JPS6337101B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides novel 4-hydroxypyrazole derivatives of the general formula [In the formula, Y represents a lower alkyl group, lower alkoxy group, lower alkylthio group, halogen atom, nitro group or trifluoromethyl group, n represents an integer of 1, 2 or 3, and when n is 2, Yn is may represent an alkylidene dioxy group]. The present inventors have conducted research on a new industrially advantageous method for producing the compound of general formula (), and have developed an industrial method for producing the compound of general formula () under mild conditions and in high yield. We have discovered a very valuable route and further discovered that the compound of general formula () is useful as a raw material compound for pyrazole-based phosphate esters having insecticidal and acaricidal effects. In the above general formula (), the lower alkyl group represented by Y means a linear or branched alkyl group having 1 to 4 carbon atoms, such as methyl,
Ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, etc., and lower alkoxy group means an alkoxy group having 1 to 4 carbon atoms, such as methoxy, ethoxy,
n-propoxy, isopropoxy, sec-butoxy groups, etc., and lower alkylthio groups have 1 to 1 carbon atoms.
4 alkylthio group, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec
-butylthio group, etc., and as the halogen atom, fluorine, chlorine, bromine, and iodine atom are used. n represents the number of substituents Y, and when Y has two or more, these substituents may be the same or different. Further, when the group represented by Y is a lower alkoxy group and n is 2, two alkoxy groups are combined, for example, methylenedioxy,
It may also represent an alkylidene dioxy group such as propylidene dioxy. The compound represented by the general formula () of the present invention is
It can be manufactured by the following route. [In the above formula, Hal represents, for example, a halogen atom such as chlorine, bromine, or iodine, and other symbols have the same meanings as above. ] In this method, 4-haloacetoacetic acid represented by general formula () is reacted with a diazonium salt represented by general formula () in the presence of a base to form 3-halopyrvaldehyde phenyl hydra represented by general formula (). After obtaining the zones, this is subjected to a ring-closing reaction in the presence of a base to obtain a compound of general formula (). The reaction to obtain the 3-halopyrvaldehyde phenylhydrazole represented by the general formula () is generally carried out at a temperature of -10° to 30°C. Water is suitable as a solvent, but alcohols such as methanol, ethanol, propanol, etc. may be added to prevent the formed crystals from blowing up as carbon dioxide gas is generated. As a base, organic carboxylic acids of alkali metals and alkaline earth metals such as sodium acetate, potassium acetate, sodium propionate, potassium propionate, sodium carbonate, potassium carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, etc. Salts, carbonates, hydrogen carbonates, hydroxides, etc. are used. Next, the reaction to obtain the compound of general formula () from the compound of general formula () is carried out in the presence of a base. Examples of bases include hydroxides and carbonates of alkali metals and alkaline earth metals such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium methylate, and sodium ethylate. Hydrogen carbonates and alkali metal alcoholates are used, and among them, strongly basic ones such as sodium hydroxide, potassium hydroxide, and alkali metal alcoholates are preferred. The amount of base used in the reaction is economically appropriate to be used in an amount of 1 to 3 moles relative to compound (), but there is no problem in using a large excess. The reaction is preferably carried out in a solvent, for example, water, methanol, ethanol, n-propanol, isopropanol, n-butanol, t
