WO2020084846A1

WO2020084846A1 - Ester compound and use thereof

Info

Publication number: WO2020084846A1
Application number: PCT/JP2019/028042
Authority: WO
Inventors: かおり井狩
Original assignee: 住友化学株式会社
Priority date: 2018-10-23
Filing date: 2019-07-17
Publication date: 2020-04-30

Abstract

[4-Methoxymethyl)-2,3,6-trifluorophenyl]methyl 2,2-dimethyl-3-((Z)-1-propenyl)cyclopropanecarboxylate has an excellent controlling effect on ixodid ticks and, therefore, is usable as an active ingredient of a composition for controlling ixodid ticks.

Description

Ester compound and its use

The present invention relates to an ester compound and its use for controlling ticks.

[4- (Methoxymethyl) -2,3,5,6-tetrafluorophenyl] methyl 2,2-dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylate

Is known to have pest control activity. (Patent Document 1)
Also, [4- (methoxymethyl) -2,3,6-trifluorophenyl] methyl 2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylate

Is known to have pest control activity. (Patent Document 2)

US6224495 Japanese Patent Laid-Open No. 2007-145781

The present invention relates to [4- (methoxymethyl) -2,3,6-trifluorophenyl] methyl 2,2-dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylate.

And its use for controlling ticks.

The compound of the present invention, [4- (methoxymethyl) -2,3,6-trifluorophenyl] methyl 2,2-dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylate, is 2,2 -Production by esterification reaction of dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylic acid or its derivative with [4- (methoxymethyl) -2,3,6-trifluorophenyl] methanol You can More specifically, 1-tert-butyldimethylsilyloxymethyl-4-obtained by reacting 1,4-bis (hydroxymethyl) -2,3,5,6-tetrafluorobenzene with tert-butyldimethylchlorosilane Reduction of hydroxymethyl-2,3,5,6-tetrafluorobenzene with lithium aluminum hydride leads to 1-tert-butyldimethylsilyloxymethyl-4-hydroxymethyl-2,3,6-trifluorobenzene [4- (methoxymethyl) -2,3,6-trifluorophenyl] methanol via methylation and deprotection of the tert-butyldimethylsilyl group, and then can be produced by an esterification reaction. If necessary, the examples described below can be referred to.

When the compound of the present invention is used for controlling ticks, it is usually used in the form of a composition for controlling ticks, which is a composition containing the compound and an inert carrier.

The composition is usually prepared by mixing the compound of the present invention with an inert carrier such as a solid carrier and a liquid carrier, and optionally adding a surfactant and other auxiliary agents for formulation to prepare an emulsion, an oil agent, an oily agent. It can be obtained by formulating into a liquid preparation such as a liquid preparation, an aqueous liquid preparation, a solution, a shampoo and a suspension, a powder preparation, a cream preparation, an ointment preparation, an aerosol preparation and a sheet preparation.

Examples of solid carriers include clay (kaolin clay, diatomaceous earth, bentonite, acid clay, etc.), dry silica, wet silica, talc, ceramics, and other inorganic minerals (serisite, quartz, sulfur, activated carbon, calcium carbonate, and other fine particles). Powders and granules and synthetic resins (polyester resins such as polypropylene, polyacrylonitrile, polymethylmethacrylate and polyethylene terephthalate, polyamide resins such as nylon-6, nylon-11 and nylon-66, polyvinyl chloride, polyvinylidene chloride, chloride Vinyl-propylene copolymers and the like).

Examples of liquid carriers include water, alcohols (methanol, ethanol, propanol, isopropyl alcohol, butanol, isobutyl alcohol, hexanol, 2-ethylhexanol, octanol, etc.), ketones (acetone, methyl ethyl ketone, etc.), aromatic hydrocarbons (toluene). , Xylene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, etc.), esters (ethyl acetate, butyl acetate, diethyl phthalate, diisobutyl adipate, benzyl benzoate, etc.), nitriles (acetonitrile, etc.), ethers (diisopropyl ether, diethylene glycol) Dimethyl ether etc.), amides (N, N-dimethylformamide etc.), sulfoxides (dimethyl sulfoxide etc.) and vegetable oils (soybean oil, cottonseed oil etc.).

