyridine, picoline, lutidine, diazabicycloundecene, diazabicyclooctane and imidazole can be used. A so-called catalytic amount of the base is sufficient with respect to the substrate, but even if it is used in excess, there is no problem, and the target product can be obtained in good yield.
The reaction can be carried out at a temperature appropriately selected from the range from −78 ° C. to the solvent reflux temperature, although it varies depending on the base used and the reaction conditions.

  In the reaction of Step-3, the desired 3-hydroxypyrazole-4-carboxamide derivative (4) is produced via the precursor 3- (alkoxycarbonyloxy) pyrazole-4-carboxamide derivative (4 ′). Therefore, in some cases, a pyrazole-4-carboxamide derivative (4 ′) may be obtained as a by-product. However, the precursor (4 ′) can be easily converted to the target product (4) by hydrolysis.

(In the formula, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ and n represent the same meaning as described above.)
Step-4 is a step of producing the pyrazole derivative (1) of the present invention by reacting the 3-hydroxypyrazole-4-carboxamide derivative (4) with the sulfonylating agent (5) in the presence of a base, for example, It can implement according to the method of the said patent document 1.

Moreover, although the said process-3 and process-4 can obtain each manufacture intermediate body by a batch type reaction, process-3 and process-4 can also be implemented continuously.
The pyrazole derivative (1) of the present invention is useful as an insecticide / acaricide for agriculture and horticulture. Pests to be controlled include Lepidoptera such as Lotus moth, Konaga, Chanocokakumon-Hamakaki, Kononogaiga, Nikameichu, etc .; Hemiptera such as Butterfly, Red-bellied beetle; Coleoptera such as Kizinogami beetle, Wormworm, Azuki beetle; And mite eggs, nymphs, larvae and adult ticks, such as citrus mite and mite dust mites. The insects and mites that are most subject to control are not limited to these.

  When the pyrazole derivative (1) of the present invention is used as an agricultural / horticultural insecticide / acaricide, it may be used alone, but preferably in the form of a composition produced using a general agricultural chemical auxiliary. use. The form of the insecticide / acaricide of the present invention is not particularly limited, and examples thereof include emulsions, wettable powders, powders, flowables, dry flowables, fine granules, granules, tablets, oils, sprays, and fumes. It is preferable to adopt a form. Moreover, the 1 type (s) or 2 or more types of the pyrazole derivative (1) of this invention can be mix | blended as an active ingredient.

The agrochemical adjuvant used for producing the insecticide / acaricide containing the pyrazole derivative (1) of the present invention as an active ingredient is, for example, an improvement in the effect of the insecticide / acaricide, stabilization, and improvement in dispersibility. It can be used for such purposes. As the agricultural chemical auxiliary, for example, a carrier (diluent), a spreading agent, an emulsifier, a wetting agent, a dispersing agent, a disintegrating agent and the like can be used.
Examples of liquid carriers include water, aromatic hydrocarbons such as toluene and xylene, alcohols such as methanol, butyl alcohol, and glycol, ketones such as acetone and cyclohexanone, amides such as dimethylformamide, sulfoxides such as dimethyl sulfoxide, Mention may be made of methylnaphthalene, cyclohexane, animal and vegetable oils, fatty acids and the like. As the solid carrier, clay, kaolin, talc, diatomaceous earth, silica, calcium carbonate, montmorillonite, bentonite, feldspar, quartz, alumina, sawdust, nitrocellulose, starch, gum arabic and the like can be used.
Usable surfactants can be used as emulsifiers and dispersants, for example, higher alcohol sodium sulfate, stearyltrimethylammonium chloride, polyoxyethylene alkylphenyl ether, anionic surfactants such as lauryl betaine, cations Surfactants, nonionic surfactants, zwitterionic surfactants, and the like can be used. In addition, spreading agents such as polyoxyethylene nonylphenyl ether and polyoxyethylene lauryl phenyl ether; wetting agents such as dialkyl sulfosuccinate; fixing agents such as carboxymethyl cellulose and polyvinyl alcohol; sodium lignin sulfonate and sodium lauryl sulfate Disintegrants can be used.

The content of the active ingredient in the insecticide / acaricide of the present invention is selected from the range of 0.01 to 99.5%, and may be appropriately determined depending on various conditions such as the preparation form and application method. About 20% by weight, preferably 1 to 10% by weight, about 1 to 90% by weight for wettable powder, preferably about 10 to 80% by weight, about 1 to 90% by weight for emulsion, preferably 10 to 40% by weight It is preferable to produce so that it may contain the active ingredient.
For example, in the case of an emulsion, it is possible to produce a stock emulsion by mixing a solvent and a surfactant with the pyrazole derivative (1) of the present invention, which is an active ingredient, and further to use this stock solution at a predetermined concentration. It can be applied diluted with water. In the case of a wettable powder, an active ingredient pyrazole derivative (1), a solid carrier, a surfactant and the like are mixed to produce a stock solution, and this stock solution can be applied by diluting with water to a predetermined concentration when used. . In the case of powders, the active ingredient pyrazole derivative (1) can be mixed and applied as it is, and in the case of granules, the active ingredient pyrazole derivative (1), solid carrier, surfactant, etc. Can be produced by mixing and granulating and applied as it is. However, the production methods of these preparation forms are not limited to these, and those skilled in the art can appropriately select them according to the type of active ingredient, application purpose, and the like.