-Alcohols such as butanol, ethers such as ethyl ether, dioxane, and tetrahydrofuran, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, acid amides such as dimethylformamide, and sulfoxides such as dimethyl sulfoxide can be used. The reaction generally proceeds in the range of -20° to 100°C, but when sodium hydroxide, potassium hydroxide, alkali metal alcoholate, etc. are used as a base in an alcoholic solvent, the reaction can occur even at temperatures below 0°C. progresses easily. Further, in this method, even if the reaction is carried out continuously without isolating compound () during the reaction, the target compound () can be obtained in high yield. The compound () of the present invention has the general formula [In the formula, R ¹ is a lower alkyl group, R ² is a lower alkoxy group or alkylthio group, X is an oxygen atom or a sulfur atom, and Y and n have the same meanings as above]. Used as a raw material compound for ester derivatives. In the general formula (), the lower alkoxy group and lower alkylthio group represented by R ² have the same meaning as each group defined for Y above, and the lower alkyl group represented by R ¹ has 1 to 4 carbon atoms. It means a linear or branched alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, etc. Among the compounds (), a particularly important group of compounds are compounds of the general formula () in which R ¹ is an ethyl group and R ² is an n-propylthio group. The above-mentioned compound () has a strong insecticidal and acaricidal effect against many insects and mites, and while maintaining this excellent effect, it has an excellent property of having relatively low acute oral toxicity to warm-blooded animals. It also has characteristics. Among the compounds (), a group of compounds in which R ¹ is an ethyl group and R ₂ is an n-propylthio group, which are particularly important compounds, have particularly excellent control effects against lepidopteran pests and mites. Moreover, it has low acute oral toxicity to warm-blooded animals. This effect can also be produced by directly spraying the compound () on plants infested with insects or by bringing them into contact with insects, but once the chemical has been absorbed by the plant through its roots, leaves, stems, etc. , this plant is sucked by pests,
It can also be caused by chewing or touching it. Compound () can be produced by a method known per se. For example, the compound of the present invention ()
or its salt with the general formula It can be produced by esterification with a compound represented by the formula [wherein Hal, R ¹ , R ² and X have the same meanings as above]. The esterification reaction is preferably carried out in the presence of an acid binder. Suitable acid binders include, in particular, tertiary amines such as trialkylamines, pyridine, gamma-collidine and sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium methylate, sodium Alkali metal and alkaline earth metal hydroxides, carbonates, bicarbonates, and alkali metal alcoholates such as ethylate are used. General formula () 4-
As the salt of the hydroxypyrazole compound, a corresponding alkali metal salt is suitable, and sodium salt, potassium salt, etc. are preferable. The reaction is generally desirably carried out in a suitable solvent, such as water, methanol,
Alcohols such as ethanol, n-propanol, isopropanol, n-butanol, t-butanol, aromatic hydrocarbons such as benzene, toluene, xylene, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, ethyl Ethers such as ether, dioxane, and tetrahydrofuran, ketones such as acetone and ethyl ethyl ketone, nitriles such as acetonitrile, nitriles such as dimethylformamide, esters such as ethyl acetate, and sulfoxides such as dimethyl sulfoxide can be used. The reaction temperature can be appropriately selected from the range of -20° to 150°C, but generally 0° to 100°C is suitable. The reaction is completed in 0.5 to 10 hours, but
The completion can be confirmed by thin layer chromatography or the like. After the reaction is completed, the reaction mixture can be subjected to a method known per se to obtain the desired product. for example,
