WO2000020409A1 - Benzylpiperidine compounds and insecticides for agricultural and horticultural use - Google Patents

Abstract

Benzylpiperidine compounds which exhibit extremely excellent insecticidal activities, do no harm to beneficial insects, and are safe for the environment and so on and lowly toxic. The compounds are represented by general formula (1) wherein R1 is halogeno, C¿1?-C4 haloalkyl, C1-C4 haloalkoxy or the like; R?2¿ is hydrogen, hydroxyl, halogeno, C¿1?-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or the like; Z is oxygen or -S(O)p- (wherein p is an integer of 0 to 2); n is 0 or 1; and m is 0 or 1.

Description

 Specification

 Benzyl piperidine compounds and pesticides for agricultural and horticultural use

 Technical field

 The present invention relates to a benzyl piperidine compound and an agricultural and horticultural insecticide.

 Background technology

 The long-term use of pesticides has made insects resistant in recent years, making it difficult to control with conventional pesticides such as organic phosphorus, carbamates, pyrethroids, etc. And new types of drugs are required. It is also desired to develop compounds that have high insecticidal activity, do not harm beneficial insects, do not adversely affect the environment, and have high safety and low toxicity.

 Conventionally, as benzylpiperidine compounds, for example, the following compounds are known to have insecticidal activity.

 U.S. Pat. No. 5,566,664 describes a general formula (A)

(A)

In, a is an integer of 1 to 3, this Tonoa Ru phenylalanine groups R ^a and R ^b are have a substituent, R ^e is a hydrogen atom, a hydroxyl group, eight androgenic atom, an alkyl group, alkoxy Kishiarukiru group, Al Oxy group, cycloalkylalkoxy group, hetero 5-membered ring It is described that a benzyl piperidine compound which is a group or a 6-membered heterocyclic group has an insecticidal activity. However, U.S. Pat. No. 5,569,664 does not disclose a compound in which R ^e in the general formula (A) is a pyridazinyl group or a pyridazinyloxy group. .

In addition, International Publication No. WO 96/36228 discloses that, in the above general formula (A), a is an integer of 1 to 3, and shaku ³ and shaku ¹⁾ are haloalkyl groups or haloalkoxy. substituted off Eniru group with a group, and the R ^e substituents Ha androgenic atom, Xia amino group, an alkyl group, eight necked alkyl group, alkoxy group, Bruno, mouth Al co alkoxy group, alkoxyalkyl Kishiarukiru group, Nono A 5-membered heterocyclic group or a 6-membered heterocyclic group which may have a low alkoxyalkyl group or an amino carbonyl group (the heterocyclic ring is optionally a group A— [ Where A is — O —, — S — or

-(CH ₂ ) _a — (where a is the same as above.) Or

-0-(CR ^d R ^e ) _b- (wherein R ^d and R ^e are the same or different and each represent a halogen atom or a methyl group; b represents 1 or 2). ] To the benzene ring. It is known that the benzyl piperidine compound which is a) has insecticidal activity. However, WO 96 Z

In the publication of No. 36 228, compounds in which R ^e in the general formula (A) is a pyridazinyl group or a pyridazinyloxy group are described. It is not described physically.

 Furthermore, these conventional benzyl piperidine compounds have satisfactory insecticidal activity but are highly toxic, while those with low toxicity have insufficient insecticidal activity. Have problems.

 Under these circumstances, there is a demand for the development of safe compounds with high insecticidal activity, yet low toxicity.

 Disclosure of the invention

 An object of the present invention is to provide a benzylpiperidine compound having a more excellent insecticidal activity than conventional benzylpiperidin compounds.

 Another object of the present invention is to prevent harm to beneficial insects, to be safe for the environment, etc., and to prevent harmful effects such as fish and other organisms even if discharged into the sea, rivers, lakes and marshes. Another object of the present invention is to provide a benzyl piperidine compound which is less toxic to mammals.

 Another object of the present invention is to provide a safe compound having high insecticidal activity, yet having low toxicity.

 Other features of the present invention will become apparent from the following description.

According to the present invention, the general formula (1)

[In the formula, R ¹ represents a halogen atom, a Ci-4 alkyl group, a C alkoxy group, a Ci-4 haloalkyl group or a C-4 haloalkoxy group. The two R ^1's may be the same or different.

R ² is a hydrogen atom, a hydroxyl group, a halogen atom, a Ci- ₄ alkyl group, an alkoxy group, a Ci- ₄ haloalkoxy group,

 (Ci-4alkoxy) represents a carbonyl group, an alkylthio group, a Ci-4alkylsulfonyl group, a phenyl group or a substituted rubamoyl group which may have a substituent.

Z represents an oxygen atom or a group S (〇) _P — (p represents an integer of 0 to 2).

 n represents 0 or 1, and m represents 0 or 1. ]

A benzylpiperidine compound represented by the formula: or a salt thereof.

Further, according to the present invention, there is provided an insecticide for agricultural and horticultural use containing at least one kind selected from the benzylpiperidine compound represented by the general formula (1) and a salt thereof. You. The benzyl piperidine compound represented by the above general formula (1) or a salt thereof of the present invention has a remarkably excellent insecticidal activity that can control not only drug-sensitive pests but also drug-resistant pests. It has low toxicity to others, and does not cause any harm to the beneficial insects or environment. The compound of the present invention is safe for the environment and the like, and has little risk of adversely affecting organisms such as fish even when discharged into the sea, rivers and lakes, and has low toxicity to mammals.

 In particular, the benzylpirididine compound represented by the above general formula (1) or a salt thereof of the present invention has a low dose and is high in various pests that damage agricultural and horticultural crops. Shows insecticidal efficacy.

 The benzylpiperidine compound represented by the general formula (1) or a salt thereof of the present invention is used for controlling agricultural and horticultural pests while minimizing harm to mammals.

 Further, the benzylpirididine compound represented by the general formula (1) or a salt thereof of the present invention provides a composition capable of controlling agricultural and horticultural pests while minimizing damage to mammals. Used for manufacturing.

In the present specification, specific examples of each group represented by R ¹ to R ⁴ include the following. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

 Examples of the Ci-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, a isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group. Examples thereof include a linear or branched alkyl group having 1 to 4 carbon atoms, such as a group.

C丄- ₄ as an alkoxy group, for example, main preparative key sheet group, e preparative alkoxy group, n - propoxy group, i Seo propoxy, n - Bed DOO alkoxy group, Lee Seo Bed preparative alkoxy group, sec - Butoxy group,

 t er t — a linear or branched alkoxy group having 1 to 4 carbon atoms such as a butoxy group.

C i - ₄ is a eight-necked alkyl group, for example Furuoro methylation group, Buromome ethyl group, ® over de methylation group, Jifuruoro main switch group, Application Benefits Furuoro methylation group, 2 - Furuoroechiru group,

2 — chloroethyl, 1 — fluoroethyl, pentafluoroethyl, 1 — fluoropropyl, 2 — chloropropyl, 3 — fluoropropyl, 3 — chloropropyl A straight- or branched-chain C 1 -C 4 substituted with 1-9 halogen atoms, such as 1-fluorobutyl group, 1-chlorobutyl group, 4-fluorobutyl group, etc. Alkyl groups can be mentioned. Examples of the Ci-4 haloalkoxy group include a fluoromethoxy group, a chloromethyoxy group, a promomethoxy group, a pseudomethoxy group, a difluoromethoxy group, and a trifluoro group. Methoxy group, 2 — Fluoroethoxy group, 2 — Curo mouth ethoxy group, 1 — Fluoroethoxy group, 2, 2, 2 — Trifluoro mouth ethoxy group, Pennofluoroethoxy group , 1—Fluoro-propoxy, 2—Cro-propoxy, 3—Fluoro-propoxy, 3—Cro-propoxy, 1—Fluoroboxy, 1—Chlorobutoxy, 4 A straight-chain or branched alkoxy group having 1 to 4 carbon atoms, which is substituted by 1 to 9 halogen atoms such as a monofluorobutoxy group.

 Examples of the (Ci-4alkoxy) carbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, an n-butoxycarbonyl group, and an i-hydroxycarbonyl group. Alkoxy moieties having 1 to 4 carbon atoms, such as sodium butoxycarbonyl, sec-butoxycarbonyl, and tert-butoxycarbonyl. Groups can be mentioned.

Examples of the Ci-4 alkylthio group include a methylthio group, an ethylthio group, an n-propylthio group, and an isopropylthio group. Straight-chain or branched-chain alkylthio groups having an alkyl portion of 14 carbon atoms, such as n-butylthio group, isobutylthio group, sec-butylthio group, tert-butylthio group, etc. It can be.

C: - ₄ is a alkylsulfonyl group, for example, main Chirusu Ruhoniru group, Echirusuruhoniru group, n - pro Pirusuruho group, I Seo pro Pirusuruhoniru group, n - Buchirusuruho group, Lee Seo butylsulfonyl group, sec Examples thereof include a linear or branched alkylsulfonyl group having 14 carbon atoms, such as a —butylsulfonyl group and a tert-butylsulfonyl group.