In addition to the pyrazole derivative (1) of the present invention, which is an active ingredient, other fungicides, insecticides, acaricides, herbicides, insect growth regulators, fertilizers Any active ingredient such as a soil conditioner may be blended.
The application method of the agricultural / horticultural insecticide / acaricide of the present invention is not particularly limited, and can be applied by any method such as foliage spraying, water surface application, soil treatment, and seed treatment. For example, in the case of foliage spraying or soil treatment, a solution having a concentration range of 0.001 to 1000 ppm, preferably 0.01 to 500 ppm can be used at an application rate of about 0.1 to 5000 L, preferably about 10 to 2000 L per 10 ares. The application amount in the case of water surface application is usually 0.1 to 10 kg per 10 ares for granules containing 0.01 to 15% of the active ingredient. In the case of soil treatment, a solution having a concentration range of 5 to 1000 ppm can be used at an application rate of about 1 to ¹⁰ L per 1 m ² . In the case of seed treatment, about 10 to 100 mL of a solution having a concentration range of 10 to 1000 ppm per 1 kg of seed weight can be applied.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist.

Example-1
2-Amino-2-ethylbutanenitrile (5.88 g, 52.4 mmol) was added to a solution of 3-ethoxycarbonyloxy-1-methylpyrazol-4-ylcarbonyl (ethyl) carbonate (1.50 g, 5.24 mmol) in acetonitrile (15 mL). After adding at 0 ° C., the mixture was stirred as it was for 30 minutes. After completion of the reaction, the reaction mixture was concentrated to obtain a crude product of N- (1-cyano-1-ethylpropyl) -3-hydroxy-1-methylpyrazole-4-carboxamide. Acetonitrile (30 mL), potassium carbonate (3.62 g, 26.2 mmol) and methylsulfonyl chloride (2.0 mL, 26.2 mmol) were sequentially added to this, and the mixture was stirred at room temperature for 6 hours and at 60 ° C. for 12 hours. After completion of the reaction, ethyl acetate (30 mL) and water (30 mL) were added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL × 2). The organic layer was washed with saturated brine (30 mL), dried over anhydrous magnesium sulfate, the desiccant was removed by filtration, and the solvent was distilled off from the filtrate under reduced pressure. By purifying the obtained crude product using a silica gel column (ethyl acetate / hexane = 1/2), N- (1-cyano-1-ethylpropyl) -1-methyl-3-methylsulfonyloxypyrazole A white solid of -4-carboxamide (0.62 g, yield: 37.8%) was obtained. Mp: 96-97 ° C .; ¹ H-NMR (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.41 (br s, 1H), 3.87 (s, 3H), 3.48 (s, 3H) , 1.91-2.20 (m, 4H), 1.09 (t, J = 7.5Hz, 6H).

Example-2
To a solution of aminoacetonitrile sulfate (3.26 g, 21.1 mmol) and potassium carbonate (3.51 g, 25.4 mmol) in acetonitrile (50 mL) was added 3-ethoxycarbonyloxy-1-propylpyrazol-4-ylcarbonyl (ethyl) carbonate (1.50 g). , 8.74 mmol) at 0 ° C. and stirred at the same temperature for 30 minutes and at room temperature for 16 hours. Next, acetonitrile (30 mL), potassium carbonate (3.50 g, 265.4 mmol), and methylsulfonyl chloride (2.0 mL, 25.4 mmol) were sequentially added thereto, followed by stirring at room temperature for 16 hours and at 60 ° C. for 8 hours. After completion of the reaction, ethyl acetate (80 mL) and water (80 mL) were added to the reaction solution, and the mixture was extracted with ethyl acetate (50 mL × 2). The organic layer was washed with saturated brine (80 mL), dried over anhydrous magnesium sulfate, the desiccant was removed by filtration, and the solvent was distilled off from the filtrate under reduced pressure. The obtained crude product was purified using a silica gel column (ethyl acetate / hexane = 2/5) to give a white solid (1.10) of N-cyanomethyl-3-methylsulfonyloxy-1-propylpyrazole-4-carboxamide. g, yield: 45.4%). mp: 96-98 ° C .; ¹ H-NMR (CDCl ₃ , TMS, ppm): δ7.91 (s, 1H), 6.59-6.83 (m, 1H), 4.31 (d, J = 5.9 Hz, 2H), 4.02 (t, J = 7.0Hz, 2H), 3.50 (s, 3H), 1.89 (dt, J = 7.0 and 7.4Hz, 2H), 0.94 (t, J = 7.4Hz, 3H).

  Examples-3 to 20 obtained pyrazole derivatives in the same manner as Example-1 or 2.

Example-3
Compound name: N-cyanomethyl-1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 12.0%, white solid, 111-113 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.89 (s, 1H), 6.69 (br t, J = 5.9Hz, 1H), 4.31 (d, J = 5.9Hz, 2H), 3.88 ( s, 3H), 3.51 (s, 3H).

Example-4
Compound name: N- (2-cyanoethyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 30.8%, white solid, 121-125 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.84 (s, 1H), 6.60-6.83 (m, 1H), 3.86 (s, 3H), 3.67 (dt, J = 6.5 and 6.6Hz, 2H), 3.49 (s, 3H), 2.70 (t, J = 6.6Hz, 2H).