The reaction solution is washed with water as it is, or after removing the solvent, it is extracted with an organic solvent such as toluene and washed with water. After drying this with anhydrous sodium sulfate or the like, the solvent is distilled off to obtain the compound of the present invention. If desired, it may be further purified by means such as distillation, recrystallization, column chromatography, etc. Furthermore, the compound () is a compound of the general formula () or a salt thereof of the general formula () A compound represented by the formula [wherein R ² , A compound represented by the formula [wherein R ² , X, Y, Hal and n have the same meanings as above] was obtained, and then this and
It can be produced by reacting a compound represented by R ¹ OH (R ¹ has the same meaning as above). The compound () is effective in controlling sanitary pests, plant parasitic insects, and mites. More specifically, the compound () as well as formulations containing it are, for example, Eurydema
rugosa), rice black stink bug (Scotinophora
lurida), Riptortus stink bug (Riptortus
clavatus), nashigunbai (Stephanitis nashi),
Planthopper (Laodelphax striatellus), leafhopper (Nephotettix cincticeps), green leafhopper (Unaspis yanonensis), soybean aphid (Aphis glycines), false radish aphid (Lipaphis pseudobrassicae), radish aphid (Brevicoryne brassicae), cotton aphid (Aphis gossypii), etc. Hemiptera pests, such as Spodoptera
Litura), Plutella xylostella, Pieris rape crucivora, Chilo suppressalis, Plusia nigrisigna, Halicoverpa
Lepidopteran pests such as fall armyworm (Leucania separata), fall armyworm (Mamestra brassicae), Adoxophyes orana, cotton borer (Syllepte derogata), brown borer (Cnaphalocrocis medinalis), and Phthorimaea operculella;
For example, Coleoptera pests such as Epilachna vigintioctopunctata, Aulacophora femoralis, Phyllotrete striolata, Oulema orgzae, and Echinocnemus squamous;
Examples include the house fly (Musca domestica), the Culex pipiens pallens, the bullfly (Tabanus trigonus), and the onion fly (Hylemya).
Antiqua), Hylemya platura and other Diptera pests, such as Locusta platura.
Orthoptera pests such as Gryllotalpa africana (migratoria), mole crickets (Gryllotalpa africana);
For example, the two-spotted spider mite (Tetranychus urticae),
Orange spider mite (Panonychus citri), Kanzawa spider mite (Tetranychus Kanzawai), false red spider mite (Tetranychus cinnabarinus), apple spider mite (Pansnychus ulmi), orange spider mite (Aculus)
It is particularly effective in controlling spider mites such as Aphelenchoidcs bessevi, and nematodes such as Aphelenchoidcs bessevi. When using the compound () as an insecticide and acaricide, it should be used in the form that general agricultural chemicals can take, that is,
One or more compounds () are dissolved or dispersed in a suitable liquid carrier depending on the purpose of use, and mixed or adsorbed with a suitable solid carrier to form an emulsion,
It is used in dosage forms such as oils, wettable powders, powders, granules, tablets, sprays, and ointments. If necessary, emulsifying agents, suspending agents, spreading agents, penetrating agents, wetting agents, mucilage agents, stabilizers, etc. may be added to these preparations, and they can be prepared by methods known per se. The content ratio of active ingredients in insecticides and acaricides varies depending on the purpose of use, but for emulsions, hydrating agents, etc. it is 10 to 90%.
Approximately 0.1% to 10% by weight is appropriate for oils, powders, etc., and 1% to 20% by weight is appropriate for granules, but depending on the purpose of use, These concentrations may be changed as appropriate. In addition, when using emulsions, hydrating agents, etc., dilute them with water as appropriate (for example, 100 to 100,000 times).
It is better to spray it. Liquid carriers used include, for example, water, alcohols (e.g., methyl alcohol, ethyl alcohol, ethylene glycol, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., dioxane, tetrahydrofuran, cellosolve, etc.). , aliphatic hydrocarbons (e.g. gasoline, kerosene, kerosene,