 The phenyl group may have 15 substituents, preferably 13 substituents. Examples of the substituent include a halogen atom, a C4 alkyl group, a C4 alkoxy group, a Ci-4 haloalkyl group, a nitro group and a cyano group. .

Among the base Njirupipe lysine compound of the present invention (1), two of R ¹ are the same or different and Ha androgenic atom, C i - ₄ C B alkyl or C - ₄ C b alkoxy group, R ² but a hydrogen atom, C androgenic atom, C i - 4 alkyl groups, C i - ₄ alkoxy groups or C! - ₄ c b alkoxy key sheet group, Z is an oxygen atom or a group

-S (O) (p is as defined above), a compound in which n is 1 and m is 0 or 1, or a salt thereof is preferred. Among the benzylpiperidine compounds (1) of the present invention, two R ¹ are the same or different and each is a Ci- ₄ haloalkyl group or a C- ₄ haloalkoxy group, R ^{2 is a} halogen atom, Z is an oxygen atom, n is 1, and m is 0 or 1 der Ru compound, or its is found salt Shi preferred Ri good Les ^ R ¹ of C i - ₄ Bruno, is a mouth alkyl group, A trifluoromethyl group is preferred, and a trifluoromethoxy group is preferred as the Ci-48 lower alkoxy group. As the halogen atom of R ² , a chlorine atom is preferable.

Among the benzylpiperidine compounds (1) of the present invention, two R ¹ are Ci- ₄ fluoroalkoxy groups, R ^{2 is a} halogen atom, Z is an oxygen atom, n is 1, and m is 0 or 1. Or a salt thereof are most preferred. As the Ci-4 fluoroalkoxy group, a trifluoromethoxy group is preferable, and as the nitrogen atom of R ² , a chlorine atom is preferable and m is 0. Benzyl piperidin compounds

(la) can be produced, for example, according to the following reaction scheme-1.

Reaction process formula 1 1

 (l a)

[Wherein, R ¹ RZ and n are the same as above. X represents a halogen atom. ]

 That is, according to the reaction process formula 11, the piperidine compound

The benzylpiperidine compound (la) of the present invention is produced by reacting (2) with benzyl halide (3).

In this reaction, the ratio of the piperidine compound (2) and the benzyl halide (3) to be used is not particularly limited and can be appropriately selected from a wide range. The molar amount may be 5 to 2 times, preferably 0.8 to 1.2 times. This reaction is usually performed in a solvent. The solvent is not particularly limited as long as it is inert to the reaction, and a wide variety of conventionally known solvents can be used. Examples of such a solvent include, for example, aliphatic hydrocarbons such as hexane, cyclohexane, and heptane, benzene, black benzene, toluene, and the like. Aromatic hydrocarbons such as xylene, halogenated hydrocarbons such as methylene chloride, dichloroethane, cycloform, carbon tetrachloride, and esters such as ethyl acetate and methyl acetate Ethers such as, acetyl ether, tetrahydrofuran, and dioxane; ketones such as acetate and ethyl methyl ketone; acetonitril and propionitol And dimethyl sulfamide, dimethyl sulfoxide, a mixed solvent of two or more of these, a mixed solvent of one or more of these with water, and the like. it can.

A base (catalyst) can be present in the reaction system of this reaction. As the base, widely known bases can be used, for example, sodium hydrogencarbonate, sodium carbonate, potassium hydrogencarbonate, potassium carbonate, sodium hydride, hydrogen hydride. Examples include inorganic bases such as potassium iodide, and organic bases such as triethylamine and pyridin. One of these bases can be used alone, or two or more can be used in combination. The amount of the base used is not particularly limited, and can be appropriately selected from a wide range. Piperidine compound (2) and benzyl halide

The amount that can capture hydrogen octogenogen generated by the reaction with (3) is usually used. The halogenation generated by the reaction between piperidine compound (2) and benzyl halide (3) is usually used. The amount that can just capture hydrogen (stoichiometric amount) or an excess amount thereof, preferably a stoichiometric amount or an excess amount of about 1 to 5 times greater than the above amount. When organic bases such as ethylamine and pyridin are used, they can be used as a solvent by using them in a large excess.

 This reaction is usually carried out at a temperature of from 20 ° C. to the boiling point of the solvent used, and is usually completed in about 0.5 to 24 hours.

The benzyl piperidine compound (la) of the present invention is obtained by reacting benzyl octalide (3) with isodipecotic acid ester (6) according to the following reaction scheme 12. The benzylisodipecotinate (4) is obtained, and then produced by reacting the obtained N-benzylisodipecotinate (4) with a Grignard reagent (5). it can. Reaction process formula 1 2

 (3) (6)

(Four)

 (1 a)

[Wherein RR ² , R ⁴ , Z, X and n are the same as above. The reaction between benzyl halide (3) and isonipecotate (6) is carried out under the same reaction conditions as the reaction between piperidine compound (2) and benzyl halide (3). Done _c

In the reaction of N-benzylisonicobetic acid ester (4) with the Grignard reagent (5), the amount of the Grignard reagent (5) used is usually 2 parts relative to the ester (4). It should be at least equivalent, preferably 2 to 5 equivalents. This reaction is usually performed in a solvent. As the solvent, for example, Ben Aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane; These solvents can be used alone or in combination of two or more. This reaction is carried out at a temperature ranging from −20 ° C. to the boiling point of the solvent used, and is usually completed in about 0.5 to 24 hours.

 Further, the benzyl piperidine compound (la) of the present invention is obtained by reacting the pyrididine compound (7) with the pyridazine compound (8) according to the following reaction process formula-3. Can also be manufactured.

Reaction process formula 1 3

(la) [Wherein, RR ² , Z, X and n are the same as above. The reaction of the pyrididine compound (7) with the pyridazine compound (8) is carried out in a suitable solvent or without a solvent, if necessary, in the presence of a base and a catalyst or a catalyst. .

 The ratio of the pyridazine compound (7) and the pyridazine compound (8) to be used is not particularly limited, and is appropriately selected from a wide range. The latter is used in an amount of about 0.5 to 5 mol, preferably about 0.9 to 2 mol, per 1 mol of the former.

The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include aliphatic or alicyclic hydrocarbons such as hexane, cyclohexane, and heptane; benzene; Aromatic hydrocarbons such as benzene, toluene, xylene, etc., octanolated hydrocarbons such as methylene chloride, dichloroethane, black mouth form, carbon tetrachloride, etc., ethyl acetate, acetic acid Esters such as methyl, ethers such as getyl ether, tetrahydrofuran, and dioxane; ketones such as acetone and ethylmethyl ketone; and acetonitril , Trimethyls such as propionitrile, dimethylformamide, dimethylsulfoxide, a mixed solvent of two or more of these, a mixed solvent of one or more of these with water, etc. Can be listed . As the base, those conventionally known can be widely used, for example, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium hydride, hydride and the like. And inorganic bases such as sodium. One base can be used alone, or two or more bases can be used in combination. The base should be used in an amount sufficient to capture the hydrogen octa- genogenide generated by the reaction of the pyrididine compound (7) with the pyridazine compound (8). Usually, the stoichiometric amount is used. It can be used in stoichiometry or in excess, but preferably in a range from stoichiometric to about 5 times excess.

 Catalysts include, for example, 18-crown ethers such as 16-crown, quaternary ammonium chlorides such as tetrabutylammonium chloride and benzyl triethylammonium chloride. Salts. One of these catalysts can be used alone, or two or more can be used in combination. The catalyst is usually used in an amount of 0.0001 to 10 equivalents, preferably 0.0001 to 1 equivalent, relative to the pyrididine compound (7).

 The reaction of the pyridazine compound (7) with the pyridazine compound (8) can usually be carried out within a temperature range from 120 ° C to the boiling point of the solvent used. The reaction is generally completed in about 0.5 to 24 hours.

Further, in the general formula (1), a benzene wherein R ² is a chlorine atom The benzyl piperidine compound (la) is reacted with a nucleophile such as an alcohol or an alkyl mercaptide to form another benzyl piperidine in which R ² is other than a chlorine atom. It can also be induced into a compound (la). This reaction is also carried out under the same reaction conditions as the reaction between the piberidine compound (2) and benzyl octalide (3).

 Among the raw material compounds used for producing the benzyl piperidine compound (la) of the present invention, the piperidine compound (2) and the piperidine compound (7) are known compounds. For example, it can be synthesized according to the method described in US Pat. No. 5,569,644, International Publication No. 96/36628, and the like.