Example-5
Compound name: N- (1-cyano-2-methylpropyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 21.9%, white solid, 100 to 102 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.88 (s, 1H), 6.70 (br d, J = 8.3Hz, 1H), 4.88 (dd, J = 5.9 and 8.3Hz, 1H), 3.87 (s, 3H), 3.50 (s, 3H), 2.15 (d septet, J = 5.9 and 6.8Hz, 1H), 1.15 and 1.16 (each d, J = 6.8Hz, total 6H).

Example-6
Compound name: N- (1-cyanopropyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 8.7%, colorless oil
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.88 (s, 1H), 6.69 (br d, J = 8.0Hz, 1H), 4.89 (dt, J = 7.0 and 8.0Hz, 1H), 3.87 (s, 3H), 3.49 (s, 3H), 1.94 (dq, J = 7.0 and 7.4Hz, 2H), 1.16 (t, J = 7.4Hz, 3H).

Example-7
Compound name: N- (1-cyano-2-methylbutyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 4.9%, colorless oil
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.88 (s, 1H), 6.70 and 6.74 (each d, J = 9.2 Hz, total 1H), 4.97 (dd, J = 5.6 and 8.6 Hz, 1H), 3.87 (s, 3H), 3.50 (s, 3H), 1.77-2.02 (m, 1H), 1.51-1.75 (m, 1H), 1.30-1.50 (m, 1H), 1.15 and 1.16 (each d , J = 6.8Hz, total 3H), 0.98 and 0.99 (each t, J = 7.4Hz, total 3H).

Example-8
Compound name: N- (1-cyano-1-methylpropyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 28.6%, white solid, 109-112 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.49 (br s, 1H), 3.86 (s, 3H), 3.48 (s, 3H), 1.89-2.18 (m , 2H), 1.74 (s, 3H), 1.15 (t, J = 7.5Hz, 3H).

Example-9
Compound name: N- (1-cyano-1-methylbutyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 23.3%, white solid, 109-112 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.51 (br s, 1H), 3.86 (s, 3H), 3.48 (s, 3H), 1.81-2.07 (m , 2H), 1.74 (s, 3H), 1.55-1.68 (m, 2H), 1.02 (t, J = 7.3Hz, 3H).

Example-10
Compound name: N- (1-cyano-1-ethylbutyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 23.5%, white solid, 108-111 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.44 (br s, 1H), 3.86 (s, 3H), 3.48 (s, 3H), 1.85-2.20 (m , 4H), 1.41-1.64 (m, 2H), 1.09 (t, J = 7.5Hz, 3H), 1.00 (t, J = 7.3Hz, 3H).

Example-11
Compound name: N- (1-cyano-1-cyclopropylethyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 25.2%, white solid, 129-131 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.73 (br s, 1H), 3.87 (s, 3H), 3.48 (s, 3H), 1.84 (s, 3H ), 1.22-1.40 (m, 1H), 0.60-0.81 (m, 4H).

Example-12
Compound name: N- (1-cyano-1,2-dimethylpropyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 37.4%, white solid, 80-82 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.49 (br s, 1H), 3.86 (s, 3H), 3.49 (s, 3H), 2.34 (septet, J = 6.8Hz, 1H), 1.70 (s, 3H), 1.19 (d, J = 6.8Hz, 3H), 1.12 (d, J = 6.8Hz, 3H).

Example-13
Compound name: N- (1-cyano-1-ethyl-2-methylpropyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 15.1%, white solid, 100-103 ℃
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.41 (br s, 1H), 3.87 (s, 3H), 3.49 (s, 3H), 2.46 (septet, J = 6.8Hz, 1H), 1.91-2.25 (m, 2H), 1.16 (d, J = 6.8Hz, 3H), 1.10 (d, J = 6.8Hz, 3H), 1.07 (t, J = 7.4Hz, 3H ).

Example-14
Compound name: N- (1-cyanocyclohexyl) -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 31.1%, white solid, 120-121 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.48 (s, 1H), 3.86 (s, 3H), 3.48 (s, 3H), 2.27-2.48 (m, 2H), 1.77-1.92 (m, 2H), 1.69-1.77 (m, 4H), 1.57-1.69 (m, 1H), 1.30-1.46 (m, 1H).

Example-15
Compound name: N- (1-cyano-1-ethylpropyl) -1-ethyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 18.3%, white solid, 100-101 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.91 (s, 1H), 6.42 (br s, 1H), 4.11 (q, J = 7.3Hz, 2H), 3.48 (s, 3H), 1.92-2.20 (m, 4H), 1.50 (t, J = 7.3Hz, 3H), 1.09 (t, J = 7.4Hz, 6H).

Example-16
Compound name: N- (1-cyano-1-methylbutyl) -1-ethyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 13.0%, white solid, 100 to 103 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.92 (s, 1H), 6.52 (br s, 1H), 4.11 (q, J = 7.3Hz, 2H), 3.48 (s, 3H), 1.82-2.08 (m, 2H), 1.75 (s, 3H), 1.55-1.69 (m, 2H), 1.49 (t, J = 7.3Hz, 3H), 1.02 (t, J = 7.3Hz, 3H).

Example-17
Compound name: N- (1-cyanocyclohexyl) -1-ethyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 23.9%, white solid, 97-101 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.92 (s, 1H), 6.49 (br s, 1H), 4.11 (q, J = 7.3Hz, 2H), 3.48 (s, 3H), 2.30-2.47 (m, 2H), 1.55-1.90 (m, 8H), 1.49 (t, J = 7.3Hz, 3H).