Examples of the surfactant include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene alkylaryl ether, and polyethylene glycol fatty acid ester, and anionic surfactants such as alkyl sulfonate, alkylbenzene sulfonate, and alkyl sulfate. An ionic surfactant is mentioned.

As other auxiliaries for formulation, fixing agents, dispersants, colorants, stabilizers and the like, specific examples include casein, gelatin, sugars (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, synthetic Water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, etc.), acidic isopropyl phosphate, 2,6-di-tert-butyl-4-methylphenol, BHA (2-tert-butyl-4-methoxyphenol) A mixture with 3-tert-butyl-4-methoxyphenol), silicone oil, triglyceride.

The tick control composition of the present invention is a veterinary composition for animals other than humans, for example, bovine, sheep, goat, pig, horse, donkey, dog, cat, rabbit, mouse, rat, hamster, squirrel, monkey and the like. When used for dogs and cats, it can effectively control ticks.

Examples of the control method using the tick control composition of the present invention include dipping, spraying, coating, bathing, washing, rubbing or spraying. Preferred administration methods include spot-on treatment and pour-on treatment. Spot-on treatment is generally a method of dropping or applying a liquid preparation onto the skin of the host animal's head, scapula, etc., and pour-on treatment is generally a method of pouring a liquid preparation along the back line of the host animal body. Is.

The dose of the compound of the present invention is usually 0.01 to 100 mg / kg.

The ticks (Ixodidae) controlled by the compound of the present invention include, for example, Haemaphysalis longicornis, Haemaphysalis flava, Haemaphysalis campanulata, and other genus Haemaphysalis; Dermacentor taiwanicus, Dermacentor andersoni, Dermacentor genus, Yamatomadani (Ixodes ovatus), Ixodes persulcatus, Black-legged Dick (Ixodes scapularis), Western black-footed ticks Ixodes genus such as Holocyclus (Ixodes holocyclus), Lone Star Tick (Amblyomma americanum), Amblyomma genus such as Ambryomma maculatum, Rhipicephalus (Boophilus) microplus, Boo Irasu-An'nuratasu (Boophilus annulatus) Boophilus genus, etc., Rhipicephalus sanguineus (Rhipicephalus sanguineus), include the Rhipicephalus species such as Ripisefarasu-a pen di queue Rei task (Rhipicephalus appendiculatus).

The compound of the present invention has the formula (A)

It is preferable to use the optically active substance represented by or an isomer mixture containing a large amount of the optically active substance.

First, a production example of the compound of the present invention is shown. In the production examples below, TBS represents a tert-butyldimethylsilyl group.

To a mixture of 15.0 g of 1,4-bis (hydroxymethyl) -2,3,5,6-tetrafluorobenzene, 4.86 g of imidazole and 60 mL of N, N-dimethylformamide, tert-butyldimethylchlorosilane 10. 76 g was slowly added, and the mixture was stirred at room temperature for 10 hours. 5% Hydrochloric acid was added to the obtained mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 1-tert-butyldimethylsilyloxymethyl-4-hydroxymethyl-2,3,5,6-tetrafluorobenzene, ie, the formula

There was obtained 15.05 g of the compound represented by.

Under a nitrogen atmosphere, to a mixture of 1.25 g of lithium aluminum hydride and 75 mL of tetrahydrofuran, 15.05 g of 1-tert-butyldimethylsilyloxymethyl-4-hydroxymethyl-2,3,5,6-tetratetrahydrofuran at 0 ° C. A solution of 75 mL of fluorobenzene and tetrahydrofuran was added slowly. The resulting mixture was stirred under reflux for 6 hours. The obtained mixture was heated to 10 ° C., 10% aqueous sulfuric acid solution was added thereto, and the obtained mixture was extracted with tert-butyl methyl ether. The obtained organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 1-tert-butyldimethylsilyloxymethyl-4-hydroxymethyl-2,3,6-trifluorobenzene, that is, the formula:

Thus, 9.93 g of the compound represented by

To a mixture of 9.93 g of 1-tert-butyldimethylsilyloxymethyl-4-hydroxymethyl-2,3,6-trifluorobenzene, 23 g of iodomethane and 75 mL of tetrahydrofuran was added sodium hydride (60% oily) at 5 ° C. It was added little by little and stirred at 5 ° C. for 12 hours. Water was added to the obtained mixture, and the mixture was extracted with tert-butyl methyl ether. The obtained organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 1-tert-butyldimethylsilyloxymethyl-4-methoxymethyl-2,3,6-trifluorobenzene, that is, the formula:

8.4 g of the compound of formula (8) was obtained. To a mixture of 8.4 g of 1-tert-butyldimethylsilyloxymethyl-4-methoxymethyl-2,3,6-trifluorobenzene and tetrahydrofuran (17 mL) was added acetic acid (17 mL) and 10%. 17 mL of hydrochloric acid was sequentially added, and the mixture was stirred at room temperature for 5 hours. The resulting mixture was extracted with tert-butyl methyl ether. The obtained organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give [4- (methoxymethyl) -2,3,6-trifluorophenyl] methanol, ie, the formula

Thus, 4.59 g of a compound represented by
¹ H-NMR (CDCl ₃ ) δ (ppm): 2.90 (1H, t), 3.40 (3H, s), 4.51 (2H, s), 4.72 (2H, d), 6.94 (1H, m).
(1R) -trans-2 prepared by a method described in US6562853 in a mixture of 4.59 g of [4- (methoxymethyl) -2,3,6-trifluorophenyl] methanol, 2.64 g of pyridine and 45 mL of toluene. , 2-Dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylic acid chloride (4.41 g) was added under ice cooling, and the mixture was stirred at room temperature for 2 hours. A 4% aqueous sulfuric acid solution was added to the obtained mixture, and the mixture was extracted with toluene. The obtained organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 7.21 g of the compound represented by the formula (A).
¹ H-NMR (CDCl ₃ ) δ (ppm): 1.13 (3H, s), 1.28 (3H, s), 1.45 (1H, d), 1.70 (3H, d), 2.17 (1H, dd), 3.44 ( 3H, s), 4.53 (2H, s), 5.10 (1H, m), 5.20 (2H, s), 5.59 (1H, m), 7.00 (1H, m).
Next, the compound of the formula (A) which is a compound of the present invention

Expression (B) for comparison with

[4- (methoxymethyl) -2,3,5,6-tetrafluorophenyl] methyl represented by (1R) -trans-2,2-dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxy Rat (see Patent Document 1) and formula (C)

[4- (methoxymethyl) -2,3,6-trifluorophenyl] methyl (1R) -trans-2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylate ( (See Patent Document 2)
A test example using and is shown.
Test example 1
An acetone solution of the compound represented by the formula (A) was poured into a container having an inner volume of 20 mL, the inner surface of the container was uniformly coated with the compound A at 0.032 mg / m ^2, and then dried. Two hours later, 5 nymphs of Haemaphysalis longicornis were placed in the container and the lid was closed. After 48 hours, the life and death of Haemaphysalis longicornis was investigated to determine the mortality rate. The mortality was calculated by the following formula.

Mortality rate (%) = (number of dead insects / number of test insects) x 100
As a result, the mortality rate was 80%.

As a result of conducting the same test using the compound represented by the formula (B) in place of the compound represented by the formula (A), the mortality rate was 20%.

As a result of conducting the same test using the compound represented by the formula (C) instead of the compound represented by the formula (A), the mortality rate was 10%.

Test example 2
An acetone solution of the compound represented by the formula (A) was poured into a container having an inner volume of 20 mL, the inner surface of the container was uniformly coated so that the compound represented by the formula (A) was 4 mg / m ^2, and then dried. . After 24 hours, 5 nymphs of Haemaphysalis longicornis were placed in the container and the lid was closed. After 48 hours, the life and death of Haemaphysalis longicornis was investigated to determine the mortality rate. As a result, the mortality rate was 60%.

As a result of conducting the same test using the compound represented by the formula (B) in place of the compound represented by the formula (A), the mortality rate was 0%.

As a result of conducting the same test using the compound represented by the formula (C) instead of the compound represented by the formula (A), the mortality rate was 0%.

Since the compound of the present invention shows an excellent controlling effect on ticks, it is useful as an active ingredient of a composition for controlling ticks.

Claims

[4- (Methoxymethyl) -2,3,6-trifluorophenyl] methyl 2,2-dimethyl-3-((Z) -1-propenyl) cyclopropanecarboxylate
A tick control composition containing the compound according to claim 1 and an inert carrier.