fuel oil, machine oil, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (e.g. chloroform, carbon tetrachloride, etc.), acid amides (e.g. (e.g., dimethylformamide), esters (e.g., ethyl acetate, butyl acetate, glycerin esters of fatty acids, etc.), nitriles (e.g.,
(e.g. acetonitrile) are suitable;
One or a mixture of two or more of these may be used. Examples of solid carriers include vegetable powders (such as soybean flour, tobacco flour, wheat flour, and wood flour), mineral powders (such as kaolin, bentonite, clays such as acid clay, talcs such as talc powder and waxite powder, and diatomaceous earth). , silica such as mica powder, etc.) Furthermore, alumina, sulfur powder, activated carbon, etc. are also used, and one or a mixture of two or more of these may be used. Examples of ointment bases include polyethylene glycol, pectin, polyhydric alcohol esters of higher fatty acids such as glyceryl monostearate, cellulose derivatives such as methyl cellulose, sodium alginate,
One or more types of bentonite, higher alcohols, polyhydric alcohols such as glycerin, petrolatum, white petrolatum, liquid paraffin, lard, various vegetable oils, lanolin, dehydrated lanolin, hydrogenated oils, resins, etc., or various interfaces thereof. Those to which an activator or the like is added can be selected as appropriate. In addition, as surfactants used as emulsifiers, spreaders, penetrants, dispersants, etc., soaps, polyoxyalkylaryl esters (e.g. Menard, manufactured by Takemoto Yushi Co., Ltd.), alkyl sulfur Salts (e.g. Emar 10, Emar 40,
(manufactured by Kao Atlas), alkyl sulfonates (e.g., Neogen, Neogen T, Daiichi Kogyo Seiyaku: Neoverex, manufactured by Kao Atlas),
Polyethylene glycol ethers (e.g., Nonipol 85, Nonipol 100, Nonipol 160,
manufactured by Sanyo Kasei), polyhydric alcohol esters (e.g.
Tween 20, Tween 80, Kao Atlas (manufactured by Kao Atlas), etc. are used. Furthermore, the compounds of the present invention may be used with other types of insecticides (pyrethrin insecticides, organophosphorus insecticides, carbamate insecticides, natural insecticides, etc.), acaricides, nematicides, herbicides, and plant hormones. , plant growth regulators, fungicides (e.g. copper fungicides, organochlorine fungicides, organic sulfur fungicides, phenolic fungicides, etc.), synergists, attractants,
It is also possible to mix and use repellents, pigments, fertilizers, etc. Synthesis examples, formulation examples, and test examples of compound () are shown below. Synthesis Example 1 Production of O-ethyl-O-[1-(4-chlorophenyl)pyrazol-4-yl]-Sn-propylthiophosphate (Compound No. 8) 1-(4-chlorophenyl)-4- Dissolve 3.9g of hydroxypyrazole in 60ml of acetonitrile,
Add 2.0 g of triethylamine. Next, O-
Ethyl-Sn-propylthiophosphoric acid chloride
Add 4.0g and stir at 50°C for 3 hours. After the reaction is completed, acetonitrile is distilled off. The residue was purified by silica gel column chromatography (developing solvent: chloroform) to obtain 5.2 g of the title compound as a pale yellow oil. n ²⁴ _D 1.5604 Synthesis Example 2 Production of O-ethyl-O-[1-(3,4-dichlorophenyl)pyrazol-4-yl]-S-n-propylthiophosphate (Compound No. 23) 1-(3 , 4-dichlorophenyl)-4-hydroxypyrazole 4.6g to methyl ethyl ketone 60g
ml, add 2.8 g of potassium carbonate and 4.0 g of O-ethyl-Sn-propylthiophosphoric acid chloride, and stir at 50°C for 2 hours. Below, Synthesis Example 1
Purification according to the method yields the title compound as a pale yellow oil.
Obtain 5.9g. n ²⁷ _D 1.5737 Synthesis Example 3 Production of O-ethyl-O-[1-(4-chlorophenyl)pyrazol-4-yl)-S-n-propylthiophosphate (Compound No. 8) O-ethyl in 60 ml of ethanol -O-[1-(4
-Chlorphenyl)pyrazol-4-yl]sodium thionate (6.8 g) and n-propyl bromide (2.7 g) were added, and the mixture was stirred at 70°C for 8 hours. Separate the formed inorganic salt, remove ethanol, add toluene to the residue, wash the toluene layer with water, and dry. The product is purified according to Synthesis Example 1 to obtain 5.0 g of the title compound as a pale yellow oil. n ²⁴ _D 1.5604 Next, compounds synthesized in the same manner as in Synthesis Example 1-3 are listed in Table 1, including the compound obtained in Synthesis Example 1-3.