Example-18
Compound name: N- (1-cyano-1-ethylpropyl) -3-methylsulfonyloxy-1-propylpyrazole-4-carboxamide Yield, shape, melting point: 17.9%, white solid, 98-99 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.89 (s, 1H), 6.43 (br s, 1H), 4.01 (t, J = 7.0Hz, 2H), 3.48 (s, 3H), 1.97-2.20 (m, 4H), 1.88 (tq, J = 7.0 and 7.4Hz, 2H), 1.09 (t, J = 7.4Hz, 6H), 0.93 (t, J = 7.4Hz, 3H).

Example-19
Compound name: N- (1-cyano-1-methylbutyl) -3-methylsulfonyloxy-1-propylpyrazole-4-carboxamide Yield, shape, melting point: 9.2%, white solid, 89-90 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.89 (s, 1H), 6.52 (br s, 1H), 4.01 (t, J = 7.0Hz, 2H), 3.47 (s, 3H), 1.80-2.05 (m, 4H), 1.75 (s, 3H), 1.47-1.68 (m, 2H), 1.02 (t, J = 7.3Hz, 3H), 0.93 (t, J = 7.4Hz, 3H).

Example-20
Compound name: N- (1-cyanocyclohexyl) -3-methylsulfonyloxy-1-propylpyrazole-4-carboxamide Yield, shape, melting point: 28.3%, white solid, 125-126 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.90 (s, 1H), 6.49 (br s, 1H), 4.01 (t, J = 7.0Hz, 2H), 3.74 (s, 3H), 2.27-2.47 (m, 2H), 1.64-1.89 (m, 7H), 1.88 (tq, J = 7.0 and 7.4Hz, 2H), 1.25-1.51 (m, 1H), 0.93 (t, J = 7.4Hz, 3H).

Example-21
To a solution of aminoacetonitrile sulfate (13.7 g, 89 mmol) in acetonitrile (50 mL) was added 3-ethoxycarbonyloxy-1-ethylpyrazol-4-ylcarbonyl (ethyl) carbonate (2.0 g, 6.67 mmol) and triethylamine (10 mL) at room temperature. And stirred for 2 days. After completion of the reaction, the reaction solution was extracted with ethyl acetate (100 mL) and 1M hydrochloric acid (100 mL). The organic layer was dried over anhydrous magnesium sulfate, the desiccant was removed by filtration, and the solvent was distilled off from the filtrate under reduced pressure. The obtained crude product was purified using a silica gel column (ethyl acetate = 100%) to give N-cyanomethyl-3-hydroxy-1-ethylpyrazole-4-carboxamide as a white solid (70 mg, yield: 5.4 %). mp: 233-240 ° C .; ¹ H-NMR (DMSO, ppm): δ 7.97 (s, 1H), 7.83 (t, J = 5.8 Hz, 1H), 4.23 (d, J = 5.8 Hz, 2H), 3.95 (q, J = 7.2Hz, 2H), 1.32 (t, J = 7.2Hz, 3H). (Hydroxyl proton could not be assigned.)

Example-22
2-Amino-2-ethylbutanenitrile (3.10 g, 27.7 mmol) was added to a solution of 3-ethoxycarbonyloxy-1-propylpyrazol-4-ylcarbonyl (ethyl) carbonate (1.45 g, 4.61 mmol) in acetonitrile (20 mL). After adding at 0 ° C., the mixture was stirred for 30 minutes and then for 1 day. After completion of the reaction, the reaction mixture was concentrated, and the resulting crude product was purified using a silica gel column (ethyl acetate = 100%) to give N- (1-cyano-1-ethylpropyl) -3-hydroxy. A white solid (82 mg, yield: 6.7%) of -1-propylpyrazole-4-carboxamide was obtained. mp: 196-198 ° C; ¹ H-NMR (CDCl ₃ , ppm): δ 7.75 (s, 1H), 6.96 (s, 1H), 3.91 (t, J = 7.0 Hz, 2H), 2.11 (q, J = 7.4Hz, 2H), 2.10 (q, J = 7.4Hz, 2H), 1.87 (tq, J = 7.0 and 7.4Hz, 2H), 1.10 (t, J = 7.4Hz, 6H), 0.94 (t, J = 7.4Hz, 3H) (The proton of the hydroxyl group could not be assigned.)

Reference Example-1
A solution of N- (1-cyano-1-ethylpropyl) -3-benzyloxy-1-tert-butylpyrazole-4-carboxamide (1.50 g, 4.07 mmol) in ethanol (120 mL) was placed in a stainless steel autoclave and 10% Palladium / carbon (100 mg) was added. After fully replacing the interior of the autoclave with hydrogen gas, the mixture was stirred at room temperature for 12 hours under a hydrogen gas pressure of 5 atm. After completion of the reaction, the catalyst was filtered off using celite, and the filtrate was evaporated under reduced pressure to give N- (1-cyano-1-ethylpropyl) -1-tert-butyl-3-hydroxypyrazole-4-carboxamide. Of a white solid (1.10 g, yield: 97.3%) was obtained. mp: 186 ° C .; ¹ H-NMR (CDCl ₃ , TMS, ppm): δ 7.47 (s, 1H), 1.95-2.19 (m, 4H), 1.61 (s, 9H), 1.08 (t, J = 7.5 Hz, 6H). (NH and OH protons could not be assigned.)
Reference Examples-2 to 4 obtained pyrazole derivatives in the same manner as Reference Example-1.