Benzyl halide (3) can be produced according to known methods. Benzyl halide (3a) in which n is 1 in the general formula (3), for example, 4 — (6 — black mouth pyridazine — 3 — yloxy) benzyl bromide (general formula ( In 3), R ² = chlorine atom, X = bromine atom) can be converted from p-cresole and 3,6-dichloropyridazine in the presence of a solvent and a base, if necessary. To give 41- (6-chlorodiazin-13-yloxy) toluene, which is then reacted with a halogenating agent such as N-promoconoimide. It can be manufactured by processing. In the general formula (3), n is 0 Benzyl halide (3b) such as, for example, 4 — (6 — pyridazine-1 3 -yl) benzyl bromide (in the general formula (3), R ² = chlorine atom, X = The bromine atom) is reacted with 4-methylacetylphenone and glycolic acid, and then treated with hydrazine to obtain 4— (6—hydroxypyridazine—3 —Yl) Toluene is obtained, and this is reacted with a chlorinating agent such as phosphorus oxychloride to obtain 4 — (6 — black mouth pyridazine-1 3 — yl) toluene. It can be manufactured by treating with a halogenating agent such as N-bromocono or citrate imid.

 The Grignard reagent (5) is commercially available or can be easily produced from an octa-logenobenzene derivative by a method well known to those skilled in the art.

 Isodipecotinic acid ester (6) and pyridazine compound (8) are commercially available or can be prepared by methods well known to those skilled in the art.

 The benzyl piperidine compound (la) of the present invention obtained by each of the above-mentioned methods can be prepared by a conventional method such as filtration, solvent extraction, distillation, recrystallization, and column chromatography. Thus, it can be easily isolated and purified from the reaction system.

The benzylpiperidine compound (la) of the present invention is, for example, an organic peroxide or peroxide such as m-chloroperbenzoic acid. It is easily converted to N-oxide by hydrogen, etc., and organic acids such as hydrochloric acid, sulfuric acid, nitric acid, etc., acetic acid, propionic acid, succinic acid, malonic acid, fumaric acid, oxalic acid, etc. A salt can be easily formed with an acid or the like.

 The benzylpiperidine compound (1) of the present invention can be used, for example, as an active ingredient of an insecticide.

 The benzylpiperidine compound (1) of the present invention can be used as it is as an insecticide, but it can be used for oils, emulsions, wettable powders, flouropulants, granules, powders, aerosols, aerosols and the like. It can be formulated into any form and used. At this time, the content of the benzylpiperidine compound (1) of the present invention is not particularly limited, and the formulation form, target pests and types of crops, degree of damage by pests, application place, application time, Various methods such as application methods, concomitant chemicals (pesticides, nematicides, acaricides, fungicides, herbicides, plant growth regulators, synergists, soil conditioners, etc.) and the amount and types of fertilizers Depending on the conditions, it can be selected from a wide range as appropriate, but it is usually about 0.1 to 95% by weight, preferably about 0.1 to 50% by weight of the total amount of insecticide. .

In preparing an insecticide containing the benzylpiperidine compound (1) of the present invention, a conventionally known method can be applied. For example, a benzylpiperidine compound (1) and a carrier such as a solid carrier, a liquid carrier, and a gaseous carrier are used. May be mixed and, if necessary, surfactants and other pharmaceutical auxiliaries may be added to form a pharmaceutical preparation.

 As the carrier, any of those commonly used in this field can be used.

 Examples of the solid carrier include clays (kaolin clay, diatomaceous earth, synthetic hydrous silicon oxide, bentonite, fubasa mikure, acid clay, etc.), talc, ceramics, and other materials. Fine powders and granular materials such as inorganic minerals (cerite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica, etc.) and chemical fertilizers (ammonium sulfate, phosphorous ammonium, ammonium nitrate, urea, salt ammonium, etc.) It is possible to list.

Examples of the liquid carrier include water, alcohols (e.g., methanol, ethanol), ketones (e.g., acetate, methylethylketone), and aromatic hydrocarbons. (Benzene, toluene, xylene, ethylbenzene, methylnaphthalene, etc.). Aliphatic hydrocarbons (hexane, cyclohexane, kerosene, gas oil, etc.), esters (ethyl acetate, butyl acetate, etc.), Trils (acetonitrile, isobutylonitrile, etc.), ethers (diisopropyl ether, dioxane, etc.) Acid amides (N, N-dimethylformamide, N, N-dimethyl acetate amide, etc., halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.) Vegetable oils such as methyl sulfoxide, soybean oil, and cottonseed oil can be mentioned.

 Gaseous carriers or propellants include, for example, butane gas,

LPG (liquefied petroleum gas), dimethyl ether, carbon dioxide, and the like.

 Examples of surfactants include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and their polyoxyethylenates, polyethylene glycol ethers , Polyhydric alcohol esters, sugar alcohol compounds and the like.

Pharmaceutical adjuvants include, for example, casein, gelatin, polysaccharides (starch, arabic gum, cellulose compounds, alginic acid, etc.), lignin compounds, bentonite, saccharides, synthetic water-soluble polymers (Polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.), PAP (isopropyl acid phosphate), BBH (2,6-di-tert — Butyl-4 — methyl phenol), BHA (mixture of 2-tert-butyl-4 — methoxyphenol and 3-tert-butyl — butyl-4 — methoxyphenol), vegetable oil And stabilizers such as mineral oil, fatty acids and their esters, and the like. The preparation of the insecticide of the present invention thus obtained may be used as it is or may be used after being diluted with water or the like. It may be used in combination with other insecticides, nematicides, acaricides, fungicides, herbicides, plant growth regulators, synergists, soil conditioners, animal feed, etc., or They can be used simultaneously without mixing.

When the insecticide of the present invention is used for agricultural and horticultural purposes, the application rate is not particularly limited, and the concentration of the active ingredient, the formulation, the type of the target pest or crop, the degree of damage by the pest, the application location, and the application time , Application methods, concomitant drugs (such as insecticides, nematicides, pesticides, fungicides, herbicides, plant growth regulators, synergists, soil conditioners, etc.) and the amount and type of fertilizer Although it can be appropriately selected from a wide range according to various conditions, the amount of the benzylpiperidine compound (1) of the present invention is usually about 100 m ^2.

 It should be about 0.001 to 100 g. When an emulsion, a wettable powder, a flowable or the like is diluted with water, the application concentration of the benzylpiperidine compound (1) of the present invention is usually from 1 to about LOOO ppm, preferably. Or about 1 to 500 ppm. Granules, powders, etc. are applied as is without dilution.

The agricultural and horticultural insecticide of the present invention can be used, for example, for controlling the following pests. Hemiptera: Tsumaguro-Kyozo, Chino-Midori-Hyo-ko-Bai, Seduro-nuka, Tobi-iron-Bon, Hime-Tin-Bin, Hoshi-Heri-kamushi, Minamiokakamushi, Nashigumbai, Honshikojijimi, Tobacco Chijimi, Silver Leaf Chijimi, Ita Aphid, Momoka Aphid, Konakaji Aphid, Yano Kanekikai Aphid , ヮ カ ラ ム 、 、, ミ ド ド メ ガ 、 、 チ, ク ヘ ヘ 等 等 等 等 等 等 等

Lepidoptera: Butterfly moth, Bryant moth, Bryde moth, Bryde moga, Bryde mogul, Lingkog mogul, Lingy gully, Ginge mogul mog, Micah mogul mog, Masu Shinga, Momoshinga, Kobunomeiga, Nikkamega, Anomeiga, Totoga, Ayouto, Hasumonyouto, Nashihimeshikui, Ichimonjiseri, Monashirocho, Ageha, Otobacuga, Jaga, Omogi Edashak etc.

Coleoptera: Pterodactyla buoy, mame beetle, locust beetle, beetle beetle, beech beetle, beetle beetle, beetle beetle, beetle marca tsuboushimushi, kokunusto, kokuzomu Towels, squirrels, azukizombushi, pine woodpeckers, beetles, etc. Hymenoptera: Powers, Prague Wasp, Rurichu Range, etc.

Diptera: Nettai-y 力, N 夕 y イ -y マ -y マ -y 力, Mameha-mog リ fly, Soybean 夕 y 夕 y 夕 -y マ y マ y マ, バ y バ y エ y イ, イ y バ y エ y ゥ, ゥ y ミ min, yeno, Mog リ fly, ン y ノ n 、, and others

Larvae: human flea, wild flea, etc.

Coleoptera: Chenopodium azurosa, Nekozami azuma, Minamia azuma, Mikankia azuma, Japanese azuma, Hirazana azuma, etc.

Lice eyes: White lice, lice, etc.

Orthoptera: Kochiya Vertical, Flat-bottomed Orchid, etc. Orthoptera: Kera, Tono-Samabat Evening, Kobanei Nago, Chiba Negro, Black Cockroach, etc.

 BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in detail with reference to Reference Examples, Production Examples, Formulation Examples, and Test Examples.