【table】

[Table] Formulation Example 1 Emulsion compound No. 8 20% by weight Xylene 75% by weight Polyoxyethylene glycol ether (Nonipol 85 5% by weight) An emulsion prepared by mixing the following components. Formulation Example 2 Wettable powder Compound No. 9 30 Weight% Sodium ligninsulfonate 5% by weight Polyoxyethylene glycol ether (Nonipol 85) 5% by weight White carbon 30% by weight Clay 30% by weight A wettable powder produced by mixing the following ingredients. Formulation Example 3 Powder Compound No. 23 A powder prepared by mixing the following ingredients: 3% by weight White carbon 3% by weight Clay 94% by weight Formulation example 4 Granule Compound No. 1 10% by weight Sodium ligninsulfonate 5% by weight Clay 85% by weight Granules that can be granulated by
(a) The test compound was made into an emulsion according to the formulation of Formulation Example 1, and diluted with water to prepare a 40 ppm treatment solution.
Pour 2.5 ml of this treatment solution into a test tube (diameter 1.7 cm, depth 4
cm), place three sprouted paddy rice seedlings (7 days after germination) in this, and soak the roots for 2 hours.Then, transfer the soaked seedlings to a test tube with 1 ml of water in the bottom. The test tube into which 10 insects were released was placed indoors (28°C) for 24 hours, and the number of dead insects was determined. The test was conducted twice, and the test results are shown in Table 2 () as a mortality rate. b Prepare a powder from the test compound according to the recipe in Formulation Example 3, and pour 500ml of this powder into a pot (1/5000a).
Powder was applied to the planted paddy rice using the Benjiya duster method. After dusting, cut the rice leaves (15 cm long) and
I put it in a test tube with 1 ml of water in the bottom, and released 10 adult brown planthoppers into it. The test tube was placed indoors (28°C), and the number of dead insects was determined 24 hours after the insects were released. The test was conducted twice, and the test results are shown in Table 2 () as a mortality rate.

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[Table] Test Example 2 Spodoptera litura
Effect on a 500 ppm of test compound (formulation example 1 formulation emulsion)
20ml diluted with water (added 3000 times the spreading agent Dyne)
The mixture was sprayed on soybean seedlings (10 days after germination) hydroponic in ice cream cups using a spray gun (spray pressure 1 Kg/cm ² ) in a spray chamber. Two hours after spraying, cut off two true leaves of the dice, place each one in an ice cream cup (6 cm in diameter, 4 cm in depth), release 10 2nd instar larvae of Spodoptera larvae, and place the cup indoors (25 cm). The number of dead insects was determined after 48 hours.
The test was repeated twice, and the test results are shown in Table 3 as mortality rates.

【table】

[Table] Test Example 3 Unaspis
yanonensis) The test compound was made into a wettable powder according to the formulation of Formulation Example 2, diluted with water (3000 times the spreading agent Dyne was added),
A 500 ppm water suspension was prepared. This water suspension 20
ml was sprayed on second instar female larvae (number of parasitized individuals: 10 to 50) of the Japanese scale insect, which were parasitized on Japanese trifoliate seedlings (2 months after germination) planted in pots (diameter: 9 cm). After spraying, the pots were transferred to a greenhouse (25-30°C), and the number of adults that had grown into adults was determined 20 days after spraying. The test was repeated twice, and the test results are shown in Table 4 as mortality rates. Mortality rate (%) was calculated using the following formula. Mortality rate (%) = 100 - Number of living and growing insects / Number of 2nd instar larvae tested x 1
00

[Table] Test Example 4 Two-spotted spider mite (Tetranychus urticae)
The test compound was made into an emulsion according to the formulation of Formulation Example 1, diluted with water (added 3000 times the spreading agent Dyne), and added to 500 ppm.
An aqueous solution was prepared. 10 female adult two-spotted spider mites on green bean seedlings grown hydroponic in an ice cream cup
The heads were inoculated and placed in a glass room (28 °C) for 24 hours, and 20 ml of the aqueous solution was sprayed on the beans. After spraying, the cups were returned to the glass chamber, and the number of young adults living on the leaves was examined on the 2nd and 7th day after spraying. The test was repeated twice, and the test results were calculated using the following formula to determine the reduction rate, and are shown in Table 5 according to the efficacy level. Reduction rate (%) = Number of sampled mites - Number of living adult larvae on each survey day/Number of sampled mites x 100

【table】

【table】

[Table] Test column 5 Toxicity test Shows the acute oral toxicity value for 5-week-old ddY-SLC mice (〓).