Reference example-2
Compound name: N- [1-cyano-1-methyl-2- (phenoxy) ethyl] -3-hydroxy-1-methylpyrazole-4-carboxamide Yield, shape, melting point: 95.1%, white solid, 217-219 ℃
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.97 (s, 1H), 7.74 (br s, 1H), 7.23-7.41 (m, 2H), 6.92-7.11 (m, 3H), 4.42 (d, J = 9.5Hz, 1H), 4.31 (d, J = 9.5Hz, 1H), 3.67 (s, 3H), 1.79 (s, 3H). (OH proton could not be assigned.)

Reference example-3
Compound name: N- [1-cyano-1-methyl-2- (4-fluorophenoxy) ethyl] -3-hydroxy-1-methylpyrazole-4-carboxamide Yield, shape, melting point: 96.7%, white solid, 198-199 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.71 (s, 1H), 7.23-7.35 (m, 1H), 6.84-7.05 (m, 4H), 4.35 (d, J = 9.1 Hz, 1H), 4.27 (d, J = 9.1Hz, 1H), 3.66 (s, 3H), 1.92 (s, 3H). (OH proton could not be assigned.)

Reference example-4
Compound name: N- [1-cyano-1-methyl-2- (4-trifluoromethylphenoxy) ethyl] -3-hydroxy-1-methylpyrazole-4-carboxamide Yield, shape, melting point: quantitative, white Solid, 196-198 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ7.73 (s, 1H), 7.56 (d, J = 8.6Hz, 2H), 7.04 (d, J = 8.6Hz, 2H), 4.49 (d , J = 9.1Hz, 1H), 4.36 (d, J = 9.1Hz, 1H), 3.66 (s, 3H), 1.94 (s, 3H). (OH and NH protons could not be assigned.)

Reference Example-5
N- (1-cyano-1-ethylpropyl) -1-tert-butyl-3-hydroxypyrazole-4-carboxamide (0.50 g, 1.79 mmol) and potassium carbonate (0.37 g, 2.69 mmol) in acetonitrile (20 mL) To the mixture, methylsulfonyl chloride (0.20 mL, 2.69 mmol) was added at 0 ° C., the temperature was gradually raised to room temperature, and the mixture was stirred for 16 hours at 60 ° C. for 4 hours. After completion of the reaction, ethyl acetate (30 mL) and water (30 mL) were added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL × 2). The organic layer was washed with saturated brine (30 mL), dried over anhydrous magnesium sulfate, the desiccant was removed by filtration, and the solvent was distilled off from the filtrate under reduced pressure. The obtained crude product was purified using a silica gel column (ethyl acetate / hexane = 1/5) to give N- (1-cyano-1-ethylpropyl) -1-tert-butyl-3-methylsulfonyl. A white solid (0.46 g, yield: 71.8%) of oxypyrazole-4-carboxamide was obtained. mp: 119-122 ° C; ¹ H-NMR (CDCl ₃ , TMS, ppm): δ7.53 (s, 1H), 5.64 (brs, 1H), 3.65 (s, 3H), 1.96-2.17 (m, 4H ), 1.68 (s, 9H), 1.09 (t, J = 7.5Hz, 6H).
Reference Examples-6 to 8 obtained pyrazole derivatives in the same manner as Reference Example-5.

Reference Example-6
Compound name: N- [1-cyano-1-methyl-2- (phenoxy) ethyl] -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 31.7%, white solid, 98 ~ 100 ℃
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 7.27-7.36 (m, 2H), 6.93-7.07 (m, 3H), 6.87 (br s, 1H), 4.34 (d, J = 9.1Hz, 1H), 4.30 (d, J = 9.1Hz, 1H), 3.87 (s, 3H), 3.43 (s, 3H), 1.91 (s, 3H).

Reference Example-7
Compound name: N- [1-cyano-1-methyl-2- (4-fluorophenoxy) ethyl] -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 53.1%, white Solid, 91-96 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 6.89-7.05 (m, 4H), 6.85 (br s, 1H), 4.31 (d, J = 9.1Hz, 1H ), 4.25 (d, J = 9.1Hz, 1H), 3.87 (s, 3H), 3.45 (s, 3H), 1.90 (s, 3H).

Reference Example-8
Compound name: N- [1-cyano-1-methyl-2- (4-trifluoromethylphenoxy) ethyl] -1-methyl-3-methylsulfonyloxypyrazole-4-carboxamide Yield, shape, melting point: 49.8% White solid, 152-153 ° C
¹ H-NMR spectrum (CDCl ₃ , TMS, ppm): δ 7.87 (s, 1H), 7.56 (d, J = 8.6Hz, 2H), 7.05 (d, J = 8.6Hz, 2H), 6.84 (br s, 1H), 4.41 (d, J = 9.1Hz, 1H), 4.35 (d, J = 9.1Hz, 1H), 3.87 (s, 1H), 3.45 (s, 1H), 1.92 (s, 3H).

  The pyrazole derivatives according to the present invention that can be synthesized by the method exemplified above are listed in Table 1 below.