Reference example 1

 4 1 (6 — Black mouth pyridazine 1 3 — Siloxy) Manufacture of benzyl chloride

6.3 g (0.16 mol) of sodium hydride (60% oily) was suspended in 100 ml of dry dimethylformamide, and 50 ml of dry dimethylformamide was stirred under cooling and stirring. 16.2 g (0.15 mol) of P-cres dissolved in 1 It was dropped. After stirring at room temperature for 30 minutes, the solution was cooled again, and 22.4 g (0.15 mol) of 3,6-dichloropyridazine was added little by little. After stirring at room temperature for 2 hours, the reaction solution was poured into ice water, and the precipitated crystals were separated by filtration. The crude crystals were recrystallized from ethanol to give 31 g of colorless crystals of 3—Cro-6- (4—methylphenoxy) pyridazine. (94% yield).

Melting point 1 10 to 11 1 ° C

¹ H-NMR (<5 ppm / CDCl ₃ ): 2.4 (3 H, s), 7.0 (1 H, d, J = 9.1 Hz), 7.1

(2H, d, J = 8.2Hz), 7.2 (2H, d, J = 8.2Hz), 7.5 (1H, d, J = 9.1Hz)

3 — Black mouth 6 — (4 — methyl ethoxy) pyridazine 3.0 g (13.6 mimol), N — Chloroconodic acid imid 2. A mixture of 27 g (17.1 mmol), benzene peroxide 0.33 g (1.36 mmol) and carbon tetrachloride 50 m 1 was heated to reflux for 2 hours. . After cooling the reaction solution, insolubles were removed by filtration, and the filtrate was washed with water, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline in this order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude crystals obtained were recrystallized from hexane Z-ethyl acetate to give the title compound 2.lg as colorless crystals (yield 60%). %).

Melting point 89-90 ° C

^{X H - NMR (<3 ppm} / CDC l 3): 4. 6 (2 H, s), 7. 2 (3 H, m), 7. 4 (3 H, m) Reference Example 2

 4-(6-black mouth pyridazine 1-3-yl)

 4 — To 30 g (0.224 mol) of methyl acetate phenone was added 42 g (0.457 mol) of glyoxylic acid monohydrate, and the mixture was heated at 120 ° C for 1 hour. Stir for 5 hours. After cooling the reaction solution, 20.0 ml of ethanol and 20 ml of concentrated sulfuric acid were added, and the mixture was heated to reflux. The reaction solution was concentrated under reduced pressure to half the volume, added with 300 ml of water, and extracted with 500 ml of ethyl acetate. After the ethyl acetate extract was dried over anhydrous magnesium sulfate, 100 ml of ethanol and 30 g (0.6 mol) of hydrazine monohydrate were added to the obtained residue. Refluxed for 2 hours. The reaction mixture was cooled, and the precipitated crystals were collected by filtration to obtain 14 g of 3—hidoxyl 6—p—tripyridazine as yellow crystals (yield 34%). ).

Melting point 2 13 to 2 16 ° C

¹ H-NMR (5 ppm / CDCl ₃ ): 2.4 (3 H, s), 7.1 (1 H, d, J = 9 Hz), 7.2 — 7.4 (2H, m), 7.7-7.9 (3H, m)

3 — Hydroxy-1 6 — p — Tripyrididazine 10 g (54 mmol) was added to 50 ml of phosphorus oxychloride, stirred at 80 ° C for 1 hour, and further 3 hours Heated to reflux. The reaction solution was concentrated under reduced pressure, the obtained residue was poured into ice, and extracted with 300 ml of ethyl acetate. The ethyl acetate extract was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane ethyl acetate = 41). Recrystallization from xanthine ethyl acetate afforded 4.0 g of 3—curo mouth—6—p—tripyridazine as colorless crystals (36% yield). .

Melting point 1 4 8 to 15 1

¹ H-NMR (<5 pp mZ CDCl ₃ ): 2.4 (3 H, s), 7.3 (2 H, d, J = 8.0 Hz), 7.5

(1H, d, J = 9.0Hz), 7.8 (1H, d, J = 9.0Hz), 8.0 (2H, d, J = 8.0Hz) 3 — Black mouth 6 — p-Tripyrididazine 3.0 g (14.7 mimol), N—promoconodicolic acid imid 3.13 g (17.6 mi) Mol), 0.36 g of benzoyl peroxide and 5 O ml of carbon tetrachloride were heated to reflux for 3 hours. After cooling the reaction mixture, insolubles were removed by filtration. The solution is washed with water, a saturated aqueous solution of sodium hydrogencarbonate and saturated saline in this order, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and recrystallized from ethylethyl acetate. Thus, 3.0 g of the title compound was obtained as colorless crystals (yield: 72%).

Melting point 140-150 ° C

^{1 H - NMR (5 ppm /} CDC l 3): 4. 6 (2 H, s), 7. 6 (3 H, m), 7. 8 (1 H, d, J = 8. 9 H z) , 8.1 (2H, d, J = 8.3Hz) Reference Example 3

 N— [4— (Pyridazin-1-3—yloxy) benzyl] Preparation of ethyl ethyl sonipeccotate

4 — (6 — Black mouth pyridazine-1 3 — yloxy) benzil chloride 2.55 g (10 mimol), ethyl isonepecotinate 1.57 g (10 mmol) and 1.52 g (11 mmol) of calcium carbonate were suspended in 50 ml of acetonitrile and stirred under reflux for 2 days. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl hexanoacetate = 2/1 to 1Z4), and as colorless crystals, N— [4— (6—black mouth pyridazi) was obtained. 3.16 g of ethyl 3- (yloxy) benzyl] isodipecotinate was obtained (84% yield). ¹ H-NMR (<5 ppm / CDCl ₃ ): 1.3 (3 H, t, J = 7.1 Hz), 1.6 — 2.0 (4 H, m), 2.0 — 2.1 (2 H, m), 2.2-2.3 (1 H, m), 2.8 — 2.9 (2 H, m), 3.5 (2 H, s)

4.1 (2H, qJ = 7.1Hz), 77.2 (3H, m), 74 (2H, d, J = 85Hz) 7.5 (1H, d J = 9.1 Hz)

 N— [4— (6-cyclopyridazine-1-3—yloxy) benzyl] ethyl ethyl isodipecotate 1.0 g (2.7 millimoles) and sodium hydroxide 0 Dissolve 1 g (2.75 Umol) in 10 ml of methanol, add a catalytic amount of 10% palladium carbon, and complete the reaction under a hydrogen atmosphere until the reaction is completed. Stirred. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. To the residue was added 50 ml of ethyl acetate, washed with water and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 0.94 g of the title compound as colorless crystals. Obtained (quantitative).

¹ H-NMR (5 ppm / CDCl ₃ ): 1.3 (3 H, t, J = 7.1 Hz), 1.6 — 2.0 (4 H, m), 2.0 — 2 1 (2 H, m), 2.2-2.3 (1 H, m), 2, 8 — 2.9 (2 H, m), 3.5 (2 H, s), 4.1 (2 H, q, J = 7.1 Hz), 7.1-7.2 (3H, m), 7.4 (2H, d, J = 8.5Hz), 7.4-7.5 (1H, m), 8.9 (1H, d) Reference example Four

 4— (6—Methanesulfonylpyridazine-1 3—Iroxy) Manufacture of benzilb mouth mid

 3 — Black mouth 6_ (4—Methylphenoxy) pyridazine 1.0 g (4.55 mimol) and thiourea 0.45 g (5.91 mimol) ) Was dissolved in 10 ml of ethanol and heated under reflux for 2 hours. After adding 4 g (10 mmol) of sodium hydroxide and stirring at room temperature for 30 minutes, adding 0.71 g (5.0 mmol) of methyl iodide and adding 15 Stirred for hours. The reaction solution was poured into water, and the precipitated crystals were separated by filtration to obtain 95 g of 4-((6-methylthiopyridazine-13-yloxy) toluene as colorless crystals (yield). 8 9%).

 'H-NMR (^ ppm / CDCla): 2.35 (3H, s), 2.65 (3H, s), 6.90-7.30 (6H, m).

 4 0.95 g (4.1 mimol) of toluene (6.1-methylthiopyridazine-13-yloxy) toluene

Dissolve it in 30 ml, add 1.4 g (8.2 mmol) of m-chloroperbenzoic acid under cooling and stirring, and stir at room temperature for 2 days. did. The reaction mixture is washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give colorless crystals of 4 — (6 — methanesulfonylpyridazine). 0.8 g of 1-3- (yloxy) toluene was obtained (yield: 83%).

^{1 H - NMR (S ppm /} CDC la): 2. 3 8 (3 H, s), 3. 3 8 (3 H, s), 7. 1 0 (2 H, d, J = 8. 3 5 Hz), 7.26 (2H, d, J = 8.35Hz), 7.36 (1H, d, J = 9.20Hz), 8.13 (1 H, d, J = 9.20 Hz)

 4 _ (6 — methanesulfonylpyridazine-1 3-yloxy) toluene 0.81 g (3.4 mmol), N-bromosuccinate imide 0.74 g (4 .1 mmol), a mixture of a catalytic amount of benzoyl peroxide and 30 ml of carbon tetrachloride were heated to reflux for 3 hours. After cooling the reaction mixture, insoluble materials were removed by filtration, and the filtrate was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline in this order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give brown crystals. As a result, 0.75 g of the title compound was obtained (yield: 63%).