【table】

[Table] Next, Examples and Reference Examples will be described to further explain the present invention in detail. Example 1 Synthesis of 1-(4-chlorophenyl)-4-hydroxypyrazole (compound No. d) Dissolve 4.0 g of sodium hydroxide in 50 ml of methanol and prepare 3-chloropyruvaldehyde 4-chlorophenyl hydrazone at room temperature. When 9.3g is added, it immediately dissolves and the liquid temperature rises to approximately 40℃. After stirring for 1 hour, methanol was distilled off, and 50 ml of water was added to the residue to remove insoluble matter. Neutralize with concentrated hydrochloric acid, collect the precipitated crystals, wash with water, and dry. Recrystallization from toluene yields 6.4 g of the title compound in the form of needle-like crystals.
Melting point: 127-128°C (decomposition) Example 2 Synthesis of 1-(4-chlorophenyl)-4-hydroxypyrazole (compound No. d) Dissolve 4.0 g of sodium hydroxide in 50 ml of water, then dissolve 3-chloropyruvaldehyde. Suspend 9.3 g of 4-chlorophenylhydrazone and stir at 50℃ for 3
Stir for an hour. The crystals gradually dissolve into a dark red homogeneous solution. After cooling, remove insoluble matter, neutralize with concentrated hydrochloric acid, collect precipitated crystals, wash with water, and dry. Recrystallization from toluene yields 5.7 g of the title compound.
Melting point 127-128℃ (decomposition) Example 3 Synthesis of 1-(2,4-dichlorophenyl)-4-hydroxypyrazole (compound No.m) 3-Chlorpyruvaldehyde 2,4-dichlorophenylhydra in 100ml of ethanol zone 27.0
To this suspension, add 12 g of sodium hydroxide dissolved in 10 ml of water at room temperature. After stirring for 2 hours, ethanol was distilled off, and water was added to the residue to dissolve it. Insoluble matter is removed, the liquid is neutralized with glacial acetic acid, and the precipitated crystals are collected, washed with water, and dried. Recrystallization from toluene yields 17.3 g of the title compound. Yield 87%, melting point 148−
149°C Compounds of general formula () synthesized according to Examples 1 to 3 are illustrated in the following table.

[Table] Reference example 1 Synthesis of 3-chlorpyruvaldehyde 4-chlorphenylhydrazone (compound No. O) Parachloroaniline in 500ml of water and 250ml of concentrated hydrochloric acid
Dissolve 128 g of sodium nitrite and dropwise add 69 g of sodium nitrite dissolved in 100 ml of water while keeping the temperature at 0°C. Next, 136.5 g of 4-chloroacetoacetic acid dissolved in 200 ml of water is added while maintaining the temperature at 0° to 5° C., followed by 164 g of sodium acetate dissolved in 300 ml of water. Yellow crystals immediately precipitate and foam violently. After stirring at room temperature until gas evolution ceases, the crystals are collected, washed with water, and dried to obtain 224 g of the title compound. Yield 97%, melting point 190-192°C (decomposition) Next, the raw material compound of general formula () synthesized in the same manner as in Reference Example 1 is illustrated in the following table.

【table】

[Table] * All melting points are decomposition temperatures

Claims (1)

[Claims] 1. General formula [In the formula, Y represents a lower alkyl group, lower alkoxy group, lower alkylthio group, halogen atom, nitro group or trifluoromethyl group, n represents an integer of 1, 2 or 3, and when n is 2, Yn is A compound represented by [which may represent an alkylidenedioxy group]. 2 General formula [In the formula, Y represents a lower alkyl group, lower alkoxy group, lower alkylthio group, halogen atom, nitro group or trifluoromethyl group, n represents an integer of 1, 2 or 3, Hal represents a halogen atom, n
is 2, Yn may represent an alkylidene dioxy group] is subjected to a ring-closing reaction in the presence of a base. A method for producing a compound represented by [the symbols in the formula have the same meanings as above].