Table-1. Pyrazole derivative
――――――――――――――――――――――――――――――
No. R ¹ R ² R ³ R ⁴ R ⁵ n
――――――――――――――――――――――――――――――
1 Methyl Methyl HHH 0
2 Methyl Methyl HHH 1
3 Methyl Methyl Methyl HH 2
4 Methyl Methyl Methyl HH 3
5 Methyl Methyl Methyl HH 4
6 Methyl Methyl Methyl HH 5
7 Methyl Methyl Methyl HH 6
8 Methyl Methyl Methyl Methyl H 0
9 Methyl Methyl Methyl Ethyl H 0
10 Methyl Ethyl Methyl Ethyl H 0
11 Methyl Propyl Methyl Ethyl H 0
12 Methyl Hexyl Methyl Ethyl H 0
13 Methyl 4-Me-C ₆ H ₄ Methyl Ethyl H 0
14 Methyl C ₆ H ₅ Methyl Ethyl H 0
15 Methyl CF ₃ Methyl Ethyl H 0
16 Methyl Methyl Methyl Propyl H 0
17 Methyl Methyl Methyl Isopropyl H 0
18 Methyl Methyl Methyl Cyclopropyl H 0
19 Methyl Methyl Methyl Butyl H 0
20 Methyl Methyl Methyl Pentyl H 0
21 Methyl Methyl Methyl Dodecyl H 0
22 Methyl Methyl Ethyl HH 0
23 Methyl Methyl Ethyl Ethyl H 0
24 Methyl Methyl Ethyl Ethyl Cl 0
――――――――――――――――――――――――――――――

Table-1. Pyrazole derivatives (continued)
――――――――――――――――――――――――――――――
No. R ¹ R ² R ³ R ⁴ R ⁵ n
――――――――――――――――――――――――――――――
25 Methyl Methyl Ethyl Ethyl Br 0
26 Methyl Methyl Ethyl Ethyl Me 0
27 Methyl Methyl Ethyl Propyl H 0
28 Methyl Methyl Ethyl Isopropyl H 0
29 Methyl Methyl Ethyl Cyclopropyl H 0
30 Methyl Methyl Ethyl Butyl H 0
31 Methyl Methyl Propyl HH 0
32 Methyl Methyl Propyl Propyl H 0
33 Methyl Methyl Propyl Isopropyl H 0
34 Methyl Methyl Isopropyl HH 0
35 Methyl Methyl Butyl HH 0
36 Methyl Methyl Butyl Propyl H 0
37 Methyl Methyl Butyl Isopropyl H 0
38 Methyl Methyl Butyl Cyclopropyl H 0
39 Methyl Methyl Butyl Butyl H 0
40 Methyl Methyl sec-Butyl HH 0
41 Methyl Methyl Pentyl Dodecyl H 0
42 Methyl Methyl-(CH ₂ ) ₂ -H 0
43 Methyl Methyl-(CH ₂ ) ₃ -H 0
44 Methyl Methyl-(CH ₂ ) ₄ -H 0
45 Methyl Methyl-(CH ₂ ) ₅ -H 0
46 Methyl Methyl Methyl MeOCH ₂ H 0
47 Methyl Methyl Methyl EtOCH ₂ H 0
48 Methyl Methyl Methyl PrOCH ₂ H 0
49 Methyl Methyl Methyl PhOCH ₂ H 0
50 Methyl Methyl Methyl 4-FC ₆ H ₄ OCH ₂ H 0
51 Methyl Methyl Methyl 4-CF ₃ -C ₆ H ₄ OCH ₂ H 0
52 Methyl Methyl Methyl MeSCH ₂ H 0
53 Methyl Methyl Methyl EtSCH ₂ H 0
54 Methyl Methyl Methyl PhSCH ₂ H 0
55 Methyl Methyl Methyl MeSOCH ₂ H 0
56 Methyl Methyl Methyl EtSOCH ₂ H 0
57 Methyl Methyl Methyl PhSOCH ₂ H 0
58 Methyl Methyl Methyl MeSO ₂ CH ₂ H 0
59 Methyl Methyl Methyl EtSO ₂ CH ₂ H 0
60 Methyl Methyl Methyl PhSO ₂ CH ₂ H 0
61 Ethyl Methyl Methyl HH 0
62 Ethyl Methyl Methyl Methyl H 0
63 Ethyl Methyl Methyl Ethyl H 0
64 Ethyl Methyl Methyl Propyl H 0
65 Ethyl Methyl Methyl Isopropyl H 0
66 Ethyl Methyl Methyl Cyclopropyl H 0
67 Ethyl Methyl Methyl Butyl H 0
68 Ethyl Methyl Ethyl Ethyl H 0
――――――――――――――――――――――――――――――