'H - NMR (5 ppm / CDC l 3): 3. 3 8 (3 H s), 4. 5 2 (2 H, s), 7. 0 - 8. 2 (6 H, m) Production Example 1

 N— [4— (6—Cross-mouth pyridazine-1 3—yloxybenzyl)] — 4— [Bis (4—trifluoromethoxyphenyl) hydroxymethyl] piperidine (compound 6) of manufacture

 4-bis [4- (trifluoromethoxyphenyl) hydroxymethyl] pyridin hydrochloride 0.50 g (1.1 millimol), 4— (6_chloro Mouth pyridazine 1-3-yloxy) Benzyl chloride 0.27 g (1.1 mimol) and potassium carbonate 0.32 g (2.3 mimol) The suspension was suspended in 20 ml of nitrile and stirred under reflux for 15 hours. After cooling, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate in hexane = 5/1 to 2/1) to obtain 0.62 g of the title compound as an amorphous solid. Rate 89%).

'H-NMR ((5 ppm / CDCl ₃ ): 1.3-1.5 (4 H, m), 1.9-2.1 (2 H, m), 2.2 (1 H, bs ), 2.3 — 2.5 (1H, m), 2.9 (2H, m), 3.5 (2H, s), 7.0 — 7.2 (7H, m), 7.3 (2H, d, J = 8.5Hz), 7.4-7.6 (5H, m)

Production Example 2 N— [4- (Pyridazin 1-3-yloxy) benzyl] 1-4— [bis (4—trifluoromethyl phenyl) hydrochloride xymethyl] piperidine (compound 15) Manufacture

 4 — Bromobenzotrifluoride 2.37 g (11 mmol) and 0.28 g (12 mmol) of magnesium, dried tetrahydrochloride of Grignard reagent N— [4— (pyridazine-13-yloxy) dissolved in 10 ml of dry tetrahydrofuran in 10 ml of the drofuran solution under cooling and stirring ) Benzyl] 0.90 g (2.6 mmol) of ethyl isodipecotinate was added dropwise. After stirring at room temperature for 1 hour, the mixture was heated under reflux for 15 hours. After cooling, the reaction solution was filtered through celite, and the filtrate was concentrated. The residue was purified by silica gel chromatography (chloroform methanol = 100 Z1), and 0.63 g of the title compound was converted to an amorphous solid. Was obtained (yield: 41%).

'H - NMR ((5 ppm / CDC l 3): 1. 3 - 1. 6 (4 H, m), 2. 0 - 2. 1 (3 H, m), 2. 4 - 2. 6 ( 1 H, m), 3.0 (2 H, m), 3.5 (2 H, s), 7.1 — 7.2 (3 H, m), 7.3 (2 H d, J = 8.5 Hz), 7.5 (1 H, m), 7.5-7.7 (8 H, m), 8.9 (1 H, m)

Production Example 3 N— [4- (6—Methanesulfonyl pyridazine-1-3—yloxybenzyl)] — 4— [Bis (4—trifluoromethyl phenyl) hydroxymethyl] piperidine (compound Production of object 20)

4— [Bis (4—trifluormethyl phenyl) hydroxime] piperidine hydrochloride 0.72 g (1.6 millimoles), 4— (6—Methanesulfonylpyridazine 1 3—Iroxy) Benzyl bromide 0.75 g (2.2 mmol) and potassium carbonate 0.6 g (4.4 mmol) in acetonitrile 20 The mixture was suspended in m 1 and stirred under reflux for 15 hours. The reaction solution was poured into 30 ml of water, and extracted twice with 30 ml of getyl ether. After washing the combined ether extracts with saturated saline, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel chromatography (Cross-mouth Holm Z Methanol = 100 Z1) to give the title compound as an amorphous solid. 73 g (yield 67%) 'H-NMR (<5 pm / CDCl ₃ ): 1.4—1.7 (4H, m), 1.9—2.2 (2 H, m), 2.4 (1H, s), 2.5 (1H, m), 3.0 (2H, m) 3.4 (3H, s), 3.5 (2H , s), 7.1 (2 H, d, J = 8.5 Hz), 7.4 (2 H, d, J = 8.5 Hz), 7.4 (1 H, d, J = 9. l H z), 7. 5 — 7. 7 (8H, m), 8.2 (1H, d, J = 9.1Hz)

Production Example 4

 N— [4— (p—tripyridazine-1 3—yloxy) benzyl] —41-bis (4—trifluoromethoxyphenyl) hydroxymethyl Of compound (Compound No. 14)

 N- (4—Hydroxybenzil) — 4— [Bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine 0.54 g (l.0 mimol ), 3-chloro-6- (p-tolyl) pyridazine 0.20 g (1.0 millimol), potassium carbonate 0.14 g (1.0 millimol) ) And 18—crown—60.03 g (0.11 mmol) were suspended in 10 ml of dry dimethyl sulfoxide.

 The mixture was stirred at 130 ° C for 15 hours. After cooling, the reaction solution was diluted with 60 ml of ethyl acetate, washed three times with 100 ml of water, further washed with a saturated saline solution, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the obtained residue was purified by silica gel chromatography (hexane / ethyl acetate = 41-2/1) to obtain the title compound as an amorphous solid. 0.35 g of the target product was obtained (yield 49%).

'H - NMR (<5 ppm / CDC l 3): 1. 4 - 1. 5 (4 H, m), 1.9 — 2.1 (2 H, m), 2.2 (1 H, m), 2.3 — 2.5 (1 H, m), 2.4 (3 H, s), 3.0 (2H, m), 3.5 (2H, s),

7.1 — 7.4 (11H, m), 7.5 (4H, m), 7.8 (1H, d, J = 9.2Hz), 7.9 (2H, m) d, J = 8.2 Hz)

Production Example 5

 N- [4— (6—methylthiopyridazine-1 3—yloxobenzyl)] — 4— [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine Preparation of (Compound 19)

 4— [bis (4-trifluoromethyoxyphenyl) hydroxymethyl] Instead of pyridin hydrochloride, 4 _ [bis (4—trifluoromethyoxyphenyl) hydride Roxymethyl] piridin hydrochloride was used in the same manner as in Production Example 1 except that N— [4— (6—chiro-mouth pyridazine-13-yloxy) benzyl ] — 4 — [Bis (4—trifluoromethylphenyl) hydroxymethyl] pyridine was obtained.

N— [4— (6—pyridazine-1-3-yloxy) benzyl] —41-bis ((4-trifluoromethyl phenyl) hydroxymethyl) obtained above 0.8 g (1.3 mmol) of pyridin and methyl melamine 0.18 g (2.6 mmol) of the tritium salt was suspended in 30 ml of dry tetrahydrofuran and stirred under reflux for 4 hours. 30 ml of water was added to the reaction solution, and the mixture was extracted twice with 30 ml of ethyl acetate. The combined ethyl acetate extract was washed with saturated saline and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue obtained was purified by silica gel chromatography with benzene / ethyl acetate (benzene / ethyl acetate = 12) to give an amorphous solid. 0.3 g (yield 37%) was obtained.

1 H - NMR (ά ppm / / C Ό C 1 3): 1. 4 - 1. 6 (4 H, m), 1. 8 (1 H, bs), 2. 0 - 2. 1 (2 H , m), 2 • 5 (1H, m), 2.6 (3H, s), 2.9-3.0 (2H, m), 3.5 (2Hs), 7.0 (1 H, d, J = 9.2 H z), 7.1

(2H, d, J = 8.5Hz), 7.2-7.3 (3H: m), 7.5 (4H, d, J = 9.0Hz), 7.6 (4 H, d, J = 9.0 Hz)

Production Example 6

N- [41- (6-piridazine-1-3-yloxy) benzyl] — 4— [bis (4-trifluoromethoxyphenyl) hydroxymethyl] pyridine Of N-oxide (Compound 7) N- [4- (6—pyridazine-1-3—yloxy) benzyl] —4— [bis (4—trifluoromethoxyphenyl) hydroxymethyl] piperidine Dissolve 0.65 g (1 mmol) in 30 ml of methylene chloride, and cool and stir the mixture to obtain 0.22 g (1.25 mmol) of m-cycloperoxybenzoic acid. ) Was added. After stirring at room temperature for 1 hour, the reaction solution was washed with a 10% aqueous sodium hydroxide solution and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crude crystals were washed with hexane / ethyl acetate and dried to give 0.445 g of the title compound as colorless crystals (yield 67%). Melting point 1997-198 ° C

^{1 H - NMR (δ ppm /} CDC 1 3 / DMSO - d 6): 1. 2 - 1. 4 (2 H, m), 2. 0 (1 H, bs), 2. 4 (1 H, m ), 2.8—2.9 (2H, m), 3.0—3.2 (2H, m), 3.2—3.3 (2H, m), 4.4 (2H , s), 7.0 — 7.1 (4 H, m), 7.2 — 7.3 (3 H, m), 7.5 — 7.7 (7 H, m)

¹ H-NMR (S ppm / DMSO-de): 0.9 — 1.0 (2 H, m), 2.1 — 2.3 (2 H, m),

2.5 — 2.6 (1 H, m), 2.8 — 2.9 (2 H, m), 3.0 — 3.2 (2 H, m), 4.2 (2 H, s ), 6.7 (1 H, bs), 7.1 — 7.2 (6 H, m), 7.5-7.6 (7 H, m), 7.9 (1 H, d, J = 9 . 2 H z)

Production Example 7

N-[4 — (6 — Black mouth pyridazine 1 3 — Illoxy) benzyl] — 4 — [Bis (4-trifluoromethoxyphenyl) hydroxymethyl] pyridin Preparation of fumarate (Compound 10)

 N- [4— (6—Cross-mouth pyridazine-1 3—yloxybenzyl)] — 4— [Bis (4—trifluoromethoxyphenyl) hydroxymethyl] pyridine 0.3 g

 (0.46 mimol), fumaric acid 0.053 g

 (0.46 mmol) and 30 ml of dehydrated ethanol were heated under reflux for 2 hours. The reaction solution was concentrated under reduced pressure, and further dried under reduced pressure over phosphorus pentoxide for 3 hours to obtain 0.35 g of the title compound as colorless crystals (quantitative). Melting point 1 19-120 ° C, decomposition

^{1 H - NMR (δ ppm /} DMSO - de): 1. 2 (2 H, m), 1. 5 (2 H, m), 2. 2 (2 H, m), 2. 6 (1 H, m), 2.9 (2H, m), 3.6 (2H, s), 6.6 (2H, s), 7.2 (2H, d, J = 7.8Hz) , 7.3 (4 H, d, J = 8.5 H z), 7.4 (2H, d, J = 7.8Hz), 7.5 (1H, d, J = 9.2Hz), 7.6 (4H, d, J = 8.5) Hz), 8.0 (1H, d, J = 9.2Hz)

 Table 1 shows the compounds produced according to any of the methods described in the above Production Examples and their physicochemical properties. Table 2 shows NMR spectrum data of each compound shown in Table 1.

The NMR spectrum data of each compound was measured using tetramethylsilylane (TMS) as a reference substance. As a Solvent for the measurement of Compound No. 7 and Compound No. 1 0 compound DMS 〇 - had use of d _6. Also, the measurement of the compound No. 7及beauty Compound No. 1 7 compounds, the these compounds were suspended in CDC 1 _3, further to the DMSO-d ₆ few drops of Caro Ete clear solution, NMR spectrum It was used for toll measurement. The measurement of a compound other than the above had use the CDC 1 ₃ as a solvent.

o. R ¹ R ² (Z) nm Melting point (° c)

1 CFaO OH ― 0 120-125

2 CFsO OCHs ― 0 Amorphous solid

3 CFsO SCHa ― 0 Amorphous solid

4 CFsO CI 0 105-108

5 CFsO H 0 0 Amorphous solid

8 CFsO CI 0 0 hydrochloride 123-1132

9 CFaO Br 0 0 Amorphous solid

11 CFsO CH ₃ 0 0 amorphous solid

12 CFsO OCHs 0 0 Amorphous solid

13 CFsO OCH2CF3 0 0 Amorphous solid

16 CF ₃ CI 0 0

17 CF ₃ CI 0 1 N—Aged oxide 192-195

18 CF ₃ OCHs 0 0 Amorphous solid

21 CFs CO2CH3 0 0 Amorphous solid

 23 F CI 0 0 85-87

24 CI CI 0 0 amorphous solid

25 CH ₃ CI 0 0 amorphous solid

26 CHaO CI 0 0 Amorphous solid (ZHS "8 = Γ 'Ρ Ή2) 0 · 8' (ΖΗΟ '6 = f' Ρ Ήΐ) 8 · L '(ΖΗΟ" 6 = f

 'Τ) 9' I 'Η9) S, one

'Ρ' Η) I · '(s Ή2) 9 · ε' 'ΚΖ) 6' Ζ

 '(υι' Ηΐ) 9 — '(s q' HT) S

 '(ui' ΗΖ) I one 0 'Z' (ui 'H 9 · ΐ— * ΐ

'8

 = Γ * Ρ ΉΖ) 0 "8 '(ΖΗ I' 6 = Γ 'Ρ' ΗΤ)

 9 'I' 'Η) 9 -ε-L' (ΖΗΖ · 8 = Γ ε

'Ρ Ήΐ ⁷ ) Τ "Ζ' (s ΉΖ) 9 · ε '(s ΉΖ) 9 ΐ

0 • ε '(s Ήε) 8' ζ '' ζ) s' ζ-ζ · ζ

 Ζ-0 'Ζ' 'Η) 9' I

(ZHS * 8 = f 'Ρ ΉΖ) 6' L

 '(ΖΗ2 · 6 = Γ' Ρ Ή Τ) Ζ · L '' 8 = Γ

 'Ρ' Ηΐ S 'L' (ZHS * 8 = Γ 'Ρ ΊίΖ)' I

 '(ΖΗ2 · 8 = Γ' Ρ 'Η) I · I' · 6 = Γ Ζ

 Οΐ

Ρ 'ΗΤ) 0 · Ζ' (s' HS) C '(S Ή2) 9' £

 '(ui' ΗΖ) 6 'Ζ' (s q Ή Τ) Ζ 'Ζ' (m Ή Τ) 'Ζ

 '(ui Ή2) I one 0' τ '(冚' Η) 9 'l--

(ΪΠ Ήε) ζ ί

 '(ΖΗ9' 8 = Γ 'Ρ' Η) S · ί '(ΖΗΙ · 8 f

 'Ρ' ΗΖ) 'ί' (ΖΗ9 "8 = Γ 'Ρ' U) I Ζ

 '(ZHC' 6 = Γ 'Ρ ΉΙ) 0' Ζ '(S' ΚΖ) 9 ε

 (ui ΉΖ) 0 'ε' (s q 'ΗΙ) 6' Ζ '(ui Ή Τ) ζ

 '(ui ΉΖ) Τ' 2-6I '(ΐπ Ή ^) Ζ' l-τ

( ^ε ΐ OQO 'uid dp) ΗΡΜΝ-Ηχ

Ζ 挲

iZSS0 / 66 «If / XDd 60tOZ / 00 Ο (ZH8 '8 = Γ

'Ρ' Η) 9L '(ui' HS) Ί-2 'L' (UJ 'H) 2--0''(S^< H2) 9 -S

 '(Ui Ή2) 0 · ε— 6' Ζ '(s Ήε) 9' Ζ

 '(ui' ΗΤ) 'Ζ- £' Ζ '(s q Ή Τ) Ζ' Ζ

 (lu I 'Ζ-Ο' Ζ '(ui' Η) S · Ι— 'I

(ΖΗ Τ "6 = Γ 'Ρ Ή I) 9 L 9 ΐ' (ΖΗ8 '8 = f' Ρ 'ΗΙ-L' (ΖΗ · 8 Γ

'Ρ ⁽ ΗΖ) S''(ui Ή9) Τ · ί' (ΖΗ Τ · 6 Γ 6

 Ρ 'ΗΙ) 0 "Ζ' (s' Η ^) 9 'ε' ΉΖ) 6 Ζ

 '(ui' ΗΤ) 'Ζ- £' τ '(s q' ΗΤ) Ζ Ζ

 2-0 'τ' (ui 'Η) 9 "I-^ I

(tu 'ΗΖ) Ζ "Z-S" Ζ' (ui Ή8) 2 "Ζ

 Οΐ

(ZHS '8 = Γ' Ρ 'Η I' Ζ '(s' ΗΖ) Ζ'

 '(s * Η τ) ο ·' (ΐπ Ή ^) s

 '(ui ΉΖ) 8-' Ζ 'Ή Τ) 9 * Ζ

(uj 'HS) g ε' τ 'Ή ^) L · Τ— S · Τ

(ui ΉΤ) 6 '8 Ή3) 5 · Ζ—' Ζ '(ΖΗ' 8

 = r 'ρ Ή2) ε ζ' (ui ΉΖ) τ ι-\ Ί

 '(s ΉΖ) s' ε' (t ο 'ε-6' τ S

 '(ui' ΗΤ) 9 "2 '(s q' ΗΤ) 2 '2

 '(tu Ή2) I' 2-0 'τ' (u 'Η) 9 · ΐ—' τ

( ^ε ΐ OQO 'd 9) Head Ν— Η _τ ON

() Z Halla

S

ZtSS0 / 66df / X3d 6o / oo OAV Table 2 (continued)