Table-1. Pyrazole derivatives (continued)
――――――――――――――――――――――――――――――
No. R ¹ R ² R ³ R ⁴ R ⁵ n
――――――――――――――――――――――――――――――
69 Ethyl Methyl Ethyl Propyl H 0
70 Ethyl Methyl Ethyl Isopropyl H 0
71 Ethyl Methyl Ethyl Cyclopropyl H 0
72 Ethyl Methyl Propyl HH 0
73 Ethyl Methyl Propyl Propyl H 0
74 Ethyl Methyl Propyl Isopropyl H 0
75 Ethyl Methyl sec-Butyl HH 0
76 Ethyl Methyl-(CH ₂ ) ₅ -H 0
77 Propyl Methyl HHH 0
78 Propyl Methyl Methyl Methyl H 0
79 Propyl Methyl Methyl Ethyl H 0
80 Propyl Methyl Methyl Propyl H 0
81 Propyl Methyl Methyl Isopropyl H 0
82 Propyl Methyl Methyl Cyclopropyl H 0
83 Propyl Methyl Methyl Butyl H 0
84 Propyl Methyl Ethyl Ethyl H 0
85 Propyl Methyl Ethyl Propyl H 0
86 Propyl Methyl Ethyl Isopropyl H 0
87 Propyl Methyl Ethyl Cyclopropyl H 0
88 Propyl Methyl Propyl HH 0
89 Propyl Methyl Propyl Propyl H 0
90 Propyl Methyl Propyl Isopropyl H 0
91 Propyl Methyl sec-Butyl HH 0
92 Propyl Methyl-(CH ₂ ) ₅ -H 0
93 Isopropyl Methyl Methyl HH 0
94 Isopropyl Methyl Methyl Methyl H 0
95 Isopropyl Methyl Methyl Ethyl H 0
96 Isopropyl Methyl Methyl Propyl H 0
97 Isopropyl Methyl Methyl Isopropyl H 0
98 Isopropyl Methyl Methyl Cyclopropyl H 0
99 Isopropyl Methyl Methyl Butyl H 0
100 Isopropyl Methyl Ethyl Ethyl H 0
101 Isopropyl Methyl Ethyl Propyl H 0
102 Isopropyl Methyl Ethyl Isopropyl H 0
103 Isopropyl Methyl Ethyl Cyclopropyl H 0
104 Isopropyl Methyl Propyl HH 0
105 Isopropyl Methyl Propyl Propyl H 0
106 Isopropyl Methyl Propyl Isopropyl H 0
107 Isopropyl Methyl sec-Butyl HH 0
108 Isopropyl Methyl-(CH ₂ ) ₅ -H 0
109 Butyl Methyl Ethyl Ethyl H 0
110 t-Butyl Methyl Ethyl Ethyl H 0
111 Hexyl Methyl Ethyl Ethyl H 0
112 FCH ₂ CH ₂ Methyl Methyl Ethyl H 0
――――――――――――――――――――――――――――――

Table-1. Pyrazole derivatives (continued)
――――――――――――――――――――――――――――
No. R ¹ R ² R ³ R ⁴ R ⁵ n
――――――――――――――――――――――――――――
113 FCH ₂ CH ₂ Methyl Ethyl Ethyl H 0
114 ClCH ₂ CH ₂ Methyl Methyl Ethyl H 0
115 ClCH ₂ CH ₂ Methyl Ethyl Ethyl H 0
116 CHF ₂ Methyl Methyl Ethyl H 0
117 CHF ₂ Methyl Ethyl Ethyl H 0
118 CH ₃ SCH ₂ Methyl Methyl Ethyl H 0
119 CH ₃ SCH ₂ Methyl Ethyl Ethyl H 0
120 CH ₃ OCH ₂ Methyl Methyl Ethyl H 0
121 CH ₃ OCH ₂ Methyl Ethyl Ethyl H 0
―――――――――――――――――――――――――――――

  Hereinafter, formulation examples and test examples of the agricultural and horticultural insecticide / acaricide of the present invention are shown. The compound “No.” used in each test corresponds to the compound “No.” in the above table.

Formulation example-1: wettable powder 20 parts by weight of the compound of the present invention, 20 parts by weight of Carplex # 80 (white carbon, Shionogi Pharmaceutical Co., Ltd., trade name), ST kaolin clay (Kaolinite, Tsuchiya Kaolin, trade name) ) 52 parts by weight, 5 parts by weight of Solpol 9047K (anionic surfactant, Toho Chemical Co., Ltd., trade name), 3 parts by weight of Lunox P65L (anionic surfactant, Toho Chemical Co., Ltd., trade name) The resulting mixture was uniformly mixed and ground to obtain a wettable powder containing 20% by weight of the active ingredient.

Formulation Example-2: Powder Powder 2 parts by weight of the present compound, 93 parts by weight of clay (manufactured by Nippon Talc Co., Ltd.), and 5 parts by weight of Carplex # 80 (white carbon, Shionogi & Co., Ltd., trade name) are uniformly mixed and ground. Thus, a powder of 2% by weight of active ingredient was produced.

Formulation Example-3: Emulsion The compound of the present invention is added to and dissolved in 20 parts by weight of a mixed solvent consisting of 35 parts by weight of xylene and 30 parts by weight of dimethylformamide, and then dissolved in Solpol 3005X (nonionic surfactant and anionic surfactant). A mixture of the agents, Toho Chemical Co., Ltd., 15 parts by weight) was added to obtain an emulsion containing 20% by weight of the active ingredient.

Formulation Example 4: Flowable Agent 30 parts by weight of the present compound, 5 parts by weight of Solpol 9047K (same as above), 3 parts by weight of Sorbon T-20 (nonionic surfactant, Toho Chemical Co., Ltd., trade name), ethylene glycol 8 parts by weight and 44 parts by weight of water were wet pulverized with Dynomill (manufactured by Shinmaru Enterprises Co., Ltd.), 10 parts by weight of a 1% by weight xanthan gum (natural polymer) aqueous solution was added to this slurry mixture, and well mixed and pulverized. A flowable agent containing 30% by weight of the active ingredient was obtained.

Test Example-1: Insecticidal effect on leafhopper leafhopper larvae Insecticide (emulsion) of the present invention produced by setting rice seedling seedlings in a plastic cylindrical container (inner diameter 6 cm × length 9 cm) and according to the formulation of Preparation Example-3 The water diluted solution (3.5 mL) was sprayed onto the plastic cylindrical container using a spray tower (manufactured by Mizuho Rika) (1 concentration, 2 repetitions). After air-drying, 5 larvae of the leafhopper were infested. Three days after the treatment, the mortality and bitterness of the larvae were examined, and the insecticidal rate (%) was determined for the bitter worms as dead insects. The results are shown in Table-2.