'H-NMR (<5 p pm, CDG 1 3)

1.4-1.5 (4H, m), 2.0—2.1 (2H, m) 2.2 (1H, bs), 2.3.2.4 (1H, m),

2.9 (2H, m), 3.5 (2H, s), 4.0 (3H, s), 7.0 (1H, d, J = 9.3Hz), 7.1-7.2

 (7H, m), 7.3 (2H, d, J = 8.4Hz),

7.5 (4H, d, J = 8.8Hz)

1.4-1.5 (4H, m), 1.9-2.1 (2H, m), 2.2 (1H, bs), 2.3-2.4 (lH, m),

2.9—3.0 (2H, m), 3.5 (2H, s), 4.8 (2H, q, J = 8.4 Hz), 7.0—7.2 (7H, m) 7 .2 (1H, d, J = 9.3Hz), 7.3 (2H, d, J = 8.5Hz), 7.5 (4H, d, J = 8.8Hz)

1.4—1.6 (4H, m), 2.0—2.1 (2H, m), 2.4 (1H, bs), 2.5 (1H, m), 3.0 (2H , m), 3.5 (2H, s), 7.1-7.2 (3H, m), 7.3 (2H, d, J = 8.4 Hz), 7.5 (1H, d, J = 9.2Hz), 7.5-7.7 (8H, m)

1.2—1.3 (2H, m), 2.3—2.5 (2H, m),

2.7-2.8 (1H, m), 3.0—3.1 (2H, m),

4.4 (2H, s), 6.4 (1H, bs), 7.2 (2H, d, J = 8.5Hz), 7.5 (1H, d, J = 9.2Hz)

7.6 (4H, d, J = 8.3 Hz), 7.65 (2H, d, J = 8.5 Hz), 7.7 (4H, d, J = 83 Hz),

7. 8 (1 H, d, J = 9.2 Hz)

≠ (2 Table 2 (continued)

^{No. J H-NMR (ά p} pm, CDC 1 3)

1.3-3.1.5 (4H, m), 1.9-2. 1 (2H, m) 2.2 (1H, b s), 2.3-2.4 (1H, m),

24 2.9 (2H, m), 3.5 (2H, s), 7.1-7.2

 (3H, m), 7.2-7.5 (1 OH, m), 7.5

(1 H, d, J = 9.1 Hz)

1. 4-1.6 (4H, m), 1.9.2-2.1 (3H, m)

25 2.3 (6H, s), 2.4 (1H, m), 2.9 (2H, m),

 3.5 (2H, s), 7.0-7.2 (7H, m), 7.3

(6H, m), 7.5 (1 H, d, J = 9.2Hz)

1.3—1.6 (4H, m), 1.9-2.0 (2H, m),

2.2 (1H, b s), 2.2.2.4 (1H, m),

 26 2.9 (2H, m), 3.5 (2H, s), 3.7 (6H, s),

 6.8 (4H, d, J = 8.7Hz), 7.1 (3H, m),

7.3-7.4 (6H, m), 7.4 (1H, d, J = 9.1Hz) The following are examples of preparations. In addition, "parts" simply means parts by weight.

Formulation Example 1

Dissolve 10 parts of each of the compounds of the present invention in 150 parts of Solvesso 150 and 35 parts of N-methylpyrrolidone, and add solpol 3005X (Emulsifier manufactured by Toho Chemical Co., Ltd.) ) 10 parts were added and mixed by stirring to obtain 10% emulsions of each. Formulation Example 2

 20 parts of each of the compounds of the present invention were mixed with 2 parts of sodium lauryl sulfate, 4 parts of sodium ligninsulfonate, 20 parts of synthetic hydrous silicon oxide fine powder and 54 parts of clay. The mixture was stirred and mixed with a juice mixer to obtain a 20% wettable powder.

Formulation Example 3

 To 5 parts of each of the compounds of the present invention, 2 parts of sodium dodecylbenzenesensulfonate, 10 parts of bentonite, and 83 parts of Cray were added and mixed with sufficient stirring. An appropriate amount of water was added, the mixture was further stirred, granulated by a granulator, and dried by ventilation to obtain 5% granules.

Formulation Example 4

 One part of each of the compounds of the present invention is dissolved in an appropriate amount of acetone, and 5 parts of synthetic hydrous silicon oxide fine powder, 0.3 part of acid phosphate (PAP), 0.3 part of clay and 93 parts of clay are added. 7 parts were added, and the mixture was stirred and mixed with a juice mixer, and the acetate was removed by evaporation to obtain a 1% powder.

Formulation Example 5

Each of 20 parts of the compound of the present invention, 3 parts of poly (oxyethylenetrisylphenylphenyl ether phosphate ester, triethanolamine, and rhodazyl (RH0D0RSIL) 42 6 R 0.2 20 parts of water containing water, and wet milling using a die mill, then 8 parts of propyl alcohol, and Xanthan gum

It was mixed with 60 parts of water containing 0.32 parts to obtain a 20% suspension in water.

 Next, Test Examples show that the compounds of the present invention are useful as active ingredients of insecticides.

Test example 1

Insecticidal test on snow monkey

 An aqueous solution (100 ppm) of Solpol 3.55 (manufactured by Toho Chemical Co., Ltd.) is added to the methanol solution of the test compound to prepare a chemical solution (200 ppm), and the chemical solution is added to cabbage leaf pieces (200 ppm). (5 x 5 cm) Two pieces were air-dried. Put the leaf pieces into a plastic cup covered with filter paper moistened with tap water, release 30 second-instar larvae of Lotus monkey, and close the lid with a small hole. It was left in a constant temperature room at 25 ± 2 ° C and 50% humidity. Two days after the treatment, the mortality of Lotus sprout was investigated.

 As a result, the compound of compound number 2, 5, 6, 7, 8, 9, 10, 10, 11, 12, 13, 15, 15, 16, 17, 18, 19, and 24 has 1 compound. It showed a mortality of 00%.

Test example 2

Insecticidal activity comparison test against Lotus root Compound No. 6 of the present invention and U.S. Pat.

 A comparative test was carried out on the insecticidal activity of compound A described in the specification of 5, 569, 644 against eight squirrels.

Compound A:

 To a methanol solution of the test compound was added an aqueous solution (lOOppm) of Solpol 3.55 (manufactured by Toho Chemical Co., Ltd.) to prepare a drug solution (lOppm). The following test method is the same as Test Example 1.

 As a result, the compound of the present invention of compound No. 6 showed a mortality of 100%. On the other hand, Compound A exhibited a mortality of 45%.

Test example 3

 Comparative test of insecticidal activity against Japanese long moth

 Compound No. 6 of the present invention and U.S. Pat.

 A comparative test was conducted on the insecticidal activity of compound A described in the specification of 5, 5, 6, 9, 644 against Japanese moth.

Solvent in the methanol solution of the test compound A chemical solution (20 ppm) was prepared by adding an aqueous solution (100 ppm, manufactured by Kokusan Chemical Co., Ltd.), and this chemical solution was sprayed on a single cabbage leaf piece (5 × 5 cm) and air-dried. Put the leaf pieces into a plastic cup lined with filter paper moistened with tap water, release 15 second-instar larvae of the conger, and close the lid with a small hole. It was left in a constant temperature room at a temperature of 2 ° (: 50% humidity. Two days after the treatment, the mortality and the degree of food damage of the Japanese long moth were examined.

As a result, the compound of the present invention of compound No. 6 exhibited a mortality of 100% and a degree of cabbage damage of 5%. Compound A, on the other hand, had a mortality of 8% and a cabbage damage of 85%.

Test example 4

 Insecticidal activity comparison test against mosquito moth

 A comparative test was conducted on the insecticidal activity of the compounds of the present invention of Compound Nos. 6 and 16 and Compound B described in WO96 / 36228 to Ginger pest.

 Compound B:

Solvent in the methanol solution of the test compound An aqueous solution (100 ppm) was added to prepare a chemical solution (100 ppm), and this solution was sprayed on two pieces of cabbage leaf (5 x 5 cm) and air-dried. Put the leaf pieces into a plastic cup lined with filter paper moistened with tap water, release 20 third instar larvae of the larva, and close the lid with a small hole. It was left in a constant temperature room at ± 2 ° C and 50% humidity. Four days after the treatment, the mortality of the mosquito moth and the degree of damage to untreated plots were examined.

 As a result, the compounds of the present invention of Compound Nos. 6 and 16 both showed a mortality of 100%. In addition, the cabbage damage rates of the compounds of the present invention of Compound Nos. 6 and 16 were 20% and 16%, respectively. On the other hand, Compound B had a mortality of 16% and a cabbage damage of 90%. Test example 5

Insecticidal activity comparison test and toxicity test for various pests

Using the test compounds shown below, an insecticidal activity comparison test against various pests was performed.

Test compound;

Compound of the present invention No. 7

Compound c

Compound D

Compound C and compound D used for comparison with the compound of the present invention (No. 7) were both W〇96Z

The chemical structure of the compound described in W〇96 / 36228 but not specifically described in It is included in the formula, and is a compound (Compound D) which is most likely to have the same chemical structure as the compound of the present invention (No. 7) (Compound C) or the strongest insecticidal activity. .

 Dissolve each of the above test compounds in methanol and concentrate

A 400 ppm methanol solution was prepared. This methanol solution was further diluted with an aqueous solution containing 1.9 ml of a surfactant (trade name: Sorpol, manufactured by Toho Chemical Co., Ltd.) in 100 ml to give a test compound concentration of 2 ml. A chemical solution of O ppm was prepared.

 2 ml of this solution was sprayed on cabbage leaf pieces (5 cm x 5 cm) with a spray gun and air-dried. The leaf pieces are placed in a plastic cup (manufactured by Konoike Plastic Co., Ltd., diameter: 10 cm, capacity: 180 ml), the larvae of the test pests are released, and after a predetermined test time, they die. The number of insects was investigated and the survival rate was calculated. Agony insects were considered dead.

 Each test compound was tested in triplicate, and the average mortality of the three doses was determined.

The types of test pests, the number of cabbage leaf pieces put in the cup, the number of test pests released, and the test time are as shown in Table 3 below. Table 3 Tests Pests Number of cabbage Number of released larvae Test time Second instar larva of Spodoptera litura 30 individuals 48 hours Third instar larva of Japanese moth larva 15 individuals 48 hours Second instar larva of iridescent 20 individuals 96 hours Avomushi (second instar larva)

10 individuals 96 hours 3rd or 4th instar larva of Tobacco moth 1 5 individuals 96 hours On the other hand, untreated using cabbage without spraying test compound

Survival rates in the plot were calculated. Next, the corrected mortality (%) of Abbott was calculated using the following equation. Survival rate of treatment area

Abbott corrected mortality = (1-) X 100 Survival rate of untreated plots The results are shown in Table 4 below. Furthermore, an acute oral toxicity test was conducted to examine the safety of each of the above test compounds. That is, a group of 5 mice (IRC mice, weighing about 20 g) was orally administered a single solution of a test compound dissolved or suspended in a conical oil using a gastric probe. The dose of the test compound was adjusted to be 300 mg / kg of mouse body weight. 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 24 hours after administration, then once daily for 14 days And while observing, acute oral toxicity (LD _5.) Examined, usually product was classified to deleterious substances or poisons. The classification criteria are as follows.

Normal products: LD _5. > 300 mg / kg

Deleterious Substances: 3 0 mg / kg <LD 5. <300 mg Z kg Toxin: LD ^ SO mg Z kg

With the compound of the present invention (No. 7), no mouse death was observed even after 14 days, and LD ₅ . > Classified as 300 mg Z kg ordinary. Compound C was classified as deleterious to poisonous in 2 days after death of all mice. Compound D was classified as deleterious to toxic because three mice died one day later.

 Table 4

 Compound of the present invention Comparative compound

No. 7 D E

Abbott Lotus cutworm larva 84 62 85 Compensation Diamondback larva 100 100 100 Mortality

(%) Aphid 90 100 100 Tobacco moth larva 100 60 100 Safety

~ Poison ~ poison Table 4 The following are clear:

 The compound of the present invention (No. 7) shows a strong insecticidal activity against any of the test pests, and is a highly safe compound classified as an ordinary product.

 Compound C has an insecticidal activity equal to or less than that of the compound of the present invention, and is a compound classified as a deleterious substance or a toxic substance, and has a problem in safety.

 Compound D shows almost no insecticidal activity, especially against Ginger, and is insufficient in insecticidal activity. Furthermore, it is a compound classified as a deleterious substance or a toxic substance, and its safety is low.

Claims

Range of request

 General formula (1)

Wherein, R ¹ represents C androgenic atom, - 4 alkyl groups, C § Turkey alkoxy groups, C i - shows the ₄ Nono b alkoxy group - ₄ C B alkyl or C i. Two R ^{1 s} may be the same or different.

R ² is a hydrogen atom, a hydroxyl group, a halogen atom, a Ci- ₄ alkyl group, a -4 alkoxy group, a Ci- ₄ haloalkoxy group,

Shows the - (4 alkoxy C i) Karuponiru group, C i _ 4 alkylthio group, C _i-4 alkylsulfonyl group, Oh Ru phenylalanine group or force Rubamoi Le group with this having a substituent.

Z represents an oxygen atom or a group —S (〇) _P— (p represents an integer of 0 to 2).

 n represents 0 or 1, and m represents 0 or 1. ]

A benzylpiperidine compound represented by the formula: or a salt thereof.

2. In the general formula (1), R ¹ Gaha androgenic atom, C i - ₄ C B alkyl or C i ₄ C b alkoxy group, R ² is A hydrogen atom, a halogen atom, a Ci-4 alkyl group, a Ci-4 alkoxy group or a Ci_4-octaalkoxy group, wherein Z is an oxygen atom or a group — S (〇) _P — (where p is The same as above;;), the benzyl piperidine compound or a salt thereof according to claim 1, wherein n is 1, and m is 0 or 1.

3. In the general formula (1), R ¹ is a C ₄ haloalkyl group or C i- ₄ , an alkoxy group, R ^{2 is a} halogen atom, Z is an oxygen atom, n is 1, and m 3. The benzylpiperidine compound or a salt thereof according to claim 1, wherein is 0 or 1.

4. - In general formula (1), the scope of the claims wherein R ¹ is C i_ ₄ Furuoro alkoxy group, R ² Gaha androgenic atom, Z is an oxygen atom, n is 1,及beauty m is 0 or 1 4. The benzyl biperidine compound or a salt thereof according to item 1.

5. In the general formula (1), R ¹ is a trifluoromethoxyl group, R ² is a chlorine atom, Z is an oxygen atom, n is 1, and m is 0 or 1, The benzylpiperidine compound of the above or a salt thereof.

6. —General formula (1)

Wherein, R ¹ represents C androgenic atom, C i-4 alkyl groups, C physician 4 § Turkey alkoxy groups, C i - shows the 4 C B alkyl or C i ₄ C b alkoxy group. The two R ^{1 s} may be the same or different.

R ² is a hydrogen atom, a hydroxyl group, a halogen atom, a Ci- ₄ alkyl group, an alkoxy group, a Ci-4 haloalkoxy group,

 (Ci-4alkoxy) A carboxy group, a Ci-4alkylthio group, a Ci-4alkylsulfonyl group, a phenyl group or a carbamoyl group which may have a substituent.

Z represents an oxygen atom or a group —S (〇) _P— (p represents an integer of 0 to 2).

 n represents 0 or 1, and m represents 0 or 1. ]

An agricultural and horticultural insecticide comprising at least one selected from benzylpiperidine compounds represented by the formula: and salts thereof.

7. —In the general formula (1), R ^{1 is a} halogen atom,

C i- ₄ haloalkyl group or C- ₄ haloalkoxy group, R ² is a hydrogen atom, a halogen atom, a C 4 alkyl group, a C i-4 alkyl A alkoxy group or a Ci-4 haloalkoxy group, wherein Z is an oxygen atom or a group S (〇) _P — (wherein p is as defined above;), n is 1, and is 0 or 1. 7. The insecticide for agricultural and horticultural use according to claim 6, comprising at least one selected from a benzyl piperidine compound and a salt thereof.

8. In the general formula (1), R ¹ is a C ぃ₄ haloalkyl group or a Ci- ₄ haloalkoxy group, R ^{2 is a} halogen atom, Z is an oxygen atom, n is 1, and m is 7. The insecticide for agricultural and horticultural use according to claim 6, comprising at least one selected from a benzyl piperidine compound which is 0 or 1, and a salt thereof.

9. In general formula (1), R ¹ is C _ ₄ Furuoro alkoxy group, R ² Gaha androgenic atom, Z is an oxygen atom, n is 1,及beauty m is 0 or 1 base Njirupipe Li di down 7. The agricultural and horticultural insecticide according to claim 6, comprising at least one selected from compounds and salts thereof.

10. The ^{first claim} of the general formula (1) wherein R ¹ is a trifluoromethoxy group, R ² is a chlorine atom, Z is an oxygen atom, n is 1 and m is 0 or 1. The agricultural and horticultural insecticide according to claim 6, comprising at least one selected from the benzylpiperidine compound and the salt thereof according to claim 6. 1 1 Agricultural and horticultural damage while minimizing harm to mammals Use of the benzyl piperidine compound or a salt thereof according to any one of claims 1 to 5 for controlling insects. 12.The benzylpiperidine compound or the benzyl piperidine compound according to claim 1 for producing a composition capable of controlling agricultural and horticultural pests while suppressing harm to mammals as much as possible. Use of these salts.