Table-2. Insecticidal effect of leafhoppers on larvae ――――――――――――――――――
Compound No. Concentration (ppm) Insecticide (%)
――――――――――――――――――
9 125 100
16 125 100
18 125 100
22 125 100
27 125 100
28 125 100
51 125 100
64 125 100
68 125 100
80 125 100
84 125 100
――――――――――――――――――

Test Example-2: Insecticidal effect on larvae of diamondback moth Cabbage cut leaves (4 cm × 4 cm) were immersed for 1 minute in an aqueous dilution of the insecticide (hydrating agent) of the present invention produced according to the formulation of Preparation Example-1. . After soaking, it was air-dried and placed in a plastic cup (inner diameter: 7 cm), and 5 third instar larvae were released in this cup (1 concentration, 2 repetitions). The mortality of the larvae and the bitter melon were investigated two days after the release, and the insecticidal rate (%) was determined as the dead worm. The results are shown in Table-3.

Table-3. Insecticidal effect on the larvae of the diamondback moth ―――――――――――――――――――
Compound No. Concentration (ppm) Insecticide (%)
―――――――――――――――――――
16 500 80
51 500 100
64 500 100
―――――――――――――――――――

Test Example-3: Effect of mite killing on adult spider mites Sponges moistened with water were placed in a petri dish with a diameter of 9 cm, filter paper was placed thereon, and kidney leaf slices (3 cm × 3 cm) were further placed thereon. Ten adult spider mites were released on the kidney beans. A liquid (3.5 mL) obtained by diluting the acaricide (hydratant) of the present invention prepared according to the formulation of Formulation Example-1 with water to a predetermined concentration is applied to the above-mentioned kidney leaf by a rotary spray tower (manufactured by Mizuho Rika). (1 concentration, 2 repetitions). The life and death of adults were investigated 24 hours after the treatment, and the mite killing rate (%) was determined. The results are shown in Table-4.

Test Example-4: Ovicidal effect on the egg of the spider mite Sponges moistened with water were placed in a petri dish having a diameter of 9 cm, a filter paper was placed thereon, and a kidney leaf slice (3 cm × 3 cm) was further placed thereon. Five adult nymph spider mites were released on the kidney beans. Eggs were spawned on kidney beans for 24 hours after the release, and then adult females were removed. A liquid (3.5 mL) obtained by diluting the acaricide (hydrating agent) of the present invention prepared according to the formulation of Formulation Example-1 to a predetermined concentration with water, and a rotary spray tower (manufactured by Mizuho Rika Co., Ltd.) on the kidney beans. (1 concentration, 2 repetitions). Seven days after the treatment, the number of unhatched eggs and the number of hatched larvae were examined to determine the egg killing rate (%). The results are shown in Table-4.

Table-4. Effects of miticide on adult worms and eggs of the spider mite -――――――――――――――――――――――
Compound No. Concentration (ppm) Mite killing rate (%) Ovicidal rate (%)
―――――――――――――――――――――――
1 125 100 100
2 125 71.4 94.8
9 125 100 100
16 125 100 67.1
17 125 100 100
18 125 100 100
22 125 100 94.3
28 125 100 100
34 125 100 100
51 125 100 95.5
68 125 100 98.6
84 125 100 87.6
―――――――――――――――――――――――

Claims (4)

General formula (1)
Wherein R ¹ represents an optionally substituted C _{1 to} C ₁₂ alkyl group, and R ² represents an optionally substituted C _{1 to} C ₆ alkyl group or an optionally substituted phenyl group. R ³ and R ⁴ are the same or different and each represents a hydrogen atom, an optionally substituted C ₁ -C ₁₂ alkyl group or an optionally substituted C ₃ -C ₈ cycloalkyl group. Alternatively, the carbon atom to which R ³ and R ⁴ are bonded together may form a C _{3 to} C ₈ cycloalkyl group, n represents an integer of 0 to ^5. R ⁵ represents hydrogen. atom, insecticidal and acaricidal agent containing as an active ingredient a pyrazole derivative represented by the representative.) the alkyl group or a halogen atom C ₁ -C _6. The insecticide / acaricide containing the pyrazole derivative according to claim 1, wherein R ² is a C ₁ -C ₄ alkyl group, n is 0 or 1, and R ⁵ is a hydrogen atom. General formula (2)
(Wherein R ¹ and R ⁵ represent the same meaning as described above, and R ⁶ represents a C _{1 to} C ₆ alkyl group, benzyl group or allyl group), and a general formula (3)
(Wherein R ³ , R ⁴ and n have the same meaning as described above), in some cases, in the presence of a base,
(Wherein R ¹ , R ³ , R ⁴ , R ⁵ and n represent the same meaning as described above), a 3-hydroxypyrazole-4-carboxamide derivative represented by general formula (5) is obtained.

(Wherein R ² represents the same meaning as described above, and X represents a leaving group), and is reacted in the presence of a base.
(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and n represent the same meaning as described above). General formula (2)
(Wherein R ¹ , R ⁵ and R ⁶ represent the same meaning as described above), and a general formula (3)
(Wherein R ³ , R ⁴ and n have the same meaning as described above), in some cases, in the presence of a base,
(Wherein R ¹ , R ³ , R ⁴ , R ⁵ and n represent the same meaning as described above), a method for producing a 3-hydroxypyrazole-4-carboxamide derivative.